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Red blood cell (RBC) metabolic reprogramming upon exposure to high altitude contributes to physiological human adaptations to hypoxia, a multifaceted process critical to health and disease. To delve into the molecular underpinnings of this phenomenon, first, we performed a multi-omics analysis of RBCs from six lowlanders after exposure to high-altitude hypoxia, with longitudinal sampling at baseline, upon ascent to 5,100 m and descent to sea level. Results highlighted an association between erythrocyte levels of 2,3-bisphosphoglycerate (BPG), an allosteric regulator of hemoglobin that favors oxygen off-loading in the face of hypoxia, and expression levels of the Rhesus blood group RHCE protein. We then expanded on these findings by measuring BPG in RBCs from 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. These data informed a genome-wide association study using BPG levels as a quantitative trait, which identified genetic polymorphisms in the region coding for the Rhesus blood group RHCE as critical determinants of BPG levels in erythrocytes from healthy human volunteers. Mechanistically, we suggest that the Rh group complex, which participates in the exchange of ammonium with the extracellular compartment, may contribute to intracellular alkalinization, thus favoring BPG mutase activity.

Decompensated cirrhotic patients experience severely increased intestinal permeability and bacterial translocation. Thus, autologous blood salvaged during deceased donor liver transplantation (DDLT) may be contaminated with enteric bacteria. We aimed to evaluate bacterial contamination of autologous blood salvaged during DDLT and its association with post-transplant bacteremia. In 30 patients undergoing DDLT, bacterial culture was performed in salvaged autologous blood samples: one before graft reperfusion (non-leukoreduced) and two after graft reperfusion (non-leukoreduced and leukoreduced). The primary outcome was bacterial contamination of salvaged autologous blood. Seven of 30 patients (23.3%) were positive for bacteria (3 enteric/4 non-enteric) before graft reperfusion while 11 patients (36.7%) were positive (5 enteric/6 non-enteric) after graft reperfusion. Six of 7 patients who were positive for bacteria before graft reperfusion were positive after graft reperfusion with the same bacteria. Only 4 of 11 contaminated blood samples were converted to negative after leukoreduction. Post-transplant bacteremia risk was insignificantly greater in patients who received autologous blood with bacteria than in patients without bacteria (30.0% vs. 5.0%, P = 0.06). We found contamination of salvaged autologous blood with enteric bacteria throughout DDLT and incomplete performance of leukoreduction, indicating high bacterial load. The potential association between contaminated autotransfusion and post-transplant bacteremia warrants further validation in a larger prospective study. Clinical trial notation: This study was registered at the Clinical Research Information Service (CRiS; https://cris.nih.go.kr; No. KCT0007223; principal registration investigator: Sangbin Han, date of registration: April 25, 2022). [ABSTRACT FROM AUTHOR]

Red blood cells respond to fluctuations in blood plasma pH by changing the rate of biochemical and physical processes that affect the specific functions of individual cells. This study aimed to analyze the effect of pH changes on red blood cell morphology and structure. The findings revealed that an increase or decrease in pH above or below the physiological level of pH 7.4 results in the transformation of discocytes into echinocytes and causes significant alterations in the membrane, including its roughness, cytoskeleton structure, and the cell's elastic modulus. Furthermore, the study shown a strong connection between critical acidosis and alkalosis with increased intracellular reactive oxygen species production. [ABSTRACT FROM AUTHOR]

• We screened the expression profiles of miRNAs in the late stage of RBC preservation. • We identified miRNAs that changed during different storage times as well as potential target genes. • We predicted the potential regulatory effects of these differential miRNAs through bioinformatics. To detect the differentially expressed regulatory miRNAs in the late stage of red blood cell (RBC) preservation and predict their roles. Suspended RBCs with different storage periods of 35 day, 42 day, and 50 day were collected for routine blood tests, RNA extraction, and preparation of small RNA sequencing libraries. The constructed libraries were sequenced and the biological functions of differential miRNAs in RBCs in the late storage were analyzed by bioinformatics. Routine indicators of RBCs in the late stage were not significantly affected by preservation time. The Pearson correlation analysis performing on RBC miRNAs with different storage days revealed that RBC miRNAs changed with the increase of storage days. RBC miRNAs from day 35 (D35), day 42 (D42) and day 50 (D50) showed significant differences (P < 0.05). Compared RBC miRNAs from D42 with these from D35, there were 690 up-regulated miRNAs and 82 down-regulated miRNAs; compared RBC miRNAs from D50 with these from D35, there were 638 up-regulated miRNAs and 123 down-regulated miRNAs; compared RBC miRNAs from D42 with these from D50, there were 271 up-regulated miRNAs and 515 down-regulated miRNAs. GO enrichment analysis of target genes of differential miRNAs were mainly involved in cell metabolism, biosynthesis, protein modification, gene expression and transcriptional regulation of biological processes. KEGG pathway enrichment analysis of miRNA target genes showed that differential miRNA target genes were closely related to pathways in cancer. MiRNAs were differentially expressed in the late stage of RBC preservation, and may be involved in various biological processes, especially cancer. [ABSTRACT FROM AUTHOR]

Background: Erythrocytes are susceptible to oxidative stress throughout their lifespan. While compounds like vitamin C can help mitigate oxidative stress, the exploration of natural herbal products continues to be a compelling area of research. To examine the impact of subfractions derived from acidified chloroform fractions of fenugreek (Trigonella foenum-graecum L.) on red blood cells in the presence of H2O2 as an oxidant, we assessed the factors associated with erythrocyte aging and oxidative stress. Methods: The maceration technique was employed for extracting fenugreek seeds. Through chromatography, a total of 12 subfractions were isolated from the acidified chloroform extract of fenugreek seeds. Following an initial assessment, four subfractions exhibiting lower erythrocyte toxicity were chosen for further investigation. The objective was to evaluate their impact on erythrocyte aging by measuring the levels of phosphatidylserine (PS), sialic acid, CD47 on the erythrocyte surface, as well as oxidative stress biomarkers. The obtained results were presented as mean ± standard deviation (SD), and data analysis was performed by using ANOVA. Results: The results of this study revealed, that among the 12 subfractions derived from the acidified chloroform fraction of fenugreek, four subfractions demonstrated protective effects against H2O2-induced hemolysis and oxidative stress. Furthermore, flow cytometry analysis indicated that treatment with three of these subfractions led to elevated levels of CD47 and reduced levels of phosphatidylserine on the surface of erythrocytes. Conclusions: The results suggest that the subfractions of fenugreek extract which likely contain a higher concentration of flavonoids and a lower content of saponins could be responsible for the observed protection against erythrocyte aging processes. It appears that fenugreek seeds have the ability to safeguard human erythrocytes from oxidative damage by reducing oxidative stress, preserving the activity of antioxidative enzymes, and maintaining the integrity of erythrocyte structure. [ABSTRACT FROM AUTHOR]

Background: Individuals undergoing cardiac surgery face an increased risk of bleeding, as well as alterations in biochemical and coagulation patterns. Therefore, assessing the effectiveness of systems such as Cell Salvage is necessary to prevent potential surgical complications. Objective: To evaluate the efficacy of Cell Salvage in relation to the biochemical parameters of the red blood series and coagulation, as well as the risk of hemorrhage. Methods: A systematic review, accompanied by a meta-analysis, was executed via an extensive literature exploration encompassing Medline, CINAHL, Scopus, Web of Science, and the Cochrane Library. The inclusion criteria comprised studies in English or Spanish, without year restrictions, conducted in adults and with a randomized controlled trial design. Results: Twenty-six studies were included in the systematic review, involving a total of 2850 patients (experimental group = 1415; control group = 1435). Cell Salvage did not demonstrate superior outcomes compared to allogeneic transfusions in the management of post-surgical hemorrhage, as well as in total blood loss, platelet count, fresh frozen plasma, and fibrinogen. However, Cell Salvage showed a greater effectiveness for hemoglobin (moderate evidence), hematocrit (low evidence), post intervention D-dimer (low evidence), and some coagulation-related parameters (low evidence) compared to allogeneic transfusions. Finally, better results were found in the control group for INR parameters. Conclusions: The use of the Cell Salvage system holds high potential to improve the postoperative levels of biochemical and coagulation parameters. However, the results do not provide definitive evidence regarding its effectiveness for hemorrhage control, platelet count, fresh frozen plasma, and fibrinogen. Therefore, it is recommended to increase the number of studies to assess the impact of the Cell Salvage system on improvements in the red blood cell count and patient coagulation patterns. In addition, protocols should be homogenized, and variables such as the sex of the participants should be taken into account. [ABSTRACT FROM AUTHOR]

Serine and folate metabolism play critical roles in erythroid development in both embryonic and adult mice; however, the precise roles of these metabolic pathways in erythropoiesis and the pathophysiology of anemia remain inadequately characterized in the literature. To delineate the contributions of serine and folate metabolism to erythroid differentiation, we focused on serine hydroxymethyltransferase 2 (SHMT2), a key regulatory enzyme within these metabolic pathways. Using gene-editing techniques, we created fetal and adult mouse models with targeted deletion of Shmt2 in the hematopoietic system. Our findings demonstrated that the deletion of Shmt2 within the hematopoietic system led to the distinctive anemia phenotype in both fetal and adult mice. Detailed progression analysis of anemia revealed that Shmt2 deletion exerts stage-specific effects on the development and maturation of erythroid cells. Specifically, Shmt2 deficiency promoted erythroid differentiation in the R2 (CD71+ Ter119−) cell population residing in the bone marrow while concurrently inhibiting the proliferation and erythroid differentiation of the R3 (CD71+ Ter119+) cell population. This disruption resulted in developmental arrest at the R3 stage, significantly contributing to the anemia phenotype observed in the models. This study elucidates the critical role of Shmt2 in erythroid development within the hematopoietic system, highlighting the underlying mechanisms of erythroid developmental arrest associated with Shmt2 loss. [ABSTRACT FROM AUTHOR]

The elasticity of red blood cells (RBCs) is crucial for their ability to fulfill their role in the blood. Decreased RBC deformability is associated with various pathological conditions. This study explores the application of machine learning to predict the elasticity of RBCs using both image data and detailed physical measurements derived from simulations. We simulated RBC behavior in a microfluidic channel. The simulation results provided the basis for generating data on which we applied machine learning techniques. We analyzed the surface-area-to-volume ratio of RBCs as an indicator of elasticity, employing statistical methods to differentiate between healthy and diseased RBCs. The Kolmogorov–Smirnov test confirmed significant differences between healthy and diseased RBCs, though distinctions among different types of diseased RBCs were less clear. We used decision tree models, including random forests and gradient boosting, to classify RBC elasticity based on predictors derived from simulation data. The comparison of the results with our previous work on deep neural networks shows improved classification accuracy in some scenarios. The study highlights the potential of machine learning to automate and enhance the analysis of RBC elasticity, with implications for clinical diagnostics. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) often have impaired immune function, making them more prone to infections that can lead to sepsis. The coexistence of these conditions can result in decreased hemoglobin levels and is associated with a higher mortality rate. To investigate whether the transfusion of red blood cells (RBCs) improves the prognosis of septic patients with concomitant CKD and to explore the indications for red blood cell transfusion. This retrospective cohort study utilizes data from the MIMIC-IV (v2.0) database. The study enrolled 6,604 patients with sepsis and concomitant CKD admitted to the Intensive Care Unit (ICU). Propensity score matching (PSM) was applied to adjust for confounding factors. Multivariate Cox regression analysis revealed an association between RBC transfusion and a decreased risk of 28-day mortality (HR: 0.61, 95% CI: 0.54–0.70, P < 0.001). Following a meticulous 1:1 propensity score matching analysis between the two cohorts, the matched population revealed a notable decrease in 28-day mortality within the RBC transfusion group (HR: 0.60, 95% CI: 0.51–0.71; P < 0.001). Additionally, we observed that a SOFA score ≥ 5, a Base Excess (BE) value < 3, and an estimated Glomerular Filtration Rate (eGFR) < 30 may be considered when evaluating the potential need for RBC transfusion. This study demonstrated an association between RBC transfusion and decreased 28-day mortality in patients with sepsis accompanied by CKD. The patient's BE value, SOFA score, and eGFR are crucial factors influencing the treatment outcome and should be considered when deciding on RBC transfusion. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) pathogenesis is strongly related to diminished nitric oxide (NO) bioavailability and enhanced oxidative stress. Emerging evidence suggests that red blood cells (RBCs) eNOS enzyme contributes to systemic NO bioavailability by its ability of both NO and ROS generation. We aimed to investigate RBC eNOS enzyme activity, NO and ROS generation capacity, eryptosis index and aggregation levels in preeclamptic and uncomplicated pregnant women. Fifty-eight PE patients and 36 healthy pregnant women were included to the investigation. RBC eNOS enzyme activity, intracellular NO, calcium and ROS concentrations and eryptosis levels were determined via flow cytometric methods. RBC deformability and aggregation were measured via LORRCA. Intracellular NO and phosphorylated RBC eNOS levels decreased in PE group compared to healthy pregnant group (p < 0.05, p < 0.001 respectively). Intracellular ROS and calcium levels, eryptosis values and aggregation indexes in the PE group were significantly higher than healthy pregnant group (p < 0.05, p < 0.01, p < 0.05, p < 0.05 respectively). Our results demonstrate for the first time that RBC produce lower NO and higher ROS under PE conditions. Further, RBC of PE patients were more prone to eryptosis and aggregation compared to control group. Our results suggest that, in addition to endothelial cells, RBC also contribute to decreased plasma NO bioavailability via producing less NO and high ROS in PE. Considering increased tendency to eryptosis and aggregation, RBC seem to play role in haemodynamic changes of PE pathogenesis. [ABSTRACT FROM AUTHOR]

Introduction: Donor leucocyte survival following red blood cell (RBC) transfusion, known as transfusion‐associated microchimerism (TAM), can occur in some patients. In Australia, despite the introduction of leucocyte filtration (leucodepletion) during RBC manufacture, TAM has been detected in adult trauma patients. However, the incidence of TAM in Australian pediatric patients has not been analyzed. Methods: Patients aged 0–16 years were recruited across two cohorts. Retrospective participants had RBC transfusion between January 1, 2002 and November 15, 2017 and prospective participants received RBC transfusion between December 1, 2016 and November 25, 2020. Twelve bi‐allelic insertion/deletion (InDel) polymorphisms were used to detect microchimerism amplification patterns using real‐time PCR (RT‐PCR) and droplet digital PCR (ddPCR). Results: Of the retrospective cohort (n = 40), six patients showed amplification of InDel sequences indicating potential microchimerism. For three patients, minor InDel sequences were detected using RT‐PCR only, two patients had minor InDel amplification using ddPCR only, and one patient had minor InDel amplification that was confirmed using both techniques. Amplification of minor sequences occurred in three patients who had received a bone marrow transplant in addition to RBC transfusion. In the prospective cohort (n = 25), no InDel amplification indicating potential microchimerism was detected using RT‐PCR. Discussion: Cell‐based therapies had been administered in three patients where microchimerism amplification patterns were detected. Three patients have microchimerism that may be attributed to RBC transfusion. In prospective patients, who received leucodepleted and gamma‐irradiated RBC units, no potential microchimerism amplification were detected. ddPCR may be a suitable technique for TAM analysis but requires further evaluation. [ABSTRACT FROM AUTHOR]

Carbonic anhydrase (CA) activity is ubiquitously found in all vertebrate species, tissues and cellular compartments. Most species have plasma-accessible CA (paCA) isoforms at the respiratory surfaces, where the enzyme catalyzes the conversion of plasma bicarbonate to carbon dioxide (CO2) that can be excreted by diffusion. A notable exception are the teleost fishes that appear to lack paCA at their gills. The present review: (i) recapitulates the significance of CA activity and distribution in vertebrates; (ii) summarizes the current evidence for the presence or absence of paCA at the gills of fishes, from the basal cyclostomes to the derived teleosts and extremophiles such as the Antarctic icefishes; (iii) explores the contribution of paCA to organismal CO2 excretion in fishes; and (iv) the functional significance of its absence at the gills, for the specialized system of O2 transport in most teleosts; (v) outlines the multiplicity and isoform distribution of membrane-associated CAs in fishes and methodologies to determine their plasma-accessible orientation; and (vi) sketches a tentative time line for the evolutionary dynamics of branchial paCA distribution in the major groups of fishes. Finally, this review highlights current gaps in the knowledge on branchial paCA function and provides recommendations for future work. [ABSTRACT FROM AUTHOR]

An optical sensor that recognizes various blood constituent types is demonstrated in this work and is based on a pentagonal-shaped cladding photonic crystal fiber (PCF) model with a decagonal core. The terahertz frequency, which spans from 1.2 to 3 THz, has been examined with the goal of improving relative sensitivity with minimal confinement loss. COMSOL Multiphysics software is used to analyze the sensor’s sensing and guiding properties through an implementation of the finite element method (FEM) technique. Regarding the chosen analytes, comprising red blood cells (RBCs), hemoglobin (HB), white blood cells (WBCs), plasma, and water, notable relative sensitivity responses of 97.26%, 96.52%, 95.62%, 95.08%, and 93.84% are attained at a frequency of 2.2 THz. In order the same analytes and THz frequency in y-polarization mode, small confinement loss (CL) of 2.92 × 10−11 dB/m and effective material loss (EML) of 0.0052 cm−1 are also acquired respectively. All of these typical values for the optical characteristics show the biosensor’s potential because they assure higher sensitivity for detecting blood components while minimizing confinement and material loss. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) commonly damages the blood system and often manifests as blood cell abnormalities. The performance of biomarkers for predicting SLE activity still requires further improvement. This study aimed to analyze blood cell parameters to identify key indicators for a SLE activity prediction model. Clinical data of 138 patients with SLE (high activity, n = 40; moderate activity, n = 44; mild activity, n = 37; low activity, n = 17) and 100 healthy controls (HCs) were retrospectively analyzed. Data from 89 paired admission–discharge patients with SLE were collected. Differences and associations between blood cell parameters and disease indicators, as well as the relationship between the these parameters and organ damage, were examined. Machine-learning methods were employed to develop a prediction model for disease activity evaluation. Most blood cell parameters (22/26, 84.62%) differed significantly between patients with SLE and HCs. Analysis of 89 paired patients with SLE revealed significant changes in most blood cell parameters at discharge. The standard deviation of lymphocyte volume (SD-V-LY), red blood cell (RBC) count, lymphocyte percentage (LY%), hemoglobin(HGB), hematocrit(HCT), and neutrophil percentage(NE%) correlated with disease activity. By employing machine learning, an optimal model was established to predict active SLE using SD-V-LY, RBC count, and LY% (area under the curve [AUC] = 0.908, sensitivity = 0.811). External validation indicated impressive performance (AUC = 0.940, sensitivity = 0.833). Correlation analysis revealed that SD-V-LY was positively correlated with ESR, IgG, IgA, and IgM but was negatively correlated with C3 and C4. The RBC count was linked to renal and hematopoietic system impairments, whereas LY% was associated with joint/muscle involvement. In conclusion, SD-V-LY is associated with SLE disease activity. SD-V-LY combined with RBC count and LY% contributes to a prediction model, which can be utilized as an effective tool for assessing SLE activity. [ABSTRACT FROM AUTHOR]

Disrupting the conserved multivalent binding of hemagglutinin (HA) on influenza A virus (IAV) to sialic acids (SAs) on the host cell membrane offers a robust strategy to block viral attachment and infection, irrespective of antigenic evolution or drug resistance. In this study, we exploit red blood cell‐derived small extracellular vesicles (RBC sEVs) as nanodecoys by harnessing their high abundance of surface‐displayed SAs to interact with IAV through multivalent HA‐SA interactions. This high‐avidity binding inhibits viral adhesion to the cell surface, effectively preventing both attachment and infection in a dose‐dependent manner. Notably, enzymatic removal of SAs from RBC sEVs significantly diminishes their anti‐IAV efficacy. Our findings indicate that RBC sEVs possess intrinsic anti‐IAV properties due to their native multivalent SAs and hold considerable promise as antiviral therapeutics. [ABSTRACT FROM AUTHOR]

Sex and gender differences play a crucial role in health and disease outcomes. This study used data from the National Health and Nutrition Examination Survey to explore how environmental exposures affect health-related traits differently in males and females. We utilized a sex-stratified phenomic environment-wide association study (PheEWAS), which allowed the identification of associations across a wide range of phenotypes and environmental exposures. We examined associations between 272 environmental exposures, including smoking-related exposures such as cotinine levels and smoking habits, and 58 clinically relevant blood phenotypes, such as serum albumin and homocysteine levels. Our analysis identified 119 sex-specific associations. For example, smoking-related exposures had a stronger impact on increasing homocysteine, hemoglobin, and hematocrit levels in females while reducing serum albumin and bilirubin levels and increasing c-reactive protein levels more significantly in males. These findings suggest mechanisms by which smoking exposure may pose higher cardiovascular risks and greater induced hypoxia for women, and greater inflammatory and immune responses in men. The results highlight the importance of considering sex differences in biomedical research. Understanding these differences can help develop more personalized and effective health interventions and improve clinical outcomes for both men and women. [ABSTRACT FROM AUTHOR]

The study of red blood cell dynamics is an important research field. Understanding physiologic and pathologic characteristics of red blood cell can provide a new perspective to diagnosis and treatment of several diseases. In this work, a numerical model has been developed using the smoothed particle hydrodynamics which is a Lagrangian, meshless particle method to investigate red blood cell dynamics in oscillatory flow. The developed model is parallelized in graphic processing units using Compute Unified Device Architecture developed by NVIDIA that resulted in a seventeen fold reduction in computational cost. The effect of frequency of oscillation and phase difference on red blood cell dynamics is investigated. In addition, the dynamics of healthy and infected red blood cell in oscillatory flow is compared in this work to understand relevance of oscillatory flow in cell separation devices. [ABSTRACT FROM AUTHOR]

Objective: Although the blood transfusion required due to bleeding caused by the large incision area during craniosynostosis surgery is necessary to maintain the oxygen-carrying capacity of the blood, it carries significant risks. Our aim in this study is to determine the effect of the storage period of erythrocyte suspensions (ESs) on patient outcomes in the postoperative period in a pediatric patient group who underwent craniosynostosis surgery. Methods: Fifty-six patients aged 2-24 months who had undergone craniosynostosis surgery between 2018 and 2021 were included in our retrospective study. The patients were divided into two groups according to whether the storage time of the given ES and fresh frozen plasma (FFP) (time elapsed from the day it was received from the donor to the day it was transfused into the patients) was less or more than 10 days. Demographic data of the patients, mean arterial blood pressure, body temperature, hemoglobin (Hb), INR, platelet (plt) values, intraoperative bleeding, amount of transfusion, amount of crystalloid and colloid fluid administered, duration of operation, duration of anesthesia, complications, duration of stay in the postoperative intensive care unit (ICU), amount of transfusion given by drainage, and length of hospital stay were recorded. Results: The mean age of the patients was 8.27±6.294 months. A positive correlation was found between the storage time of ESs used in the intraoperative period, ES and crystalloid amount, and postoperative drainage. A negative correlation was found between intraoperative FFP transfusion and the change in Hb values measured in the ICU, and between intraoperative ES transfusion and plt values on ICU discharge (p<0.05). Conclusion: Our study concluded that the shortening of the storage time of ESs and FFPs may have a positive effect on postoperative drainage. However, since it was found to have no effect on hospital and ICU stay, it is thought that larger-scale studies are needed. [ABSTRACT FROM AUTHOR]

Objective To evaluate the preservation effect of normothermic mechanical perfusion with red blood cells from humanized genetically modified pig on severed human limbs. Methods Severed human limbs were perfused with red blood cells from humanized genetically modified pigs for 6 h. Perfusion solution was taken every hour to measure the oxygen partial pressure, Na+, K+, Ca2+, pH value, glucose, lactic acid and creatine kinase levels. Superficial flexor muscle was sampled to detect the changes of tumor necrosis factor (TNF)-α, interleukin (IL)-2 and IL-1 levels. At 0 and 6 h after perfusion, the superficial flexor muscles of the forearm were taken for pathological examination. Intercellular space and glycogen consumption of skeletal muscles were observed. An appropriate amount of forearm vessels was collected every 2 h to detect the apoptosis of vascular endothelial cells. X-ray angiography was performed before perfusion and 6 h after perfusion to observe the filling degree of finger-tip peripheral vessels. Results The oxygen partial pressure was observed in the normal range throughout the perfusion. Na+ concentration peaked at 1 h, reaching 138.7 mmol/L, and then fluctuated within the normal range. K+ level peaked at 2 h up to 6.08 mmol/L, then decreased and fluctuated within the normal range. Ca2+ concentration reached the peak at 4 h, up to 1.03 mmol/L. Glucose level was gradually decreased at the beginning of perfusion, reaching the lowest value of 17.7 mmol/L at 2h after perfusion, and then maintained a dynamic balance. The pH value was decreased to 7.28 at 6 h after perfusion. The lactic acid level was increased to 9.6 mmol/L at 1 h after perfusion, and then gradually decreased. The creatine kinase level was increased at the start of perfusion, reached the peak at 2 h up to 20 030 U/L, then decreased and remained stable at the end of perfusion. At the end of perfusion, the morphology of muscle fibers was normal, the gap among muscle fibers was expanded slightly, and the glycogen of skeletal muscles was not significantly accumulated. At 0 h perfusion, the number of apoptotic cells in vascular endothelial cells was large, which was declined at 6 h perfusion. Evident vascular filling was observed at 0 h, and the filling degree of some finger-tip vessels was decreased at 6 h. Conclusions Normothermic mechanical perfusion of severed human limbs with red blood cells from humanized genetically modified pigs may continuously and stably supply energy and oxygen, adjust the ion pH balance of perfusion solution, maintain normal cellular metabolism and exerts certain protective effect upon severed human limbs. [ABSTRACT FROM AUTHOR]

Abstract Patients with chronic kidney disease (CKD) often have impaired immune function, making them more prone to infections that can lead to sepsis. The coexistence of these conditions can result in decreased hemoglobin levels and is associated with a higher mortality rate. To investigate whether the transfusion of red blood cells (RBCs) improves the prognosis of septic patients with concomitant CKD and to explore the indications for red blood cell transfusion. This retrospective cohort study utilizes data from the MIMIC-IV (v2.0) database. The study enrolled 6,604 patients with sepsis and concomitant CKD admitted to the Intensive Care Unit (ICU). Propensity score matching (PSM) was applied to adjust for confounding factors. Multivariate Cox regression analysis revealed an association between RBC transfusion and a decreased risk of 28-day mortality (HR: 0.61, 95% CI: 0.54–0.70, P

Abstract The effect of the duration of red blood cell (RBC) storage on the outcomes of transfused patients remains controversial, and studies on patients in the emergency department (ED) are limited. This study aimed to determine the association between RBC storage duration and outcomes of patients receiving transfusions in the ED. For RBCs issued to patients in the ED between 2017 and 2022, the storage period of the RBC and data on the transfused patient were obtained. Patients were divided into fresh (≤ 7 days) and old (> 7 days) RBC groups, and the associations between storage duration, outcomes, and laboratory changes were evaluated. There was no significant difference in outcomes between the two groups in the 28-day mortality (adjusted odds ratio [OR] 0.91, 95% confidence interval [CI] 0.75–1.10, P = 0.320) and the length of stay (fresh 13.5 ± 18.1 vs. old 13.3 ± 19.8, P = 0.814). Regarding changes in laboratory test results, the increase in hemoglobin and hematocrit levels was not affected by the storage durations. The study revealed that transfusion of older RBCs is not associated with inferior outcomes or adverse clinical consequences when compared to that of fresh RBCs in patients in the ED.

Abstract Systemic lupus erythematosus (SLE) commonly damages the blood system and often manifests as blood cell abnormalities. The performance of biomarkers for predicting SLE activity still requires further improvement. This study aimed to analyze blood cell parameters to identify key indicators for a SLE activity prediction model. Clinical data of 138 patients with SLE (high activity, n = 40; moderate activity, n = 44; mild activity, n = 37; low activity, n = 17) and 100 healthy controls (HCs) were retrospectively analyzed. Data from 89 paired admission–discharge patients with SLE were collected. Differences and associations between blood cell parameters and disease indicators, as well as the relationship between the these parameters and organ damage, were examined. Machine-learning methods were employed to develop a prediction model for disease activity evaluation. Most blood cell parameters (22/26, 84.62%) differed significantly between patients with SLE and HCs. Analysis of 89 paired patients with SLE revealed significant changes in most blood cell parameters at discharge. The standard deviation of lymphocyte volume (SD-V-LY), red blood cell (RBC) count, lymphocyte percentage (LY%), hemoglobin(HGB), hematocrit(HCT), and neutrophil percentage(NE%) correlated with disease activity. By employing machine learning, an optimal model was established to predict active SLE using SD-V-LY, RBC count, and LY% (area under the curve [AUC] = 0.908, sensitivity = 0.811). External validation indicated impressive performance (AUC = 0.940, sensitivity = 0.833). Correlation analysis revealed that SD-V-LY was positively correlated with ESR, IgG, IgA, and IgM but was negatively correlated with C3 and C4. The RBC count was linked to renal and hematopoietic system impairments, whereas LY% was associated with joint/muscle involvement. In conclusion, SD-V-LY is associated with SLE disease activity. SD-V-LY combined with RBC count and LY% contributes to a prediction model, which can be utilized as an effective tool for assessing SLE activity.

Abstract Sex and gender differences play a crucial role in health and disease outcomes. This study used data from the National Health and Nutrition Examination Survey to explore how environmental exposures affect health-related traits differently in males and females. We utilized a sex-stratified phenomic environment-wide association study (PheEWAS), which allowed the identification of associations across a wide range of phenotypes and environmental exposures. We examined associations between 272 environmental exposures, including smoking-related exposures such as cotinine levels and smoking habits, and 58 clinically relevant blood phenotypes, such as serum albumin and homocysteine levels. Our analysis identified 119 sex-specific associations. For example, smoking-related exposures had a stronger impact on increasing homocysteine, hemoglobin, and hematocrit levels in females while reducing serum albumin and bilirubin levels and increasing c-reactive protein levels more significantly in males. These findings suggest mechanisms by which smoking exposure may pose higher cardiovascular risks and greater induced hypoxia for women, and greater inflammatory and immune responses in men. The results highlight the importance of considering sex differences in biomedical research. Understanding these differences can help develop more personalized and effective health interventions and improve clinical outcomes for both men and women.

Introduction: Haemolytic Disease of the Foetus and Newborn (HDFN) is widely known to be caused by the presence of irregular Red Blood Cell (RBC) antibodies in pregnant females. To prevent HDFN, it is crucial to identify these antibodies in pregnant women. Aim: To evaluate the prevalence of irregular red cell antibodies in pregnant women in a tertiary care hospital. Materials and Methods: A cross-sectional retrospective study was conducted in the Department of Transfusion Medicine at Indraprastha Apollo New Delhi, from November 2009 to December 2017. A total of 8,217 prenatal females were examined for irregular red cell antibodies. Antibody screening and blood grouping were performed. The Capture-R ready screen was used to confirm screen-positive tests. Adsorption, elution, and other advanced techniques were utilised as needed. Data was collected from patient records and entered into a Microsoft excel spreadsheet. The statistical analysis was conducted using Statistical Package for Social Sciences (SPSS) software version 14.0 (USA). Statistical tests, including the Chi-squared and Fisher’s exact test, were performed, with a p-value less than 0.05 considered statistically significant. Results: Out of the 8,217 prenatal females examined, 105 (1.27%) had positive screening results with the four cell panel. Red cell alloimmunisation was observed in groups that were RhD negative (n=93/105; 88.57%) and positive (n=12/105; 11.42%). The most prevalent alloantibody among RhD negative individuals was alloantibody anti-D (n= 83/93; 89.24%), followed by alloantibody anti C+ anti D (n=13/93; 13.97%). Anti-D was the most prevalent alloantibody overall (n=83/105; 79.04%). Conclusion: Alloimmunisation rates were notably high among women lacking the Rh D antigen. Individuals with a history of adverse obstetric outcomes showed a statistically significant association with alloimmunisation. Therefore, it is recommended to screen such individuals for alloantibodies to enable early detection and improve the management of HDFN.

Abstract Red blood cells (RBCs) express the nucleic acid-binding toll-like receptor 9 (TLR9) and bind CpG-containing DNA. However, whether human RBCs express other nucleic acid-binding TLRs is unknown. Here we show that human RBCs express the RNA sensor TLR7. TLR7 is present on the red cell membrane and is associated with the RBC membrane protein Band 3. In patients with SARS-CoV2-associated sepsis, TLR7-Band 3 interactions in the RBC membrane are increased when compared with healthy controls. In vitro, RBCs bind synthetic ssRNA and RNA from ssRNA viruses. Thus, RBCs may serve as a previously unrecognized sink for exogenous RNA, expanding the repertoire of non-gas exchanging functions performed by RBCs.

Background and Study Aim. A recent study indicates that Ethiopian middle- and long-distance athletes originate from diverse geographical regions, including areas of varying elevation. This study aimed to analyze the impact of altitude training on hematological parameters and recovery heart rates among young male endurance trainees training at sites located at different altitude levels. Material and Methods. The study employed a quasi-experimental, counterbalanced approach involving 15 male trainees. Five individuals from each training center experienced the standard training program across three distinct geographical locations and elevations. Pre- and post-test data were collected on red blood cells, hemoglobin, hematocrit, platelet count, and recovery heart rate before and after six months, from 6:00–8:00 AM. ANCOVA was utilized to analyze the data. Results. Following the intervention, the mean Red Blood Cell (RBC) count was observed to be higher in trainees from low altitude (5.18±0.33) compared to those from moderate altitude (4.48±0.14 and 5.21±0.22), with a significance level of p0.05). Similarly, the mean Hematocrit (HCT) count was low for both low altitude (46.04±3.49) and moderate altitude trainees (46.46±3.9 and 45.42±1.54), with no significant difference noted (p>0.05). The mean Platelet (PLT) count was 226.8±75.88 for low altitude trainees and 265.8±23.18, 276±53.96 for moderate altitude trainees, with no significant difference between the groups (p>0.05). As for the recovery heart rate, mean values showed no significant difference between the pre-and post-test groups. In the pretest, the mean recovery heart rate was 30.00±14.70 for low-altitude trainees and 43.20±8.90, 43.20±13.68 for moderate-altitude trainees (p>0.05). In the post-test, the mean recovery heart rate was 25.20±7.82 for low-altitude trainees and 32.40±10.04, 36.00±7.35 for moderate-altitude trainees (p>0.05). Conclusions. The findings indicate that training at different altitudes impacts the hematological and cardiovascular systems of endurance athletes in varied ways. This underscores the importance of developing tailored training programs to optimize performance and recovery. These results are particularly relevant for coaches and athletes seeking to enhance endurance training outcomes through altitude training strategies.

Background: Multiple studies, including both humans and animals, have demonstrated that gasoline, kerosene, and diesel fuel exhaust emissions include chemical components harmful to the bone marrow, lymph nodes, and spleen. This study aimed to evaluate the impact of kerosene and naphtha vapors on several blood parameters in rats. Methods and Results: The study was conducted on 10–12-week-old male Wistar albino rats (Rattus norvegicus) (n=20) weighing 150–200g. The experimental rats were categorized into two groups, each including five animals. The rats were exposed to kerosene and naphtha vapors for 15, 30, and 45 days, with six hours of daily exposure. Two control groups of animals, each including five animals, were exposed to room air. One group of rats was allowed to inhale the vapors emitted by the evaporating kerosene. Another group underwent an identical process for the naphtha vapors. Both groups of animals were exposed to daily vapors for six hours, from 9:00 a.m. to 3:00 p.m., six days a week, for three different durations: 15, 30, and 45 days. Blood samples were tested for hematological indices using a Cell Dyn Ruby Hematology Analyzer (Abbott, USA). On days 15, 30, and 45 of the experiment, rats exposed to kerosene and naphtha vapors had an increase in the total number of leukocytes, an increase in the percentage of lymphocytes, and a decrease in the percentage of neutrophils, compared to the control group (P

The growing world population and increasing life expectancy are driving the need to improve the quality of blood transfusion, organ transplantation, and preservation. Here, to improve the ability of red blood cells (RBCs) for normothermic machine perfusion, a biocompatible blood silicification approach termed "shielding-augmenting RBC-in-nanoscale amorphous silica (SARNAS)" has been developed. The key to RBC surface engineering and structure augmentation is the precise control of the hydrolysis form of silicic acid to realize stabilization of RBC within conformal nanoscale silica-based exoskeletons. The formed silicified RBCs (Si-RBCs) maintain membrane/structural integrity, normal cellular functions (e.g., metabolism, oxygen-carrying capability), and enhance resistance to external stressors as well as tunable mechanical properties, resulting in nearly 100% RBC cryoprotection. In vivo experiments confirm their excellent biocompatibility. By shielding RBC surface antigens, the Si-RBCs provide universal blood compatibility, the ability for allogeneic mechanical perfusion, and more importantly, the possibility for cross-species transfusion. Being simple, reliable, and easily scalable, the SARNAS strategy holds great promise to revolutionize the use of engineered blood for future clinical applications. [ABSTRACT FROM AUTHOR]

Objectives: Milk thistle has long been used in the treatment of liver and biliary disorders. In the present study, to make a long-acting delivery system for silibinin (SBN, a major active constituent of milk thistle seeds with antioxidant and hepatoprotective function), mesoporous silica composite nanoparticles (NC) were synthesized and coated with RBC membrane. Methods: A modified Stöber method was used for NC synthesis, which was then characterized using FE-SEM, DLS, TEM, FTIR, and EDAX techniques. A suitable lysis buffer was used to prepare RBC-ghost, and sonication was used to coat SBN-loaded NC (SBN-NC). The RBC-ghost coated SBN-NC (SBN-NC-RBCG) was evaluated by SDS-PAGE, Bradford, TEM, EDAX, and DLS methods. SBN release was then compared for the SBN-NC and SBN-NC-RBCG samples. Key findings: the RBC membrane proteins were recovered from the coating of SBN-NC-RBCG, and SBN release was sustained over 24 h when compared with the SBN-NC. Conclusions: Overall, through prolonging circulation in the bloodstream and evading the immune system, the developed system can improve SBN bioavailability in liver inflammation and fibrosis conditions that need further research. [ABSTRACT FROM AUTHOR]

Improving the activity of uricase and lowering its immunogenicity remain significant challenges in the enzyme replacement management of hyperuricemia and related inflammatory diseases. Herein, an immunogenicity-masking strategy based on engineered red blood cells (RBCs) was developed for effective uricase delivery against both hyperuricemia and gout. The dynamic membrane of RBCs enabled high resistance to protease inactivation and hydrogen peroxide accumulation. Benefiting from these advantages, a single infusion of RBC-loaded uricase (Uri@RBC) performed prolonged blood circulation and sustained hyperuricemia management. Importantly, RBCs masked the immunogenicity of uricase, leading to the maintenance of UA-lowering performance after repeated infusion through reduced antibody-mediated macrophage clearance. In an acute gout model, Uri@RBC profoundly alleviated joint edema and inflammation with minimal systemic toxicity. This study supports the employment of immunogenicity-masking tools for efficient and safe enzyme delivery, and this strategy may be leveraged to improve the usefulness of enzyme replacement therapies for managing a wide range of inflammatory diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between the storage time of transfused red blood cells (RBCs) and risks of infections after cleancontaminated surgery. Background: Storage lesions of RBCs can aggravate transfusion-related immunomodulation. Very few randomized controlled trials have investigated the impacts of storage time on postoperative outcomes in noncardiac patients. Methods: We included adult patients who had undergone cleancontaminated surgery from 2014 to 2018 and received allogeneic RBC transfusion. In transfusion episode-level analysis, the exposure was the storage time of each transfusion episode. In patient-level analysis, the exposures were the mean, weighted mean, maximum storage time, and Scalar Age of Blood Index of RBCs transfused into each patient. The primary outcome was infections that developed after transfusions within postoperative day 30. Results: The 4046 patients were included who received 11604 transfusion episodes. Of these, 1025 (25.3%) patients developed postoperative infections. An increased storage time of transfused RBCs was not associated with increased odds of postoperative infections in either transfusion episode-level analysis [odds ratio (OR), 1.03 per 5 days, 95% CI, 0.95-1.11] or patient-level analysis (mean: OR, 1.02, 95% CI, 0.95-1.10; weighted mean: OR, 1.02, 95% CI, 0.95-1.10; maximum: OR, 1.06, 95% CI, 0.98-1.14; Scalar Age of Blood Index: OR, 0.99, 95% CI, 0.96-1.03), after adjusting 17 confounders. Conclusions: Prolonged storage time of transfused RBCs was not associated with increased risks of infections after clean-contaminated surgery. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) comprises inherited red blood cell disorders due to a mutation in the β-globin gene (c20A > T, pGlu6Val) and is characterized by the presence of abnormal hemoglobin, hemoglobin S, hemolysis, and vaso-occlusion. This mutation, either in a homozygous configuration or in compound states with other β-globin mutations, leads to polymerization of hemoglobin S in deoxygenated conditions, causing modifications in red blood cell shape, particularly sickling. Vaso-occlusive crisis (VOC) is the hallmark of the disease, but other severe complications may arise from repeated bouts of VOCs. SCD is considered a global health problem, and its incidence has increased in some areas of the world, particularly the Americas and Africa. Management of the disease varies according to the region of the world, mainly due to local resources and socioeconomic status. This review aimed to describe more recent data on SCD regarding available treatment options, especially in Brazil. New treatment options are expected to be available to all patients, particularly crizanlizumab, which is already approved in the country. [ABSTRACT FROM AUTHOR]

Backround and Objectives: Blood transfusion therapy is vital for many patient groups. They can cause many complications, and the development of anti‐red blood cell (RBC) antibodies is of significant importance. Molecules of class II human leucocyte antigens (HLA) are one of the several factors that influence antibody development in patients. Materials and Methods: In this study, we investigated 108 patients who developed antibodies against different erythrocyte antigens and 115 patients on multiple transfusion therapies who did not develop anti‐RBC antibodies. The HLA loci HLA‐DRB1 and HLA‐DQB1 were typed using commercial molecular assays routinely used in HLA laboratories. Results: An increased frequency of the HLA‐DRB1*04 allele group was observed in patients who developed antibodies. Additionally, HLA‐DRB1*09 was also significant for anti‐E development and in patients with multi‐specific alloimmunization. It was found that the HLA‐DRB1*07 allele group is associated with antibodies to antigents of the Rh and MNS systems but also lacks an association with anti‐K development. The HLA‐DRB1*11 and ‐DRB1*01 allele groups displayed a protective mechanism for anti‐E development, similar to that of HLA‐DQB1*02 for anti‐K. Conclusion: There is an association between various HLA class II alleles and anti‐RBC development. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aim to establish associations between metabolic syndrome (MetS) and erythrocyte and platelet markers, contributing to improved diagnostic tests for identifying individuals at risk. Observational studies and Randomized Controlled Trials (RCTs) were included. The standardized mean difference (SMD) and 95% confidence intervals (CI) of erythrocyte and platelet markers between individuals with and without MetS were used as effect size (inverse variance model). Methodological quality assessment was conducted using the Newcastle-Ottawa scale (NOS) for observational studies and the Cochrane Risk of Bias tool 2.0 for RCTs. The analysis included 51 articles. Compared to controls, individuals with MetS exhibited significantly higher concentrations of mean red blood cell count [Standardized Mean Difference (95% CI): 0.15 (0.13−0.18); p<0.00001], hemoglobin [0.24 (0.18−0.31); p<0.00001], blood platelet count [5.49 (2.78–8.20); p<0.0001], and red blood cell distribution width [(0.55 (0.05–1.04); p=0.03]. Regarding mean platelet volume [0.16 (– 0.03 to 0.35); p=0.10] and platelet-to-lymphocyte ratio (PLR) [7.48 (–2.85–17.81); p=0.16], a non-significant difference was observed in patients with MetS. There was no statistically significant difference in hematocrit counts between the two groups [0.47 (–0.40 to –1.34); p=0.29]. Biomarkers such as mean red blood cell count, hemoglobin, blood platelet count, and RDW are associated with higher levels in patients in MetS, whereas mean platelet volume and PLR tend to be lower. These markers can potentially provide new avenues for early diagnosis of MetS. [ABSTRACT FROM AUTHOR]

Significance: Sickle cell disease (SCD) is the most common inherited diathesis affecting mostly underserved populations globally. SCD is characterized by chronic pain and fatigue, severe acute painful crises requiring hospitalization and opioids, strokes, multiorgan damage, and a shortened life span. Symptoms may appear shortly after birth, and, in less developed countries, most children with SCD die before attaining age 5. Hematopoietic stem cell transplant and gene therapy offer a curative therapeutic approach, but, due to many challenges, are limited in their availability and effectiveness for a majority of persons with SCD. A critical unmet need is to develop safe and effective novel targeted therapies. A wide array of drugs currently undergoing clinical investigation hold promise for an expanded pharmacological armamentarium against SCD. Recent Advances: Hydroxyurea, the most widely used intervention for SCD management, has improved the survival in the Western world and more recently, voxelotor (R-state-stabilizer), l-glutamine, and crizanlizumab (anti-P-selectin antibody) have been approved by the Food and Drug Administration (FDA) for use in SCD. The recent FDA approval emphasizes the need to revisit the advances in understanding the core pathophysiology of SCD to accelerate novel evidence-based strategies to treat SCD. The biomechanical breakdown of erythrocytesis, the core pathophysiology of SCD, is associated with intrinsic factors, including the composition of hemoglobin, membrane integrity, cellular volume, hydration, andoxidative stress. Critical Issues and Future Directions: In this context, this review focuses on advances in emerging nongenetic interventions directed toward the therapeutic targets intrinsic to sickle red blood cells (RBCs), which can prevent impaired rheology of RBCs to impede disease progression and reduce the sequelae of comorbidities, including pain, vasculopathy, and organ damage. In addition, given the intricate pathophysiology of the disease, it is unlikely that a single pharmacotherapeutic intervention will comprehensively ameliorate the multifaceted complications associated with SCD. However, the availability of multiple drug options affords the opportunity for individualized therapeutic regimens tailored to specific SCD-related complications. Furthermore, it opens avenues for combination drug therapy, capitalizing on distinct mechanisms of action and profiles of adverse effects. [ABSTRACT FROM AUTHOR]

Background and purpose: Patients who underwent red blood cell (RBC) transfusion from donors who later developed multiple spontaneous intracerebral hemorrhages (ICHs) have recently been identified to have increased risk of ICH themselves. This increased risk of ICH was hypothesized to be related to iatrogenic cerebral amyloid angiopathy (iCAA) transmission. Two cases are presented who had RBC transfusion as an infant and presented with CAA at a relatively young age decades later. Method: Cases were identified by prospectively asking all patients at our CAA outpatient clinic (November 2023 to January 2024) about a medical history with RBC transfusion or history with a high likelihood for RBC transfusion (e.g., hemolytic disease, trauma with massive hemorrhage). Eligible patients were all diagnosed with CAA, CAA with concomitant hypertensive arteriopathy or iCAA, and without hereditary CAA. Results: Between November 2023 and January 2024, 2/35 (6%, 95% confidence interval 2%–19%) outpatient clinic patients had a history of RBC transfusion and none had a high likelihood medical history. The cases presented at age 47 and 57 and had already developed severe CAA. Conclusions: Red blood cell transfusion might be a possible mechanism for iCAA; however, further prospective data collection and experimental evidence concerning blood transmission of amyloid‐β are needed. [ABSTRACT FROM AUTHOR]

Background: Australian Red Cross Lifeblood (Lifeblood) performs human erythrocyte antigen (HEA) genotyping for a subset of repeat whole‐blood donors through preferential selection which aims to maximise variation of results and possibility of identifying donors lacking high frequency red cell antigens. Materials and Methods: The HEA Molecular Bead chip™ assay is used by Lifeblood for donor genotyping. A review of all donor HEA genotype data from March 2019 to May 2022 (3 years) was conducted. Results: HEA genotyping was performed for 20,185donors. Due to selective genotyping of donors, a higher frequency of R1R1 predicted phenotype was identified. However, frequencies of other red cell phenotypes were relatively similar to previous reported in the Australian population. A small number of donors with rare red cell phenotypes was identified. Conclusion: Genotyping of blood donors provides an available pool of extended matched red blood cell products for matching to recipients. Additionally genotyping can improve the identification of donors with rare phenotypes. Whilst limitations exist, genotyping may reduce the need for labour intensive serotyping, improve blood inventory management, and may be useful in donor recruitment and retention. [ABSTRACT FROM AUTHOR]

IntroductionSevere hypoxemia is the leading cause of admission in intensive care (ICU) in patients with COVID-19 related acute respiratory distress syndrome (ARDS). In these patients, several studies reported a left shift of the oxyhemoglobin dissociation curve associated with a lower mortality. However, these results are conflicting, as these studies include few patients and often no control groups. Moreover, the calculation of P50, representing the PaO2 value at which 50% of hemoglobin is saturated, is not corrected for factors known to influence it (pH, PaCO2 or temperature). For all of these reasons, we compared the corrected P50 between ICU patients with severe COVID-19 related ARDS on mechanical ventilation or not, and ARDS from other causes. We investigated the evolution of the corrected P50 during the first 3 days of ICU and its relationship with ICU mortality.Methods and PatientsWe retrospectively calculated the corrected P50 in three groups of patients: intubated and mechanically ventilated COVID-19 related ARDS, non-intubated COVID-19 related ARDS and intubated patients with ARDS due to other infectious causes. The corrected P50 was calculated, on the worst blood gas analysis on days 1 and 3 of ICU admission, by the formula of Hill but modified by Dash et al., controlled for pH, PaCO2 and temperature. We collected ICU mortality.Results463 blood gas analysis at days 1 and 3 from 214 ICU COVID-19 related ARDS patients (114 with intubation and 100 without) and 35 ICU patients with ARDS from other causes were analyzed. All patients were severely hypoxemic: PaO2/FiO2 of 76 [58-108] mmHg for intubated COVID-19, 79 [60-108] mmHg for non-intubated COVID-19 and 142 [78-197] mmHg for the third group (p < 0.001). The mortality rate was higher in intubated COVID-19 related ARDS patients (44.7 versus 14 versus 37% in ARDS from other causes; p < 0.001). The corrected P50 was significantly lower in COVID-19 patients, especially in non- intubated patients (21.2 [18.8–25.2] mmHg vs. 25.5 [19.2–30.3] mmHg in intubated patients; compared to ARDS from other causes: 27.2 [23.3-35.4] mmHg; p < 0.001. The corrected P50 does not change over the first 3 days, except for the non intubated COVID-19 related ARDS and is not correlated with ICU mortality (odds ratio = 0.98 [0.95-1.03]; p = 0.51), in contrast of PaO2/FiO2 and ICU gravity scores.ConclusionThe oxyhemoglobin dissociation curve at ICU admission was left shifting in severe COVID-19 related ARDS patients regardless of the type of ventilation. This deviation increases the third day only in non-intubated COVID-19 related ARDS and was not related to the outcome.

Abstract Researchers have attempted to generate transfusable oxygen carriers to mitigate RBC supply shortages. In vitro generation of RBCs using stem cells such as hematopoietic stem and progenitor cells (HSPCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) has shown promise. Specifically, the limited supplies of HSPCs and ethical issues with ESCs make iPSCs the most promising candidate for in vitro RBC generation. However, researchers have encountered some major challenges when using iPSCs to produce transfusable RBC products, such as enucleation and RBC maturation. In addition, it has proven difficult to manufacture these products on a large scale. In this review, we provide a brief overview of erythropoiesis and examine endeavors to recapitulate erythropoiesis in vitro using various cell sources. Furthermore, we explore the current obstacles and potential solutions aimed at enabling the large-scale production of transfusable RBCs in vitro.

ABSTRACTThrombosis, a leading contributor to global health burden, is a complex process involving the interplay of various cell types, including vascular endothelial cells, platelets, and red blood cells. Oxidative stress, characterized by an overproduction of reactive oxygen species (ROS), can significantly impair the function of these cells, thus instigating a cascade of events leading to thrombus formation. In this review, we comprehensively explore the role of oxidative stress within these cells, and its mechanistic contribution to thrombogenesis, and the application of oxidative therapy in inhibiting thrombosis. By dissecting the intricacies of oxidative stress and its impact on thrombosis, we underscore its potential as a viable therapeutic target. Therefore, further research in this direction is warranted to enhance our understanding and management of thrombotic disorders.

The utilizations of microfluidic chips for single RBC (red blood cell) studies have attracted great interests in recent years to filter, trap, analyze, and release single erythrocytes for various applications. Researchers in this field have highlighted the vast potential in developing micro devices for industrial and academia usages, including lab-on-a-chip and organ-on-a-chip systems. This article critically reviews the current state-of-the-art and recent advances of microfluidics for single RBC analyses, including integrated sensors and microfluidic platforms for microscopic/tomographic/spectroscopic single RBC analyses, trapping arrays (including bifurcating channels), dielectrophoretic and agglutination/aggregation studies, as well as clinical implications covering cancer, sepsis, prenatal, and Sickle Cell diseases. Microfluidics based RBC microarrays, sorting/counting and trapping techniques (including acoustic, dielectrophoretic, hydrodynamic, magnetic, and optical techniques) are also reviewed. Lastly, organs on chips, multi-organ chips, and drug discovery involving single RBC are described. The limitations and drawbacks of each technology are addressed and future prospects are discussed.

Malaria is a disease that affects millions of people worldwide, particularly in developing countries. The development of accurate and efficient methods for the detection of malaria-infected cells is crucial for effective disease management and control. This paper presents the electrical impedance spectroscopy (EIS) of normal and malaria-infected red blood cells. An EIS microfluidic device, comprising a microchannel and a pair of coplanar electrodes, was fabricated for single-cell measurements in a continuous manner. Based on the EIS results, the aim of this work is to discriminate Plasmodium falciparum-infected red blood cells from the normal ones. Different from typical impedance spectroscopy, our measurement was performed for the cells in a low-conductivity medium in a frequency range between 50 kHz and 800 kHz. Numerical simulation was utilized to study the suitability parameters of the microchannel and electrodes for the EIS experiment over the measurement frequencies. The measurement results have shown that by using the low-conductivity medium, we could focus on the change in the conductance caused by the presence of a cell in the sensing electrode gap. The results indicated a distinct frequency spectrum of the conductance between the normal and infected red blood cells, which can be further used for the detection of the disease. [ABSTRACT FROM AUTHOR]

Researchers have attempted to generate transfusable oxygen carriers to mitigate RBC supply shortages. In vitro generation of RBCs using stem cells such as hematopoietic stem and progenitor cells (HSPCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) has shown promise. Specifically, the limited supplies of HSPCs and ethical issues with ESCs make iPSCs the most promising candidate for in vitro RBC generation. However, researchers have encountered some major challenges when using iPSCs to produce transfusable RBC products, such as enucleation and RBC maturation. In addition, it has proven difficult to manufacture these products on a large scale. In this review, we provide a brief overview of erythropoiesis and examine endeavors to recapitulate erythropoiesis in vitro using various cell sources. Furthermore, we explore the current obstacles and potential solutions aimed at enabling the large-scale production of transfusable RBCs in vitro. [ABSTRACT FROM AUTHOR]

Global prevalence of hypertension is on the rise, burdening healthcare, especially in developing countries where infectious diseases, such as malaria, are also rampant. Whether hypertension could predispose or increase susceptibility to malaria, however, has not been extensively explored. Previously, we reported that hypertension is associated with abnormal red blood cell (RBC) physiology and anemia. Since RBC are target host cells for malarial parasite, Plasmodium, we hypothesized that hypertensive patients with abnormal RBC physiology are at greater risk or susceptibility to Plasmodium infection. To test this hypothesis, normotensive (BPN/3J) and hypertensive (BPH/2J) mice were characterized for their RBC physiology and subsequently infected with Plasmodium yoelii (P. yoelii), a murine-specific non-lethal strain. When compared to BPN mice, BPH mice displayed microcytic anemia with RBC highly resistant to osmotic hemolysis. Further, BPH RBC exhibited greater membrane rigidity and an altered lipid composition, as evidenced by higher levels of phospholipids and saturated fatty acid, such as stearate (C18:0), along with lower levels of polyunsaturated fatty acid like arachidonate (C20:4). Moreover, BPH mice had significantly greater circulating Ter119+ CD71+ reticulocytes, or immature RBC, prone to P. yoelii infection. Upon infection with P. yoelii, BPH mice experienced significant body weight loss accompanied by sustained parasitemia, indices of anemia, and substantial increase in systemic pro-inflammatory mediators, compared to BPN mice, indicating that BPH mice were incompetent to clear P. yoelii infection. Collectively, these data demonstrate that aberrant RBC physiology observed in hypertensive BPH mice contributes to an increased susceptibility to P. yoelii infection and malaria-associated pathology. Graphical Abstract [ABSTRACT FROM AUTHOR]

Objective To investigate the differences and the immunocompatibility of wild-type (WT), four-gene modified (TKO/hCD55) and six-gene modified (TKO/hCD55/hCD46/hTBM) pig erythrocytes with human serum. Methods The blood samples were collected from 20 volunteers with different blood groups. WT, TKO/hCD55, TKO/hCD55/hCD46/hTBM pig erythrocytes, ABO-compatible (ABO-C) and ABO-incompatible (ABO-I) human erythrocytes were exposed to human serum of different blood groups, respectively. The blood agglutination and antigenantibody binding levels (IgG, IgM) and complement-dependent cytotoxicity were detected. The immunocompatibility of two types of genetically modified pig erythrocytes with human serum was evaluated. Results No significant blood agglutination was observed in the ABO-C group. The blood agglutination levels in the WT and ABO-I groups were higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (all P<0.001). The level of erythrocyte lysis in the WT group was higher than those in the ABO-C, TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups. The level of erythrocyte lysis in the ABO-I group was higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (both P<0.01). The pig erythrocyte binding level with IgM and IgG in the TKO/hCD55 group was lower than those in the WT and ABO-I groups. The pig erythrocyte binding level with IgG and IgM in the TKO/hCD55/hCD46/hTBM group was lower than that in the WT group and pig erythrocyte binding level with IgG was lower than that in the ABO-I group (all P<0.05). Conclusions The immunocompatibility of genetically modified pig erythrocytes is better than that of wild-type pigs and close to that of ABO-C pigs. Humanized pig erythrocytes may be considered as a blood source when blood sources are extremely scarce. [ABSTRACT FROM AUTHOR]

Background and Study Aim: A recent study indicates that Ethiopian middle- and long-distance athletes originate from diverse geographical regions, including areas of varying elevation. This study aimed to analyze the impact of altitude training on hematological parameters and recovery heart rates among young male endurance trainees training at sites located at different altitude levels. Material and Methods: The study employed a quasi-experimental, counterbalanced approach involving 15 male trainees. Five individuals from each training center experienced the standard training program across three distinct geographical locations and elevations. Pre- and post-test data were collected on red blood cells, hemoglobin, hematocrit, platelet count, and recovery heart rate before and after six months, from 6:00-8:00 AM. ANCOVA was utilized to analyze the data. Results: Following the intervention, the mean Red Blood Cell (RBC) count was observed to be higher in trainees from low altitude (5.18±0.33) compared to those from moderate altitude (4.48±0.14 and 5.21±0.22), with a significance level of p<0.05. The mean Hemoglobin (HGB) count was found to be higher in moderate altitude trainees (17.00±0.70 and 16.31±0.65) than in low altitude trainees (15.82±1.37), although this difference was not statistically significant (p>0.05). Similarly, the mean Hematocrit (HCT) count was low for both low altitude (46.04±3.49) and moderate altitude trainees (46.46±3.9 and 45.42±1.54), with no significant difference noted (p>0.05). The mean Platelet (PLT) count was 226.8±75.88 for low altitude trainees and 265.8±23.18, 276±53.96 for moderate altitude trainees, with no significant difference between the groups (p>0.05). As for the recovery heart rate, mean values showed no significant difference between the pre-and post-test groups. In the pretest, the mean recovery heart rate was 30.00±14.70 for low-altitude trainees and 43.20±8.90, 43.20±13.68 for moderate-altitude trainees (p>0.05). In the post-test, the mean recovery heart rate was 25.20±7.82 for low-altitude trainees and 32.40±10.04, 36.00±7.35 for moderate-altitude trainees (p>0.05). Conclusions: The findings indicate that training at different altitudes impacts the hematological and cardiovascular systems of endurance athletes in varied ways. This underscores the importance of developing tailored training programs to optimize performance and recovery. These results are particularly relevant for coaches and athletes seeking to enhance endurance training outcomes through altitude training strategies. [ABSTRACT FROM AUTHOR]

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Background: Several laboratory markers derived from a complete blood count (CBC) have been proposed as potential indicators for assessing the risk of cerebral venous thrombosis (CVT). However, limited and conflicting evidence exists regarding this association. This study aimed to evaluate the role of CBC parameters in CVT development and their link to disease characteristics. Methods: This case-control study included patients diagnosed with CVT between March 2018 and March 2021. [ABSTRACT FROM AUTHOR]