Tailoring therapy for heart failure: the pharmacogenomics of adrenergic receptor signaling.

Heart failure is one of the leading causes of mortality in Western countries, and β-blockers are a cornerstone of its treatment. However, the response to these drugs is variable among individuals, which might be explained, at least in part, by genetic differences. Pharmacogenomics is the study of genetic contributions to drug response variability in order to provide evidence for a tailored therapy in an individual patient. Several studies have investigated the pharmacogenomics of the adrenergic receptor system and its role in the context of the use of β-blockers in treating heart failure. In this review, we will focus on the most significant polymorphisms described in the literature involving adrenergic receptors and adrenergic receptor-related proteins, as well as genetic variations influencing β-blocker metabolism

Neuro-hormonal effects of physical activity in the elderly.

Thanks to diagnostic and therapeutic advances, the elderly population is continuously increasing in the western countries. Accordingly, the prevalence of most chronic age-related diseases will increase considerably in the next decades, thus it will be necessary to implement effective preventive measures to face this epidemiological challenge. Among those, physical activity exerts a crucial role, since it has been proven to reduce the risk of cardiovascular diseases, diabetes, obesity, cognitive impairment and cancer. The favorable effects of exercise on cardiovascular homeostasis can be at least in part ascribed to the modulation of the neuro-hormonal systems implicated in cardiovascular pathophysiology. In the elderly, exercise has been shown to affect catecholamine secretion and biosynthesis, to positively modulate the renin-angiotensin-aldosterone system and to reduce the levels of plasma brain natriuretic peptides. Moreover, drugs modulating the neuro-hormonal systems may favorably affect physical capacity in the elderly. Thus, efforts should be made to actually make physical activity become part of the therapeutic tools in the elderly. © 2013 Femminella, de Lucia, Iacotucci, Formisano, Petraglia, Allocca, Ratto, DAmico, Rengo, Pagano, Bonaduce, Rengo and Ferrara

25th International Congress of the European Association for Endoscopic Surgery (EAES) Frankfurt, Germany, 14-17 June 2017 : Oral Presentations

Introduction: Ouyang has recently proposed hiatal surface area (HSA) calculation by multiplanar multislice computer tomography (MDCT) scan as a useful tool for planning treatment of hiatus defects with hiatal hernia (HH), with or without gastroesophageal reflux (MRGE). Preoperative upper endoscopy or barium swallow cannot predict the HSA and pillars conditions. Aim to asses the efficacy of MDCT’s calculation of HSA for planning the best approach for the hiatal defects treatment. Methods: We retrospectively analyzed 25 patients, candidates to laparoscopic antireflux surgery as primary surgery or hiatus repair concomitant with or after bariatric surgery. Patients were analyzed preoperatively and after one-year follow-up by MDCT scan measurement of esophageal hiatus surface. Five normal patients were enrolled as control group. The HSA’s intraoperative calculation was performed after complete dissection of the area considered a triangle. Postoperative CT-scan was done after 12 months or any time reflux symptoms appeared. Results: (1) Mean HSA in control patients with no HH, no MRGE was cm2 and similar in non-complicated patients with previous LSG and cruroplasty. (2) Mean HSA in patients candidates to cruroplasty was 7.40 cm2. (3) Mean HSA in patients candidates to redo cruroplasty for recurrence was 10.11 cm2. Discussion. MDCT scan offer the possibility to obtain an objective measurement of the HSA and the correlation with endoscopic findings and symptoms. The preoperative information allow to discuss with patients the proper technique when a HSA[5 cm2 is detected. During the follow-up a correlation between symptoms and failure of cruroplasty can be assessed. Conclusions: MDCT scan seems to be an effective non-invasive method to plan hiatal defect treatment and to check during the follow-up the potential recurrence. Future research should correlate in larger series imaging data with intraoperative findings

Age estimation based on pulp–tooth volume ratio of anterior teeth in cone-beam computed tomographic images in a selected population: A cross-sectional study

The present study aimed to investigate the correlation between chronological age and pulp– tooth volume ratio in anterior teeth using cone beam computed tomographic (CBCT) images and provide equations for age estimation based on pulp–tooth volume ratio. In this cross-sectional study, CBCT images of 312 anterior teeth of the maxilla and mandible were examineαd. The chronological age and the sex of the patients were recorded. Tooth volume and pulp volume of the anterior teeth were measured using Mimics software, and then tooth–pulp volume ratio was calculated. Statistical analysis of data was performed using chi-square test, independent T-test, Pearson’s correlation, and linear regression (α = 0.05). Finally, equations were made based on the results of the regression analysis for age estimation in general and for males and females. The age of the subjects ranged between 16 and 69 years (mean 40.6 ± 12.74). The pulp–tooth volume ratio of the maxillary teeth was generally higher than the mandibular teeth. A significant inverse relationship between age and pulp–tooth volume ratio was observed for all anterior teeth. (p < 0.05). The strongest correlation between age and pulp–tooth volume ratio was reported for mandibular central incisor (r = −0.58, p < 0.001) and the weakest was for mandibular lateral incisor (r = −0.36, p = 0.012). Age estimation was most accurate among females using the maxillary central incisors (p < 0.001) and among males using the mandibular central incisors and maxillary canines (p = 0.003). Pulp–tooth volume ratio of mandibular central incisors, maxillary lateral incisors, and maxillary canines in males and maxillary and mandibular central incisors, maxillary lateral incisors, and maxillary and mandibular canines in females can be used for age estimation

Radiogenomics in clear cell renal cell carcinoma: correlations between advanced CT imaging (texture analysis) and microRNAs expression

Purpose: A relevant challenge for the improvement of clear cell renal cell carcinoma management could derive from the identification of novel molecular biomarkers that could greatly improve the diagnosis, prognosis, and treatment choice of these neoplasms. In this study, we investigate whether quantitative parameters obtained from computed tomography texture analysis may correlate with the expression of selected oncogenic microRNAs. Methods: In a retrospective single-center study, multiphasic computed tomography examination (with arterial, portal, and urographic phases) was performed on 20 patients with clear cell renal cell carcinoma and computed tomography texture analysis parameters such as entropy, kurtosis, skewness, mean, and standard deviation of pixel distribution were measured using multiple filter settings. These quantitative data were correlated with the expression of selected microRNAs (miR-21-5p, miR-210-3p, miR-185-5p, miR-221-3p, miR-145-5p). Both the evaluations (microRNAs and computed tomography texture analysis) were performed on matched tumor and normal corticomedullar tissues of the same patients cohort. Results: In this pilot study, we evidenced that computed tomography texture analysis has robust parameters (eg, entropy, mean, standard deviation) to distinguish normal from pathological tissues. Moreover, a higher coefficient of determination between entropy and miR-21-5p expression was evidenced in tumor versus normal tissue. Interestingly, entropy and miR-21-5p show promising correlation in clear cell renal cell carcinoma opening to a radiogenomic strategy to improve clear cell renal cell carcinoma management. Conclusion: In this pilot study, a promising correlation between microRNAs and computed tomography texture analysis has been found in clear cell renal cell carcinoma. A clear cell renal cell carcinoma can benefit from noninvasive evaluation of texture parameters in adjunction to biopsy results. In particular, a promising correlation between entropy and miR-21-5p was found

State of the art: iterative CT reconstruction techniques

Owing to recent advances in computing power, iterative reconstruction (IR) algorithms have become a clinically viable option in computed tomographic (CT) imaging. Substantial evidence is accumulating about the advantages of IR algorithms over established analytical methods, such as filtered back projection. IR improves image quality through cyclic image processing. Although all available solutions share the common mechanism of artifact reduction and/or potential for radiation dose savings, chiefly due to image noise suppression, the magnitude of these effects depends on the specific IR algorithm. In the first section of this contribution, the technical bases of IR are briefly reviewed and the currently available algorithms released by the major CT manufacturers are described. In the second part, the current status of their clinical implementation is surveyed. Regardless of the applied IR algorithm, the available evidence attests to the substantial potential of IR algorithms for overcoming traditional limitations in CT imaging

Exercise promotes angiogenesis and improves beta-adrenergic receptor signalling in the post-ischaemic failing rat heart.

We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated beta-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise.Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 +/- 5\%), increased LV end diastolic pressure (20.9 +/- 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac beta-adrenergic receptor downregulation and desensitization.Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF