Erythrocytes Research Articles

Investigation of age-related in-hospital outcomes of left atrial appendage occlusion in germany

Abstract Background The aim of this study was to assess demographics, in-hospital mortality and baseline characteristics of hospital cases with a left atrial appendage occlusion (LAAO) procedure in relation to patient age. Methods This is a retrospective observational analysis of all German in-hospital cases from 2016 to 2022 with a coded LAAO procedure using the Diagnose Related Groups (DRG) statistics database of the Research Data Center of the Federal Statistical Office. Results In total 40435 cases were observed in the investigated time period. Over the 5 years studied we found a significant shift towards an older patient collective. Compared to 28,3% in 2016, in 2022 40,1% of all patients were over 80 years of age (a rise of 152 %). Cases of patients with over 85 years of age increased from 7.7 % to 11.4 % during the same time period. We observed an in-hospital death rate for patients <70, 70-75, 80-85 and >85 years of age in 0.8, 1.0, 1.4 and 2.2 % respectively. Further we saw significant higher rates of intensified care treatment, pericardial effusion, acute kidney injury and red blood cell transfusion for patients >80 years of age. In unadjusted and adjusted logistic regression models age was significantly associated with a higher rate of in-hospital death. Conclusions In this study we present real world data from a health-care-system level. Our main findings were an increasing age in patients undergoing LAAO procedures and an independent association of age with in-house mortality and complications. This data provides a further basis to balance risks and benefits of LAAO procedure as a preventive treatment.

Effect of four hemoglobin transfusion threshold strategies in patients with acute myocardial infarction and anemia: a target trial emulation using MINT trial data

Abstract Background The hemoglobin (Hgb) threshold at which red blood cell transfusion affords greatest benefit, without increasing transfusion-associated risks, is uncertain for patients with acute myocardial infarction (MI). The Myocardial Ischemia and Transfusion (MINT) trial recently showed a restrictive transfusion strategy (Hgb threshold <7-8g/dL) resulted in a 15% increased risk of 30-day all-cause death or recurrent MI (death/MI) compared with a liberal strategy (Hgb threshold <10g/dL) in 3,504 adults with acute MI and anemia. However, the transfusion effect at different Hgb thresholds remains uncertain. Purpose To better understand the gradient of effects from Hgb threshold transfusion triggers between 7g/dL and 10g/dL. We estimated the effects of four Hgb transfusion thresholds on 30-day death/MI and death in patients with acute MI and anemia. Methods We used data from the MINT trial and applied an innovative causal inference method, target trial emulation, to assess four Hgb thresholds. We emulated a hypothetical, 4-arm target trial of <10g/dL, <9g/dL, <8g/dL, and <7g/dL transfusion strategies in adults with acute MI and Hgb <10g/dL using a "cloning" procedure. The target trial protocol closely mirrored that of the MINT trial. We conducted a per-protocol analysis of the emulated target trial using censoring and inverse probability (IP) weighting; we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) by fitting pooled logistic regression models with a time-dependent intercept for time free of the outcomes. We estimated IP weighted Kaplan-Meier cumulative incidence curves under each strategy for 30-day outcomes. Results Of the MINT trial participants, 3,492 (99.7%) met eligibility criteria for the hypothetical target trial of four transfusion strategies. The unadjusted rate of 30-day death/MI was lowest in the <10g/dL strategy and highest in the <9g/dL strategy, and the rate of transfusions decreased monotonically as Hgb thresholds decreased. Relative to the <10g/dL strategy, the estimated HRs (95% CI) from the IP weighted model of 30-day death/MI were 1.07 (0.77-1.50) for the <9g/dL strategy, 1.14 (0.84-1.55) for the <8g/dL strategy, and 1.44 (0.99-2.09) for the <7g/dL strategy (Figure). A log-linear estimate over strategy thresholds between 7-10g/dL estimated a 1.12 (95% CI 1.00-1.27) times greater average risk of death/MI and a 1.12 (95% CI 0.92, 1.37) times greater average risk of death over 30 days for each 1g/dL decrease in the Hgb threshold. The IP weighted cumulative incidence curves showed similar increase in risk of death/MI as transfusion thresholds decreased throughout 30 days post-randomization. Conclusions Relative to a <10g/dL transfusion strategy, we estimated a progressively greater risk of 30-day death/MI as transfusion Hgb thresholds decreased within the range of 7-10g/dL. Targeting a Hgb concentration of 10g/dL in patients with a recent acute MI may avoid serious risks associated with anemia.Hazard ratios for 30-day death/MI

Recent secular trends of catheter-directed therapy for treatment of pulmonary embolism: a retrospective cohort study based on German national data

Abstract Background Various approaches exist for treatment of pulmonary embolism, including systemic lysis, catheter-directed therapy, or anticoagulation. Purpose This study aimed to describe recent secular trends of treatment strategies for patients with pulmonary embolism. Methods Data were interrogated from the Research Data Centre of the German Federal Statistical Office by ICD- and OPS-codes. 800,119 patients with pulmonary embolism, who were treated in German hospitals between 2007 and 2021, were analyzed and grouped according to the therapeutic strategy: no lysis or intervention, systemic lysis, ultrasound-assisted thrombolysis, catheter-directed lysis without ultrasound, retriever system, other transluminal thrombus removal, or surgical thrombectomy. In-hospital outcomes were investigated with focus on the last 8 years. Results Of all patients examined, 37,885 were treated with systemic lysis, 1,383 with ultrasound-assisted thrombolysis, 2,520 with catheter-directed lysis without ultrasound, 181 with a retriever system, 695 with other transluminal thrombus removal, and 1,037 with surgical thrombectomy. There was an increase in all catheter-directed therapies between 2007 and 2021 (from 102 to 735 procedures per year) with more than twice as many procedures from 2019 to 2021 (from 343 to 735 procedures). Between 2014 and 2021, 453,893 patients with main diagnosis of pulmonary embolism were included in the analysis. Mean age was 58.4-68.1 years in the observed groups. 42.5-52.2% were female. Highest rates of cor pulmonale were observed in patients undergoing surgical thrombectomy (87.7%) and systemic lysis (80.1%), which also applied to shock (26.2% and 25.7%), while both rates were lowest in patients without lysis or intervention (cor pulmonale: 25.4%, shock: 1.8%). The overall in-hospital mortality rate was 8.3%, ranging between 6.5% in the ultrasound-assisted thrombolysis group and 38.4% in the systemic lysis group. In catheter-directed therapies, the rate of major bleeding (>5 units of red blood cells) was 4.9%, ranging from 3.1% for catheter-directed lysis without ultrasound to 10.1% for other transluminal thrombus removal. The rate of intracerebral bleeding was 1.4%, with 0.0% for ultrasound-assisted thrombolysis and 4.4% for treatment with a retriever system. Conclusion In recent years, the use of catheter-directed therapy for pulmonary embolism has steadily increased. Rates of in-hospital major bleeding events and intracerebral bleeding were low.

Mortality, Clinical Complications, and Healthcare Resource Utilization Associated with Managing Transfusion-Dependent β-Thalassemia and Sickle Cell Disease with Recurrent Vaso-occlusive Crises in Italy.

To examine the clinical burden and healthcare resource utilization (HCRU) among patients with transfusion-dependent β-thalassemia (TDT) and patients with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) in Italy. Eligible patients were identified from an administrative claims database from 1 January 2010 and 1 February 2019. Patients with TDT had ≥ 1 iron chelation treatment, ≥ 8 red blood cell transfusions (RBCTs) during any 12-month period, and ≥ 12 months of available data pre- and post-index (i.e., first RBCT claim). Patients with SCD with recurrent VOCs had ≥ 2 VOCs/year in ≥ 2 consecutive years and ≥ 12 months of available data pre- and post-index (second VOC claim in the second of 2 consecutive years). Patients were propensity score matched to five controls by age, sex, geographic area, and index year. Clinical and HCRU outcomes were evaluated post-index. In total, 214 patients with TDT and 111 patients with SCD with recurrent VOCs were matched to 1070 and 555 controls, respectively. Both patient groups had substantially higher mortality rates than controls (TDT: 4.8 versus 0.8 deaths per 100 person-years; SCD: 1.6 versus 0.4 deaths per 100 person-years). Clinical complications were prevalent in both patient groups. Compared with controls, both patient groups had significantly higher mean rates of all-cause hospitalizations (TDT: 1.4 versus 0.1; SCD: 2.0 versus 0.1) and outpatient services (TDT: 21.9 versus 1.6; SCD: 6.2 versus 1.0) per patient per year (all: p < 0.05). Management of TDT and SCD in Italy is associated with significant clinical and health system burden, highlighting the need for new treatments that eliminate RBCTs and VOCs.

Red blood cell distribution width to albumin ratio as novel prognostic biomarker in cardiovascular disease

Abstract Background The red blood cell distribution width-to-albumin ratio (RAR) is a novel, cost-effective, and accessible biomarker for inflammation. Although numerous studies have investigated the relationship between RAR values and mortality in cardiovascular diseases (CVD), the generalizability and robustness of these individual studies' results remain uncertain, underscoring the necessity for a meta-analysis. Purpose To explore the pooled association between RAR and all-cause mortality in several CVDs. Methods A systematic search for eligible studies was conducted across scientific databases, including Scopus, Web of Science, PubMed, and ProQuest, up to February 1, 2024. Mortality hazard ratios (HRs) for the highest versus lowest RAR categories were pooled using the Generic Inverse Variance method. A dose-response meta-analysis was performed using generalized least-squares regression to estimate trends of HRs across dose categories. Publication bias was assessed by inspecting funnel plots and performing Egger's test. Subgroup analyses were based on the underlying CVDs. Statistical analyses were executed in RStudio software, with the significance threshold set at p &amp;lt; 0.05. Results This systematic review and meta-analysis reviewed 16 high-quality studies published between 2021 and 2024 with 30,933 participants. The underlying diseases in the included studies were Acute Myocardial Infarction (AMI), Heart Failure (HF), Atrial Fibrillation (AF), aortic valvular disease, stroke and pulmonary embolism. The lowest quartile range for RAR was 0.80–1.20 ml/g, while the highest quartile ranged from 6.09 to 15.45 ml/g. Pooled results with a random-effect model showed that patients with higher RAR had significantly increased risk of all-cause mortality (HR 1.88, 95%CI 1.59–2.23, p&amp;lt;0.0001, I² = 91%). Non-linearity was observed in the dose-response relationship; thus, it was primarily illustrated using the restricted cubic spline model, with the linear model provided for comparison. A 1 ml/g increase in RAR corresponded to a 27% rise in the predicted HR for all-cause mortality (HR 1.27, 95%CI 1.16–1.39; p &amp;lt; 0.0001). Subgroup analyses based on the primary CVD diagnoses in the included studies confirmed a significant association between RAR values and all-cause mortality across all subgroups (AMI: HR 2.43, 95%CI 1.52–3.87, I² = 45%; HF: HR 1.78, 95%CI 1.13–2.81, I² = 94%; Stroke: HR 1.58, 95%CI 0.94–2.67, I² = 90%; Other CVD: HR 1.97, 95%CI 1.34–2.89, I² = 57%; p for interaction 0.24). Conclusion This is the first meta-analysis demonstrating the positive dose-response association between RAR values and all-cause mortality in CVD. Thus, RAR may be considered as a simple and practical prognostic biomarker in CVD.Forest plot based on CVD diagnosisDose-response RAR value to HR

Construction of an inflammatory, nutritional, and metabolic prognostic risk score in patients with heart failure with preserved ejection fraction: a machine learning-based approach

Abstract Background Chronic inflammation, malnutrition, and metabolic syndrome contribute to the underlying mechanisms of heart failure with preserved ejection fraction (HFpEF). Inflammatory, nutritional, and metabolic biomarkers often interact with each other and affect the prognosis of patients. Purpose We aimed to identify the most predictive indicators from a pool of 21 biomarkers encompassing inflammation, nutritional status, as well as lipid, glucose, thyroid, and uric acid metabolism. Subsequently, predictive biomarkers were used to develop a risk score to enhance risk prediction for patients with HFpEF. Methods We included patients diagnosed with HFpEF and without infective or systemic disease. The primary outcome was all-cause mortality. We employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression to screen the biomarkers. A machine learning-based approach was utilized to fine-tune the optimal model parameters. Additionally, we generated 1000 bootstrapping datasets to identify biomarkers recurring above a 95% frequency in repetitions, which were then employed to formulate the biomarker risk score. The discrimination of incorporating the risk score into the basic model was evaluated using 100 iterations of 5-fold cross-validation to assess the predictive efficacy. Results Among the 1311 included patients (with a median age of 64 years and 42.6% female), 363 patients (27.7%) experienced mortality over a median follow-up period of 2.7 years. The final risk score model was derived from 5 biomarkers—albumin (ALB), red blood cell distribution width-standard deviation (RDW-SD), lymphocytes, triiodothyronine (T3), and uric acid—each selected in over 95% of 1000 bootstrapping iterations. Integration of this risk score into the basic model notably enhanced discrimination (∆C-index=0.015, 95% CI 0.005-0.023) and reclassification (IDI: 3.3%, 95% CI 1.7%-5.8%; NRI: 15.2%, 95% CI 6.5%-22.5%) for risk stratification. In time-dependent receiver operating characteristic (ROC) analysis, the mean area under the curve (AUC) of the risk score was 0.688, 0.710, and 0.738 at 1, 3, and 5 years post-discharge, respectively, in the cross-validation sets. Incorporating the risk score into the basic model significantly improved the AUC at 1, 3, and 5 years (DeLong test P-value&amp;lt;0.05). Furthermore, in multivariable Cox regression, the risk score demonstrated an independent association with all-cause mortality (HR: 1.81, 95% CI 1.51-2.16, P&amp;lt;0.001 per 1 score increase). Conclusions A risk score derived from 5 commonly used inflammatory, nutritional, thyroid and uric acid metabolic biomarkers can effectively identify high-risk patients with HFpEF. This approach supports the development of potential individualized management strategies for patients with HFpEF.Study population and model constructionPredictive performance of the risk score

Is it useful to washing stored red blood cells in cardiopulmonary bypass priming fluid for neonatal cardiac surgery

Abstract Background The small blood volume and immature physiology of neonates necessitate careful consideration of the priming fluid composition during cardiopulmonary bypass (CPB) surgery, as it has a substantial impact on their physiologic stability. This study aimed to investigate the impact of allogeneic stored RBCs processed by an autotransfusion system into the CPB priming fluid for neonatal cardiac surgery. Methods This retrospective cohort study investigated the effects of incorporating unwashed (n=56) or washed (n=45) RBCs into the CPB priming fluid for elective neonatal cardiac surgery. We compared perioperative blood parameters, inflammatory mediators, coagulation indicators, vasoactive inotrope score (VIS), other relevant blood parameters and clinical outcomes between the two groups. The regression models were employed to evaluate the independent association between RBCs washing and prognostic outcomes. Results The autotransfusion system can effectively improve the quality of stored RBCs. During CPB, washed group exhibited higher peak hematocrit (P &amp;lt; 0.01), peak hemoglobin (P = 0.04), increased oxygen delivery index during rewarming (P &amp;lt; 0.05). The washed group exhibited significantly lower early postoperative lactate levels and VIS scores (P &amp;lt; 0.05). Despite demonstrating fluctuations in inflammatory (IL-6, IL-8, IL-10）and coagulation parameters(DD, FIB, FDP) compared to baseline, the two groups exhibited no significant divergence. Notably, the washed group experienced a lower incidence of hyperlactacidemia and delayed sternal closure at weaning from CPB. Conclusions The addition of washed allogeneic stored RBCs to neonatal CPB priming fluid significantly attenuated postoperative lactate elevation and lowered VIS without improving early alterations in the inflammatory and coagulation systems.

Effect of Whole Blood Dietary Mineral Concentrations on Erythrocytes: Selenium, Manganese, and Chromium: NHANES Data.

Selenium (Se), Manganese (Mn), and Chromium (Cr) are dietary minerals ingested from specific grains, vegetables, and animal meats. Prior research showed that these minerals affect animal erythrocyte health but have unknown effects on human red blood cells (RBCs) and hematology. This study evaluated the effects of these dietary minerals on RBC count, hematocrit, and hemoglobin. We conducted a cross-sectional analysis of 23,844 American participants from the 2015-2016 and 2017-2020 National Health and Nutrition Examination Survey. We evaluated sex, age, ethnicity, education, income, and smoking status as covariates. Linear regression analyses were conducted to evaluate the effect of Cr, Se, and Mn on RBC count, hematocrit, and hemoglobin levels. We employed subpopulation-exclusion regressions further to explore the distinct effects of mineral elevation and deficiency. Additional analyses were performed to examine the relationship between Mn and RBC hemoglobin, RBC distribution width, transferrin receptor concentrations, transferrin saturation, and serum iron levels to support the interpretation of our findings. Optimizable ensemble machine learning models were used to corroborate regression results. Adjusting for covariates, Cr was inversely associated with RBC count (Exp(b) = 0.954), hemoglobin (Exp(b) = 0.868), and hematocrit (Exp(b) = 0.668). Conversely, Se was positively associated with RBC count (Exp(b) = 1.003), hemoglobin (Exp(b) = 1.012), and hematocrit (Exp(b) = 1.032). Mn was positively associated with RBC count (Exp(b) = 1.020) but inversely associated with hemoglobin (Exp(b) = 0.945) and hematocrit (Exp(b) = 0.891). Cr was harmful to RBC health in all subpopulations, whereas Se was protective. Mn appears to contribute to the development of microcytic anemia, but only in subjects with clinically elevated Mn levels. Thus, excessive consumption of foods and supplements rich in Cr and Mn may harm human erythrocyte health and hematology.

An analysis of decipherable red blood cell abnormality detection under federated environment leveraging XAI incorporated deep learning

In recent times, automated detection of diseases from pathological images leveraging Machine Learning (ML) models has become fairly common, where the ML models learn detecting the disease by identifying biomarkers from the images. However, such an approach requires the models to be trained on a vast amount of data, and healthcare organizations often tend to limit access due to privacy concerns. Consequently, collecting data for traditional centralized training becomes challenging. These privacy concerns can be handled by Federation Learning (FL), which builds an unbiased global model from local models trained with client data while maintaining the confidentiality of local data. Using FL, this study solves the problem of centralized data collection by detecting deformations in images of Red Blood Cells (RBC) in a decentralized way. To achieve this, RBC data is used to train multiple Deep Learning (DL) models, and among the various DL models, the most efficient one is considered to be used as the global model inside the FL framework. The FL framework works by copying the global model’s weight to the client’s local models and then training the local models in client-specific devices to average the weights of the local model back to the global model. In the averaging process, direct averaging is performed and alongside, weighted averaging is also done to weigh the individual local model’s contribution according to their performance, keeping the FL framework immune to the effects of bad clients and attacks. In the process, the data of the client remains confidential during training, while the global model learns necessary information. The results of the experiments indicate that there is no significant difference in the performance of the FL method and the best-performing DL model, as the best-performing DL model reaches an accuracy of 96% and the FL environment reaches 94%-95%. This study shows that the FL technique, in comparison to the classic DL methodology, can accomplish confidentiality secured RBC deformation classification from RBC images without substantially diminishing the accuracy of the categorization. Finally, the overall validity of the classification results has been verified by employing GradCam driven Explainable AI techniques.

Efficacy of Epoetin Alfa in Managing Symptomatic Anaemia in Low-Risk Myelodysplastic Syndromes: A Retrospective Analysis.

Background Myelodysplastic syndromes (MDS) are clonal myeloid disorders characterised by ineffective haematopoiesis, leading to anaemia that often requires dependence on red blood cell (RBC) transfusions. Epoetin alfa (Eprex®) is now a mainstay in the management of symptomatic anaemia in low-risk MDS patients, reducing transfusion dependence and improving the quality of life in this patient group. Objective This retrospective study aimed to assess the efficacy of epoetin alfa in treating symptomatic anaemia in low-risk MDS patients, focusing on transfusion independence and its relationship with baseline erythropoietin (EPO) levels and haemoglobin (Hb) response. Methods Data from 56 patients with low-risk MDS treated with epoetin alfa at Norfolk and Norwich University Hospital,Norwich, United Kingdom, between 2018 and 2023 were retrospectively analysed. Baseline EPO levels, transfusion history, Hb response, and the duration of transfusion independence were assessed. Statistical analyses were performed to evaluate the correlation between baseline characteristics and treatment outcomes. Results Among the patients, 98.2% had baseline EPO levels below the 500 IU/L threshold, with a median EPO level of 74.3 IU/L. Following an eight-week trial of 30,000 units of epoetin-alfa, 41.1% of patients showed improved Hb levels, 41.1% maintained stable Hb levels, and 17.9% experienced a decline. A significant correlation was found between lower baseline EPO levels (<250 IU/L) and a positive treatment response (p = 0.0065). Additionally, patients who required fewer transfusions before treatment had longer durations of transfusion independence (correlation coefficient = -0.40, p = 0.015). Dose escalation to 60,000 units provided a benefit to 53.3% of patients with initially stable Hb levels. The average duration of transfusion independence was 8.1 months, and patients with improved Hb levels had the longest periods of transfusion independence (p = 0.005). Conclusion Epoetin alfa is an effective therapy for managing symptomatic anaemia in low-risk MDS patients. This study highlights its efficacy and provides valuable predictive information, particularly showing that patients with lower baseline EPO levels are more likely to respond to treatment. While prior transfusion dependence did not significantly predict response to therapy in this cohort, it was associated with the duration of transfusion independence.

Increased calcification by erythrophagocytosis in aortic valvular interstitial cells.

Calcific aortic valve disease (CAVD) progresses over time to severe aortic stenosis and eventually heart failure. Recent evidence indicates that intraleaflet haemorrhage (ILH) strongly promotes CAVD progression. However, it remains poorly understood how it mechanistically contributes to valvular calcification. ILH was identified as iron deposition by morphological analysis. To elucidate the underlying mechanism, human valvular interstitial cells (VIC) were cultured in the presence of fresh or senescent red blood cells (RBC), simulating ILH in vivo conditions. ILH was common in aortic valves derived from patients with severe aortic stenosis. VIC undergo erythrophagocytosis of senescent RBC, leading to intracellular iron accumulation analogous to observed following exposure to extracellular iron. The presence of senescent RBC significantly intensified VIC calcification, which was significantly mitigated by ferroptosis inhibition. Our results identify erythrophagocytosis by VIC, leading to iron accumulation and enhanced calcification through ferroptosis. This may be a crucial component of the pathophysiological mechanisms that links ILH to valvular calcification and accelerated aortic stenosis progression.

Criteria for identifying a risk group for iron deficiency anemia from among healthy women of reproductive age

The article presents the results of a survey of healthy women of reproductive age with the definition of criteria for identifying a risk group for anemia from among them. The criteria were the indicators of peripheral blood: a decrease in the concentration of Hb (below 120.0 g/l) of blood and hematocrit, an expansion of RDW, a decrease in the volume of red blood cells (MCV), as well as a decrease in the amount of serum iron, ferritin, total protein that do not reach the lower limit of normal and the presence of a history of diagnosis of somatoform dysfunction of the autonomic nervous system. The application of the identified criteria for the early diagnosis of iron deficiency will allow effective timely preventive measures to prevent the development of iron deficiency anemia in women of reproductive age.

Linolenic acid stimulates eryptosis and hemolysis through oxidative stress and CK1α/MLKL: protective role of melatonin, urea, and polyethylene glycol

Anticancer medications cause anemia in patients through ill-defined mechanisms, including hemolysis and eryptosis. Although α-linolenic acid (ALA) possesses anticancer properties against a variety of cancer cells, there is a dearth of evidence regarding how it modulates red blood cell (RBC) physiology. RBCs from healthy donors were subjected to anticancer concentrations of ALA (2.5, 5, 10, 20, 40, 80, and 100 μM) at 37 °C for 24 h, and colorimetric tests were used to determine hemolysis and acetylcholinesterase (AChE) activity. Meanwhile, flow cytometry was employed to identify eryptotic cells using annexin-V-FITC and forward scatter (FSC), Fluo4/AM to detect Ca2+, and H2DCFDA to assess oxidative stress. ALA significantly increased hemolysis and eryptosis in a concentration-dependent manner, along with elevated Fluo4 and DCF fluorescence, and erythrocyte sedimentation rate, and reduced FSC and AChE activity. Moreover, the addition of D4476, necrosulfonamide, melatonin, isosmotic urea, and polyethylene glycol 8000 – but not sucrose – significantly inhibited ALA toxicity. In conclusion, ALA stimulates hemolysis and eryptosis through Ca2+ buildup, oxidative stress, anticholinesterase activity, casein kinase 1α (CK1α), and mixed lineage kinase domain-like protein (MLKL). The anticancer activity of ALA may be potentiated by the use of Ca2+ channel blockers and chelators, antioxidants, and CK1α and MLKL inhibitors to ameliorate its toxicity to RBCs.

Risk factors of pediatric steroid-induced ocular hypertension.

Steroid-induced ocular hypertension (SIOH) is a significant ocular complication of pediatric steroid administration. In this study, we analyzed the risk factors associated with pediatric SIOH. We retrospectively collected data from 78 children under 20 years of age who received systemic steroids during hospitalization. The data included age, gender, primary disease, intraocular pressure (IOP) before and one month after administration, total monthly steroid dose adjusted for body weight (BW), and one-month changes in red blood cell, white blood cell, and platelet counts. A multivariate analysis was used to identify risk factors related to steroid responsiveness. Thirty patients (38.5%) were classified as steroid responders, and 48 as non-responders. The median IOP during the first month of steroid treatment was 24.0 mmHg (IQR; 23.0-28.3) for responders and 15.0 mmHg (IQR; 12.3-18.0) for non-responders. The Generalized Estimating Equations analysis revealed that younger age, male sex, primary disease, increase the amount of white blood cell (WBC) and total steroid dose per BW in one month were independently associated variables. The receiver operating characteristic analysis also revealed that the cutoff values for age, total monthly steroid dose, the increase amount of WBC were 11.0 years, 40.7mg/kg and 3.40 × 10²/µl respectively. High-dose steroid administration, especially in male, younger patients, necessitates careful monitoring for IOP changes during treatment. WBC count also needs to be monitored during IOP follow-ups. What is known Steroid-induced ocular hypertension (SIOH) is one of the essential complicationsduring steroid administration,but onlylimited analyses have been performed in children. What is new A comprehensive analysis of multiple factors was performed that are predicted to be associated with pediatric SIOH from previous literature. Younger age, male sex, primary disease, increase the amount of WBC, and highertotal monthly steroid dose were extracted as risk factors of SIOH. This study can contribute to the prediction of cases in which ophthalmologic examinations are particularly important during systemic steroid administration in children.

The evaluation of complete blood count parameters in the patients with idiopathic versus secondary cerebral venous thrombosis

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 and March 2021. All participants with CVT were registered in the organized registry system at the Neurology Research Center of Shiraz University of Medical Sciences, Shiraz, Iran (CVT registry code: 9001013381). The control group consisted of age- and sex-matched individuals without systemic diseases. CBC results from the control group and the first recorded hospital CBC of the patient group were collected. Results: The study included 295 patients with CVT [49 with idiopathic CVT (iCVT) and 246 with secondary CVT (sCVT)] and 341 healthy individuals. Among the CVT group, 72.54% were women. Patients with CVT had higher red cell distribution width (RDW) and lower red blood cell (RBC) count, hemoglobin (Hb) levels, and hematocrit compared to the non-CVT group. In iCVT cases, male gender, RBC count, Hb levels, and hematocrit were notably higher compared to sCVT cases. Logistic regression analysis showed that female gender, smoking, and higher hematocrit values were associated with increased probability of iCVT. Conclusion: The study suggests that certain CBC parameters may serve as potential markers for assessing CVT risk and differentiating between iCVT and sCVT cases. Validation and further research are needed to explore the underlying mechanisms.March 2021.

IMM2520, a novel anti-CD47/PD-L1 bispecific antibody for cancer immune therapy

PD-1/PD-L1 is an important signaling pathway in the adaptive immune system. The CD47/SIRPα signaling pathway is a crucial “do not eat me” signal for innate immunity. This study evaluated the anti-tumor mechanism of IMM2520 in vitro and in vivo. IMM2520 was generated using the “mab-trap” platform. IMM2520 showed high affinity to PD-L1 and relatively lower affinity to CD47, displaying preferential binding to PD-L1 on tumor cells. IMM2520 had the potent ability to inhibit the PD-1/PD-L1 and CD47/SIRPα signaling pathways and killed tumor cells through ADCC and ADCP. Importantly, IMM2520 did not bind to human red blood cells or induce erythrocyte agglutination. IMM2520 demonstrated a tendency to bind to CD47+/PD-L1+ tumor cells, reducing its binding to CD47 single-positive cells. In mouse transplantation models, compared with the first-generation CD47/PD-L1 BsAb (IMM2505), IMM2520 exhibited stronger and dose-dependent antitumor activity. These findings imply that IMM2520 may offer a novel therapeutic alternative for cancer patients.

Sickle Cell Anemia and Pregnancy Hemolysis: Clinical Considerations

Sickle cell anemia (SCA) is a hereditary blood disorder characterized by abnormal hemoglobin production, leading to chronic hemolysis and episodic vaso-occlusive crises (VOCs). Pregnancy in women with SCA poses significant clinical challenges due to the increased physiological demands, which exacerbate hemolysis and increase maternal and fetal risks. This review explores the pathophysiology of hemolysis in SCA during pregnancy, its clinical implications, and management strategies aimed at improving maternal and fetal outcomes. Hemolysis can result in severe anemia, acute chest syndrome, increased risk of infections, and adverse fetal outcomes, such as intrauterine growth restriction and preterm delivery. Management strategies for hemolysis in pregnancy include blood transfusions, pharmacological therapies, nutritional supplementation, and emerging treatments like gene therapy. Blood transfusions are widely used to mitigate anemia and reduce the number of circulating sickled cells, while pharmacological agents such as L-glutamine help address oxidative stress. Nutritional support, particularly with folic acid and antioxidants, is essential in promoting healthy red blood cell production and mitigating oxidative damage. Emerging therapies like gene editing offer promising future directions for more effective management of SCA and pregnancy-related hemolysis.

Biomechanics of phagocytosis of red blood cells by macrophages in the human spleen

The clearance of senescent and altered red blood cells (RBCs) in the red pulp of the human spleen involves sequential processes of prefiltration, filtration, and postfiltration. While prior work has elucidated the mechanisms underlying the first two processes, biomechanical processes driving the postfiltration phagocytosis of RBCs retained at interendothelial slits (IES) are still poorly understood. We present here a unique computational model of macrophages to study the role of cell biomechanics in modulating the kinetics of phagocytosis of aged and diseased RBCs retained in the spleen. After validating the macrophage model using in vitro phagocytosis experiments, we employ it to probe the mechanisms underlying the kinetics of phagocytosis of mechanically altered RBCs, such as heated RBCs and abnormal RBCs in hereditary spherocytosis (HS) and sickle cell disease (SCD). Our simulations show pronounced deformation of the flexible and healthy RBCs in contrast to minimal shape changes in altered RBCs. Simulations also show that less deformable RBCs are engulfed faster and at lower adhesive strength than flexible RBCs, consistent with our experimental measurements. This efficient sensing and engulfment by macrophages of stiff RBCs retained at IES are expected to temper splenic congestion, a common pathogenic process in malaria, HS, and SCD. Altogether, our combined computational and in vitro experimental studies suggest that mechanical alterations of retained RBCs may suffice to enhance their phagocytosis, thereby adapting the kinetics of their elimination to the kinetics of their mechanical retention, an equilibrium essential for adequately cleaning the splenic filter to preserve its function.

Observation of the effect of single dose intravenous infusion of tranexamic acid on white blood cell, erythrocyte sedimentation rate and C-reactive protein after double segmental posterior lumbar interbody fusion

To observe the safety and effectiveness of single dose intravenous infusion of tranexamic acid (TXA) in dual level posterior lumbar interbody fusion (PLIF), and to explore the changes and trends in perioperative white blood cell (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Between October 2020 and September 2022, 46 patients with lumbar degenerative disease were treated with dual level PLIF, including 18 males and 28 females, with an average age of (60.24±10.68) years old, from 34 to 80 years old. They were divided into observation group and control group according to different treatment methods. There were 28 patients in the observation group, including 12 males and 16 females, with an average age of (61.04 ± 9.03) years old. There were 3 cases with lumbar disc herniation (LDH), lumbar spinal stenosis (LSS) 18 cases, lumbar spondylolisthesis (LS) 7 cases. TXA (1 g/100 ml) was administered intravenously 15 min before skin incision after general anesthesia. The control group consisted of 18 patients, including 6 males and 12 females, with an average age of (59.00±13.04) years old. There were 5 cases with LDH, LSS 9 cases, LS 4 cases, and TXA was not used. The operation time, intraoperative bleeding volume, postoperative drainage volume, postoperative deep vein thrombosis (DVT), postoperative hospital stay, postoperative activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (FIB), platelet (PLT), red blood cell (RBC), hemoglobin (HB), hematocrit (HCT), the first day, the fourth day, the seventh day and the last tested after operation WBC, ESR and CRP were recorded. The postoperative wounds of the patients healed well and there was no DVT. 46 patients were followed up from 3 to 6 months. The intraoperative blood loss was 400.0 (300.0, 500.0) ml and the postoperative drainage was 260.0 (220.0, 450.0) ml in the observation group, which were lower than the control group[600.0(400.0, 1000.0) ml, 395.0 (300.0, 450.0) ml], P<0.05. There was no significant difference between the two groups in operation time, postoperative hospital stay, postoperative APTT, PT, TT, FIB, PLT, RBC, HB, HCT, and postoperative WBC, ESR and CRP at different times (P>0.05). Single dose intravenous infusion of TXA can reduce the blood loss of bi-segmental PLIF, and has no significant effect on WBC, ESR and CRP after operation.

Solvent Choice during Flow Assembly of Photocross-Linked Single-Chain Nanoparticles and Micelles Affects Cellular Uptake.

Polymeric micelles have widely been used as drug delivery carriers, and recently, single-chain nanoparticles (SCNPs) emerged as potential, smaller-sized, alternatives. In this work, we are comparing both NPs side by side and evaluate their ability to be internalized by breast cancer cells (MCF-7) and macrophages (RAW 264.7). To be able to generate these NPs on demand, the polymers were assembled by flow, followed by the stabilization of the structures by photocross-linking using blue light. The central aim of this work is to evaluate how the type of solvent affects self-assembly and ultimately the structure of the final NP. Therefore, a library of copolymers with different sequences, including block copolymers (AB, ABA, BAB), and statistical copolymers (rAB and rAC) was synthesized using PET-RAFT with A denoting poly(ethylene glycol) methyl ether acrylate (PEGMEA), B as 2-hydroxyethyl acrylate (HEA), and C as 4-hydroxybutyl acrylate (HBA). The polymers were conjugated with a quinoline derivative to enable the formation of cross-linked structures by photocross-linking during flow assembly. Using water as the dispersant for photocross-linking led to the preassembly of these amphiphilic polymers into compact SCNPs and cross-linked micelles, resulting in a quick photoreaction. In contrast, acetonitrile led to fully dissolved polymers but a low rate of the photoreaction. These intramolecularly cross-linked polymers were then placed in water to result in more dynamic micelles and looser SCNPs. Small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and size exclusion chromatography (SEC) coupled with a viscosity detector show that cross-linking in acetonitrile results in better-defined NPs with a shell rich in PEGMEA. Cross-linking in acetonitrile led to NPs with significantly higher cellular uptake. Interestingly, passive transport was identified as the main pathway for the delivery of our NPs on MCF-7 cells, confirmed by the uptake of NPs on cells treated with inhibitors and by red blood cells. This work underscored the importance of the polymer precursor's structure and the choice of solvent during intramolecular cross-linking in determining the drug delivery efficiency and biological behavior of SCNPs.