Transfusion

IntroductionAntivenom neutralizes the effects of snake venom toxins. Its timely administration can by critical in reducing the risk of complications, including serious clinical hemorrhage. The objective of this study was to evaluate the relationship between the late administration of antivenom and the persistence of venom-induced consumption coagulopathy (VICC) in patients with Bothrops snakebite envenomation. MethodsWe conducted a retrospective observational study in three hospitals referent in the management of snakebite envenomation in a region of Colombia. Patients were identified through ICD10 codes. The information was extracted from patients clinical records. Late and early antivenom administration patients were compared; "late" was defined as a period between snakebite and antivenom administration >4h. Definition of persistence of VICC was as an International Normalized Ratio >1.5 between 25-72h after snakebite. The clinical bleeding (as reported by clinicians) was also explored. Groups were compared through X2 of association; binary and multiple logistic regressions were ran to estimate the magnitude of the crude and adjusted relative risk (RR) for the analyzed outcomes. Results304 patients with snakebite from Bothrops spp.were analyzed; 138 (45.3%) with late antivenom administration, and 166 (54.7%) early. The persistence of VICC was more frequent in the late antivenom group (2.06 [95% IC 1.11-3.83]), as well as for clinical bleeding and major bleeding (1.97[1.30-2.98]; 3.00 [1.19-7.54], respectively). DiscussionLate antivenom administration was associated with increased risk in the persistence of VICC and major bleeding in patients with envenomation by a Bothrops complex snakebite. The results reported in the literature are diverse; inter and intra species variability and definitions can influence the finding. ConclusionsThe Timely administration of antivenom was associated with an increased risk in persistence of VICC. SynopsisSnakebites can cause different levels of damage to humans, depending on the type of venom. The venom produced by pit vipers, specifically those of the genus Bothrops, can change blood clotting and cause bleeding that can be life-threatening. Most snakebites from these vipers occur in tropical areas where the most affected are farmers and rural people. There is often a lack of access to antivenom treatment, depending on access to and provision of health services. It seems that giving the antivenom at the right time can reduce the risk of complications. However, it is still unclear whether waiting to give the antivenom increases the risk of continued envenoming and bleeding. This study shows that waiting to treat a patient can lead to a higher chance of bleeding. This information can help doctors, decision makers, and lawmakers improve treatment options and access in remote areas.

BackgroundSnakebite envenoming (SBE) remains a major neglected tropical disease in Sudan. Venom-induced consumption coagulopathy (VICC) is the most frequent and fatal systemic complication, particularly following envenoming by hemotoxic Echis species. Robust clinical data on VICC in Sudan are limited. MethodsWe conducted a prospective hospital-based cohort study at Sinja Teaching Hospital, Sennar state, Sudan, from March to September 2022. All patients admitted with SBE were enrolled. VICC was diagnosed using the 20-minute whole blood clotting test (WBCT20) and laboratory coagulation assays. Clinical features, laboratory abnormalities, management, and outcomes were recorded until discharge or death. ResultsAmong 119 patients with SBE (mean age 34.5 {+/-} 9 years; 79.8% male), VICC developed in 96 (80.7%). Echis spp. were implicated in 86.6% of cases based on patient recognition. Spontaneous systemic bleeding occurred in 88.5% of VICC patients, and life-threatening hemorrhage in 30.2%, most commonly intracerebral hemorrhage. Acute kidney injury occurred in 36.5% of VICC cases. WBCT20 was positive in all VICC patients and showed high diagnostic sensitivity. Despite administration of fresh frozen plasma, mortality among VICC patients was 30.2%. All paediatric patients died. ConclusionsVICC was highly prevalent and associated with severe hemorrhage, acute kidney injury, and high mortality in this snakebite-endemic region of Sudan. Supportive therapy alone was insufficient to prevent fatal outcomes, reflecting delayed presentation and the absence of effective Echis-specific antivenom. Improved access to species-appropriate antivenom, early referral, and adherence to evidence-based management are critical to reducing snakebite-related mortality in Sudan. Author SummarySnakebite envenoming is a neglected tropical disease that disproportionately affects rural and agricultural communities in low-resource settings. In Sudan, snakebite remains a major but underreported cause of illness and death. One of its most serious complications is venom-induced consumption coagulopathy (VICC), a disturbance of blood clotting that can lead to severe bleeding and organ failure. We studied all patients admitted with snakebite envenoming to a teaching hospital in southeastern Sudan over six months. More than 80% of patients developed VICC, most often following bites attributed to Echis species, which are common in this region. Many patients experienced spontaneous bleeding, and nearly one-third developed life-threatening hemorrhage, most frequently bleeding in the brain. Acute kidney injury was common. Despite supportive treatment, almost one-third of patients with VICC died, and all children in the study died. Our findings highlight the severe and largely preventable burden of snakebite envenoming in this setting. Delayed presentation to hospital, reliance on traditional healers, and the lack of effective antivenom against locally prevalent snake species contributed to poor outcomes. This study highlights the urgent need to improve access to appropriate antivenom, strengthen health-care systems, and implement evidence-based management of snakebite envenoming to reduce avoidable deaths and disability in Sudan.

Amatoxin-induced acute liver failure complicates misidentified foraged mushroom ingestion worldwide; abrupt multisystem collapse punctuates apparent improvement. Our prospective single-arm clinical trial investigated proactive toxicokinetic-based management to preserve elimination capacity: sustained enhanced hydration to maintain renal clearance; fasting plus octreotide to suppress meal-driven enterohepatic circulation; and intravenous silibinin to inhibit OATP1B3-mediated hepatic uptake, enabling safe passage and elimination of gallbladder-confined amatoxin-laden bile. Safety population (N=99) transplant-free recovery (TFR): 88.0% (87 recoveries, 6 transplants, 6 deaths). Protocol-adherent Efficacy population (n=86) TFR: 98.8% (85 recoveries, 1 transplant, 0 deaths). Multivariable analysis identified uninterrupted hydration as strongest TFR predictor (P<0.001), followed by earlier silibinin initiation (P=0.003); octreotide shortened INR recovery by 11 hours (P=0.033). These findings support a toxin elimination model in which preserved renal clearance and biliary sequestration are central recovery determinants. The kinetic balance between renal clearance and hepatic uptake governs both recovery and collapse.

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSObjectiveC_ST_ABSExperts in poison control centers must accurately and efficiently assess the severity of an exposure, neither delaying care nor pointlessly sending patients to the hospital, using only the information given during a first phone call. To help healthcare professionals (HP) make these difficult decisions, we developed and evaluated a machine learning-based algorithm that predicts whether a patient should seek medical help or not, based solely on the information provided during their first call to the poison control center, for all kinds of mono-intoxications. MethodsWe extracted data recorded by clinicians at the Lyon PCC between 2000 and 2025. Cases with missing original recommendations were excluded. We trained and compared several machine-learning models, emphasizing decision-tree-based and gradient-boosted tree approaches. Two classification tasks were defined: (1) binary triage (recommend emergency or non-emergency healthcare facility vs. stay at home) and (2) three-class triage (stay at home / non-emergency healthcare facility / emergency healthcare facility). Missing data were left as-is. Cross-validation and bootstrapping were used to ensure stable and statistically significant results. Model explainability was assessed with SHAP to identify the most important features for predictions. Model performance was evaluated using F1-score and ROC AUC; class imbalance was addressed during training. We compared our results to published algorithms that focus on single-substance intoxications. ResultsAfter processing, 220,825 cases remained. Recommended dispositions were: stay at home 66.6%, emergency facility 25.4%, and non-emergency facility 7.4%. For the binary task, XGBoost achieved the best performance (F1 = 0.748; ROC AUC = 0.820). For the three-class task, XGBoost again performed best (macro F1 = 0.657; multiclass ROC AUC = 0.859). The delay from exposure to call, SNOMED symptom codes, and the circumstance of exposure were the most influential features. Our results were competitive with algorithms focusing on intoxication due to a single substance. ConclusionGradient-boosted tree models can produce accurate, interpretable, and clinically relevant predictions of poisoning severity from routine PCC data. With external validation and prospective testing, such tools could complement expert judgment to improve triage consistency and patient outcomes.

BackgroundModern natural language tools have potential to improve clinical workflows, but few have been successfully deployed in practice. Here, we present the development, deployment, and evaluation of an AI language tool for generating preliminary clinical sign-outs in a urine drug testing service. MethodsLarge language models (LLMs) were used to extract substance use patterns from 83,553 urine drug test interpretations. We then trained an AI model using these data to predict substance use from qualitative and quantitative urine testing results. Predicted substance use patterns were used to create preliminary clinical sign-out statements, which were then integrated into an existing clinical workflow. Pre- and post-deployment user studies were performed to evaluate model performance and user experience within this workflow. ResultsLLM-based extraction of substance-use patterns was 99.9% accurate, outperforming human labelling. Substance use prediction was similarly accurate, with area under the ROC curve > 0.99 across 33 drug categories. Workflow integration reduced clinical sign-out times by 65s per case (51% efficiency gain), with the greatest benefits seen for less experienced users. ConclusionsAI-based interpretation of urine drug testing was fast and accurate, providing significant efficiency gains to the clinical service. This demonstrates that natural language tool integration can provide substantial clinical benefit, without comprising quality of care.

Despite significant advancements in diagnostic methodologies, the fundamental approach to venous blood collection has remained largely unchanged since its widespread adoption in the mid-20th century. This stagnation poses considerable challenges, particularly in scenarios involving difficult venous access (DVA). The Bloody-Easy (BE) device represents a novel, passive, low-volume blood collection system engineered to optimize phlebotomy outcomes, especially in these challenging clinical contexts. Our prospective, randomized, crossover study involving 90 healthy volunteers demonstrates that BE achieved comparable or superior sample quality while significantly reducing the volume of blood drawn per session. Furthermore, the device garnered substantial positive feedback from both patients and clinicians. BE offers a potentially cost-neutral and low-risk solution for improving blood collection efficiency and patient experience in critical care, emergency medicine, and paediatric settings, where conventional phlebotomy techniques frequently encounter limitations.

BackgroundFatal insulin intoxication remains difficult to diagnose because insulin undergoes rapid degradation after death, limiting the reliability of direct biochemical measurements. This creates diagnostic uncertainty when objective molecular confirmation of insulin excess are required. We hypothesised that insulin excess induces systemic metabolic alterations that persist beyond insulin degradation and can be captured using postmortem metabolomics in a forensic setting. MethodsHigh-resolution mass spectrometry (HRMS)-based metabolomics was applied to a national cohort comprising 51 fatal insulin intoxications. Orthogonal partial least squares-discriminant analysis (OPLS-DA) models were trained on cases collected between 2017-2022 to identify insulin-associated metabolite features using a shared-and-unique-structures approach. Performance was evaluated using two temporally distinct test sets (2023-2024): a matched validation cohort and a heterogeneous forensic cohort reflecting biological variability. ResultsHere we show that an insulin-associated metabolomic fingerprint comprising 91 features demonstrated reproducible discrimination across independent cohorts. In the matched cohort (n=59, including 14 insulin cases), insulin intoxication classification achieved 100% sensitivity and 73% specificity within the applicability domain. In the heterogeneous cohort (n=154, including 14 insulin cases), 100% sensitivity was maintained with a 72% specificity despite increased biological variability. Univariate analyses demonstrated significant alterations across multiple metabolite classes, including acylcarnitines, fatty acids/lipids, and purine/nucleoside metabolites, with moderate effect sizes, consistent with systemic effects of insulin-induced hypoglycaemia. ConclusionsFatal insulin intoxication is associated with a reproducible metabolomic fingerprint detectable after death. These findings demonstrate that postmortem metabolomics may serve as a complementary decision-support tool when conventional biomarkers are unreliable.

AimsTo evaluate the association between platelet indices and platelet count severity in patients with primary immune thrombocytopenia during routine post-treatment follow-up. MethodsThis retrospective observational study included patients with primary immune thrombocytopenia followed at a single tertiary care center between 2011 and 2025. Demographic and laboratory data were obtained from medical records. Platelet count severity was categorized as less than 30 x 10^9/L, 30 to 100 x 10^9/L, and greater than 100 x 10^9/L. Platelet indices, including mean platelet volume (MPV) and platelet distribution width (PDW), were analyzed using the most recent complete blood count obtained during routine follow-up after treatment initiation. Continuous variables were summarized as median and interquartile range. Comparisons across platelet count categories were performed using the Kruskal-Wallis test with post hoc Mann-Whitney U testing. Correlation analysis and simple linear regression were also conducted. ResultsA total of 243 patients were identified, of whom 232 met the inclusion criteria. Platelet distribution width differed significantly across platelet count severity categories (Kruskal-Wallis p < 0.001) and demonstrated a strong inverse association with platelet count. Mean platelet volume also showed a statistically significant difference across platelet count groups (Kruskal-Wallis p = 0.007), although the association was weaker and less consistent compared with PDW. Regression analysis confirmed a significant association between platelet count and PDW. ConclusionPlatelet distribution width is more closely associated with platelet count severity than mean platelet volume in patients with primary immune thrombocytopenia during routine post-treatment follow-up. PDW may represent a useful adjunctive laboratory parameter when interpreted alongside platelet count in routine clinical practice.

BackgroundPreoperative evaluation is essential for ensuring patient safety prior to vascular surgery. However, overutilization of routine tests without clinical indication can impose significant financial burden on people, especially those who are living in resource-limited settings. This study aim was to assess preoperative evaluation in vascular patients with its associated direct patient cost and cost drivers in Tikur Anbessa Specialized Hospital (TASH). ObjectiveTo assess the direct cost, and key cost drivers of preoperative investigations among patients who underwent elective vascular surgery at Tikur Anbessa Specialized Hospital (TASH) from Jan2022 to December 2024. MethodsAn institutional-based retrospective cross-sectional study was conducted for vascular patients operated from January 2022 to December 2024 at TASH , assessing costs associated with preoperative investigations. Data were collected from medical records, and finance logs. Investigations were categorized as indicated or unnecessary based on National Institute for Health and Care Excellence (NICE) guidelines 2016. Costs were determined using TASH service fees and private center rates and patients information. Data were analyzed using SPSS version 21. ResultsA total of 165 elective vascular surgery patients were randomly selected; the mean age of participants was 49.6 years, with 53.3% male and 46.7% female. Peripheral artery disease was the most common diagnosis (47.3%). The average hospital stay was 13.7 days. The mean total cost of preoperative investigations per patient was 9,717.40 Ethiopian Birrs (ETB), with imaging averaging 8,797 ETB and laboratory tests averaging 1,328 ETB. HIV screening was not commonly provided for elective vascular patients. Linear Regression was conducted to explore relationships between patient demographics, clinical factors, and both the number and cost of investigations. Age, ASA class, comorbidity and longer hospital days were positively associated with increased total cost. ConclusionPreoperative evaluation in vascular surgery at TASH is characterized by excessive use of routine and advanced investigations, some of which lack clinical indication. These practices contribute to substantial patient expenses, primarily through out of pocket payments. There is also gap in providing some investigation tests like serum albumin and calcium. Developing and implementing evidence based testing guidelines could limit the cost.

Pregnant women with HIV control viral replication with antiretrovirals and give birth to HIV-exposed uninfected infants (HEU). The children, however, exhibit increased morbidity and mortality due to severe infections, as well as cognitive and growth abnormalities. In this study, we performed high-resolution, untargeted metabolomics on 123 HIV-exposed mother-baby pairs and 117 control pairs without HIV. High concentrations of the antiretroviral efavirenz and its metabolites were detected in maternal blood and cord blood. The metabolomic differences between HEU participants and controls reflect perturbed pathways of steroids, tryptophan and bile acids, and they largely consisted of metabolites that were correlated with efavirenz concentrations within the HEU group. The results suggest a major contribution of the drug to the abnormal biochemical profile of HEU infants born to mothers treated with efavirenz.

Key pointsO_LIWe report findings from a phase 2 study of MY008211A among Chinese men and women aged [&ge;]18 years with paroxysmal nocturnal hemoglobinuria C_LIO_LIIncreases in hemoglobin of [&ge;]20 g/L were maintained for up to 44 weeks of treatment with MY008211A in all 34 patientsiv C_LI Explanation of noveltyParoxysmal nocturnal hemoglobinuria is characterized by red blood cell (RBC) destruction and a prothrombotic state.v Treatments exist such as complement 5 inhibitors but these carry the risk for iatrogenic extravascular hemolysis and anemia.vi As reported here, the novel, oral complement factor B inhibitor MY008211A yielded increases in hemoglobin and RBC levels, while adverse events over 44 weeks were largely mild to moderate in severity, and infections generally consisted of respiratory infections.vii Paroxysmal nocturnal hemoglobinuria (PNH) is a life-threatening disease characterized by red blood cell (RBC) destruction, blood clots, and impaired bone marrow function.viii We evaluated the efficacy and safety of 3 dosages of MY008211A, a novel complement factor B inhibitor,ix for treating PNH.x This was a multicenter, open-label, phase 2, dose-finding study of MY008211A among Chinese men and women with complement inhibitor-naive PNH and signs of active hemolysis.xi Patients with hemoglobin <100 g/L were assigned to oral MY008211A 400 mg twice daily (BID), 600 mg BID, or 800 mg once daily (QD) for 12 weeks and could then continue treatment with 400 mg BID during a 32-week extension.xii The primary endpoint was the proportion of patients achieving an increase in hemoglobin concentration of [&ge;]20 g/L vs baseline on day (D)84, without RBC transfusions after 4 weeks of dosing.xiii Safety assessments included adverse events (AEs).xiv Fifteen, 9, and 10 patients were assigned to MY008211A 400 mg BID, 600 mg BID, and 800 mg QD, respectively.xv All patients completed the study and its 32-week extension.xvi On D84, all 34 patients achieved increases in hemoglobin concentration of [&ge;]20 g/L from baseline;xvii all patients maintained this increase at D308.xviii Through D308, grade [&ge;]3 AEs occurred in 5 (33%), 5 (56%), and 4 (40%) patients in the 400-, 600-, and 800-mg groups, respectively.xix There were no deaths.xx In this multicenter, open-label study of 3 dosages of MY008211A for PNH, all patients achieved and maintained increases in hemoglobin of [&ge;]20 g/L from baseline without RBC transfusions.

BackgroundAntibiotic stewardship during stem cell transplantation (SCT) is challenging.. Procalcitonin (PCT) has been employed successfully in critical care patients to safely guide stewardship. However, procalcitonin guided stewardship has not been robustly assessed in SCT recipients. We sought to evaluate the potential utility of PCT to guide antimicrobial de-escalation during engraftment. Methods100 SCT patients were prospectively enrolled in a "strategy trial" and had infectious complications documented. Lab parameters - CBC, BMP, CRP were obtained daily as standard of care (SOC) while PCT was obtained for research purposes. Providers were blinded to PCT results. We compared duration of antimicrobial escalation between actual events (SOC model) and a proposed PCT model. In this hypothetical PCT model, antibiotic de-escalation would occur if CRP remained <100 mg/dl and PCT <0.25 ng/ml after 3 days of escalation. Escalation events were defined as a substitution or addition of an antimicrobial agent after initiation of prophylactic antimicrobials. Results77 patients had escalation events and of these, 33 had bacterial infections. A total of 136 antimicrobial escalations events were identified, and of these only 39(28.7%) were associated with documented infections. The standard of care model had a mean duration (+SD) of 9.08 (+ 6.08) antibiotic days. If the PCT model were employed, the mean duration (+SD) would be 4.44 (+ 6.16) days (p<0.001). The PCT model, however, would have missed 11 infections\ ConclusionProcalcitonin-guided antimicrobial stewardship during autologous stem cell transplantation is feasible however optimization is necessitated for utilization as a tool to guide antibiotic prophylaxis during SCT.

IntroductionThe adoption of biologic therapies imposes a substantial financial burden on the Jordanian healthcare system. Ranibizumab is prescribed for various retinal disorders, and its associated costs are considerable. The introduction of biosimilars is beneficial in retaining desired clinical parameters while providing cost relief and enhanced access to patients. ObjectiveTo examine the budget impact and expanded access of switching to ranibizumabs biosimilar for the management of retinal diseases in guideline-based practice and in real-world practice in Jordan. MethodA 4-year budget impact analysis from Jordanian public sector payers sector was performed (2023 to 2026) that included patient prevalence and incidence, average ranibizumab dose per year, and anticipated shifts in the market share of ranibizumab and aflibercept. The model took into account the anticipated price erosion of the biosimilar in 2025 and 2026. Sensitivity analyses were performed to assess the effect of changes in uptake rates, price, and market share. ResultsThe annual cost savings per patient when switching from aflibercept to ranibizumabs biosimilar were from 20.55 JOD (Jordanian Dinar) to 1519.93 JOD, translating to a percentage saving of 2.68% to 35.12% across the various scenarios and indications. The total budget impact ranged widely from 6.9 M JOD to 21.2 M JOD based on treatment regimens adjusted to current practice, PRN (Pro re nata), or T&E (Treat and extend). Patient access improved between 2.75% to 124.76% in the different scenarios. ConclusionThe introduction of ranibizumabs biosimilar significantly reduces the expenditures and enhances treatment access.

Point-of-care (POC) blood testing enables rapid, decentralized diagnostics with transformative promise, yet its innovation landscape remains poorly mapped. To this end, we focused on features that we believe are key to make progress in areas of precision healthcare and predictive medicine, such as longitudinal data collection and data analytics integration. While no review can be complete, this work attempts to address this gap by analyzing 86 POC blood testing devices worldwide and proposing a unified framework to compare them across technology principles, diagnostic breadth, usability, regulatory pathway, deployment feasibility (via a custom index), and data/AI integration. Electrochemical biosensors were the single largest platform (29.1%), strongly associated with glucose testing ({chi}2=237.8, p<0.001), while spectroscopic and microfluidic systems remained niche due to higher costs and specialized requirements. Regulatory approval skewed toward moderate risk (44.2% FDA II; 27.4% IVDR C), while approval times lengthened with risk class (e.g., IVDR D {approx}540 days). A trade-off was observed between usability and panel breadth: tools for home or low-resource settings emphasize simplicity and affordability, whereas clinical systems expand diagnostic range at higher complexity and cost. Deployment feasibility scores favored handhelds, while benchtops were penalized by workflow and capital demands, and microfluidics by consumables. Innovation clusters in North America, Europe, and East Asia reinforce global leadership and disparities.

Maternal smoking during pregnancy is associated with adverse effects on offspring health through impaired placental structure and function. Nicotine and other tobacco-related compounds readily cross the placental barrier, disrupt metabolic pathways, and increase the risk of long-term developmental disorders in newborn. Here, placental metabolic alterations associated with maternal smoking exposure were examined with metabolomics. We used placental samples from the Kuopio Birth Cohort study from 23 nonsmoking controls pregnancies, 19 pregnancies with early smoking exposure (cotinine detected in first-trimester but not in at-term samples), and 13 pregnancies with continuous smoking-exposure (cotinine detected in both first-trimester and at-term samples). Differences in placental metabolomic profiles were seen between controls and both smoking-exposed groups. For example, increased activity of xenobiotic metabolism pathways showed as elevated CYP1A2-related metabolites, e.g., aminoamide local anesthetic metabolite detected in both smoking-exposure groups (p=0.0042 and 0.0019, respectively). Disruptions in amino acid metabolism were observed, e.g., reduced placental tryptophan levels (p=0.0209 and 0.0237). Placentas from women who quit smoking during showed markers of reduced oxidative stress, lower oxidized glutathione (p=0.0119) and higher ergothioneine (p=0.0426) levels. These findings indicate that many smoking-related effects on the placental metabolome persist beyond acute nicotine exposure, showing long-term biological effects of maternal smoking during pregnancy. Plain language summarySmoking during pregnancy can possibly change how the placenta functions, which also affects the newborns long-term health. In this study, we compared placentas from nonsmokers, women who quit during pregnancy, and those who kept smoking. Clear chemical differences were seen in the placentas of smoking exposed pregnant women. The main changes included lowered levels of tryptophan and glutathione, which are important for growth and protection from stress. These results show that smoking-related changes in the placenta can persist beyond active nicotine exposure.

BackgroundThe hyperpolymorphic nature and structural complexity of the human leukocyte antigen (HLA) genomic region present challenges for accurate and scalable typing across diverse sample types. While wholegenome sequencing (WGS) offers the opportunity to infer HLA genotypes without targeted enrichment, systematic benchmarks across sequencing platforms, biospecimens and coverage levels remain limited. ResultsWe assembled a multi-platform resource of WGS datasets derived from short-read (Illumina, MGI) and long-read (Oxford Nanopore Technologies R9 and R10) sequencing, spanning 29 biospecimens including cell lines, blood, buccal swab and saliva. We evaluated the performance of the HLA caller HLA*LA across 13 HLA genes, using a clinically validated assay as reference. WGSbased HLA genotyping achieved [~]95% accuracy across sequencing platforms, with Class I loci exhibiting higher accuracy than Class II. Crossplatform concordance was high, and performance remained consistent across Illumina, MGI and Oxford Nanopore chemistries. Analysis of blood, buccal swab and saliva samples showed that blood and buccal swabs supported accurate HLA inference, whereas saliva yielded reduced concordance. Downsampling experiments demonstrated that 15x coverage was sufficient to retain >95% accuracy at twofield resolution, with lower depths supporting lower-resolution typing. ConclusionsOur results demonstrate that WGS provides a robust, platformagnostic framework for accurate HLA genotyping across sample types and coverage levels. These benchmarks establish practical conditions for reliable HLA inference and underscore the utility of WGS for populationscale HLA analyses and future clinical applications.

BackgroundErythrocyte indices are essential for the diagnosis and monitoring of hematologic diseases, but their determination depends on automated hematology analyzers, which limits access in regions with limited laboratory infrastructure. Although artificial intelligence approaches have been proposed for hematologic analysis, they usually rely on slide scanners or digitization systems. To date, no validated approaches have been identified in the literature that estimate these indices directly from images obtained through the eyepiece of conventional optical microscopes. ObjectiveTo evaluate the feasibility of automated prediction of erythrocyte indices from blood smear images obtained directly through the eyepiece of conventional microscopes using convolutional neural networks. MethodsTwo hundred blood samples stained using the May-Grunwald-Giemsa method were analyzed and photographed using a standard optical microscope. Four architectures, DenseNet-121, EfficientNet-B0, ResNet-18, and ResNet-34, were evaluated at different resolutions using 10-fold K-Fold cross-validation. ResultsFor RBC, HGB, and HCT, ResNet-34 at a resolution of 1024x1024 pixels achieved superior performance, with R2 between 0.90 and 0.92, Pearson correlation r > 0.95, and mean absolute errors of 0.184 x106/{micro}L, 0.524 g/dL and 1.292%, respectively. For RDW-CV, DenseNet-121 achieved R2 = 0.49 and r = 0.71, reflecting the greater complexity of this parameter. Bland-Altman analysis confirmed adequate agreement, with biases close to zero and more than 94% of observations within the limits of agreement. ConclusionArtificial intelligence demonstrated excellent predictive performance in estimating the erythrocyte indices RBC, HGB, and HCT, with R2 > 0.90, from images obtained using a conventional microscope and accessible hardware. This approach has significant potential to democratize access to hematologic analysis in resource-limited settings, although multicenter validation and regulatory evaluation are required before clinical implementation.

BackgroundTransfusion-transmitted malaria remains a concern in non-endemic regions due to asymptomatic parasitemia in donors with prior residence in or travel to malaria-endemic areas. Nucleic acid testing (NAT)-based screening has been proposed to mitigate this risk, and supplemental assays are needed to confirm reactive donations. We developed a pan-Plasmodium reverse transcription quantitative PCR (RT-qPCR) assay with species identification capability as a supplemental tool for malaria donor screening. Study design and methodsThe assay targets a conserved region of the 18S rRNA shared by all five human-infecting Plasmodium species and is compatible with whole blood lysed using Grifols Parasite Transport Medium (PTM). Analytical performance was evaluated using in vitro transcripts and infected red blood cells (iRBCs), with the limit of detection (LoD) determined by probit analysis. Specificity was assessed against Babesia microti and 300 non-exposed U.S. donor samples. Clinical sensitivity was evaluated using infected specimens; species identification was performed by sequencing of RT-qPCR amplicons. ResultsThe assay demonstrated high amplification efficiency (97.2%) and linearity (R{superscript 2} = 0.99). The 95% LoD was 5.3 iRBCs/mL (95% CI: 3.2-8.6), comparable to the Procleix Plasmodium Assay. Clinical sensitivity was 100% across all five Plasmodium species, and clinical specificity was 100% (95% CI: 99-100%), with no cross-reactivity with Babesia. Amplicon sequencing enabled accurate species-level identification of all sequenced specimens. DiscussionThis assay provides a sensitive confirmatory tool for malaria NAT-based donor screening. Its compatibility with PTM lysates and species identification capabilities supports regulatory applications and research into asymptomatic parasitemia in semi-immune donors.

A substantial proportion of recovered deceased-donor (DD) kidneys go unused. Accumulated refusals by transplant centers during the offer process may signal nonuse risk, and quantifying this phenomenon could inform frameworks for rescue strategies or out-of-sequence (OOS) placement. Using OPTN data on adult DD kidneys offered for transplant in 2024, we empirically estimated the probability of nonuse as a function of accumulated refusal count (ARC). Kidneys transplanted OOS were excluded from analysis. Among recovered adult DD kidneys offered in-sequence, risk of nonuse exceeded 50% after ARC=6 for blood type O kidneys, ARC=4 for type A and type B, and after ARC=1 for type AB. Risk exceeded 80% after ARC=128 (type O), ARC=55 (type A), ARC=50 (type B), and ARC=14 (type AB), and exceeded 90% after 980, 414, 278, and 41 refusals, respectively. The C-statistic of the ARC by blood type ranged from 0.896 to 0.933. ARC thresholds offer a pragmatic trigger for rescue allocation, incorporating center perception of kidney quality not easily captured in standard metrics. A policy allowing OPOs to offer kidneys OOS or deploy alternative rescue strategies once a certain ARC threshold is reached may improve utilization of hard-to-place donor kidneys while keeping easier-to-place kidneys in-sequence.

IntroductionThere is no comparison of iron phenotypes and menses, pregnancies, and live births reports of women with HFE-related hemochromatosis (HFE p.C282Y (rs1800562) homozygosity) and HFE wt/wt (absence of p.C282Y and HFE p.H63D (rs1799945)). Subjects and MethodsWe compared phenotypes and reports of non-Hispanic white women women aged [&ge;]25 y in post-population screening evaluations using univariable methods. ResultsThere were 153 p.C282Y/p.C282Y and 273 wt/wt. Median ages were 50 y (25, 86) and 55 y (25, 92), respectively (p=0.0019). Median transferrin saturation (TS), median serum ferritin (SF), and provisional iron overload prevalence were higher in p.C282Y/p.C282Y (p [&le;]0.0001, each comparison). Prevalences of documented iron overload (3.3% p.C282Y/p.C282Y vs. 0.7% wt/wt), iron overload-related disease (2.0% vs. 0.4%, respectively), and iron deficiency (3.9% vs. 2.6%, respectively) were not significantly different. Median ages at menarche (13 y p.C282Y/p.C282Y vs. 13 y wt/wt) and menopause (50 y vs. 49 y, respectively) were not significantly different. Reports of "in-between bleeding?" (24.2% p.C282Y/p.C282Y vs. 25.2% wt/wt, respectively), "early stopping of periods?" (11.8% vs. 13.9%, respectively), and "had a hysterectomy?" (30.1% vs. 35.9%, respectively) were not significantly different. Respective percentage pairs of women with p.C282Y/p.C282Y and wt/wt who reported 0, 1, 2, 3, or [&ge;]4 pregnancies (or live births) did not differ significantly. Live births/pregnancies were 287/363 (79.1%, p.C282Y/p.C282Y) and 534/673 (79.3%, wt/wt) (p=0.7549). ConclusionsMedian TS, median SF, and provisional iron overload prevalence are greater in women with HFE p.C282Y/p.C282Y than those with wt/wt, although reports of menses, pregnancies, and live births are similar.