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).

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.

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.

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.

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.

An International Continence Society (ICS)/ International Urogynecological Association (IUGA) joint report on the terminology for the assessment and management of obstetric pelvic floor disorders.

Aims: The terminology of obstetric pelvic floor disorders should be defined and reported as part of a wider clinically oriented consensus.

Methods: This Report combines the input of members of two International Organizations, the International Continence Society (ICS) and the International Urogynecological Association (IUGA). The process was supported by external referees.

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 ).

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).

Outcome reporting in randomized controlled trials (RCTs) on the pharmacological management of idiopathic overactive bladder (OAB) in women; a systematic review for the development of core outcome sets (COS).

Introduction And Hypothesis: Evidence on OAB management remains suboptimal and methodological limitations in randomized control trials (RCTs) affect their comparability. High quality meta-analyses are lacking. This study aimed to compare selection and reporting of outcomes and outcome measures across RCTs as well as evaluate methodological quality and outcome reporting quality as a first stage in the process of developing core outcome sets (COS).

Outcome reporting in trials on conservative interventions for pelvic organ prolapse: A systematic review for the development of a core outcome set.

Background: Significant risk of bias and limitations in outcome selections in trials evaluating conservative treatments for the management of Pelvic Organ Prolapse (POP) have been highlighted and preclude comparability of outcomes, synthesis of primary studies and high quality evidence.

Objectives: As systematic review of the reported outcomes is the first step in the process of development of a Core Outcome Set (COS), we aimed to systematically review reporting of outcomes and outcome measures in Randomised Control Trials (RCTs) on conservative treatments for POP and develop an inventory of them for consideration as core outcome and outcome measures sets. We evaluated methodological quality, outcome reporting quality and publication characteristics and their associations among published RCTs.

Developing Core Outcome Sets (COS) and Core Outcome Measures Sets (COMS) in Cosmetic Gynecological Interventions: Protocol for a Development and Usability Study.

Background: Studies evaluating cosmetic gynecological interventions have followed variable methodology and reported a diversity of outcomes. Such variations limit the comparability of studies and the value of research-based evidence. The development of core outcome sets (COS) and core outcome measures sets (COMS) would help address these issues, ensuring a minimum of outcomes important to all stakeholders, primarily women requesting or having experienced cosmetic gynecological interventions.

A meta-synthesis of qualitative studies on stress urinary incontinence in women for the development of a Core Outcome Set: A systematic review.

Objective: Given the high variation of perceptions of women with stress urinary incontinence (SUI), qualitative meta-synthesis in this field appears warranted. We aimed to synthesize evidence on women's experiences of SUI by analyzing qualitative data.

Methods: A literature search of Medline, Embase, Scopus, PsycInfo, and CINAHL databases was performed by a CHORUS Working Group, from inception to August 2020.

Patient-reported outcomes and outcome measures in childbirth perineal trauma research: a systematic review.

Introduction And Hypothesis: In evaluating the effectiveness of interventions in perineal trauma research, outcomes reported by patients should have a prominent focus. There is no international consensus regarding the use of either patient-reported outcomes (PROs) or tools used to determine these outcomes (patient-reported outcome measures, PROMs). The objective was to evaluate the selection, reporting and geographical variations of PROs and PROMs in randomised controlled trials (RCTs) on perineal trauma.

Mutational profile of ZBTB16-RARA-positive acute myeloid leukemia.

Background: The ZBTB16-RARA fusion gene, resulting from the reciprocal translocation between ZBTB16 on chromosome 11 and RARA genes on chromosome 17 [t(11;17)(q23;q21)], is rarely observed in acute myeloid leukemia (AML), and accounts for about 1% of retinoic acid receptor-α (RARA) rearrangements. AML with this rare translocation shows unusual bone marrow (BM) morphology, with intermediate aspects between acute promyelocytic leukemia (APL) and AML with maturation. Patients may have a high incidence of disseminated intravascular coagulation at diagnosis, are poorly responsive to all-trans retinoic acid (ATRA) and arsenic tryoxyde, and are reported to have an overall poor prognosis.

What's new in the pathogenesis and treatment of therapy-related myeloid neoplasms.

Therapy-related myeloid neoplasms (t-MNs) include diseases onsetting in patients treated with chemo- and/or radiotherapy for a primary cancer, or an autoimmune disorder. Genomic variants, in particular, in familial cancer genes, may play a predisposing role. Recent advances in deep sequencing techniques have shed light on the pathogenesis of t-MNs, identifying clonal hematopoiesis of indeterminate potential (CHIP) as a frequent first step in the multihit model of t-MNs.

Quality assessment of outcome reporting, publication characteristics and overall methodological quality in trials on synthetic mesh procedures for the treatment of pelvic organ prolapse for development of core outcome sets.

Introduction And Hypothesis: Variations in outcome measures and reporting of outcomes in trials on surgery for pelvic organ prolapse (POP) using synthetic mesh have been evaluated and reported. However, the quality of outcome reporting, methodology of trials and their publication parameters are important considerations in the process of development of Core Outcome Sets. We aimed to evaluate these characteristics in randomized controlled trials on surgery for POP using mesh.

From Clonal Hematopoiesis to Therapy-Related Myeloid Neoplasms: The Silent Way of Cancer Progression.

Clonal hematopoiesis (CH) has been recognized as a predisposing factor for the development of myeloid malignancies. Its detection has been reported at different frequencies across studies, based on the type of genome scanning approach used and the population studied, but the latest insights recognize its virtual ubiquitous presence in older individuals. The discovery of CH in recent years paved the way for a shift in the paradigm of our understanding of the biology of therapy-related myeloid malignancies (t-MNs).