Blood Count Research Articles

Unlocking the complete blood count as a risk stratification tool for breast cancer using machine learning: a large scale retrospective study

Optimizing early breast cancer (BC) detection requires effective risk assessment tools. This retrospective study from Brazil showcases the efficacy of machine learning in discerning complex patterns within routine blood tests, presenting a globally accessible and cost-effective approach for risk evaluation. We analyzed complete blood count (CBC) tests from 396,848 women aged 40–70, who underwent breast imaging or biopsies within six months after their CBC test. Of these, 2861 (0.72%) were identified as cases: 1882 with BC confirmed by anatomopathological tests, and 979 with highly suspicious imaging (BI-RADS 5). The remaining 393,987 participants (99.28%), with BI-RADS 1 or 2 results, were classified as controls. The database was divided into modeling (including training and validation) and testing sets based on diagnostic certainty. The testing set comprised cases confirmed by anatomopathology and controls cancer-free for 4.5–6.5 years post-CBC. Our ridge regression model, incorporating neutrophil–lymphocyte ratio, red blood cells, and age, achieved an AUC of 0.64 (95% CI 0.64–0.65). We also demonstrate that these results are slightly better than those from a boosting machine learning model, LightGBM, plus having the benefit of being fully interpretable. Using the probabilistic output from this model, we divided the study population into four risk groups: high, moderate, average, and low risk, which obtained relative ratios of BC of 1.99, 1.32, 1.02, and 0.42, respectively. The aim of this stratification was to streamline prioritization, potentially improving the early detection of breast cancer, particularly in resource-limited environments. As a risk stratification tool, this model offers the potential for personalized breast cancer screening by prioritizing women based on their individual risk, thereby indicating a shift from a broad population strategy.

Idiopathic Immune Mediated Haemolytic Anaemia (IMHA) in a 2.5-Month-old Puppy: A Case Report

Background: A 2.5-month-old puppy was presented to the Veterinary Clinical Complex of the College of Veterinary Sciences and AH, Jalukie, Nagaland with a complaint of emesis for one week, inappetence, icterus of the lower abdominal area and other visible mucous membrane. Detailed clinical history was collected and clinical examination was conducted. Methods: 4 ml blood peripheral blood was collected from the cephalic vein in the Lev-Lock blood clot activator vacutainer to harvest serum for biochemical analysis. Another 2 ml of whole blood was also collected in Lev-Lock K3 EDTA vacutainer for complete blood count, blood smear examination for blood parasites, morphological changes in the RBC and IDEXX SNAP 4Dx Plus test kit was also used for diagnosis of the blood parasites test. Result: Peripheral blood smear examination and IDEXX SNAP 4Dx Plus test were found to be negative for blood parasites, but spherocytosis could be observed in the blood smears. A complete blood count (CBC) examination revealed severe anaemia of macrocytic normochromic type, neutrophilic leucocytosis and thrombocytopenia. Serum biochemistry revealed a decrease in blood urea nitrogen (BUN) and creatinine with normal alanine transaminase (ALT). Treatment with whole blood transfusion, corticosteroid and other supportive therapy was successful in this case. Based on the clinical presentation, laboratory findings and its response to the treatment with prednisolone, it was diagnosed as an idiopathic immune-mediated haemolytic anaemia (IMHA) with an extravascular mechanism of haemolysis. A follow-up review after 1 year and 4 months post-treatment reported that the dog was still alive and healthy.

Complete Blood Count Reference Intervals for Children Aged Less Than 1 to 12 Years in the Northern Region of Ghana

Reliable laboratory diagnostic results are key for evaluating and improving children’s health. To interpret these results, child-specific reference intervals (RIs), which account for constant biological changes and physiological development with sex and age, are required, as recommended by the Clinical and Laboratory Standards Institute (CLSI). This study presents age- and sex-specific reference intervals for complete blood count (CBC) parameters in children (<1–12 years old) in the Northern Region of Ghana. In this cross-sectional study, 600 healthy children from randomly sampled schools in Tamale (the Northern Region) were recruited and screened. Data from 388 eligible children were used to nonparametrically determine the reference intervals of CBC parameters at the 2.5th and 97.5th percentiles. The CBC reference intervals were compared for variations in sex and age groups using the Wilcoxon rank-sum test. There were no statistically significant differences in most CBC parameters by sex (RBC, Hb, HCT, MCH, RDW (CV/SD), WBC, LYM#, MON#(%) NEU#(%), EOS#(%), and BAS#(%); p>0.05) and age group (RBC, MCV, RDW (CV/SD), WBC, LYM#, MON#(%) NEU#(%), EOS#(%), and BAS%; p>0.05). However, there were observable differences between this locally established CBC reference interval and that used for children at Tamale Teaching Hospital (manufacturer’s RIs). This study emphasises the importance of determining reference intervals representative of the local child population and incorporating them into the current reporting system of laboratories in the Northern Region to ensure the provision of effective and efficient healthcare services.

General practitioners’ management of mastitis in breastfeeding women: a mixed method study in Australia

BackgroundMastitis is a common reason new mothers visit their general practitioner (GP). In Australia, the Therapeutic Guidelines: Antibiotic provides practical advice to GPs managing a range of infections, including mastitis. It is not known if Australian GPs prescribe antibiotics and order investigations as recommended for the management of mastitis.MethodsA convergent mixed methods design integrated quantitative analysis of a general practice dataset with analysis of interviews with GPs. Using the large-scale primary care dataset, MedicineInsight, (2021–2022), antibiotics prescribed and investigations ordered for mastitis encounters were extracted. Mastitis encounters were identified by searching ‘Encounter reason’, ‘Test reason’ and ‘Prescription reason’ free text field for the term ‘mastitis’; ‘granulomatous mastitis’ was excluded. Clinical encounters for mastitis occurring within 14 days of a previous mastitis encounter were defined as belonging to the same treatment episode. Semi-structured interviews were conducted with 14 Australian GPs using Zoom or telephone in 2021–2022, and analysed thematically. The Pillar Integration Process was used to develop a joint display table; qualitative codes and themes were matched with the quantitative items to illustrate similarities/contrasts in findings.ResultsDuring an encounter for mastitis, 3122 (91.7%) women received a prescription for an oral antibiotic; most commonly di/flucloxacillin ([59.4%]) or cefalexin (937 [27.5%]). Investigations recorded ultrasound in 303 (8.9%), blood tests (full blood examination [FBE]: 170 [5.0%]; C-reactive protein [CRP]: 71 [2.1%]; erythrocyte sedimentation rate [ESR]: 34 [1.0%]) and breast milk or nipple swab cultures in approximately 1% of encounters. Analysis using pillar integration showed consistency between quantitative and qualitative data regarding mastitis management. The following themes were identified:- GPs support continued breastfeeding.- Antibiotics are central to GPs' management.- Antibiotics are mostly prescribed according to Therapeutic Guidelines.- Analgesia is a gap in the Therapeutic Guidelines.- Low use of breast milk culture.ConclusionsPrescribing antibiotics for mastitis remains central to Australian GPs’ management of mastitis. Interview data clarified that GPs were aware that antibiotics might not be needed in all cases of mastitis and that delayed prescribing was not uncommon. Overall, GPs followed principles of antibiotic stewardship, however there is a need to train GPs about when to consider ordering investigations.

Complete blood count, coagulation biomarkers, and lung function 6 months after critical COVID-19.

Understanding the recovery of post-COVID-19 organ dysfunction is essential. We evaluated coagulation 6 months post-COVID-19, examining its recovery and association with lung function. Patients treated for COVID-19 at intensive care units between 3/2020 and 1/2021 were analyzed for complete blood count (CBC) and coagulation biomarkers (prothrombin time activity (%) (PT%), activated partial thromboplastin time (APTT), fibrinogen, coagulation factor VIII (FVIII), antithrombin (AT), and D-dimer) during the 6 months post-hospitalization. Results were compared with acute phase values and correlated with pulmonary function tests (PFT), including forced vital capacity (FVC) and hemoglobin-corrected diffusing capacity percentage of predicted (DLCOc%), recorded 6 months post-hospitalization. We examined the association between coagulation biomarkers and DLCOc% using linear regression with age, sex, and invasive mechanical ventilation (IMV) duration, and FVIII (correlated with DLCOc%) as covariates. Most CBCs and coagulation biomarkers had median values within the normal range. However, only 21% (15/70) of patients achieved full normalization of all biomarkers. Compared to acute COVID-19, hemoglobin, PT%, and AT increased, while leukocytes, fibrinogen, FVIII, and D-dimer decreased. Despite decreased levels, FVIII remained elevated in 46% (31/68), leukocytes in 26% (18/70), and D-dimer in 27% (18/67) at 6 months. A weak negative correlation (r = -0.37, p = .036) was found between DLCOc% and FVIII. Multivariable analysis revealed a weak, independent association between DLCOc% and FVIII. Excluding patients with anticoagulation therapy, FVIII no longer correlated with DLCOc%, while AT showed a moderate correlation with DLCOc%. Only a few patients had normal CBC and coagulation biomarker values 6 months after critical COVID-19. A weak negative correlation between DLCOc% and FVIII suggests that deranged coagulation activity may be associated with reduced diffusing capacity.

Predicting in-hospital mortality in infective endocarditis: insights from complete blood count parameters and NT-proBNP

Abstract Funding Acknowledgements None. Introduction Infective endocarditis (IE) is a rare condition with an increasing incidence rate and complexity of cases over the last few years, accompanied by a high mortality rate ranging from 18% to 25%. Recent studies have shown the utility of new outcome predictors based on complete blood count (CBC), such as red blood cell distribution width (RDW) and neutrophils/lymphocytes ratio (NLR). Drawing retrospectively from an 8-year experience, we provide a perspective from a tertiary center on predictors of in-hospital mortality based on basic laboratory test results in patients with valve-related IE. Purpose The aim of the study was to assess the clinical accuracy of CBC-based parameters as in-hospital mortality predictors. Methods From a tertiary center database (serving a stable population of 2.5 million citizens), we selected all patients hospitalized due to valve-related infective endocarditis between 2015 and 2022. We analyzed clinical data (including sex, age, IE localization, and etiological factors, number of cases, management and mortality), laboratory test results at admission (including CBC parameters, C-reactive protein - CRP, procalcitonin - PCT, N-terminal prohormone of brain natriuretic peptide - NT-proBNP, estimated glomerular filtration rate - eGFR, Creatinine - Crea, urea - UR). For three NT-proBNP, NLR, and RDW we provided a further analysis to compare their clinical accuracy. Univariable logistic regression was used to assess the impact of specific factors on mortality. To determine the optimal cutoff values for predicting mortality, we analyzed the area under the curve (AUC) from receiver operating characteristic (ROC) curves and used Youden's index. P-values < 0.05 were considered statistically significant. Results A total of 194 consecutive patients with confirmed IE were included in the study, the majority of whom were men (75.3%) with an overall median age of 62 years. The overall mortality rate was 27.8%. The most common localization was left-sided IE (92.3%). In 39.7% of cases, the etiological factor was unidentified, while Staphylococcus spp. were the most common bacteria among the identified cases. We identified significant impacts on mortality in most of the analyzed laboratory tests (RDW, platelet count, hemoglobin, NLR, PCT, NT-proBNP, eGFR, Crea, UR). Results showed that for every 1000pg/ml of NT-proBNP the risk of in-hospital death increases by 6%. ROC analysis was performed for the three parameters (RDW, NLR, and NT-proBNP), and each parameter showed an acceptable area under the curve - AUC (RDW: 0.69; NLR: 0.62; NT-proBNP: 0.78). Although we found the highest AUC for NT-proBNP (p<0.001). Conclusions Although CBC parameters are easy to assess and useful in predicting in-hospital death in IE, the accuracy of NT-proBNP is higher. The management of IE cases requires a complex approach, and NT-proBNP, which also reflects the clinical state of patients, still remains a more useful tool.In-hospital deaths ROC analysis

Assessment of Medical Test Overuse and Its Impact on Pediatric Emergency Department Outcomes in Upper Respiratory Tract Infections in a University Hospital in Lithuania

Medical overuse poses potential risks to patients and contributes to increasing healthcare costs, pediatric emergency departments (PED) in particular. Often, upper respiratory tract infection (URTI) cases are viral-induced and self-limiting, and they do not require specific investigations or treatment. We conducted a retrospective study from 1 December 2021 to 31 January 2022, thereby aiming to identify the common tests and factors influencing specific diagnostic and treatment decisions for URTI in PED. In total, 307 (74.9%) URTI cases underwent complete blood count (CBC) tests, 312 (76.1%) were subjected to C-reactive protein (CRP) tests, and 110 (26.8%) received urinalysis tests. Patients with a longer duration of fever and a physician‘s suspicion of bacterial infection were more likely to receive CBC, CRP, and/or urinalysis tests (p < 0.05). Moreover, 75.1% of the cases were classified as viral URTIs, 9.8% were bacterial URTIs, and 15.1% were unspecified. Notably, 86 (20.1%) children received antibiotics and antibiotic prescription correlated with age, tonsillitis diagnosis, CRP values higher than 30 mg/L, and a CBC of p < 0.05. Patients triaged in the second or third categories were three times more likely to be observed for 24 h compared to patients with URTI and the fourth triage category (p < 0.05). This study highlights the need for interventions to improve the appropriateness of emergency service utilization, thereby emphasizing the importance of judicious decision making in managing pediatric URTIs.

Contribution of parasite and host genotype to immunopathology of schistosome infections

BackgroundThe role of pathogen genotype in determining disease severity and immunopathology has been studied intensively in microbial pathogens including bacteria, fungi, protozoa and viruses but is poorly understood in parasitic helminths. The medically important blood fluke Schistosoma mansoni is an excellent model system to study the impact of helminth genetic variation on immunopathology. Our laboratory has demonstrated that laboratory schistosome populations differ in sporocyst growth and cercarial production in the intermediate snail host and worm establishment and fecundity in the vertebrate host. Here, we (i) investigate the hypothesis that schistosome genotype plays a significant role in immunopathology and related parasite life history traits in the vertebrate mouse host and (ii) quantify the relative impact of parasite and host genetics on infection outcomes.MethodsWe infected BALB/c and C57BL/6 mice with four different laboratory schistosome populations from Africa and the Americas. We quantified disease progression in the vertebrate host by measuring body weight and complete blood count (CBC) with differential over a 12-week infection period. On sacrifice, we assessed parasitological (egg and worm counts, fecundity), immunopathological (organ measurements and histopathology) and immunological (CBC with differential and cytokine profiles) characteristics to determine the impact of parasite and host genetics.ResultsWe found significant variation between parasite populations in worm numbers, fecundity, liver and intestine egg counts, liver and spleen weight, and fibrotic area but not in granuloma size. Variation in organ weight was explained by egg burden and intrinsic parasite factors independent of egg burden. We found significant variation between infected mouse lines in cytokine levels (IFN-γ, TNF-α), eosinophils, lymphocytes and monocyte counts.ConclusionsThis study showed that both parasite and host genotype impact the outcome of infection. While host genotype explains most of the variation in immunological traits, parasite genotype explains most of the variation in parasitological traits, and both host and parasite genotypes impact immunopathology outcomes.Graphical

Residual polycyclic aromatic hydrocarbons and firefighters' hematological profile

IntroductionFirefighters are exposed to polycyclic aromatic hydrocarbons (PAHs) during fire suppression, but the extent of PAH penetration through turnout gear and its impact on blood cell components remains uncertain. The main objective of this study is to investigate the residual levels of PAHs on turnout gear and skin, and to assess their potential effects on blood cell components in firefighters. We hypothesize that firefighting activities lead to increased PAH exposure, which in turn may induce alterations in blood cell composition. We also hypothesize that differences in PAH exposure and corresponding blood cell changes will be observed between volunteer and career firefighters.MethodsForty-seven firefighters were recruited from 11 fire departments in Oklahoma. PAH levels on gear and skin were measured, and complete blood count (CBC) parameters were analyzed. Parametric and non-parametric tests were used to examine differences in PAH exposures and hematological profiles between volunteer and career firefighters and possible changes over time. Generalized estimating equation (GEE) models were performed to assess the relationships between PAHs and blood cells.ResultsOur analysis revealed significant hematological differences between volunteer and career firefighters, with volunteers exhibiting lower aerobic capacity and higher systemic inflammation. Increased levels of specific PAHs were found on volunteers' gear post-fire.ConclusionOur findings indicate an association between PAH exposure and changes in blood parameters, emphasizing the need for improved decontamination protocols and protective measures, particularly for volunteer firefighters.

187 Polyphenols as a partial replacement for vitamin E in nursery pig diets

Abstract A total of 300 pigs [241×600; DNA, Columbus, NE; initial body weight (BW) = 6.0 ± 0.01 kg] were used in a 42-d trial to determine the effects of vitamin E levels and partially replacing vitamin E with a polyphenol (Cabanin CSD, R2 Argo, Denmark) on growth performance, complete blood count (CBC), serum thiobarbituric acid reactive substances (TBARS), serum superoxide dismutase (SOD), and serum cytokines. Sixty pens of pigs were weighed and allotted to 1 of 5 dietary treatments in a completely randomized design with 12 pens/treatment with 5 pigs/pen. A control treatment was formulated to provide 15 IU/kg of vitamin E. This control treatment was then used as a base for 3 replacement strategies to determine the effects of replacing an additional 60 IU/kg of vitamin E above baseline with polyphenol in diets containing a basal level of vitamin E (15 IU/kg). First, an additional 60 IU/kg of vitamin E was added for a total of 75 IU/kg of vitamin E. Second, 50% of the additional vitamin E (30 IU/kg) was replaced with the vitamin E equivalency of polyphenol. Third, all 60 IU/kg of the additional vitamin E was replaced with the equivalency of polyphenol. To evaluate whether there are negative effects of feeding nursery pigs a high level of polyphenol, a fifth treatment was formulated to provide 575 IU/kg of vitamin E equivalence with 75 IU/kg from vitamin E and 500 IU/kg from polyphenol. Whole blood and serum samples were collected on d 10 and 42, and pig BW and feed disappearance measured on d 10, 21, 31, 38, and 42. For growth performance, there was no evidence of differences (P > 0.10) in average daily gain (ADG) and average daily feed intake (ADFI) as vitamin E equivalence increased or between replacement strategies throughout the entire 42-d experimental period (Table). From d 10 to 21, increasing vitamin E equivalence from 15 to 75 IU/kg increased (quadratic, P = 0.086) gain to feed ratio (G:F) with no further increase at 575 IU/kg. From d 21 to 42 and overall, there was a tendency for increased (linear, P < 0.10) G:F as the vitamin E equivalence increased. There was a vitamin E equivalence × day interaction (P = 0.050) for serum SOD activity where increasing vitamin E equivalence increased (linear, P < 0.05) serum SOD activity on d 42, but not on d 10 (P > 0.10). For serum TBARS, there was no evidence of differences (P > 0.10) between treatments, vitamin E equivalence levels, or day, and negligible differences in complete blood count parameters and serum cytokines. In summary, increasing vitamin E equivalence tended to increase G:F, which may be related to the improved SOD activity. These data indicate that when diets contain requirement levels of vitamin E, additional vitamin E equivalency can be provided by polyphenol or vitamin E to achieve similar levels of performance.

Enhancing pneumonia prognosis in the emergency department: a novel machine learning approach using complete blood count and differential leukocyte count combined with CURB-65 score

BackgroundPneumonia poses a major global health challenge, necessitating accurate severity assessment tools. However, conventional scoring systems such as CURB-65 have inherent limitations. Machine learning (ML) offers a promising approach for prediction. We previously introduced the Blood Culture Prediction Index (BCPI) model, leveraging solely on complete blood count (CBC) and differential leukocyte count (DC), demonstrating its effectiveness in predicting bacteremia. Nevertheless, its potential in assessing pneumonia remains unexplored. Therefore, this study aims to compare the effectiveness of BCPI and CURB-65 in assessing pneumonia severity in an emergency department (ED) setting and develop an integrated ML model to enhance efficiency.MethodsThis retrospective study was conducted at a 3400-bed tertiary medical center in Taiwan. Data from 9,352 patients with pneumonia in the ED between 2019 and 2021 were analyzed in this study. We utilized the BCPI model, which was trained on CBC/DC data, and computed CURB-65 scores for each patient to compare their prognosis prediction capabilities. Subsequently, we developed a novel Cox regression model to predict in-hospital mortality, integrating the BCPI model and CURB-65 scores, aiming to assess whether this integration enhances predictive performance.ResultsThe predictive performance of the BCPI model and CURB-65 score for the 30-day mortality rate in ED patients and the in-hospital mortality rate among admitted patients was comparable across all risk categories. However, the Cox regression model demonstrated an improved area under the ROC curve (AUC) of 0.713 than that of CURB-65 (0.668) for in-hospital mortality (p<0.001). In the lowest risk group (CURB-65=0), the Cox regression model outperformed CURB-65, with a significantly lower mortality rate (2.9% vs. 7.7%, p<0.001).ConclusionsThe BCPI model, constructed using CBC/DC data and ML techniques, performs comparably to the widely utilized CURB-65 in predicting outcomes for patients with pneumonia in the ED. Furthermore, by integrating the CURB-65 score and BCPI model into a Cox regression model, we demonstrated improved prediction capabilities, particularly for low-risk patients. Given its simple parameters and easy training process, the Cox regression model may be a more effective prediction tool for classifying patients with pneumonia in the emergency room.

Abstract PO1-07-05: Preliminary Evaluation in Breast Cancer of PointCheck: a Noninvasive AI-Based Neutropenia Monitoring Device

Abstract Background Febrile neutropenia (FN) is a common complication that can arise in breast cancer patients receiving myelosuppressive chemotherapy and increases the risk of fatal infections. Despite better preventive strategies there are between 140,000 to 200,000 FN-related hospitalizations yearly. Quick detection and awareness of grade III neutropenia (Absolute Neutrophil Count [ANC] &amp;lt; 1,000/µL) or greater can be critical to managing FN and treatment scheduling and dosing in patients with breast cancer. The current gold standard for neutropenia detection is a peripheral blood collection that requires patients to come into the clinic. PointCheck™ is a novel, noninvasive technology that can monitor for grade III neutropenia or greater and enable prompt detection in the home by acquiring microscopy videos of superficial capillaries through the nailfold skin and analyzing those videos with computer vision AI algorithms. To evaluate the usability, diagnostic performance, and preliminary clinical utility of PointCheck™ on FN detection we conducted a multi-center observational usability and diagnostic study. Methods The present study included an overall cohort of 175 diverse cancer patients, with 70 breast cancer patients. The primary endpoint was to achieve a score over 80.8 on a standardized System Usability Scale (SUS). Secondary endpoint was achievement of diagnostic performance with an area under the curve (AUC) above 0.80. We also performed an exploratory analysis on the device's clinical utility. Eligible participants were introduced to the device, watched a tutorial video and were given a user manual. They used the device autonomously under the supervision of the clinical team. Usability data was collected using the SUS, the scoring system that has a scale between 0-100. PointCheck™ measurements were analyzed using AI algorithms and compared to same-day Complete Blood Counts (CBCs) collected within 90 minutes of the measurement to assess accuracy in classifying patients as grade III neutropenic or greater (&amp;lt; 1,000/µL), or non-grade III neutropenic (≥1,000/µL). In the exploratory clinical utility analysis, clinicians provided narrative insights by completing a Likert survey assessing how PointCheck™ would support or impact their clinical decisions. Results 81.4% of breast cancer patients scored above 80.8 on the SUS scale across all sites, with a mean SUS score of 87.7 (SD=13.2). Furthermore, the AI-based PointCheck™ classifier accurately discriminated neutropenia patients with an AUC = 0.90 in the overall cohort. In the exploratory analysis, a majority of clinicians (65.2%) agreed that the device could have helped better evaluate their patients (Table 1). Whereas almost 3 out of 4 clinicians (72.4%), described that the use of PointCheck™ could have avoided preparing a chemotherapy infusion if the patient was not ready due to grade III neutropenia or greater. Conclusions The present study showed that there is a high perception of usability of PointCheck™, indicating an above average user experience and falling within the top 10% of systems. Furthermore, we found that PointCheck™ can accurately detect grade III neutropenia or greater in a large cohort of patients including breast cancer patients. Application of PointCheck™ to clinical practice as a monitoring system can contribute to the early detection of FN and antineoplastic therapy management. Table 1: Clinical Utility Survey Results Citation Format: Juan Garcia-Mosquera, Manuel Alva, Toshiaki Iwase, Ganimete Lamaj, Pablo Tolosa, Rodrigo Sánchez-Bayona, José Pelaez-Escobar, Alberto Pablo-Trinidad, Ryan Benasutti, Aurélien Bourquard, Ian Butterworth, Alvaro Sánchez-Ferro, Carlos Castro-González, José Manuel Pérez-García, Alejandro Martínez-Bueno, Eva Ciruelos, Azadeh Nasrazadani. Preliminary Evaluation in Breast Cancer of PointCheck: a Noninvasive AI-Based Neutropenia Monitoring Device [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-07-05.

Integrating Routine Hematological and Extended Inflammatory Parameters as a Novel Approach for Timely Diagnosis and Prognosis in Sepsis Management.

Sepsis is one of the major causes of morbidity and mortality in hospitals, especially in low- and middle-income countries, and represents a challenge to health care providers to carry out early detection, and accurate diagnosis and prognosis with cost-effective diagnostic tools. An observational prospective study was conducted from December 2021 to December 2022 to investigate the extended inflammatory parameters (EIPs) for sepsis management and analyze the survival of septic patients in the emergency unit, intensive care unit (ICU) and inpatient ward. Patients suspected of having sepsis underwent a sequential organ failure assessment (SOFA) evaluation and had blood drawn for complete blood counts (CBCs). Significant changes were observed in various CBC parameters and EIPs, and the sepsis group was followed up with for 30-day mortality. The study highlighted a significant difference yet strong discriminatory power to differentiate sepsis with an AUC of 0.924 against the non-sepsis group and an AUC of 0.991 against the healthy control group using combination of white blood cells and EIPs. Furthermore, the study showed good predictive ability for 30-day mortality with a hazard ratio of 2.311. In summary, this study provides evidence that the utilization of EIPs may be valuable in diagnosing and predicting patient outcomes, and thus will be beneficial for sepsis management in the hospital.

Short Prewarming at 41°C to Correct the Interference in Samples with the Presence of Cold Agglutination.

Cold agglutinins (CAs) in blood samples can cause a reversible agglutination of red blood cell (RBC) which result in an incorrect complete blood count (CBC). So, it is important to explore new simple and feasible treatment conditions for clinical work. The CAs group included 32 samples with CAs. The parameters of CBC at room temperature or after prewarming at 37°C or 41°C for different time periods were compared. The consistency and correlation of those parameters were analyzed. The morphology of erythrocytes in the CAs group was observed manually. The control group included 45 samples without CAs and prewarmed at 37°C or 41°C for different time periods. The differences were also analyzed. CAs have a significant effect on CBC. After prewarming at 37°C or 41°C the interferences are all corrected. Consider prewarming at 37°C for 120 minutes as the standard procedure. The consistency and correlation analysis showed there was no statistical difference between the results of each subgroup and standard group, except the MCHC of group 41°C 10 minutes. The correlation of parameters between all subgroups and the standard group is satisfied. Microscopic examination showed no RBC aggregation or fragmentation after prewarming at 41°C or 37°C. According to the maximum bias requirements for expert performance in Validation, Verification, and Quality Assurance of Automated Hematology Analyzers, 2nd Edition (CLSI H26-A2), the differences in overall results in control group are negligible. The 41°C 2 minutes prewarming method is a rapid and effective way for treating samples with CAs. It is an efficient way to obtain more reliable CBC results, without specific instruments.

A machine learning model for the early diagnosis of bloodstream infection in patients admitted to the pediatric intensive care unit.

Bloodstream infection (BSI) is associated with increased morbidity and mortality in the pediatric intensive care unit (PICU) and high healthcare costs. Early detection and appropriate treatment of BSI may improve patient's outcome. Data on machine-learning models to predict BSI in pediatric patients are limited and neither study included time series data. We aimed to develop a machine learning model to predict an early diagnosis of BSI in patients admitted to the PICU. This was a retrospective cohort study of patients who had at least one positive blood culture result during stay at a PICU of a tertiary-care university hospital, from January 1st to December 31st 2019. Patients with positive blood culture results with growth of contaminants and those with incomplete data were excluded. Models were developed using demographic, clinical and laboratory data collected from the electronic medical record. Laboratory data (complete blood cell counts with differential and C-reactive protein) and vital signs (heart rate, respiratory rate, blood pressure, temperature, oxygen saturation) were obtained 72 hours before and on the day of blood culture collection. A total of 8816 data from 76 patients were processed by the models. The machine committee was the best-performing model, showing accuracy of 99.33%, precision of 98.89%, sensitivity of 100% and specificity of 98.46%. Hence, we developed a model using demographic, clinical and laboratory data collected on a routine basis that was able to detect BSI with excellent accuracy and precision, and high sensitivity and specificity. The inclusion of vital signs and laboratory data variation over time allowed the model to identify temporal changes that could be suggestive of the diagnosis of BSI. Our model might help the medical team in clinical-decision making by creating an alert in the electronic medical record, which may allow early antimicrobial initiation and better outcomes.

Systemic-inflammatory indices and clinical outcomes in patients with anterior circulation acute ischemic stroke undergoing successful endovascular thrombectomy

BackgroundThere is a lack of comprehensive profile assessment on complete blood count (CBC)-derived systemic-inflammatory indices, and their correlations with clinical outcome in patients with anterior circulation acute ischemic stroke (AIS) who achieved successful recanalization by endovascular thrombectomy (EVT). MethodsPatients with anterior circulation AIS caused by large vessel occlusion (AIS-LVO) were retrospectively screened from December 2018 to December 2022. Systemic-inflammatory indices including ratios of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and platelet-to-neutrophil (PNR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate inflammation systemic index (AISI) on admission and the first day post-EVT were calculated. Their correlations with symptomatic intracranial hemorrhage (sICH) and unfavorable 90-day functional outcome (modified Rankin Scale score of 3-6) were analyzed. ResultsA total of 482 patients [65 (IQR, 56-72) years; 33% female] were enrolled, of which 231 (47.9%) had unfavorable 90-day outcome and 50 (10.4%) developed sICH. Day 1 neutrophil and monocyte counts, NLR, MLR, PLR, SII, SIRI, and AISI were increased, while lymphocyte and PNR were decreased compared to their admission levels. In multivariate analyses, neutrophil count, NLR, SII, and AISI on day 1 were independently associated with 90-day functional outcome. Moreover, day 1 neutrophil count, NLR, MLR, PLR, PNR, SII, and SIRI were independently linked to the occurrence of sICH. No admission variables were identified as independent risk factors for patient outcomes. ConclusionCBC-derived systemic-inflammatory indices measured on the first day after successful EVT are predictive of 90-day functional outcome and the sICH occurrence in patients with anterior circulation AIS-LVO.

Coronary microvascular dysfunction and inflammation: Insights from the Coronary Microvascular Disease Registry

BackgroundCoronary microvascular dysfunction (CMD) is associated with various inflammatory conditions that worsen endothelial dysfunction. This study aimed to investigate the relationship between CMD and inflammation using common inflammatory markers derived from complete blood count (CBC) analysis. MethodsInformation was gathered from the Coronary Microvascular Disease Registry to examine the neutrophil-to-lymphocyte ratio (NLR), eosinophil-to-monocyte ratio (EMR), and monocyte-to-high-density lipoprotein ratio (MHR) in a cohort of patients with angina who showed non-obstructive coronary arteries and underwent invasive physiological assessments for CMD. ResultsOf the 171 patients studied, 126 were CMD-negative and 45 were CMD-positive, constituting two groups of interest. The average age of all patients was 61.7 ± 11.1 years, and 63.7 % were female. No significant differences were observed between the two groups in terms of baseline characteristics, cardiovascular risk factors, or potential anti-inflammatory medications. Furthermore, there were no statistically significant differences in NLR (2.54 ± 3.71 vs. 2.52 ± 2.28, p = 0.97), EMR (0.3 ± 0.21 vs. 0.34 ± 0.29, p = 0.31), or MHR (0.02 ± 0.01 vs. 0.01 ± 0.01, p = 0.54) between CMD-positive and CMD-negative patients. ConclusionOur findings did not show a noteworthy connection between CMD and inflammation, as suggested by various simple CBC-based biomarkers.

Blood parameters in pediatric myelin oligodendrocyte glycoprotein antibody-associated disorders

Patients with myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) clinically present e.g. with acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), transverse myelitis (TM) or aquaporin-4-IgG (AQP4-IgG) negative neuromyelitis optica spectrum disorders (NMOSD)-like phenotypes. We aimed to analyze and compare blood parameters in children with MOGAD, AQP4-IgG-positive NMOSD (hence NMOSD), multiple sclerosis (MS) and healthy controls (HC). We evaluated differences in complete blood counts (CBC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and C-reactive protein (CRP) between these four groups and within the groups between clinical attack, acute treatment and remission. Our cohort consisted of 174 children and adolescents with a total of 550 timepoints: 66 patients had MOGAD (202 timepoints), 11 NMOSD (76 timepoints), 58 MS (219 timepoints) and 39 were HC (53 timepoints). At clinical attack, leukocyte counts were elevated in MOGAD compared to remission (p<0.001) and compared to all other groups (p<0.001). NLR was high in MOGAD and NMOSD, and PLR was high in NMOSD, however, after correction for multiple testing these findings did not remain significant. While glucocorticoids caused an increase of leukocyte counts and NLR in NMOSD and MS, these values remained stable during acute treatment in MOGAD. In remission, NLR normalized in MOGAD, while it stayed high in NMOSD. PLR increased in NMOSD and was significantly higher compared to all other groups. Some blood parameters, mainly leukocyte and differential counts, might help clinicians to evaluate disease activity, differentiate relapses from pseudo-relapses and even distinguish between different disease entities.

Development and therapeutic evaluation of 5D3(CC-MLN8237)3.2 antibody-theranostic conjugates for PSMA-positive prostate cancer therapy

Prostate cancer (PC) is an aggressive cancer that can progress rapidly and eventually become castrate-resistant prostate cancer (CRPC). Stage IV metastatic castrate-resistant prostate cancer (mCRPC) is an incurable late-stage cancer type with a low 5-year overall survival rate. Targeted therapeutics such as antibody-drug conjugates (ADCs) based on high-affinity monoclonal antibodies and potent drugs conjugated via smart linkers are being developed for PC management. Conjugating further with in vitro or in vivo imaging agents, ADCs can be used as antibody-theranostic conjugates (ATCs) for diagnostic and image-guided drug delivery. In this study, we have developed a novel ATC for PSMA (+) PC therapy utilizing (a) anti-PSMA 5D3 mAb, (b) Aurora A kinase inhibitor, MLN8237, and (c) for the first time using tetrazine (Tz) and trans-cyclooctene (TCO) click chemistry-based conjugation linker (CC linker) in ADC development. The resulting 5D3(CC-MLN8237)3.2 was labeled with suitable fluorophores for in vitro and in vivo imaging. The products were characterized by SDS-PAGE, MALDI-TOF, and DLS and evaluated in vitro by optical imaging, flow cytometry, and WST-8 assay for cytotoxicity in PSMA (+/−) cells. Therapeutic efficacy was determined in human PC xenograft mouse models following a designed treatment schedule. After the treatment study animals were euthanized, and toxicological studies, complete blood count (CBC), blood clinical chemistry analysis, and H&amp;amp;E staining of vital organs were conducted to determine side effects and systemic toxicities. The IC50 values of 5D3(CC-MLN8237)3.2-AF488 in PSMA (+) PC3-PIP and PMSA (−) PC3-Flu cells are 8.17 nM and 161.9 nM, respectively. Pure MLN8237 shows 736.9 nM and 873.4 nM IC50 values for PC3-PIP and PC3-Flu cells, respectively. In vivo study in human xenograft mouse models confirmed high therapeutic efficacy of 5D3(CC-MLN8237)3.2-CF750 with significant control of PSMA (+) tumor growth with minimal systemic toxicity in the treated group compared to PSMA (−) treated and untreated groups. Approximately 70% of PSMA (+) PC3-PIP tumors did not exceed the threshold of the tumor size in the surrogate Kaplan-Meyer analysis. The novel ATC successfully controlled the growth of PSMA (+) tumors in preclinical settings with minimal systemic toxicities. The therapeutic efficacy and favorable safety profile of novel 5D3(CC-MLN8237)3.2 ATC demonstrates their potential use as a theranostic against aggressive PC.

Platelet indices as a predictive marker in neonates with respiratory distress

BackgroundThe neonatal intensive care unit (NICU) frequently gets admissions due to respiratory distress (RD). Platelet indices are a beneficial biomarker in order to gauge the severity of neonatal RD. We aimed to assess platelet indices as a potential predictor in neonates with RD.MethodsThis prospective research involved 120 neonates who had been admitted to the NICU with evidence of RD. On admission and after respiratory support was reduced; a complete blood count (CBC) was performed to determine platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT), platelet distribution width (PDW), platelet mass index (PMI), and platelet large cell ratio (PLCR).ResultsMPV and PDW were significantly higher after respiratory support reduction. PC and PMI were significantly higher in neonates exhibiting moderate and severe distress. PC of 276.5*109/L had the highest degree of predictability of RD severity (area under curve (AUC) 0.762, sensitivity 81.5%, specificity 64.3%), 95% confidence interval (0.7–0.9), while PMI of 2473.5 fL/nL was the best cut-off point to predict severity of RD (AUC 0.663, sensitivity 63%, specificity 57.1%) 95% confidence interval (0.6–0.8). There was a significant difference in the average PC between different oxygen modes.ConclusionHigher PMI and PC are associated with moderate and severe RD and can be used to predict the severity of neonatal RD.