Genetic and epigenetic profiling of BRCA1/2 in ovarian tumors reveals additive diagnostic yield and evidence of a genomic BRCA1/2 DNA methylation signature

Poly-ADP-ribose-polymerase inhibitor (PARPi) treatment is indicated for advanced-stage ovarian tumors with BRCA1/2 deficiency. The “BRCAness” status is thought to be attributed to a tumor phenotype associated with a specific epigenomic DNA methylation profile. Here, we examined the diagnostic impact of combined BRCA1/2 sequence, copy number, and promoter DNA methylation analysis, and evaluated whether genomic DNA methylation patterns can predict the BRCAness in ovarian tumors. DNA sequencing of 172 human tissue samples of advanced-stage ovarian adenocarcinoma identified 36 samples with a clinically significant tier 1/2 sequence variants (point mutations and in/dels) and 9 samples with a CNV causing a loss of function in BRCA1/2. DNA methylation analysis of the promoter of BRCA1/2 identified promoter hypermethylation of BRCA1 in two mutation-negative samples. Computational modeling of genome-wide methylation markers, measured using Infinium EPIC arrays, resulted in a total accuracy of 0.75, sensitivity: 0.83, specificity: 0.64, positive predictive value: 0.76, negative predictive value: 0.74, and area under the receiver’s operating curve (AUC): 0.77, in classifying tumors harboring a BRCA1/2 defect from the rest. These findings indicate that the assessment of CNV and promoter DNA methylation in BRCA1/2 increases the cumulative diagnostic yield by 10%, compared with the 20% yield achieved by sequence variant analysis alone. Genomic DNA methylation data can partially predict BRCAness in ovarian tumors; however, further investigation in expanded BRCA1/2 cohorts is needed, and the effect of other double strand DNA repair gene defects in these tumors warrants further investigations

Association of CT-Derived Extracardiac Features and Aortic Annulus Size in Patients Planned for TAVI

Introduction: Transcatheter aortic valve implantation (TAVI) is commonly used to treat patients with stenosed aortic valves. CT is one of the crucial steps in planning TAVI to obtain measurements of the aortic annulus to choose an appropriately sized prosthesis. Incorrect measurements can lead to patient-prosthesis mismatch and other complications. However, some patients cannot undergo ECG-gated CT with radiocontrast because of the presence of radiopaque objects in the thorax, arrhythmia, renal failure, etc. Aim: To explore supplementary methods to improve aortic annulus sizing for TAVI by extracardiac measurements. Methods: We included all patients who underwent CT as part of TAVI planning. Measurements of femoral and iliac arteries and the femoral head cross-sectional area were performed. Results: CT scans of 139 patients were included in this study. Sixty-three patients (45%) were males. Mean age of the female patients was 79.6 ± 7.1 years and of the male patients was 81.3 ± 6.1 years. Mean aortic annulus perimeter among female patients was 74.3 ± 6 mm (range 61.9–88.2) and 83 ± 7.9 mm among male patients (range 70.1–74.3 mm). Mean diameters of common iliac, external iliac, and common femoral arteries were 9.2 ± 1.8, 7.6 ± 1, 7.6 ± 1 mm, respectively, for females and 10.2 ± 1.8, 8.5 ± 1.3, and 8.6 ± 1.4 mm for males. Mean perimeter of the femoral head (average value of right and left femoral heads) among the female patients was 137.8 ± 6.3 mm, and among male patients was 155 ± 9.6 mm. A significant correlation was observed between the perimeter of the aortic annulus and the perimeter of the femoral head (Pearson’s R2 = 0.224). The correlation between the aortic annulus perimeter and the femoral head perimeter was stronger among men than among women (Pearson’s R2 = 0.66 and 0.19, respectively). Conclusion: Femoral head diameter is associated with annulus size. This may help size the appropriate prosthesis in cases where the measurements by CT are in the border zone if corroborated by clinically driven data

Circulating Soluble TREM2 and Cardiovascular Outcome in Cohort Study of Coronary Atherosclerosis Patients

Triggering Receptor Expressed in Myeloid Cells 2 (TREM2) is a membrane receptor in myeloid cells that mediates cellular phagocytosis and inflammation. TREM2 and its soluble extracellular domain are clearly implicated in neuroinflammation and neurodegeneration. sTREM2 is also expressed in atherosclerotic macrophages. We hypothesized that sTREM2 would predict cardiovascular mortality in patients with established coronary atherosclerosis (CAD). Consecutive patients undergoing coronary angiography with the establishment of the diagnosis of CAD (n = 230) and without CAD (n = 53) were tested for their baseline serum sTREM2 levels. All patients were followed up for 84 months or until death occurred. sTREM2 correlated with age; however, no association was found between sTREM2 and the number of atherosclerotic vessels involved (p = 0.642). After 84 months of follow-up, 68 out of the 230 CAD patients had died. After adjusting for age and other risk factors, the adjusted hazard ratio for the highest quartile of sTREM2 was 2.37 (95% confidence interval 1.17–4.83) for death. In patients with established CAD, serum sTREM2 appears to predict cardiovascular death as a potential surrogate for plaque rupture. TREM2 and its soluble extracellular form might be implicated in the fate of the atherosclerotic plaque, but corroboration within larger studies is needed

Utilization of Drug-Coated Balloons for the Treatment of Coronary Lesions in the Elderly Population

Introduction: The use of drug-coated balloons (DCBs) has become more prevalent in the past few years for the treatment of in-stent restenosis (ISR) and de novo lesions. The absence of foreign polymer implantations potentially shortens the duration of dual anti-platelet therapy (DAPT), which can be beneficial for the elderly population. We aimed to investigate the safety and efficacy of the use of DCBs for the treatment of coronary lesions in elderly patients as compared to the younger population. Materials and methods: A database of 446 consecutive patients who underwent a procedure of DCB inflation in our institution was divided into two groups, below 70 years old and above 80 years old. We compared and analyzed the endpoints of total major adverse cardiovascular events (MACE), cardiovascular (CV) death, and all-cause mortality in both groups. Results: The difference in MACE between the two age groups was non-significant (p = 0.225); the difference in cardiovascular death was also non-significant (p = 0.086). All-cause mortality was significantly different (p < 0.0001) and can be attributed to the age of the patients. Conclusion: The utilization of DCBs for the treatment of coronary lesions may be as safe and effective for the elderly population as for the younger population and may allow a shorter period of DAPT therapy, which can lower the risk of bleeding

Mid-Term Clinical Outcomes Following Drug-Coated Balloons in Coronary Artery Disease

Objective: The aim of this study was to evaluate the mid-term efficacy of drug-coated balloons (DCB) in percutaneous coronary intervention (PCI) in two different pathophysiologic scenarios. Background: There are different underlying pathological processes in coronary artery disease. Mid-term safety and efficacy of DCB approach is still limited. Methods: Medical records of all consecutive patients undergoing DCB were evaluated. The primary endpoint was the rate of clinically driven target lesion revascularization (TLR) after 24 months. Results: Between January 2011 and December 2017, 442 patients were included, representing 4.4% of all PCIs in our institution. A total of 460 DCB lesions were treated, of which 328 (71.3%) were de novo and 132 (28.7%) were combined bare metal or drug-eluting stents with in-stent restenosis (ISR). The patients&rsquo; mean age was 66.2 &plusmn; 11.7 years with a diabetes prevalence of 45.3%. The TLR rate was lower in the de novo group (5.3%) compared to the ISR group (9.4%) (p = 0.04). No differences were observed in major adverse cardiovascular events (MACE) between the de novo group (38.9%) and ISR group (42.5%) (p = 0.47). No significant differences were detected in the TLR occurrence in the subgroup analysis. Conclusion: Our extended experience demonstrates that the mid-term DCB approach in these two pathophysiologic settings represent a reasonable option, with low TLR rate