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.

Multiple drug intolerance in antihypertensive patients: what is known and what is missing.

Drug allergy and intolerance are increasingly recognized as significant public health concerns, leading to adverse reactions in patients undergoing pharmacological treatments. Multiple drug intolerance syndrome (MDIS), characterized by adverse reactions to at least three different drug classes without a clear immunological mechanism, poses a substantial challenge, particularly in hypertensive patients. Despite its link to suboptimal adherence and uncontrolled blood pressure, MDIS in the context of hypertension remains insufficiently explored. This review synthesizes existing literature on MDIS, emphasizing clinical characteristics, pathogenesis, and psychiatric comorbidity. Furthermore, it delves into MDIS in the context of hypertension, highlighting the importance of a multidisciplinary approach in diagnosis and management, including innovative therapeutic strategies such as novel therapeutic algorithms or renal denervation. The review concludes by emphasizing the necessity for further research and clinical trials to enhance our understanding and address MDIS, especially in hypertensive patients.

Prevalence, Clustering, and Current Management of Cardiovascular Risk Factors Upon First Referral to Hypertension Specialists: the APPROACH Study.

INTRODUCTION: Several observational studies have been conducted to assess the prevalence of cardiovascular risk factors in hypertensive patients; however, none has yet investigated prevalence, clustering, and current management of cardiovascular risk factors upon first referral to hypertension specialists, which is the aim of the present study. METHODS: Consecutive adult outpatients with essential/secondary hypertension were included at the time of their first referral to hypertension specialists at 13 Italian centers in the period April 2022-2023 if they had at least one additional major cardiovascular risk factor among LDL-hypercholesterolemia, type 2 diabetes, and cigarette smoking. Prevalence, degree of control, and current management strategies of cardiovascular risk factors were assessed. RESULTS: A total of 255 individuals were included, 40.2% women and 98.4% Caucasian. Mean age was 60.3±13.3 years and mean blood pressure [BP] was 140.3±17.9/84.8±12.3 mmHg). Most participants were smokers (55.3%), had a sedentary lifestyle (75.7%), suffered from overweight/obesity (51%) or high LDL-cholesterol (41.6%), had never adopted strategies to lose weight (55.7%), and were not on a low-salt diet (57.4%). Only a minority of patients reported receiving specialist counseling, and 27.9% had never received recommendations to correct unhealthy lifestyle habits. Nearly 90% of individuals with an estimated high/very high cardiovascular risk profile did not achieve recommended LDL-cholesterol targets. CONCLUSIONS: In patients with hypertension, both pharmacological and lifestyle therapeutic advice are yet to improve before referral to hypertension specialists. This should be considered in the primary care setting in order to optimize cardiovascular risk management strategies.

Developing the Physical Performance in Youth Soccer: Short-Term Effect of Dynamic-Ecological versus Traditional Training Approach for Sub-Elite U13 Players-An Ecological Exploratory Cluster Randomised Trial.

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.

Hypotensive episodes at 24-h ambulatory blood pressure monitoring predict adverse outcomes in Parkinson's disease.

PURPOSE: Neurogenic orthostatic hypotension (nOH) is a frequent nonmotor feature of Parkinson's disease (PD), associated with adverse outcomes. Recently, 24-h ambulatory blood pressure monitoring (ABPM) showed good accuracy in diagnosing nOH. This study aims at evaluating the prognostic role of ABPM-hypotensive episodes in predicting PD disability milestones and mortality and comparing it to the well-defined prognostic role of bedside nOH. METHODS: Patients with PD who underwent ABPM from January 2012 to December 2014 were retrospectively enrolled and assessed for the development of falls, fractures, dementia, bed/wheelchair confinement, hospitalization, and mortality, during an up-to-10-year follow-up. Significant ABPM-hypotensive episodes were identified when greater than or equal to two episodes of systolic BP drop ≥ 15 mmHg (compared with the average 24 h) were recorded during the awakening-to-lunch period. RESULTS: A total of 99 patients (74% male, age 64.0 ± 10.1 years, and PD duration 6.4 ± 4.0 years) were enrolled. At baseline, 38.4% of patients had ABPM-hypotensive episodes and 46.5% had bedside nOH. On Kaplan-Meier analysis, patients with ABPM-hypotensive episodes showed earlier onset of falls (p = 0.001), fractures (p = 0.004), hospitalizations (p = 0.009), bed/wheelchair confinement (p = 0.032), dementia (p = 0.001), and shorter survival (8.0 versus 9.5 years; p = 0.009). At Cox regression analysis (adjusted for age, disease duration, Charlson Comorbidity Index, and Hoehn and Yahr stage) a significant association was confirmed between ABPM-hypotensive episodes and falls [odds ratio (OR) 3.626; p = 0.001), hospitalizations (OR 2.016; p = 0.038), and dementia (OR 2.926; p = 0.008), while bedside nOH was only associated with falls (OR 2.022; p = 0.039) and dementia (OR 1.908; p = 0.048). CONCLUSIONS: The presence of at least two ABPM-hypotensive episodes independently predicted the development of falls, dementia, and hospitalization, showing a stronger prognostic value than the simple bedside assessment.

Hypotensive episodes at 24-h Ambulatory Blood Pressure Monitoring predict adverse outcomes in Parkinson's Disease.

Purpose: Neurogenic orthostatic hypotension (nOH) is a frequent non-motor feature of Parkinson's disease (PD), associated with adverse outcomes. Recently, 24-hour ambulatory BP monitoring (ABPM) has been shown to diagnose nOH with good accuracy (in the presence of at least 2 episodes of systolic BP drop ≥ 15 mmHg compared to the average 24-h). This study aims at evaluating the prognostic role of ABPM-hypotensive episodes in predicting PD disability milestones and mortality and comparing it to well-defined prognostic role of nOH. Methods: PD patients who underwent ABPM from January 2012 to December 2014 were retrospectively enrolled and assessed for the development of falls, fractures, dementia, bed/wheelchair confinement, hospitalization, mortality, during an up-to-10-year follow-up. Results: Ninety-nine patients (male 74%; age: 64.0 ± 10.1 years; PD duration: 6.4 ± 4.0 years) were enrolled. At baseline, 38.4% of patients had ABPM-hypotensive episodes and 46.5% had bedside nOH.At Kaplan-Meier analysis patients with ABPM-hypotensive episodes had an earlier onset of falls (p = 0.001), fractures (p = 0.004), hospitalizations (p = 0.009), bed/wheelchair confinement (p = 0.032), dementia (p = 0.001), and showed a shorter survival (8.0vs9.5 years; p = 0.009). At Cox regression analysis (adjusted for age, disease duration, Charlson Comorbidity Index, and H&Y stage at baseline) a significant association was confirmed between ABPM-hypotensive episodes and falls (OR:3.626; p = 0.001), hospitalizations (OR:2.016; p = 0.038), and dementia (OR:2.926; p = 0.008), while bedside nOH was only associated with falls (OR 2.022; p = 0.039) and dementia (OR:1.908; p = 0.048). Conclusion: The presence of at least two ABPM-hypotensive episodes independently predicted the development of falls, dementia, and hospitalization, showing a stronger prognostic value than the simple bedside assessment.

Long-Term Follow-Up of Patients With Elevated Aldosterone-to-Renin Ratio but Negative Confirmatory Test: The Progression of Primary Aldosteronism Phenotypes.

BACKGROUND: About 10% of patients with arterial hypertension have a positive screening test for primary aldosteronism (PA) and 50% to 70% of them have a negative confirmatory test: the appropriate follow-up of these patients is currently unknown. We investigated the incidence of PA in patients with previous negative confirmatory testing, after at least a 2-year follow-up. METHODS: One hundred eighty-four patients with a previously elevated aldosterone-to-renin ratio followed by a negative confirmatory test were recruited in 2 hypertension centers (Torino and Munich). We repeated the screening test for PA and, if positive, the confirmatory test (seated saline infusion test or captopril challenge test). Primary end point of the study was the incidence of newly diagnosed overt PA, as defined by a positive confirmatory test. RESULTS: After a mean follow-up of 5 years, 20% of patients developed overt PA. When subtype diagnosis was offered systematically, one-third of patients displayed unilateral PA. Patients who developed PA showed worsening of blood pressure control and a higher rate of cardiac organ damage, despite similar implementation of antihypertensive therapy, compared with patients without PA. A mild progression of autonomous aldosterone secretion was evident even in patients without confirmed PA but with relatively stable control of blood pressure levels over time. CONCLUSIONS: About one-fifth of patients with a negative confirmatory test develop overt PA over time. A clinical follow-up of patients with a negative confirmatory test is advisable, along with the repetition of PA investigation, primarily in patients with worsening of blood pressure control.

Physical strength levels and short-term memory efficiency in primary school children: a possible match?

BACKGROUND: Physical strength stimulation and, in general, physical activity induces brain plasticity (functional and structural adaptations) in different cerebral areas, benefiting executive function, cognition, attention and academic performance, which is usually estimated by measuring the Intelligent Quotient (IQ), and IQ is related to short-term memory, generally during school age. However, very little is known about the role of physical strength on short-term memory efficiency. Therefore, the primary aim of this study is to examine whether the level of physical strength can positively impact short-term memory efficiency in primary school children. Additionally, if this effect is observed, the secondary goal of this study is to determine whether the age of the participants plays a role in mediating and moderating this influence. METHODS: Seventy-five children from a primary school in the metropolitan area of Turin were recruited for this study. Each subject performed the overhead medicine ball toss (backwards) test to assess physical strength and the Digit Span test from the Wechsler Intelligence Scale for Children (WISC) to evaluate short-term memory efficiency. Firstly, a simple mediation model was used to identify the possible impact of physical strength levels on short-term memory efficiency and the potential role of participants' chronological age. Secondly, a moderation model was carried out to observe if age could moderate the impact of physical training on short-term memory efficiency and the different significance levels of the moderator. Significance was assumed at P<0.05. RESULTS: The results showed a statistically significant direct effect of physical strength on short-term memory (Β=0.429, t(72)=3.247, P<0.01). On the contrary, age was not statistically significant (Β=0.167, t(72)=3.247, P=0.211). Furthermore, a significant interaction between strength and age was identified by the moderation model (ß=-0.270, P<0.01). Specifically, the impact of physical strength levels on short-term memory increased for individuals who were above the mean age (ß=0.755, P<0.001). but not for those under the mean age (ß=0.215, P=0.153). This model explains 37.2% of the variance in memory (R2=0.372, F(3, 71)=14.031, P<0.001). CONCLUSIONS: These findings suggest that physical strength can positively influence short-term memory. In addition, this impact is enhanced in older-age children. Thus, primary school programs should stimulate physical strength to help children develop cognitive abilities.

The Influence of Subjective Perceptions and the Efficacy of Objective Evaluation in Soccer School Players' Classification: A Cross-Sectional Study.

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.

Blood pressure variability: methodological aspects, clinical relevance and practical indications for management - a European Society of Hypertension position paper ∗.

Blood pressure is not a static parameter, but rather undergoes continuous fluctuations over time, as a result of the interaction between environmental and behavioural factors on one side and intrinsic cardiovascular regulatory mechanisms on the other side. Increased blood pressure variability (BPV) may indicate an impaired cardiovascular regulation and may represent a cardiovascular risk factor itself, having been associated with increased all-cause and cardiovascular mortality, stroke, coronary artery disease, heart failure, end-stage renal disease, and dementia incidence. Nonetheless, BPV was considered only a research issue in previous hypertension management guidelines, because the available evidence on its clinical relevance presents several gaps and is based on heterogeneous studies with limited standardization of methods for BPV assessment. The aim of this position paper, with contributions from members of the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability and from a number of international experts, is to summarize the available evidence in the field of BPV assessment methodology and clinical applications and to provide practical indications on how to measure and interpret BPV in research and clinical settings based on currently available data. Pending issues and clinical and methodological recommendations supported by available evidence are also reported. The information provided by this paper should contribute to a better standardization of future studies on BPV, but should also provide clinicians with some indications on how BPV can be managed based on currently available data.

Carfilzomib-Based Regimen and Cardiotoxicity in Multiple Myeloma: Incidence of Cardiovascular Events and Organ Damage in Carfilzomib-Dexamethasone versus Carfilzomib-Lenalidomide-Dexamethasone. A Real-Life Prospective Study.

Carfilzomib-mediated cardiotoxicity in multiple myeloma (MM) is a well-established adverse effect, however limited data are available on the comparison of cardiovascular complications in patients treated with Carfilzomib-dexamethasone (target dose of K 56 mg/m2) versus Carfilzomib-lenalidomide-dexamethasone (target dose of K 27 mg/m2) beyond controlled trials. A total of 109 patients were enrolled, 47 (43%) received Kd and 62 (57%) KRd. They then underwent a baseline and follow-up evaluation including trans-thoracic echocardiography and arterial stiffness estimation. All types of cardiovascular and hypertensive events occurred more frequently in the Kd group compared with the KRd (59% vs. 40% and 55% vs. 35.5% patients, respectively, p ≤ 0.05), with higher incidence of hypertensive. The time of onset of any type of CVAE, and of major and hypertensive events was shorter in the Kd regimen (p ≤ 0.05). At follow-up, Kd patients more frequently developed signs of cardiac (decline of global longitudinal strain) and vascular organ damage (rise of pulse wave velocity), as compared with KRd. Despite the older age, longer history of MM and longer period of pre-treatment of Kd patients, these factors did not increase the probability of incidence for all types of cardiovascular events at multivariate analysis (p > 0.05). In conclusion, the Kd regimen showed greater cardiovascular toxicity and earlier onset of events with respect to KRd. Thus, a closer and thorough follow-up should be considered.

Patients with Very High Risk of Cardiovascular Adverse Events during Carfilzomib Therapy: Prevention and Management of Events in a Single Center Experience.

Carfilzomib (CFZ) improves the prognosis of multiple myeloma (MM) patients but has shown cardiovascular toxicity. The risk stratification of cardiovascular adverse events (CVAEs) now seems well established, while little is known about the course and management of patients with a high-cardiovascular-risk profile or experiencing CVAEs during therapy. Therefore, we aimed to describe our experience in decision making to support health professionals in selecting the best management strategies to prevent and treat CVAEs. A total of 194 patients with indication to CFZ underwent baseline evaluation of CVAEs risk and were prospectively followed. We propose a novel approach, which includes advanced cardiac imaging testing for patients at high baseline CV risk to rule out clinical conditions that could contraindicate starting CFZ. After baseline evaluation, 19 (9.8%) patients were found at high risk of CVAEs: 13 (6.7%) patients underwent advanced cardiac testing and 3 (1.5%) could not receive CFZ due to CV contraindications. A total of 178 (91.7%) patients started CFZ: 82 (46%) experienced arterial-hypertension-related events and 37 (20.8%) major CVAEs; 19 (10.7%) patients had to discontinue or modify the CFZ dosing regimen. Along with baseline risk stratification, subsequent cardiovascular clinical events and diagnostic follow-up both provided critical data to help identify conditions that could contraindicate the anticancer therapy.

Prevalence of Functioning Adrenal Incidentalomas: A Systematic Review and Meta-analysis.

CONTEXT: Adrenal hyperfunction is associated with an increased risk of cardiometabolic complications in subjects with adrenal incidentaloma (AI). Reliable prevalence estimates of functioning AIs are important to direct resources allocations. OBJECTIVE: To assess the prevalence of autonomous/possible autonomous cortisol secretion (ACS), primary aldosteronism (PA), pheochromocytoma (PHEO), and Cushing syndrome (CS) in patients with AI. METHODS: We performed a comprehensive search of multiple databases (PubMed, Ovid MEDLINE, Web of Science) for potentially relevant studies without language restriction, up to February 2022. Of the 1661 publications evaluated at title and abstract levels, 161 were examined as full text and 36 were included. Study level clinical data were extracted by 3 independent reviewers. RESULTS: The overall prevalence of functioning AIs was 27.5% (95% CI 23.0, 32.5). ACS/possible ACS, with a prevalence of 11.7% (95% CI 8.6, 15.7), was the most frequent hormonal alteration, while PA occurred in 4.4% of the patients (95% CI 3.1, 6.2). Subgroup analysis showed that PA was more prevalent in patients from Asia than in patients from Europe/America; in contrast, ACS/possible ACS had a lower prevalence in Asian countries. At meta-regression analysis, the prevalence of ACS/possible ACS was influenced by the proportion of female patients, while the prevalence of PA was positively associated with the proportion of patients with hypertension and the publication year. Finally, PHEO and CS prevalence were 3.8% (95% CI 2.8, 5.0) and 3.1% (95% CI 2.3, 4.3) respectively. CONCLUSION: This meta-analysis provides extensive data on the prevalence of functioning AIs and the factors affecting heterogeneity in prevalence estimates.

Primary aldosteronism: Pathophysiological mechanisms of cell death and proliferation.

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.

Approach to the Patient on Antihypertensive Therapy: Screen for Primary Aldosteronism.

Primary aldosteronism (PA) is a condition that is still largely overlooked, resulting in a considerable burden of mortality and morbidity. This is despite decades of clinical and translational research on the deleterious effects of aldosterone on the cardiovascular system and the publication of several guidelines and consensuses on its diagnosis and treatment. One of the main reasons for the low rate of testing is the difficulty of screening patients on antihypertensive therapy that potentially interferes with aldosterone and renin levels and thus confound the interpretation of the aldosterone to renin ratio, the accepted and conventionally used screening test. To avoid interference, usually the therapies that affect the renin-angiotensin aldosterone system are withdrawn and substituted with noninterfering medications. However, in many cases the screening test can be confidently interpreted even when such therapies are not discontinued. In this review, we will evaluate the effects of antihypertensive therapies on the screening test for PA and suggest a practical approach for its interpretation.

Cardiovascular Hypertension-Mediated Organ Damage in Hypertensive Urgencies and Hypertensive Outpatients.

Background: The 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. Aim: This study aimed to investigate cardiac and vascular HMOD in hypertensive urgencies (HU) and asymptomatic outpatients with grade 1-3 hypertension. Methods: Patients 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). Results: A 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). Conclusions: Patients 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.

From SGAP-Model to SGAP-Score: A Simplified Predictive Tool for Post-Surgical Recurrence of Pheochromocytoma.

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.

Correction: Gender differences in predictors of intensive care units admission among COVID-19 patients: The results of the SARS-RAS study of the Italian Society of Hypertension.

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