Clinical risk factors and outcomes of carbapenem-resistant Escherichia coli nosocomial infections in a Chinese teaching hospital: a retrospective study from 2013 to 2020.

The emergence of carbapenem-resistant Escherichia coli strains poses a considerable challenge to global public health, and little is known about carbapenemase-producing E. coli strains in Tianjin, China. This study aimed to investigate the risk factors for infections with carbapenem-resistant E. coli (CREC) strains. This retrospective case-control study was conducted at a tertiary teaching hospital. A total of 134 CREC clinical isolates were collected from the General Hospital of Tianjin Medical University between 2013 and 2020. The control group was selected at a ratio of 1:1 from patients with nosocomial carbapenem-susceptible E. coli infection. Risk factors for nosocomial CREC infection and clinical outcomes were analyzed using univariate and multivariate analyses. Multivariate analysis revealed that cephalosporin exposure (odd ratio OR = 2.01), carbapenem exposure (OR = 1.96), glucocorticoid exposure (OR = 32.45), and surgical history (OR = 3.26) were independent risk factors for CREC infection. The in-hospital mortality rate in the CREC group was 29.1%, and age >65 years (OR = 3.19), carbapenem exposure (OR = 3.54), and central venous catheter insertion (OR = 4.19) were independent risk factors for in-hospital mortality in patients with CREC infections. Several factors were identified in the development of nosocomial CREC infections. The CREC isolates were resistant to most antibiotics. Reducing CREC mortality requires a comprehensive consideration of appropriate antibiotic use, underlying diseases, and invasive procedures.IMPORTANCEEscherichia coli is an opportunistic pathogen that causes severe hospital-acquired infections. The spread of carbapenem-resistant E. coli is a global threat to public health, and only a few antibiotics are effective against these infections. Consequently, these infections are usually associated with poor prognosis and high mortality. Therefore, understanding the risk factors associated with the causes and outcomes of these infections is crucial to reduce their incidence and initiate appropriate therapies. In our study, several factors were found to be involved in nosocomial carbapenem-resistant E. coli (CREC) infections, and CREC isolates were resistant to most antibiotics. Reducing CREC mortality needs a comprehensive consideration of whether antibiotics are used appropriately, underlying diseases, and invasive interventions. These findings provide valuable evidence for the development of anti-infective therapy, infection prevention, and control of CREC-positive infections.

TiO2/Polystyrene Nanocomposite Antibacterial Material as a Hemoperfusion Adsorbent for Efficient Bilirubin Removal and Prevention of Bacterial Infection.

The use of hemoperfusion adsorbents for the removal of bilirubin in patients with liver failure has become a critical treatment. However, the insufficient clearance of bilirubin and the possibility of bacterial infection during hemoperfusion limit the application. In this work, we designed a novel antibacterial bilirubin adsorbent (PSVT) through the suspension polymerization reaction between double-bond functionalized TiO2 nanoparticles and styrene. PSVT showed an excellent bilirubin adsorption ability and antibacterial performance, ensuring efficient clearance of bilirubin in liver failure patients during hemoperfusion and preventing bacterial infection. The experimental results indicated that TiO2 was uniformly dispersed in the microspheres, which improved the mesoporous structure and increased the specific surface area. Composite adsorbent PSVT showed an exceptional bilirubin adsorption capacity, with the maximum adsorption capacity reaching 24.3 mg/g. In addition, the introduction of TiO2 endowed PSVT with excellent antibacterial ability; the ultimate antibacterial rates against Escherichia coli and Staphylococcus aureus reached 97.31 and 96.47%, respectively. In summary, PSVT served as a novel antibacterial bilirubin adsorbent with excellent bilirubin clearance capacity and antibacterial performance, providing excellent application prospects for treating liver failure patients.

Photorenewable Azobenzene Polymer Brush-Modified Nanoadsorbent for Selective Adsorption of LDL in Serum.

The elevated concentration of low-density lipoprotein (LDL) is recognized as a leading factor of hyperlipidemia (HLP), and selective adsorption of serum LDL is regarded as a practical therapy. Based on the superior structure-function characteristics of stimuli-responsive materials, a photorenewable nanoadsorbent (SiO2@Azo@Gly) with high selectivity and reusability was developed using azobenzene as the functional ligand. Its principle was certified by the preparation of silicon nanoparticles with atom transfer radical polymerization (ATRP)-initiating groups via a sol-gel reaction and their subsequent grafting of azobenzene polymer brushes by surface-initiated ATRP, followed by modification with glycine. Immobilization of carboxylated azobenzene polymer brushes onto the nanoparticles endowed SiO2@Azo@Gly with high adsorption selectivity and reusability. The advanced nanoadsorbent exhibited excellent LDL adsorption capacity at about 27 mg/g and could be regenerated by illumination with high efficiency (circulations ≥ 5); this was further verified by transmission electron microscopy (TEM) and Fourier-transform infrared (FTIR) analysis. SiO2@Azo@Gly also demonstrated superior adsorption efficiency and selectivity in serum from HLP patients, the respective adsorption capacities of LDL, triglyceride, and total cholesterol were about 15.65, 24.48, and 28.36 mg/g, and the adsorption to high-density lipoprotein (cardioprotective effect) was only about 3.66 mg/g. Green regeneration of the nanoadsorbent could be achieved completely through a simple photoregeneration process, and the recovery rate was still 97.9% after five regeneration experiments.

Amphiphilic shell nanomagnetic adsorbents for selective and highly efficient capture of low-density lipoprotein from hyperlipidaemia serum.

Removal of low-density lipoprotein (LDL) from hyperlipemia patients' blood represents an effective approach to prevent the progression of atherosclerotic cardiovascular disease. Based on the LDL structural characteristics and intermolecular interactions, a tailored nano-adsorbent (Fe3O4@SiO2@PAA-PE) was prepared aimed at the removal of LDL from hyperlipemia serum with high selectivity. The core-shell structured magnetic nanoparticles were embedded in an amphiphilic layer composed of hydrophilic poly(acrylic acid) and lipophilic phospholipids to provide multifunctional binding for LDL particles. The results of dynamic light scattering, water contact angle and zeta-potential measurements, thermal gravimetric analysis, and X-ray photoelectron spectroscopy together with Fourier transform infrared spectroscopy confirmed the core-shell structured nanoparticles bearing amphiphilic poly acrylic acid and phospholipid molecules. Because of the superior electronegativity of the functional layer, the nano-adsorbent demonstrated favorable adsorption selectivity against high-density lipoprotein, which possesses a similar structure to LDL but has a cardio-protective function in the human body. The respective adsorption capacity of Fe3O4@SiO2@PAA-PE towards LDL, total cholesterol and triglycerides reached up to 6.26 mg g-1, 8.41 mg g-1 and 9.19 mg g-1, which was 7.03, 9.45 and 10.32 times that towards HDL (0.89 mg g-1). The kinetic and isothermal studies revealed that multiple interactions containing both physical and chemical adsorption occurred in the binding procedure between LDL and Fe3O4@SiO2@PAA-PE, and chemical adsorption may play a more predominant role in LDL adsorption. The nano-adsorbent also had negligible effects on blood cells, and possessed satisfactory recyclability, low cytotoxicity and hemolysis ratios, indicating its good application prospects as a hemoperfusion adsorbent in the treatment of hyperlipidaemia.

Protein corona-coated immunomagnetic nanoparticles with enhanced isolation of circulating tumor cells.

Immunomagnetic nanoparticles (IMNs) have been widely developed as a detection tool to isolate rare circulating tumor cells (CTCs) from whole blood as a potential method for early cancer diagnosis, metastasis examination, and treatment guidance. However, a spontaneous interaction between nanoparticles and proteins results in the formation of a protein corona that reduces the performance of IMNs when they enter body fluids. To address this issue, the protein corona was precoated onto magnetic nanoparticles (C-MNs), and then their surfaces were conjugated with an immuno-antibody. The adsorption of proteins on C-MNs was decreased 6-fold and non-specific cell binding was reduced 5-fold, compared with magnetic nanoparticles (MNs). Furthermore, the immuno-antibody functionalized C-MNs (IC-MNs) maintained highly specific CTC capture performance when exposed to blood plasma. By using artificial spiked blood samples, IC-MNs exhibited 90.2% CTC isolation efficiency, compared with 60.3% by using IMNs. IC-MNs also successfully captured CTCs with high purity in 24 out of 26 female breast cancer patient blood samples. This work demonstrated that a novel preformed protein corona strategy can provide a useful clinically applicable diagnostic tool.

Biomembrane-mimetic hemoperfusion adsorbent for efficient removal of low-density lipoprotein from hyperlipemia blood.

Lowering of low-density lipoprotein (LDL) levels in blood of patients with hyperlipidaemia can effectively prevent the progression of atherosclerosis and coronary heart disease. The present study demonstrated a facile synthesis strategy to prepare biomembrane-mimetic LDL adsorbent (PVA@COOH-PE) via directional immobilization of phospholipid onto macro-porous cross-linked poly(vinyl alcohol) spheres. The binding between the prepared adsorbent and LDL particles simulates the cytosolic lipid droplets to form a lipid-packing structure. The adsorbent possesses satisfactory removal efficiency for LDL and total cholesterol (TCH) in hyperlipemia serum, while remains high-density lipoprotein (HDL) concentration within the normal range. The adsorption capacities for LDL and TCH are about 1.13 and 1.74 mg/ml respectively, which are nearly three and four times higher than that of HDL (0.42 mg/ml). The adsorbent also possesses satisfactory anticoagulant properties, causes negligible effect on blood cells and produces low hemolysis ratios. The excellent blood compatibility plus LDL removal efficiency of PVA@COOH-PE indicates its good application prospect as hemoperfusion adsorbent in the treatment of hyperlipidaemia.

Bio-inspired dual-functional phospholipid-poly(acrylic acid) brushes grafted porous poly(vinyl alcohol) beads for selective adsorption of low-density lipoprotein.

Elevated levels of low-density lipoproteins (LDL) are recognized as a crucial indicator of hyperlipidemia (HLP) and lowering of LDL levels represents an effective clinical treatment strategy. Inspired by the conjugation of phospholipid monolayers and the lipid content of the LDL particle, the current study describes the preparation of an innovative hemoperfusion adsorbent. The adsorbent was prepared by attachment of phosphatidyl ethanolamine to poly(acrylic acid) modified poly(vinyl alcohol-co-triallyl isocyanurate) beads (PVA@PAA-PE). The interaction between LDL and adsorbent mimics the lipoprotein microemulsion present in the blood and thus promotes efficient binding with high affinity. In vitro adsorption using serum from patients with HLP revealed that the LDL adsorption of PVA@PAA-PE was 4.44 times higher than that of controls and the removal rate of LDL using PVA@PAA-PE was about twice as high as that of the anti-atherogenic high-density lipoprotein (HDL). In vivo whole blood perfusion demonstrated the superior affinity of PVA@PAA-PE for LDL since LDL concentration was significantly reduced from 10.71 ± 2.36 mmol L-1 to 6.21 ± 1.45 mmol L-1, while the HDL level was not severely reduced (from 0.98 ± 0.12 mmol L-1 to 0.56 ± 0.15 mmol L-1). Additionally, PVA@PAA-PE exhibited excellent hemocompatibility and low cytotoxicity. Therefore, PVA@PAA-PE is a potential adsorbent for whole blood perfusion to treat hyperlipidemia.

Hydroxyapatite reinforced inorganic-organic hybrid nanocomposite as high-performance adsorbents for bilirubin removal in vitro and in pig models.

Highly efficient removal of bilirubin from whole blood directly by hemoperfusion for liver failure therapy remains a challenge in the clinical field due to the low adsorption capacity, poor mechanical strength and low biocompatibility of adsorbents. In this work, a new class of nanocomposite adsorbents was constructed through an inorganic-organic co-crosslinked nanocomposite network between vinyltriethoxysilane (VTES)-functionalized hydroxyapatite nanoparticles (V-Hap) and non-ionic styrene-divinylbenzene (PS-DVB) resins (PS-DVB/V-Hap) using suspension polymerization. Notably, our adsorbent demonstrated substantially improved mechanical performance compared to the pure polymer, with the hardness and modulus increasing by nearly 3 and 2.5 times, respectively. Moreover, due to the development of a mesoporous structure, the prepared PS-DVB/V-Hap3 exhibited an ideal adsorption capacity of 40.27 mg g-1. More importantly, the obtained adsorbent beads showed outstanding blood compatibility and biocompatibility. Furthermore, in vivo extracorporeal hemoperfusion verified the efficacy and biosafety of the adsorbent for directly removing bilirubin from whole blood in pig models, and this material could potentially prevent liver damage and improve clinical outcomes. Taken together, the results suggest that PS-DVB/V-Hap3 beads can be used in commercial adsorption columns to threat hyperbilirubinemia patients through hemoperfusion, thus replacing the existing techniques where plasma separation is initially required.

Targeting regulation of the tumour microenvironment induces apoptosis of breast cancer cells by an affinity hemoperfusion adsorbent.

The cytokine network of tumour microenvironment (TME) plays an important role in cancer growth and progression. The current work aims to provide a new strategy for cancer therapy based on the targeted regulation of cytokines in the TME. Here, heparin-coupled polyvinyl alcohol (PVA-H) microspheres have been developed as an adsorbent for selectively remove tumour-induced immunosuppressive cytokines, such as vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-ß), but not tumour necrosis factor-alpha (TNF-α) which has an immune-stimulating effect and can inhibit tumour growth. The proliferation and apoptosis of breast cancer cells after perfusion were tested by cell viability assays, flow cytometry analysis and mRNA microarray assays. Results showed that the PVA-H microspheres efficiently absorbed the majority of VEGF (74.39%) and TGF-ß (86.39%), but much less TNF-α (4.16%). The regulation of the cytokines had remarkable anti-proliferative and pro-apoptotic effects on breast cancer cells, which was further confirmed from the change of mRNA expression levels. Thus, targeting regulatory pathways within the TME by an affinity adsorbent that selectively depletes immunosuppressive cytokines is potentially a new and promising strategy for cancer therapy.

Functionalized Carbon Nanotube-Embedded Poly(vinyl alcohol) Microspheres for Efficient Removal of Tumor Necrosis Factor-α.

Tumor necrosis factor (TNF)-α has an important role in the pathogenesis of autoimmune and inflammatory diseases such as rheumatoid and septic arthritis. Removal of excess tumor necrosis factor-α (TNF-α) is a promising treatment. In this study, a series of functionalized carbon nanotube-embedded poly(vinyl alcohol) (PVA) nanocomposite adsorbents were prepared for TNF-α removal for the first time. The resulting nanocomposites were characterized by scanning electron microscopy and Raman spectroscopy, which demonstrated that carbon nanotubes were well-dispersed on the surface of PVA macroporous microspheres. Adsorption tests showed that the carboxylated carbon nanotube-embedded composite microspheres (PVA/MWCNTs-COOH) possessed much better adsorption capacity for TNF-α in both simulated serum solution and rat plasma compared to the aminated (PVA/MWCNTs-NH2) and raw carbon nanotube-embedded microspheres (PVA/MWCNTs-raw). In addition, the effects on hemolytic activity, the anticoagulant property, and the components of blood were negligible, indicating the excellent blood compatibility of composite beads. Our findings suggest that the carboxylated carbon nanotube-embedded composite microspheres may be potentially useful for the treatment of autoimmune and inflammatory diseases by removing TNF-α from the blood.

Bead-type polystyrene/nano-CaCO3 (PS/nCaCO3) composite: a high-performance adsorbent for the removal of interleukin-6.

A novel nano-CaCO3 (nCaCO3) particle composite-derived polystyrene (PS) resin was successfully synthesized by a suspension polymerization method. The nCaCO3 reinforced PS material (PS/nCaCO3) possessed a structure with abundant mesopores of high porosity, high specific surface area (828.3 m2 g-1) and large pore volume (1.83 cm3 g-1). It was revealed that the incorporation of nCaCO3 into the PS matrix enhanced both the mechanical strength which can prevent the fragmentation and its adsorption capacity for interleukin-6 (IL-6, MW = 24.0 kDa) from human plasma. The adsorption isotherm could be described by the Langmuir model and classified as S-3 type, showing an IL-6 uptake of up to 25.6 ng g-1 at an equilibrium concentration of about 500 ng L-1. The adsorption capacity for IL-6 of PS/nCaCO3 is not only significantly higher than that of PS (without nCaCO3), but also superior to those of currently available adsorbents that are under clinical studies (e.g., CytoSorb™ towards cytokines). In addition, the PS/nCaCO3 adsorbent also had good hemocompatibility and showed no leakage of nCaCO3 in the plasma in a flowing model system. Therefore, the synthesized PS/nCaCO3 nano-composite has a great potential to be used as an efficient adsorbent for the removal of interleukin-6 (IL-6) from blood of inflammatory and auto-immune disease patients through hemoperfusion.

Selective adsorption of bilirubin against albumin to alkylamine functionalized PVA microspheres.

Adsorbents are widely used in hemoperfusion for bilirubin removal. However, their performance is often compromised by the presence of plasma proteins. In this study, the bilirubin adsorption capacity of polyvinyl alcohol microspheres (PVAm) functionalized with different amino-alkane ligands has been investigated, with the aim of gaining binding selectivity over albumin. Octylamine-functionalized PVA microspheres (PVAm-8) exhibited an excellent adsorption capacity for bilirubin (75% and 3.95 mg/mL in PBS vs 72% and 3.84 mg/mL in albumin solution) when compared to the clinical adsorbent BPR (92% and 4.84 mg/mL in PBS vs 71%, and 3.80 mg/mL in albumin solution). The bilirubin adsorption capacities of PVAm-8 were largely unaffected by the presence of albumin. Adsorption of bilirubin to PVAm-8 occurs mainly through hydrophobic effects, with adsorption consistent with the monolayer model and the pseudo-first-order model operating in both PBS and albumin solution. The effects of PVAm-8 on hemolytic activity, blood component stability and coagulant activity were negligible, indicating that PVAm-8 has good potential as a high-affinity bilirubin adsorbent for hemoperfusion applications.

Preparation of nano-CaCO3/polystyrene nanocomposite beads for efficient bilirubin removal.

A novel nano-CaCO3/polystyrene nanocomposite adsorbent (NPS-8) was synthesized for efficient bilirubin removal from human plasma. A comparison with the polystyrene adsorbent (PS-8), which was without the incorporation of nano-CaCO3, revealed that NPS-8 had superior bilirubin adsorption capacity and mechanical strength. The resulting nano-CaCO3 reinforced PS-8 (NPS-8) was tested by transmission electron microscopy (TEM), scanning electron microscopy (SEM), mechanical strength test, and bilirubin adsorption assays. The adsorption results indicated that NPS-8 displayed better adsorption capacity for bilirubin (91%) than that of PS-8 (75.88%). The mechanical strength of NPS-8 was significantly greater than that of PS-8. In addition, both PS-8 and NPS-8 possessed good blood compatibility properties (a negligible hemolytic activity and platelet adhesion). Therefore, a conclusion could be drawn that NPS-8 has a high potential as an efficient bilirubin adsorbent for blood purification in clinical practice. At the same time, the success of organic-inorganic nanocomposite adsorbents might provide a new insight into the improvement of adsorbents in hemoperfusion.

Polystyrene-divinylbenzene based nano-CaCO3 composites for the efficient removal of human tumor necrosis factor-α.

PS-DVB/nano-CaCO3, a novel abundant mesoporous structured polymer nano-composite, was successfully synthesized via suspension polymerization. Characterization of this type of bead nano-composite demonstrated that it exhibits significantly enhanced TNF-α adsorption from blood plasma and possesses good mechanical strength.