Transfusion

BACKGROUND: The transport and storage conditions of thawed plasma are not strictly regulated by the FDA and applying red blood cell transport standard of 1-10 degrees Celcius to recently thawed plasma often results in high discard rates. This study evaluated the extended 120-hour (5-day) coagulation factor stability and sterility of thawed plasma frozen within 24 hours (PF24) following a 6-hour transport cooler simulation. STUDY DESIGN AND METHODS: Fourteen PF24 units (8 group O, 6 group B) were thawed at 30-37 degrees Celcius and assigned as control (n=7, direct 1-6 degrees Celcius refrigeration) or experiment (n=7) units. Experiment units were held at room temperature for 30 minutes, stored in validated transport coolers for 6 hours, and then transferred to 1-6 degrees Celcius refrigeration. Measurements of temperature, prothrombin time (PT), Factor V (FV) activity, and Factor VIII (FVIII) activity were conducted at 0-, 6-, 24-, and 120-hour post-thaw. Sterility testing was performed at 0-hour and 120-hour using automated aerobic and anaerobic blood cultures. RESULTS: No statistically significant differences were observed between control and experiment units at 120-hour for mean PT (15.09 vs. 15.16 seconds, p = .44), FV activity (81.14 vs. 74.57%, p = .23), or FVIII activity (61.86 vs. 53.00%, p = .22). Delta analysis (120h-0h) confirmed equivalent factor decay rates between groups. All bacterial cultures showed no growth at 120-hour. CONCLUSION: A 6-hour cooler time of thawed PF24 does not accelerate coagulation factor degradation or compromise sterility over an extended 5-day shelf life. These findings validate flexible inventory return policies, allowing blood banks to reduce product waste.

Background and Objectives: Preterm infants are commonly transfused, yet direct cardiorespiratory effects of red blood cell (RBC) transfusions remain poorly understood. We explored the feasibility of using multicentre electronic health data (EHD) to study such cardiorespiratory responses. Methods: Highly granular routine EHD were collected from preterm infants born <32 weeks gestational age at three European centres. Heart rate, oxygen saturation, and respiratory rate were evaluated 12 hours before and after the RBC transfusion. Results: A total of 321 transfusions in 164 infants were analysed. Overall, there was no significant change in the rate of bradycardia and apnoea following transfusion. Cardiorespiratory parameters varied substantially between infants; e.g. 20% of transfusions were associated with an unexpected, significant increase in heart rate. Respiratory rate and oxygen saturation exhibited similarly heterogenous patterns following transfusion. In sub-group analysis, the proportion of transfusions with increased heart rate was significantly higher within the first two weeks than later (32% vs 13%, p=0.0019). Conclusions: Multicentre EHD extraction allows to identify otherwise masked short-term effects of RBC transfusions on cardiorespiratory parameters, possibly indicating cardiac or pulmonary overload. Such effects may vary with adaptation to anaemia. Analysing EHD may ultimately enable personalized transfusion practice.

Objective: To investigate the distribution frequencies of Rh blood group antigens (C, c, D, E, e) and phenotypes in the population of Hengyang, Hunan Province, and to analyze the production of Rh alloantibodies in repeatedly transfused patients, thereby providing a basis for developing precise transfusion strategies. Methods: Rh phenotyping, antibody screening, and antibody identification were performed on 3,635 hospitalized patients and 5,326 blood donors using Rh blood group typing cards. A blood transfusion management system was used to identify and track patients' historical specific antibodies, with automatic alerts for inconsistent results. Results: The antigen frequency distribution in patients was D (99.56%) > e (94.69%) > C (91.64%) > c (48.06%) > E (38.79%). The phenotypic distribution frequencies among Rh(D)-positive patients were as follows: CCDee (51.31%) > CcDEe (30.01%) > CcDee (9.37%) > ccDEE (5.00%) > ccDEe (2.79%) > CCDEe (0.80%) > ccDee (0.39%) > CcDEE (0.28%) > CCDEE (0.05%). From March to October 2023, after implementing Rh phenotyping and antigen-matched compatible transfusions for five antigens, the antibody screening positivity rate decreased to 0.97%, compared to 1.14% during the same period in 2022 (p < 0.05). Antibody identification in 276 antibody-positive samples revealed that alloantibodies against the Rh system accounted for the highest proportion (46.01%, 127/276), which was lower than the 55.21% observed in 2022 (p < 0.05). Unexpected antibodies in the Rh system were the primary cause of crossmatch incompatibility in clinical transfusions, accounting for 46.01%. Conclusion: Rh phenotyping and sustained antigen-matched compatible transfusions in repeatedly transfused patients can effectively prevent and reduce alloantibody production. Continuous tracking of specific antibodies and transfusion efficacy evaluation can be achieved through an efficient blood transfusion management system.

Background aimsThe development of next-generation therapies for sickle cell disease (SCD) and beta thalassemia (beta thal), including fetal globin-inducing small molecules and gene therapy approaches, depends on patient-derived CD34+ hematopoietic stem and progenitor cells (HSPCs) for discovery and preclinical validation, but commercial vendors stock only healthy donor material and disease-specific banks hold limited inventories. Recent US Food and Drug Administration and National Institutes of Health guidance favoring human cell-based methods over animal testing underscores the value of authentic patient cells. Methods: Over 14 months we recovered, purified, and biobanked CD34+ HSPCs from clinical apheresis product waste and mobilized peripheral blood (PB) otherwise discarded after clinical procedures, using immunomagnetic selection adapted for hemoglobinopathy specimens; a microfluidic technology was evaluated separately. We quantified yield and purity for bead-selected material and cell number and viability for the microfluidic pilot; engraftment was tested in NBSGW mice. Results: Immunomagnetic selection recovered a median of 4.71 x 106 CD34+ cells from just 1 to 2 mL of apheresis product waste, comparable to the 6.0 x 106 cells from a 10 to 40 fold larger volume of PB waste, with similar purity across sources and diagnoses. Because apheresis product waste is far more concentrated, it reaches equivalent yields without the density-gradient steps required for PB waste, approximately halving processing time. Recovered cells engrafted NBSGW mice, confirming preserved repopulating capacity. The microfluidic pilot (two patients, 11 specimens) recovered 2.17 x 106 CD34+ cells per specimen at greater than 90% viability and purity. Conclusions: A center with existing apheresis infrastructure can reproducibly recover, bank, and distribute research-grade patient CD34+ HSPCs, addressing a recognized gap in the hemoglobinopathy pipeline. HighlightsO_LIClinical apheresis waste is used to generate a single-center biobank of high-quality, research-grade CD34+ HSPCs from patients with sickle cell disease and beta-thalassemia. C_LIO_LIConcentrated apheresis waste matches large-volume PB waste in CD34+ yield and purity. C_LIO_LIMicrofluidic enrichment recovers CD34+ cells at >90% viability and purity across 2 patients. C_LIO_LIRecovered CD34+ HSPCs engraft mice and form erythroid cells, preserving function. C_LI

Preoperative anaemia is common in adults undergoing cardiac surgery and may identify patients at increased perioperative risk. This systematic review and meta-analysis synthesised contemporary observational evidence in accordance with PRISMA 2020. Five databases were searched for peer-reviewed English language studies published from 2017 to July 2026. Random effects meta-analyses used restricted maximum likelihood estimation with Hartung-Knapp confidence intervals; crude exact count estimates were synthesised primarily and adjusted estimates separately. Fourteen observational cohort studies involving 74,571 adults, including 17,349 (23.3%) with anaemia, were included. Preoperative anaemia was associated with red cell transfusion (OR, 3.66; 95% CI, 2.14-6.24), acute kidney injury or renal failure (OR, 2.43; 95% CI, 1.84-3.21), early mortality (OR, 2.11; 95% CI, 1.40-3.17), and postoperative infection (OR, 1.49; 95% CI, 1.21-1.82), but not postoperative stroke (OR, 1.16; 95% CI, 0.43-3.17). Certainty was low for renal outcomes and very low for the other outcomes. Preoperative anaemia is an important perioperative risk marker, particularly for transfusion and renal complications, although causality cannot be established.

Quantitative measurement of fetal hemoglobin (HbF) using high-performance liquid chromatography (HPLC) is standard but expensive and widely unavailable in low-income settings. The newer Gazelle method, which employs single-use alkaline electrophoresis cartridges, provides a portable and relatively inexpensive potential alternative. In the current study, we tested 3055 venous blood samples collected from 1780 children with sickle cell anemia who were enrolled into the H-PRIME trial by both Gazelle and the Bio-Rad D-10 HPLC instrument, before and during hydroxyurea treatment. Data reinterpretation was required to quantify accurately high HbF values derived using the D-10. Mean (standard deviation) baseline HbF values by HPLC and Gazelle (N=2042) were 11.4% (SD 5.9%) versus 16.3% (SD 7.5%), respectively, while mean on-treatment HbF values (N=1013) were 18.9% (SD 9.0%) versus 25.4% (SD 11.5%), respectively. While overall agreement was good (Lins concordance 0.76, 95% CI 0.75-0.78), HbF values derived using Gazelle were modestly higher than HPLC values (Bland-Altman agreement mean +5.4%, 95%CI -2.4% to +13.2%), with the difference between measures increasing at higher HbF percentages. With strong concordance and more easily interpretable HbF values, Gazelle represents an attractive and inexpensive alternative to HPLC for HbF quantification in the low-income settings where most patients with sickle cell anemia live.

Objectives: Capturing adequate blood volume for blood cultures is critical for accurate detection of bloodstream infections. Pediatric volume targets vary by age and weight, whereas adult targets are standardized. The BD BACTEC FXI Culture System (FXI) contains an integrated calibrated load cell capable of automatically reporting blood volume measurements for each vial loaded onto the system. This study evaluated the accuracy of the FXI's blood volume measurements in simulated pediatric and adult patients. Methods: Mock pediatric and adult blood draws were performed, using bagged whole blood, to replicate real-world collection protocols. Syringe-collected blood volumes ranged from 2.0 to 15.0 mL for pediatric patients, depending on mock patient weight, and were fixed at 40.0 mL for adults. Samples were inoculated into BD BACTEC Peds Plus/F, Plus Aerobic/F, and Lytic/10 Anaerobic/F Culture Vials, with a target volume of 2.0 to 10.0 mL per bottle. Reference blood volumes were determined gravimetrically using manually obtained pre- and post-inoculation weights with a blood-specific gravity of 1.055 g/mL and were compared to the automatically measured, gravimetric-based blood volumes reported by the BACTEC FXI Culture System. Results: Automated volume estimates were accurate to a mean error of -0.03 mL per bottle (SD, 0.40 mL; n=168; 95% CI, -0.09 mL, 0.03 mL) and -0.08 mL (SD, 0.79 mL; n=72; 95% CI, -0.26 mL, 0.10 mL) when assessing total volume collected per patient. Conclusions: Our findings demonstrate that the automated system can quantify blood volumes in BACTEC culture vials and support blood volume monitoring for pediatric and adult collections. The gravimetric approach is also amenable to full automation for efficient and accurate blood volume determination.

Background: Delayed diagnosis of immunoglobulin light-chain cardiac amyloidosis (AL-CA) worsens prognosis, partly because AL-CA and wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) are difficult to distinguish at the initial cardiology visit. We developed and validated a practical score to triage AL-CA from ATTRwt-CA. Methods: We retrospectively analyzed 541 consecutive patients with cardiac amyloidosis (91 AL-CA, 450 ATTRwt-CA) at our institution's amyloidosis center, randomly divided into derivation (n=378) and validation (n=163) cohorts. Candidate first-visit variables underwent LASSO selection after multiple imputation, with estimates pooled by Rubin's rules. Performance was assessed by bootstrap validation, calibration, and decision curve analysis. The model was converted into a simplified point-based score. Results: Seven variables were retained: age, absence of atrial fibrillation, absence of carpal tunnel syndrome, low serum albumin, proteinuria ([&ge;]1+), low voltage, and thinner left ventricular posterior wall thickness. Areas under the curve (AUC) were 0.97 in the derivation cohort and 0.99 in the validation cohort; the bootstrap optimism-corrected AUC was 0.96. The model provided net benefit across threshold probabilities of 0.01-0.50. Risk tiering categorized the validation cohort into low (0-5 points; AL-CA 0%), intermediate (6?9 points; 26%), and high (10-13 points; 95%) probability groups. Discrimination remained high for AL-CA versus monoclonal protein-positive ATTRwt-CA at a cutoff of [&ge;]8 points (AUC 0.90). Adding this score to monoclonal protein testing significantly improved diagnostic performance compared with monoclonal protein testing alone. Conclusions: This simple first-visit score may help cardiologists rapidly triage suspected AL-CA and prioritize urgent hematology referral and subtype-specific confirmatory testing.

Abstract Objective Fungal infections can represent opportunistic infections leading to the diagnosis of immunocompromise. Specific inborn errors of immunity are associated with aspergillus but it is unclear how sensitive aspergillus is for the subsequent diagnosis of those inborn errors of immunity. Methods The patient registry USIDNET was utilized to extract clinical conditions and laboratory values from patients with candida and aspergillus diagnosis codes. We restricted the diagnoses to deep infections and then identified the associated clinical conditions along with potential settings, such as bone marrow transplant. Results We identified 41 patients with aspergillus as a diagnosis code. The types of diagnoses associated with aspergillus included T cell disorders, antibody disorders, as well as the anticipated myeloid disorders. Bone marrow transplant was identified as a potential predisposing condition. 64. Patients were identified with candida as a diagnosis code. Similarly, T cell disorders, antibody disorders, and myeloid disorders were found. Conclusions Candida and aspergillus are generally considered sentinel infections for myeloid disorders and T cell disorders. However, we found these infections associated with a broad range of inborn errors of immunity. This suggests that diagnostic testing should be broadened when facing patients with these infections.

Platelet-leukocyte aggregates (PLAs) are a proposed interface between coagulation and immune regulation, but their distribution across leukocyte subsets beyond monocytes and neutrophils, and their behavior in acute disorders of immune regulation, such as sepsis and severe trauma, remain largely undefined. The study of thromboimmune mechanisms in these acute conditions has relied heavily on murine sepsis models, whose species differences in platelet and leukocyte biology limit translation to human disease. Direct measurement in human whole blood is needed yet reported PLA frequencies vary widely because quantification is highly sensitive to sample handling. Here we present a robust, minimally manipulative 27-color spectral flow cytometry protocol that allows simultaneous deep immunophenotyping and classification of PLAs across >40 leukocyte subpopulations. In healthy donors, PLA frequency ranged from 1.7% on memory CD4 T cells to over 50% on monocyte subsets, with monocytes contributing 25% of all PLAs. We also found novel platelet-binding leukocyte populations, including Th9 and Th22 CD4+ T cells. Optimization identified anticoagulant choice, centrifugation conditions, dilution, and sample processing time as key determinants of reproducible measurement; PLA quantification was validated by imaging flow cytometry. In a small validation cohort of sepsis and trauma patients, the assay recapitulated established immunophenotypic features of critical illness, including neutrophilia and myeloid-derived suppressor cells (MDSC) expansion, and quantified PLAs within each subset. This protocol provides a reference framework for studying thromboinflammation and other dysregulated immune response diseases directly in human blood, and a foundation for further studies, defining the mechanisms and clinical relevance of platelet-leukocyte interactions in disease.

Background: Erythritol and xylitol, naturally present in fruits and vegetables, are widely used as alternative sweeteners with minimal glycemic and insulinemic effects. Both are also produced endogenously, with elevated plasma concentrations reported in metabolic disorders and cardiovascular disease. Recently, two interventional studies reported enhanced platelet aggregation after acute oral intake of erythritol or xylitol, raising concerns about potential prothrombotic effects. We investigated whether acute exposure to erythritol or xylitol increases platelet reactivity in healthy individuals. Methods: We conducted a randomized, single-blind, crossover study in 14 healthy participants who received erythritol (50 g), xylitol (33.5 g), or water. Platelet aggregation was assessed ex vivo, together with circulating markers of platelet activation (P-selectin), endothelial activation (sVCAM-1), and coagulation (D-dimer), as well as plasma erythritol and xylitol concentrations. Complementary in vitro experiments were performed using platelet-rich plasma from 11 healthy participants exposed to increasing concentrations of erythritol or xylitol, followed by assessment of platelet aggregation. Results: Despite substantial increases in circulating erythritol and xylitol concentrations following oral intake, neither erythritol nor xylitol increased ex vivo platelet aggregation compared with water. Consistently, no relevant changes were observed in P-selectin, sVCAM-1, or D-dimer concentrations. Direct in vitro exposure of platelet-rich plasma to increasing concentrations of erythritol or xylitol likewise did not enhance platelet aggregation. Conclusions: In healthy individuals, acute oral intake of erythritol or xylitol did not increase platelet aggregation or circulating markers of platelet activation, endothelial activation, or coagulation. These findings were supported by in vitro experiments showing no direct effect of erythritol or xylitol on platelet aggregation. Our results do not support an acute platelet-activating effect of erythritol or xylitol under the conditions studied. Registration: URL: https://clinicaltrials.gov/study/NCT04966299; Unique identifier: NCT04966299.

Introduction: Hospitals face increasing financial pressures. Hospital reimbursement is tied to the Case Mix Index (CMI). The CMI is a measure of complexity of care provided by the hospital and the total reimbursement is the CMI multiplied by a base pay factor, multiplied by the total number of discharges from the hospital. The few studies in the literature have involved logistically complex attempts to improve documentation. We sought to determine whether limited, structured chart review by surgeons can improve CMI in a multihospital system. Methods: We performed a prospective, observational study in a four-hospital academic medical system on all surgical patients from 10/2022 to 7/2026. Two clinically busy trauma surgeons performed limited structured chart reviews for select surgical patients. In the limited intervention period (1/2024-9/2024) this focused only on the trauma division. In the full intervention period (10/2024-7/2026) expanded to all surgical patients across the system. The main outcome was surgical case mix index (CMI). Results: A total of 35,695 patients were included (13,811 pre-intervention, 9,337 limited intervention, 12,547 full intervention). CMI increased significantly among surgical patients across the whole system (2.68 (95%CI 2.65-2.71) to 2.87 (95%CI 2.82-2.92) to 2.97 (95%CI 2.93-3.01), ANOVA p <0.001). Overall length of stay was unchanged among surgical patients across the whole system. The estimated increase in revenue per patient attributable to this intervention was $3,912 in surgical patients across the system. Conclusion: Having trauma surgeons review targeted surgical patients for high value documentation capture significantly enhanced the CMI and estimated revenue of surgical services across a multi-hospital integrated health system. Such documentation reviews may represent a practical method to improve hospital documentation and revenue.

Objective: Rare STAB2 loss-of-function variants emerged in population studies as being associated with elevated venous thromboembolism (VTE) risk. STAB2 encodes the cell-surface scavenger receptor stabilin-2, and reduced stabilin-2 function might increase VTE risk via elevated plasma levels of its ligands, including von Willebrand factor (VWF) and coagulation factor VIII (FVIII). Approach and Results: A 13-year-old patient with dependency on parenteral nutrition had experienced episodes of central venous catheter-related thrombosis, including the complete thrombotic occlusion of the deep pelvic veins, and pulmonary embolism. Exome sequencing for increased VTE risk identified a homozygous STAB2 splice-site variant and its effect on splicing was characterized in fibroblast-derived RNA and in a minigene splicing system. Plasma VWF, FVIII, and fibrinogen and serum hyaluronic acid (HA) levels were determined. Immunohistochemistry was performed on liver biopsy tissue. The STAB2 splice-site variant caused aberrant STAB2 mRNA splicing. The patient's healthy mother and one healthy sibling were also homozygous for the STAB2 splice-site variant but had no history of VTE. Plasma FVIII levels and VWF activity were elevated in all three, and VWF antigen was elevated in two homozygous individuals. Strikingly, approximately 1000-fold elevated HA levels were observed in all three homozygous individuals. Stabilin-2 immunohistochemistry on a liver biopsy from the proband's mother revealed no detectable signal, whereas control human liver showed strong labelling of liver sinusoidal endothelial cells. The STAB2 splice-site variant thus results in loss of detectable stabilin-2 protein. Conclusion: To current knowledge, this is the first family-based report of stabilin-2 deficiency with markedly elevated circulating HA, VWF, and FVIII levels in humans. These findings support impaired stabilin-2-dependent ligand clearance as a thrombosis susceptibility state with incomplete penetrance. The data are consistent with a significant role for stabilin-2 in circulating HA clearance in humans, but do not establish elevated HA itself as a cause of VTE.

BACKGROUND: The protein 4.1a/4.1b ratio is an intrinsic molecular marker of mean red blood cell (RBC) age resulting from progressive deamidation of protein 4.1b during RBC circulation. Despite its potential for estimating mean RBC age from a single blood sample, its application has been limited by labor-intensive RBC membrane preparation, and its interindividual variability has not been characterized in a large human population. METHODS: We developed a low-volume method for direct RBC membrane isolation from whole blood using saponin permeabilization and differential centrifugation without prior RBC washing. Membrane proteins were separated by SDS-PAGE, and protein 4.1a/4.1b ratios were determined by densitometric analysis with Gaussian peak fitting. Assay conditions, sample-volume requirements, membrane protein recovery, and analytical reproducibility were evaluated. The method was subsequently applied to 114 anonymized residual samples from routine diagnostic testing selected for complete blood count parameters within the corresponding laboratory reference intervals. RESULTS: The optimized procedure used 50 uL of whole blood, 0.06% saponin, and centrifugation at 9000 g, although protein 4.1a/4.1b remained measurable from starting volumes as low as 5 uL. Mean within-subject CVs were 3.90% for electrophoretic/densitometric determination and 5.39% for membrane protein recovery; whole-procedure CVs in 3 subjects were 1.40% to 3.50%. In the population analysis, the mean protein 4.1a/4.1b ratio was 1.428 (SD 0.146), with an observed range of 1.052 to1.799 and a central 95% interval of 1.151 to 1.695. Ratios did not differ significantly between females and males (P=0.246) or among females aged 18 to 50 years, females aged >50 years, and males (P=0.151). The ratio showed modest positive correlations with chronological age in females (Spearman p=0.26, P=0.047) and males (p=0.33, P=0.015), while substantial interindividual variability remained across the age range. CONCLUSIONS: Direct isolation of RBC membranes from small volumes of whole blood enables reproducible determination of the protein 4.1a/4.1b ratio using a simplified workflow. Application of the assay to a comparatively large human population revealed substantial interindividual variation in this molecular marker of mean RBC age that was not explained by sex or chronological age alone. The method provides a practical approach for investigating biological variation in mean RBC age and its potential contribution to laboratory measurements influenced by RBC survival.

Abstract Background: Mean arterial pressure (MAP) is pharmacologically augmented in selected perioperative and critical care settings, including acute neurological conditions and after cardiac arrest, with the aim of improving cerebral perfusion, although it remains uncertain whether higher arterial pressure translates into increased cerebral blood flow (CBF). We investigated the CBF response to MAP augmentation with norepinephrine (NE), a commonly used vasopressor in perioperative and critical care settings, during propofol-based general anesthesia. Methods: In this prospective within-subject interventional study, 16 neurologically intact patients with ASA physical status I-II undergoing elective surgery were studied using phase-contrast magnetic resonance imaging. CBF was quantified in the awake state and during propofol-based general anesthesia before and after NE-induced MAP augmentation. During general anesthesia, NE was titrated to increase MAP by approximately 25% from baseline. Concurrent systemic hemodynamics were assessed. Results: General anesthesia was associated with a 50.1% (interquartile range, 42.1?55.7%) reduction in CBF and a 24.2% (20.3-29.2%) reduction in MAP compared with the awake state (both P<0.001). During general anesthesia, NE-induced MAP augmentation increased MAP by 25.7% (21.9-32.0%; P<0.001), whereas CBF remained unchanged (P=1.000). Cardiac output remained unchanged (P=0.163), whereas systemic vascular resistance index and cerebrovascular resistance increased by 40.0% (28.7-45.2%) and 36.2% (17.7-42.8%), respectively (both P<0.001). Changes in CBF during MAP augmentation were not associated with concurrent changes in MAP, cardiac output, or systemic vascular resistance index. Conclusions: In neurologically intact patients undergoing propofol-based general anesthesia, clinically relevant NE-induced MAP augmentation did not increase CBF despite an approximately 50% lower CBF than in the awake state. These findings challenge the assumption that pharmacological elevation of an otherwise adequate MAP improves cerebral perfusion in this setting. While maintaining adequate arterial pressure remains essential, further MAP augmentation should not be assumed to increase CBF. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT06855407; NCT06855407.

Background. Cardiovascular-kidney-metabolic (CKM) syndrome affects nearly 90% of US adults, yet most individuals at early, modifiable stages remain unidentified outside clinical care. Blood donation centers offer a scalable, non-clinical venue for CKM screening, but the potential benefit of screening in this context remains unclear. We projected the population-level impact of effective digital return of results (ROR) to inform the design of a pragmatic trial. Methods. We developed a Monte Carlo simulation (100,000 iterations) of the incident major adverse cardiovascular events (MACE), end-stage renal disease (ESRD), and type 2 diabetes (T2DM) preventable by ROR-prompted, guideline-concordant follow-up among donors in CKM Stages 1-2. The estimand counts only events averted by donors who act because of ROR; the intervention effect was modeled directly on strictly positive support, and action was translated into prevented events through a hazard-based cumulative-incidence difference that counts each donor at most once. We evaluated 18 design cells (donor volumes 300,000, 1 million, and 8 million/year; 5- and 10-year horizons; action-rate gains of +10, +20, and +30 percentage points [pp]) and, in a complementary two-arm simulation, the assurance (expected power) of detecting the effect in a single deployment. Results. Under the primary +20 pp scenario, ROR at a single large blood center (300,000 donors/year) is projected to prevent a median of 2,201 events (95% uncertainty interval [UI], 1,099-4,364) over 10 years, scaling to 58,526 (29,154-116,769) at the national donor pool. All 18 design cells had strictly positive 95% lower bounds. The number needed to screen was 136 and the screening cost $2,045 per event prevented (at $15/donor), both invariant to donor volume. Impact scaled linearly with volume and effect size but sub-linearly with the horizon. Detection of the effect was effectively certain at gains of +20 pp or larger (assurance [&ge;]99.6% in every cell and >99.9% in all but the smallest 5-year cell). Conclusions. Even under the conservative scenario, digital CKM ROR at blood donation centers is projected to prevent hundreds to tens of thousands of incident cardiometabolic events at a screening cost per event well within accepted prevention benchmarks, providing prospective, quantitative justification for a pragmatic, randomized evaluation of digital ROR in non-clinical screening settings.

BACKGROUND: Machine learning (ML) models have been used to evaluate one-year post-transplant mortality in donor-recipient pairs. Previous modeling utilizing noninterpretable ML methods (deep neural networks [DNN] and XGBoost) showed modest gains in area under the receiver operating curve (AUC) beyond logistic regression, but suffered a significant drop in predictive AUC applied to the subsequent years' data and lacked statistical significance in validating previously identified risk factors. METHODS: Using balanced SRTR datasets, we evaluated non-interpretable models against interpretable ML models (adaptive logistic regression with interaction terms [aLR], Classification and Regression tree [CART], and conditional inference tree [CIT]) for one-year mortality, including comprehensive clinician-supervised data curation and inclusion of variables describing pre- and post-2018 listing status changes. Models were trained/tested using rolling-window validation across years and further analyzed with repeated ten-fold crossvalidation. Interaction terms were obtained via Adaptive Best-Subset Selection (ABESS). RESULTS: Predictive validation before the listing policy change in 2018 showed similar AUCs between DNN (0.579), aLR (0.642), CART (0.579), and CIT (0.584), with XGBoost having a higher (0.763) AUC. However, in the post-2018 predictive analysis, aLR outperformed XGBoost (AUC 0.613 vs. 0.586). The interpretable ML models confirm the significance of previously reported risk factors (recipient bilirubin and creatinine) and identify risk factors not previously reported (donor pH, potential recipient distance, and recipient transfusion), as well as clinically relevant interaction terms. CONCLUSIONS: Carefully developed interpretable ML models of one-year transplant mortality have similar predictive performance to black-box models, while identifying novel risk factors, and showing improved performance after recent listing policy changes. With appropriate validation and additional data, interpretable ML modeling may allow real-time data-driven donor selection.

Background Perioperative Patient Blood Management (PBM), a patient-centred, evidence-based approach to improve outcomes by preserving and optimising a patient own blood, remains unimplemented in most low- and middle-income countries. Few studies have assessed health-system readiness for PBM implementation, anaemia management, or transfusion practices in sub-Saharan Africa. This study provides a pre-implementation baseline assessment of perioperative PBM readiness in Ethiopia. Materials and Method A mixed-methods approach evaluated 12 public hospitals in Addis Ababa, with the PBM Facility Assessment Tool to determine readiness scores. Data from 1,236 surgical patients assessed anaemia, transfusions, and predictors. Interviews with clinicians, blood bank staff, and policymakers explored decision-making and barriers. Findings were integrated through triangulation. Results The composite PBM-FAT score was 6.6 (SD, 0.7) (range 5.5-7.5); however, this reflects general perioperative and transfusion-service infrastructure rather than PBM-specific capability. Domain analysis revealed critical gaps: 75% of facilities lacked intravenous iron, viscoelastic testing was absent in all, and 66.7% lacked point-of-care haemoglobin testing. Fibrinogen and haematinic tests were rarely available (66-92% never tested). Preoperative anaemia was documented in 7.1% of patients, a minimum estimate reflecting detection failure due to non-systematic haemoglobin testing, and perioperative transfusion occurred in 2.4%, more consistent with supply rationing than with optimised clinical practice. Independent transfusion predictors included cancer surgery (AOR 11.28, 95% CI 3.00-42.36) and blood loss greater or equal to 500 mL (AOR 9.76, 95% CI 3.94-24.17). Interviews revealed blood shortages, the absence of national PBM governance, transfusion as the default treatment for anaemia, and highly variable thresholds. Conclusion Ethiopian hospitals have functional transfusion services but lack the anaemia management pathways, diagnostics, therapeutics, and governance structures required for Patient Blood Management. PBM is not yet operationalised as a patient-centred, preventive care strategy. Priority implementation steps, aligned with the WHO 2024 PBM guidance, include systematic preoperative haemoglobin screening, access to intravenous iron, blood utilisation governance, and a national PBM framework to improve patient outcomes. Keywords: Patient blood management; anaemia; blood transfusion; perioperative care; Ethiopia, health system

Objective: This study aimed to evaluate whether PVi and IJV-VI demonstrate sufficient agreement and trending ability to support their clinical interchangeability during laparoscopic living donor nephrectomy. Methods: A prospective observational concordance study was conducted in adult patients undergoing elective laparoscopic living donor nephrectomy under mechanical ventilation. Simultaneous paired measurements of PVi and IJV-VI were obtained every 15 minutes during surgery. Agreement between methods was assessed using repeated-measures Bland Altman analysis. Trending ability was evaluated using polar plot and four-quadrant plot analyses. Results: Thirty-six patients were included, providing 366 paired intraoperative measurements. Bland Altman analysis demonstrated a small overall bias of 0.06% (95%CI;0.21 to 0.39), with wide 95% limits of agreement ranging from -5.10% to 5.22% and a global percentage error of 55.96% (95%CI 37.81-74.17). Polar plot analysis showed poor trending ability, with an angular bias of 14.2o, angular dispersion of 117o, and only 34.5% of vectors within the clinically acceptable +/-30o zone. Four-quadrant analysis demonstrated an overall concordance rate of 84.7% after applying a central exclusion zone. Conclusion: Although PVi and IJV-VI demonstrated a strong positive association during laparoscopic living donor nephrectomy, agreement and trending ability between methods were limited.

Background: Blood volume (BV) in patients with chronic heart failure (HF) is characterized by heterogeneity in volume profiles; one profile being "normal BV". While overall intravascular volume may be considered normal clinically, the relative contributions of red blood cell (RBC) mass and plasma volume (PV) may not be. Objective: Assess how normal is a "normal BV" based on quantitative measures of RBC mass and PV. Methods: Retrospective analysis was undertaken in 395 patients with Class II-III HF. BV was quantitated using indicator-dilution methodology. Cohort was stratified by normal and hypervolemic BV. Results: Of the cohort, 31% (123/395) demonstrated normal total BV and 62% (244/395) hypervolemic BV. Of patients with "normal BV", 36% (44/123) demonstrated normal RBC mass and 60% normal PV (74/123). Importantly, 60% (74/123) demonstrated a deficit in RBC mass (true anemia), while a low hemoglobin (<12 g/dL) was present in just 29% (36/123). An excess in RBC mass (erythrocytosis) in 4% (5/123). Notably, true normal BV (i.e., normal RBC mass and normal PV) was observed in only 30% (37/123) of patients with an overall "normal" intravascular volume. Conclusions: Findings reveal that "normal BV" can be misleading by concealing substantial variability in RBC mass (including unrecognized anemia and erythrocytosis) as well as different degrees of PV expansion and contraction. An actual normal BV was identified in a minority of "normal BV" patients. This underscores the importance of looking beyond overall "normal BV" to the contributing elements of RBC mass and PV with significant implications for patient management and outcomes.