May Measure Month 2022 in Italy: A Focus on Fixed-dose Combination, Therapeutic Adherence, and Medical Inertia in a Nationwide Survey.

INTRODUCTION: Hypertension is the main risk factor for cardiovascular diseases (CVD). Notably, only about half of hypertensive patients manage to achieve the recommended blood pressure (BP) control. Main reasons for the persistence of uncontrolled BP during treatment are lack of compliance on the patients' side, and therapeutic inertia on physicians' side. METHODS: During the global BP screening campaign "May Measure Month" (MMM) (May 1st to July 31st, 2022), a nationwide, cross-sectional, opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥ 18 years to raise awareness of the health issues surrounding high BP. A questionnaire on demographic/clinical features and questions on the use of fixed-dose single-pills for the treatment of hypertension was administered. BP was measured with standard procedures. RESULTS: A total of 1612 participants (mean age 60.0±15.41 years; 44.7% women) were enrolled. Their mean BP was 128.5±18.1/77.1±10.4 mmHg. About half of participants were sedentary, or overweight/obese, or hypertensive. 55.5% individuals with complete BP assessment had uncontrolled hypertension. Most were not on a fixed-dose combination of antihypertensive drugs and did not regularly measure BP at home. Self-reported adherence to BP medications was similar between individuals with controlled and uncontrolled BP (95% vs 95.5%). CONCLUSIONS: This survey identified a remarkable degree of therapeutic inertia and poor patients' involvement in the therapeutic process and its monitoring in the examined population, underlining the importance of prevention campaigns to identify areas of unsatisfactory management of hypertension, to increase risk factors' awareness in the population with the final purpose of reducing cardiovascular risk.

Simulation-guided auscultatory training before graduation is associated with better auscultatory skills in residents.

INTRODUCTION: A growing body of scientific evidence shows that simulation-guided auscultatory training can significantly improve the skills of medical students. Nevertheless, it remains to be elucidated if this training has any long-term impact on auscultatory skills. We sought to ascertain whether there were differences in heart and lung auscultation among residents who received simulation-guided auscultatory training before graduation vs. those who did not. MATERIALS AND METHODS: A total of 43 residents were included in the study; 20 of them entered into Cardiology specialty school (C) and 23 of them entered into Internal and Occupational Medicine specialty schools (M) at the University of Trieste. Based on the history of simulation-guided auscultatory training before graduation (yes = Y; no = N), four groups were formed: CY, CN, MY, and MN. Residents were evaluated in terms of their ability to recognize six heart and five lung sounds, which were reproduced in a random order with the Kyoto-Kagaku patient simulator. Associations between history of simulation training, specialty choice and auscultatory skills were evaluated with Kruskal-Wallis test and logistic regression analysis. RESULTS: Auscultatory skills of residents were associated with simulation-guided training before graduation, regardless of the specialty chosen. Simulation-guided training had a higher impact on residents in Medicine. Overall, heart and lung sounds were correctly recognized in 41% of cases. Logistic regression analysis showed that simulation-guided training was associated with recognition of aortic stenosis, S2 wide split, fine crackles, and pleural rubs. Specialty choice was associated with recognition of aortic stenosis as well as aortic and mitral regurgitation. DISCUSSION: History of simulation-guided auscultatory training was associated with better auscultatory performance in residents, regardless of the medical specialty chosen. Choice of Cardiology was associated with better scores in aortic stenosis as well as aortic and mitral regurgitation. Nevertheless, overall auscultatory proficiency was quite poor, which suggests that simulation-guided training may help but is probably still too short.

Preliminary Study on Pulse Wave Changes in Patients with Inflammatory Arthropathies Treated with bDMARDs.

Background: Patients with inflammatory arthropathies exhibit an increased cardiovascular disease (CVD) risk as compared to the general population, which is not fully quantified by the conventional CVD risk scores. Biotechnological disease-modifying drugs (bDMARDs) have proved beneficial to reduce the overall CVD risk in these patients, although CVD remains a major cause of increased mortality. Since it has been shown that pulse wave parameters and in particular carotid-femoral pulse wave velocity (cfPWV) are predictors of CVD risk, the aim of this study was to evaluate their changes in patients with inflammatory arthropathies before and after bDMARD therapy. Methods: Pulse wave parameters were evaluated with applanation tonometry in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), and rheumatoid arthritis (RA), before and after two years of bDMARD therapy. Results: At baseline, cfPWV was significantly associated with age (p < 0.001) and, among pulse wave parameters, the subendocardial viability ratio was negatively associated with C-reactive protein (CRP) (p = 0.04) and the HAQ-disability index (p = 0.03). At baseline, PsA patients showed a higher percentage of male subjects, higher CRP, and the highest cfPWV values (p = 0.048). After two years, pulse wave parameters improved in the AS and RA groups, but not in the PsA group. Conclusions: Our data confirm that pulse wave parameters are potentially reversible after bDMARD therapy, as they improved in AS and RA patients. In PsA patients, there were no changes, which may be due to the higher percentage of male subjects and higher baseline cfPWV values.

Myocardial oxygen supply and demand imbalance predicts mortality in older nursing home residents: The PARTAGE study.

BACKGROUND: A mismatch between myocardial oxygen supply and demand is the most common cause of ischemic myocardial injury in older persons. The subendocardial viability ratio (SEVR) can usefully estimate the degree of myocardial perfusion relative to left-ventricular workload. The aim of the present study was to evaluate the ability of SEVR to predict long-term mortality in the older population. Additionally, we aimed to identify the SEVR cutoff value best predicting total mortality. METHODS: This is a multicenter, longitudinal study involving a large population of individuals older than 80 years living in nursing homes. Patients with cancer, severe dementia, and very low level of autonomy were excluded from the study. Participants were monitored for 10 years. Adverse outcomes were recorded every 3 months from inclusion to the end of the study. SEVR reflects the balance between subendocardial oxygen supply and demand, and was estimated non-invasively by analyzing the carotid pressure waveform recorded by applanation arterial tonometry. RESULTS: A total of 828 people were enrolled (mean age: 87.7 ± 4.7 years, 78% female). 735 patients died within 10 years and 24 were lost to follow-up. SEVR was inversely associated with mortality at univariate Cox-regression model (risk ratio, 0.683 per unit increase in SEVR; 95% confidence interval (CI) [0.502-0.930], p = 0.015) and in a model including age, sex, body mass index, Activity of Daily Living index and Mini-Mental State Examination score (risk ratio, 0.647; 95% CI [0.472-0.930]). The lowest tertile of SEVR was associated with higher 10-years total mortality than the middle (p < 0.001) and the highest (p < 0.004) tertile. A SEVR cutoff value of 83% was identified as the best predictor of total mortality. CONCLUSIONS: SEVR may be considered as a marker of "cardiovascular frailty." An accurate non-invasive estimation of SEVR could be a useful and independent parameter to assess survival probability in very old adults. TRIAL REGISTRATION: NCT00901355, registered on ClinicalTrials.gov website.

A longitudinal study on the effect of obesity upon circulating renin-angiotensin system in normal pregnancy.

BACKGROUND AND AIMS: Obesity is the most common health issue in women of reproductive age, which profoundly affects maternal-fetal health. Despite progress in understanding key inflammatory and metabolic changes, the pathogenesis of the cardiovascular phenotype of obese pregnant women remains to be fully understood. This study aimed at: (i) evaluating the changes of the renin-angiotensin system (RAS) throughout pregnancy in obese vs normal weight (control) women, and (ii) evaluating the presence of any associations between maternal hemodynamic status and RAS changes. METHODS AND RESULTS: Thirty-eight normal weight and nineteen obese pregnant women were included. Clinical assessment, blood samples and maternal hemodynamic evaluation were performed at 12, 20, 30, and 36 weeks, while ultrasound assessment was scheduled at 20, 30, and 36 weeks of gestation. Measurements of sFlt-1, PlGF, Angiotensinogen, Renin, AngII, Ang1-7, ACE and ACE2 were performed by ELISA. Our data show that normotensive obese women had lower placental blood supply, as assessed by UV-Q and UV-Q/EFW, as compared to controls, and significantly higher levels of AngII and AngII/Ang1-7 ratio, which were inversely related to placental blood supply. CONCLUSIONS: Our study shows for the first time that normotensive obese women exhibited a significant progressive increase of AngII and AngII/Ang1-7 throughout pregnancy, which were inversely related to placental blood supply as assessed by UV-Q and UV-Q/EFW. Our data shed light on the early changes in pregnant obese women and suggest that RAS dysregulation is a prerequisite rather than a consequence of hypertensive disorders of pregnancy and other maternal neonatal complications.

Real-World Retrospective Study into the Effects of Oral Semaglutide (As a Switchover or Add-On Therapy) in Type 2 Diabetes.

(1) Background: Oral semaglutide represents the first oral GLP-1 RA approved for the treatment of type 2 diabetes mellitus (T2DM). This real-world retrospective study aimed at evaluating its effectiveness and tolerability in the treatment of patients with T2DM when patients switched from a glucose-lowering agent to it and when it was added to the usual therapy. (2) Methods: Adult patients with T2DM taking oral semaglutide and followed in the ASUGI Diabetes Center were identified with the use of electronic medical records between October 2022 and May 2023. (3) Results: A total of 129 patients were recruited. The median follow-up was 6 months. Be it as a switchover or as an add-on therapy, oral semaglutide significantly reduced HbA1c and BMI. Switching from DPPIV inhibitors to oral semaglutide was associated with a significant reduction in HbA1c and BMI, switching from SGLT2 inhibitors was associated with a significant reduction in HbA1c, and switching from sulphonylureas was associated with a significant reduction in BMI. The median HbA1c change was associated with baseline HbA1c. SBP significantly decreased in the add-on group. Oral semaglutide was well tolerated. (4) Conclusions: This study shows that in the real-world setting, oral semaglutide is effective and safe as a switchover or as an add-on therapy for the treatment of T2DM.

Preliminary Study on the Effect of a Night Shift on Blood Pressure and Clock Gene Expression.

Night shift work has been found to be associated with a higher risk of cardiovascular and cerebrovascular disease. One of the underlying mechanisms seems to be that shift work promotes hypertension, but results have been variable. This cross-sectional study was carried out in a group of internists with the aim of performing a paired analysis of 24 h blood pressure in the same physicians working a day shift and then a night shift, and a paired analysis of clock gene expression after a night of rest and a night of work. Each participant wore an ambulatory blood pressure monitor (ABPM) twice. The first time was for a 24 h period that included a 12 h day shift (08.00-20.00) and a night of rest. The second time was for a 30 h period that included a day of rest, a night shift (20.00-08.00), and a subsequent period of rest (08.00-14.00). Subjects underwent fasting blood sampling twice: after the night of rest and after the night shift. Night shift work significantly increased night systolic blood pressure (SBP), night diastolic blood pressure (DBP), and heart rate (HR) and decreased their respective nocturnal decline. Clock gene expression increased after the night shift. There was a direct association between night blood pressure and clock gene expression. Night shifts lead to an increase in blood pressure, non-dipping status, and circadian rhythm misalignment. Blood pressure is associated with clock genes and circadian rhythm misalignement.

Clinical Characterization and Predictive Factors for Progression in a Cohort of Patients with Interstitial Lung Disease and Features of Autoimmunity: The Need for a Revision of IPAF Classification Criteria.

Background and Objectives: The "interstitial pneumonia with autoimmune features" (IPAF) criteria have been criticized because of the exclusion of usual interstitial pneumonia (UIP) patients with a single clinical or serological feature. To classify these patients, the term UIPAF was proposed. This study aims to describe clinical characteristics and predictive factors for progression of a cohort of interstitial lung disease (ILD) patients with at least one feature of autoimmunity, applying criteria for IPAF, specific connective tissue diseases (CTD), and a definition of UIPAF when possible. Methods: We retrospectively evaluated data on 133 consecutive patients with ILD at onset associated with at least one feature of autoimmunity, referred by pulmonologists to rheumatologists from March 2009 to March 2020. Patients received 33 (16.5-69.5) months of follow-up. Results: Among the 101 ILD patients included, 37 were diagnosed with IPAF, 53 with ILD-onset CTD, and 11 with UIPAF. IPAF patients had a lower prevalence of UIP pattern compared to CTD-ILD and UIPAF patients (10.8% vs. 32.1% vs. 100%, p < 0.01). During the follow-up, 4 IPAF (10.8%) and 2 UIPAF (18.2%) patients evolved into CTD-ILD. IPAF patients presented features not included in IPAF criteria, such as sicca syndrome (8.1%), and were more frequently affected by systemic hypertension (p < 0.01). Over one year, ILD progression (greater extent of fibrosis on HRCT and/or decline in PFTs) was less frequent in the IPAF group compared to CTD-ILD and UIPAF (32.3% vs. 58.8% vs. 72.7, p = 0.02). A UIP pattern and an IPAF predicted a faster (OR: 3.80, p = 0.01) and a slower (OR: 0.28, p = 0.02) ILD progression, respectively. Conclusions: IPAF criteria help identify patients who might develop a CTD-ILD, even though a single clinical or serological feature is respected. Future revisions of IPAF criteria should include sicca syndrome and separate UIP-pattern into a different definition (UIPAF), given its association with a different prognosis, independently from ILD classification.

Children With Short Stature Display Reduced ACE2 Expression in Peripheral Blood Mononuclear Cells.

Background: The cause of short stature remains often unknown. The renin-angiotensin system contributes to growth regulation. Several groups reported that angiotensin-converting enzyme 2 (ACE2)-knockout mice weighed less than controls. Our case-control study aimed to investigate if children with short stature had reduced ACE2 expression as compared to controls, and its significance. Materials and Methods: children aged between 2 and 14 years were consecutively recruited in a University Hospital pediatric tertiary care center. Cases were children with short stature defined as height SD ≤ -2 diagnosed with growth hormone deficiency (GHD) or idiopathic short stature (ISS), before any treatment. Exclusion criteria were: acute diseases, kidney disease, endocrine or autoimmune disorders, precocious puberty, genetic syndromes, SGA history. ACE and ACE2 expression were measured in peripheral blood mononuclear cells, angiotensins were measured by ELISA. Results: Children with short stature displayed significantly lower ACE2 expression, being 0.40 fold induction (0.01-2.27) as compared to controls, and higher ACE/ACE2, with no differences between GHD and ISS. ACE2 expression was significantly and inversely associated with the risk of short stature, OR 0.26 (0.07-0.82), and it had a moderate accuracy to predict it, with an AUC of 0.73 (0.61-0.84). The cutoff of 0.45 fold induction of ACE2 expression was the value best predicting short stature, identifying correctly 70% of the children. Conclusions: Our study confirms the association between the reduction of ACE2 expression and growth retardation. Further studies are needed to determine its diagnostic implications.

Is the Adrenal Incidentaloma Functionally Active? An Approach-To-The-Patient-Based Review.

Adrenal incidentalomas are a common occurrence. Most of them are adrenocortical adenomas that do not cause harm and do not require surgery, but a non-negligible proportion of incidentalomas is represented by functionally active masses, including cortisol-secreting adenomas (12%), pheochromocytomas (3-6%), aldosterone-secreting adenomas (2-3%), as well as malignant nodules, such as adrenocortical carcinomas (2-5%), which can be either functioning or non-functioning. All patients with an adrenal incidentaloma should undergo a few biochemical screening and confirmatory tests to exclude the presence of a functionally active mass. In this approach-to-the-patient-based review, we will summarize current recommendations on biochemical evaluation and management of functionally active adrenal incidentalomas. For this purpose, we will present four case vignettes, whereby we will describe how patients were managed, then we will review and discuss additional considerations tied to the diagnostic approach, and conclude with practical aspects of patient perioperative management. To improve the perioperative management of patients with functional adrenal incidentalomas, multidisciplinary meetings are advocated.

Estimation of Aortic Stiffness with Bramwell-Hill Equation: A Comparative Analysis with Carotid-Femoral Pulse Wave Velocity.

Aortic stiffness is an important clinical parameter for predicting cardiovascular events. Carotid-femoral pulse wave velocity (cf-PWV) has been proposed for performing this evaluation non-invasively; however, it requires dedicated equipment and experienced operators. We explored the possibility of measuring aortic stiffness using ultrasound scans of the abdominal aorta coupled with the Bramwell-Hill equation. Healthy subjects were investigated; measurements of cf-PWV were taken by arterial tonometry and aortic systo-diastolic pressure difference was estimated using a validated model. Pulsatility of an abdominal tract of aorta was assessed by automated processing of ultrasound scans. Through a Bland-Altmann analysis, we found large biases when estimating each parameter by applying the Bramwell-Hill equation to the measured values of the other two paramters (bias, ± 1.96 SD; PWV, about 2.1 ± 2.5 m/s; pulsatility, 12 ± 14%; pressure jump, 47 ± 55 mmHg). These results indicate that the two measures are not interchangeable, and that a large part of the bias is attributable to blood pressure estimation. Further studies are needed to identify the possible sources of bias between cf-PWV and aortic pulsatility.

Arterial Stiffness in Thyroid and Parathyroid Disease: A Review of Clinical Studies.

Growing evidence shows that arterial stiffness measurement provides important prognostic information and improves clinical stratification of cardiovascular risk. Thyroid and parathyroid diseases are endocrine diseases with a relevant cardiovascular burden. The objective of this review was to consider the relationship between arterial stiffness and thyroid and parathyroid diseases in human clinical studies. We performed a systematic literature review of articles published in PubMed/MEDLINE from inception to December 2021, restricted to English languages and to human adults. We selected relevant articles about the relationship between arterial stiffness and thyroid and parathyroid diseases. For each selected article, data on arterial stiffness were extracted and factors that may have an impact on arterial stiffness were identified. We considered 24 papers concerning hypothyroidism, 9 hyperthyroidism and 16 primary hyperparathyroidism and hypoparathyroidism. Most studies evidenced an increase in arterial stiffness biomarkers in hypothyroidism, hyperthyroidism and primary hyperparathyroidism, even in subclinical and mild forms, although heterogeneity of measurement methods and of study designs prevented a definitive conclusion, suggesting that the assessment of arterial stiffness may be considered in the clinical evaluation of cardiovascular risk in these diseases.

Discriminatory Value of Adiponectin to Leptin Ratio for COVID-19 Pneumonia.

Purpose: Obesity is a risk factor for severe coronavirus disease 2019 (COVID-19). Circulating adipokines have been associated with inflammatory burden and amplified or dysregulated immune responses. This study aimed to evaluate the discriminatory ability of adipokines to identify COVID-19 pneumonia and to assess disease severity. Methods: We conducted an observational case-control study, with a prospective design, and recruited patients with diagnosis of COVID-19 pneumonia (n = 48) and healthy controls (n = 36), who were matched by age, sex, and BMI. Leptin, adiponectin, IL-6, and TNF-α were measured by ELISA. Results: Patients with COVID-19 pneumonia had higher levels of leptin, lower adiponectin/leptin (Adpn/Lep) ratio, and higher expression of IL-6. Leptin had an acceptable discriminatory accuracy for COVID-19 pneumonia in patients with BMI >30 (AUC 0.74 [0.58, 0.90]) with a cutoff of 7852 pg/mL and it was associated with maximum respiratory support. By contrast, Adpn/Lep had an excellent discriminatory accuracy for COVID-19 pneumonia in patients with BMI <25 (AUC 0.9 [0.74, 1.06]) with a cutoff of 2.23. Conclusion: Our data indicate that high Adpn/Lep (>2.23) in lean patients is consistent with a state of good health, which decreases in case of inflammatory states, ranging from adipose tissue dysfunction with low-grade inflammation to COVID-19 pneumonia.

Type 1 diabetes is associated with significant changes of ACE and ACE2 expression in peripheral blood mononuclear cells.

BACKGROUND AND AIMS: The renin-angiotensin system (RAS), which is a key mediator of cardiovascular homeostasis, has two main axes. The classic one, including angiotensin-converting enzyme (ACE) and Angiotensin (Ang) II, promoting vasoconstriction, and the "alternative" one, including ACE2 and Ang1-7, with opposed actions to AngII. ACE2 has been identified as the main receptor of SARS-CoV2, whereby it enters the cells, leading to the downregulation of surface ACE2 and RAS tissue unbalance. Given that diabetes is associated with an increase in COVID-19 severity and death, we aimed at evaluating RAS expression in patients with type 1 diabetes (T1D). METHODS AND RESULTS: This is a case-control study comparing 39 T1D patients to 33 controls, with a median age of 29 and 32 years, and no comorbidities. ACE and ACE2 gene expression was assessed in peripheral blood mononuclear cells. T1D patients had higher ACE expression and circulating AngII, which were related to glucose levels. T1D patients had lower ACE2 expression. However, ACE2 expression was also related to the sex of participants, being higher in the female group. T1D women did not show the same increase of ACE2 expression that was seen in control women. CONCLUSION: T1D promotes the increase of ACE, AngII, and ACE/ACE2, which might contribute to the higher cardiovascular risk, as well as to severe tissue injury induced by SARS-CoV2 in these patients. The ratio ACE/ACE2 does not differ between men and women with T1D, which might explain why CVD or COVID-19 do not show substantial gender differences in these patients.

Meta-analysis on the Association Between Thyroid Hormone Disorders and Arterial Stiffness.

Context: Aortic stiffness is an emerging predictor of cardiovascular morbidity and mortality. Current data about the effect of subclinical and overt thyroid hormone disorders on aortic stiffness are often conflicting. Objective: Primary outcome was to investigate if subclinical and overt thyroid hormone disorders were associated with aortic stiffness. Secondary outcome was to identify disease effect modifiers. Methods: Data sources were PubMed, Google Scholar, SCOPUS, Web of Sciences, and the Cochrane Library. Eligible studies included reports of pulse wave velocity (PWV), which is the gold standard method for measuring aortic stiffness, in patients with subclinical and overt thyroid disorders. Two investigators independently identified eligible studies and extracted data. Pooled mean difference was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Univariate meta-regression analysis was used to identify effect modifiers. Results: Eleven observational studies were selected, including 1239 patients with subclinical hypothyroidism, 81 patients with overt hypothyroidism, 338 patients with thyrotoxicosis, and 12 715 controls. PWV was significantly higher in subclinical (P < .001) and overt hypothyroidism (P < .001), as well as in patients with thyrotoxicosis (P = .027) compared with controls. Age was an effect modifier in hypothyroid patients. Conclusion: This study shows that both overt and subclinical hypothyroidism as well as thyrotoxicosis were associated with an increase of aortic stiffness. The impact of treatment of these conditions on aortic stiffness should be assessed in clinical trials.

TRAIL/DR5 pathway promotes AKT phosphorylation, skeletal muscle differentiation, and glucose uptake.

TNF-related apoptosis-inducing ligand (TRAIL) is a protein that induces apoptosis in cancer cells but not in normal ones, where its effects remain to be fully understood. Previous studies have shown that in high-fat diet (HFD)-fed mice, TRAIL treatment reduced body weight gain, insulin resistance, and inflammation. TRAIL was also able to increase skeletal muscle free fatty acid oxidation. The aim of the present work was to evaluate TRAIL actions on skeletal muscle. Our in vitro data on C2C12 cells showed that TRAIL treatment significantly increased myogenin and MyHC and other hallmarks of myogenic differentiation, which were reduced by Dr5 (TRAIL receptor) silencing. In addition, TRAIL treatment significantly increased AKT phosphorylation, which was reduced by Dr5 silencing, as well as glucose uptake (alone and in combination with insulin). Our in vivo data showed that TRAIL increased myofiber size in HFD-fed mice as well as in db/db mice. This was associated with increased myogenin and PCG1α expression. In conclusion, TRAIL/DR5 pathway promotes AKT phosphorylation, skeletal muscle differentiation, and glucose uptake. These data shed light onto a pathway that might hold therapeutic potential not only for the metabolic disturbances but also for the muscle mass loss that are associated with diabetes.

Comparison Between Invasive and Noninvasive Methods to Estimate Subendocardial Oxygen Supply and Demand Imbalance.

Background Estimation of the balance between subendocardial oxygen supply and demand could be a useful parameter to assess the risk of myocardial ischemia. Evaluation of the subendocardial viability ratio (SEVR, also known as Buckberg index) by invasive recording of left ventricular and aortic pressure curves represents a valid method to estimate the degree of myocardial perfusion relative to left ventricular workload. However, routine clinical use of this parameter requires its noninvasive estimation and the demonstration of its reliability. Methods and Results Arterial applanation tonometry allows a noninvasive estimation of SEVR as the ratio of the areas directly beneath the central aortic pressure curves obtained during diastole (myocardial oxygen supply) and during systole (myocardial oxygen demand). However, this "traditional" method does not account for the intra-ventricular diastolic pressure and proper allocation to systole and diastole of left ventricular isometric contraction and relaxation, respectively, resulting in an overestimation of the SEVR values. These issues are considered in the novel method for SEVR assessment tested in this study. SEVR values estimated with carotid tonometry by "traditional" and "new" method were compared with those evaluated invasively by cardiac catheterization. The "traditional" method provided significantly higher SEVR values than the reference invasive SEVR: average of differences±SD= 44±11% (limits of agreement: 23% - 65%). The noninvasive "new" method showed a much better agreement with the invasive determination of SEVR: average of differences±SD= 0±8% (limits of agreement: -15% to 16%). Conclusions Carotid applanation tonometry provides valid noninvasive SEVR values only when all the main factors determining myocardial supply and demand flow are considered.

Current Status and Challenges of US-Guided Radiofrequency Ablation of Thyroid Nodules in the Long Term: A Systematic Review.

BACKGROUND: US-guided minimally-invasive techniques, such as radiofrequency ablation (RFA) have emerged as an alternative treatment for benign and malignant thyroid nodules. This systematic review aims to provide an overview on the long-term outcomes of US-guided RFA in patients with benign and malignant thyroid nodules. METHODS: We systematically searched PubMed/MEDLINE, EMBASE, and Scopus to identify articles reporting the outcomes of thyroid RFA after a follow-up of at least 3 years. RESULTS: A total of 20 studies met the inclusion criteria and were included in the review. In patients with benign thyroid nodules, RFA significantly reduced nodule volume and this was generally maintained for the following 5 years. However, a small but not negligible proportion of nodules regrew and some of them required further treatments over time. In patients with malignant nodules, RFA has been used not only to treat differentiated thyroid cancer (DTC) neck recurrences, but also to treat papillary thyroid microcarcinoma (PTMC). In most patients with PTMC, RFA led to complete disappearance of the tumor. When it was compared to surgery, RFA was not inferior in terms of oncologic efficacy but it had a lower complication rate. However, RFA did not allow for final pathology, disease staging and accurate risk stratification. CONCLUSIONS: US-guided RFA significantly reduces benign thyroid nodules and destroys most PTMC, and this is generally maintained for at least 5 years after the initial treatment. Further studies addressing the risk of regrowths in patients with benign thyroid nodules, as well as the risk of recurrence in patients with PTMC are needed.

Meta-analysis on the Effect of Mild Primary Hyperparathyroidism and Parathyroidectomy Upon Arterial Stiffness.

CONTEXT: Current data about the cardiovascular manifestations of mild primary hyperparathyroidism (pHPT) are often conflicting. Pulse wave velocity (PWV) is the gold standard for assessing aortic stiffness, and it predicts cardiovascular morbidity and mortality. OBJECTIVE: Primary outcomes were to investigate if mild pHPT was associated with higher PWV and if parathyroidectomy (PTX) reduced PWV in mild pHPT. Secondary outcome was to investigate blood pressure changes after PTX. METHODS: Sources were PubMed, Google Scholar, SCOPUS, Web of Science, and the Cochrane Library. Eligible studies included reports of PWV in patients with mild pHPT and controls, or in patients with mild pHPT before and after PTX. Two investigators independently identified eligible studies and extracted data. Pooled mean difference (MD) was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Nine observational studies and one randomized clinical trial were selected, including 433 patients with mild pHPT, 171 of whom underwent PTX, and 407 controls. PWV was significantly higher in mild pHPT than in controls (MD = 1.18, 0.67 to 1.68, P < .0001). Seven studies evaluated the effect of PTX on PWV. PTX significantly reduced PWV (MD = -0.48, -0.88 to -0.07, P = .022). CONCLUSION: Aortic stiffness is increased in patients with mild pHPT, supporting the notion that mild pHPT is also associated with adverse cardiovascular manifestations. PTX significantly reduced arterial stiffness in mild pHPT, indicating that the benefit of PTX over cardiovascular manifestations should not be dismissed but it deserves further studies.