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.

Tracking Response and Resistance in Acute Myeloid Leukemia through Single-Cell DNA Sequencing Helps Uncover New Therapeutic Targets.

Acute myeloid leukemia (AML) is an aggressive hematologic neoplasia with a complex polyclonal architecture. Among driver lesions, those involving the gene represent the most frequent mutations identified at diagnosis. The development of tyrosine kinase inhibitors (TKIs) has improved the clinical outcomes of -mutated patients (Pt).

Circulating Multiple Myeloma Cells (CMMCs) as Prognostic and Predictive Markers in Multiple Myeloma and Smouldering MM Patients.

In recent years, liquid biopsy has emerged as a promising alternative to the bone marrow (BM) examination, since it is a minimally invasive technique allowing serial monitoring. Circulating multiple myeloma cells (CMMCs) enumerated using CELLSEARCH were correlated with patients' prognosis and measured under treatment to assess their role in monitoring disease dynamics. Forty-four MM and seven smouldering MM (SMM) patients were studied.

Impact of SARS-CoV-2 Pandemic on the Diagnosis of Cervical Cancer and Precursor Lesions-A Single-Center Retrospective Study.

: Our aim was to perform a retrospective analysis of the volume of cervical screening tests, the number of patients treated with an excision method, and the incidence of invasive and non-invasive cervical during a pandemic and pre-pandemic period of 24 months. : The study compared 404 patients who underwent cervical cone biopsy for cervical cancer. The study examined patients' specimens based on histopathological characteristics and categorized cervical lesions based on pap smear.

Multi-dimensional scaling techniques unveiled gain1q&loss13q co-occurrence in Multiple Myeloma patients with specific genomic, transcriptional and adverse clinical features.

The complexity of Multiple Myeloma (MM) is driven by several genomic aberrations, interacting with disease-related and/or -unrelated factors and conditioning patients' clinical outcome. Patient's prognosis is hardly predictable, as commonly employed MM risk models do not precisely partition high- from low-risk patients, preventing the reliable recognition of early relapsing/refractory patients. By a dimensionality reduction approach, here we dissect the genomic landscape of a large cohort of newly diagnosed MM patients, modelling all the possible interactions between any MM chromosomal alterations.

Maternal and Newborn Characteristics-A Comparison between Healthy and Thrombophilic Pregnancy.

A thrombophilic woman is more likely to experience difficulties during pregnancy, difficulties that will also affect the development of the newborn. This study aims to compare maternal and newborn characteristics between healthy and thrombophilic pregnancy. The following characteristics were analysed: maternal characteristics (BMI- body mass index, haemostasis parameters, thrombophilia-specific treatment) and newborn characteristics (gestational period, birth weight, the Apgar score).

High levels of CRBN isoform lacking IMiDs binding domain predicts for a worse response to IMiDs-based upfront therapy in newly diagnosed myeloma patients.

In recent years, the immunoderivative (IMiD) agents have been extensively used for the treatment of multiple myeloma (MM). IMiDs and their newer derivatives CRBN E3 ligase modulator bind the E3 ligase substrate recognition adapter protein cereblon (CRBN), which has been recognized as one of the IMiDs' direct target proteins, and it is essential for the therapeutic effect of these agents.High expression of CRBN was associated with improved clinical response in patients with MM treated with IMiDs, further confirming that the expression of IMiDs' direct target protein CRBN is required for the anti-MM activity.

Long term follow-up of humoral and cellular response to mRNA-based vaccines for SARS-CoV-2 in patients with active multiple myeloma.

Long-term kinetics of antibody (Ab) and cell-mediated immune (CMI) response to full anti-SARS-CoV-2 vaccine schedule and booster doses in Multiple Myeloma (MM) patients remain unclear. We prospectively evaluated Ab and CMI response to mRNA vaccines in 103 SARS-CoV-2-naïve MM patients (median age 66, 1 median prior line of therapy) and 63 health-workers. Anti-S-RBD IgG (Elecsysassay) were measured before vaccination and after 1 (T1), 3 (T3), 6 (T6), 9 (T9) and 12 (T12) months from second dose (D2) and 1 month after the introduction of the booster dose (T1D3).

Assessment of the Particularities of Thrombophilia in the Management of Pregnant Women in the Western Part of Romania.

: Thrombophilia in pregnant women is a condition whose incidence is constantly increasing worldwide, and, under these conditions, the development of preventive procedures is becoming essential. In this study, we aimed to evaluate thrombophilia in pregnant women in the western part of Romania and to establish anthropometric characteristics, socioeconomic features, and genetic and risk factors. : 178 pregnant women were divided into three study groups, according to the type of thrombophilia, aiming to carry out the genetic profile and the acquired one.

Identification of a Maturation Plasma Cell Index through a Highly Sensitive Droplet Digital PCR Assay Gene Expression Signature Validation in Newly Diagnosed Multiple Myeloma Patients.

DNA microarrays and RNA-based sequencing approaches are considered important discovery tools in clinical medicine. However, cross-platform reproducibility studies undertaken so far have highlighted that microarrays are not able to accurately measure gene expression, particularly when they are expressed at low levels. Here, we consider the employment of a digital PCR assay (ddPCR) to validate a gene signature previously identified by gene expression profile.

The : How to define the hemodilution of bone marrow samples in lymphoproliferative diseases.

Introduction: Minimal residual disease (MRD) is commonly assessed in bone marrow (BM) aspirate. However, sample quality can impair the MRD measurement, leading to underestimated residual cells and to false negative results. To define a reliable and reproducible method for the assessment of BM hemodilution, several flow cytometry (FC) strategies for hemodilution evaluation have been compared.

: A copy number clustering tool designed to refit and recalibrate the baseline region of tumors' profiles.

Human cancer arises from a population of cells that have acquired a wide range of genetic alterations, most of which are targets of therapeutic treatments or are used as prognostic factors for patient's risk stratification. Among these, copy number alterations (CNAs) are quite frequent. Currently, several molecular biology technologies, such as microarrays, NGS and single-cell approaches are used to define the genomic profile of tumor samples.

Clonal and subclonal TP53 molecular impairment is associated with prognosis and progression in multiple myeloma.

Aberrations on TP53, either as deletions of chromosome 17p (del17p) or mutations, are associated with poor outcome in multiple myeloma (MM), but conventional detection methods currently in use underestimate their incidence, hindering an optimal risk assessment and prognostication of MM patients. We have investigated the altered status of TP53 gene by SNPs array and sequencing techniques in a homogenous cohort of 143 newly diagnosed MM patients, evaluated both at diagnosis and at first relapse: single-hit on TP53 gene, either deletion or mutation, detected both at clonal and sub-clonal level, had a minor effect on outcomes. Conversely, the coexistence of both TP53 deletion and mutation, which defined the so-called double-hit patients, was associated with the worst clinical outcome (PFS: HR 3.

Evaluation of the Relapse Risk and Survival Rate in Patients with Hodgkin Lymphoma: A Monocentric Experience.

Hodgkin lymphoma (HL) is characterized by the presence of malignant Reed Sternberg cells. Although the current curability rate in patients with HL has increased, up to 30% of those in the advanced stages and 5% to 10% of those in limited stages of the disease, relapse. According to the studies, the relapse risk in HL decreases after 2 years.

Liver Impairment and Hematological Changes in Patients with Chronic Hepatitis C and COVID-19: A Retrospective Study after One Year of Pandemic.

: The COVID-19 pandemic is an ongoing public health emergency. Patients with chronic diseases are at greater risk for complications and poor outcomes. The objective of this study was to investigate the liver function abnormalities and clinical outcomes in patients with COVID-19 and chronic hepatitis C.

High Carbohydrate Diet Is Associated with Severe Clinical Indicators, but Not with Nutrition Knowledge Score in Patients with Multiple Myeloma.

Although the survival rate of patients diagnosed with multiple myeloma has doubled over the last few decades, due to the introduction of new therapeutic lines and improvement of care, other potential contributors to the therapeutic response/relapse of disease, such as nutrient intake, along with nutrition knowledge, have not been assessed during the course of the disease. The purpose of this research was to assess nutrition knowledge and diet quality in a group of patients with a diagnosis of multiple myeloma. Anthropometric, clinical and biological assessments and skeletal survey evaluations, along with the assessment of nutritional intake and general nutrition knowledge, were performed on 61 patients with a current diagnosis of multiple myeloma.

Targeting the Endothelin-1 Receptors Curtails Tumor Growth and Angiogenesis in Multiple Myeloma.

The endothelin-1 (ET-1) receptors were recently found to mediate pro-survival functions in multiple myeloma (MM) cells in response to autocrine ET-1. This study investigated the effectiveness of macitentan, a dual ET-1 receptor antagonist, in MM treatment, and the mechanisms underlying its activities. Macitentan affected significantly MM cell (RPMI-8226, U266, KMS-12-PE) survival and pro-angiogenic cytokine release by down-modulating ET-1-activated MAPK/ERK and HIF-1α pathways, respectively.

Opposite activation of the Hedgehog pathway in CD138+ plasma cells and CD138-CD19+ B cells identifies two subgroups of patients with multiple myeloma and different prognosis.

Hyperactivation of the Hedgehog (Hh) pathway, which controls refueling of multiple myeloma (MM) clones, might be critical to disease recurrence. Although several studies suggest the Hh pathway is activated in CD138- immature cells, differentiated CD138+ plasma cells might also be able to self-renew by producing themselves the Hh ligands. We studied the gene expression profiles of 126 newly diagnosed MM patients analyzed in both the CD138+ plasma cell fraction and CD138-CD19+ B-cell compartment.