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.

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.

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.

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.

Real options analysis for valuation of climate adaptation pathways with application to transit infrastructure.

Climate change and sea-level rise (SLR) are expected to increase the frequency and intensity of coastal flood events, posing risks to coastal communities and infrastructure. While regional climate adaptation investments can provide substantive flood protection, existing plans often neglect uncertainty in future climate conditions and adaptation performance, consequently neglecting the option value of flexibly implementing proposed projects. Addressing this gap, we develop and employ a generalizable real options analysis (ROA) valuation framework that considers how uncertainty in adaptation project costs, SLR, flood severity, and flood losses inform the full range of adaptation performance outcomes.

Supplemented Very Low Protein Diet (sVLPD) in Patients with Advanced Chronic Renal Failure: Clinical and Economic Benefits.

The supplemented very low-protein diet (sVLPD) has proven effective in slowing the progression of stage 5 chronic renal failure and postponing the start of the dialysis treatment. However, sVLPD could expose the patient to the risk of malnutrition. This diet is also difficult to implement due to the required intake of large number of keto-analogue/amino acid tablets.

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).

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.

Droplet digital polymerase chain reaction for the assessment of disease burden in hairy cell leukemia.

BRAF mutation is the pathogenic driver of hairy cell leukemia (HCL) found in the vast majority of cases both at onset and during recurrences. The identification of the mutated allele in blood and marrow correlates with the presence of neoplastic cells and can be considered a marker of active disease. Likewise, the absence of the mutation after treatment may indicate a state of deep response.

Benefits of Sebastiania hispida (Euphorbiaceae) extract and photobiomodulation therapy as potentially adjunctive strategies to be explored against snake envenoming.

The purpose of this study was to assess the topic use of Sebastiania hispida extract and low-level gallium-arsenide laser irradiation (GaAs, 904 nm) to reduce the local myonecrosis and edema of Bothrops moojeni snake venom-injected gastrocnemius. Wistar rats receiving intramuscular venom injection (VBm) were compared with saline control (S) and envenomed rats receiving local exposure to plant extract (VExt) or laser irradiation (VL). The phytochemistry and thin-layer chromatography of S.

Evaluation of remnant cholesterol levels and Monocyte-to-HDL-cholesterol ratio in South Asian patients with acute coronary syndrome.

Background And Aims: In the present study, we aimed to compare the clinical and coronary angiography features between South Asian and Caucasian patients with Acute Coronary Syndrome (ACS). In particular, we focused our analysis on the evaluation of recent cardiovascular risk markers, such as remnant cholesterol, corresponding to all plasma cholesterol minus HDL-C (high-density lipoprotein cholesterol) and LDL-C (low-density lipoprotein cholesterol), and the Monocyte-to-HDL-cholesterol ratio. We also compared values of several lipoprotein ratios and the Platelet-to-lymphocyte ratio, accurate predictors of coronary events and coronary artery disease.

[SARS CoV-2 related disease features in a population of chronic hemodialysis patients].

Patients on chronic dialysis have an increased risk for SARS CoV-2 virus disease and its complications because of multiple comorbidities and alterations in the immune response caused by renal disease. In this retrospective observational study we describe the clinical features and the evolution of SARS CoV-2-related disease in 19 patients of our Pesaro and Fano facilities, where incidence and mortality of the epidemic were among the highest in Italy. A total of 176 patients were undergoing chronic treatment, 153 hemodialysis and 23 peritoneal dialysis.

A real-world efficacy and safety analysis of combined carfilzomib, lenalidomide, and dexamethasone (KRd) in relapsed/refractory multiple myeloma.

Carfilzomib-lenalidomide-dexamethasone (KRd) has been approved for the treatment of relapsed/refractory multiple myeloma (RRMM). We conducted a retrospective analysis of 197 RRMM patients (pts) between January 2016 and March 2018 in six Italian hematologic centers, with the aim to evaluate efficacy and safety of KRd in real-life. At KRd initiation 27% carried high risk cytogenetic abnormalities (HRCA) [del17p and/or t(4;14) and/or t(14;16)], median number of prior lines of therapy was 2 (1-8), nearly all pts (96%) received prior bortezomib (18% refractory) while 45% were exposed to lenalidomide (R; 22% refractory).

Disease-Specific Derangement of Circulating Endocannabinoids and -Acylethanolamines in Myeloproliferative Neoplasms.

Growing evidence highlights the endocannabinoid (EC) system involvement in cancer progression. Lipid mediators of this system are secreted by hematopoietic cells, including the ECs 2-arachidonoyl-glycerol (2AG) and arachidonoyl-ethanolamide (AEA), the 2AG metabolite 1AG, and members of N-acylethanolamine (NAE) family-palmitoyl-ethanolamide (PEA) and oleoyl-ethanolamide (OEA). However, the relevance of the EC system in myeloproliferative neoplasms (MPN) was never investigated.

Next-Generation Sequencing for Clinical Management of Multiple Myeloma: Ready for Prime Time?

Personalized treatment is an attractive strategy that promises increased efficacy with reduced side effects in cancer. The feasibility of such an approach has been greatly boosted by next-generation sequencing (NGS) techniques, which can return detailed information on the genome and on the transcriptome of each patient's tumor, thus highlighting biomarkers of response or druggable targets that may differ from case to case. However, while the number of cancers sequenced is growing exponentially, much fewer cases are amenable to a molecularly-guided treatment outside of clinical trials to date.

Integrative analysis of the genomic and transcriptomic landscape of double-refractory multiple myeloma.

In multiple myeloma, novel treatments with proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs) have prolonged survival but the disease remains incurable. At relapse, next-generation sequencing has shown occasional mutations of drug targets but has failed to identify unifying features that underlie chemotherapy resistance. We studied 42 patients refractory to both PIs and IMiDs.

Minimal Residual Disease Assessment Within the Bone Marrow of Multiple Myeloma: A Review of Caveats, Clinical Significance and Future Perspectives.

There is an increasing clinical interest in the measure and achievement of minimal residual disease (MRD) negativity in the bone marrow of Multiple Myeloma (MM) patients, as defined equally either by Multicolor Flow Cytometry (MFC) or by Next Generation Sequencing (NGS) technologies. At present, modern technologies allow to detect up to one on 104 or on 105 or even on 106 cells, depending on their throughput. MFC approaches, which have been progressively improved up to the so-called Next Generation Flow (NGF), and NGS, which proved clear advantages over ASO-PCR, can detect very low levels of residual disease in the BM.

Relapsed ovarian cancer - diagnosis using 18F-FDG PET/CT; 4.

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize procedures to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Nurses' Perceptions of Engaging With Patients to Reduce Restrictive Practices in an Inpatient Psychiatric Unit.

Despite the evidence of harmful effects of restrictive practices on patients and nurses, restrictive practices are still commonly used in the inpatient psychiatric settings. There has been a paradigm shift of a collaborative approach and implementation of patient engagement to reduce the use of restrictive practices. The purpose of this study was to explore nurses' perceptions of engaging with patients to reduce the use of restrictive practices in an inpatient psychiatric unit.

Multicenter study on parathyroidectomy (PTX) in Italy: preliminary results.

Background: When medical therapy is unable to achieve biochemical control of secondary hyperparathyroidism, parathyroidectomy (PTX) is indicated, fortunately in a minority of patients. Thus, data on PTX prevalence and biochemical control are limited and, in particular in Italy, date back to 1999.

Methods: We designed a prospective, observational and multicenter study to collect data from dialysis units distributed throughout the Italian regions.