Addressing Endothelial Dysfunction in Heart Failure: The Role of Endothelial Progenitor Cells and New Treatment Horizons.

Heart failure (HF) is closely linked to endothelial dysfunction, which contributes significantly to its progression. Endothelial dysfunction in HF is marked by reduced nitric oxide bioavailability, increased oxidative stress and inflammation, all of which impair vascular function. Endothelial progenitor cells (EPCs) - vital for vascular repair - are particularly affected, with their dysfunction further exacerbating HF outcomes.

Case Report: Disseminated leishmaniasis and rheumatoid arthritis: navigating a clinical conundrum.

Background: Leishmaniasis is a potentially life-threatening protozoan infection that presents with many clinical manifestations, including cutaneous, mucocutaneus and visceral forms. In patients with rheumatoid arthritis (RA), cutaneous leishmaniasis can persist or re-emerge due to treatment-induced immunosuppression. However, it remains unclear whether this severe opportunistic infection is primarily driven by medication-induced immunosuppression or other poorly understood immune-mediated mechanisms that increase susceptibility.

How to manage hypersensitivity reactions to enzyme replacement therapy in lysosomal storage diseases?

Lysosomal Storage Diseases (LSDs) encompass a range of genetic disorders characterized by enzyme deficiencies that lead to substrate accumulation and progressive tissue damage. Enzyme Replacement Therapy (ERT) is the primary treatment for LSDs, yet it is often associated with hypersensitivity reactions (HSRs), ranging from mild rashes to severe anaphylaxis. These reactions, frequently driven by anti-drug antibodies, pose significant challenges in treatment adherence and patient outcomes.

Spatial imaging unlocks the potential of charting multiple myeloma and extramedullary disease.

Extramedullary disease (EMD) in multiple myeloma (MM) represents a significant clinical challenge, with a limited understanding of the spatial architecture and its pathobiological impact. To address this unmet need, we examined 10 matched samples from bone marrow (BM) and cognate EMD sites. This investigation provides critical insights into the distinct features of EMD, offering potential avenues for more effective diagnosis and targeted therapies.

Ocular Side Effects of Dupilumab: A Comprehensive Overview of the Literature.

Dupilumab, a monoclonal antibody targeting the interleukin (IL)-4 receptor alpha subunit and IL-13, has markedly advanced the treatment of atopic conditions such as dermatitis, asthma, and chronic rhinosinusitis. However, its expanding use has brought increased attention to a range of ocular adverse events-conjunctivitis, blepharitis, keratitis, corneal ulcers, and cicatricial conjunctivitis-that remain underrecognized and frequently underestimated in clinical practice. These manifestations often emerge in patients with atopic dermatitis and display varying severity, posing diagnostic and therapeutic challenges.

Non-Anticoagulation Strategies Aimed at Primary Stroke Prevention in Nascent Atrial Fibrillation.

At its earliest appearance, atrial fibrillation (AF) is often unnoticed, asymptomatic, and/or merely device-detected. Widespread use of heart-rate monitoring technologies has facilitated such "nascent atrial fibrillation (nAF)" recognition. Consequently, clinicians face a growing number of patients affected by new-onset AF in the absence of a definite indication for anticoagulation due to several counterarguments: (1) a CHADS-VA score ≤ 1 in otherwise apparently healthy subjects; (2) an uncertain embolic/hemorrhagic benefit/risk ratio with anticoagulation; (3) EKG demonstration and confirmation of AF; and (4) existence of a pathogenic mechanism other than atrial hypercoagulability.

Successful rapid desensitization to zoledronic acid in a multiple myeloma patient.

Background: Multiple myeloma (MM) is a malignancy characterized by the proliferation of abnormal plasma cells in the bone marrow, leading to osteolytic lesions. This condition is accompanied by a serum accumulation of monoclonal immunoglobulin. Zoledronic acid (ZA) is a new-generation bisphosphonate commonly used to prevent bone complications.

Aberrant single-cell phenotype and clinical implications of genotypically defined polyclonal plasma cells in myeloma.

Multiple myeloma (MM) is driven by clonal plasma cell (cPC)-intrinsic factors and changes in the tumor microenvironment (TME). To investigate whether residual polyclonal PCs (pPCs) are disrupted, single-cell (sc) RNA sequencing (scRNA-seq) and sc B-cell receptor analysis were applied in a cohort of 46 samples with PC dyscrasias and 21 healthy donors (HDs). Of 234 789 PCs, 64 432 were genotypically identified as pPCs with frequencies decreasing over different disease stages, from 23.

Genomic profiling at a single center cracks the code in inborn errors of immunity.

Inborn errors of immunity (IEI) entail a diverse group of disorders resulting from hereditary or de novo mutations in single genes, leading to immune dysregulation. This study explores the clinical utility of next-generation sequencing (NGS) techniques in diagnosing monogenic immune defects. Eight patients attending the immunodeficiency clinic and with unclassified antibody deficiency were included in the analysis.

Two-year follow-up after drug desensitization in mucopolysaccharidosis.

Background: Mucopolysaccharidosis (MPS) type 1 S and type 2 are rare lysosomal storage disorders characterized by impaired enzyme production, resulting in glycosaminoglycans accumulation within lysosomes. Enzyme Replacement Therapy (ERT) with laronidase and idursulfase are first line treatments, respectively. However, infusion-related hypersensitivity reactions (HR) may lead to ERT discontinuation.

High level of circulating cell-free tumor DNA at diagnosis correlates with disease spreading and defines multiple myeloma patients with poor prognosis.

Multiple myeloma (MM) is a plasma cell (PC) disorder characterized by skeletal involvement at the time of diagnosis. Recently, cell-free DNA (cfDNA) has been proven to recapitulate the heterogeneity of bone marrow (BM) disease. Our aim was to evaluate the prognostic role of cfDNA at diagnosis according to disease distribution, and to investigate the role of the MM microenvironment inflammatory state in supplying the release of cfDNA.

Decoding the Intricate Landscape of Pancreatic Cancer: Insights into Tumor Biology, Microenvironment, and Therapeutic Interventions.

Pancreatic ductal adenocarcinoma (PDAC) presents significant oncological challenges due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) plays a critical role in progression and treatment resistance. Non-neoplastic cells, such as cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), contribute to tumor growth, angiogenesis, and immune evasion.

Comprehensive analysis of clinical outcomes, infectious complications and microbiological data in newly diagnosed multiple myeloma patients: a retrospective observational study of 92 subjects.

Patients with multiple myeloma (MM) have an increased risk of sepsis due to underlying disease- and treatment-related immunosuppression. However, data on sepsis incidence, causative pathogens, and impact on outcomes in newly diagnosed MM (NDMM) are limited. We conducted a retrospective observational study of 92 NDMM patients who developed sepsis between 2022 and 2023 at a tertiary care center in Italy.

Navigating Lymphomas through BCR Signaling and Double-Hit Insights: Overview.

Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of lymphoproliferative disorders originating from B, T, or NK lymphocytes. They represent approximately 4-5% of new cancer cases and are classified according to the revised WHO system based on cell lineage, morphology, immunophenotype, and genetics. Diagnosis requires adequate biopsy material, though integrated approaches are used for leukemic presentations.

A Novel Automatic Algorithm to Support Lung Ultrasound Non-Expert Physicians in Interstitial Pneumonia Evaluation: A Single-Center Study.

Introduction: Lung ultrasound (LUS) is widely used in clinical practice for identifying interstitial lung diseases (ILDs) and assessing their progression. Although high-resolution computed tomography (HRCT) remains the gold standard for evaluating the severity of ILDs, LUS can be performed as a screening method or as a follow-up tool post-HRCT. Minimum training is needed to better identify typical lesions, and the integration of innovative artificial intelligence (AI) automatic algorithms may enhance diagnostic efficiency.

The Complexity of the Tumor Microenvironment in Hepatocellular Carcinoma and Emerging Therapeutic Developments.

This review explores various aspects of the HCC TME, including both cellular and non-cellular components, to elucidate their roles in tumor development and progression. Specifically, it highlights the significance of cancer-associated fibroblasts (CAFs) and their contributions to tumor progression, angiogenesis, immune suppression, and therapeutic resistance. Moreover, this review emphasizes the role of immune cells, such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T-cells (Tregs), in shaping the immunosuppressive microenvironment that promotes tumor growth and immune evasion.

Changes in Lipids in Granulomatosis with Polyangiitis Relates to Glucocorticoids and History of Hypertension.

Granulomatosis with polyangiitis (GPA) is an ANCA-associated small-vessel vasculitis. Vessel wall inflammation induces multiple vascular damages, leading to accelerated atherosclerosis. Metabolic profile and cardiovascular risk are somewhat understood in GPA patients.

Immune disturbance leads to pulmonary embolism in COVID-19 more than classical risk factors: a clinical and histological study.

COVID-19 induces endotheliitis and one of the main complications is enhanced coagulation. The incidence of pulmonary embolism (PE) in COVID-19 (CPE) has increased and clinical features for a rigorous analysis still need to be determined. Thus, we evaluated the clinical characteristics in CPE and the immune infiltration that occurred.

Uptake-Dependent and -Independent Effects of Fibroblasts-Derived Extracellular Vesicles on Bone Marrow Endothelial Cells from Patients with Multiple Myeloma: Therapeutic and Clinical Implications.

Extracellular vesicles (EVs) have emerged as important players in cell-to-cell communication within the bone marrow (BM) of multiple myeloma (MM) patients, where they mediate several tumor-associated processes. Here, we investigate the contribution of fibroblasts-derived EVs (FBEVs) in supporting BM angiogenesis. We demonstrate that FBEVs' cargo contains several angiogenic cytokines (i.

microRNAs as Biomarkers of Endothelial Dysfunction and Therapeutic Target in the Pathogenesis of Atrial Fibrillation.

The pathophysiology of atrial fibrillation (AF) may involve atrial fibrosis/remodeling and dysfunctional endothelial activities. Despite the currently available treatment approaches, the progression of AF, its recurrence rate, and the high mortality risk of related complications underlay the need for more advanced prognostic and therapeutic strategies. There is increasing attention on the molecular mechanisms controlling AF onset and progression points to the complex cell to cell interplay that triggers fibroblasts, immune cells and myofibroblasts, enhancing atrial fibrosis.

Targeting the immune microenvironment in Waldenström macroglobulinemia via halting the CD40/CD40-ligand axis.

Recent investigations have improved our understanding of the molecular aberrations supporting Waldenström macroglobulinemia (WM) biology; however, whether the immune microenvironment contributes to WM pathogenesis remains unanswered. First, we showed how a transgenic murine model of human-like lymphoplasmacytic lymphoma/WM exhibits an increased number of regulatory T cells (Tregs) relative to control mice. These findings were translated into the WM clinical setting, in which the transcriptomic profiling of Tregs derived from patients with WM unveiled a peculiar WM-devoted messenger RNA signature, with significant enrichment for genes related to nuclear factor κB-mediated tumor necrosis factor α signaling, MAPK, and PI3K/AKT, which was paralleled by a different Treg functional phenotype.