Analisi delle mutazioni dei geni di suscettibilità del cancro della mammella in una coorte di pazienti "triple negative" non selezionate per storia familiare e valutazione dell' outcome.

Negli ultimi anni sono stati identificati e studiati numerosi geni responsabili della trasmissione ereditaria del tumore della mammella, in particolare BRCA1 e BRCA2 per i quali oggi si conoscono diverse mutazioni germinali patogenetiche note; ci sono, poi, numerosi altri geni ancora in fase di studio (ad esempio BARD1, PALB2, BRIP1, CDH1, PTEN, CHEK2 e TP53) che mostrano delle implicazioni sempre più concrete in relazione alla patologia in questione, nonostante ad oggi mutazioni di questi non rappresentino ancora un fattore di rischio certo e concreto per lo sviluppo del cancro della mammella (si parla, al momento, solo di “geni predetti patogenetici”). La conoscenza di questi e delle loro implicazioni risulta di grande importanza soprattutto nell’ approccio ai tumori mammari “tripli negativi”, dotati di caratteristiche solitamente aggressive e per i quali sussiste la necessità di individuare un trattamento terapeutico specifico, efficace ed adeguato. In questo elaborato è presente una revisione della letteratura sull’ argomento e vengono illustrati i risultati di un’ analisi retrospettiva che ha indagato il possibile ruolo delle mutazioni di molti geni di suscettibilità del tumore della mammella, in un gruppo di pazienti “triple negative” non selezionate per storia familiare, mediante la valutazione del loro andamento clinico

Distribution of different HBV DNA forms in plasma and peripheral blood mononuclear cells (PBMCs) of chronically infected patients with low or undetectable HBV plasma viremia

Few studies have documented hepatitis B virus (HBV) DNA in peripheral blood mononuclear cells (PBMCs). We developed real-time PCR methods for differential amplification of covalently closed circular (cccDNA) and total HBV DNA (tDNA). The different distribution of cccDNA and tDNA in plasma and PBMCs was evaluated in 37 patients with low or undetectable viremia. Plasma tDNA measured by the Abbott reference system and the in-house assay correlated well (Spearman rho = 0.804; P<0.0001). tDNA was detected in four PBMC samples, all from patients with detectable plasma viremia (range 633-6,406 IU/ml), cccDNA was not detected in any sample. The reasons for apparently discrepant results need further investigation but possibly include the high diversification of HBV status and plasma viremia levels

PreImplantation Factor immunohistochemical expression correlates with prostate cancer aggressiveness

Background: The PreImplantation Factor (PIF)—a peptide secreted by viable embryos—exerts autotrophic protective effects, promotes endometrial receptivity and controls trophoblast invasion. Synthetic PIF (sPIF) has both immune-protective and regenerative properties, and reduces oxidative stress and protein misfolding. PIF is detected by immunohistochemistry (IHC) in hyperplastic endometriotic lesions and advanced uterine cancer. sPIF reduces graft-versus-host disease while maintaining a graft-versus-leukemia effect. Methods: PIF detection in prostate cancer was assessed in 50 human prostate samples following radical prostatectomy using tumor-microarray-based IHC correlating PIF immune staining with Gleason score (GS) and cancer aggressiveness. Results: PIF was detected in moderate-to-high risk prostate cancer (GS 4+3 and beyond, prognostic groups 3 to 5). In prostate cancer (GS (WHO Grade Group (GG)5), PIF was detected in 50% of cases; in prostate cancer (GS 4+4 GG4), PIF was observed in 62.5% of cases; in prostate cancer (GS 4+3 GG3), PIF immunostaining was observed in 57.1% of cases. In prostate cancer, (GS 3+4 GG2) and (GS 3+3 GG1) cases where PIF staining was negative to weak, membranous staining was observed in 20% of cases (staining pattern considered negative). High-grade prostate intraepithelial neoplasia PIF positive stain in 28.57% of cases (6 of 21) was observed. In contrast, PIF was not detected in normal prostate glands. Importantly, sPIF added to the PC3 cell line alone or combined with prostate cancer fibroblast feeder-cells did not affect proliferation. Only when peripheral blood mononuclear cells were added to the culture, a minor increase in cell proliferation was noted, reflecting local proliferation control. Conclusions: Collectively, PIF assessment could be a valuable, simple-to-use immunohistochemical biomarker to evaluate aggressiveness/prognosis in specimens from prostate cancer patients

Inherited mutations in breast cancer susceptibility genes among a triple negative breast cancer color unselected for family history of breast cancer

Abstract not availabl

MicroRNAs as a Potential New Preventive Approach in the Transition from Asymptomatic to Symptomatic Multiple Myeloma Disease

Multiple myeloma (MM) is a hematological malignancy characterised by proliferation of clonal plasma cells (PCs) within the bonemarrow (BM). Myelomagenesis is a multi-step process which goes from an asymptomatic phase, defined as monoclonal gammopathy of undetermined significance (MGUS), to a smouldering myeloma (SMM) stage, to a final active MM disease, characterised by hypercalcemia, renal failure, bone lesions anemia, and higher risk of infections. Overall, microRNAs (miRNAs) have shown to significantly impact onMMtumorigenesis, as a result of miRNA-dependent modulation of genes involved in pathways known to be crucial for MM pathogenesis and disease progression. We aim to revise the literature related to the role of miRNAs as potential diagnostic and prognostic biomarkers, thus highlighting their key role as novel players within the field of MM and related premalignant conditions

B cell response after SARS-CoV-2 mRNA vaccination in people living with HIV

Background: Limited longitudinal data are available on immune response to mRNA SARS-CoV-2 vaccination in people living with HIV (PLWHIV); therefore, new evidence on induction and persistence of spike-specific antibodies and B cells is needed. Methods: In this pilot study we investigated the spike-specific humoral and B cell responses up to six months after vaccination with two doses of mRNA vaccines in 84 PLWHIV under antiretroviral therapy compared to 79 healthy controls (HCs). Results: Spike-specific IgG persisted six months in PLWHIV with no significant differences compared to HCs, even though a significantly lower IgG response was observed in patients with CD4+ T cells < 350/mmc. The frequency of subjects with antibodies capable of inhibiting ACE2/RBD binding was comparable between PLWHIV and HCs a month after the second vaccine dose, then a higher drop was observed in PLWHIV. A comparable percentage of spike-specific memory B cells was observed at month six in PLWHIV and HCs. However, PLWHIV showed a higher frequency of spike-specific IgD- CD27- double-negative memory B cells and a significantly lower rate of IgD- CD27+ Ig-switched memory B cells compared to HCs, suggesting a reduced functionality of the antigen-specific memory B population. Conclusions: The mRNA vaccination against SARS-CoV-2 elicits humoral and B cell responses quantitatively similar between PLWHIV and HCs, but there are important differences in terms of antibody functionality and phenotypes of memory B cells, reinforcing the notion that tailored vaccination policies should be considered for these patients

Outcomes and Predictors of Mortality in Patients With KPC-Kp Infections Treated With Meropenem Vaborbactam: An Observational Multicenter Study

Background Meropenem-vaborbactam is a recent and promising option for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections, including those resistant to ceftazidime-avibactam.Methods We conducted a retrospective analysis of observational data from 19 Italian hospitals on use and outcomes of patients treated with meropenem-vaborbactam for at least >= 24 hours for KPC-Kp infections. Crude and propensity-weighted multiple Cox regression models were performed to ascertain risk factors independently associated with 30-day mortality.Results The cohort included 342 adults with bloodstream infections (n = 172) and nonbacteremic infections (n = 170), of which 107 were lower respiratory tract infections, 30 were complicated urinary tract infections, and 33 were infections involving other sites. Most infections (62.3%) were managed with meropenem-vaborbactam monotherapy, or in combination with at least 1 other active drug (usually fosfomycin, tigecycline, or gentamicin) (37.7%). The 30-day mortality rate was 31.6% (108/342). In multiple Cox regression model, 30-day mortality was independently associated with septic shock at infection onset, Charlson comorbidity index >= 3, dialysis, concomitant COVID-19, and INCREMENT score >= 8. Administration of meropenem-vaborbactam within 48 hours from infection onset was a negative predictor of mortality. All predictors, except administration of meropenem-vaborbactam within 48 hours, remained significant when the multiple Cox regression model was repeated after adjustment for the propensity score for receipt of combination therapy.Conclusions Despite the limits of a retrospective study, the data derived from this multicenter cohort provide additional evidence on the efficacy of meropenem-vaborbactam in treating severe KPC-Kp infections, even when used as monotherapy

COVID-19 in Infants Less than 3 Months: Severe or Not Severe Disease?

Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores are reported in the literature