A systematic review of second-generation FLT3 inhibitors for treatment of patients with relapsed/refractory acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a complex disease with diverse mutations, including prevalent mutations in the FMS-like receptor tyrosine kinase 3 (FLT3) gene that lead to poor prognosis. Recent advancements have introduced FLT3 inhibitors that have improved outcomes for FLT3-mutated AML patients, however, questions remain on their application in complex conditions such as relapsed/refractory (R/R) disease. Therefore, we aimed to evaluate the clinical effectiveness of second-generation FLT3 inhibitors in treating patients with R/R AML. METHODS: A systematic literature search of PubMed, MEDLINE, SCOPUS and Google Scholar databases was made to identify relevant studies up to January 30, 2024. This study was conducted following the guidelines of the PRISMA. RESULTS: The ADMIRAL trial revealed significantly improved overall survival and complete remission rates with gilteritinib compared to salvage chemotherapy, with manageable adverse effects. Ongoing research explores its potential in combination therapies, showing synergistic effects with venetoclax and promising outcomes in various clinical trials. The QuANTUM-R trial suggested longer overall survival with quizartinib compared to standard chemotherapy, although concerns were raised regarding trial design and cardiotoxicity. Ongoing research explores combination therapies involving quizartinib, such as doublet or triplet regimens with venetoclax, showing promising outcomes in FLT3-mutated AML patients. CONCLUSION: These targeted therapies offer promise for managing this subgroup of AML patients, but further research is needed to optimize their use. This study underscores the importance of personalized treatment based on genetic mutations in AML, paving the way for more effective and tailored approaches to combat the disease.

Cardiac Complications and COVID-19: A Review of Life-threatening Co-morbidities.

The novel 2019 coronavirus disease (COVID-19) was first reported in the last days of December 2019 in Wuhan, China. The presence of certain co-morbidities, including cardiovascular diseases (CVDs), are the basis for worse outcomes in patients with COVID-19. Relevant English-language literature was searched and retrieved from the Google Scholar search engine and PubMed database up to 2023 using COVID-19, SARS-CoV-2, Heart failure, Myocardial infarction, and Arrhythmia and Cardiac complication as keywords. Increased hemodynamic load, ischemia-related dysfunction, ventricular remodeling, excessive neurohumoral stimulation, abnormal myocyte calcium cycling, and excessive or insufficient extracellular matrix proliferation are associated with heart failure (HF) in COVID-19 patients. Inflammatory reaction due to the excessive release of inflammatory cytokines, leads to myocardial infarction (MI) in these patients. The virus can induce heart arrhythmia through cardiac complications, hypoxia, decreased heart hemodynamics, and remarkable inflammatory markers. Moreover, studies have linked cardiac complications in COVID-19 with poor outcomes, extended hospitalization time, and increased mortality rate. Patients with COVID-19 and CVDs are at higher mortality risk and they should be given high priority when receiving the treatment and intensive care during hospitalization.

Emerging roles of HOTAIR lncRNA in the pathogenesis and prognosis of cardiovascular diseases.

Highlights HOTAIR, a long noncoding RNA, plays a role in the regulation of proteins involved in the pathogenesis of cardiovascular disease. Furthermore, it has been identified as a biomarker of this type of disease. Several factors and cells contribute to atherosclerosis, a progressive disease. However, the prognosis of HOTAIR in this disease varies depending on the path in which it plays a role. For this condition, there is no single prognosis to consider.

Association of Free Radical Product and Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis.

PURPOSE: Polycystic ovary syndrome (PCOS) is an endocrine disorder that primarily affects women of reproductive age. It is recognized as the leading cause of infertility due to anovulation. This research aims to evaluate the diagnostic potential of oxidative stress biomarkers, including advanced oxidation protein products (AOPP), malondialdehyde (MDA), uric acid (UA), and nitric oxide (NO), in identifying PCOS. METHODS: A literature search was conducted in the EMBASE, PubMed, Cochrane Library, and Scopus databases. The standardized mean difference (SMD) and 95% confidence interval (CI) were employed to assess the correlation between free radical product and PCOS. Moreover, the presence of heterogeneity among the studies was assessed utilizing the I2 statistic and Cochran Q test. The methodological rigor of the incorporated studies was assessed through the application of the Newcastle-Ottawa Scale. Furthermore, the presence of publication bias was determined via Begg and Egger tests. RESULTS: This meta-analysis reviewed 38 observational studies, including 17,845 women. The results revealed a significant association between PCOS in women and alterations in free radical levels. The study revealed that the PCOS group had significantly higher levels of AOPP (SMD = 3.193; 95% CI, 2.86 to 3.25), UA (SMD = 0.68; 95% CI, 0.24 to 1.13), and MDA (SMD = 1.16; 95% CI, 0.77 to 1.56) compared to the healthy control group. Furthermore, the analysis found a significantly lower level of NO (SMD = (- 0.59); 95% CI, - 1.15 to - 0.03) in the PCOS patient. CONCLUSION: Screening of specific biomarkers associated with free radical products could provide valuable benefits in the prognosis and diagnosis of PCOS.

Correlation of miR-155-5p, KRAS, and CREB Expression in Patients with Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a type of blood cancer involving numerous aberrant genes and microRNAs. MiRNAs are non-coding sequences that have been proven to be players in the biological processes of various cancers. The present study is designed to illustrate the relationship between miR-155, KRAS, and CREB. METHODS: This case-control study was conducted on 21 patients with AML and 9 healthy individuals. The expressions of miR-155, KRAS, and CREB were measured using RT-PCR. Demographic data were extracted from the documents of individuals. SPSS and GraphPad Prism software were used to analyze the data. RESULTS: The expression of miR-155 in patients with AML was 35 times higher than in the control group (p < 0.0001). Also, CREB fold change increased by 1.92-fold in patients compared to the controls (p = 0.034), but no difference in KRAS was observed between the control and AML groups (p > 0.05). There was no change in miR-155, CREB, and KRAS expression based on gender, age, and blast percentage (p > 0.5). Nevertheless, there was a direct correlation between CREB and KRAS expressions (p = 0.0002). Our result showed that overexpression of CREB and KRAS would cause an increase in white blood cells (WBCs) (p = 0.001, 0.045 respectively), but there was no correlation between miR-155 with WBCs (p > 0.5). CONCLUSIONS: Our study revealed that miR-155 and CREB had overexpression compared to the control group.

lncRNA TUG1 as potential novel biomarker for prognosis of cardiovascular diseases.

Globally, cardiovascular diseases (CVDs) are among the leading causes of death. In light of the high prevalence and mortality of CVDs, it is imperative to understand the molecules involved in CVD pathogenesis and the signaling pathways that they initiate. This may facilitate the development of more precise and expedient diagnostic techniques, the identification of more effective prognostic molecules and the identification of potential therapeutic targets. Numerous studies have examined the role of lncRNAs, such as TUG1, in CVD pathogenesis in recent years. According to this review article, TUG1 can be considered a biomarker for predicting the prognosis of CVD.

Considering that cardiovascular diseases (CVDs) are very common and can be fatal, we must have a method for assessing heart health and its probability of worsening in order to prevent and treat these diseases. In order to accomplish this, it is possible to look for biomarkers in bodily fluids that are indicative of CVD. The purpose of this article is to examine a molecule called TUG1, which is found in varying levels in patients suffering from CVD. There is an impact of TUG1 on the growth, death and inflammation response of heart cells. The potential application of TUG1 as a biomarker to predict the severity and progression of heart disease is therefore not surprising.

Epigenetic and metabolic reprogramming in inflammatory bowel diseases: diagnostic and prognostic biomarkers in colorectal cancer.

BACKGROUND AND AIM: "Inflammatory bowel disease" (IBD) is a chronic, relapsing inflammatory disease of the intestinal tract that typically begins at a young age and might transit to colorectal cancer (CRC). In this manuscript, we discussed the epigenetic and metabolic change to present a extensive view of IBDs transition to CRC. This study discusses the possible biomarkers for evaluating the condition of IBDs patients, especially before the transition to CRC. RESEARCH APPROACH: We searched "PubMed" and "Google Scholar" using the keywords from 2000 to 2022. DISCUSSION: In this manuscript, interesting titles associated with IBD and CRC are discussed to present a broad view regarding the epigenetic and metabolic reprogramming and the biomarkers. CONCLUSION: Epigenetics can be the main reason in IBD transition to CRC, and Hypermethylation of several genes, such as VIM, OSM4, SEPT9, GATA4 and GATA5, NDRG4, BMP3, ITGA4 and plus hypomethylation of LINE1 can be used in IBD and CRC management. Epigenetic, metabolisms and microbiome-derived biomarkers, such as Linoleic acid and 12 hydroxy 8,10-octadecadienoic acid, Serum M2-pyruvate kinase and Six metabolic genes (NAT2, XDH, GPX3, AKR1C4, SPHK and ADCY5) expression are valuable biomarkers for early detection and transition to CRC condition. Some miRs, such as miR-31, miR-139-5p, miR -155, miR-17, miR-223, miR-370-3p, miR-31, miR -106a, miR -135b and miR-320 can be used as biomarkers to estimate IBD transition to CRC condition.

Immune thrombocytopenia: a review on the pathogenetic role of immune cells.

INTRODUCTION: Immune thrombocytopenia [ITP] is a common bleeding disorder with an isolated platelet count of less than 100 × 109/L. AREAS COVERED: Relevant literature from 2003 to 2022 was retrieved and reviewed from the Google Scholar search engine and PubMed database. Antibodies produced by autoreactive B lymphocytes and the phagocytic function of macrophages are considered the most critical factors in platelet destruction. Also, macrophages present the antigen to T lymphocytes and activate them. Follicular helper T-cells [TFH] play a role in stimulating, differentiating, and activating autoreactive B cells, while cluster of differentiation [CD]-8+ T plays a role in platelet destruction through apoptosis. The classical pathway of the complement system also causes platelet destruction. By inhibiting platelet production, low levels of thrombopoietin and an immune response against megakaryocytes in the bone marrow worsen thrombocytopenia. EXPERT OPINION: T-cell subset changes and an increase in activated autoreactive B cells, in addition to the function of components of the innate immune system [the complement system, dendritic cells, and natural killer cells], play a critical role in the pathogenesis of the ITP. Accurate detection of these changes may lead to developing new therapeutic strategies and identifying better prognostic/diagnostic factors.

Implications of Complement Imbalance in COVID-19: A Molecular Mechanistic Discussion on the Importance of Complement Balance.

Two central questions in COVID-19 treatment which should be considered are: "How does the imbalance of the complement system affect the therapeutic approaches?" and "Do we consider complement inhibitors in therapeutic protocols?". The complement system is a double-edged sword since it may either promote immune responses against COVID-19 or contribute to destructive inflammation in the host. Therefore, it is crucial to regulate this system with complement inhibitors. In this manuscript, we discuss the molecular mechanisms of complement and complement inhibitors in COVID-19 patients. We searched the terms "COVID-19", "Complement", "Complement inhibitor", "SARS-CoV-2", and all complement fragments and inhibitors from 2000 to 2022 in PubMed and google scholar and checked the pathways in "KEGG pathway database". Complement is not well-appreciated in the treatment protocols despite its multiple roles in the disease, and most of the preventive anti-inflammatory therapeutic approaches did not include a complement inhibitor in COVID-19 therapeutic protocols. In this review article, we discussed the most recent studies regarding complement components mediated interventions and the mechanism of these interventions in COVID-19 patients. Since the control of the complement system overactivation is associated with a better prognosis in the initial stages of COVID-19, heparin, anti-thrombin, C1-inhibitor, montelukast, and hydralazine can be effective in the initial stages of this viral infection. Recombinant complement activation (RCA) proteins are more effective in regulating complement compared to terminal pathway therapeutic approaches such as the C3a and C5a inhibitors.

Cytokines and their role in cardiovascular diseases.

The evaluation of diagnostic and prognostic biomarkers has always been a hot topic in various diseases. Considering that cardiovascular diseases (CVDs) have the highest mortality and morbidity rates in the world, various studies have been conducted so far to find CVD associated biomarkers, including cardiac troponin (cTn) and NT-proBNP. Cytokines are components of the immune system that are involved in the pathogenesis of CVD due to their contribution to the inflammation process. The level of cytokines varies in many cardiovascular diseases. For instance, the plasma level of IL-1α, IL-18, IL-33, IL-6 and IL-8 is positively correlated with atherosclerosis and that of some other interleukins such as IL-35 is negatively correlated with acute myocardial infarction or cardiac angina. Due to its pivotal role in the inflammation process, IL-1 super family is involved in many CVDs, including atherosclerosis. IL-20 among the interleukins of IL-10 family has a pro-atherogenic role, while others, such as IL-10 and IL-19, play an anti-atherogenic role. In the present review, we have collected the latest published evidence in this respect to discuss valuable cytokines from the diagnostic and prognostic stand point in CVDs.

Regulation and Functions of α6-Integrin (CD49f) in Cancer Biology.

Over the past decades, our knowledge of integrins has evolved from being understood as simple cell surface adhesion molecules to receptors that have a complex range of intracellular and extracellular functions, such as delivering chemical and mechanical signals to cells. Consequently, they actively control cellular proliferation, differentiation, and apoptosis. Dysregulation of integrin signaling is a major factor in the development and progression of many tumors. Many reviews have covered the broader integrin family in molecular and cellular studies and its roles in diseases. Nevertheless, further understanding of the mechanisms specific to an individual subunit of different heterodimers is more useful. Thus, we describe the current understanding of and exploratory investigations on the α6-integrin subunit (CD49f, VLA6; encoded by the gene itga6) in normal and cancer cells. The roles of ITGA6 in cell adhesion, stemness, metastasis, angiogenesis, and drug resistance, and as a diagnosis biomarker, are discussed. The role of ITGA6 differs based on several features, such as cell background, cancer type, and post-transcriptional alterations. In addition, exosomal ITGA6 also implies metastatic organotropism. The importance of ITGA6 in the progression of a number of cancers, including hematological malignancies, suggests its potential usage as a novel prognostic or diagnostic marker and useful therapeutic target for better clinical outcomes.

Evaluation of HLA-B*05, *07, *08, *27 and *51 Allele Expression in Adults with Immune Thrombocytopenic Purpura.

Background: Immune thrombocytopenic purpura (ITP) is an immune mediated acquired disease characterized by isolated thrombocytopenia. Since there is no specific and sensitive biomarkers to guide treatment of ITP patients, this study aimed to evaluate the possible application of human leukocyte alleles HLA-B5, 7, 8, 27 and 51 and their association with patients' laboratory data and clinical findings. Methods:Thirty-one adult patients with chronic ITP were included in the present study. Human leukocyte antigen (HLA) typing was done using the standard lymphocytotoxicity HLA typing method. Moreover, patients' medical records were used to collect data about disease presentations, platelet count at diagnosis. Results:Our study included 31 patients (25 females and six males) with a mean age of 40.23±17.06 years. Among all participants, HLA-B5 (25.8%) and HLA-B51 (22.6%) alleles were the most prevalent alleles, followed by HLA-B7 (9.7%) and HLA-B8 (9.7%), HLA-B27 (3.2%). The mean platelet count significantly was lower in patients with HLA-B5 (16.13x10³/µL versus 36.63x10³/µL) (P=0.01) and HLA-B51 (14.14x10³/µL versus 36.24x10³/µL) (P=0.04). Also, epistaxis and gingival bleeding were observed in patients with 11.5x10³/µL mean platelet count (P=0.04). In addition, lymphocyte and neutrophil cell counts were significantly associated with the expression of HLA-B*05 and HLA-B*51 antigens (P <0.05). Conclusions:According to the present study results, it seems that HLA-B5 and HLA-B51 alongside complete blood count test parameters may have a positive relationship in ITP patients.

Interesting effects of interleukins and immune cells on acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a medical condition characterized by widespread inflammation in the lungs with consequent proportional loss of gas exchange function. ARDS is linked with severe pulmonary or systemic infection. Several factors, including secretory cytokines, immune cells, and lung epithelial and endothelial cells, play a role in the development and progression of this disease. The present study is based on Pubmed database information (1987-2022) using the words "Acute respiratory distress syndrome", "Interleukin", "Cytokines" and "Immune cells". Cytokines and immune cells play an important role in this disease, with particular emphasis on the balance between pro-inflammatory and anti-inflammatory factors. Neutrophils are one of several important mediators of Inflammation, lung tissue destruction, and malfunction during ARDS. Some immune cells, such as macrophages and eosinophils, play a dual role in releasing inflammatory mediators, recruitment inflammatory cells and the progression of ARDS, or releasing anti-inflammatory mediators, clearing the lung of inflammatory cells, and helping to improve the disease. Different interleukins play a role in the development or inhibition of ARDS by helping to activate various signaling pathways, helping to secrete other inflammatory or anti-inflammatory interleukins, and playing a role in the production and balance between immune cells involved in ARDS. As a result, immune cells and, inflammatory cytokines, especially interleukins play an important role in the pathogenesis of this disease Therefore, understanding the relevant mechanisms will help in the proper diagnosis and treatment of this disease.

Complete Blood Count Test in Rheumatology: Not Just a Screening Test.

BACKGROUND: Rheumatic disorders are chronic and common diseases, which especially involve connective tissue and may be associated with the damage to vital organs such as heart and kidney. Diagnosis, prognosis, determining the probability of severe complications, monitoring and evaluation of the response to treatment in such patients require specialized, expensive and time-consuming laboratory tests. METHODS: In this review article, we assessed the value of parameters of routine, inexpensive, and available Complete Blood Count (CBC) in detecting disease activity and explaining the prognosis of a number of rheumatic disorders, including systemic lupus erythematosus and rheumatoid arthritis by reviewing the results of searching Google Scholar search engine and PubMed databases over 2000 - 2021. RESULTS: Review of previous articles showed that while traditional Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) tests do not have sufficient specificity to appraise disease activity, CBC derived inflammatory biomarker Neutrophil-to-Lymphocyte Ratio (NLR) is able to assess disease activity and response to treatment in Rheumatoid Arthritis (RA). Also, Mean Platelet Volume (MPV) and NLR can determine the prognosis of renal involvement in Systemic lupus erythematosus (SLE). CONCLUSIONS: Although CBC-based parameters are not completely specific and sensitive to rheumatic disorders, but based on the results of previous studies, these parameters, particularly red cell distribution width (RDW), MPV, NLR and platelet to lymphocyte ratio (PLR) are inflammatory biomarkers with a prognostic role in rheumatic disorders that can also assess activity of the disease.

Regulatory factors involved in Th17/Treg cell balance of immune thrombocytopenia.

Immune thrombocytopenia is a common heterogeneous autoimmune disease that is characterized by decreasing peripheral blood platelet counts and increasing risk of bleeding. Studies have shown that an imbalance between T helper 17 (Th17) and Regulatory T (Treg) cells differentiated from CD4+T-cells is a key factor influencing the development and pathogenesis of immune thrombocytopenia. Th17 cells promote the development of chronic inflammatory disorders and induce autoimmune diseases, whereas Treg cells regulate immune homeostasis and prevent autoimmune diseases. Several regulators affecting the production and maintenance of these cells are also essential for proper regulation of Th17/Treg balance; these regulatory factors include cell surface proteins, miRNAs, and cytokine signaling. In this review, we focus on the function and role of balance between Th17 and Treg cells in immune thrombocytopenia, the regulatory factors, and therapeutic goals of this balance in immune thrombocytopenia.

Biomarkers of endothelial dysfunction are associated with poor outcome in COVID-19 patients: A systematic review and meta-analysis.

Numerous studies have linked coronavirus disease 2019 (COVID-19) with endothelial dysfunction and reported elevated levels of endothelial biomarkers in this disease. We conducted a systematic review and meta-analysis of the published evidence in this respect. A systematic literature search of PubMed and Scopus databases was performed to find studies investigating biomarkers of endothelial dysfunction in COVID-19 patients. Pooled standardized mean differences and their 95% confidence intervals were calculated for each biomarker using random effect model. 74 studies with 7668 patients were included. In comparison to patients with good outcome, those with poor outcome had higher levels of von Willebrand factor (vWF) (SMD: 0.83, 95% CI: 0.59-1.07, p < 0.00001), vWF:ADAMTS13 (1.23, (0.77-1.7), p < 0.00001), angiopoietin-2 (Ang-2) (1.06 (0.6-1.51), p < 0.0001), E-selectin (1.09 (0.55-1.63), p < 0.0001), P-selectin (0.59 (0.24-0.94), p = 0.001), syndecan-1 (0.99 (0.6-1.37), p < 0.00001), mid-regional pro-adrenomedullin (MR-proADM) (1.52 (1.35-1.68), p < 0.00001), vascular endothelial growth factor (0.27 (0.02-0.53), p = 0.03), soluble fms-like tyrosine kinase-1 (sFLT-1) (1.93 (0.65-3.21), p = 0.03) and lower levels of ADAMTS13 antigen (-0.69 (-0.9 to -0.47) p < 0.00001) and activity (-0.84 (-1.06 to -0.61) p < 0.0000). Plasminogen activator inhibitor-1 and tissue plasminogen activator levels were not different between the two groups (p < 0.05). There were elevated levels of endothelial dysfunction biomarkers in COVID-19 patients with poor outcome, indicating their possible role in disease severity and prognosis. In particular, MR-proADM, vWF, syndecan-1 and sFLT-1 showed a significant association with poor outcome in these patients.

Association of human papillomavirus with breast cancer: a new perspective on an old debate.

Breast cancer is a common cancer in the female population. Despite remarkable progress in the treatment of this cancer, its exact etiology is still unknown. Since the first evidence of an association between breast cancer and human papillomavirus (HPV) was provided in 1992, numerous studies have explored this subject but have reached contradictory results. In this review, the authors examine the existing evidence and hypotheses regarding the pathways whereby HPV infection can reach breast cells and the mediators linking HPV oncoproteins to breast cancer pathogenesis. Furthermore, the authors discuss contradictory findings regarding the association of HPV with breast cancer. Showing the link between HPV infection and increased genomic instability, reduced apoptosis, immune system dysfunction and progression of metastasis, the reviewed findings highlight the importance of active presence or history of HPV infection as a prognostic factor for breast tumor development.

Breast cancer is a common cancer in the female population. Although the exact cause of this cancer is still unknown, it has several major risk factors including family history, hormonal problems and age. It has been suggested that various viral infections, including human papillomavirus, can increase the likelihood of developing breast cancer. This review discusses the evidence regarding the association of human papillomavirus with breast cancer.

Involvement of progranulin (PGRN) in the pathogenesis and prognosis of breast cancer.

Breast cancer constitute a common type of oncological disease with a highlighted mortality rate. In recent years, researchers have introduced progranulin (PGRN) as an novel potential biomarker and associated its function with higher risk factor for development of breast cancer. The present review article collects evidence on the association of PGRN with clinicopathological features and drug resistance in the patients with breast cancer. The results of this study suggested the use of routine determination of PGRN in the clinic as a reliable biomarker for screening people at high risk or as early indication of breast cancer. Targeting PGRN and its associated signaling pathways and receptors, such as sortilin (SORT1), could also cover a novel therapeutic strategy in the breast cancer.

Application of Bayesian Decision Tree in Hematology Research: Differential Diagnosis of ß-Thalassemia Trait from Iron Deficiency Anemia.

OBJECTIVE: Several discriminating techniques have been proposed to discriminate between ß-thalassemia trait (ßTT) and iron deficiency anemia (IDA). These discrimination techniques are essential clinically, but they are challenging and typically difficult. This study is the first application of the Bayesian tree-based method for differential diagnosis of ßTT from IDA. METHOD: This cross-sectional study included 907 patients with ages over 18 years old and a mean (±SD) age of 25 ± 16.1 with either ßTT or IDA. Hematological parameters were measured using a Sysmex KX-21 automated hematology analyzer. Bayesian Logit Treed (BLTREED) and Classification and Regression Trees (CART) were implemented to discriminate ßTT from IDA based on the hematological parameters. RESULTS: This study proposes an automatic detection model of beta-thalassemia carriers based on a Bayesian tree-based method. The BLTREED model and CART showed that mean corpuscular volume (MCV) was the main predictor in diagnostic discrimination. According to the test dataset, CART indicated higher sensitivity and negative predictive value than BLTREED for differential diagnosis of ßTT from IDA. However, the CART algorithm had a high false-positive rate. Overall, the BLTREED model showed better performance concerning the area under the curve (AUC). CONCLUSIONS: The BLTREED model showed excellent diagnostic accuracy for differentiating ßTT from IDA. In addition, understanding tree-based methods are easy and do not need statistical experience. Thus, it can help physicians in making the right clinical decision. So, the proposed model could support medical decisions in the differential diagnosis of ßTT from IDA to avoid much more expensive, time-consuming laboratory tests, especially in countries with limited recourses or poor health services.