Pathological and genomic features of myeloproliferative neoplasms associated with splanchnic vein thrombosis in a single-center cohort.

Here, we reviewed clinical-morphological data and investigated mutational profiles by NGS in a single-center series of 58 consecutive MPN-SVT patients admitted to our hospital between January 1979 and November 2021. We identified 15.5% of PV, 13.

Early Antibody Dynamics in a Prospective Cohort of Children At Risk of Celiac Disease.

Introduction: The purpose of this study was to identify possible serum biomarkers predicting celiac disease (CD) onset in children at risk.

Methods: A subgroup from an ongoing, international prospective study of children at risk of CD was classified according to an early trajectory of deamidated gliadin peptides (DGPs) immunoglobulin (Ig) G and clinical outcomes (CD, potential CD, and CD autoimmunity).

Results: Thirty-eight of 325 children developed anti-tissue transglutaminase IgA antibody (anti-tTG IgA) seroconversion.

Effects of Physiological and Pathological Urea Concentrations on Human Microvascular Endothelial Cells.

Urea is the uremic toxin accumulating with the highest concentration in the plasma of chronic kidney disease (CKD) patients, not being completely cleared by dialysis. Urea accumulation is reported to exert direct and indirect side effects on the gastrointestinal tract, kidneys, adipocytes, and cardiovascular system (CVS), although its pathogenicity is still questioned since studies evaluating its side effects lack homogeneity. Here, we investigated the effects of physiological and pathological urea concentrations on a human endothelial cell line from the microcirculation (Human Microvascular Endothelial Cells-1, HMEC-1).

Single-Cell RNA Sequencing for the Detection of Clonotypic V(D)J Rearrangements in Multiple Myeloma.

Multiple myeloma (MM) has a highly heterogeneous genetic background, which complicates its molecular tracking over time. Nevertheless, each MM patient's malignant plasma cells (PCs) share unique V(D)J rearranged sequences at immunoglobulin loci, which represent ideal disease biomarkers. Because the tumor-specific V(D)J sequence is highly expressed in bulk RNA in MM patients, we wondered whether it can be identified by single-cell RNA sequencing (scRNA-seq).

Nuclear Biophysical Changes during Human Melanoma Plasticity.

Tumor plasticity is an emerging property of tumor cells which allows them to change their phenotype in dependence on the environment. The epithelial-mesenchymal transition plays a crucial role in helping cells acquire a more aggressive phenotype when they are in the mesenchymal state. Herein, we investigated the biophysical changes occurring during phenotypic switching in human melanoma cells, considering the blebbiness of the nuclei, their stiffness, and the involvement of polycombs with lamins.

FLIM-FRET Investigation of Heterogeneous Huntingtin Aggregation in HeLa Cells.

Fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer (FLIM-FRET) technique is a novel tool to study protein-protein interaction combining FRET detection, lifetime measurements, and high-resolution imaging. This chapter describes a FLIM-FRET protocol for the detection and quantification of heterogeneous huntingtin aggregates in HeLa cells co-transfected with huntingtin variants containing polyglutamine tracts of different lengths.

Effects of the uremic toxin indoxyl sulphate on human microvascular endothelial cells.

Indoxyl sulphate (IS) is a uremic toxin accumulating in the plasma of chronic kidney disease (CKD) patients. IS accumulation induces side effects in the kidneys, bones and cardiovascular system. Most studies assessed IS effects on cell lines by testing higher concentrations than those measured in CKD patients.

MGUS and clonal hematopoiesis show unrelated clinical and biological trajectories in an older population cohort.

Monoclonal gammopathy of undetermined significance (MGUS) and clonal hematopoiesis (CH) are 2 preclinical clonal expansions of hematopoietic cells whose prevalence rises with age, reaching almost 10% in people of aged 70 years and older. The increased risk of myeloid malignancies in patients with myeloma is well defined, and the study of the association between CH and MGUS could help explain this phenomenon. Here, we analyzed a fully clinically annotated dataset of 777 older subjects (median age, 91 years) previously screened for prevalence of CH.

Metabolic Bone Disease in Children with Intestinal Failure and Long-Term Parenteral Nutrition: A Systematic Review.

Metabolic bone disease (MBD) is a possible complication of intestinal failure (IF), with a multi-factorial pathogenesis. The reduction of bone density (BMD) may be radiologically evident before manifestation of clinical signs (bone pain, vertebral compression, and fractures). Diagnosis relies on dual-energy X-ray absorptiometry (DXA).

The Dynamics of Nucleotide Variants in the Progression from Low-Intermediate Myeloma Precursor Conditions to Multiple Myeloma: Studying Serial Samples with a Targeted Sequencing Approach.

Multiple myeloma (MM), or Kahler's disease, is an incurable plasma cell (PC) cancer in the bone marrow (BM). This malignancy is preceded by one or more asymptomatic precursor conditions, monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering multiple myeloma (SMM). The molecular mechanisms and exact cause of this progression are still not completely understood.

Transcriptomic Analysis in Multiple Myeloma and Primary Plasma Cell Leukemia with t(11;14) Reveals Different Expression Patterns with Biological Implications in Venetoclax Sensitivity.

Mechanisms underlying the pathophysiology of primary Plasma Cell Leukemia (pPCL) and intramedullary multiple myeloma (MM) need to be further elucidated, being potentially relevant for improving therapeutic approaches. In such a context, the MM and pPCL subgroups characterized by t(11;14) deserve a focused investigation, as the presence of the translocation is mainly associated with sensitivity to venetoclax. Herein, we investigated a proprietary cohort of MM and pPCL patients, focusing on the transcriptional signature of samples carrying t(11;14), whose incidence increases in pPCL in association with an unfavorable outcome.

Functional Impact of Genomic Complexity on the Transcriptome of Multiple Myeloma.

Purpose: Multiple myeloma is a biologically heterogenous plasma-cell disorder. In this study, we aimed at dissecting the functional impact on transcriptome of gene mutations, copy-number abnormalities (CNA), and chromosomal rearrangements (CR). Moreover, we applied a geno-transcriptomic approach to identify specific biomarkers for personalized treatments.

Genomics of Smoldering Multiple Myeloma: Time for Clinical Translation of Findings?

Smoldering multiple myeloma (SMM) is an asymptomatic disorder of clonal bone marrow (BM) plasma cells (PCs) in between the premalignant condition known as monoclonal gammopathy of undetermined significance and overt multiple myeloma (MM). It is characterized by a deep biological heterogeneity that is reflected in a markedly variable progression risk among patients. Recently proposed risk stratification models mainly rely on indirect markers of disease burden and are unable to identify cases in whom clonal PCs have already undergone the "malignant switch" but major clonal expansion has not occurred yet.

Synergistic effects of contaminants in Lombardy waters.

Quantifying synergistic environmental effects in water contamination is still an open issue. Here, we have analyzed geolocalized data of pollutants recorded in 2018 in surface and groundwater of Lombardy, one of the areas with the highest agricultural production rates, not only in Italy, but also in Europe. Both herbicides and insecticides are present at concentration levels above the legal limit, mainly in surface waters.

Optical Coherence Tomography Angiography Findings After Intravitreal Ranibizumab in Patients With Coats Disease.

The aim of this retrospective study was to describe the vascular features in eyes with Coats disease, using optical coherence tomography angiography (OCTA), at baseline and after 3 monthly intravitreal injections of ranibizumab. Fifteen eyes of 15 consecutive patients affected by Coats' disease were recruited in this study. All patients underwent the best-corrected visual acuity (BCVA) evaluation, fundus examination, fluorescein angiography (FA), indocyanine green angiography (ICGA), multicolor imaging, structural Spectral Domain (SD)-OCT and OCTA at baseline and 1 month after the third monthly ranibizumab injection (loading phase).

Cost comparison of extracorporeal photopheresis technologies at the European Institute of Oncology.

Background: Stem Cell Mobilization and Collection Unit at Istituto Europeo di Oncologia (IEO; Milan, Lombardia) provides extracorporeal photopheresis (ECP) therapy to treat graft-vs-host disease (GvHD) using offline procedures. ECP can be administered via an integrated single device (online procedure). Total cost of performing ECP at IEO vs an integrated device was assessed using a micro-costing approach.

Time to first treatment and P53 dysfunction in chronic lymphocytic leukaemia: results of the O-CLL1 study in early stage patients.

Chronic lymphocytic leukaemia (CLL) is characterised by a heterogeneous clinical course. Such heterogeneity is associated with a number of markers, including TP53 gene inactivation. While TP53 gene alterations determine resistance to chemotherapy, it is not clear whether they can influence early disease progression.

MicroRNA-222 Regulates Melanoma Plasticity.

Melanoma is one of the most aggressive and highly resistant tumors. Cell plasticity in melanoma is one of the main culprits behind its metastatic capabilities. The detailed molecular mechanisms controlling melanoma plasticity are still not completely understood.