Blood Count Research Articles

Complete Blood Count in Children With COVID-19: A Predictor of Disease Severity.

Blood count abnormalities are frequent in patients with severe COVID-19 disease and there is still a lack of information in pediatric complete blood count (CBC) results. Thus, this study aims to correlate the CBC in the emergency room of children with COVID-19 between 0 and 10 years old and the clinical severity of the disease. A retrospective cohort study was performed in children with COVID-19 who collected at the emergency room CBC, C-reactive protein (CRP), platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), neutrophil to monocyte ratio (NMR), lymphocyte to neutrophil ratio (LNR), lymphocyte to monocyte ratio (LMR), monocyte to neutrophil ratio (MNR) and monocyte to lymphocyte ratio (MLR). In total, demographic data from 93 children with median age of 19 months (0.3-126), 60.2% males, were included. The main changes in the CBC were atypical lymphocytes (51.6%) and eosinopenia (49.5%). From 69 hospitalized children, 21 were considered severe. There was no association between age, gender, and CRP value with clinical severity. The presence of underlying disease was five times higher (odds ratio [OR] = 5.08) in patients who required hospitalization and a higher NLR value was 54% (OR = 1.54) more likely to occur. Eosinopenia was three times more frequent in inpatients with disease severity criteria (OR = 3.05). In conclusion, children younger than 10 years of age with COVID-19 have changes in the CBC collected in the emergency room, mainly atypical lymphocytes and eosinopenia. The presence of a comorbidity or a higher NLR increases the chance of hospitalization. In addition, eosinopenia was a predictor of severity in inpatient children due to COVID-19.

C-reactive protein/albumin ratio versus lactate/albumin ratio as an outcome predictor for patients with sepsis and septic shock in hospital stay

Background & Objective: Pre-emptively identifying individuals at risk of developing sepsis and septic shock remains challenging. In septic patients, the Lactate/Albumin Ratio (LAR) and C-reactive protein (CRP)/Albumin ratio (CAR) have been suggested to be promising prognostic indicators for prediction of intensive care unit (ICU) mortality. We compared the prognostic values of CAR and LAR in patients with sepsis and septic shock. Methodology: Eighty adult patients diagnosed with sepsis and admitted to the ICUs of Ain Shams University Hospitals, were included in this observational prospective study. CRP levels, serum lactate, serum albumin, complete blood count (CBC), procalcitonin levels, and SOFA scores were assessed upon admission, with subsequently observing 28-day mortality among the selected patients. Results: CAR values were comparable between the mortality and survival groups (P = 0.807). However, LAR values were significantly elevated in the mortality group vs the survival group (P = 0.044). ROC analysis for mortality indicated that LAR had an AUC of 0.633 at a cutoff value > 0.68, achieving sensitivity and specificity of 89.4% and 21.2%, respectively. In contrast, CAR had an AUC of 0.484 at a cutoff value ≥ 1.54, with sensitivity and specificity values of 63.8% and 57.6%, respectively. Length of ICU stay (P < 0.001), duration of mechanical ventilation (P < 0.001), cardiovascular support (P < 0.001) and the need for renal replacement therapy (P < 0. 039), were increased in the mortality group compared to the survival group. Conclusion: Lactate/albumin ratio is superior and more reliable bio-marker predictor compared to C-reactive protein (CRP)/albumin ratio for ICU mortality. Abbreviations: CAR - C-reactive protein/albumin ratio; CRP - C-reactive protein; ICU - intensive care unit; LAR - Lactate/Albumin Ratio; Keywords: Albumin; CRP To Albumin Ratio; Lactate; Lactate to Albumin Ratio; Mortality; Sepsis; Septic Shock; SOFA; Survival Citation: Abdou K, Mounir M, Abdelmohsen S, Salem S, Ali A. C-reactive protein/albumin ratio versus lactate/albumin ratio as an outcome predictor for patients with sepsis and septic shock in hospital stay. Anaesth. pain intensive care 2023;28(5):901−907; DOI: 10.35975/apic.v27i5.2571 Received: July 29, 2024; Reviewed: August 23, 2024; Accepted: August 28, 2024

The early biomarker of immature granulocyte count in predicting right-side colonic complicated acute diverticulitis: a retrospective cohort study

ObjectiveEarly identification of complicated acute diverticulitis(cAD) is especially significant for clinical physician and surgeon to reduce the antibiotic usage and the risk of emergency surgery. This study was aimed to investigate the significance of immature granulocyte(IG) count in early prediction for right-side(Rt-side) cAD.MethodsThe patients with Rt-side colonic acute diverticulitis was enrolled between January, 2019 and March, 2024, and divided into complicated and simple acute diverticulitis group(cAD and sAD). The data about demographic, clinical and laboratory parameters were collected and compared. Logistic regression analysis and receiver operator characteristic(ROC) curves were used to assess the predictive values of these parameters for Rt-side complicated diverticulitis.Results289 participants who met the inclusion criteria were followed as 31 patients in cAD group and 258 in sAD group. Compared to sAD group, cAD group had the higher body mass index(BMI) and peripheral blood routine parameters, especially IG count, systemic immune inflammation index(SII) and neutrophil-to-lymphocyte ratio(NLR), with the statistically significant differences(P<0.001). Moreover, logistic regression analysis indicated that IG count was a significant and independent predictors for cAD(OR 4.92, 95%CI 3.86–8.39). In the ROC analysis, area under the ROC curves (AUC) was found for IG count(0.93(95%CI 0.88–0.99) ) and SII(0.88(95%CI 0.820–0.95)). The optimal cut-off value of IG count was 0.10 with the largest sensitivity of 80.60% and specificity of 100.00% for identifying Rt-side colonic complicated diverticulitis.ConclusionIG count was a more comparable and independent predictor for Rt-side colonic complicated diverticulitis with a largest AUC than other markers in complete blood count (CBC). Given its early arise, easy accessibility and no-radiation, it can largely convince physicians’ decision-making of antibiotic abuse and surgeons’ early intervention in Rt-side colonic cAD.

Comparison between statistical and machine learning methods to detect the hematological indices with the greatest influence on elevated serum levels of low-density lipoprotein cholesterol

IntroductionElevated levels of low-density lipoprotein-cholesterol (LDL-C) is a significant risk factor for the development of cardiovascular diseases (CVD)s. Furthermore, studies have revealed an association between indices of the complete blood count (CBC) and dyslipidemia. We aimed to investigate the relationship between CBC parameters and serum levels of LDL. MethodIn a prospective study involving 9704 participants aged 35–65 years, comprehensive screening was conducted to estimate LDL-C levels and CBC indicators. The association between these biomarkers and high LDL-C (LDL-C≥130 mg/dL (3.25 mmol/L)) was investigated using various analytical methods, including Logistic Regression (LR), Decision Tree (DT), Random Forest (RF), Neural Network (NN), and Support Vector Machine (SVM) methodologies. ResultThe present study found that age, hemoglobin (HGB), hematocrit (HCT), platelet count (PLT), lymphocyte (LYM), PLT-LYM ratio (PLR), PLT-High-Density Lipoprotein (HDL) ratio (PHR), HGB-LYM ratio (HLR), red blood cell count (RBC), Neutrophil-HDL ratio (NHR), and PLT-RBC ratio (PRR) were all statistically significant between the two groups (p<0.05). Another important finding was that red cell distribution width (RDW) was a significant predictor for higher LDL levels in women. Furthermore, in men, RDW-PLT ratio (RPR) and PHR were the most important indicators for assessing the elevated LDL levels. ConclusionThe study found that sex increases LDL-C odds in females by 52.9 %, while age and HCT increase it by 4.1 % and 5.5 %, respectively. RPR and PHR were the most influential variables for both genders. Elevated RPR and PHR were negatively correlated with increased LDL levels in men, and RDW levels was a statistically significant factor for women. Moreover, RDW was a significant factor in women for high levels of HDL-C.The study revealed that females have higher LDL-C levels (16 % compared to 14 % of males), with significant differences across variables like age, HGB, HCT, PLT, RLR, PHR, RBC, LYM, NHR, RPR, and key factors like RDW and SII.

Clinician-Ordered Peripheral Smear Review by a Pathologist Has Low Clinical Utility-A Reference Laboratory Perspective.

Clinician-ordered peripheral smear review by pathologist (CPSR) is commonly ordered and has been recommended for decades. However, the clinical utility of this labor-intensive test in the reference laboratory has not been examined. The objective of this study is to assess hematologic abnormalities identified in CPSR orders and to correlate them with complete blood count (CBC) and laboratory-derived smear review (LDSR) in the reference laboratory. Two hundred consecutive CPSRs with corresponding CBCs from April 2023 were run by Sysmex® XN-11 analyzers, and their peripheral smears were examined by a board-certified hematopathologist. Hematologic abnormalities of CPSRs were assessed, and the correlation between CPSR and CBC/LDSR was reviewed. Nearly one-third of CPSRs (29%) had normal peripheral smears and CBCs. The majority of CPSRs showed nonspecific quantitative abnormalities. When compared against CPSR results, LDSR criteria identified 100% of hematologic abnormalities appropriately. Samples that were not flagged for review by LDSR rules were also reviewed (n = 174) to rule out clinically meaningful false negatives. One minor discrepancy (0.6% of cases) of small platelet aggregates was observed in a patient with a reported platelet count of 139 K/uL that was missed by the LDSR process. In the reference laboratory setting, our findings demonstrate that LDSR adequately detects significant hematologic abnormalities and, therefore, CPSR should be discontinued.

Copeptin as an inflammatory marker in diagnosis and prognosis of neonatal sepsis

BackgroundCopeptin is an immediate biomarker of individual stress response; many life-threatening diseases are causing a high elevation of its concentration in plasma, such as myocardial infarction and cardiovascular shock. Moreover, copeptin is a promising marker in sepsis. We aimed to evaluate copeptin as a diagnostic and prognostic marker in neonatal sepsis for the early initiation of appropriate therapy and the prediction of mortality. A prospective case-control study involved 237 neonates (165 cases had neonatal sepsis, and 72 served as controls). Cases were admitted to the neonatal intensive care unit (NICU) and followed up for symptoms and signs of sepsis confirmed by laboratory data: complete blood count (CBC), c-reactive protein (CRP), and cultures. Serum copeptin level by the enzyme-linked immunosorbent assay (ELISA) was measured for all included neonates. We observed that the copeptin level was significantly higher in cases than control (3.51 ± 1.4, 1.61 ± 0.51 pmol/liter, respectively). The cut-off value of copeptin at which we can discriminate between cases and controls was above 2.065 pmol/liter. Among cases, copeptin was higher in early-onset sepsis (EOS) than late-onset sepsis (LOS) neonates, and there was a significant correlation between its level and all the following: age at admission, birth weight, gestational age, history of perinatal asphyxia, maternal chorioamnionitis, and premature rupture of membrane (PROM). Also, copeptin was strongly associated with CRP level and the poor prognosis of patients. Copeptin can predict the death of cases at a cut-off value above 2.995 pmol/liter.ConclusionSerum copeptin level can be used as a diagnostic and prognostic marker in neonatal sepsis.

Screening Characteristics of Hemoglobin and Mean Corpuscular Volume for Detection of Iron Deficiency in Pregnancy.

Iron deficiency in pregnancy remains underdiagnosed despite professional society recommendations for first-trimester complete blood count (CBC) screening. To determine the effectiveness of the CBC hemoglobin and mean corpuscular volume (MCV) to identify iron deficiency in pregnancy, we conducted a retrospective analysis of 20,550 pregnancies from 2009 to 2022 at the University of California, San Francisco, obstetrics clinics. A total of 16,547 (80.5%) pregnant individuals had first-trimester screening CBC; 345 (2.1%) had a coincident ferritin test. Hemoglobin level less than 11 g/dL and MCV level less than 80 fL each had sensitivity of only 30% (95% CI, 20-41%) to detect first-trimester iron deficiency (ferritin level less than 30), corresponding to a negative likelihood ratio of 0.90 (95% CI, 0.77-1.05) and 0.85 (95% CI, 0.73-0.99), respectively. More than 50% of the 1,749 women with documented iron deficiency anytime during pregnancy were neither anemic nor microcytic at the time of diagnosis.

Impact of Gold Nanoparticles Intraperitoneal Injection on Mice's Erythrocytes and Renal Tissue.

The purpose of this study was to investigate the effects of two different types of gold nanoparticles (AuNPs) delivered by intraperitoneal (IP) injection on blood and kidney tissue changes in a mouse model. Three groups of fifteen adult male BALB/c healthy mice, weighing approximately 25-30 g, were used for the experiment and designated G1, G2, and G3, respectively. G1 mice received vehicle, whereas G2 and G3 received an IP injection of 10 mg/kg body weight of methoxy poly ethylene glycol gold nanoparticles (PEG-AuNPs) and fluorescently dye labeled gold nanoparticles (Dye-AuNPs), respectively. Hematological parameters were measured based on the standard complete blood cell count (CBC) technique. The two nanoparticles, i.e., PEG-AuNPs and Dye-AuNPs, significantly reduced most red blood cell (RBC) parameters in the groups with the exception of a nonsignificant effect on hemoglobin (HBG) levels. Both gold nanoparticles, i.e., PEG-AuNPs and Dye-AuNPs, led to a reduced RBC count, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) level when compared with the control. Notably, Dye-AuNPs and PEG-AuNPs resulted in a considerably higher RBC distribution RDW-(CV % and SD fL). Glomerular injury was suggested based on the development of hydropic degeneration and the presence of a protein-rich fluid inside the tubules. Renal tissue and blood indices changed significantly in response to the two nanoparticles, suggesting possible organ injury.

A-167 Hematologic setpoints are a deep physiologic phenotype which enable personalized blood count reference intervals

Abstract Background The complete blood count (CBC) is an important screening tool for healthy adults, commonly ordered at periodic physical exams. However, test results are typically interpreted using one-size-fits-all reference intervals (RIs), which don’t account for the low index-of-individuality of most CBC markers. This undermines the goal of precision medicine - to tailor patient care based on individual characteristics. Methods Here we utilize a database of &amp;gt;50,000 healthy outpatients with yearly CBCs, to investigate the value of patient-specific reference intervals (PRIs) for 9 CBC markers. We use Gaussian mixture modelling to calculate each patient’s setpoints, and to construct associated PRIs. Mechanistic drivers of setpoints were investigated through GWAS and via analysis of excess clinical specimens. Clinical outcomes were analyzed by comparing sensitivity of RIs and PRIs for detection of future cytopenia/cythemia and mortality. Results We found healthy adults had patient-specific setpoints that were stable over decades, and distinctly identifiable from 98% of other patients. Setpoints reflected a deep physiologic phenotype, enabling improved detection of genetic determinants of hematologic regulation (Fig1A), including discovery of multiple novel loci via GWAS analysis. Deviation from PRIs was associated with greater risk of cytopenia/cythemia and mortality (Fig1B) than deviation from the RI for all setpoints except MCHC. Setpoints were significantly correlated with long-term all-cause mortality, even when limited to those within the RI (Fig1C). Conclusions We show that hematologic setpoints reflect a deep, patient-specific phenotype. This phenotype can enhance mechanistic studies, and allow for increased diagnostic sensitivity, through calculation of a personalized reference interval. Setpoints are sufficiently stable and patient-specific to help realize the promise of precision medicine for healthy adults.Fig1A.Significance of GWAS hits using setpoints versus single CBCs. Fig1B. 10yr mortality hazard ratio for tests outside the RI and PRI. Fig1C. Association of WBC setpoint with mortality (limited to WBC setpoints inside the RI).

A-169 Artificial Intelligence based Complete Blood Count

Abstract Background The OLO device (Sight diagnostics, Israel) is an artificial intelligence based blood counter. OLO contains a fluorescent microscope and a camera embedded inside it. The pictures are processed by an image processing algorithm based on “machine-vision technology” to identify and quantify cells. The measurement analysis is accompanied by messages (flags) that are used to warn of deviations in the counted parameters, which help the operator refer the sample for microscopic analysis. In this study, we compared the results of 19 complete blood count (CBC) parameters obtained from OLO to the CBC parameters obtained from the ADVIA 2120 device (Siemens, USA). In addition we examined the reliability of OLO alerts (flags) by comparing it to the microscopic analysis findings. Methods 99 blood samples from patients aged &amp;gt;3 months were sampled by the ADVIA and OLO devices. Regression analysis was performed in comparing the results of 19 parameters between the devices. Specificity and sensitivity values ​​of the OLO device alerts were calculated. Results A good correlation was found for CBC parameters between OLO and ADVIA with Pearson correlation (R) of 0.992 (WBC), 0.985 (RBC), 0.991 (HB) and 0.983 (PLT). A fundamental difference in measurement and classification technologies between OLO and ADVIA lead to low correlation measured for monocytes. By comparing OLO alerts against blood smears findings, a total of 14 samples were alerted by OLO but only slight left shift/single pathological cell were found in the smears which is below threshold defined by the manufacturer. These 14 samples were transferred to the true positive category, therefore OLO device alerts showed sensitivity and specificity of 81.8% and 90% (respectively) in identifying pathological cells. Conclusions The comparison findings present a technology based on image processing and artificial intelligence that have a good correlation to the ADVIA reference device. In addition, OLO has the ability to warn of pathological findings even below the threshold defined by the manufacturer. The artificial learning is expected to be improved so that this device can integrate CBC and microscopic differentiation simultaneously, a great advantage to the hematology laboratories workflow.

B-128 Delivering Predictable Operational efficiency gains at our core central reference laboratory with strategic deployment of navify® Lab Operation informatics automation solution

Abstract Background Metropolis Healthcare Limited (‘MHL’) operates a network of 200 clinical labs in India, our Global Reference Lab (GRL) in Mumbai processes over 25000 tests in a 17 hour daily operation. We are an ISO15189 and CAP accredited laboratory. Our strategic goals have been to bring operational standardization across the network &amp; Improve speed of service with a predictable 90 percentile production TAT. To achieve this goal, we chose digitalization of our laboratory operation with the deployment of navify ® Lab Operations informatics automation solution in. This poster explains our journey of planning, implementing, and delivering on our goal of predictable operational efficiency. The digital solution is at the forefront of all digitalization IQC processes, auto validation and auto approval of patient results passing through a framework of autoverification rules and complete traceability of processes. Methods The poster will explain the scope, planning and implementation approach of this digital automation project at Global reference Lab in 5 stepsHL7 order structure for communication between LIS and navify ® Lab Operations22 analyzers from 11 different manufacturers being connected to the Informatics solution. the corresponding testingTest &amp; IQC (Internal Quality Control) Master with specific ranges and rules10 steps AV (Auto verification) Rules decision framework of concentric sieves across lab disciplines (155 AV Algorithms have been configured at GRL)Structured user acceptance testing framework before Go Live. Results This poster discusses the outcomes that we have seen on deployment of this digital solution.Over 25,000 test results are subject AV engine daily with AV rate of 75 % of all results in Biochemistry, Immunoassays.66 % of all Complete Blood Count (CBC) reports 95 % of all HbA1c results 93 % of all ESR resultsOver 1750 QC results are subject to QC rules dailyThere is an improvement of 4 hours observed in production TAT Conclusions Laboratory Informatics solution has enhanced lab performance in terms of TAT &amp; efficiency of review. The staff satisfaction (both technical and medical) has increased and we see an impact on production outcome. The poster will also show an incremental effectiveness analysis by comparing key performance areas such as predictability in production, staff time saved, before and after technology deployment.

A-334 Vital one: a point-of-care platform for rapid, comprehensive, central-lab quality blood testing

Abstract Background Diagnostic tools are fundamental to informed healthcare decisions, but the current state of in vitro diagnostics presents barriers to providing timely access to a wide menu of tests. This poster discusses a method for overcoming these challenges with a novel and miniaturized point-of-care (PoC) solution, the VitalOneTM. While many PoC solutions have limited test menus tailored for specific scenarios, Vital Biosciences introduces a comprehensive test menu in a compact PoC format that uses centrifugal microfluidic workflows to deliver quantitative results for over 50 analytes spanning hematology, clinical chemistry, and immunoassay modalities, ensuring central-lab quality results for a wide variety of use cases in a 20-min time frame (or 15 min for a Comprehensive Metabolic Panel (CMP) lipid panel, and liver panel). The VitalOneTM is designed to perform a complete blood count (CBC), a comprehensive panel with a full array of immunoassays and clinical chemistry assays, returning over 50 results with as little as 300-750 µL of whole blood. This poster provides a comprehensive and transparent view of both our results and underlying methods of operation. By comparing the VitalOneTM system with established benchmarks like Roche, Sysmex, and Beckman Coulter instrument systems, we demonstrate consistent assay performance, resilience to interference, and performance that is compliant with CLIA Total Allowable Error standards. Methods A method comparison analysis of measurements on VitalOneTM platform was performed against predicate instruments that are commonly used in centralized laboratories (Roche Cobas, Beckman AU480, Beckman Coulter DxH500, Beckman Access 2, and Sysmex 140). Additionally, a 5-8 point calibration curve was generated for each analyte across the desired assay measuring range (AMR) using commercially available validation kits on three separate days, resulting in a master calibration curve. To check for sensitivity to potential interferences that may be present in patient samples, endogenous and exogenous interference testing was performed following Clinical &amp; Laboratory Standards Institute (CLSI) guidelines. Lastly, robustness testing was carried out to mimic the extremes of variances in volumes, times, or temperatures that may be encountered when running an assay protocol. Results The method comparison analysis (n = 840 samples) and precision studies revealed that the VitalOne exhibited a strong correlation with the benchmark instruments and were in compliance with CLIA's total allowable error limits, reinforcing the reliability and clinical relevance of our diagnostic system. Assays across Hematology, Clinical Chemistry, and immunoassays demonstrated &amp;gt;95% of data within CLIA TEa% and run-to-run imprecision ≤ 5%. Additionally, linearity studies revealed that each analyte AMR spans across physiologically relevant concentrations, defined by medical decision levels and reference intervals for each analyte. Our robustness and endogenous and exogenous interference testing performed as per CLSI guidelines has demonstrated that the VitalOneTM system closely matches, and in certain parameters, such as biotin interference, even surpasses that of the predicate instruments. Conclusions In summary, the VitalOneTM platform represents a significant advancement in point-of-care diagnostics, offering a comprehensive, accurate, and efficient alternative to traditional laboratory testing. This innovation is poised to transform the way clinicians approach diagnostics, enabling more informed decision-making and ultimately enhancing patient outcomes.

A-141 Ferritin Test Utilization to Differentiate Microcytic Anemia

Abstract Background Mean corpuscular volume (MCV) of the Red Blood Cells (RBC) is a component test of the commonly ordered Complete Blood Count (CBC) panel and is an important parameter when evaluating a patient diagnosed with anemia. MCV is used to classify anemia as microcytic (low MCV), normocytic (normal MCV), or macrocytic (high MCV). Microcytic anemia occurs most commonly from iron deficiency or from an inherited blood disorder caused when the body does not produce enough hemoglobin (thalassemia trait), often resulting in iron overload. Clinical management for each of these microcytic anemia contributors varies greatly and requires appropriate differentiation. Laboratory testing of serum ferritin level helps to distinguish iron deficiency from thalassemia and is therefore the first laboratory test recommended in the evaluation of microcytosis. However, initial laboratory findings indicate that ferritin tests do not always accompany low MCV results. The objective of this study was to quantify the frequency of ferritin orders proximate to abnormally low MCV results across two hospitals to assess utilization of ferritin testing for differentiating microcytic anemia. Methods A retrospective study was performed on the ordering patterns of MCV and ferritin tests at two different hospitals. Abnormally low MCV values were selected from both adult and pediatric populations during an eight-month period from March through October. All ferritin values from January through December of that same calendar year were selected and joined with the MCV data. Patients with a ferritin test 60 days before or after the MCV test were considered to have a ferritin order associated with the abnormally low MCV. The ratio of the total count of these ferritin orders to the total count of low MCV values was calculated as a percent. Results Results showed that 46% (619/1351) of all abnormal low MCV values at Hospital One (Pediatric) had a ferritin ordered within 60 days. An additional 57 cases had a ferritin ordered beyond 60 days, and 675 lacked ferritin orders during the calendar year. During that same period and using the same criteria, Hospital Two (Adult) had ferritin ordered 43% (2301/5320) of the time. An additional 135 had a ferritin ordered beyond 60 days, and 2884 lacked ferritin orders during the calendar year. Conclusions Establishing test utilization benchmarks can be a useful stewardship tool for clinical laboratories. The data presented here suggested an underutilization of ferritin testing in the presence of abnormally low MCV values across two healthcare organizations. This study lays the groundwork to further assess MCV and ferritin ordering patterns and a standardized means to quantify these observations across diverse healthcare settings to establish a more robust benchmark.

B-136 From Result to Response: The Development of Laboratory-Based Scoring Models to Predict COVID-19 Patient Outcomes

Abstract Background Patient characteristics relating to increased risk for COVID-19 severity are well-documented, including older age and pre-existing health concerns; however, methods to accurately predict patients’ acute reaction to SARS-CoV-2 infections remain lacking. Identification of specific laboratory tests informative of patient outcomes could effectively screen incoming patients and better inform physicians regarding optimal treatment plans. The aim of this study was to examine associations between frequently ordered laboratory markers and COVID-19 patient mortality to develop an objective laboratory-based scoring system that estimates patients’ risk of mortality. Methods Study participants included inpatients from 3 hospitals recruited into the GENCOV project based in Ontario, Canada. Participants (n=325) were at least 18 years of age, provided consent, and were hospitalized within 1 month of having a PCR confirmed COVID-19 infection between January 2020 and February 2022. Extensive clinical data including patient demographics, laboratory results, and treatment outcomes were extracted from patient’s electronic medical records (EMR). Results for 32 biochemical and hematological tests including complete blood cell counts, coagulation (activated partial thromboplastin time, D-dimer, fibrinogen, prothrombin time), general chemistry (albumin, blood gases, creatine kinase, electrolytes, glucose, triglycerides), inflammatory (lactate dehydrogenase, ferritin, C-reactive protein), liver (alanine aminotransferase, aspartate aminotransferase, total bilirubin), renal (creatinine, urea) and cardiac (troponin, NT-proBNP, BNP) markers were collected from each chart. Univariable logistic regression with nested likelihood ratio tests were used to determine significant associations between laboratory results and patient outcomes. Significant markers were incorporated into multivariable models and variable risk values were assigned. Total calculated risk scores for each participant were compared using univariable and multivariable risk values. Validation of each scoring method was performed on a 20% subset of inpatients. Receiver operating characteristic (ROC) curves evaluated model performance. Results Six laboratory markers were associated with COVID-19 patient mortality when controlling for age and sex. Univariable regression showed that elevated creatinine, elevated lactate, elevated white blood cell, low base excess, low bicarbonate, or low pH results upon admission were significantly associated with increased odds of mortality, in comparison to test results within the reference range for these same markers. Multivariable regression revealed fewer markers (only low bicarbonate and low base excess) showing significant associations with COVID-19 mortality. Area under the ROC curves (AUC) determined that risk scores derived from univariable values performed similarly to multivariable values in validation (0.800 vs 0.802) and development cohorts (0.821 vs 0.829). Total risk scores calculated from the univariable vs multivariable models suggest higher sensitivity (90% vs 85%) than specificity (58% vs 67%) in the validation cohort, whereas the development cohort had higher sensitivity (88%) than specificity (66%) with univariable scores, and higher specificity (81%) than sensitivity (74%) with multivariable scores. Conclusions Laboratory results associated with COVID-19 mortality following both univariable and multivariable analyses suggest hospitalized patients infected with SARS-CoV-2 may present with acidosis. Total risk scores derived from univariable and multivariable values performed similarly in predicting mortality; however, differences in marker significance between models indicate discrepancies with risk interpretation. Further comparison of the created risk score assessments with equivalent models in other populations is warranted.

Complete blood count as a biomarker for preeclampsia with severe features diagnosis: a machine learning approach

ObjectiveThis study introduces the complete blood count (CBC), a standard prenatal screening test, as a biomarker for diagnosing preeclampsia with severe features (sPE), employing machine learning models.MethodsWe used a boosting machine learning model fed with synthetic data generated through a new methodology called DAS (Data Augmentation and Smoothing). Using data from a Brazilian study including 132 pregnant women, we generated 3,552 synthetic samples for model training. To improve interpretability, we also provided a ridge regression model.ResultsOur boosting model obtained an AUROC of 0.90±0.10, sensitivity of 0.95, and specificity of 0.79 to differentiate sPE and non-PE pregnant women, using CBC parameters of neutrophils count, mean corpuscular hemoglobin (MCH), and the aggregate index of systemic inflammation (AISI). In addition, we provided a ridge regression equation using the same three CBC parameters, which is fully interpretable and achieved an AUROC of 0.79±0.10 to differentiate the both groups. Moreover, we also showed that a monocyte count lower than 490/mm3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$490 /mm^{3}$$\\end{document} yielded a sensitivity of 0.71 and specificity of 0.72.ConclusionOur study showed that ML-powered CBC could be used as a biomarker for sPE diagnosis support. In addition, we showed that a low monocyte count alone could be an indicator of sPE.SignificanceAlthough preeclampsia has been extensively studied, no laboratory biomarker with favorable cost-effectiveness has been proposed. Using artificial intelligence, we proposed to use the CBC, a low-cost, fast, and well-spread blood test, as a biomarker for sPE.

Prognostic Relevance of Immunophenotyping in Adult Patients with Acute Leukemia in Turkey: A Single-Center Experience.

In acute leukemia, many associations have been identified between prognosis and some factors, such as individual antigen expression, cytogenetics, gender, age, high leukocyte level (WBC), platelet count (PLT), and lactate dehydrogenase (LDH), but few are consistent. In this study, we aimed to investigate the cell surface markers and other clinical pathological features for prognosis determination in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients in our population. This cross-sectional study was performed from January 2017 to December 2023 in İstanbul Training and Research Hospital and included 113 patients (86 AML and 27 ALL) newly diagnosed with AML (non-APL) and ALL. The following tests were fulfilled for the included patients: complete blood count (CBC), LDH, and flow cytometric analysis using a blood sample or bone marrow aspirate. The effects of surface markers, gender, age, WBC, PLT, and LDH on 24-month survival were evaluated retrospectively. Among the investigated parameters, lack of CD13 expression and positive CD10, cTdT expressions were associated with poor prognosis in AML patients (p = 0.01, p = 0.04, and p = 0.04, respectively). We have found no association between the surface markers and other parameters with prognosis in ALL patients. Age > 65 years was associated with poor prognosis in both AML and ALL patients (p < 0.001). CD10, cTdT positivity, and CD13 negativity may predict poor prognosis for AML and can be considered as prognostic biomarkers for AML patients.

Therapeutic potential of oleanolic acid in modulation of PI3K/Akt/mTOR/STAT-3/GSK-3β signaling pathways and neuroprotection against methylmercury-induced neurodegeneration

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that gradually deteriorates motor neurons, leading to demyelination, muscle weakness, and eventually respiratory failure. The disease involves several pathological processes, such as increased glutamate levels, mitochondrial dysfunction, and persistent neuroinflammation, often exacerbated by environmental toxins like mercury. This study explores the therapeutic potential of Olea europaea active phytoconstituents oleanolic acid (OLA) against ALS by targeting the overactivated PI3K/Akt/mTOR/STAT-3/GSK-3β signalling pathways. Methods involved in-silico studies, in vitro and in vivo experiments in which varying doses of methylmercury 5 mg/kg, p.o. and OLA (100 and 200 mg/kg, i.p.) were administered to rats for 42 days. Behavioural assessments, gross morphological, histopathological, and neurochemical parameters were measured in cerebrospinal fluid (CSF), blood plasma, and brain homogenates (cerebral cortex, hippocampus, striatum, midbrain, cerebellum) along with complete blood count (CBC) analysis. Results revealed OLA's significant neuroprotective properties. OLA effectively modulated targeted pathways, reducing pro-inflammatory cytokines, restoring normal levels of myelin basic protein (MBP) and neurofilament light chain (NEFL), and reducing histopathological changes. Gross pathological studies indicated less tissue damage, while CBC analysis showed improved hematology parameters. Additionally, the combination of OLA and edaravone (10 mg/kg, i.p.) demonstrated enhanced efficacy, improving motor functions and extending survival in ALS model rats. In conclusion, OLA exhibits significant therapeutic potential for ALS, acting as a potent modulator of key pathological signaling pathways. The findings suggest the feasibility of integrating OLA into existing treatment regimens, potentially improving clinical outcomes for ALS patients. However, further research must validate these findings in human clinical trials.

Derivation of Russian-specific reference intervals for complete blood count, iron markers and related vitamins.

This study aimed to establish reference intervals (RIs) for Russian adults for hematological parameters including related iron markers and vitamins. Sources of variation of reference values (RVs) and needs for secondary exclusion were explored for proper derivations of RIs. Following the harmonized protocol of the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL), 506 healthy Russians (age 18-80; 46% male) were recruited. Complete blood counts (CBC) and leukocyte differentials, iron markers, vitamin B12, and folate were measured by Beckman Coulter's analyzers. Sources of variation were analyzed by multiple regression analysis, and ANOVAs, and the need for partitioning RVs was decided accordingly. Two schemes of excluding latent anemia were compared: (1) latent abnormal values exclusion method (LAVE) based on associations among CBC parameters, or (2) explicit exclusion of individuals with either ferritin or iron below the respective lower limit of the manufacturer. RIs were determined by the parametric method using two-parameter Box-Cox formula. Gender-specific RIs were required for most analytes, while age-specific RIs were set only for ferritin in females. A BMI-related increase in RVs was prominently observed for reticulocyte parameters, hence we chose to exclude individuals with BMI>28 kg/m2 when establishing the RIs. The LAVE method was more effective in excluding individuals with latent anemia, than exclusion based on low ferritin and/or iron values. International comparison revealed that Russian RIs featured a lower side shift of platelet counts. Similar to African countries, Russian RIs for total leukocyte and neutrophil counts were lower compared to most of other countries. RIs for the Russian population for 34 hematological and related parameters were established using up-to-date methods proposed by C-RIDL. Reducing the influences of latent anemia and obesity on RIs was crucial for erythrocyte parameters. Low levels of Russian RIs observed for platelet and neutrophil counts need further investigation.

Impact of iron deficiency anemia on academic achievement among female university students in Saudi Arabia.

Anemia, particularly iron deficiency anemia (IDA), is a prevalent health issue globally and in Saudi Arabia, especially among young adult females. This study investigates the association between anemia and academic achievement among female students at the Female Health Campus of Jazan University, Jazan, Saudi Arabia. This cross-sectional study included 118 randomly selected participants aged 18-22. A validated questionnaire was administered to the study participants. The participants underwent blood tests for complete blood count (CBC) parameters and iron profile analysis. The study reported that 52.5% of the female students had anemia and low serum iron levels. Regarding academic performance, significant positive correlations were found between various CBC parameters including white cell count, hemoglobin, hematocrit, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, and serum iron. However, no significant correlations were observed between red blood cell count and platelet count with academic performance. Demographic variables were also associated with a higher odds ratio of anemia. The study highlights the prevalence of anemia among female students and its potential impact on academic achievement. The current study underscores the importance of addressing anemia in young adult females and implementing appropriate interventions to improve their educational outcomes.

The prognostic role of pan-immune inflammation value in patients with metastatic castration resistance prostate cancer treated with Lutetium-177 (177Lu)-PSMA-617.

Pan-immune inflammation value (PIV) is a newly defined biomarker that includes whole cellular components that are indicators of systemic inflammation in complete blood count (CBC), easily accessible and has the potential to reflect both the body's immune response and systemic inflammation status. This study evaluated the pretreatment PIV for its prognostic impact on overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with Lutetium-177 (177Lu)-PSMA-617. The PIV was based on the earliest CBC obtained within 1 month before treatment initiation. Patients were categorized into low and high PIV groups based on the median pretreatment PIV, and the relationship between OS and PIV groups was assessed by multivariable analysis. A total of 43 patients with mCRPC treated with (177Lu)-PSMA-617 were included. The median OS was longer in the low PIV group (15.1 months [95% confidence interval [CI] 10.6-19.5]) than in the high PIV group (4.2 months [95% CI 1.7-6.6]) (p < 0.001). In multivariable analysis, high PIV (hazard ratio [HR]: 4.3, 95% CI 1.194-15.93, p = 0.026) and high Eastern Cooperative Oncology Group performance score (HR: 7.05, 95% CI 1.48-33.46, p = 0.014) were associated with shorter OS. This study showed that pretreatment PIV might be a prognostic factor in patients with mCRPC treated with (177Lu)-PSMA-617.