Factors associated with failure of high-flow nasal cannula oxygen therapy in patients with severe COVID-19: a retrospective case series.

OBJECTIVE: To identify factors associated with high-flow nasal cannula (HFNC) therapy failure in patients with severe COVID-19. METHODS: We retrospectively examined clinical and laboratory data upon admission, treatments, and outcomes of patients with severe COVID-19. Sequential Organ Failure Assessment (SOFA) scores were also calculated. RESULTS: Of 54 patients with severe COVID-19, HFNC therapy was successful in 28 (51.9%) and unsuccessful in 26 (48.1%). HFNC therapy failure was more common in patients aged ≥60 years and in men. Compared with patients with successful HFNC therapy, patients with HFNC therapy failure had higher percentages of fatigue, anorexia, and cardiovascular disease; a longer time from symptom onset to diagnosis; higher SOFA scores; a higher body temperature, respiratory rate, and heart rate; more complications, including acute respiratory distress syndrome, septic shock, myocardial damage, and acute kidney injury; a higher C-reactive protein concentration, neutrophil count, and prothrombin time; and a lower arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2). However, male sex, a low PaO2/FiO2, and a high SOFA score were the only independent factors significantly associated with HFNC therapy failure. CONCLUSIONS: Male sex, a low PaO2/FiO2, and a high SOFA score were independently associated with HFNC therapy failure in patients with severe COVID-19.

Engineered Bacterial Bioreactor for Tumor Therapy via Fenton-Like Reaction with Localized H2 O2 Generation.

Synthetic biology based on bacteria has been displayed in antitumor therapy and shown good performance. In this study, an engineered bacterium Escherichia coli MG1655 is designed with NDH-2 enzyme (respiratory chain enzyme II) overexpression (Ec-pE), which can colonize in tumor regions and increase localized H2 O2 generation. Following from this, magnetic Fe3 O4 nanoparticles are covalently linked to bacteria to act as a catalyst for a Fenton-like reaction, which converts H2 O2 to toxic hydroxyl radicals (•OH) for tumor therapy. In this constructed bioreactor, the Fenton-like reaction occurs with sustainably synthesized H2 O2 produced by engineered bacteria, and severe tumor apoptosis is induced via the produced toxic •OH. These results show that this bioreactor can achieve effective tumor colonization, and realize a self-supplied therapeutic Fenton-like reaction without additional H2 O2 provision.

Multifunctional Nanosystem for Synergistic Tumor Therapy Delivered by Two-Dimensional MoS2.

A multifunctional nanosystem based on two-dimensional molybdenum disulfide (MoS2) was developed for synergistic tumor therapy. MoS2 was stabilized with lipoic acid (LA)-modified poly(ethylene glycol) and modified with a pH-responsive charge-convertible peptide (LA-K11(DMA)). Then, a positively charged photosensitizer, toluidine blue O (TBO), was loaded on MoS2 via physical absorption. The negatively charged LA-K11(DMA) peptide was converted into a positively charged one under acidic conditions. Charge conversion of the peptide could reduce the binding force between positively charged TBO and MoS2, leading to TBO release. Furthermore, the positively charged nanosystem was easily endocytosed by cells. Photo-induced hyperthermia of MoS2 in the tumor areas could promote TBO release and exhibited photothermal therapy. In vitro and in vivo results demonstrated that fluorescence and photo-induced reactive oxygen species (ROS) generation of TBO were severely decreased by MoS2 under normal conditions. While in the acidic condition, the pH-responsive nanosystem exhibited a highly specific and efficient antitumor effect with TBO release and photo-induced ROS generation, suggesting to be a promising accessory for synergistic tumor therapy.

A positive feedback strategy for enhanced chemotherapy based on ROS-triggered self-accelerating drug release nanosystem.

Here, a positive feedback strategy was utilized to amplify the concentration of intracellular reactive oxygen species (ROS) and a ROS-triggered self-accelerating drug release nanosystem (defined as T/D@RSMSNs) was demonstrated for enhanced tumor chemotherapy. The mesoporous silica nanoparticles (MSNs) based nanocarriers were gated by ß-cyclodextrin (ß-CD) through the ROS-cleavable thioketal (TK) linker to encapsulate the anticancer drug doxorubicin hydrochloride (DOX) and ROS producing agent α-tocopheryl succinate (α-TOS), whose surface was further anchored with adamantane conjugated poly(ethylene glycol) chain (AD-PEG) via host-guest interaction. It was found that in human breast cancer (MCF-7) cells, T/D@RSMSNs could not only release DOX and α-TOS initiatively, but also lead to increased concentration of intracellular ROS, which could be used as new trigger to cut away TK linkage and then in turn facilitate the further release of DOX for enhanced chemotherapy. Both in vitro and in vivo experiments demonstrated that T/D@RSMSNs exhibited more significant antitumor activity in the human breast cancer than the traditional single-DOX loaded ROS-responsive nanocarrier. This novel ROS-triggered self-accelerating drug release nanosystem with remarkably improved therapeutic effects could provide a general strategy to branch out the applications of existing ROS-responsive drug delivery systems (DDSs).

Self-defensive nano-assemblies from camptothecin-based antitumor drugs.

Camptothecin (CPT)-based drugs always undergo the reversible, pH-dependent lactone ring-opening reaction, yielding the inactive but toxic carboxylate form. Self-assembly strategy provides an effective route for preserving their bio-stability. In this article, nano-sized self-assemblies from CPT-based antitumor drugs were simply built up by directly diluting the stock dimethylsulfoxide solutions of (S)-(+)-CPT, (S)-10-hydroxyl camptothecin and carboxylic CPT with water/phosphate-buffered saline solution. Because of their different molecular structures in A-ring or modification on the 20-OH group, CPT self-assembled into helical nano-ribbons, whereas 10-hydroxycamptothecin and carboxylic CPT self-aggregated into flat nano-ribbons and cylindric nano-rods, respectively. Attractively, the self-assembly of CPT-based drugs could occur within 1 min at a low concentration of 1 × 10(-5 )M. Adopting the J-type self-aggregation, self-assemblies were stable in aqueous solution and could effectively protect the CPT-based drugs from hydrolysis, which thereby kept their bioactivity for tumor therapy.

An innovative pre-targeting strategy for tumor cell specific imaging and therapy.

A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the "biotin-avidin" interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.