Modification of metabolic syndrome parameters following the administration of polyglucosamine L112: results of a subgroup analysis of subjects enrolled in a double blind randomised placebo controlled clinical investigation.

Background: Up to now, scientific literature has not reported studies evaluating the efficacy of polyglucosamine L112 on body weight, insulin resistance, and cholesterol levels in patients with metabolic syndrome, despite its known antioxidant properties and potential to reduce these parameters, making it a promising candidate for treating metabolic syndrome.

Objective: The aim of this study was to examine the activity of L112 in a subgroup of cases suffering from metabolic syndrome (MS).

Methods: A subgroup of 26 subjects (8 males and 18 females; age 55 ± 11.

Mesenchymal stromal cells from myeloproliferative neoplasms support healthy and malignant hematopoiesis in a humanized scaffold model in vivo.

Myeloproliferative Neoplasms (MPN) are malignancies of hematopoietic stem and progenitor cells (HSPCs) that lead to the overproduction of mature blood cells. These disorders include Essential Thrombocythemia (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (PMF), primarily driven by somatic mutations such as . Research indicates that mesenchymal stromal cells (MSCs) support fibrosis in PMF, though their role in ET and PV remains less clear.

Synthetic Data Generated by Artificial Intelligence to Optimize Surgical Trial Design.

Objective: This study aimed to assess artificial intelligence (AI)-based synthetic data (SD) generation technology in surgery, evaluating the accuracy of the generated data and comparing the derived outcomes with real-world data.

Summary Background Data: Trials evaluating new surgical techniques face numerous challenges. SD can play a pivotal role in optimizing clinical trial design but must be used alongside real-world data to ensure accuracy.

Phase 1 first-in-human dose-expansion study of the oral SF3B1 modulator H3B‑8800 in lower-risk myelodysplastic syndrome.

Objective: To assess the efficacy and safety of H3B-8800 at two dose regimens in patients with transfusion-dependent lower-risk myelodysplastic neoplasms (LR-MDS) with somatic SF3B1 mutations.

Methods: In this Phase 1 multicenter study, adults with LR-MDS with SF3B1 mutations were enrolled in two expansion cohorts: 10 mg and 5 mg twice a day (BID). Patients were red blood cell (RBC) transfusion-dependent, defined as ≥ 4 RBC units in 8 weeks in cohort 1 and ≥ 3 RBC units in ≥ 2 transfusions in 16 weeks in cohort 2 (patients naïve to hypomethylating agents and lenalidomide).

IPSS-M risk and specific sex-associated somatic mutations predict response to ESA therapy in LR-MDS: building a new score.

Acquired somatic mutations are incorporated in the classification and prognosis of myelodysplastic syndromes/neoplasms (MDS). However, the predictive role of molecular features in MDS need to be elucidated, especially in the lower-risk subtypes (LR-MDS), where treatment has become more heterogenous, and specific predictive biomarkers are lacking. In this study we investigated genetic markers associated with erythropoiesis stimulating agent (ESA) response in LR-MDS.

Long-Term Transfusion Independence with Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent-Naive, Lower-Risk Myelodysplastic Syndromes in the COMMANDS Trial.

Introduction: The efficacy of erythropoiesis-stimulating agents (ESAs) for transfusion-dependent (TD) anemia in lower-risk myelodysplastic syndromes (LR-MDS) is limited. Luspatercept achieved significantly greater rates of red blood cell (RBC) transfusion independence (TI) versus epoetin alfa (an ESA) in the phase 3 COMMANDS trial. This analysis assessed long-term RBC-TI, cumulative response, and safety with luspatercept in COMMANDS.

Unmet Needs and Their Impact on Quality of Life and Symptoms in Myelodysplastic Neoplasm Patients and Caregivers.

Background/objectives: The aim of this study was to assess the unmet needs of myelodysplastic neoplasm (MDS) patients and their caregivers, focusing on how these needs impact quality of life (QoL) and daily functioning. MDS predominantly affects older adults. It is often complicated by severe red blood cell transfusion-dependent anemia and may require frequent hospital visits, conferring a substantial burden on patients and caregivers.

Characterization and Clinical Implications of p53 Dysfunction in Patients With Myelodysplastic Syndromes.

Purpose: Tumor Protein 53 (p53) expressed from gene is a seminal tumor suppressor. We aimed to characterize mutational and nonmutational mechanisms of p53 dysfunction in myelodysplastic syndromes (MDS) and to investigate their clinical effect.

Patients And Methods: We analyzed a cohort of 6,204 patients with MDS and subsets of patients with available information on RNA sequencing of tumor cells (n = 109), high-dimensional phenotype of immune cells (n = 77), and multiomics analysis (RNA sequencing and proteomics) on single cells (n = 15).

Natural killer cells' functional impairment drives the immune escape of pre-malignant clones in early-stage myelodysplastic syndromes.

Dissecting the preneoplastic disease states' biological mechanisms that precede tumorigenesis can lead to interventions that can slow down disease progression and/or mitigate disease-related comorbidities. Myelodysplastic syndromes (MDS) cannot be cured by currently available pharmacological therapies, which fail to eradicate aberrant hematopoietic stem cells (HSCs), most of which are mutated by the time of diagnosis. Here, we sought to elucidate how MDS HSCs evade immune surveillance and expand in patients with clonal cytopenias of undetermined significance (CCUS), the pre-malignant stage of MDS.

Reducing clinical trial eligibility barriers for patients with MDS: an icMDS position statement.

Excessively restrictive inclusion and exclusion criteria in clinical trials are one of many barriers to clinical trial enrollment for patients with myelodysplastic syndromes/neoplasms (MDSs). Many organizations are developing efforts to increase clinical trial eligibility; yet, several recent publications focused on patients with MDS suggest that many patients with this disease may be excluded from clinical trials unnecessarily. Clinical trial eligibility should reflect the phase of the study and risks of the agent being studied.

Standardization of Bone Marrow Reporting for Myelodysplastic Syndromes/Neoplasms on Behalf of the International Consortium for Myelodysplastic Syndromes/Neoplasms.

Context.—: Standardized bone marrow reporting specifically for myelodysplastic syndromes/neoplasms (MDS) is currently lacking in the literature and much needed in practice.

Objective.

Safety run-in and part 1 of GIMEMA AML1718: venetoclax combined with FLAI as induction treatment in non-low-risk AML.

The standard induction treatment for acute myeloid leukemia (AML) has limited efficacy for patients with non-low-risk AML. We conducted a multicenter study phase 1b/2, Gruppo Italiano Malattie EMatologiche dell'Adulto AML1718, to investigate the safety and efficacy of venetoclax (VEN) combined with fludarabine, cytarabine, and idarubicin (V-FLAI) as an induction therapy for patients with non-low-risk AML aged <65 years and at intermediate or high European LeukemiaNet risk. After a safety run-in, patients were randomly allocated to VEN 400 mg or VEN 600 mg cohorts.

Iron trapping in macrophages reshapes the homeostasis of the haematopoietic system.

Iron is required for key physiological processes, like oxygen transport, energy production and cell proliferation. Body iron homeostasis is regulated by the erythroferrone-hepcidin-ferroportin (FPN) axis, which mainly acts on absorptive duodenal cells and macrophages involved in iron recycling from red blood cell breakdown. In addition to systemic iron regulation, macrophages are also involved in local iron release to neighbouring cells.

Clinical-genomic profiling of MDS to inform allo-HCT: recommendations from an international panel on behalf of the EBMT.

For patients with myelodysplastic neoplasm/syndrome (MDS), allogeneic hematopoietic cell transplantation (allo-HCT) represents the only potentially curative treatment, capable of eradicating disease-related mutant hematopoietic cells and establishing normal donor hematopoiesis. Biologic-assignment clinical trials have indicated that in eligible patients, allo-HCT is associated with superior clinical outcomes compared with nontransplant therapy. However, this therapeutic option is only available to a subset of patients, and the outcome is influenced by multiple factors inherent to the patient, the MDS subtype, and the allo-HCT procedure itself.

Response to luspatercept can be predicted and improves overall survival in the real-life treatment of LR-MDS.

We explored the impact of luspatercept therapy on overall survival (OS) and possible predictors of response in low-risk (LR) myelodysplastic syndrome (MDS) patients. We evaluated 331 anemic patients treated with luspatercept. Hematological response (HI) was defined as (i) hemoglobin (Hb) increase of ≥1.

VAE-Surv: A novel approach for genetic-based clustering and prognosis prediction in myelodysplastic syndromes.

Background And Objectives: Several computational pipelines for biomedical data have been proposed to stratify patients and to predict their prognosis through survival analysis. However, these analyses are usually performed independently, without integrating the information derived from each of them. Clustering of survival data is an underexplored problem, and current approaches are limited for biomedical applications, whose data are usually heterogeneous and multimodal, with poor scalability for high-dimensionality.

Emerging Signatures of Hematological Malignancies from Gene Expression and Transcription Factor-Gene Regulations.

Hematological malignancies are a diverse group of cancers developing in the peripheral blood, the bone marrow or the lymphatic system. Due to their heterogeneity, the identification of novel and advanced molecular signatures is essential for enhancing their characterization and facilitate its translation to new pharmaceutical solutions and eventually to clinical applications. In this study, we collected publicly available microarray data for more than five thousand subjects, across thirteen hematological malignancies.

Translational Research on Azacitidine Post-Remission Therapy of Acute Myeloid Leukemia in Elderly Patients (QOL-ONE Trans-2).

The achievement of complete remission (CR) is crucial for acute myeloid leukemia (AML) patients undertaking curative therapy, but relapse often occurs within months, highlighting the need for strategies to prolong disease-free survival (DFS). Our phase III study compared the efficacy and safety of azacitidine (AZA) to best supportive care (BSC) in elderly AML patients who achieved CR following intensive induction and consolidation therapy. This ancillary study (QOL-ONE Trans-2) evaluated biological changes in bone marrow using Next-Generation Sequencing (NGS).

Digital innovations in breast cancer care: exploring the potential and challenges of digital therapeutics and clinical decision support systems.

Modern healthcare is experiencing a significant transformation, utilizing technology to improve patient outcomes and make processes more efficient. Breast cancer, being the most commonly diagnosed cancer in women globally, requires innovative approaches for effective management. Digital Therapeutics (DTx) and Clinical Decision Support Systems (CDSSs) have emerged as pivotal technologies, offering personalized, patient-centered care and optimizing clinical decision-making.

Future directions in myelodysplastic syndromes/neoplasms and acute myeloid leukaemia classification: from blast counts to biology.

Myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukaemia (AML) are neoplastic haematopoietic cell proliferations that are diagnosed and classified based on a combination of morphological, clinical and genetic features. Specifically, the percentage of myeloblasts in the blood and bone marrow is a key feature that has historically separated MDS from AML and, together with several other morphological parameters, defines distinct disease entities within MDS. Both MDS and AML have recurrent genetic abnormalities that are increasingly influencing their definitions and subclassification.

Magnesium: A Defense Line to Mitigate Inflammation and Oxidative Stress in Adipose Tissue.

Magnesium (Mg) is involved in essential cellular and physiological processes. Globally, inadequate consumption of Mg is widespread among populations, especially those who consume processed foods, and its homeostasis is impaired in obese individuals and type 2 diabetes patients. Since Mg deficiency triggers oxidative stress and chronic inflammation, common features of several frequent chronic non-communicable diseases, interest in this mineral is growing in clinical medicine as well as in biomedicine.