Malignant ventricular arrhythmias induction by programmed electrical stimulation of the right ventricular outflow tract only during type 1 brugada ECG maximization

OBJECTIVE: The role of electrophysiology study in Brugada syndrome (BS) sudden cardiac death risk stratification remains controversial and seems to depend on the phenotypic expression of the channelopathy. Ajmaline has a key role in the diagnosis of BS. We observed that programmed electrical stimulation (PES) of the right ventricular outflow tract (RVOT), only when type 1 BS ECG is unmasked by ajmaline administration, induces ventricular arrhythmias. CASE REPORT: We describe a case of ventricular fibrillation induction by PES of the RVOT when type 1 BS ECG is revealed by ajmaline, in a patient with a baseline dynamic intermittent type 1 and 2 BS ECG. CONCLUSIONS: The heterogeneous clinical presentations of BS are due to the underlying mechanisms. PES of the RVOT during positive ajmaline test maximizes the channelopathy and therefore sudden cardiac death risk-stratification in BS

Chapter The coastal lakes of Campi Flegrei: between biodiversity and anthropization

Campi Flegrei (from Greek phlegraios = burning) is a volcanic area north west of Naples, extended from Agnano crater until Cuma. Pozzuoli, Bacoli, Monte di Procida e Quarto, some northern neighboroughs of Naples are included along with Ischia, Procida and Vivara islands. In this area there are three coastal lakes: Fusaro, Miseno, Lucrino. Our study analyses geomorphological, botanical, historicaland anthropic features of their ecosystems

Breastfeeding: a reproductive factor able to reduce the risk of luminal B breast cancer in premenopausal White women

In the medical literature, the role of breastfeeding and reproductive factors in the risk of breast carcinoma is still an open debate in premenopausal women. We highlight the role of breastfeeding and reproductive factors in luminal A and luminal B, the most frequent breast cancers. This case-control study analyzes a White premenopausal population of 286 breast cancer patients, divided into molecular subtypes, and 578 controls matched by age. Multivariate logistic regression models were used to assess the relationships of breastfeeding and other reproductive factors (age at menarche, parity, age at first pregnancy, number of children) with the risk of breast cancers. Among the variables examined, reproductive factors did not alter the risk of cancer, whereas breastfeeding up to 12 months was a significant protective factor against luminal B breast cancer (multivariate odds ratio: 0.22, 95% confidence interval: 0.09-0.59, P=0.002). In contrast, luminal A cases did not significantly correlate with breastfeeding or other reproductive factors. Breastfeeding up to 12 months is strongly protective against the more aggressive luminal B, but not against the less aggressive luminal A breast cancer in premenopausal White women

Current Status of Fibroblast Growth Factor Receptor-Targeted Therapies in Breast Cancer

Breast cancer (BC) is the most common malignancy and second only to lung cancer in terms of mortality in women. Despite the incredible progress made in this field, metastatic breast cancer has a poor prognosis. In an era of personalized medicine, there is an urgent need for better knowledge of the biology leading to the disease, which can lead to the design of increasingly accurate drugs against patients’ specific molecular aberrations. Among one of the actionable targets is the fibroblast growth factor receptor (FGFR) pathway, triggered by specific ligands. The Fibroblast Growth Factor Receptors/Fibroblast Growth Factors (FGFRs/FGFs) axis offers interesting molecular targets to be pursued in clinical development. This mini-review will focus on the current knowledge of FGFR mutations, which lead to tumor formation and summarizes the state-of-the-art therapeutic strategies for targeted treatments against the FGFRs/FGFs axis in the context of BC

Comparison between male and female breast cancer survival using propensity score matching analysis

Male breast cancer (MBC) is a rare disease. The few studies on MBC reported conflicting data regarding survival outcomes compared to women. This study has two objectives: to describe the characteristics of a single-cohort of MBC and to compare overall survival (OS) and disease-free survival (DFS) between men and women using the propensity score matching (PSM) analysis. We considered MBC patients (n = 40) diagnosed between January 2004 and May 2019. Clinical, pathological, oncological and follow-up data were analyzed. Univariate analysis was performed to determine the prognostic factors on OS and DFS for MBC. We selected female patients with BC (n = 2678). To minimize the effect of the imbalance of the prognostic factors between the two cohorts, the PSM method (1:3 ratio) was applied and differences in survival between the two groups were assessed. The average age of MBC patients was 73 years. The 5-year OS and DFS rates were 76.7% and 72.2% respectively. The prognostic factors that significantly influenced OS and DFS were tumor size and lymph node status. After the PSM, 5 year-OS was similar between MBC and FBC (72.9% vs 72.3%, p = 0.70) while we found a worse DFS for MBC (72.2% vs 91.4%, p = 0.03). Our data confirmed previous reported MBC characteristics: we found a higher risk of recurrence in MBC compared to FMC but similar OS. MBC and FMC are different entities and studies are needed to understand its epidemiology and guide its management

A Case–Control Study by ddPCR of ALU 260/111 and LINE-1 266/97 Copy Number Ratio in Circulating Cell-Free DNA in Plasma Revealed LINE-1 266/97 as a Potential Biomarker for Early Breast Cancer Detection

Background: In Western countries, breast cancer (BC) is the most common cancer in women. Early detection has a positive impact on survival, quality of life, and public health costs. Mammography screening programs have increased early detection rates, but new approaches to more personalized surveillance could further improve diagnosis. Circulating cell-free DNA (cfDNA) in blood could provide a potential tool for early diagnosis by analyzing cfDNA quantity, circulating tumor DNA mutations, or cfDNA integrity (cfDI). Methods: Plasma was obtained from the blood of 106 breast cancer patients (cases) and 103 healthy women (controls). Digital droplet PCR was used for the determination of ALU 260/111 bp and LINE-1 266/97 bp copy number ratio and cfDI. cfDNA abundance was calculated using copies of the EEF1A2 gene. The accuracy of biomarker discrimination was analyzed with receiver operating characteristic curve (ROC). Sensitivity analyses were performed to account for age as a potential confounder. Results: Cases had significantly lower ALU 260/111 or LINE-1 266/97 copy number ratios (median; ALU 260/111 = 0.08, LINE-1 266/97 = 0.20), compared with control (median; ALU 260/111 = 0.10, LINE-1 266/97 = 0.28) (p < 0.001). ROC analysis showed that copy number ratio discriminated cases from controls (area under the curve, AUC = 0.69, 95% CI: 0.62–0.76 for ALU and 0.80, 95% CI: 0.73–0.86 for LINE-1). ROC from cfDI confirmed the better diagnostic performance of LINE-1 compared with ALU. Conclusions: Analysis of LINE-1 266/97 copy number ratio or cfDI by ddPCR appears to be a useful noninvasive test that could aid in early BC detection. Further studies in a large cohort are needed to validate the biomarker

Tumour infiltrating lymphocytes and immune-related genes as predictors of outcome in pancreatic adenocarcinoma

Background: We investigated the correlation between pancreatic ductal adenocarcinoma patient progno- sis and the presence of tumour infiltrating lymphocytes and expression of 521 immune sys- tem genes. Methods: Intratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochem- istry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenect- omy. The results were correlated with gene expression profile using the digital multiplexed NanoString nCounter analysis system (NanoString Technologies, Seattle, WA, USA). Results: Twenty immune system genes were significantly differentially expressed in patients with a good prognosis relative to patients with a worse prognosis: TLR2 and TLR7 (Toll-like recep- tor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell develop- ment); TNF, TNFRF1A (TNF superfamily); HCK (leukocyte function); C1QA (complement system); BAX, PNMA1 (apoptosis); IKBKE (NF\u3baB pathway). Differential expression was more than twice log 2 for TLR7, TNF, C1QA, FOXP3, and CD37. Discussion: Tumour infiltrating lymphocytes were present at higher levels in samples from patients with better prognosis. Our findings indicate that tumour infiltrating lymphocyte levels and expres- sion level of the immune system genes listed above influence pancreatic ductal adenocarcinoma prognosis. This information could be used to improve selection of best responders to immune inhibitors

Machine learning applied to ambulatory blood pressure monitoring: a new tool to diagnose autonomic failure?

BACKGROUND: Autonomic failure (AF) complicates Parkinson’s disease (PD) in one-third of cases, resulting in complex blood pressure (BP) abnormalities. While autonomic testing represents the diagnostic gold standard for AF, accessibility to this examination remains limited to a few tertiary referral centers. OBJECTIVE: The present study sought to investigate the accuracy of a machine learning algorithm applied to 24-h ambulatory BP monitoring (ABPM) as a tool to facilitate the diagnosis of AF in patients with PD. METHODS: Consecutive PD patients naïve to vasoactive medications underwent 24 h-ABPM and autonomic testing. The diagnostic accuracy of a Linear Discriminant Analysis (LDA) model exploiting ABPM parameters was compared to autonomic testing (as per a modified version of the Composite Autonomic Symptom Score not including the sudomotor score) in the diagnosis of AF. RESULTS: The study population consisted of n = 80 PD patients (33% female) with a mean age of 64 ± 10 years old and disease duration of 6.2 ± 4 years. The prevalence of AF at the autonomic testing was 36%. The LDA model showed 91.3% accuracy (98.0% specificity, 79.3% sensitivity) in predicting AF, significantly higher than any of the ABPM variables considered individually (hypotensive episodes = 82%; reverse dipping = 79%; awakening hypotension = 74%). CONCLUSION: LDA model based on 24-h ABPM parameters can effectively predict AF, allowing greater accessibility to an accurate and easy to administer test for AF. Potential applications range from systematic AF screening to monitoring and treating blood pressure dysregulation caused by PD and other neurodegenerative disorders

Interval Breast Cancer Versus Screen-Detected Cancer: Comparison of Clinicopathologic Characteristics in a Single-Center Analysis

Interval breast cancers (IBC) have been of great concern since breast mammogram screening programs were introduced. We compared IBC to screen-detected cancers (SDC). IBC accounted for one-fifth of all breast cancers diagnosed in women who followed the regional screening program. IBC appeared to be more aggressive than SDC in terms of tumor invasiveness, size, and St Gallen molecular subtype, leading to worse overall and disease-free survival. Background: The introduction of breast screening programs has raised the problem of interval breast cancers (IBC). The aims of this study were to analyze the impact of IBC on the screening program, to compare IBC and screendetected cancers (SDC), and to identify possible predictors of mortality. Patients and Methods: Patients with breast cancer diagnosed during the regional breast screening program between January 2008 and December 2013 at a single center in Italy were included. Demographic, preoperative, and postoperative data were prospectively collected and retrospectively analyzed. Results: Five hundred thirty-four patients were enrolled; 106 women (19.9%) had IBC and 428 women (80.1%) SDC. IBC presented more aggressive features compared to SDC, such as tumor invasiveness (95% vs. 85%; P \ubc .005), tumor size ( pT2 37% vs. 21%; P \ubc .001), grade (G3 39% vs. 17%; P < .001), and St Gallen molecular subtype (triple negative 22% vs. 7%; P < .001), resulting in higher distant recurrence rate (8% vs. 2%; P \ubc .009) and worse overall and disease-free survival (P \ubc .03 and P \ubc .001, respectively). Cox multivariate regression analysis identified St Gallen molecular subtype as the only predictor of mortality in patients with breast cancer (P \ubc .03). Conclusion: IBC accounted for one-fifth of all breast cancers diagnosed in women who followed the regional screening program. Furthermore, IBC appeared to have more aggressive features compared to SDC, leading to worse survival. These worse survivals depended on St Gallen molecular subtype

Comparative Genomic Profiling of Second Breast Cancers following First Ipsilateral Hormone Receptor-Positive Breast Cancers

Purpose: We compared the mutational profile of second breast cancers (SBC) following first ipislateral hormone receptor-positive breast cancers of patient-matched tumors to distinguish new primaries from true recurrences. Experimental design: Targeted next-generation sequencing using the Oncomine Tumor Mutation Load Assay. Variants were filtered according to their allele frequency ≥ 5%, read count ≥ 5X, and genomic effect and annotation. Whole genome comparative genomic hybridization array (CGH) was also performed to evaluate clonality. Results: Among the 131 eligible patients, 96 paired first breast cancer (FBC) and SBC were successfully sequenced and analyzed. Unshared variants specific to the FBC and SBC were identified in 71.9% and 61.5%, respectively. Paired samples exhibited similar frequency of gene variants, median number of variants per sample, and variant allele frequency of the reported variants except for GATA3. Among the 30 most frequent gene alterations, ARIDIA, NSD2, and SETD2 had statistically significant discordance rates in paired samples. Seventeen paired samples (17.7%) exhibited common variants and were considered true recurrences; these patients had a trend for less favorable survival outcomes. Among the 8 patients with available tissue for CGH analysis and considered new primaries by comparison of the mutation profiles, 4 patients had clonally related tumors. Conclusions: Patient-matched FBC and SBC analysis revealed that only a minority of patients exhibited common gene variants between the first and second tumor. Further analysis using larger cohorts, preferably using single-cell analyses to account for clonality, might better select patients with true recurrences and thereby better inform the decision-making process