BRCA 1/BRCA 2 Pathogenic/Likely Pathogenic Variant Patients with Breast, Ovarian, and Other Cancers.

The demographic and clinical characteristics of patients who have BRCA 1/BRCA 2 pathogenic/likely pathogenic variants may differ from their relatives who had BRCA-related cancer. In this study, we aimed to demonstrate the clinical and demographic findings of patients who had BRCA-related cancer and to assess the differences comparing their relatives who had BRCA-related cancer with breast, genital tract, prostate, and pancreas cancers as well. The results of sequencing analysis of 200 cancer patients (190 women, 10 men) who have been directed to genetic counseling with an indication of BRCA1/BRCA2 testing from different regions across 9 medical oncology centers were retrospectively analyzed. A total of 200 consecutive cancer patients who harbored the BRCA1/BRCA2 pathogenic/likely pathogenic variant (130 (65%) patients harbored BRCA 1 pathogenic/likely pathogenic variant, and 70 harbored BRCA 2 pathogenic/likely pathogenic variant) were included. Of these, 64.0% had breast cancer (43.8% of them had the triple-negative disease, and about 2.3% had only the HER-2 mutant), 31.5% had genital cancers (92.1% of them had ovarian cancer, 3.2% had endometrium, and 1.6% had peritoneum cancer as the primary site and mostly serous adenocarcinoma was the most common histopathology and 14.3% of the patients had endometrioid adenocarcinoma), 3.5% had prostate (median time from metastasis to castration-resistant status was 28 months) and 1.0% had pancreas cancer. Newly diagnosed cancer (breast and ovary) patients who had BRCA 1/BRCA 2 pathogenic/ likely pathogenic variant were younger than their previous cancer diagnosed (breast, ovary, and pancreas) parents who harbored BRCA pathogenic/likely pathogenic variant. We suggest that the genetic screening of BRCA 1/ BRCA 2 pathogenic/likely pathogenic variant is needed as a routine screening for those with a personal or family history of breast, ovarian, tubal, or peritoneal cancer. In addition, once BRCA 1 or BRCA 2 germline pathogenic variant has been identified in a family, testing of at-risk next-generation relatives earlier can identify those family members who also have the familial pathogenic variant, and thus need increased surveillance.

Higher red cell distribution width values are associated with impaired exercise capacity during exercise treadmill testing in patients without obstructive coronary disease: a preliminary study.

BACKGROUND: Red cell distribution width (RDW) is associated with poor cardiovascular outcomes. We aimed to find out if this association could be explained by impaired exercise capacity in patients without obstructive coronary artery disease (CAD). PATIENTS AND METHODS: The patients who underwent exercise treadmill test (ETT) who have non-obstructive CAD and were free of heart failure symptoms were evaluated. Total of 132 patients were enrolled, and patients were divided into three groups according to their Metabolic Equivalent Task (MET) level measured by exercise treadmill test (ETT): Less than 7 METs (group 1), 7-10 METs (group 2) and greater than 10 METs (group 3). RESULTS: The patients in Group 1 had significantly higher RDW levels (16.46 ± 2.79) compared to Group 2 (15.05 ± 2.03) and Group 3 (14.52 ± 1.37), independent of hemoglobin and hematocrit values. Significant differences for age, gender, duration of ETT and Duke Treadmill Score were also found in proportion to the reduced exercise capacity. In multivariate analysis, only duration of ETT (ß = 1.017, p = < 0.001) and RDW (ß = 0.040, p = 0.026) were found as independent variables, which had statistically significant effects on METs. CONCLUSIONS: We found an independent association between RDW and exercise capacity in patients free of obstructive coronary disease suggesting that patients with elevated RDW values are expected to have impaired exercise capacity.

Increased sympathetic activation in patients with vasovagal syncope is associated with higher mean platelet volume levels.

OBJECTIVES: Vasovagal syncope (VVS) is supposed to be modulated by increased sympathetic tone following an orthostatic maneuver. Increased sympathetic activity may have an important role in mean platelet volume (MPV), either by peripheral activation or by effects on thrombocytopoiesis. We aimed to show the effects of increased sympathetic activity on platelet size in patients with VVS in the present study. PATIENTS AND METHODS: Thirty-seven patients with VVS were compared with age- and sex-matched 33 patients without VVS. All patients have undergone 24 hour holter monitoring for heart rate variability (HRV) and time-domain HRV analysis. Blood samples for MPV measurements were taken before 24 hour holter monitoring. RESULTS: Group 1 was consisted of 37 patients with VVS and group 2 was consisted of 33 patients without VVS. We observed that SDNN, SDNN index, SDSD, RMSDD, PNN50 count were significantly lower and MPV was found significantly higher in patients with VVS (p < 0.05 for all). Pearson's correlation analysis showed that MPV was moderately negatively correlated with SDNN (r = -0.421), SDSD (r = -0.396), NN50 count (r = -0.395) and RMSDD (r = -0.393). Multivariate regression analysis showed that SDNN was the only independent variable, which had a significant effect on increased MPV level (ß = -0.295 , p = 0.016). CONCLUSIONS: We found that MPV was closely associated with increased sympathetic activity in patients with VVS. Our analysis supports the hypothesis that alterations in autonomic status might play a role in the development of platelet size.

Association between microvascular angina and erectile dsyfunction.

Although the origin of cardiac syndrome X (CSX) is still debated, endothelial dysfunction leading to reduced coronary microvascular dilatory response and increased coronary resistance is thought to have an important role in the pathogenesis. Erectile dysfunction (ED) is associated with risk factors resulting in endotelial dysfunction. Although the relationship between cardiovascular disease and ED has been well established; the relation between CSX and ED has not been extensively studied so far. We herein aimed to study ED in patients with CSX. The study was designed as a prospective case-control study. Blood samples were analyzed with respect to concentrations of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides. The subjects answered the native language five-item version of the International Index of Erectile Function Questionnaire (IIEF)-5. Each question was scored from 0 to 5 with a maximum score of 25 denoting healty subjects. We investigated the IIEF-5 score in 51 men with CSX (mean age=48.2±6.4 years), 53 men with demonstrated coronary artery disease (CAD) (mean age=48.3±4.8 years) and 52 male controls with normal coronary arteries (mean age=47.2±6.0 years). Mean IIEF-5 scores were 19.88±3.07 for CSX group, 18.83±3.31 for CAD group and 21.40±2.94 for control group. IIEF-5 scores in CSX group were found to be significantly lower than the those of control group (P<0.001). There were no significant differences in IIEF-5 scores between CSX and CAD groups (P=0.09). We have shown for the first time that patients with CSX have lower IIEF-5 scores compared with controls with normal coronary angiograms. This study suggests that ED and CSX may be different manifestations of a common underlying vascular pathology and vasculogenic ED is frequently seen in CSX at least as much as in CAD.

Vascular inflammation and aortic stiffness relate to early left ventricular diastolic dysfunction in prehypertension.

Prehypertension is characterized by an increased cardiovascular risk and by an increased prevalence of target organ damage compared with the pure normotensive state. The present study was designed to assess in prehypertensive subjects the possible relationships between early left ventricular dysfunction, vascular inflammation and aortic stiffness. The study population consisted of 31 untreated prehypertensive subjects (age: 34 ± 6 years, mean ± SD) and 31 age-matched pure normotensive controls. Left ventricular function was assessed by echocardiography, aortic distensibility parameters were derived from aortic diameters measured by ultrasonography, and high-sensitivity C-reactive protein was assessed by latex-enhanced reagent. Prehypertensive subjects displayed a significantly lower E/A ratio and a significantly greater deceleration time and isovolumetric relaxation time compared with normotensive controls. They also displayed aortic systolic diameter, diastolic diameter and mean aortic stiffness index beta significantly increased while systo-diastolic diameter change, mean aortic distensibility and aortic strain were significantly reduced compared with controls. Values of inflammatory markers were increased. At multiple regression analysis, E/A ratio was significantly related to high-sensitivity C-reactive protein and aortic stiffness index beta, after correction for age, left ventricular mass index and mean blood pressure (ß coefficient = -0.49, overall r(2) = 0.24, p = 0.01 and ß coefficient =-0.46, overall r(2) = 0.21, p = 0.02, respectively). Thus, in prehypertension, left ventricular dysfunction is significantly related to vascular inflammation and aortic stiffness, suggesting that early cardiac and vascular alterations may have an increased inflammatory process as a common pathophysiological link.

Sustained idiopathic ventricular tachycardia originating from the posteroseptal tricuspid annulus.

Tricuspid annular ventricular tachycardia (VT) is a rarely encountered entity. Despite abundant data on idiopathic VTs, the prevalence and clinical characteristics of this infrequent form are not well defined and the efficacy of radiofrequency (RF) catheter ablation treatment remains unknown. We report on a case of a 44-year-old male presenting with symptomatic sustained idiopathic VT originating from the posteroseptal tricuspid annulus.

The relationship of gamma-glutamyltransferase to aortic elastic properties in young patients with prehypertension.

Some cross-sectional studies have demonstrated a positive association between serum gamma-glutamyltransferase (GGT) levels and blood pressure. Accordingly, we aimed to analyze serum GGT levels in patients with prehypertension and examine the relationship with aortic elasticity parameters. The study population consisted of 25 newly diagnosed prehypertensive individuals and 25 healthy control subjects. Aortic strain, distensibility index, and stiffness index beta were calculated from aortic diameters measured by echocardiography and blood pressures simultaneously measured by sphygmomanometry. Prehypertensive patients were detected to have significantly lower aortic distensibility and strain indexes compared to control subjects aortic distensibility. However, aortic stiffness index beta of the prehypertensive group was significantly higher compared to that of the control group (3.73 ± 1.41 vs. 2.97 ± 0.82, p = 0.02). The mean GGT levels were found to be higher in patients with prehypertension compared to those of controls (47.9 ± 15.9 U/L vs. 36.1 ± 9.4 U/L, p = 0.003). When multiple linear regression analysis was done to clarify the contributions of GGT to aortic elasticity adjusting for age, body mass index, uric acid, serum glucose, heart rate, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglyceride, we observed that only serum GGT levels were significantly associated with aortic elasticity parameters (for aortic strain beta = -0.247, p < 0.001; for aortic distensibility beta = -0.108, p < 0.001; for stiffness index beta = 0.063, p < 0.001). Whatever the mechanism is, young patients with prehypertension have higher serum GGT levels compared to healthy control subjects. More importantly, increased GGT levels are independently associated with impaired aortic elasticity in patients with prehypertension.

Woven right coronary artery: a case report and review of the literature.

Woven coronary artery is an extremely rare and is still not a clearly defined coronary anomaly in which epicardial coronary artery is divided into multiple thin channels at any segment of the coronary artery, and subsequently, these multiple channels merge again in a normal conduit. A few cases have been reported till now. In this case report, we present a 58-year-old male with a woven right coronary artery.

Increased platelet activation in patients with slow coronary flow.

We tested the hypothesis that increased platelet activation may be present in patients with slow coronary flow (SCF) and may contribute to the pathogenesis of slow coronary flow phenomenon (SCFP). Fifty patients angiographically proven normal coronary flow (control group; mean age = 61.3 +/- 7.0 years, 43 male) and 50 patients with angiographically proven SCF in all coronary arteries (patient group; man age = 62.7 +/- 6.7 years, 38 male) were included in the present study. Coronary flow rates of all subjects were documented by Thrombolysis In Myocardial Infarction frame count (TIMI frame count). Patients with a corrected TIMI frame count greater than two standard deviations from normal published range for the particular vessel were considered as having SCF. Complete blood count and mean platelet volume (MPV) was measured from whole blood sample with Abbott Cell-Dyne 4000 cell counter. Plasma sP-selectin concentrations were analyzed with sP-Selectin ELISA kit. There were no statistically significant differences between the two groups with respect to baseline demographic, clinical and lipid parameters. Not only MPV values but also plasma sP-selectin levels were significantly higher in patients with the patients with SCF compared to those of controls (for MPV; 8.2 +/- 0.7 vs. 7.2 +/- 0.6 fl, P < 0.001, for sP-Selectin; 1.5 +/- 0.3 vs. 1.0 +/- 0.2 ng/ml, P < 0.001). Interestingly, significant positive correlations were detected between mean TIMI frame counts and MPV and sP-selectin levels (for MPV; r = 0.56, P < 0.001, for sP-selectin r = 0.67, P < 0.001). The current study demonstrates that platelet activity is increased in the patients with SCF compared to that of the patients with normal coronary flow.

The small intestine: a critical linkage in pathophysiology of cardiac cachexia.

Impaired functioning of the gastrointestinal system may also contribute to malnutrition and cardiac cachexia (CC) in patients with chronic heart failure (CHF). Targets for future interventions include the deranged hormonal systems involved in energy balance as well as malabsorption from the gut and dietary supplementation. Other targets are the inhibition of proteasome-dependent protein degradation and the direct inhibition of pro-inflammatory pathways. The beneficial effects of ACE inhibitors, aldesterone inhibitors and beta-blockers in preventing or delaying the collagen deposition in the small intestine wall need to be elucidated. We strongly believe that by improving our understanding of the role of the gut in CC will lead to the development of novel therapeutic strategies in the near future.