Transfusion-transmitted infections.

The risk of transfusion-transmitted infection (TTI) has always existed because transfused blood products are biological materials derived from humans. To prevent TTIs, screening strategies have been developed for various infectious diseases, such as hepatitis B virus, hepatitis C virus, and human immunodeficiency virus, contributing significantly to reducing TTI globally. Nevertheless, septic transfusion reactions (STRs) due to bacterial contamination remain an unresolved issue. Various infectious diseases can be transmitted through blood products, and preventive and selective screening strategies have been applied across different regions. Although multiple strategies, including culture-based and rapid detection kit-based methods, have been introduced to overcome STRs, complete prevention has not yet been achieved. Recently, pathogen inactivation methods have been developed to eliminate non-specific organisms rather than screening specific organisms. This approach is anticipated to contribute significantly to diminishing the risk of TTIs in the future.

Trends in category and grade for therapeutic plasma exchange in the latest guideline on therapeutic apheresis by the American Society for Apheresis: Hurdles in pursuing evidence-based medicine.

BACKGROUND AND OBJECTIVES: The Writing Committee of American Society for Apheresis released the ninth edition of guidelines for therapeutic apheresis in 2023. Categories have been a part of the guidelines since the first edition, and the grading system was introduced in the fifth edition, with updates in every new edition. In this study, we investigated the category and grade change trends through the latest five editions, focusing on therapeutic plasma exchange, to suggest future directions as part of evidence-based medicine. MATERIALS AND METHODS: Categories and grades for therapeutic plasma exchange (TPE) were collected and analysed from the fifth through ninth editions. We aligned classification changes to the ninth edition's clinical context and compared its categories and grades with those introduced in the guideline. RESULTS: Among 166 total indications in the ninth edition, 118 included TPE procedure, either as a sole treatment or as one of the therapeutic apheresis techniques. The total number of indications changed, but Category III remained predominant throughout the editions. Similarly, Grade 2C consistently emerged as the most prevalent grade. Notably, 24 cases had grade changes. Of the 16 cases with evidence quality changes, the quality weakened in six and improved in 10. Evidence levels were not improved throughout the study period for 102 clinical conditions. CONCLUSION: To address gaps in evidence quality, international collaboration is imperative to establish comprehensive large-scale studies or randomized controlled trials. This will refine the use of therapeutic apheresis, including TPE, to foster evidence-based advancements in clinical practice.

Clinical significances and distribution of unexpected antibodies found in infants.

INTRODUCTION: The unexpected antibody test is an essential for ensuring the safety of blood transfusions. In infants, different pre-transfusion tests and transfusion strategies are needed due to their immature antigen/antibody system. This study aims to analyze the pattern of unexpected antibodies and their clinical significance in infants. METHODS: A retrospective analysis was conducted on the results of unexpected antibody identification tests performed on infants under one year of age at Asan Medical Center from 1999 to 2022. Patients' unexpected antibody identification test results and clinical information were investigated. The results of unexpected antibody identification and phenotype of each patient's mother were collected. RESULTS: 45 cases of antibody results were studied. 25 cases were found in infants under 4 months of age, and 18 cases (76%) were associated with hemolytic disease of the fetus and newborn (HDFN). The most common unexpected antibody in infants was anti-M (17 cases). There was one case of severe HDFN caused by anti-M. In 10 cases, anti-E and anti-c were found together, and 9 of these cases were associated with HDFN. There were four cases with a history of previous transfusion. CONCLUSIONS: Non-ABO antibodies found in infants showed a different pattern compared to adults. Interpreting unexpected antibody tests in infants, it is important to consider the clinical status of the infant and the test results of the mother, due to possibility of HDFN. To our knowledge, this is the first study to reveal the distribution and clinical significances of unexpected antibodies found in infants in Korea.

Investigation of variables affecting the immunogenicity of blood group antigens using a calculation formula.

Previous studies on the immunogenicity of blood group antigens have utilized a formula incorporating antigen frequencies and relative frequencies of unexpected antibodies to the corresponding antigens. This study was aimed at investigating other variables potentially affecting the estimation of immunogenicity using this formula. We examined the effect of multiple transfusions, as there are more chance for a recipient to receive repeated transfusions rather than only once; the effect of antigen density, which may vary depending on homozygote/heterozygote; and the effect of unreliability of the observed frequency of rare antibodies and antigens. For multiple transfusions, the expected antibody frequency increased as the number of transfusions increased. For antigen density, the immunogenicity was falsely low for the low-prevalence antigen, and this tendency intensified as the effect of antigen density increased. Expected antibody frequencies were significantly affected by the uncertainties caused by estimation of small numbers. This study showed that the effects of various factors on the immunogenicity of blood group antigens depended on the antigen frequency. Estimating the immunogenicity of blood group antigens requires acknowledging the diverse factors that can affect it and interpreting the findings with caution.

Transfusion thresholds: the need for a patient-centered approach in hematologic disorders that require chronic transfusion therapy.

Transfusion is an essential life-sustaining treatment for many patients. However, unnecessary transfusion has been reported to be related to worse patient outcomes. Further, owing to the recent pandemic, blood supply has been more challenging to maintain. Many studies have been conducted to elucidate the optimal transfusion threshold for many clinical conditions, and most suggested that a restrictive transfusion strategy has advantages over a liberal transfusion strategy. Hematologic disorders, which require chronic transfusion in many cases, have not been the main subjects of such studies, and only little evidence is available regarding the optimal transfusion threshold in these patients. According to several recent studies, a liberal transfusion strategy is preferable for patients with hematologic disorders due to their quality of life. A patient-centered approach is needed for proper management of hematologic disorders.

Chitosan polymer matrix-derived nanocomposite (CuS/NSC) for non-enzymatic electrochemical glucose sensor.

In this study, N and S co-doped chitosan polymer matrix-derived composite (CuS/NSC) was synthesized via a one-step hydrothermal technique using a low-cost copper complex of chitosan polymer. Cyclic voltammetry and chronoamperometry revealed excellent electrocatalytic performance. The glucose sensor exhibited a linear range of 160 µM to 11.76 mM, a low detection limit 2.72 µM and a sensitivity of 13.62 mA mM-1 cm-2 with an excellent linear response. Furthermore, the sensor also displayed selectivity for glucose over potential interfering agents and exhibited a satisfactory recovery percentage using real sample in human serum. The results demonstrate that, CuS/NSC is an efficient nanocomposite material for non-enzymatic glucose sensors and is applicable for glucose detection in biological fluids.

Outcome of ABO-Incompatible Kidney Transplantation According to ABO Type of Transfused Plasma: Comparative Analysis Between "Universal" AB and Donor-Type Plasma.

OBJECTIVE: We compared the clinical outcomes of recipients of ABO-incompatible (ABOi) kidney transplantation (KT) according to the blood group of the plasma transfused. MATERIALS AND METHODS: We retrospectively analyzed the data of 60 recipients of ABOi-KT with blood type O and A or B donors. Demographic and clinical characteristics were compared between 2 groups of recipients: 1 group received AB plasma regardless of the donor's blood type (n = 30), and the other group received donor-type plasma (n = 30). RESULTS: There were no significant differences between the groups in terms of demographic characteristics. Transfusion of donor-type plasma was noninferior to transfusion of type AB plasma in terms of both rejection-free survival and rejection rate (P = .455, P = .335). CONCLUSION: There was no significant prognostic difference between the 2 groups. In terms of blood supply and inventory management, we suggest that the blood group of the plasma should match the donor's type.

Perceptions of Heated Tobacco Products (HTPs) and Intention to Quit Among Adult Tobacco Users in Korea.

BACKGROUND: The popularity of heated tobacco products (HTPs) has been growing globally but, limited information exists on tobacco use behaviors and its impact on tobacco control. This study investigates awareness and perception of HTPs among tobacco users and whether perceptions of HTPs are associated with HTP use and intention to quit. METHODS: We invited 2,000 tobacco users aged 19-65 years with countrywide representation to an online survey in November 2018. Information on general characteristics, tobacco use behaviors, awareness and perception of HTPs, and intention to quit were gathered. Multinomial logistic regression analysis and ANCOVA were used for estimation of association and comparison. RESULTS: Among all tobacco users, 36.8% were classified as ever users, whereas 28.3% had used HTPs in the past 30 days, which was higher than expected. Users of liquid-based e-cigarettes (odds ratio [OR] 1.578; 95% confidence interval [CI], 1.210-2.056) and poly-product users (OR 2.029; 95% CI, 1.121-3.671) showed higher intention to quit within 1 month when compared to users of conventional cigarettes (CCs), whereas HTP users and dual product users did not. HTP users rated HTPs more favorably than CCs in terms of smoke, smell, harm, aid in quitting, design, and price than users of other products did (P-value < 0.001). CONCLUSION: We find that positive perception of HTPs following strategic marketing from tobacco companies could have contributed to a greater increase in HTP use than expected in Korea. However, HTPs might not be considered substitutes for CCs for quitting tobacco use because a significant proportion of dual product users reported a lower intention to quit.

Is Cryoprecipitate-Reduced Plasma an Efficacious Replacement Fluid for Therapeutic Plasma Exchange for Patients with Thrombotic Microangiopathy? A Single-Center Retrospective Experience.

OBJECTIVE: We designed a study to compare the efficacy of cryoprecipitate-reduced plasma (CRP) and fresh frozen plasma (FFP), at the level of individual sessions, for treating refractory thrombotic microangiopathy (TMA) with therapeutic plasma exchange (TPE). MATERIALS AND METHODS: Platelet counts (× 10³/µL) and lactate dehydrogenase (LD; IU/L) levels were measured before and after each session. We compared the mean-percentage and absolute changes in platelet count and LD after each TPE session. RESULTS: The data from 33 patients treated for TMA between 2009 and 2018 were collected for this study. Both absolute and percentage increases in the platelet count were statistically significant (P = .003 and P = .011, respectively) when CRP was used. However, when patients were divided into subgroups according to specific diagnosis, no significant differences were found among the groups, except in terms of the absolute platelet count increase in the thrombotic thrombocytopenic purpura group (P <.001). CONCLUSION: The platelet count increase was higher when patients received CRP than when they received FFP. We found that CRP may be a rescue option for patients with refractory TMA.

Infection of Brain Organoids and 2D Cortical Neurons with SARS-CoV-2 Pseudovirus.

Since the global outbreak of SARS-CoV-2 (COVID-19), infections of diverse human organs along with multiple symptoms continue to be reported. However, the susceptibility of the brain to SARS-CoV-2, and the mechanisms underlying neurological infection are still elusive. Here, we utilized human embryonic stem cell-derived brain organoids and monolayer cortical neurons to investigate infection of brain with pseudotyped SARS-CoV-2 viral particles. Spike-containing SARS-CoV-2 pseudovirus infected neural layers within brain organoids. The expression of ACE2, a host cell receptor for SARS-CoV-2, was sustained during the development of brain organoids, especially in the somas of mature neurons, while remaining rare in neural stem cells. However, pseudotyped SARS-CoV-2 was observed in the axon of neurons, which lack ACE2. Neural infectivity of SARS-CoV-2 pseudovirus did not increase in proportion to viral load, but only 10% of neurons were infected. Our findings demonstrate that brain organoids provide a useful model for investigating SARS-CoV-2 entry into the human brain and elucidating the susceptibility of the brain to SARS-CoV-2.

Facile synthesis of graphitic carbon-nitride supported antimony-doped tin oxide nanocomposite and its application for the adsorption of volatile organic compounds.

Antimony-doped tin oxide (ATO) nanoparticles with an average size of ~ 6 nm were prepared by co-precipitation and subsequent heat treatment. Graphitic carbon nitride (g-CN)/ATO hybrid nanocomposite was designed by the combination of thermally synthesized g-CN and ATO nanoparticles by ultrasonication. The materials were characterized using N2 adsorption/desorption (BET), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). A mixture of five volatile organic compounds (VOCs, chloroform, benzene, toluene, xylene and styrene) was used to compare the adsorption capacity of the samples. The adsorption capacity of ATO nanoparticles was improved by the addition of g-CN. Experimental data showed that, among the five VOCs, chloroform was the least adsorbed, regardless of the samples. The g-CN/ATO showed nearly three times greater adsorption capacity for the VOC mixture than pure ATO. The unchanged efficiency of VOC adsorption during cyclic use demonstrated the completely reversible adsorption and desorption behavior of the nanocomposite at room conditions. This economically and environmentally friendly material can be a practical solution for outdoor and indoor VOC removal.

Electrospinning Directly Synthesized Porous TiO2 Nanofibers Modified by Graphitic Carbon Nitride Sheets for Enhanced Photocatalytic Degradation Activity under Solar Light Irradiation.

We report a direct approach to the fabrication of a composite made of porous TiO2 nanofibers (NFs) and graphitic carbon nitride (g-C3N4) sheets, by means of an angled two-nozzle electrospinning combined with calcination process. Different wt % amounts of g-C3N4 particles in a polymer solution from one nozzle and TiO2 precursors containing the same polymer solution from another nozzle were electrospun and deposited on the collector. Structural characterizations confirm a well-defined morphology of the TiO2/g-C3N4 composite in which the TiO2 NFs are uniformly attached on the g-C3N4 sheet. This proper attachment of TiO2 NFs on the g-C3N4 sheets occurred during calcination. The prepared composites showed the enhanced photocatalytic activity over the photodegradation of rhodamine B and reactive black 5 under natural sunlight. Here, the synergistic effect between the g-C3N4 sheets and the TiO2 NFs having anisotropic properties enhanced the photogenerated electron-hole pair separation and migration, which was confirmed by the measurement of photoluminescence spectra, cyclic voltammograms, and electrochemical impedance spectra. The direct synthesis approach that is established here for such kinds of sheetlike structure and porous NFs composites could provide new insights for the design of high-performance energy conversion catalysts.

Cellulose reinforced nylon-6 nanofibrous membrane: Fabrication strategies, physicochemical characterizations, wicking properties and biomimetic mineralization.

The aim of the present study is to develop a facile, efficient approach to reinforce nylon 6 (N6) nanofibers with cellulose chains as well as to study the effect that cellulose regeneration has on the physicochemical properties of the composite fibers. Here, a cellulose acetate (CA) solution (17wt%) was prepared in formic acid and was blended with N6 solution (20%, prepared in formic acid and acetic acid) in various proportions, and the blended solutions were then electrospun to produce hybrid N6/CA nanofibers. Cellulose was regenerated in-situ in the fiber via alkaline saponification of the CA content of the hybrid fiber, leading to cellulose-reinforced N6 (N6/CL) nanofibers. Electron microscopy studies suggest that the fiber diameter and hence pore size gradually decreases as the mass composition of CA increases in the electrospinning solution. Cellulose regeneration showed noticeable change in the polymorphic behavior of N6, as observed in the XRD and IR spectra. The strong interaction of the hydroxyl group of cellulose with amide group of N6, mainly via hydrogen bonding, has a pronounced effect on the polymorphic behavior of N6. The γ-phase was dominant in pristine N6 and N6/CA fibers while α- phase was dominant in the N6/CL fibers. The surface wettability, wicking properties, and the tensile stress were greatly improved for N6/CL fibers compared to the corresponding N6/CA hybrid fibers. Results of DSC/TGA revealed that N6/CL fibers were more thermally stable than pristine N6 and N6/CA nanofibers. Furthermore, regeneration of cellulose chain improved the ability to nucleate bioactive calcium phosphate crystals in a simulated body fluid solution.

Three-dimensional cellulose sponge: Fabrication, characterization, biomimetic mineralization, and in vitro cell infiltration.

In this study, cellulose based scaffolds were produced by electrospinning of cellulose acetate (CA) solution followed by its saponification with NaOH/ethanol system for 24h. The resulting nonwoven cellulose mat was treated with sodium borohydride (SB) solution. In situ hydrolysis of SB solution into the pores of the membrane produced hydrogen gas resulting a three-dimensional (3D) cellulose sponge. SEM images demonstrated an open porous and loosely packed fibrous mesh compared to the tightly packed single-layered structure of the conventional electrospun membrane. 3D cellulose sponge showed admirable ability to nucleate bioactive calcium phosphate (Ca-P) crystals in simulated body fluid (SBF) solution. SEM-EDX and X-ray diffraction studies revealed that the minerals deposited on the nanofibers have the nonstoichiometric composition similar to that of hydroxyapatite, the mineralized component of the bone. 3D cellulose sponge exhibited the better cell infiltration, spreading and proliferation compared to 2D cellulose mat. Therefore, a facile fabrication of 3D cellulose sponge with improved mineralization represents an innovative strategy for the bone tissue engineering applications.

Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial.

BACKGROUND: Currently, metastatic renal cell carcinoma is treated with sequential single agents targeting VEGF or mTOR. Here, we aimed to assess lenvatinib, everolimus, or their combination as second-line treatment in patients with metastatic renal cell carcinoma. METHODS: We did a randomised, phase 2, open-label, multicentre trial at 37 centres in five countries and enrolled patients with advanced or metastatic, clear-cell, renal cell carcinoma. We included patients who had received treatment with a VEGF-targeted therapy and progressed on or within 9 months of stopping that agent. Patients were randomised via an interactive voice response system in a 1:1:1 ratio to either lenvatinib (24 mg/day), everolimus (10 mg/day), or lenvatinib plus everolimus (18 mg/day and 5 mg/day, respectively) administered orally in continuous 28-day cycles until disease progression or unacceptable toxic effects. The randomisation procedure dynamically minimised imbalances between treatment groups for the stratification factors haemoglobin and corrected serum calcium. The primary objective was progression-free survival in the intention-to-treat population. This study is closed to enrolment but patients' treatment and follow-up is ongoing. This study is registered with ClinicalTrials.gov, number NCT01136733. FINDINGS: Between March 16, 2012, and June 19, 2013, 153 patients were randomly allocated to receive either the combination of lenvatinib plus everolimus (n=51), single-agent lenvatinib (n=52), or single-agent everolimus (n=50). Lenvatinib plus everolimus significantly prolonged progression-free survival compared with everolimus alone (median 14·6 months [95% CI 5·9-20·1] vs 5·5 months [3·5-7·1]; hazard ratio [HR] 0·40, 95% CI 0·24-0·68; p=0·0005), but not compared with lenvatinib alone (7·4 months [95% CI 5·6-10·2]; HR 0·66, 95% CI 0·30-1·10; p=0·12). Single-agent lenvatinib significantly prolonged progression-free survival compared with everolimus alone (HR 0·61, 95% CI 0·38-0·98; p=0·048). Grade 3 and 4 events occurred in fewer patients allocated single-agent everolimus (25 [50%]) compared with those assigned lenvatinib alone (41 [79%]) or lenvatinib plus everolimus (36 [71%]). The most common grade 3 or 4 treatment-emergent adverse event in patients allocated lenvatinib plus everolimus was diarrhoea (ten [20%]), in those assigned single-agent lenvatinib it was proteinuria (ten [19%]), and in those assigned single-agent everolimus it was anaemia (six [12%]). Two deaths were deemed related to study drug, one cerebral haemorrhage in the lenvatinib plus everolimus group and one myocardial infarction with single-agent lenvatinib. INTERPRETATION: Lenvatinib plus everolimus and lenvatinib alone resulted in a progression-free survival benefit for patients with metastatic renal cell carcinoma who have progressed after one previous VEGF-targeted therapy. Further study of lenvatinib is warranted in patients with metastatic renal cell carcinoma. FUNDING: Eisai Inc.

In Situ Generation of Cellulose Nanocrystals in Polycaprolactone Nanofibers: Effects on Crystallinity, Mechanical Strength, Biocompatibility, and Biomimetic Mineralization.

Post-electrospinning treatment is a facile process to improve the properties of electrospun nanofibers for various applications. This technique is commonly used when direct electrospinning is not a suitable option to fabricate a nonwoven membrane of the desired polymer in a preferred morphology. In this study, a representative natural-synthetic hybrid of cellulose acetate (CA) and polycaprolactone (PCL) in different ratios was fabricated using an electrospinning process, and CA in the hybrid fiber was transformed into cellulose (CL) by post-electrospinning treatment via alkaline saponification. Scanning electron microscopy was employed to study the effects of polymer composition and subsequent saponification on the morphology of the nanofibers. Increasing the PCL content in the PCL/CA blend solution caused a gradual decrease in viscosity, resulting in smoother and more uniform fibers. The saponification of fibers lead to pronounced changes in the physicochemical properties. The crystallinity of the PCL in the composite fiber was varied according to the composition of the component polymers. The water contact angle was considerably decreased (from 124° to less than 20°), and the mechanical properties were greatly enhanced (Young's Modulus was improved by ≈20-30 fold, tensile strength by 3-4 fold, and tensile stress by ≈2-4 fold) compared to those of PCL and PCL/CA membranes. Regeneration of cellulose chains in the nanofibers increased the number of hydroxyl groups, which increased the hydrogen bonding, thereby improving the mechanical properties and wettability of the composite nanofibers. The improved wettability and presence of surface functional groups enhanced the ability to nucleate bioactive calcium phosphate crystals throughout the matrix when exposed to a simulated body fluid solution. Experimental results of cell viability assay, confocal microscopy, and scanning electron microscopy imaging showed that the fabricated nanofibrous membranes have excellent ability for MC3T3-E1 cell proliferation and growth. Given the versatility and widespread use of cellulose-synthetic hybrid systems in the construction of tissue-engineered scaffolds, this work provides a novel strategy to fabricate the biopolymer-based materials for applications in tissue engineering and regenerative medicine.

Immobilization of TiO2 nanofibers on reduced graphene sheets: Novel strategy in electrospinning.

A simple and efficient approach is developed to immobilize TiO2 nanofibers onto reduced graphene oxide (RGO) sheets. Here, TiO2 nanofiber-intercalated RGO sheets are readily produced by two-step procedure involving the use of electrospinning process to fabricate TiO2 precursor containing polymeric fibers on the surface of GO sheets, followed by simultaneous TiO2 nanofibers formation and GO reduction by calcinations. GO sheets deposited on the collector during electrospinning/electrospray can act as substrate on to which TiO2 precursor containing polymer nanofibers can be deposited which give TiO2 NFs doped RGO sheets on calcinations. Formation of corrugated structure cavities of graphene sheets decorated with TiO2 nanofibers on their surface demonstrates that our method constitutes an alternative top-down strategy toward fabricating verities of nanofiber-decorated graphene sheets. It was found that the synthesized TiO2/RGO composite revealed a remarkable increased in photocatalytic activity compared to pristine TiO2 nanofibers. Therefore, engineering of TiO2 nanofiber-intercalated RGO sheets using proposed facile technique can be considered a promising method for catalytic and other applications.

In-situ deposition of silver-iron oxide nanoparticles on the surface of fly ash for water purification.

In this study, a fly ash based composite, Ag-iron oxide/fly ash, was synthesized via a facile one-pot hydrothermal process using fly ash, ferrous chloride, and silver nitrate as precursors. Field emission scanning electron microscopy (FE-SEM), EDX, transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infra-red spectroscopy (FTIR), Photoluminescence (PL) and Brunauer-Emmett-Teller (BET) surface area measurement confirmed the formation of composite particle. FA provided a suitable surface for the in-situ deposition of Fe3O4 and Ag NPs during hydrothermal treatment. As a result, the particle size of Fe3O4 and Ag NPs was sufficiently decreased, and the surface area of the NPs as well as, a whole matrix was increased. The antimicrobial activity of the composite was accessed by Escherichia coli inhibition assay. Lead(II) ion adsorption efficiency of the composite was analyzed from a series of batch adsorption experiments (the effects of concentration, contact time, pH and adsorbent dose on the adsorption of Pb(II) ion from aqueous solution). Results indicated that as-synthesized composite has high antibacterial capacity, and the metal ions uptake efficiency compared to fly ash particle. Furthermore, incorporation Fe3O4 NPs onto the fly ash make it easily separable from a reaction system using an external magnet. The composite synthesis protocol is a simple method that utilizes a readily available industrial byproduct to produce a unique composite for environmental remediation.