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.

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.

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.

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.

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.

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.

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.

Chemo/radiotherapy-Induced Bone Marrow Niche Alterations.

Bone marrow (BM) niche is a specific microenvironment for hematopoietic stem cells (HSCs) as well as non-hematopoietic cells. Evidence shows that chemo/radiotherapy can lead to the disruption of different properties of HSCs such as proliferation, differentiation, localization, self-renewa, and steady-state of cell populations. Investigations have shown that the deregulation of balance within the marrow cavity due to chemo/radiotherapy could lead to bone loss, abnormal hematopoiesis, and enhanced differentiation potential of mesenchymal stem cells towards the adipogenic lineage. Therefore, understanding the underlying mechanisms of chemo/radiotherapy induced BM niche changes may lead to the application of appropriate therapeutic agents to prevent BM niche defects. Highlights Chemo/radiotherapy disrupts the steady-state of bone marrow niche cells and result in deregulation of normal balance of stromal cell populations. Chemo/radiotherapy agents play a significant role in reducing of bone formation as well as fat accumulation in the bone marrow niche. Targeting molecular pathways may lead to recovery of bone marrow niches after chemo/radiotherapy.

Aplastic anemia, cellular and molecular aspects.

Aplastic anemia (AA) is an autoimmune disorder characterized by bone marrow and peripheral blood pancytopenia. Different environmental and genetical conditions could be effective in an outbreak of this disease. The exact pathogenesis of this disease, however, is still idiopathic. The present study is based on Pubmed database information (2002-2021) using the words "Aplastic Anemia," "Hematopoietic Stem Cells niche," "Signaling pathway," "Cytokines," and "Immuno cells." In this disease, both hematopoietic stem cells and mesenchymal stromal cells are impaired, which is associated with impaired hematopoiesis and decreased hematopoietic cells. Inflammatory cytokines increase, which changes the ratio of T lymphocytes and leads to disease progression. In addition, the most common mechanism of AA is damage by the immune system, which leads to increased apoptosis in progenitor cells. We have shown in this review that the disease involves quantitative defects in stem cell numbers and qualitative abnormalities in the function of these cells and the activity of many different cellular and molecular factors can damage hematopoietic cells and the protective substrate of these cells in this disease.

The effect of inflammatory factors and their inhibitors on the hematopoietic stem cells fate.

Inflammatory cytokines exert different effects on hematopoietic stem cells (HSCs), lead to the development of various cell lineages in bone marrow (BM) and are thus a differentiation axis for HSCs. The content used in this article has been obtained by searching PubMed database and Google Scholar search engine of English-language articles (1995-2020) using "Hematopoietic stem cell," "Inflammatory cytokine," "Homeostasis," and "Myelopoiesis." Inflammatory cytokines are involved in the differentiation and proliferation of hematopoietic progenitors to compensate for cellular death due to inflammation. Since each of these cytokines differentiates HSCs into a specific cell line, the difference in the effect of these cytokines on the fate of HSC progenitors can be predicted. Inhibitors of these cytokines can also control the inflammatory process as well as the cells involved in leukemic conditions. In general, inflammatory signaling can specify the dominant cell line in BM to counteract inflammation and leukemic condition via stimulating or inhibiting hematopoietic progenitors. Therefore, detection of the effects of inflammatory cytokines on the differentiation of HSCs can be an appropriate approach to check inflammatory and leukemic conditions and the suppression of these cytokines by their inhibitors allows for control of homeostasis in stressful conditions.

COVID-19: imbalance of multiple systems during infection and importance of therapeutic choice and dosing of cardiac and anti-coagulant therapies.

The renin-angiotensin-aldosterone system and its metabolites play an important role in homeostasis of body, especially the cardiovascular system. In this study, we discuss the imbalance of multiple systems during the infection and the importance of therapeutic choice, dosing, and laboratory monitoring of cardiac and anti-coagulant therapies in COVID-19 patients. The crosstalk between angiotensin, kinin-kallikrein system, as well as inflammatory and coagulation systems plays an essential role in COVID-19. Cardiac complications and coagulopathies imply the crosstalks between the mentioned systems. We believe that the blockage of bradykinin can be a good option in the management of COVID-19 and CVD in patients and that supportive treatment of respiratory and cardiologic complications is needed in COVID-19 patients. Ninety-one percent of COVID-19 patients who were admitted to hospital with a prolonged aPTT were positive for lupus anticoagulant, which increases the risk of thrombosis and prolonged aPTT. Therefore, the question that is posed at this juncture is whether it is safe to use the prophylactic dose of heparin particularly in those with elevated D-dimer levels. It should be noted that timing is of high importance in anti-coagulant therapy; therefore, we should consider the level of D-dimer, fibrinogen, drug-drug interactions, and risk factors during thromboprophylaxis administration. Fibrinogen is an independent predictor of resistance to heparin and should be considered before thromboprophylaxis. Alteplase and Futhan might be a good choice to assess the condition of heparin resistance. Finally, the treatment option, dosing, and laboratory monitoring of anticoagulant therapy are critical decisions in COVID-19 patients.

Aspirin exacerbated respiratory disease (AERD): molecular and cellular diagnostic & prognostic approaches.

Aspirin-exacerbated respiratory disease (AERD) is characterized by immune cells dysfunction. This study aimed to investigate the molecular mechanisms involved in AERD pathogenesis. Relevant literatures were identified by a PubMed search (2005-2019) of english language papers using the terms "Aspirin-exacerbated respiratory disease", "Allergic inflammation", "molecular mechanism" and "mutation". According to the significant role of inflammation in AERD development, ILC-2 is known as the most important cell in disease progression. ILC-2 produces cytokines that induce allergic reactions and also cause lipid mediators production, which activates mast cells and basophils, ultimately. Finally, Monoclonal antibody and Aspirin desensitization in patients can be a useful treatment strategy for prevention and treatment.

PEAR1 polymorphisms as a prognostic factor in hemostasis and cardiovascular diseases.

Platelet Endothelial Aggregation Receptor (PEAR1), as a platelet receptor, plays a vital role in hemostasis. This receptor, by its extracellular part, causes platelet adhesion and consequently initiates platelet aggregation. Dysfunction of PEAR1 can disrupt platelet aggregation in patients with cardiovascular diseases (CVDs). The content used in this paper has been taken from English language articles (2005-2020) retrieved from Pubmed database and Google scholar search engine using "Cardiovascular Disease", "PEAR1", "Polymorphism", and "Platelet Aggregation" keywords. Some PEAR1 polymorphisms can disrupt homeostasis and interfere with the function mechanism of cardiac drugs. Since polymorphisms in this gene affect platelet function and the platelet aggregation process, PEAR1 could be further studied in the future as an essential factor in controlling the treatment process of patients with cardiovascular diseases. PEAR1 polymorphisms through disruption of the platelet aggregation process can be a risk factor in patients with CVDs. Therefore, controlling patients through genetic testing and the evaluation of PEAR1 polymorphisms can help improve the treatment process of patients. According to the studies on the PEAR1 gene and the effect of different polymorphisms on some crucial issues in CVDs patients (changes in platelet activity), it is clear that if there is a significant relationship between polymorphisms and CVDs, they can be used as prognostic and diagnostic markers. This study aims to evaluate the prognosis and drug treatment of the PEAR1 gene in CVDs patients.

Altering chromatin methylation patterns and the transcriptional network involved in regulation of hematopoietic stem cell fate.

Hematopoietic stem cells (HSCs) are quiescent cells with self-renewal capacity and potential multilineage development. Various molecular regulatory mechanisms such as epigenetic modifications and transcription factor (TF) networks play crucial roles in establishing a balance between self-renewal and differentiation of HSCs. Histone/DNA methylations are important epigenetic modifications involved in transcriptional regulation of specific lineage HSCs via controlling chromatin structure and accessibility of DNA. Also, TFs contribute to either facilitation or inhibition of gene expression through binding to enhancer or promoter regions of DNA. As a result, epigenetic factors and TFs regulate the activation or repression of HSCs genes, playing a central role in normal hematopoiesis. Given the importance of histone/DNA methylation and TFs in gene expression regulation, their aberrations, including changes in HSCs-related methylation of histone/DNA and TFs (e.g., CCAAT-enhancer-binding protein α, phosphatase and tensin homolog deleted on the chromosome 10, Runt-related transcription factor 1, signal transducers and activators of transcription, and RAS family proteins) could disrupt HSCs fate. Herewith, we summarize how dysregulations in the expression of genes related to self-renewal, proliferation, and differentiation of HSCs caused by changes in epigenetic modifications and transcriptional networks lead to clonal expansion and leukemic transformation.

Prognostic role and therapeutic susceptibility of cathepsin in various types of solid tumor and leukemia: A systematic review.

Cathepsins (CTSs) are multifunctional proteins that can play prominent roles in cancer progression and metastasis. In this systematic review, we compared the prognosis of CTS subtypes overexpression in leukemia and solid tumors, and investigated the effect of different factors on CTS prognosis. We systematically searched published articles indexed in PubMed, Scopus, Cochrane library, ISI Web of Science, and EmBase databases from February 2000 until January 2020. Among the selected leukemia and solid tumors studies, overexpression of CTS subtypes in newly diagnosed and treated patients were with poor prognosis in 43 studies (79.6%) and with good prognosis in 9 studies (16.6%). However, there were 2 studies (3.8%) with either good or poor prognosis, depending on conditions and caner stage and host cell. The relation between CTS and human leukocyte antigen (HLA) in leukemia and solid tumors was mentioned in 7 studies (13%). Overexpression of CTS subtypes in all new case patients had contributed to the induction of poor prognosis. It seems that CTS subtypes, based on the type of cancer and its stage, the type of host cells, and the probable relation with HLA, breed good or poor prognosis in patients with cancer. Therefore, monitoring the overexpression of CTS subtypes and determining the effect of each of these factors on CTS prognosis could be helpful in predicting cancer prognosis both in newly diagnosed or under treatment patients. They could also be useful in finding ways for improving the efficiency of contemporary therapeutic strategies in various types of leukemia and solid tumors.

The role of exogenous Fibrinogen in cardiac surgery: stop bleeding or induce cardiovascular disease.

The surgical treatment contributes to broad variety of cardiovascular diseases (CVD). Due to many involved factors in preoperative bleeding, it is almost difficult to perform better Haemostatic approach. Fibrinogen is a major blood glycoprotein and a coagulation factor which decreases postoperative bleeding. It has a potential role in platelet activation and bleeding inhibition; it may reflect the inflammatory responses and be related to the endothelial dysfunction. Fibrinogen can act as a pro-inflammatory element via increasing some inflammatory markers including IL-6, tumor necrosis factor-α (TNF-α), monocyte chemo attractant protein (MCP-1), macrophage inflammatory protein-1 (MIP-1a and b), matrix metalloproteinase (MMP-1 and MMP-9) and Toll-like Receptors (TLRs); through activation of these factors, fibrinogen may induce some inflammatory mechanisms such as focal adhesion kinase (FAK), mitogen-activated protein kinases (MAPK) and nuclear factor κB (NF-κB) pathways. It may cause endothelial dysfunction by increasing P and E-selection, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels which activate MAPK and NF-κB pathways. This factor is also associated with increased exocytosed von Willebrand factor (vWF) as well as activation of Rho-GTPase mechanism. All of these data demonstrate the dual role of fibrinogen in cardiac surgeries, bleeding inhibition and CVD. Therefore, identifying the CVD factors is helpful for designing preventive strategies and alternative drugs.

Essential thrombocythemia: a hemostatic view of thrombogenic risk factors and prognosis.

Essential thrombocythemia (ET) is a classical myeloproliferative neoplasm that is susceptible to hypercoagulable state due to impaired hemostatic system, so that thrombotic complications are the leading cause of mortality in ET patients. The content used in this article has been obtained by the PubMed database and Google Scholar search engine from English-language articles (2000-2019) using the following keywords: "Essential thrombocythemia," "Thrombosis," "Risk factors" and "Hemostasis. In this neoplasm, the count and activity of cells such as platelets, leukocytes, endothelial cells, as well as erythrocytes are increased, which can increase the risk of thrombosis through rising intercellular interactions, expression of surface markers, and stimulation of platelet aggregation. In addition to these factors, genetic polymorphisms in hematopoietic stem cells (HSCs), including mutations in JAK2, CALR, MPL, or genetic abnormalities in other genes associated with the hemostatic system may be associated with increased risk of thrombotic events. Moreover, disruption of coagulant factors can pave the way for thrombogeneration. Therefore, the identification of markers related to cell activation, genetic abnormalities, or alternation in the coagulant system can be used together as diagnostic and prognostic markers for the occurrence of thrombosis among ET patients. Thus, because thrombotic complications are the main factors of mortality in ET patients, a hemostatic viewpoint and risk assessment of cellular, genetic, and coagulation factors can have prognostic value and contribute to the choice of effective treatment and prevention of thrombosis.

HLA-B5, 7, 8, 27, and 51 Antigens and Immune Thrombocytopenic Purpura: Is There an Association?

BACKGROUND: Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by low platelet counts in peripheral blood, impairment of thrombopoiesis in bone marrow, and risk of mild to severe bleedings. ITP can be seen among both sexes in different ages. Although definitive pathogenesis of this disorder is still ambiguous, some of risk factors for ITP are recognized, including human leukocyte antigens (HLAs). OBJECTIVE: Our goal was to evaluate the possible association between HLA-B5, 7, 8, 27, and 51 antigens with ITP for the first time. We were hoping to achieve new hypothetical diagnostic/prognostic biomarkers to introduce a new subject for further studies on HLA class I antigens as possible risk factors for ITP. MATERIALS AND METHODS: A total of 37 patients with ITP were included in this study. After confirmation of ITP diagnosis, peripheral blood samples were collected from them. The expression of each of HLA antigens was evaluated by standard lymphocytotoxicity technique. RESULTS: Compared with other studied antigens, the expression of HLA-B5 and HLA-B51 was more prevalent among our patients. According to the results, 22% of patients were positive for HLA-B5 and HLA-B51. Furthermore, no significant association was found between HLAs expressions with complete blood count parameters. CONCLUSIONS: We conclude that there is an association between HLA-B5 and HLA-B51 with ITP and that they are not likely to be used as diagnostic or prognostic biomarkers. We suggest studying the association between HLA-B antigens and ITP in large-scale studies to determine whether or not there is a significant association.

The HLA-DRB1*11 group-specific allele is a predictor for alloantibody production in the transfusion-dependent thalassemia patients.

BACKGROUND AND OBJECTIVES: Recently, researchers have shown an increased interest in thalassemia for detecting susceptible factors in alloimmunization development. Alloimmunization, especially against Rh and Kell blood, occurs in 30% of thalassemia dependent transfusion (TDT) patients. The aim of this study is to determine the role of HLA-DRB1*11 and HLA-DRB1*13 group-specific alleles in the production of Rh and Kell alloantibodies. MATERIALS AND METHODS: 106 TDT patients were recruited for this study (54 responders and 52 non-responders). Responder patients developed Rh, Kell and/or specificities alloantibodies. HLA genotyping was done with Sequence-Specific Primers (SSP-PCR) and the results were compared between two groups. RESULTS: A significant association was found between anti-K (P=0.021, OR=2.546, 95%CI) and anti-E (P=0.049, OR=2.304, 95%CI) alloantibodies production with DRB1*11, respectively. Development of Anti-K and Anti-E alloantibodies were associated with DRB1*11 (P = 0.021, OR = 2.546, 95%CI) (P = 0.049, OR = 2.304, 95%CI), respectively. Further analysis showed that DRB1*11 is more frequent in multi responders (responder with both Rh and Kell alloantibodies) than mono-responders, 71% Versus 29%. There was not found any association between the DRB1*13 group-specific allele and the production of alloantibodies (P = 0.584, OR = 0.308, 95%CI). CONCLUSIONS: The evidence from this study suggests that detecting the DRB1*11 group-specific allele before starting transfusion can be useful to identify susceptible patients, increase HSCT transplantation compatibility and blood transfusion management.

Flow cytometric Immunophenotyping and Hematological Findings at Diagnosis and Relapse of Pediatric Acute Lymphoblastic Leukemia Patients.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a common pediatric leukemia caused by lymphoid precursor proliferation. We analyzed immunophenotyping and hematological findings, as the risk of relapse, of pediatric ALL patients at diagnosis and relapse. METHODS: Peripheral blood and bone marrow samples of 30 pediatric ALL patients were collected at diagnosis and at relapse. The latter was evaluated for immunophenotyping and cytochemical staining (Periodic Acid Schiff stain (PAS)), while hematological findings were assessed in the former one. RESULTS: The percentage of PAS-positive patients, TdT, and CD4 expression were significantly higher at diagnosis than relapse (p = 0.027, 0.004, and 0.043, respectively), whereas the platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio were significantly lower at diagnosis (p = 0.004 and 0.032, respectively). There were correla-tions between immunophenotyping and hematology data, including: a) a negative correlation between CD4 expression with blast percentage (r = -0.927, p = 0.003) and hemoglobin level (r = -0.991, p < 0.001) at diagnosis and TdT expression with platelet count (r = -0.441, p = 0.017) at relapse, and b) a positive correlation between CD3 expression with PLR (r = 0.367, p = 0.046) at relapse. CONCLUSIONS: Results suggest that changes in immunophenotyping and hematology findings could be applied as relapse prognostic factors in ALL.