A blue blood toddler- a case report of methemoglobinemia and literature review.

Background: Methemoglobinemia (MetHb) is a rare and potentially life-threatening condition caused by oxidation of ferrous hemoglobin (Fe2+) to the ferric (Fe3+) state, making it incapable of binding oxygen and resulting in cyanosis and tissue ischemia.

Case Presentation: This case presentation describes a 1-year-old boy who developed sudden cyanosis and reduced consciousness disorder. An initial assessment showed decreased oxygen saturation (SpO2 85%) despite oxygen therapy, while point-of-care venous blood gas (VBG) analysis assessed high rates of MetHb (72.

Acute Promyelocytic Leukemia-like AML: Genetic Perspective and Clinical Implications.

Acute promyelocytic leukemia (APL) is a rare type of AML, characterized by the t(15;17) translocation and accounting for 8-15% of cases. The introduction of target therapies, such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), radically changed the management of APL, making it the most curable AML subtype. However, a small percentage (estimated to be 2%) of AML presenting with APL-like morphology and/or immunophenotype lacks t(15;17).

The role of clonal progression leading to the development of therapy-related myeloid neoplasms.

Therapy-related myeloid neoplasms (t-MN) are characterized by aggressive features and a dismal prognosis. Recent evidence suggests a higher incidence of t-MN in individuals harboring clonal hematopoiesis of indeterminate potential (CHIP). In order to gain insight into CHIP-driven malignant progression, we gathered data from ten published reports with available detailed patient characteristics at the time of primary malignancy and t-MN development.

Atomistic description of the OCTN1 recognition mechanism via in silico methods.

The Organic Cation Transporter Novel 1 (OCTN1), also known as SLC22A4, is widely expressed in various human tissues, and involved in numerous physiological and pathological processes remains. It facilitates the transport of organic cations, zwitterions, with selectivity for positively charged solutes. Ergothioneine, an antioxidant compound, and acetylcholine (Ach) are among its substrates.

Therapy-Related Myeloid Neoplasms: Predisposition and Clonal Evolution.

Therapy-related Myeloid Neoplasm (t-MN) represents one of the worst long-term consequences of cytotoxic therapy for primary tumors and autoimmune disease. Poor survival and refractoriness to current treatment strategies characterize affected patients from a clinical point of view. In our aging societies, where newer therapies and ameliorated cancer management protocols are improving the life expectancy of cancer patients, therapy-related Myeloid Neoplasms are an emerging problem.

Investigating the Molecular Mechanisms Underlying Early Response to Inflammation and Infection in Human Gastric Epithelial Cells.

is a leading cause of chronic gastric inflammation, generally associated with gastritis and adenocarcinoma. Activation of the NF-κB pathway mainly contributes to the inflammatory phenotype observed in infection in humans and experimental models. Since the gastric epithelium undergoes rapid turnover, inflammation and pathogenicity of result from early phase and chronically activated pathways.

Expression profiling of extramedullary acute myeloid leukemia suggests involvement of epithelial-mesenchymal transition pathways.

Extramedullary (EM) colonization is a rare complication of acute myeloid leukemia (AML), occurring in about 10% of patients, but the processes underlying tissue invasion are not entirely characterized. Through the application of RNAseq technology, we examined the transcriptome profile of 13 AMLs, 9 of whom presented an EM localization. Our analysis revealed significant deregulation within the extracellular matrix (ECM)-receptor interaction and focal-adhesion pathways, specifically in the EM sites.

Microenvironment in acute myeloid leukemia: focus on senescence mechanisms, therapeutic interactions, and future directions.

Acute myeloid leukemia (AML) is a disease with a dismal prognosis, mainly affecting the elderly. In recent years, new drugs have improved life expectancy and quality of life, and a better understanding of the genetic-molecular nature of the disease has shed light on previously unknown aspects of leukemogenesis. In parallel, increasing attention has been attracted to the complex interactions between cells and soluble factors in the bone marrow (BM) environment, collectively known as the microenvironment.

Bone Marrow Microenvironment Involvement in t-MN: Focus on Mesenchymal Stem Cells.

Therapy-related myeloid neoplasms (t-MN) are a late complication of cytotoxic therapy (CT) used in the treatment of both malignant and non-malignant diseases. Historically, t-MN has been considered to be a direct consequence of DNA damage induced in normal hematopoietic stem or progenitor cells (HSPC) by CT. However, we now know that treatment-induced mutations in HSC are not the only players involved in t-MN development, but additional factors may contribute to the onset of t-MN.

Reliability of flow-cytometry in diagnosis and prognostic stratification of myelodysplastic syndromes: correlations with morphology and mutational profile.

Diagnosis and prognostic stratification of myelodysplastic syndromes (MDS) have been complemented by new techniques, including flow cytometry and NGS. To analyze the relationship between molecular and cytofluorimetric data, we enrolled in this retrospective study, 145 patients, including 106 diagnosed with MDS and 39 controls. At disease onset, immunophenotypic (IF), cytogenetic tests, and cytomorphological (CM) examination on bone marrow were carried out in all patients, while NGS was performed in 58 cases.

Correlation analysis between auto-immunological and mutational profiles in myelodysplastic syndromes.

Objective And Design: Systemic-Inflammatory-Autoimmune-Diseases (SIAD) is increasingly considered in Myelodysplastic-Syndromes (MDS). In this line, we evaluated the MDS auto-immunological profile, correlating it to the mutational landscape, trying to identify a molecular-genetic trigger agent related to SIAD.

Methods And Materials: Eighty-one MDS were enrolled and t-NGS was performed.

Drowning in Children and Predictive Parameters: A 15-Year Multicenter Retrospective Analysis.

Background: Drowning is a serious and underestimated public health problem, with the highest morbidity and mortality reported among children. Data regarding pediatric outcomes of drowning are often inadequate, and data collection is poorly standardized among centers. This study aims to provide an overview of a drowning pediatric population in pediatric emergency department, focusing on its main characteristics and management and evaluating prognostic factors.

Applicability of 2022 classifications of acute myeloid leukemia in the real-world setting.

The increasing knowledge of molecular genetics of acute myeloid leukemia (AML) necessitated the update of previous diagnostic and prognostic schemes, which resulted in the development of the World Health Organization (WHO), the International Consensus Classification (ICC), and the new European LeukemiaNet (ELN) recommendations in 2022. We aimed to provide a real-world application of the new models, unravel differences and similarities, and test their implementation in clinical AML diagnosis. A total of 1001 patients diagnosed with AML were reclassified based on the new schemes.

Writing letters in two graphic systems: Behavioral and neural correlates in Latin-Arabic biscripters.

Biscriptuality is the ability to read and write using two scripts. Despite the increasing number of biscripters, this phenomenon remains poorly understood. Here, we focused on investigating graphomotor processing in French-Arabic biscripters.

Ellagitannins from Mill. Leaf Extracts Impair Viability and Infection-Induced Inflammation in Human Gastric Epithelial Cells.

() is an etiologic factor of peptic ulcer disease and gastric cancer. Virulent strains of are correlated with the severity of gastritis, due to NF-κB activation and IL-8 expression at the epithelial level. Ellagitannins have been documented for antibacterial and anti-inflammatory activities, thus suggesting their potential use in gastritis.

In silico investigation on structure-function relationship of members belonging to the human SLC52 transporter family.

Riboflavin is an essential water-soluble vitamin that needs to be provided through the diet because of the conversion into flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), important cofactors in hundreds of flavoenzymes. The adsorption and distribution of riboflavin is mediated by transmembrane transporters of the SLC52 family, namely RFVT1-3, whose mutations are mainly associated with two diseases, MADD and the Brown-Vialetto-Van Laere syndrome. Interest in RFVTs as pharmacological targets has increased in the last few years due to their overexpression in several cancer cells, which can be exploited both by blocking the uptake of riboflavin into the cancerous cells, and by performing cancer targeted delivery of drugs with a high affinity for RFVTs.

Impairment of FOXM1 expression in mesenchymal cells from patients with myeloid neoplasms, de novo and therapy-related, may compromise their ability to support hematopoiesis.

Bone marrow mesenchymal stem cells (BM-MSCs) exhibit multiple abnormalities in myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML), including reduced proliferative and clonogenic capacity, altered morphology, impaired immunoregulatory properties and capacity to support hematopoiesis. Here, we investigated expression of the FOXM1 gene, a transcription factor driving G2/M gene expression, in BM-MSCs isolated from patients with MDS and AML, de novo and therapy-related, compared to BM-MSCs isolated from healthy donors (HD). We observed a statistically significant downregulation of FOXM1 expression in BM-MSCs isolated from MDS and AML patients, as compared to controls.

Vitamin C Deficiency in Patients With Acute Myeloid Leukemia.

Vitamin C has been shown to play a significant role in suppressing progression of leukemia through epigenetic mechanisms. We aimed to study the role of vitamin C in acute myeloid leukemia (AML) biology and clinical course. To this purpose, the plasma levels of vitamin C at diagnosis in 62 patients with AML (including 5 cases with acute promyelocytic leukemia, APL),7 with myelodysplastic syndrome (MDS), and in 15 healthy donors (HDs) were studied.

De Novo and Therapy-Related Myelodysplastic Syndromes: Analogies and Differences.

The aim of our review has been to give an appropriate idea of analogies and differences between primitive MDS (p-MDS) and t-MDS throughout an accurate reviewing of English peer-reviewed literature focusing on clinical, cytogenetic, epigenetic, and somatic mutation features of these two groups of diseases. Therapy-related MDS (t-MDS) are classified by WHO together with therapy-related acute myeloid leukemia (t-AML) in the same group, named therapy-related myeloid neoplasm. However, in clinical practice, the diagnosis of t-MDS is made with the same criteria as for primitive MDS (p-MDS), and the only difference is a previous non-myeloid neoplasm.

The Venetoclax/Azacitidine Combination Targets the Disease Clone in Acute Myeloid Leukemia, Being Effective and Safe in a Patient with COVID-19.

The addition of Venetoclax (VEN) to Hypomethylating agents (HMAs) significantly improves the probability of complete remission and prolongs survival in patients with Acute Myeloid Leukemia (AML) when compared to HMA alone. However, the mutated clone composition may impact the probability of response and its duration. Here, we describe the molecular profile of a patient with AML rapidly evolved from a previous therapy-related-Chronic MyeloMonocytic Leukemia, who achieved safely complete remission after treatment with the VEN/Azacitidine combination, even in the presence of SARS-COVID-2 infection.

Atypical Rearrangements in APL-Like Acute Myeloid Leukemias: Molecular Characterization and Prognosis.

Acute promyelocytic leukemia (APL) accounts for 10-15% of newly diagnosed acute myeloid leukemias (AML) and is typically caused by the fusion of promyelocytic leukemia with retinoic acid receptor α () gene. The prognosis is excellent, thanks to the all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) combination therapy. A small percentage of APLs (around 2%) is caused by atypical transcripts, most of which involve or other members of retinoic acid receptors ( or ).

Variation in Child Serum Cholesterol and Prevalence of Familiar Hypercholesterolemia: The Health Oriented Pedagogical Project (HOPP).

Early stages of atherosclerosis may develop in childhood due to hyperlipidemia. The aims are to investigate the prevalence of familiar hypercholesterolemia in 6 to 12-year-old children and to study the deviation in cholesterol measures. Anthropometric data and venous blood were collected from children participating in the Health Oriented Pedagogical Project (HOPP).

Clonal haematopoiesis as a risk factor for therapy-related myeloid neoplasms in patients with chronic lymphocytic leukaemia treated with chemo-(immuno)therapy.

Clonal haematopoiesis of indeterminate potential (CHIP) may predispose for the development of therapy-related myeloid neoplasms (t-MN). Using target next-generation sequencing (t-NGS) panels and digital droplet polymerase chain reactions (ddPCR), we studied the myeloid gene mutation profiles of patients with chronic lymphocytic leukaemia (CLL) who developed a t-MN after treatment with chemo-(immuno)therapy. Using NGS, we detected a total of 30 pathogenic/likely pathogenic (P/LP) variants in 10 of 13 patients with a t-MN (77%, median number of variants for patient: 2, range 0-6).