Infection Is Not Associated With Plasma or Cryoprecipitate Transfusion Volumes in Trauma: A Retrospective Study Using the National Trauma Data Bank.

Background: Packed red blood cell (PRBC) transfusion has been shown to increase nosocomial infection risk in the injured population; however, the post-traumatic infectious risk profiles of non-PRBC blood products are less clear. We hypothesized that plasma (fresh frozen plasma [FFP]), platelet (PLT), and cryoprecipitate administration would not be associated with increased rates of nosocomial infections. Patients and Methods: We performed a retrospective, matched, case-control study utilizing the American College of Surgeons National Trauma Data Bank data for 2019. We included all patients who received any volume of PRBC within four hours of presentation. Our outcome of interest was any infection. Controls were matched to cases using individual matching with a desired 1:3 case:control ratio. Bivariable analysis according to infection status, and multivariable logistic regression modeling the development of infection were then performed upon the matched data. Results: A total of 1,563 infectious cases were matched to 3,920 non-infectious controls. First four-hour transfusion volumes for FFP, PLT, and cryoprecipitate in the infection group exceeded those in the control group. The first four-hour FFP transfusion volume (per unit odds ratio [OR], 1.02; 95% confidence interval [CI], 0.99-1.04; p = 0.28) and cryoprecipitate transfusion volume (per unit OR, 1.01; 95% CI, 0.99-1.02; p = 0.43) were similar in cases and controls whereas PLT transfusion volume (per unit OR, 0.92; 95% CI, 0.86-0.98; p = 0.01) was lower in cases of infection than in controls. Conclusions: Fresh frozen plasma, PLT, and cryoprecipitate transfusion volumes were not independent risk factors for the development of nosocomial infection in a trauma population. PLT transfusion volume was associated with less infection.

Comparison of Whole Blood and Plasma for Monitoring Cytomegalovirus and Epstein-Barr Virus.

Monitoring Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection after transplantation is recommended to enable preemptive therapy. However, the most suitable sample type remains unclear. Patients who underwent hematopoietic stem cell or liver transplantation were included in this study. Viral loads in sequential whole-blood and plasma samples were retrospectively analyzed. EBV DNA was detected more frequently in whole blood (55%) than in plasma (18%). The detection rate of CMV DNA was similar between the two sample types. The correlation of viral loads between the two sample types were 0.515 and 0.688 for EBV and CMV, respectively. Among paired samples in which EBV DNA was detected in whole blood, the plasma EBV detection rate was significantly higher in patients who underwent hematopoietic stem cell transplantation than in those who underwent liver transplantation. The viral DNA load in whole blood and plasma showed similar trends. The EBV detection rate was higher in whole blood, and a high correlation was observed between CMV DNA loads and whole blood and plasma. These results indicate that whole blood is more sensitive for monitoring both EBV and CMV, whereas plasma is a potential alternative sample for monitoring CMV.

Nutritional, molecular, and functional properties of a novel enzymatically hydrolyzed porcine plasma product.

In the present study, an enzymatically hydrolyzed porcine plasma (EHPP) was nutritionally and molecularly characterized. EHPP molecular characterization showed, in contrast to spray-dried plasma (SDP), many peptides with relative molecular masses (Mr) below 8,000, constituting 73% of the protein relative abundance. IIAPPER, a well-known bioactive peptide with anti-inflammatory and antioxidant properties, was identified. In vivo functionality of EHPP was tested in C. elegans and two different mouse models of intestinal inflammation. In C. elegans subjected to lipopolysaccharide exposure, EHPP displayed a substantial anti-inflammatory effect, enhancing survival and motility by 40% and 21.5%, respectively. Similarly, in mice challenged with Staphylococcus aureus enterotoxin B or Escherichia coli O42, EHPP and SDP supplementation (8%) increased body weight and average daily gain while reducing the percentage of regulatory Th lymphocytes. Furthermore, both products mitigated the increase of pro-inflammatory cytokines expression associated with these challenged mouse models. In contrast, some significant differences were observed in markers such as Il-6 and Tnf-α, suggesting that the products may present different action mechanisms. In conclusion, EHPP demonstrated similar beneficial health effects to SDP, potentially attributable to the immunomodulatory and antioxidant activity of its characteristic low Mr bioactive peptides.

Plasma Redox Balance in Advanced-Maternal-Age Pregnant Women and Effects of Plasma on Umbilical Cord Mesenchymal Stem Cells.

Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal-fetal complications with possible repercussions even in the long term. Here, we analyzed the changes in plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timings of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that, throughout pregnancy until after delivery in patients, the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients. They could have clinical relevance for the prevention of complications related to AMA pregnancy.

Maze-solving in a plasma system based on functional analogies to reinforcement-learning model.

Maze-solving is a classical mathematical task, and is recently analogously achieved using various eccentric media and devices, such as living tissues, chemotaxis, and memristors. Plasma generated in a labyrinth of narrow channels can also play a role as a route finder to the exit. In this study, we experimentally observe the function of maze-route findings in a plasma system based on a mixed discharge scheme of direct-current (DC) volume mode and alternative-current (AC) surface dielectric-barrier discharge, and computationally generalize this function in a reinforcement-learning model. In our plasma system, we install two electrodes at the entry and the exit in a square lattice configuration of narrow channels whose cross section is 1×1 mm2 with the total length around ten centimeters. Visible emissions in low-pressure Ar gas are observed after plasma ignition, and the plasma starting from a given entry location reaches the exit as the discharge voltage increases, whose route converging level is quantified by Shannon entropy. A similar short-path route is reproduced in a reinforcement-learning model in which electric potentials through the discharge voltage is replaced by rewards with positive and negative sign or polarity. The model is not rigorous numerical representation of plasma simulation, but it shares common points with the experiments along with a rough sketch of underlying processes (charges in experiments and rewards in modelling). This finding indicates that a plasma-channel network works in an analog computing function similar to a reinforcement-learning algorithm slightly modified in this study.

Convalescent plasma transfusion for immunocompromised viremic patients with COVID-19: A retrospective multicenter study.

This study aims to assess the safety, virological, and clinical outcomes of convalescent plasma transfusion (CPT) in immunocompromised patients hospitalized for coronavirus disease 2019 (COVID-19). We conducted a retrospective multicenter cohort study that included all immunosuppressed patients with COVID-19 and RNAemia from May 2020 to March 2023 treated with CPT. We included 81 patients with hematological malignancies (HM), transplants, or autoimmune diseases (69% treated with anti-CD20). Sixty patients (74%) were vaccinated, and 14 had pre-CPT serology >264 BAU/mL. The median delay between symptom onset and CPT was 23 days [13-31]. At D7 post-CPT, plasma PCR was negative in 43/64 patients (67.2%), and serology became positive in 25/30 patients (82%). Post-CPT positive serology was associated with RNAemia negativity (p < 0.001). The overall mortality rate at D28 was 26%, being higher in patients with non-B-cell HM (62%) than with B-cell HM (25%) or with no HM (11%) (p = 0.02). Patients receiving anti-CD20 without chemotherapy had the lowest mortality rate (8%). Positive RNAemia at D7 was associated with mortality at D28 in univariate analysis (HR: 3.05 [1.14-8.19]). Eight patients had adverse events, two of which were severe but transient. Our findings suggest that CPT can abolish RNAemia and ameliorate the clinical course in immunocompromised patients with COVID-19.

A Case of Pregnancy-Induced Hereditary Thrombotic Thrombocytopenic Purpura Complicated by Cerebral Vasospasm.

BACKGROUND: The aim was to explore the treatment of a case of congenital thrombotic thrombocytopenic purpura induced by pregnancy complicated with cerebral vasospasm. METHODS: We present a case study of congenital TTP where disease onset occurred during two separate pregnancies. Interestingly, the disease course exhibited distinct differences on each occasion. Additionally, following plasma transfusion therapy, there was a transient occurrence of cerebral vasospasm. RESULTS: In this case, ADAMTS13 levels reached their lowest point three days after delivery during the first pregnancy, triggering morbidity. Remarkably, a single plasma transfusion of 400 mL sufficed for the patient's recovery. Nonetheless, a recurrence of symptoms transpired during her second pregnancy at 24 weeks of gestation. Plasma transfusions were administered during and after delivery. Sudden convulsions developed. ADAMTS13 ac-tivity returned to normal, but cranial MRA revealed constrictions in the intracranial segments of both vertebral arteries, the basilar artery, and the lumen of the anterior, middle, and posterior cerebral arteries. A subsequent cranial MRA conducted a month later showed no lumen stenosis, indicating spontaneous recovery. CONCLUSIONS: These findings highlight the importance of careful consideration when administering plasma transfusions in congenital TTP during pregnancy. Moreover, the development of novel therapeutic approaches such as recombinant ADAMTS13 is crucial for minimizing complications and optimizing patient care.

Identification of HIST1H2BH as the hub gene associated with multiple myeloma using integrated bioinformatics analysis.

OBJECTIVES: Identifying the specific biomarkers and molecular signatures of MM might provide novel evidence for MM prognosis and targeted therapy. METHODS: Bioinformatic analyses were performed through GEO and TCGA datasets. The differential expression of HIST1H2BH in MM sample was validated by the qRT-PCR. And the CCK-8 assay was performed to detect the proliferation activity of HIST1H2BH on MM cell lines. RESULTS: A total of 793 DEGs were identified between bone marrow plasma cells from newly diagnosed myeloma and normal donors in GSE6477. Among them, four vital genes (HIST1H2AC, HIST1H2BH, CCND1 and TCF7L2) modeling were constructed. The increased HIST1H2BH expression was correlated with worse survival of MM based on TCGA datasets. The transcriptional expression of HIST1H2BH was significantly up-regulated in primary MM patients. And knockdown HIST1H2BH decreased the proliferation of MM cell lines. CONCLUSIONS: We have identified up-regulated HIST1H2BH in MM patients associated with poor prognosis using integrated bioinformatical methods.

Cerebrospinal fluid viral escape in HIV patients on antiretroviral therapy: A systematic review of reported cases.

Cerebrospinal fluid (CSF) viral escape rarely occurs when HIV is detected in the CSF, while it is undetectable in the blood plasma or detectable in CSF at levels that exceed those in the blood plasma. We conducted this review to comprehensively synthesise its clinical presentation, diagnosis, management strategies and treatment outcomes. A review registered with PROSPERO (CRD42023475311) searched evidence across PubMed/MEDLINE, Embase, Web of Science, Scopus, and Google Scholar to gather articles (case reports/series) that report on CSF viral escape in people living with HIV (PLHIV) on antiretroviral therapy (ART). The quality of studies was assessed based on the domains of selection, ascertainment, causality, and reporting. A systematic search identified 493 articles and 27 studies that include 21 case reports, and six case series were involved in the review. The studies reported 62 cases of CSF viral escape in PLHIV. The majority were men (66.67%), with a median age of 43 (range: 28-73) years. Approximately, 31 distinct symptoms were documented, mostly being cognitive dysfunction, gait abnormalities, and tremors (12.51%). Diagnosis involved blood and CSF analysis, magnetic resonance imaging, and neuropsychological assessments. Over 36 ART regimens were employed, with a focus on ART intensification; almost one-third of the regimens contained Raltegravir (integrase strand transfer inhibitor). The outcomes showed 64.49% full recovery, 30.16% partial recovery, and 4.76% died. When neuropsychological symptoms manifest in PLHIV, monitoring for CSF viral escape is essential, regardless of plasma viral suppression. Personalised treatment strategies, particularly ART intensification, are strongly advised for optimising treatment outcomes in PLHIV diagnosed with CSF HIV escape.

Specific Binding of Alzheimer's Aß Peptides to Extracellular Vesicles.

Alzheimer's disease (AD) is the fifth leading cause of death among adults aged 65 and older, yet the onset and progression of the disease is poorly understood. What is known is that the presence of amyloid, particularly polymerized Aß42, defines when people are on the AD continuum. Interestingly, as AD progresses, less Aß42 is detectable in the plasma, a phenomenon thought to result from Aß becoming more aggregated in the brain and less Aß42 and Aß40 being transported from the brain to the plasma via the CSF. We propose that extracellular vesicles (EVs) play a role in this transport. EVs are found in bodily fluids such as blood, urine, and cerebrospinal fluid and carry diverse "cargos" of bioactive molecules (e.g., proteins, nucleic acids, lipids, metabolites) that dynamically reflect changes in the cells from which they are secreted. While Aß42 and Aß40 have been reported to be present in EVs, it is not known whether this interaction is specific for these peptides and thus whether amyloid-carrying EVs play a role in AD and/or serve as brain-specific biomarkers of the AD process. To determine if there is a specific interaction between Aß and EVs, we used isothermal titration calorimetry (ITC) and discovered that Aß42 and Aß40 bind to EVs in a manner that is sequence specific, saturable, and endothermic. In addition, Aß incubation with EVs overnight yielded larger amounts of bound Aß peptide that was fibrillar in structure. These findings point to a specific amyloid-EV interaction, a potential role for EVs in the transport of amyloid from the brain to the blood, and a role for this amyloid pool in the AD process.

[Congenital thrombotic thrombocytopenic purpura diagnosed in adulthood after repeated thrombocytopenia since neonatal period].

A 27-year-old woman was diagnosed with idiopathic thrombocytopenic purpura in the neonatal period, and was admitted to our hospital after presenting with impaired consciousness, purpura, nausea and vomiting, with a platelet count of 10×109/l. Congenital thrombotic thrombocytopenic purpura (cTTP) was suspected on the basis of recurrent thrombocytopenia and impaired consciousness, so tests for ADAMTS13 activity and inhibitor were performed. ADAMTS13 activity was severely decreased, ADAMTS13 inhibitor was negative, and platelet count increased after transfusion of fresh frozen plasma. These findings and the results of genetic testing done on all family members led to a diagnosis of cTTP. cTTP requires differential diagnosis even in adults. If a patient diagnosed with ITP in childhood has a history or findings that suggest cTTP during follow-up observation, it is necessary to actively consider ADAMTS13 testing.

TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma.

Comprehensive expression quantitative trait loci studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated loci in a tissue-specific manner. Compared to gene expressions, proteins more directly affect various biological processes, often dysregulated in disease, and are important drug targets. We previously performed and identified tissue-specific protein quantitative trait loci in brain, cerebrospinal fluid, and plasma. We now enhance this work by analyzing more proteins (1,300 versus 1,079) and an almost twofold increase in high quality imputed genetic variants (8.4 million versus 4.4 million) by using TOPMed reference panel. We identified 38 genomic regions associated with 43 proteins in brain, 150 regions associated with 247 proteins in cerebrospinal fluid, and 95 regions associated with 145 proteins in plasma. Compared to our previous study, this study newly identified 12 loci in brain, 30 loci in cerebrospinal fluid, and 22 loci in plasma. Our improved genomic atlas uncovers the genetic control of protein regulation across multiple tissues. These resources are accessible through the Online Neurodegenerative Trait Integrative Multi-Omics Explorer for use by the scientific community.

[Feasibility Analysis of Establishing Combat Readiness Blood Bank Based on Low Titer Group O Whole Blood and Group A Plasma].

OBJECTIVE: To explore the feasibility of establishing combat readiness blood bank with low titer group O whole blood and group A plasma. METHODS: The Galileo automatic blood analyzer was used to detect the titers of IgM anti-A and anti-B antibodies in the samples of group O blood donors and IgM anti-B titer in the samples of group A blood donors. Group O blood donors with antibody titers below 128 were selected and included in the mobile blood bank for combat readiness, group A plasma with anti-B titer lower than 128 and group O whole blood with antibody titers below 128 were included in the combat readiness entity blood bank. RESULTS: A total of 1 452 group O blood donors were selected, and the anti-A/B antibody titers were detected. Both antibody titers were distributed below 512, and both peak values of sample distribution were at titer 4. The proportion of samples with titers>128 for both antibodies was relatively low. There was a significant positive correlation between the titers of the two antibodies (r =0.383), and the proportion of samples with IgM anti-A titer higher than IgM anti-B titer was relatively high. 1 335(91.94%) group O blood donors with IgM anti-A and anti-B antibody titers <128 could be included in the mobile blood bank. The anti-B titer of group A blood was detected in 512 cases and the results showed that as the antibody titer increased, the proportion of blood donors gradually decreased. 99.8% of group A blood donors had anti-B antibody titer less than 128, and only one case did not meet the inclusion criteria. CONCLUSION: The proportion of group O blood donors whose whole blood meet the low antibody titer standard is high, and almost all plasma of group A blood donors meet the low titer standard, which improves the blood supply rate in emergencies.

[Analysis of Plasma Metabolic Profile in Children with Transfusion-Dependent Thalassemia].

OBJECTIVE: To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia (TDT), and reveal the changes of metabolic pattern in children with TDT. METHODS: 23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected, and 11 healthy children who underwent physical examination during the same period were selected as the control group. The routine indexes between children with TDT and the control group were compared, and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry. An OPLS-DA model was established to perform differential analysis on the detected metabolites, and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites. RESULTS: The results of routine testing showed that the indexes of ferritin, bilirubin, total bile acid, glucose and triglycerides in children with TDT were significantly higher than those in healthy controls, while hemoglobin and total cholesterol were significantly lower (all P <0.05). However there was no significant difference in lactate dehydrogenase between the two groups (P >0.05). Compared with the control group, 190 differential metabolites (VIP>1) were identified in TDT children. Among them, 168 compounds such as arginine, proline and glycocholic acid were significantly increased, while the other 22 compounds such as myristic acid, eleostearic acid, palmitic acid and linoleic acid were significantly decreased. The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism. CONCLUSION: The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group. This finding is helpful to optimize the treatment choice for children with TDT, and provides a new idea for clinical treatment.

Quality assurance of add-on testing in plasma samples: stability limit for 29 biochemical analytes.

Introduction: Clinical laboratories should guarantee sample stability in specific storage conditions for further analysis. The aim of this study is to evaluate the stability of plasma samples under refrigeration for 29 common biochemical analytes usually ordered within an emergency context, in order to determine the maximum allowable period for conducting add-on testing. Materials and methods: A total of 20 patient samples were collected in lithium heparin tubes without gel separator. All analyses were performed using Alinity systems (Abbott Laboratories, Abbott Park, USA) and samples were stored at 2-8 °C. Measurements were conducted in primary plasma tubes at specific time points up to 48 hours, with an additional stability study in plasma aliquots extending the time storage up to 96 hours. The stability limit was estimated considering the total limit of change criteria. Results: Of the 29 studied parameters, 24 demonstrated stabilities within a 48-hour storage period in primary plasma tubes. However, five analytes: aspartate aminotransferase, glucose, lactate dehydrogenase, inorganic phosphate and potassium evidenced instability at different time points (7.9 hours, 2.7 hours, 2.9 hours, 6.2 hours and 4.7 hours, respectively). The stability study in plasma aliquots showed that all parameters remained stable for 96 hours, except lactate dehydrogenase, with a stability limit of 63 hours. Conclusions: A reduced stability of primary plasma samples was observed for five common biochemical analytes ordered in an emergency context. To ensure the quality of add-on testing for these samples, plasma aliquots provide stability for a longer period.

Comparison of reversed-phase, hydrophilic interaction, and porous graphitic carbon chromatography columns for an untargeted toxicometabolomics study in pooled human liver microsomes, rat urine, and rat plasma.

INTRODUCTION: Untargeted metabolomics studies are expected to cover a wide range of compound classes with high chemical diversity and complexity. Thus, optimizing (pre-)analytical parameters such as the analytical liquid chromatography (LC) column is crucial and the selection of the column depends primarily on the study purpose. OBJECTIVES: The current investigation aimed to compare six different analytical columns. First, by comparing the chromatographic resolution of selected compounds. Second, on the outcome of an untargeted toxicometabolomics study using pooled human liver microsomes (pHLM), rat plasma, and rat urine as matrices. METHODS: Separation and analysis were performed using three different reversed-phase (Phenyl-Hexyl, BEH C18, and Gold C18), two hydrophilic interaction chromatography (HILIC) (ammonium-sulfonic acid and sulfobetaine), and one porous graphitic carbon (PGC) columns coupled to high-resolution mass spectrometry (HRMS). Their impact was evaluated based on the column performance and the size of feature count, amongst others. RESULTS: All three reversed-phase columns showed a similar performance, whereas the PGC column was superior to both HILIC columns at least for polar compounds. Comparing the size of feature count across all datasets, most features were detected using the Phenyl-Hexyl or sulfobetaine column. Considering the matrices, most significant features were detected in urine and pHLM after using the sulfobetaine and in plasma after using the ammonium-sulfonic acid column. CONCLUSION: The results underline that the outcome of this untargeted toxicometabolomic study LC-HRMS metabolomic study was highly influenced by the analytical column, with the Phenyl-Hexyl or sulfobetaine column being the most suitable. However, column selection may also depend on the investigated compounds as well as on the investigated matrix.

Improving the mechanical and biological functions of cell sheet constructs: The interplay of human-derived periodontal ligament stem cells, endothelial cells and plasma rich in growth factors.

OBJECTIVE: The aim of this study was to produce and characterize triple-layered cell sheet constructs with varying cell compositions combined or not with the fibrin membrane scaffold obtained by the technology of Plasma Rich in Growth Factors (mPRGF). MATERIALS AND METHODS: Human primary cultures of periodontal ligament stem cells (hPDLSCs) were isolated, and their stemness nature was evaluated. Three types of triple-layered composite constructs were generated, composed solely of hPDLSCs or combined with human umbilical vein endothelial cells (HUVECs), either as a sandwiched endothelial layer or as coculture sheets of both cell phenotypes. These three triple-layered constructs were also manufactured using mPRGF as cell sheets' support. Necrosis, glucose consumption, secretion of extracellular matrix proteins and synthesis of proangiogenic factors were determined. Histological evaluations and proteomic analyses were also performed. RESULTS: The inclusion of HUVECs did not clearly improve the properties of the multilayered constructs and yet hindered their optimal conformation. The presence of mPRGF prevented the shrinkage of cell sheets, stimulated the metabolic activity and increased the matrix synthesis. At the proteome level, mPRGF conferred a dramatic advantage to the hPDLSC constructs in their ability to provide a suitable environment for tissue regeneration by inducing the expression of proteins necessary for bone morphogenesis and cellular proliferation. CONCLUSIONS: hPDLSCs' triple-layer construct onto mPRGF emerges as the optimal structure for its use in regenerative therapeutics. CLINICAL RELEVANCE: These results suggest the suitability of mPRGF as a promising tool to support cell sheet formation by improving their handling and biological functions.