Hematology Research Research Articles

Changes of erythrocytes, hemoglobin and erythrocyte indices in cats with enterocolitis of unknown etiology

Purpose: Study red blood parameters in a group of cats with enterocolitis of unknown etiology using standard hematological research methods.Materials and methods. During the study, standard methods of hematological analysis were used: erythrocyte counting was performed in a Goryaev chamber using whole blood diluted with isotonic sodium chloride solution 200 times, counting was carried out using a light-optical microscope Miromed-2 var. 3-20 inf. lens x8, eyepiece x10; the amount of hemoglobin was determined by the colorimetric method, diluting whole blood 200 times with a solution of 0,04 % ammonia on a Microlab-540 device; hematocrit value was determined by centrifugation using a Vilitek DSC-100MH-2 hematocrit centrifuge; the reaction to the erythrocyte sedimentation rate was performed in Panchenkov pipettes; erythrocyte indices and blood color index were calculated using generally accepted formulas.Results. Thanks to the data obtained, we concluded that disruption of enzymatic processes, deterioration of absorption in the intestine and imbalance of symbiont microflora caused by enterocolitis can lead to the development of anemic conditions, manifested by changes in red blood parameters.

Synthetic Histopathological Images Generation with Artificial Intelligence to Accelerate Research and Improve Clinical Outcomes in Hematology

Background: Hematological malignancies are rare and complex diseases and as a consequence, multimodal data (ranging from clinical and genomic information to images) are required to improve diagnosis, prognosis and personalized treatments. However, collecting all these layers of information is challenging, in particular when collecting cytological and histological images from the bone marrow (BM) reproducing disease morphologic features. Synthetic data generation by Artificial Intelligence (AI) can circumvent these issues by generating images conditioned from textual inputs (i.e. reports from pathologists), which are widely available and contain many useful clinical information. This technology can enrich data with synthetic images, thus boosting translational research and improving the performances of precision medicine strategies based on multimodal information. Aims:This project was conducted by GenoMed4all and Synthema EU consortia, with the aim to:1)Apply generative models to real-world dataset with histological images of patients with myeloid neoplasms (MN). 2) Develop a Synthetic Images Validation Framework (SIVF) to evaluate the utility and fidelity of generated images. 3) Verify the capability of synthetic images to accelerate research and to improve clinical models. Methods:We implemented Stable Diffusion (SD) generative model fine-tuned on hematological data to generate Hematoxylin and Eosin (H&E) images of MN patients. We implemented a domain specific language model (HematoBERT) to encode textual input as condition for the generation process. Use cases were Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML) and Myeloproliferative Neoplasm (MPN) patients, with available BM biopsies and their reports from pathologists, genomic and clinical data. We applied SIVF to evaluate distributions of morphological features extracted from real and synthetic images. Clinical validation was performed on disease classification and survival probability prediction, using real and synthetic images features (experimental setting is reported in Figure 1). Results: We trained SD model on 200 patients with available BM biopsies and associated reports. We first performed SIVF to compare extracted morphological features (geometrical, color and texture features of cells nuclei) from synthetic and real images of 55 patients never seen by the model. Results proved that features distributions and correlations in both datasets were comparable. Similar results were obtained performing SIVF on each single patient data. We verified if synthetic data augmentation could improve performances on MN classification (i.e. models able to correctly assign a single patient to a specific clinical entity according to the 2022 WHO classification criteria). We implemented three XGBOOST models to classify patients' disease. Classifiers were trained and validated on morphological extracted features of images from a real set of patients (n=614), a synthetic group (n=396) and a mixed dataset (n=1010). Data augmentation improved classification performance by 10% (F1 Score) when we tested it on the three different validation sets. Finally, demographics, clinical features, genomics (cytogenetics and gene mutations) were included as covariates together with morphological features extracted from BM biopsies in L1 penalized Cox's proportional hazards models, considering Overall Survival as primary endpoint. Models were fitted on two different cohorts of real patients (n=182, n=294). Then we added 112 synthetic patients to both sets and refitted the models. We observed an improvement in performances of >10% (C-Index) for both cases (Figure 2), with morphological features (such as “major axis” of nuclei) being selected among the best predictors. All these results confirmed that data augmentation through synthetic data is a viable approach and can significantly improve the models capability to efficiently capture clinical outcomes at individual patient level. Conclusion:AI generated images preserve properties of real-world images, replicating cells morphological features relevant to identify hematological diseases and their clinical status. This approach based on widely available textual data allows effective data augmentation and effortless data sharing, thus accelerating and improving precision medicine research in hematology.

Multicenter Retrospective Evaluation of Treatment of High-Risk Acute Promyelocytic Leukemia (APL): Results from the Hematology Research Outcomes (HERO) Consortium

Background: Regimens employing all-trans retinoid acid and arsenic (ATRA+ATO) are the backbone of high-risk APL treatment. The APML4 regimen consists of a three-phase treatment approach: induction with ATRA, ATO, and idarubicin; two cycles of consolidation with ATRA+ATO; and maintenance with ATRA, methotrexate, and mercaptopurine. 1 MD Anderson Cancer Center (MDACC) developed a regimen incorporating gemtuzumab ozogamicin (GO) in addition to ATRA+ATO. 2 Differences in tolerability and efficacy between these two approaches are unknown as no comparative data exists. We aimed to describe real-world treatment outcomes for high-risk APL, comparing toxicity between APML4 and ATRA+ATO+GO. Methods We conducted a multicenter, retrospective cohort study including patients treated among six US centers participating in the pharmacist-led collaborative research consortium, HERO. Adults (>18 years) with newly diagnosed high-risk APL (t(15;17)(q24.1;q21.2)) according to the Sanz risk model 3 between April 2014 and June 2022, who received at least one dose of an induction regimen under the institution's high-risk protocol were compared based on induction regimen received. Patients with incomplete records were excluded. The primary endpoint was a composite of mortality, ICU admission, or confirmed infection during induction. Secondary endpoints included individual components of the primary endpoint, other induction-related toxicities, and complete response (CR) rate after induction. Analyses were performed as intent-to-treat which included all patients who received APML4 and ATRA+ATO+GO inductions regardless of consolidation strategies. Chi-square or Fisher's exact tests were utilized to evaluate dichotomous variables. Continuous variables were analyzed via Student's t-test or Mann-Whitney U test. Kaplan-Meier analysis with log-rank test was performed to estimate progression-free survival (PFS) and overall survival (OS). Results Fifty-seven patients with high-risk APL who started either APML4 (n=41) or ATRA+ATO+GO (n=16) as induction treatment met inclusion criteria. Baseline characteristics were balanced (Table 1) except for race and ethnicity, with a higher percentage of non-Hispanic white patients in the APML4 cohort (p=0.020) and a higher percentage of Hispanic/LatinX in the ATRA+ATO+GO cohort (p=0.011). Of evaluated molecular abnormalities, FLT3-ITD was most common (76%). Steroid prophylaxis was more common in the ATRA+ATO+GO cohort (p=0.015). Additional cytoreductive therapy was frequent in both arms: hydroxyurea used more often in the APML4 cohort (p=0.033) and idarubicin in the ATRA+ATO+GO cohort (p<0.001) (Table 1). Induction mortality was 7%, including 3 deaths in the APML4 cohort and 1 in the ATRA+ATO+GO (Table 2; p=1.000). Time to platelet recovery was longer with APML4 than ATRA+ATO+GO (median 27 vs 23 days, p=0.021) as was time to ANC recovery (median 38 vs. 29 days, p=0.020). No additional significant differences in individual safety outcomes were observed. Of note, there was no difference in differentiation syndrome that required dose changes or holds between the two cohorts. There were no detectable differences in treatment effectiveness, with 92.7% of patients in the APML4 arm and 93.8% of patients in the ATRA+ATO/GO arm achieving a CR at end of induction (Table 2). With a median follow-up of 35 months, neither group reached the median for overall survival and the estimated 36-month survival was similar between cohorts; 92.5% (95%CI 84.3-100) for APML4 and 94.1% (95%CI 83.1-100) for ATRA+ATO+GO. Conclusion ATRA+ATO-based regimens yield similar short- and long-term efficacy in a high-risk APL population, though hematologic recovery occurred earlier in the ATRA+ATO+GO cohort. No clinically significant differences in acute toxicities exist between APML4 and ATRA+ATO+GO induction strategies as demonstrated by this real-world multicenter analysis.

A 10 Year Analysis of Gender Distribution in National Institutes of Health Funding for Non-Malignant Hematology

Introduction: Historically, there has been an underrepresentation of women in the field of hematology. Consequently, this makes them less likely to receive academic research grants. Here, we present a ten year retrospective analysis of the Research Project Grants (R01) awarded by the National Institutes of Health (NIH) through the fiscal years of 2012-2022. The grants were categorized by various NIH agencies. This temporal analysis examines gender disparities under the field of non-malignant hematology research. Methods:Data was extracted for the fiscal years 2012-2022 focusing exclusively on R01 grants awarded and categorized by the various NIH agencies. Data was leveraged using the NIH RePORTER tool, Tidyverse, and janitor packages in R. The dataset incorporated key grant parameters such as grant ID, agency code, activity code, abstract text, project title, fiscal year, activity status, award amount, organization, and principal investigator's(PI) name. In order to distinguish a PI's gender, PI's first names were processed using the gender package in R, which provided a gender-wise distribution of recipients. For statistical analyses, proportions of females with accepted R01 grants were compared between 2012 to 2022; this proportion analysis was also done among each NIH agency. Further, linear regression and associated statistical tests were used to identify whether there was significant change in grants received by either gender over this time period. Results: A total of 250,031 R01 grants were awarded by the NIH during the fiscal years of 2012 to 2022. Females (n=82,152: 32.9% (95% CI 0.41-0.43) received fewer grants than males (n=167,879: 67.1%, (95% CI 0.50-0.55). Across 2012 to 2022, there was no significant change in R01 grants awarded among men (16,221 to 15,601, p-value= 0.52). In contrast, there was a significant difference for females in the R01 grants awarded across 2012 to 2022 (6,865 to 9,339, p-value <0.001). In 2012, the National Institute of General Medical Sciences (NIGMS), National Institute of Neurological Disorders and Stroke (NINDS), and National Institute of Biomedical Imaging and Bioengineering (NIBIB) awarded less than 25% of the total grants to females. By 2022, of all the agencies, the NBIB remained the agency with the most extensive gender gap with females being awarded only 23% of grants. In contrast, the National Institute of Minority Health and Disparities (NIMHD) and the National Institute of Nursing Research (NINR) were the only agencies in 2012 to award more grants to females with approximately 52% and 74% of grants respectively. In 2022, the NINR and NIHMD continued to show more grants awarded to females versus males. In addition to those agencies, by 2022, the National Institute of Child Health and Human Development(NICHD) and National Center for Complementary and Integrative Health (NCCIH) joined the NINR and NIHMD in awarding more than 50% of grants awarded to females that year. Conclusion: This analysis highlights continued gender disparity as only 33% of total R01 NIH grants were awarded to females during the fiscal years 2012-2022 in non-malignant hematologic research. Although, it is noted that while some agencies have made strides towards gender parity, others continue to have a significant gap. While this remains a systemic and multifaceted issue, identifying these areas of gender disparity will enable targeted efforts to bridge this gap and advance gender equality.

Disorders of mental health in children and adolescents with hematological malignancies

Introduction. The success in pediatric oncohematological disorders treatment cause increasing scrutiny not only to remission achievement and long-term patient survival, but also to supportive dysfunctions, which go with malignancy and anti-tumor treatment. Blood tumors cause all organs and systems disorders, and psychic dysfunctions of these are not in the last place.Aim. To characterize mental health and psychic disorders types in children and adolescents with oncohematological diseases during hospital stay.Materials and methods. It was analyzed mental health of 169 children and adolescents with hemoblastoses, who were treated at Pediatric Oncology and Hematology Research Institute of National Research Cancer Centre n. a. N. N. Blokhin (Moscow, Russia) in 2022 year. 50 (29.6 %) patients needed a psychiatric consultation. Among oncohematological disorders acute lymphoblastic leukemia was predominated – 25 (50 %), lymphomas – 17 (34 %) and acute myeloid leukemia – 8 (16 %) patients. Mental health data assessed after examination/consultation of clinical psychologist and psychiatrist.Results. Asthenia was found in all 50 (100 %) patients, who were recommended a psychiatrist consultation, in 47 (94 %) – adjustment disorder, in 15 (30 %) – vexatious and neurotic disorder, in 16 (32 %) – affective syndromes, less often (18 and 14 % respectively) – behavioral deviations and eating disorders. As single cases in 2 (4 %) patients an intellectual disability and in 1 (2 %) a psychotic syndrome were diagnosed. As a role the most pronounced psychopathological conditions were upon admission to the hospital and decreased during the treatment and adaptation.Conclusions. One third of children and adolescents, hospitalizing to oncohematological clinic need a psychiatrist consultation. Multidisciplinary care for such patients with pediatric oncologist, psychiatrist and clinical psychologist can cure psychogenic disorder effectively, improving the stay of patient at the hospital and best compliance between the doctor and patient.

Model-Guided Decision-Making for Thromboprophylaxis and Hospital-Acquired Thromboembolic Events Among Hospitalized Children and Adolescents

Rates of hospital-acquired venous thromboembolism (HA-VTE) are increasing among pediatric patients. Identifying at-risk patients for whom prophylactic interventions should be considered remains challenging. To determine whether use of a previously validated HA-VTE prognostic model, together with pediatric hematologist review, could reduce pediatric inpatient rates of HA-VTE. This pragmatic randomized clinical trial was performed from November 2, 2020, through January 31, 2022, at a single-center academic children's hospital (Monroe Carell Jr Children's Hospital at Vanderbilt). All pediatric hospital admissions (aged <22 years) under inpatient status were included and randomized. All patients had an HA-VTE probability automatically calculated daily, which was visible to the hematology research team for patients in the intervention group. Patients with an elevated risk (predicted probability ≥2.5%) underwent additional medical record review by the research team to determine eligibility for thromboprophylaxis. The primary outcome was rate of HA-VTE. Secondary outcomes included rates of prophylactic anticoagulation and anticoagulation-associated bleeding events. A total of 17 427 hospitalizations met eligibility criteria, were randomized, and were included in the primary analysis: patients had a median (IQR) age of 1.7 (0 to 11.1) years; there were 9143 (52.5%) female patients and 8284 (47.5%) male patients, and there were 445 (2.6%) Asian patients, 2739 (15.9%) Black patients, and 11 752 (67.4%) White patients. The 2 groups were evenly balanced in number (8717 in the intervention group and 8710 in the control group) and patient characteristics. A total of 58 patients (0.7%) in the control group and 77 (0.9%) in the intervention group developed HA-VTE (risk difference: 2.2 per 1000 patients; 95% CI, -0.4 to 4.8 per 1000 patients; P = .10). Recommendations to initiate thromboprophylaxis were accepted by primary clinical teams 25.8% of the time (74 of 287 hospitalizations). Minor bleeding events were rare among patients who received anticoagulation (3 of 74 [4.1%]), and no major bleeding events were observed during the study period. Among patients randomized to the control group, the model exhibited high discrimination accuracy (C statistic, 0.799, 95% CI, 0.725 to 0.856). In this randomized clinical trial of the use of a HA-VTE prognostic model to reduce pediatric inpatient rates of HA-VTE, despite the use of an accurate and validated prognostic model for HA-VTE, there was substantial reluctance by primary clinical teams to initiate thromboprophylaxis as recommended. In this context, rates of HA-VTE between the control and intervention groups were not different. Future research is needed to identify improved strategies for prevention of HA-VTE and to overcome clinician concerns regarding thromboprophylaxis. ClinicalTrials.gov Identifier: NCT04574895.

EXPERIMENTAL TOXOCARIASIS IN RABBITS

Toxocariasis as a zoonosis represents a medical and veterinary problem. In the structure of human larval helminthiases, toxocariasis accounts for more than 60%. In non-specific hosts, including humans, toxocara larvae undergo visceral larva migrans, primarily damaging the liver, lungs, and other organs and tissues. Constant reinvasion accumulates second and third-stage larvae in the bodies of nonspecific (paratenic) hosts. In our research, we considered the problem of soil parasitological contamination on rabbit farms and the risks of rabbit infection, emphasising the need to study the involvement of rabbits as paratenic hosts in toxocariasis. We selected rabbits of the Soviet chinchilla breed as experimental animals. Toxocara eggs were administered orally to the animals. Hematological studies were conducted using commonly accepted methods. To detect specific IgG class antibodies, rabbit serum was analysed by enzyme-linked immunosorbent assay (ELISA). The presence of IgG class antibodies in the blood serum of rabbits at a positive titer (1:100) in ELISA allows us to conclude that rabbits, along with other animals, serve as paratenic hosts for Toxocara canis. Haematological research results indicated the absence of significant differences and remained within the physiological norm throughout the entire experiment.

Comparing Hematological and Biochemical Profiles of Pregnant and Non-pregnant Barb Mares Raised in Tiaret, Algeria

Background: The pure-bred Barb horse is a beloved breed from the Great Maghreb. Despite the breed’s prominence in Algeria, no gestational hematological or biochemical research has been done on this breed. Objectives: This study aimed to compare the hematological and biochemical parameters of pregnant and non-pregnant Barb mares in the first, second, and third trimesters of pregnancy. Methods: From 12 pregnant and 6 non-pregnant mares, 102 venous blood samples were taken, and their glucose (Glu), cholesterol (Cho), triglycerides (TG), total protein (TP), urea (Urea), Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), iron (Fer), calcium (Ca), phosphorus (P), and ferric reducing ability of plasma (FRAP) were assessed as biochemical variables. Also, red blood cells, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration, white blood cells, and platelets were all measured as hematological variables. Results: The levels of ALP, ALT, GGT, and P decreased significantly throughout gestation, while Ca, TG, Fe, and Glu levels increased. AST concentrations decreased in the second and third trimesters, whereas Cho levels increased in the first and second trimesters. Urea levels increased significantly in the third trimester, and FRAP showed significant differences at different stages of pregnancy. Mean corpuscular hemoglobin concentration was significantly lower in the first and second trimesters, and hemoglobin values were significantly lower in the second trimester. The mean value of white blood cell count was slightly higher in late pregnancy, while platelet values significantly increased throughout all trimesters. Conclusion: The study provides valuable information on the changes in hematological and biochemical parameters during pregnancy in Barb mares. These findings can be used as a reference for future studies on the reproductive physiology of this breed.

INVESTIGATION OF CHRONIC TOXICITY OF A PHARMACOLOGICAL COMPOSITION BASED ON BACTERIOCIN-NISIN AND SILICON GLYCEROLATES

The use of new drugs on productive animals is possible only after identifying the long-term effects of the use of substances included in the composition on the functional state of organs, tissues and systems. As a result, the goal of our work was to study the chronic toxicity of the developed composition and the possibility of using it on highly productive cows in the treatment of mastitis. The studied composition was developed at the I.Ya. Postovsky Insititute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciencesand corresponds to the composition: silicon glycerolates – 3,0%, nisin – 0,3%, glycerin – 10%, distilled water – up to 100 %. Chronic toxicity studies were performed on female non-linear white laboratory rats (n=40) using hematological, biochemical, pathomorphological and histological research methods. When conducting hematological studies, it was found that the indicators of the composition of the blood elements of laboratory rats when using the studied composition in different dosages were within the limits. A study of the biochemical parameters of the blood of laboratory animals receiving the composition at a dose of 500 mg/kg and 1000 mg / kg found that the metabolic parameters corresponded to physiological values. Feeding of the studied composition at a dose of 750 mg / kg led to changes in the form of an increase in the enzymatic activity of alkaline phosphatase, a decrease in cholesterol, however, the data obtained cannot confirm the negative effect of the studied dose on the liver, due to the absence of pathological changes in this organ at the cellular level. Histological studies have established that the developed composition can cause changes in organs depending on the dosage used. Based on the research results, we determined that the composition can be recommended for clinical trials on productive animal species at a dose of no more than 500 mg/kg. The use of a dose of 750 mg / kg is recommended to be used with caution in animals with severe liver dysfunction. During further tests, it is necessary to refrain from the critical dose of 1000 mg / kg, which leads to deeper changes in the organs.

Structure of the thrombopoietin-MPL receptor complex is a blueprint for biasing hematopoiesis

Thrombopoietin (THPO or TPO) is an essential cytokine for hematopoietic stem cell (HSC) maintenance and megakaryocyte differentiation. Here, we report the 3.4Å resolution cryoelectron microscopy structure of the extracellular TPO-TPO receptor (TpoR or MPL) signaling complex, revealing the basis for homodimeric MPL activation and providing a structural rationalization for genetic loss-of-function thrombocytopenia mutations. The structure guided the engineering of TPO variants (TPOmod) with a spectrum of signaling activities, from neutral antagonists to partial- and super-agonists. Partial agonist TPOmod decoupled JAK/STAT from ERK/AKT/CREB activation, driving a bias for megakaryopoiesis and platelet production without causing significant HSC expansion in mice and showing superior maintenance of human HSCs invitro. These data demonstrate the functional uncoupling of the two primary roles of TPO, highlighting the potential utility of TPOmod in hematology research and clinical HSC transplantation.

Emerging Strategies in 3D Culture Models for Hematological Cancers.

In vitro cell cultures are fundamental and necessary tools in cancer research and personalized drug discovery. Currently, most cells are cultured using two-dimensional (2D) methods, and drug testing is mainly performed in animal models. However, new and improved methods that implement three-dimensional (3D) cell-culturing techniques provide compelling evidence that more advanced experiments can be performed, yielding valuable new insights. In 3D cell-culture experiments, the cell environment can be manipulated to mimic the complexity and dynamicity of the human tissue microenvironment, possibly leading to more accurate representations of cell-to-cell interactions, tumor biology, and predictions of drug response. The 3D cell cultures can also potentially provide alternative ways to study hematological cancers and are expected to eventually bridge the gap between 2D cell culture and animal models. The present review provides an overview of the complexity of the lymphoid microenvironment and a summary of the currently used 3D models that aim at recreating it for hematological cancer research. We here dissect the differences and challenges between, and potential advantages of, different culture methods and present our vision of the most promising future strategies in the hematological field.

Effectiveness of group therapy of calves for nonspecific bronchopneumonia by aerosol method

Nonspecific bronchopneumonia of calves causes significant economic damage to farms, and therefore, it is important to develop effective therapeutic drugs, especially for group use. Aerosolbased medicines deserve attention. The purpose of the study was to investigate the effectiveness of the group aerosol method of administering the drug “Calfmin” to calves with nonspecific bronchopneumonia. Analogue calves of two to three months of age, both clinically healthy and patients with nonspecific bronchopneumonia, were involved in the experiment. Standard clinical and haematological research methods were used to determine the diagnosis and monitor the functional state of the calves’ bodies. It was found that in the blood of calves with nonspecific bronchopneumonia, an increase in the number of white blood cells was observed by 1.3 times (P&lt;0.05) compared to clinically healthy animals. Their blood also showed an increase in the number of stab and segmented neutrophils by 2.0 times (P&lt;0.05) and 1.6 times (P&lt;0.01), respectively, and a decrease in the number of lymphocytes by 1.3 times (P&lt;0.001) and eosinophils by 1.4 times (P&lt;0.001), respectively. In sick calves, there was a 1.2-fold decrease in the number of red blood cells in the blood (P&lt;0.001) and a 1.2-fold decrease in the haemoglobin content (P&lt;0.001) compared to the control. An improvement in the clinical condition and haematological parameters in sick animals was recorded within 3-5 days, a reduction in the duration of therapy by 1.9-2.0 times, and 100% preservation of all sick calves

Improving Education and Research in Haematology and Blood Transfusion in Africa: Panacea to Improving the Health and Wellbeing of Patients in the Region

Africa bears a heavy burden of diverse diseases which includes blood diseases that overwhelm the healthcare system. A multitude of factors were believed to be responsible for this burden and it includes a lack of trained healthcare workforce, multi-disciplinary research on diseases facing the region, and a dearth of advanced diagnostic and clinical services for haematologic disorders. Measures taken to improve the situation includes increased health budgetary spending which had marginally improved. The improvement thus far achieved in haematology and blood transfusion education and research need to be determined. Three databases, namely Google Scholar, PubMed and Core, were searched for literature on haematology and blood transfusion education and research. About 2616 articles were identified, of which 7 articles were included for the review following screening and eligibility assessment by independent reviewers. The articles reviewed revealed that there was a significant improvement in haematology and blood transfusion education and research. This has translated to an improved health workforce, service delivery and research capacity and profile. However, these gains were not quantifiably presented to judge the real progress against any set standards. To fully understand the progress made and the levels that need to be reached, a comprehensive, multifaceted, and multinational study that explicitly explores the improvement measures taken and their consequential outcome is necessary.

Diversity in hematology research

Diversity in hematology research

Synthetic Data Generation by Artificial Intelligence to Accelerate Research and Precision Medicine in Hematology.

Synthetic data are artificial data generated without including any real patient information by an algorithm trained to learn the characteristics of a real source data set and became widely used to accelerate research in life sciences. We aimed to (1) apply generative artificial intelligence to build synthetic data in different hematologic neoplasms; (2) develop a synthetic validation framework to assess data fidelity and privacy preservability; and (3) test the capability of synthetic data to accelerate clinical/translational research in hematology. A conditional generative adversarial network architecture was implemented to generate synthetic data. Use cases were myelodysplastic syndromes (MDS) and AML: 7,133 patients were included. A fully explainable validation framework was created to assess fidelity and privacy preservability of synthetic data. We generated MDS/AML synthetic cohorts (including information on clinical features, genomics, treatment, and outcomes) with high fidelity and privacy performances. This technology allowed resolution of lack/incomplete information and data augmentation. We then assessed the potential value of synthetic data on accelerating research in hematology. Starting from 944 patients with MDS available since 2014, we generated a 300% augmented synthetic cohort and anticipated the development of molecular classification and molecular scoring system obtained many years later from 2,043 to 2,957 real patients, respectively. Moreover, starting from 187 MDS treated with luspatercept into a clinical trial, we generated a synthetic cohort that recapitulated all the clinical end points of the study. Finally, we developed a website to enable clinicians generating high-quality synthetic data from an existing biobank of real patients. Synthetic data mimic real clinical-genomic features and outcomes, and anonymize patient information. The implementation of this technology allows to increase the scientific use and value of real data, thus accelerating precision medicine in hematology and the conduction of clinical trials.

Carbon monoxide as a clinical marker of hemolysis.

Carbon monoxide (CO)-based tests have precisely measured hemolysis for over 40 years. End-tidal CO was the primary marker in clinical hematology research, followed by carboxyhemoglobin. Quantification of CO reflects heme oxygenases degrading heme in a 1:1 stoichiometric ratio, making CO a direct marker of hemolysis. CO in alveolar air can be quantified using gas chromatography, whose high resolution allows detecting mild and moderate levels of hemolysis. CO can be elevated in active bleeding, resorbing hematoma, and smoking. Clinical acumen and other markers remain necessary to diagnose the cause of hemolysis. CO-based tests constitute an opportunity for bench-to-bedside technology transfer.

Treatment of pets with the active substance dexpanthenol in wound processes

Animal skin is a complex organ that directly perceives the influence of the external environment and performs a barrier-protective function, helps maintain the balance of the internal environment of the body. Disruption of each of the levels of the protective system leads to the development of inflammatory skin diseases. Treatment of wounds remains one of the most pressing scientific and practical problems of modern veterinary medicine. A number of researchers are searching for and developing new veterinary drugs for the treatment of wounds of various etiologies in small pets, but the use of drugs often causes adverse skin reactions. The purpose of this study was to evaluate the effectiveness of using a veterinary drug (ointment) in the treatment of wounds in domestic animals (dogs, cats, rabbits). The paper uses standard clinical, haematological, and biochemical research methods. The studies used a drug with the active substance dexpanthenol and excipients decamethoxine, Vaseline oil, emulsifier, glycerin, methylparaben, propylparaben, and purified water. The drug under study effectively reduced the wound surface area at all observation periods. It is proved that when using dexpanthenol-based ointment (10%), a complete wound-healing effect was observed in experimental animals on the 14th day of treatment: the area of wound surfaces decreased by 93.1±1.51%. The examined indicators were statistically substantially different from those in the group of untreated animals with skin wounds. The general clinical condition of domestic animals was examined, haematological and biochemical studies of animal blood were conducted under the conditions of applying an experimental drug to damaged skin areas. In animals with skin damage without treatment, the dynamic development of an acute inflammatory process in the body, the development of endogenous intoxication syndrome, signs of wound infection, pronounced exudation and slowing of contraction were observed. The developed veterinary drug with the active substance dexpanthenol simultaneously shows a pronounced antiinflammatory and wound-healing effect and provides a rapid therapeutic effect in wound processes in small pets

Doing palliative care research on hematologic cancer patients: A realist synthesis of literature and experts' opinion on what works, for whom and in what circumstances.

Research in PC (Palliative Care) is frequently challenging for patient's frailty, study design, professional misconceptions, and so on. Little is known about specificity in PC research on Hematologic cancer patients, who have distinct characteristics that might influence the enrollment process. What works, how and for whom, in increasing enrollment in studies in PC on patients with hematologic malignancies? Realist review: a qualitative review whose goal is to identify and explain the interaction between Contexts, Mechanisms, and Outcomes (CMOs). The theory was informed by a narrative, theory-based literature research, including an initialsystematic research, and the addition of papers suggested by experts of the field. We also used 7 interviews with experts in PC about patients with hematologic malignancies research and our own experience from a PC pilot study on patients with hematologic malignancies to refine the initial theory. In our initial theory we hypothesize that: - Access to palliative care could be beneficial to hematologic patients, even in early stages - Hematologists tend to under-use palliative care services in general, due to unpredictable disease trajectories and cultural barriers. - These factors may negatively impact the patients' enrollment in PC researchWe included secondary literature as narrative reviews, if they presented interesting propositions useful for our theoretical construction. 23 papers met our inclusion criteria.We also searched for relevant CMOs impacting referral in palliative care, and we selected a list of CMOs that could be relevant also in hematology. We accordingly theorized a group of interventions that could increase the enrollment in PC research and presented them using "social exchange theory" (SET) as a theoretical framework.Prominent researchers in PC in hematologic malignancies were interviewed on their opinion on our results, and additional CMOs. Before conducting research in PC on patients with hematologic malignancies, it's probably advisable to assess: - The perception of the different actors (physicians, nurses, other professionals involved), in particular the hematologists, in terms of pros and cons of referral to PC and enrollment in PC trials - The existing relationship between PC and the Hematology departmentAccordingly, it's possible to tailor different interventions on the various actors and choose a model of trial to increase the perception of benefits from PC and, consequently, enrollment.

Influence of participant and reviewer characteristics in application scores for a hematology research training program

AbstractThe American Society of Hematology Clinical Research Training Institute (CRTI) is a clinical research training program with a competitive application process. The objectives were to compare application scores based on applicant and reviewer sex and underrepresented minority (URM) status. We included applications to CRTI from 2003 to 2019. The application scores were transformed into a scale from 0 to 100 (100 was the strongest). The factors considered were applicant and reviewer sex and URM status. We evaluated whether there was an interaction between the characteristics and time related to application scores. In total, 713 applicants and 2106 reviews were included. There was no significant difference in scores according to applicant sex. URM applicants had significantly worse scores than non-URM applicants (mean [standard error] 67.9 [1.56] vs 71.4 [0.63]; P = .0355). There were significant interactions between reviewer sex and time (P = .0030) and reviewer URM status and time (P = .0424); thus, results were stratified by time. For the 2 earlier time periods, male reviewers gave significantly worse scores than did female reviewers; this difference did not persist for the most recent time period. The URM reviewers did not give significantly different scores across time periods. URM applicants received significantly lower scores than non-URM applicants. The impact of reviewer sex and URM status changed over time. Although male reviewers gave lower scores in the early periods, this effect did not persist in the late period. Efforts are required to mitigate the impact of applicant URM status on application scores.

Choosing the Right Cell Line for Acute Myeloid Leukemia (AML) Research.

Immortalized cell lines are widely used in vitro tools in oncology and hematology research. While these cell lines represent artificial systems and may accumulate genetic aberrations with each passage, they are still considered valuable models for pilot, preliminary, and screening studies. Despite their limitations, cell lines are cost-effective and provide repeatable and comparable results. Choosing the appropriate cell line for acute myeloid leukemia (AML) research is crucial for obtaining reliable and relevant results. Several factors should be considered when selecting a cell line for AML research, such as specific markers and genetic abnormalities associated with different subtypes of AML. It is also essential to evaluate the karyotype and mutational profile of the cell line, as these can influence the behavior and response to the treatment of the cells. In this review, we evaluate immortalized AML cell lines and discuss the issues surrounding them concerning the revised World Health Organization and the French-American-British classifications.