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Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70–95%]) than MRA (20% [10–30%]), SGLT2i (30% [20–50%]) or (GLP1-RA (10% [5–15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15–40%) vs 18% [10%–25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5–5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers’ dosage reduction was the usual management.

Introduction: Traditional medical education often emphasises theory, but clinical competence relies greatly on practical, hands-on skills. This quasi-experimental study examines how a combined approach—flipped classroom learning and simulation-based internships—affects medical students’ self-assessed clinical abilities. This model seeks to build students’ understanding, practical skills, and confidence in clinical settings through online preparation and realistic simulation exercises. Methods: This study examined changes in medical students’ self-perceived clinical skills after a flipped classroom and simulation-based internship. A total of 391 third- and fourth-year students completed a nine-hour program with morning practice sessions and afternoon high-fidelity scenarios. Surveys before and after the program assessed self-perceived thoracic and abdominal/general skills. ANCOVA controlled for baseline scores, and paired Wilcoxon signed-rank tests examined overall and subgroup improvements. Results: After the program, significant improvements were observed in self-perceived clinical skills across all domains. Thoracic skills increased from a median of 2.19 to 7.36, and abdominal skills from 5.11 to 9.46. Medical history, vital signs, and blood pressure scores also improved significantly. Third-year students and those attending the Clinical Methodology course showed the greatest gains. All post-intervention improvements were statistically significant (p < 0.001). Conclusions: The combination of flipped classroom learning and intensive simulation training markedly improved students’ perceived clinical competence. These findings suggest that such methods boost students’ practical skills and confidence. Further research is recommended to explore the long-term impact of this approach on skill retention and professional practice.

This study examines the subjective attributes that coaches consider most important for identifying and developing the talent of junior élite football players. It also explores whether players’ physical fitness efficiency moderates these attributes and influences playing time during the regular season. Forty-three junior élite football players and four Italian Serie A club coaches participated in the study, contributing their unique perspectives and experiences. Players’ physical fitness was assessed using the Yo-Yo Intermittent Recovery Level 1 test, while coaches rated players’ abilities through a structured questionnaire. A significant positive relationship was found between ’understanding of the game and position on the field’ and total playing time (t = 3.498, p < 0.01, β = 0.953). Physical efficiency further strengthened this relationship when players’ fitness levels were average (b = 0.624, p < 0.001) and one standard deviation above the mean (b = 0.891, p < 0.001). These findings highlight the importance of tactical awareness in earning playing time and suggest that physical fitness enhances the effect of cognitive abilities on performance. This study provides insights into how coaches assess talent and underscores the value of integrating physical and tactical development in youth football, providing a testament to the power of collaboration in advancing our understanding of talent identification in sports.

Currently, research in youth soccer consists of methodological choices that can raise activity volumes and exercise intensity to promote proper training for youth soccer demands. Therefore, the present cluster randomised trial aims to evaluate the effects of the dynamic–ecological approach on the physical performance parameters compared with a traditional one in a group of sub-elite U13 players. Thirty-five male children (age 12.16 ± 0.55 years; weight 45.59 ± 7.15 kg; height 145.5 ± 4.2 cm; BMI 15.8 ± 2.1 kg·m−2) were recruited for this trial from two teams belonging to sub-elite soccer schools and randomly assigned to a dynamic–ecological approach (DEA) or a traditional training (TTG) group. The training program lasted six weeks and consisted of 18 training sessions of 90 min each (3 sessions per week). The sample was evaluated by the standing long jump (SLJ), hop test (HT), 10 m sprint (10 m), 10 × 5 m shuttle run test (SRT), and leg raise test (LR). The DEA group showed significantly higher results in the SLJ (p < 0.001), HT left leg (p < 0.001), 10 m sprint (p < 0.001), and SRT (p < 0.001). In conclusion, the dynamic–ecological approach provides higher performance adaptations. Therefore, this approach can be considered a suitable method to optimise pre-pubertal player training, mainly when no fitness or strength coach is available.

Abstract The onset of multiple and metachronous tumors in young patients induces to suspect the presence of genetic variants in genes associated with tumorigenesis. We describe here the unusual case of a 16-year-old patient who developed a synchronous bifocal colorectal adenocarcinoma with distant metastases. We provide high throughput molecular characterization with whole-exome sequencing (WES) and DNA targeted sequencing of different tumoral lesions and normal tissue samples that led to unveil a germline POLE mutation (p.Ser297Cys) coexisting with the PMS2 c.2174 + 1 G > A splicing mutation. This clinical scenario defines a “POLE-LYNCH” collision syndrome, which explains the ultra-mutator phenotype observed in the tumor lesions, and the presence of MMR deficiency-associated unusual signatures. The patient was successfully treated with immune checkpoint inhibitors but subsequently developed a high-grade urothelial carcinoma cured by surgery. We complement this analysis with a transcriptomic characterization of tumoral lesions with a panel targeting 770 genes related to the tumor microenvironment and immune evasion thus getting insight on cancer progression and response to immunotherapy.

Primary aldosteronism is the most common surgically curable form of hypertension. The sporadic forms of the disorder are usually caused by aldosterone overproduction from a unilateral adrenocortical aldosterone-producing adenoma or from bilateral adrenocortical hyperplasia. The main knowledge-advances in disease pathophysiology focus on pathogenic germline and somatic variants that drive the excess aldosterone production. Less clear are the molecular and cellular mechanisms that lead to an increased mass of the adrenal cortex. However, the combined application of transcriptomics, metabolomics, and epigenetics has achieved substantial insight into these processes and uncovered the evolving complexity of disrupted cell growth mechanisms in primary aldosteronism. In this review, we summarize and discuss recent progress in our understanding of mechanisms of cell death, and proliferation in the pathophysiology of primary aldosteronism.

BackgroundThe prevalence of hypertension mediated organ damage (HMOD) in patients attending the Emergency Department (ED) with symptomatic blood pressure (BP) rise is unknown, and whether HMOD varies between asymptomatic and symptomatic patients with grade 3 hypertension is unclear.AimThis study aimed to investigate cardiac and vascular HMOD in hypertensive urgencies (HU) and asymptomatic outpatients with grade 1–3 hypertension.MethodsPatients attending the ED with a symptomatic BP rise ≥180/110 mmHg were prospectively enrolled (HU group), after the exclusion of acute organ damage. HMOD and BP were assessed after 72 h from ED discharge in an office setting. These patients were matched by age and sex to outpatients with grade 3 hypertension (Grade 3 group), and by age, sex, and 72 h office BP values to outpatients with any grade hypertension (Control group).ResultsA total of 304 patients were enrolled (76 patients in the HU group, 76 in the Grade 3 group, and 152 in the Control group). Grade 3 patients had increased left ventricular mass (LVMi) compared to patients with HU (106.9 ± 31.5 vs. 96.1 ± 30.7 g/m2, p = 0.035). Severe left ventricular hypertrophy (LVH) was more frequent in grade 3 (21.1 vs. 5.3%, p = 0.004), and pulse wave velocity (PWV) was similar in the two groups. There was no difference in LVMi between ED and Control patients (96.1 ± 30.7 vs. 95.2 ± 26.6 g/m2, p = 0.807). LVH prevalence was similar (43.4 vs. 35.5%, p = 0.209, respectively), but patients with HU had thicker interventricular septum (11.9 ± 2.2 vs. 11.1 ± 2.2 mm, p = 0.007). PWV was similar between these two groups. Patients with HU needed more antihypertensive drugs than Control patients (2 vs. 1, p < 0.001).ConclusionsPatients with HU had a better cardiac HMOD profile than outpatients with grade 3 hypertension. Their cardiac and vascular HMOD is more comparable to an outpatient with similar in-office BP, although they need more antihypertensive medications.

Cancer patients receiving a potentially cardiotoxic oncologic therapy have an increased risk of cardiovascular adverse events (CVAEs), especially in presence of concomitant arterial hypertension (AH). Therefore, cancer patients should be evaluated before, during and after cardiotoxic treatments, to early identify new-onset or worsening AH or CVAEs. An expert panel of oncology networks from Piedmont and Aosta Valley (North-Western Italy) aimed to provide recommendations to support health professionals in selecting the best management strategies for patients, considering the impact on outcome and the risk–benefit ratio of diagnostic/therapeutic tools. We proposed an useful document for evaluating and managing AH related to cancer treatments. Patients should be divided into 4 cardiovascular (CV) risk groups before starting potentially cardiotoxic therapies: patients with low/moderate risk who should be entirely evaluated by oncologists and patients with high/very high risk who should be referred to a cardiologist or arterial hypertension specialist. According to the CV risk class, every patient should be followed up during cancer treatment to monitor any possible CV complications. Adequate control of AH related to antineoplastic treatments is crucial to prevent severe CVAEs. In the presence of high-profile risk or lack of response to anti-hypertensive therapy, the patients should be managed with a cardiovascular-oncology expert center.

Objectives: The first objective was to investigate the influence of subjective perceptions and the efficacy of objective evaluation regarding the classification of soccer school players by their level of performance. The second objective was to advise on accurate collocation according to objective assessment of players’ performance. Methods: An objective evaluation of the players’ motor performance abilities and coaches’ subjective perceptions of the players’ levels of performance was conducted with 34 young football players (U11) from Torino FC soccer school. The players were allocated to three groups based on their perceived performance level at the start of the season. The players were evaluated using a field test battery, and team coaches provided subjective ratings of the players’ abilities. Results: MANOVA showed significant differences between the playing levels (F = 2.185, p < 0.05; partial η2 = 0.34) in the 10 × 5 shuttle run, 20 m sprint test (objective evaluations), heading, understanding of the game, positioning on the field, speed and agility (subjective perception) (F = 1.951, p < 0.05; partial η2 = 0.43). A discriminant analysis of the field test scores revealed that 76.5% of players were correctly categorised in one of the three performance-level groups. However, the first group (the best players) had the lowest predictive accuracy rate (58.3%). By comparison, the second group (the average players) had a much higher predictive accuracy rate (83.3%), and the third (the weakest players) had the highest (90.0%). Conclusions: These findings support the role of objective performance evaluation in categorising players of different skill in soccer schools.

Objectives: Arterial hypertension is still the most frequent cause of cardiovascular and cerebrovascular morbidity and mortality. Antihypertensive treatment has proved effective in reduction of cardiovascular risk. Nevertheless, lifestyle interventions and pharmacological therapy in some cases are ineffective in reaching blood pressure target values, despite full dose and poly-pharmacological treatment. Poor adherence to medications is an important cause of treatment failure. Different methods to assess therapeutic adherence are currently available: Therapeutic drug monitoring in biological fluids has previously demonstrated its efficacy and reliability. Plasma and urine have been already used for this purpose, but they may be affected by some practical limitations. Saliva may represent a feasible alternative.Methods: Fourteen antihypertensive drugs and two metabolites were simultaneously tested in plasma, urine, and saliva. Tested molecules included: atenolol, nebivolol, clonidine, ramipril, olmesartan, telmisartan, valsartan, amlodipine, nifedipine, doxazosin, chlorthalidone, hydrochlorothiazide, indapamide, sacubitril, ramiprilat, and sacubitrilat. Therapeutic drug monitoring was performed using ultra-high performance liquid chromatography, coupled to tandem mass spectrometry (UHPLC-MS/MS). The method has been preliminarily evaluated in a cohort of hypertensive patients.Results: The method has been validated according to US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. The application on a cohort of 32 hypertensive patients has demonstrated sensibility and specificity of 98% and 98.1%, respectively, with a good feasibility in real-life clinical practice.Conclusion: Saliva may represent a feasible biological sample for therapeutic drug monitoring by non-invasive collection, prompt availability, and potential accessibility also in out-of-clinic settings.

Background: Diastolic function in patients with heart failure is usually impaired, resulting in increased left ventricular (LV) filling pressures, whose gold standard assessment is right heart catheterization (RHC). Hemodynamic force (HDF) analysis is a novel echocardiographic tool, providing an original approach to cardiac function assessment through the speckle-tracking technology. The aim of our study was to evaluate the use of HDFs, both alone and included in a new predictive model, as a potential novel diagnostic tool of the diastolic function.Methods: HDF analysis was retrospectively performed in 67 patients enrolled in the “Right1 study.” All patients underwent RHC and echocardiography up to 2 h apart. Increased LV filling pressure (ILFP) was defined as pulmonary capillary wedge pressure (PCWP) ≥ 15 mmHg.Results: Out of 67 patients, 33 (49.2%) showed ILFP at RHC. Diastolic longitudinal force (DLF), the mean amplitude of longitudinal forces during diastole, was associated with the presence of ILFP (OR = 0.84 [0.70; 0.99], p = 0.046). The PCWP prediction score we built including DLF, ejection fraction, left atrial enlargement, and e' septal showed an AUC of 0.83 [0.76–0.89], with an optimal internal validation. When applied to our population, the score showed a sensitivity of 72.7% and a specificity of 85.3%, which became 66.7 and 94.4%, respectively, when applied to patients classified with “indeterminate diastolic function” according to the current recommendations.Conclusion: HDF analysis could be an additional useful tool in diastolic function assessment. A scoring system including HDFs might improve echocardiographic accuracy in estimating LV filling pressures. Further carefully designed studies could be useful to clarify the additional value of this new technology.

Reduced or absent compliance to anti-hypertensive treatment is a major obstacle to the achievement of blood pressure target in patients with arterial hypertension. Current available methods for therapeutic adherence assessment display low accuracy, limited applicability in clinical practice and/or high costs. We designed a prospective study to evaluate the accuracy of serial measurement of ARR to assess the therapeutic compliance to RAAS inhibitors. We prospectively enrolled 80 subjects: 40 patients with arterial hypertension and 40 normotensive controls. The ARR was evaluated at baseline and 2 and 8 week after initiation of a RAAS inhibitor in patients with hypertension, and at baseline and 2 weeks for the control group. Adherence to the prescribed therapy was confirmed by therapeutic drug monitoring. We observed a significant increase of renin levels and reduction of aldosterone levels after RAAS inhibitors initiation, with consequent reduction of ARR. Delta ARR (ΔARR), defined as relative change in ARR before and after treatment initiation, provided high accuracy for determination of therapeutic compliance, with an AUC of 0.900 at 2 weeks and 0.886 at 8 weeks. A cut-off of −48% of ΔARR provided 90% sensitivity and 75% specificity, at 2 and 8 weeks. In conclusion, the measurement of ΔARR is a powerful test, cheap and widely available to accurately identify the non-adherence to RAAS inhibitors treatment. Herein we propose the implementation of ΔARR in clinical practice through a multi-step flow-chart for the management of patients with uncontrolled blood pressure, with identification of those suspected of non-adherence, reserving therapeutic drug monitoring for non-adherence confirmation.

Background: Carfilzomib improves the prognosis of multiple myeloma (MM) patients but significantly increases cardiovascular toxicity. The timing and effect of Carfilzomib therapy on the left ventricular function is still under investigation. We sought to assess the echocardiographic systo-diastolic changes, including global longitudinal strain (GLS), in patients treated with Carfilzomib and to identify predictors of increased risk of cardiovascular adverse events (CVAEs) during therapy.Methods: Eighty-eight patients with MM performed a baseline cardiovascular evaluation comprehensive of transthoracic echocardiogram (TTE) before the start of Carfilzomib therapy and after 6 months. All patients were clinically followed up to early identify the occurrence of CVAEs during the whole therapy duration.Results: After Carfilzomib treatment, mean GLS slightly decreased (−22.2% ± 2.6 vs. −21.3% ± 2.5; p < 0.001). Fifty-eight percent of patients experienced CVAEs during therapy: 71% of them had uncontrolled hypertension, and 29% had major CVAEs or CV events not related to arterial hypertension. GLS variation during therapy was not related to an increased risk of CVAEs; however, patients with baseline GLS ≥ −21% and/or left ventricular ejection fraction (LVEF) ≤ 60% had a greater risk of major CVAEs (OR = 6.2, p = 0.004; OR = 3.7, p = 0.04, respectively). Carfilzomib led to a higher risk of diastolic dysfunction (5.6 vs. 13.4%, p = 0.04) and to a rise in E/e′ ratio (8.9 ± 2.7 vs. 9.7 ± 3.7; p = 0.006).Conclusion: Carfilzomib leads to early LV function impairment early demonstrated by GLS changes and diastolic dysfunction. Baseline echocardiographic parameters, especially GLS and LVEF, might improve cardiovascular risk stratification before treatment.

A reliable prediction of the recurrence risk of pheochromocytoma after radical surgery would be a key element for the tailoring/personalization of post-surgical follow-up. Recently, our group developed a multivariable continuous model that quantifies this risk based on genetic, histopathological, and clinical data. The aim of the present study was to simplify this tool to a discrete score for easier clinical use. Data from our previous study were retrieved, which encompassed 177 radically operated pheochromocytoma patients; supervised regression and machine-learning techniques were used for score development. After Cox regression, the variables independently associated with recurrence were tumor size, positive genetic testing, age, and PASS. In order to derive a simpler scoring system, continuous variables were dichotomized, using > 50 mm for tumor size, ≤ 35 years for age, and ≥ 3 for PASS as cut-points. A novel prognostic score was created on an 8-point scale by assigning 1 point for tumor size > 50 mm, 3 points for positive genetic testing, 1 point for age ≤ 35 years, and 3 points for PASS ≥ 3; its predictive performance, as assessed using Somers’ D, was equal to 0.577 and was significantly higher than the performance of any of the four dichotomized predictors alone. In conclusion, this simple scoring system may be of value as an easy-to-use tool to stratify recurrence risk and tailor post-surgical follow-up in radically operated pheochromocytoma patients.

[This corrects the article DOI: 10.1371/journal.pone.0237297.].

Background. Vascular damage is recognized as a diagnostic landmark in systemic sclerosis (SSc), both in its limited and diffuse subtypes. Early detection at a subclinical stage with transthoracic echocardiography (TTE) and carotid femoral pulse wave velocity (cfPWV) may be helpful in therapeutic planning and management. Aim of the Study. The aim of the study was to evaluate presence of subclinical cardiovascular damage in patients with limited and diffuse SSc in comparison with a cohort of healthy individuals. Methods. Consecutive patients with limited and diffuse SSc underwent complete TTE and cfPWV and a complete review of clinical data. As controls, 23 healthy subjects with similar hemodynamic profiles were selected. Results. 41 patients (35 female, aged 56.9 years), 21 with diffuse and 20 with limited SSc, were recruited. Past medical history, cardiovascular risk factors, gender distribution, and disease duration were similar in the two groups as well as TTE parameters and hemodynamic indexes—cfPWV (6.5 [6–6.8] vs. 7.0 [6.2–8.5], p=0.24) and augmentation index (145.6 ± 14.2 vs. 149 ± 20.6, p=0.52). Patients with limited SSc were 10 years older than patients with diffuse SSc. In the multiple regression analysis, only age (p=0.0154) and disease duration (p=0.0467) resulted as the significant determinant of cfPWV. When compared to healthy controls, no significant difference emerged in TTE or hemodynamic indexes. Conclusion. In SSc, cfPWV increases with age, with no additional impact of pathology or subtype. Vascular damage in the SSc population is not accurately reflected in increased arterial stiffness, as evaluated with cfPWV, or classically defined echocardiographic findings of organ damage (i.e., left ventricular concentric remodelling and increased filling pressures).

Background and aim: Considering the amount of novel knowledge generated in the last five years, a team of experienced hypertensionlogists was assembled to furnish updated clinical practice guidelines for the management of primary aldosteronism. Methods: To identify the most relevant studies, the authors utilized a systematic literature review in international databases by applying the PICO strategy, and then they were required to make use of only those meeting predefined quality criteria. For studies of diagnostic tests, only those that fulfilled the Standards for Reporting of Diagnostic Accuracy recommendations were considered. Results: Each section was jointly prepared by at least two co-authors, who provided Class of Recommendation and Level of Evidence following the American Heart Association methodology. The guidelines were sponsored by the Italian Society of Arterial Hypertension and underwent two rounds of revision, eventually reexamined by an External Committee. They were presented and thoroughly discussed in two face-to-face meetings with all co-authors and then presented on occasion of the 36th Italian Society of Arterial Hypertension meeting in order to gather further feedbacks by all members. The text amended according to these feedbacks was subjected to a further peer review. Conclusions: After this process, substantial updated information was generated, which could simplify the diagnosis of primary aldosteronism and assist practicing physicians in optimizing treatment and follow-up of patients with one of the most common curable causes of arterial hypertension.

BackgroundThe global rate of intensive care unit (ICU) admission during the COVID-19 pandemic varies within countries and is among the main challenges for health care systems worldwide. Conflicting results have been reported about the response to coronavirus infection and COVID-19 outcomes in men and women. Understanding predictors of intensive care unit admission might be of help for future planning and management of the disease.Methods and findingsWe designed a cross-sectional observational multicenter nationwide survey in Italy to understand gender-related clinical predictors of ICU admission in patients with COVID-19. We analyzed information from 2378 charts of Italian patients certified for COVID-19 admitted in 26 hospitals. Three hundred ninety-five patients (16.6%) required ICU admission due to COVID19 infection, more frequently men (74%), with a higher prevalence of comorbidities (1,78±0,06 vs 1,54±0,03 pConclusionsOur study demonstrates that gender is the primary determinant of the disease's severity among COVID-19. Obesity is the condition more often observed among those admitted to ICU within both genders.Trial registrationClinicaltrials.gov: NCT04331574.

Prognosis in pulmonary hypertension is strictly linked to right ventricle failure, which results from uncoupling between right ventricle function and its afterload. This study sought to describe how to estimate with echocardiography right ventricular wall tension, its correlation with right ventricle haemodynamics and its prognostic role. A total of 190 patients without overt right ventricle failure but with suspected pulmonary hypertension on a previous echocardiogram underwent right heart catheterization and nearly-simultaneous echocardiography. Right ventricular wall tension was estimated according to Laplace’s law as right ventricle length × tricuspid regurgitation peak gradient and it was correlated with right ventricle haemodynamic profile; its potential prognostic impact was tested along with canonical right ventricle function parameters. Right ventricular wall tension correlated significantly with invasive estimation of right ventricle end-diastolic pressure (R: 0.343, p

Background: Aortic root dilation is an established risk factor for aortic dissection. Despite the relations between aortic root remodeling, carotid-femoral pulse wave velocity (cfPWV) and aortic blood pressure have been advocated by several clinical studies and is supported by physical law, invasive data are lacking. We aimed to investigate the relationship between aortic root remodeling, invasively-measured central blood pressure and cfPWV in patients referred for invasive hemodynamic evaluation for suspected coronary disease. Methods: In 71 patients aortic pulse pressure (aoPP) was measured in the proximal aorta with a calibrated fluid-filled pressure catheter. Before entering the hemodynamic room all patients underwent 2D echocardiographic quantification of aortic root diameter and measurement of cfPWV. Aortic root diameter was then expressed into z-score following age, sex and height adjusted reference values (1). Results: Mean age was 67 ± 10 years and 76.1% of patients were men. Invasive aortic systolic pressure was 146 ± 23 mmHg, diastolic pressure was 78 ± 13 mmHg, and aoPP was 68 ± 21 mmHg. Aortic Z-score was −0.32 ± 1.7, while CfPWV was 9.8±3 m/s. While Log10cfPWV and aoPP showed a positive relation (r=0.426, p

Q fever is an infectious disease caused by Coxiella burnetii. Its clinical presentation is often nonspecific and the serological diagnosis difficult to make, especially in the absence of specific and suspected medical history. This article presents a case of fever of unknown origin (FUO), interpreted as an autoimmune hepatitis, later proven by the liver biopsy to be a granulomatous hepatitis caused by C. burnetii. The approach to FUO, the features of granulomatous hepatitis and Q fever are presented and discussed.

Introduction: Acute and chronic aortic syndromes are associated with substantial morbidity and mortality. Silent risk factors such as arterial hypertension and aortic root dilatation can increase the likelihood of aortic dissection or rupture. The relationship between arterial hypertension and the dimensions of the aortic root dimension is a topic of active debate. Materials and methods: We reviewed the literature on the physiopathology, diagnosis, natural history, and management of thoracic aortic aneurysms. Results: Biological variables influencing the size of the aorta include age, sex, body surface area, pressure values, and stroke volume. Pathologic enlargement of the thoracic aorta can be caused by genetic, degenerative, inflammatory, traumatic, or toxic factors. Studies investigating the correlation between aortic dimensions and arterial pressures (diastolic, systolic, or pulse) have produced discordant results. Discussion: Classically, emphasis has been placed on the importance of hypertension-related degeneration of the medial layer of the aortic wall, which leads to dilatation of the thoracic aorta, reduced aortic wall compliance, and increased pulse pressures. However, there are no published data that demonstrate unequivocally the existence of a pathogenetic correlation between arterial hypertension and aortic root dilatation. Furthermore, there is no evidence that antihypertensive therapy is effective in the management of nonsyndromic forms of aortic root dilatation. An interesting branch of research focuses on the importance of genetic predisposition in the pathogenesis of thoracic aortic aneurysms. Different genetic backgrounds could explain differences in the behaviour of aortic walls exposed to the same hemodynamic stress. Further study is needed to evaluate these focal physiopathological aspects.

The hypertensive patient is the most stable phenotype in psychosomatic medicine. Hypertensive patients represent a vulnerable population that deserves special attention from health care providers and systems, and psychosomatic medicine may be an important tool in the management of high blood pressure. Depression, anxiety disorders and personality features are often associated with elevated blood pressure (BP) and they may have a role in the development of mild high-renin essential hypertension. Besides, “white coat” hypertension and “masked” hypertension demonstrate how clinic blood pressure could be strongly related to trait anxiety. Hypertension is largely asymptomatic, and patients often have little understanding of the importance of achieving BP control. Medication adverse effects may become an important factor in poor adherence to the treatment and the antidepressant use increases the risk of hypertension. So, the challenge in the management of hypertensive patients is the adherence to non-pharmacological and behavioural treatments for hypertension.

[This corrects the article DOI: 10.1371/journal.pone.0151523.].

INTRODUCTION:Current evidence suggests that aortic blood pressure has a superior prognostic value with respect to brachial pressure for cardiovascular events, but direct measurement is not feasible in daily clinical practice. AIM:The aim of the present study is the clinical validation of a multiscale mathematical model for non-invasive appraisal of central blood pressure from subject-specific characteristics. METHODS:A total of 51 young male were selected for the present study. Aortic systolic and diastolic pressure were estimated with a mathematical model and were compared to the most-used non-invasive validated technique (SphygmoCor device, AtCor Medical, Australia). SphygmoCor was calibrated through diastolic and systolic brachial pressure obtained with a sphygmomanometer, while model inputs consist of brachial pressure, height, weight, age, left-ventricular end-systolic and end-diastolic volumes, and data from a pulse wave velocity study. RESULTS:Model-estimated systolic and diastolic central blood pressures resulted to be significantly related to SphygmoCor-assessed central systolic (r = 0.65 p

Increased blood pressure represents a major cardiovascular risk factor for western populations. Usually blood pressure is measured peripherally, but current evidence suggested that central blood pressure better predicts cardiovascular events. However, central blood pressure measurement is not feasible in daily clinical practice. New instruments can estimate non-invasively central blood pressure from applanation tonometry at peripheral sites and transfer function. Accuracy of this evaluation has been questioned. Remarkable development in medical imaging and computation techniques granted the opportunity to explore mathematical models describing the cardiovascular functioning. Aim of the present study is the clinical validation of a mathematical model for appraisal of central blood pressure from subject-specific non-invasive measurements (i.e. brachial pressure, age, height, weight, ESV, EDV, etc.). A total of 52 healthy young male were selected for the present study. Central pressures were estimated with subject-specific model and compared with a common non-invasive technique (Sphygmocor). Model estimated systolic and diastolic blood pressure resulted to be significantly related to Sphygmocor central systolic (r 0.65 p