Publications by authors named "Davide Soranna"

57 Publications

When to suspect hidden hypercortisolism in type 2 diabetes: a meta-analysis.

Endocr Pract 2021 Jul 26. Epub 2021 Jul 26.

Department of Endocrine and Metabolic Diseases, IRCCS, Istituto Auxologico Italiano, Milan, Italy; Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy. Electronic address:

Objective: Among patients with type 2 diabetes (T2D), the prevalence of hidden hypercortisolism (HidHyCo, formally called subclinical hypercortisolism or mild autonomous cortisol secretion) was estimated to be 2.2-12.1%. The aim of this study was to investigate whether the available literature helps to identify the characteristics of T2D patients more frequently associated with HidHyCo.

Methods: A meta-analysis was performed using studies that assessed both the prevalence of HidHyCo in patients with T2D and the characteristics of these patients with and without HidHyCo. The DerSimonian and Laird (DSL) and the Hartung, Knapp, Sidik and Jonkman (HKSJ) methods were utilized.

Results: Among the 18 available studies, 6 studies provided the necessary data. The association between HidHyCo and advanced T2D (based on the patients' description given in each study in presence of micro/ microvascular complications, or insulin treatment plus hypertension, or hypertension treated with ≥2 drugs), hypertension, insulin treatment and dyslipidemia was reported in 5 (2184 patients), 6 (2283 patients), 3 (1440 patients), and 3 (987 patients) studies, respectively. HidHyCo was associated with advanced T2D as assessed with both DSL (odds ratio, OR, 3.47, 95% Confidence Interval, 95%CI, 2.12-5.67) and HKSJ method (OR 3.60, 95%CI 2.03-6.41) and with the prevalence of hypertension or of insulin treatment as assessed by the DSL approach (OR 1.92, 95%CI 1.05-3.50 and OR 2.29, 95%CI 1.07-4.91, respectively), but not as assessed with HKSJ method.

Conclusions: Patients with advanced T2D have a higher prevalence of HidHyCo. These data inform about the selection of T2D patients for HidHyCo screening.
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http://dx.doi.org/10.1016/j.eprac.2021.07.014DOI Listing
July 2021

Body composition assessment using bioelectrical impedance analysis (BIA) in a wide cohort of patients affected with mild to severe obesity.

Clin Nutr 2021 Jun 28;40(6):3973-3981. Epub 2021 Apr 28.

IRCCS Istituto Auxologico Italiano, Obesity Unit, Laboratory of Nutrition and Obesity Research, Department of Endocrine and Metabolic Diseases, Milan, Italy. Electronic address:

Background & Aims: Obesity is characterized by fat mass excess (FM), extra cellular water increase (ECW) and, with ageing, decrease in fat free mass (FFM). The validity of body impedance analysis (BIA) in patients with mild to severe obesity is still debated. The purpose of this study is to describe the Resistance (Rz) and Reactance (Xc) values obtained by Body Impedance Analysis (BIA) in a wide cohort of Italian patients with mild to severe obesity. The secondary endpoint is to describe the resulting body composition values (as percentage and indexes) in this population.

Methods: The study enrolled adult in-patients with mild to severe obesity (classified with class I, II and III obesity) undergoing clinical care rehabilitation program for obesity complications and weight loss. BIA values were grouped by sex, BMI and age classes.

Results: A total of 8303 patients with obesity, aged 18 to 90 y, were studied. The Resistance (Rz) and Reactance (Xc) were reported by sex, age and BMI classes. In women and men both, the phase angle (PhA) decreases with increasing BMI (kg/m) and the resulting BIA vector was significantly shifted. The FM index (FMI) was higher (p < 0.0001) in women while FFM index (FFMI) was higher in men (p < 0.0001) and significantly associated with BMI. FFMI decreased with age in both sex (p < 0.0001). Skeletal mass (SM) presents a progressive reduction in relation to age and gender both.

Conclusions: The present BIA-based body composition analysis in a wide cohort of mild to severe obese patients revealed a significantly decreased Rz and Xc values with a consequent significant decrease of PhA in a BMI-dependent manner. The body compartments estimation with available equations was BMI, sex and age dependent. These observational results could be the basis for the development of new equations adapted for patients suffering from obesity.
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http://dx.doi.org/10.1016/j.clnu.2021.04.033DOI Listing
June 2021

Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy.

BMC Infect Dis 2021 Jun 14;21(1):566. Epub 2021 Jun 14.

Department of Endocrine and Metabolic Diseases & Lab of Endocrine and Metabolic Research, IRCCS, Istituto Auxologico Italiano, Via Magnasco 2, 20149, Milan, Italy.

Background: Vitamin D deficiency has been suggested to favor a poorer outcome of Coronavirus disease-19 (COVID-19). We aimed to assess if 25-hydroxyvitamin-D (25OHD) levels are associated with interleukin 6 (IL-6) levels and with disease severity and mortality in COVID-19.

Methods: We prospectively studied 103 in-patients admitted to a Northern-Italian hospital (age 66.1 ± 14.1 years, 70 males) for severely-symptomatic COVID-19. Fifty-two subjects with SARS-CoV-2 infection but mild COVID-19 symptoms (mildly-symptomatic COVID-19 patients) and 206 subjects without SARS-CoV-2 infection were controls. We measured 25OHD and IL-6 levels at admission and focused on respiratory outcome during hospitalization.

Results: Severely-symptomatic COVID-19 patients had lower 25OHD levels (18.2 ± 11.4 ng/mL) than mildly-symptomatic COVID-19 patients and non-SARS-CoV-2-infected controls (30.3 ± 8.5 ng/mL and 25.4 ± 9.4 ng/mL, respectively, p < 0.0001 for both comparisons). 25OHD and IL-6 levels were respectively lower and higher in severely-symptomatic COVID-19 patients admitted to intensive care Unit [(ICU), 14.4 ± 8.6 ng/mL and 43.0 (19.0-56.0) pg/mL, respectively], than in those not requiring ICU admission [22.4 ± 1.4 ng/mL, p = 0.0001 and 16.0 (8.0-32.0) pg/mL, p = 0.0002, respectively]. Similar differences were found when comparing COVID-19 patients who died in hospital [13.2 ± 6.4 ng/mL and 45.0 (28.0-99.0) pg/mL] with survivors [19.3 ± 12.0 ng/mL, p = 0.035 and 21.0 (10.5-45.9) pg/mL, p = 0.018, respectively). 25OHD levels inversely correlated with: i) IL-6 levels (ρ - 0.284, p = 0.004); ii) the subsequent need of the ICU admission [relative risk, RR 0.99, 95% confidence interval (95%CI) 0.98-1.00, p = 0.011] regardless of age, gender, presence of at least 1 comorbidity among obesity, diabetes, arterial hypertension, creatinine, IL-6 and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count; iii) mortality (RR 0.97, 95%CI, 0.95-0.99, p = 0.011) regardless of age, gender, presence of diabetes, IL-6 and C-reactive protein and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count.

Conclusion: In our COVID-19 patients, low 25OHD levels were inversely correlated with high IL-6 levels and were independent predictors of COVID-19 severity and mortality.
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http://dx.doi.org/10.1186/s12879-021-06281-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200788PMC
June 2021

Effects of insomnia and restless legs syndrome on sleep arterial blood pressure: A systematic review and meta-analysis.

Sleep Med Rev 2021 Apr 30;59:101497. Epub 2021 Apr 30.

Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

Hypertension and blunted blood pressure (BP) dipping during nighttime sleep are associated with increased cardiovascular risk. Chronic insomnia and restless legs syndrome (RLS) may affect the 24-h BP profile. We systematically reviewed the association of insomnia and RLS with BP values during nighttime sleep and the relative BP dipping pattern. We searched relevant articles in any language with selection criteria including enrolment of subjects with insomnia or RLS and with obstructive sleep apnea comorbidity assessment. Of the 872 studies originally retrieved, seven were selected. Four studies enrolled subjects with insomnia. One study relied on sleep diaries to classify nighttime sleep BP, whereas three relied only on clock time. At meta-analysis, subjects with insomnia displayed an attenuated dipping of systolic BP (-2.00%; 95% confidence interval (CI): -3.61 - -0.39%) and diastolic BP (-1.58%; 95% CI: -2.66 ̶ -0.49%) during nighttime sleep compared to controls. Three studies enrolled subjects with RLS. One study relied on polysomnography to classify nighttime sleep BP, whereas two relied only on clock time. Subjects with RLS showed increases in nighttime sleep systolic BP (5.61 mm Hg, 95% CI 0.13̶-11.09 mm Hg) compared to controls. In conclusion, the limited available data suggest that insomnia and RLS are both associated with altered BP control during nighttime sleep. There is need for more clinical studies to confirm these findings, specifically focusing on measurements of BP during objectively defined sleep, on causal roles of leg movements during sleep and alterations in sleep architecture, and on implications for cardiovascular risk. PROSPERO ACKNOWLEDGEMENT OF NUMBER: CRD42020217947.
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http://dx.doi.org/10.1016/j.smrv.2021.101497DOI Listing
April 2021

Current Limitations of Invasive Exercise Hemodynamics for the Diagnosis of Heart Failure With Preserved Ejection Fraction.

Circ Heart Fail 2021 May 6;14(5):e007555. Epub 2021 May 6.

Department of Cardiology, Cliniques Universitaires de Bruxelles, Hôpital Académique Erasme, Belgium (C.D., A.B., J.-L.V.).

Background: Exercise hemodynamics can differentiate heart failure with preserved ejection fraction (HFpEF) from noncardiac dyspnea. However, respiratory pressure swings may impact hemodynamic measurements, potentially leading to misdiagnosis of HFpEF. Moreover, threshold values for abnormal hemodynamic response indicative of HFpEF are not universally accepted. Thus, we sought to evaluate the impact of respiratory pressure swings on hemodynamic data interpretation as well as the concordance among 3 proposed exercise hemodynamic criteria for HFpEF: (1) end-expiratory pulmonary artery wedge pressure (PAWP) ≥25 mm Hg; (2) PAWP/cardiac output slope >2 mm Hg/L per minute; and (3) respiratory-averaged (avg) mean pulmonary artery pressure >30 mm Hg, total pulmonary resistance >3 WU, PAWP ≥20 mm Hg.

Methods: Fifty-seven patients with unexplained dyspnea (70% women, 70±9 years) underwent exercise cardiac catheterization. The difference between end-expiratory and averaged hemodynamic values, as well as the concordance among the 3 hemodynamic definitions of HFpEF, were assessed.

Results: End-expiratory hemodynamics measurements were higher than values averaged across the respiratory cycle. During exercise, a larger proportion of patients exceeded the threshold of 25 mm Hg for PAWP rather than for PAWP (70% versus 53%, <0.01). The concordance of 3/3 HFpEF exercise hemodynamic criteria was recorded in 70% of patients. PAWP/cardiac output slope identified HFpEF more frequently than the other 2 criteria (81% versus 64% to 69%), incorporating over 97% of abnormal responses to the latter. Patients with 3/3 positive criteria had worse clinical, gas-exchange, and hemodynamic profiles.

Conclusions: Respiratory pressure swings impact on the exercise hemodynamic definitions of HFpEF that provide discordant results in 30% of patients. Equivocal diagnoses of HFpEF might be limited by adopting the most sensitive and inclusive criterion alone (ie, PAWP/cardiac output slope).
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007555DOI Listing
May 2021

Home blood pressure during COVID-19-related lockdown in patients with hypertension.

Eur J Prev Cardiol 2021 Feb 5. Epub 2021 Feb 5.

Department of Cardiovascular, Neural and Metabolic Sciences, IRCCS Istituto Auxologico Italiano, Ospedale San Luca, Via Magnasco, 2, 20149, Milan, Italy.

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http://dx.doi.org/10.1093/eurjpc/zwab010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135487PMC
February 2021

Association between renin-angiotensin-aldosterone system inhibitors and risk of dementia: A meta-analysis.

Pharmacol Res 2021 04 24;166:105515. Epub 2021 Feb 24.

Biostatistic Unit, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy.

Objective: To evaluate the association of all RAAS inhibitors, ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on dementia onset (any dementia, Alzheimer's disease and vascular dementia) using a meta-analytic approach.

Methods: A systematic MEDLINE search was carried out to identify all observational studies published up to the 30th September 2020 evaluating the association between RAAS inhibitors and risk of dementia. Studies were included if original investigations considering incident dementia cases, with ACEIs and/or ARBs as exposure and other antihypertensives (AHs) use as reference, and if reporting association estimates and relative variability measures. Random effect pooled relative risks (pRR) and the corresponding 95% confidence intervals (95%CI) were calculated according to DerSimonian and Laird's (DL) or to Hartung Knapp Sidik Jonkman (HKSJ) method depending on the number of studies and between-studies heterogeneity. A linear mixed meta-regression model (MM) was applied to take into account correlation among association estimates from the same study.

Results: 15 studies were included in the meta-analysis. ARBs but not ACEIs' use led to a significant reduction of the risk of any dementia (pRR 0.78, 95%CI 0.70-0.87) and Alzheimer's disease (pRR 0.73, 95%CI 0.60-0.90). Moreover, when compared to ACEIs, ARBs reduced of 14% the risk of any dementia (pRR 0.86, 95%CI 0.79-0.94).

Conclusions: ARBs but not ACEIs led to a reduction in the risk of any dementia. The difference between ARBs and ACEIs in terms of preventive effectiveness could be due to distinct profiles of antagonism towards independent receptor pathways or to differential influences on amyloid metabolism.
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http://dx.doi.org/10.1016/j.phrs.2021.105515DOI Listing
April 2021

Low-blood pressure phenotype underpins the tendency to reflex syncope.

J Hypertens 2021 Jul;39(7):1319-1325

Department of Clinical Sciences, Lund University.

Background: We hypothesized that cardiovascular physiology differs in reflex syncope patients compared with the general population, predisposing such individuals to vasovagal reflex.

Methods: In this multicohort cross-sectional study, we compared aggregate data of resting SBP, DBP, pulse pressure (PP) and heart rate (HR), collected from six community-based cohort studies (64 968 observations) with those from six databases of reflex syncope patients (6516 observations), subdivided by age decades and sex.

Results: Overall, in male individuals with reflex syncope, SBP (-3.4 mmHg) and PP (-9.2 mmHg) were lower and DBP (+2.8 mmHg) and HR (+5.1 bpm) were higher than in the general population; the difference in SBP was higher at ages above 60 years. In female individuals, PP (-6.0 mmHg) was lower and DBP (+4.7 mmHg) and HR (+4.5 bpm) were higher than in the general population; differences in SBP were less pronounced, becoming evident only above 60 years. Compared with male individuals, SBP in female individuals exhibited slower increase until age 40 years, and then demonstrated steeper increase that continued throughout remaining life.

Conclusion: The patients prone to reflex syncope demonstrate a different resting cardiovascular haemodynamic profile as compared with a general population, characterized by lower SBP and PP, reflecting reduced venous return and lower stroke volume, and a higher HR and DBP, suggesting the activation of compensatory mechanisms. Our data contribute to a better understanding why some individuals with similar demographic characteristics develop reflex syncope and others do not.

Video Abstract: http://links.lww.com/HJH/B580.
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http://dx.doi.org/10.1097/HJH.0000000000002800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183486PMC
July 2021

Efficacy Profile and Safety of Very Low-Dose Rituximab in Patients with Graves' Orbitopathy.

Thyroid 2021 05 31;31(5):821-828. Epub 2021 Mar 31.

Department of Clinical Sciences and Community Health, Graves' Orbitopathy Center, Endocrinology, Milan, Italy.

Rituximab (RTX), a chimeric human-murine anti-CD20 monoclonal antibody, has been used for treatment of active moderate-severe Graves' orbitopathy (GO) since 2004 as second-line therapy in patients unresponsive to intravenous steroids. We conducted an open-label prospective study (EUDRACT 2012-001980-53) in which patients were treated with a single infusion of only 100 mg RTX to analyze the efficacy and safety of this low dose. Seventeen patients, of whom nine had disease that was unresponsive to intravenous methylprednisolone and eight with newly diagnosed GO, were enrolled. Disease activity was assessed with the clinical activity score (CAS) and severity with a composite ophthalmic score. Long-term surgical treatment and quality of life were also assessed, as well as treatment-related adverse events. Mean baseline CAS was 4.56 ± 0.96 and decreased to 1.25 ± 1.14 at 24 weeks ( = 0.001). Disease inactivation occurred within 24 weeks in >90% of patients and was unrelated to disease duration. Severity improved in about 60% of patients, with no relapses. All patients showed peripheral depletion of CD20 and CD19 cells at the end of RTX infusion (60 minutes). Two patients required surgical orbital decompression because of optic neuropathy (ON). Among adverse events observed, there was one patient who developed a cytokine release syndrome. A dose of 100 mg RTX is effective in patients with active moderate-severe GO. Low doses are better tolerated, expose patients to immune suppression for a shorter period of time, and are extremely cost effective, compared with higher doses. This dose, consistently with all other immunosuppressants, does not prevent the progression of GO to dysthyroid ON.
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http://dx.doi.org/10.1089/thy.2020.0269DOI Listing
May 2021

Haemodynamic characteristics of COVID-19 patients with acute respiratory distress syndrome requiring mechanical ventilation. An invasive assessment using right heart catheterization.

Eur J Heart Fail 2020 12 7;22(12):2228-2237. Epub 2020 Dec 7.

Cardiovascular Department, ASST Papa Giovanni XXIII, Bergamo, Italy.

Aims: Interstitial pneumonia due to coronavirus disease 2019 (COVID-19) is often complicated by severe respiratory failure. In addition to reduced lung compliance and ventilation/perfusion mismatch, a blunted hypoxic pulmonary vasoconstriction has been hypothesized, that could explain part of the peculiar pathophysiology of the COVID-19 cardiorespiratory syndrome. However, no invasive haemodynamic characterization of COVID-19 patients has been reported so far.

Methods And Results: Twenty-one mechanically-ventilated COVID-19 patients underwent right heart catheterization. Their data were compared both with those obtained from non-mechanically ventilated paired control subjects matched for age, sex and body mass index, and with pooled data of 1937 patients with 'typical' acute respiratory distress syndrome (ARDS) from a systematic literature review. Cardiac index was higher in COVID-19 patients than in controls [3.8 (2.7-4.5) vs. 2.4 (2.1-2.8) L/min/m , P < 0.001], but slightly lower than in ARDS patients (P = 0.024). Intrapulmonary shunt and lung compliance were inversely related in COVID-19 patients (r = -0.57, P = 0.011) and did not differ from ARDS patients. Despite this, pulmonary vascular resistance of COVID-19 patients was normal, similar to that of control subjects [1.6 (1.1-2.5) vs. 1.6 (0.9-2.0) WU, P = 0.343], and lower than reported in ARDS patients (P < 0.01). Pulmonary hypertension was present in 76% of COVID-19 patients and in 19% of control subjects (P < 0.001), and it was always post-capillary. Pulmonary artery wedge pressure was higher in COVID-19 than in ARDS patients, and inversely related to lung compliance (r = -0.46, P = 0.038).

Conclusions: The haemodynamic profile of COVID-19 patients needing mechanical ventilation is characterized by combined cardiopulmonary alterations. Low pulmonary vascular resistance, coherent with a blunted hypoxic vasoconstriction, is associated with high cardiac output and post-capillary pulmonary hypertension, that could eventually contribute to lung stiffness and promote a vicious circle between the lung and the heart.
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http://dx.doi.org/10.1002/ejhf.2058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753704PMC
December 2020

Office and Ambulatory Arterial Hypertension in Highlanders: HIGHCARE-ANDES Highlanders Study.

Hypertension 2020 12 11;76(6):1962-1970. Epub 2020 Nov 11.

From the Department of Cardiovascular, Neural and Metabolic Sciences (G.B., M.F.P., G.P.), University of Milano-Bicocca, Milan, Italy.

Millions of people worldwide live at high altitude, being chronically exposed to hypobaric hypoxia. Hypertension is a major cardiovascular risk factor but data on its prevalence and determinants in highlanders are limited, and systematic studies with ambulatory blood pressure monitoring are not available. Aim of this study was to assess the prevalence of clinic and ambulatory hypertension and the associated factors in a sample of Andean highlanders. Hypertension prevalence and phenotypes were assessed with office and ambulatory blood pressure measurement in a sample of adults living in Cerro de Pasco, Peru (altitude 4340 m). Basic clinical data, blood oxygen saturation, hematocrit, and Qinghai Chronic Mountain Sickness score were obtained. Participants were classified according to the presence of excessive erythrocytosis and chronic mountain sickness diagnosis. Data of 289 participants (143 women, 146 men, mean age 38.3 years) were analyzed. Office hypertension was present in 20 (7%) participants, while ambulatory hypertension was found in 58 (20%) participants. Masked hypertension was common (15%), and white coat hypertension was rare (2%). Among participants with ambulatory hypertension, the most prevalent phenotypes included isolated nocturnal hypertension, isolated diastolic hypertension, and systodiastolic hypertension. Ambulatory hypertension was associated with male gender, age, overweight/obesity, 24-hour heart rate, and excessive erythrocytosis. Prevalence of hypertension among Andean highlanders may be significantly underestimated when based on conventional blood pressure measurements, due to the high prevalence of masked hypertension. In highlanders, ambulatory hypertension may be independently associated with excessive erythrocytosis.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16010DOI Listing
December 2020

Clinical benefits of sex steroids given as a priming prior to GH provocative test or as a growth-promoting therapy in peripubertal growth delays: Results of a retrospective study among ENDO-ERN centres.

Clin Endocrinol (Oxf) 2021 02 15;94(2):219-228. Epub 2020 Oct 15.

Department of Endocrine and Metabolic Diseases &, Lab of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Milan, Italy.

Objectives: Sex steroids, administered as a priming before GH stimulation tests (GHST) to differentiate between growth hormone deficiency (GHD) and constitutional delay of growth and puberty (CDGP) or as growth-promoting therapy using low-dose sex steroids (LDSS) in CDGP, are much debated. We aimed to compare auxological outcomes of CDGP or GHD children undergoing primed or unprimed GHST and to evaluate LDSS treatment in CDGP.

Design: Retrospective study among three paediatric University Hospitals in Italy and UK.

Methods: 184 children (72 females) aged 12.4 ± 2.08 years underwent primed (/P ) or unprimed (/P ) GHST and were followed up until final height (FH). CDGP patients were untreated (CDG P ) or received LDSS (CDGP ). The cohort included 34 CDG P /P , 12 CDGP /P , 51 GHD/P , 29 CDG P /P , 2 CDGP /P and 56 GHD/P . FH standard deviation score (SDS), Δ SDS FH-target height (TH) and degree of success (-1 ≤ Δ SDS FH-SDS TH ≤ +1) were outcomes of interest.

Results: GHD/P had better FH-SDS (-0.87 vs -1.49; P = .023) and ΔSDS FH-TH (-0.35 vs -0.77; P = .002) than CDGP /P . Overall, GHD/P showed the highest degree of success (90%, P = .006). Regardless of priming, both rhGH and LDSS improved degree of success compared to no treatment (89% and 86% vs 63%, P = .0009). GHD/P showed a trend towards a higher proportion of permanent GHD compared to GHD/P (30.43% vs 15.09%; P = .067).

Conclusion: In peripubertal children, priming before GHST improves diagnostic accuracy of GHST for idiopathic GHD. LDSS treatment improves auxological outcomes in CDGP.
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http://dx.doi.org/10.1111/cen.14337DOI Listing
February 2021

Determinants of the Lifestyle Changes during COVID-19 Pandemic in the Residents of Northern Italy.

Int J Environ Res Public Health 2020 08 28;17(17). Epub 2020 Aug 28.

Research laboratory of Preventive Medicine, IRCCS Istituto Auxologico Italiano, 20122 Milan, Italy.

Background: The confinement recommended during COVID-19 pandemic could affect behavior and health.

Methods: We conducted a self-reported survey in northern Italy to observe the lockdown effects on lifestyle changes and to assess their determinants. Prevalence Odds Ratio and Prevalence Risk Ratio were determined.

Results: 490 adults (84% female) completed the survey: 13% and 43% reported improved and unchanged sleep quality, respectively, while 43% had insomnia symptoms. Among the 272 active subjects in pre-lockdown, 14% continued habitual exercising, 18% increased it and 68% reduced it; 27% of sedentary subjects started physical exercise; 34% reported an improvement in diet quality; 42% increased food intake and 13% decreased it; and 38% of the smokers increased cigarette consumption. Age and the pre-lockdown habit of regular physical exercising were the mainly determinants of lifestyle changes whereas BMI, gender, and the presence of chronic diseases did not. Living with other people increased the likelihood of increasing the food intake ( = 0.002).

Conclusions: More than a third of people were able to positively reorganize their lives during the forced home confinement. It is worth to disseminate information to preserve a healthy lifestyle even when confined at home.
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http://dx.doi.org/10.3390/ijerph17176287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504331PMC
August 2020

Effect of high-altitude trekking on blood pressure and on asymmetric dimethylarginine and isoprostane production: Results from a Mount Ararat expedition.

J Clin Hypertens (Greenwich) 2020 08 6;22(8):1494-1503. Epub 2020 Aug 6.

Department of Cardiovascular Neural and Metabolic Sciences, IRCCS Istituto Auxologico Italiano, Milan, Italy.

The study aimed at exploring the mechanisms behind blood pressure and heart rate changes upon acute altitude exposure utilizing urinary excretion of biochemical factors involved in cardiovascular regulation. The study was conducted on 12 lowlander native male mountain climbers, living at sea level, exposed to altitudes ranging from 1800 to 5147 m above sea level over 4 days, during their ascent to Mount Ararat (Turkey). Blood pressure (measured by oscillometric method), heart rate, and blood oxygen saturation (SpO ) were recorded at rest (on awakening before food intake), in hypoxic conditions at 4200 m and at sea level before and after the altitude expedition. In the same study conditions (ie before-during-after the expedition), first-voided urinary samples were collected and assayed for 8-iso-prostaglandin F (8-iso-PGF ) and asymmetric dimethylarginine (ADMA) determination. Heart rate, and systolic and diastolic blood pressures were higher (P < .05) at high altitude than at the sea level. Furthermore, both urinary 8-iso-PGF and ADMA were significantly elevated (P < .01) at high altitude and returned to normal levels soon after returning to sea level. A 4-day exposure to high-altitude hypoxia induced a temporary increase in blood pressure and heart rate, confirming previous findings. Blood pressure increase at high altitude was associated with significantly enhanced production of biochemical mediators such as 8-iso-PGF2α, catecholamines, and ADMA, although we could not demonstrate a direct link between these parallel significant changes probably due to the forcefully limited sample size of our study, carried out in challenging environmental conditions at very high altitude.
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http://dx.doi.org/10.1111/jch.13961DOI Listing
August 2020

Postoperative and mid-term hemodynamic changes after replacement of the ascending aorta.

J Thorac Cardiovasc Surg 2020 May 27. Epub 2020 May 27.

Istituto Auxologico Italiano, IRCCS, Cardiology Unit, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.

Objectives: To evaluate aortic distensibility and pulse waveform patterns associated with the ascending aortic aneurysm, and to analyze the postoperative and mid-term hemodynamic changes induced by prosthetic replacement of the ascending aorta.

Methods: Central blood pressure waves were recorded at the carotid artery level by means of a validated transcutaneous arterial tonometer in 30 patients undergoing prosthetic replacement of ascending aortic aneurysm and in 30 control patients. Measurements were obtained the day before surgery and 5 to 7 days and 16 to 20 months after surgery.

Results: The ascending aortic aneurysm was associated with a less steep slope of early systolic phase of the pressure curve (pulsus tardus) compared with a control group (0.54 ± 0.18 mm Hg/ms vs 0.69 ± 0.26 mm Hg/ms; P = .011). Replacing the ascending aorta with a noncompliant vascular prosthesis steepened the pulse pressure slope during the early systolic phase in the postoperative period (0.77 ± .29 mm Hg/ms), providing values comparable with those of the control group in the mid-term (0.67 ± .20 mm Hg/ms). No change in aortic stiffness was found either postoperatively or in the mid-term after ascending aorta surgical replacement (carotid-femoral pulse wave velocity: preoperative, 9.0 ± 2.6 m/s; postoperative, 9.0 ± 2.9 m/s; mid-term postoperative, 9.3 ± 2.8 m/s).

Conclusions: This study does not confirm the assumption that substitution of the viscoelastic ascending aorta with a rigid prosthesis can cause serious hemodynamic alterations downstream, because we did not observe a worsening of global aortic distensibility after insertion of a rigid prosthetic aorta. The ascending aortic aneurysm is associated with a pulsus tardus.
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http://dx.doi.org/10.1016/j.jtcvs.2020.05.031DOI Listing
May 2020

Obstructive sleep apnoea treatment and blood pressure: which phenotypes predict a response? A systematic review and meta-analysis.

Eur Respir J 2020 05 7;55(5). Epub 2020 May 7.

Section of General Medicine and Hypertension, Dept of Medicine, University of Verona, Verona, Italy

The treatment for obstructive sleep apnoea (OSA) with continuous positive airway pressure (CPAP) or mandibular advancement devices (MADs) is associated with blood pressure (BP) reduction; however, the overall effect is modest. The aim of this systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effect of such treatments on BP was to identify subgroups of patients who respond best to treatment.The article search was performed in three different databases with specific search terms and selection criteria. From 2289 articles, we included 68 RCTs that compared CPAP or MADs with either passive or active treatment. When all the studies were pooled together, CPAP and MADs were associated with a mean BP reduction of -2.09 (95% CI -2.78- -1.40) mmHg for systolic BP and -1.92 (95% CI -2.40- -1.43) mmHg for diastolic BP and -1.27 (95% CI -2.34- -0.20) mmHg for systolic BP and -1.11 (95% CI -1.82- -0.41) mmHg for diastolic BP, respectively. The subgroups of patients who showed a greater response were those aged <60 years (systolic BP -2.93 mmHg), with uncontrolled BP at baseline (systolic BP -4.14 mmHg) and with severe oxygen desaturations (minimum arterial oxygen saturation measured by pulse oximetry <77%) at baseline (24-h systolic BP -7.57 mmHg).Although this meta-analysis shows that the expected reduction of BP by CPAP/MADs is modest, it identifies specific characteristics that may predict a pronounced benefit from CPAP in terms of BP control. These findings should be interpreted with caution; however, they are particularly important in identifying potential phenotypes associated with BP reduction in patients treated for OSA.
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http://dx.doi.org/10.1183/13993003.01945-2019DOI Listing
May 2020

Periodic limb movements during sleep and blood pressure changes in sleep apnoea: Data from the European Sleep Apnoea Database.

Respirology 2020 08 24;25(8):872-879. Epub 2019 Dec 24.

Sleep Disorders Center, Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.

Background And Objective: OSA and PLMS are known to induce acute BP swings during sleep. Our current study aimed to address the independent effect of PLMS on BP in an unselected OSA patient cohort.

Methods: This cross-sectional analysis included 1487 patients (1110 males, no previous hypertension diagnosis or treatment, mean age: 52.5 years, mean BMI: 30.5 kg/m ) with significant OSA (defined as AHI ≥ 10) recruited from the European Sleep Apnoea Cohort. Patients underwent overnight PSG. Patients were stratified into two groups: patients with significant PLMS (PLMSI > 25 events/hour of sleep) and patients without significant PLMS (PLMSI < 25 events/hour of sleep). SBP, DBP and PP were the variables of interest. For each of these, a multivariate regression linear model was fitted to evaluate the relationship between PLMS and outcome adjusting for sociodemographic and clinical covariates (gender, age, BMI, AHI, ESS, diabetes, smoking and sleep efficiency).

Results: The univariate analysis of SBP showed an increment of BP equal to 4.70 mm Hg (P < 0.001) in patients with significant PLMS compared to patients without significant PLMS. This increment remained significant after implementing a multivariate regression model (2.64 mm Hg, P = 0.044). No significant increment of BP was observed for DBP and PP.

Conclusion: PLMS is associated with a rise in SBP regardless of AHI, independent of clinical and sociodemographic confounders. A PLMS phenotype may carry an increased risk for cardiovascular disease in OSA patients.
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http://dx.doi.org/10.1111/resp.13760DOI Listing
August 2020

Acute Effects of Whole-Body Vibration Alone or in Combination With Maximal Voluntary Contractions on Cardiorespiratory, Musculoskeletal, and Neuromotor Fitness in Obese Male Adolescents.

Dose Response 2019 Oct-Dec;17(4):1559325819890492. Epub 2019 Dec 9.

Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-Endocrinological Research, Milan and Verbania, Italy.

Musculoskeletal and neuromotor fitness (MSMF) is reduced in obesity. Physical exercise (including whole-body vibration exercise [WBVE]) is reported to improve components related to MSMF. The aim of the study is to evaluate the acute effects of WBVE and maximal voluntary contraction (MVC), alone and in combination, on the cardiorespiratory and MSMF in obese adolescents. Eight obese adolescents performed 3 tests (WBVE, MVC, and MVC + WBVE) in different days and randomly. The outcome measures were diastolic blood pressure (DBP), systolic blood pressure (SBP), mean arterial pressure (MAP), heart rate (HR), peripheral oxygen saturation (SpO), handgrip strength (HS), one-leg standing balance (OLSB) test, sit-and-reach (SR) test, stair climbing test (time: and power: ), and sit-to-stand test (time: and power: ). No significant changes were observed in SBP, DBP, MAP, and SpO after the 3 tests, only an HR increase being observed after MVC + WBVE ( < .01) and MVC alone ( < .05). No significant differences were found in HS, OLSB, , and after the 3 different sessions. An increase in SR was found after MVC + WBVE, MVC, and WBVE ( < .01, < .05, and < .01, respectively), while a decrease in ( < .01) and an increase in were observed only after WBVE ( < .01). Taking into account the positive WBVE effects on cardiorespiratory and MSMF, WBVE might represent a nonimpact, viable, and safe exercise suitable for obese patients, which need MSMF improvement without overloading joints.
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http://dx.doi.org/10.1177/1559325819890492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904781PMC
December 2019

Effects of acute exposure to moderate altitude on blood pressure and sleep breathing patterns.

Int J Cardiol 2020 02 30;301:173-179. Epub 2019 Oct 30.

Istituto Auxologico Italiano, IRCCS, Dept of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy; Dept of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy. Electronic address:

Background: Acute exposure to high altitude (>2500 m) is known to induce a rise in blood pressure (BP) and the appearance of sleep related breathing alterations, in particular central sleep apneas and periodic breathing. Little information is available on whether this is the case in humans also for acute exposure to moderate altitude (between 1500 and 2500 m). Aim of this study was to evaluate the effects of acute exposure of healthy volunteers to moderate altitude on conventional and ambulatory BP as well as on the frequency and severity of breathing alterations during sleep.

Methods: Forty-four healthy lowlanders underwent 24-hour ambulatory BP monitoring and nocturnal cardio-respiratory sleep study at sea level and during acute (1-2 days after arrival) exposure to moderate altitude (2035 m, Sestriere, Italy). The key variables investigated included average systolic and diastolic BP and heart rate over daytime, night-time and 24 h, the frequency of obstructive and central apneas/hypopnoeas and the behaviour of oxygen saturation during sleep.

Results: Compared to sea level, during moderate altitude exposure mean systolic/diastolic BP increased significantly during daytime (respectively from 125.6 ± 10.9 to 130.6 ± 12.3, p = 0.0032 and from 78.8 ± 6.7 to 81.8 ± 7.7 mmHg, p = 0.0048) and during night-time (respectively from 102.4 ± 12.4 to 107.4 ± 12.7, p = 0.0028, and from 62.0 ± 8.2 to 65.8 ± 8.2 mmHg, p = 0.0014), with no change in nocturnal BP dipping. BP increase was more evident in participants aged over 40 years. Apnea-hypopnea index (AHI) increased from 1.60 (0.40-2.90) to 5.4 (2.90-10.60), p < 0.0001), mainly because of increasing frequency of hypopneas and central apneas, in particular in males aged over 40 years. No association was found between size of BP changes and AHI.

Conclusion: Our results indicate that in healthy subjects even exposure to moderate altitude may induce significant, although mild, changes in ambulatory BP and in respiratory patterns during sleep with gender and age-related differences. Further studies are needed to explore the clinical relevance of these findings.
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http://dx.doi.org/10.1016/j.ijcard.2019.09.034DOI Listing
February 2020

The impact of systolic and diastolic blood pressure variability on mortality is age dependent: Data from the Dublin Outcome Study.

Eur J Prev Cardiol 2020 03 11;27(4):355-364. Epub 2019 Sep 11.

Istituto Auxologico Italiano, IRCCS, Department of Cardiovascular Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy.

Background: Twenty-four-hour blood pressure variability (BPV) is independently related to cardiovascular outcomes, but limited and conflicting evidence is available on the relative prognostic importance of systolic and diastolic BPV. The aim of this study was to verify the hypothesis that the association of systolic and diastolic blood pressure variability over 24 h with cardiovascular mortality in untreated subjects is affected by age.

Design And Methods: The study included 9154 untreated individuals assessed for hypertension between 1982 and 2002 in the frame of the Dublin Outcome Study, in which 24 h ambulatory blood pressure monitoring was obtained (age 54.1 ± 14.3 years, 47% males). The association of short-term systolic and diastolic blood pressure variability with cardiovascular and all-cause mortality in the entire sample and separately in younger and older age subgroups was assessed over a median follow-up period of 6.3 years.

Results: Diastolic BPV was directly and independently related to cardiovascular mortality (adjusted hazard ratio (adjHR) for daytime standard deviation 1.16 (95% confidence interval 1.08-1.26)) with no significant differences among age groups. Conversely, systolic BPV was independently associated with cardiovascular mortality only in younger (<50 years) subjects (adjHR for daytime standard deviation 1.72 (95% confidence interval 1.33-2.23)), superseding the predictive value of diastolic BPV in this group.

Conclusions: Diastolic short-term BPV independently predicts cardiovascular mortality in hypertensive subjects at all ages, while systolic BPV seems a particularly strong predictor in young adults. If confirmed, these findings might improve the understanding of the prognostic value of BPV, with new perspectives for its possible clinical application.
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http://dx.doi.org/10.1177/2047487319872572DOI Listing
March 2020

Levothyroxine Replacement in Obese Adults: The Role of Metabolic Variables and Aging on Thyroid Testing Abnormalities.

J Clin Endocrinol Metab 2019 12;104(12):6265-6274

Division of Endocrinology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.

Context: General rates of over- and underreplacement in levothyroxine (LT4) users with primary hypothyroidism are variably high. No information on LT4 adequacy exists in obesity.

Objective: We explored rates and factors relating to LT4 adequacy in obese patients with primary hypothyroidism.

Setting: Tertiary care center.

Design: Among 4954 consecutive obese patients admitted between 2011 and 2014, 691 hypothyroid patients receiving LT4 therapy and 691 body mass index (BMI)-, age-, and sex-matched euthyroid controls underwent analysis of thyroid function, glucolipid profile, body composition, and indirect calorimetry. LT4 users were classified into low TSH (<0.27 mU/L), euthyroid (0.27 to 4.2 mU/L), and high TSH (>4.2 mU/L).

Results: LT4 users constituted 13.9% of the incident population. TSH was low in 7.5%, high in 17.2%, and normal in 75.2% of LT4 users. Overtreatment decreased with aging and more LT4 users ≥65 years of age had normal TSH than those <65 years of age (P < 0.05). Compared with the euthyroid obese group, LT4 users showed higher adiposity, similar insulin resistance, but a healthier lipid profile. In multivariable analyses, LT4 dose was predicted by fat-free mass, hypothyroidism cause, and sex (P < 0.0001 to < 0.05). Risk of LT4 overreplacement increased with younger age (OR 0.96; 95% CI 0.94 to 0.99), higher LT4 dose (OR 2.98; 95% CI 1.44 to 6.14), and lower BMI (OR 0.93; 95% CI 0.88 to 0.99). Male sex increased the likelihood of LT4 underreplacement (OR 2.37; 95% CI 1.10 to 5.11).

Conclusions: Obesity is associated with milder rates of inadequate LT4 treatment compared with nonobese populations. LT4 adequacy increases with aging. Age, body composition, and sex are main determinants of LT4 requirements in obesity.
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http://dx.doi.org/10.1210/jc.2019-00773DOI Listing
December 2019

Three-dimensional path of the body centre of mass during walking in children: an index of neural maturation.

Int J Rehabil Res 2019 Jun;42(2):112-119

Department of Neurorehabilitation Sciences, Istituto Auxologico Italiano, IRCCS, Ospedale San Luca, Milan.

Few studies have investigated the kinematic aspects of the body centre of mass motion, that is, its three-dimensional path during strides and their changes with child development. This study aimed to describe the three-dimensional path of the centre of mass in children while walking in order to disentangle the effect of age from that of absolute forward speed and body size and to define preliminary pediatric normative values. The three-dimensional path of the centre of mass during walking was compared across healthy children 5-6- years (n = 6), 7-8 years (n = 6), 9-10 years (n = 5), and 11-13 years of age (n = 5) and healthy adults (23-48 years, n = 6). Participants walked on a force-sensing treadmill at various speeds, and height normalization of speed was conducted with the dimensionless Froude number. The total length and maximal lateral, vertical, and forward displacements of the centre of mass path were calculated from the ground reaction forces during complete strides and were scaled to the participant's height. The centre of mass path showed a curved figure-of-eight shape. Once adjusted for speed and participants' height, as age increased, there was a decrease in the three-dimensional parameters and in the lateral displacement, with values approaching those of adults. At each step, lateral redirection of the centre of mass requires brisk transient muscle power output. The base of support becomes relatively narrower with increasing age. Skilled shortening of the lateral displacement of the centre of mass may therefore decrease the risk of falling sideways. The three-dimensional path of the centre of mass may represent maturation of neural control of gait during growth.
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http://dx.doi.org/10.1097/MRR.0000000000000345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493692PMC
June 2019

MASked-unconTrolled hypERtension management based on office BP or on ambulatory blood pressure measurement (MASTER) Study: a randomised controlled trial protocol.

BMJ Open 2018 12 19;8(12):e021038. Epub 2018 Dec 19.

Department of Medicine, University of Perugia, Perugia, Italy.

Introduction: Masked uncontrolled hypertension (MUCH) carries an increased risk of cardiovascular (CV) complications and can be identified through combined use of office (O) and ambulatory (A) blood pressure (BP) monitoring (M) in treated patients. However, it is still debated whether the information carried by ABPM should be considered for MUCH management. Aim of the MASked-unconTrolled hypERtension management based on OBP or on ambulatory blood pressure measurement (MASTER) Study is to assess the impact on outcome of MUCH management based on OBPM or ABPM.

Methods And Analysis: MASTER is a 4-year prospective, randomised, open-label, blinded-endpoint investigation. A total of 1240 treated hypertensive patients from about 40 secondary care clinical centres worldwide will be included -upon confirming presence of MUCH (repeated on treatment OBP <140/90 mm Hg, and at least one of the following: daytime ABP ≥135/85 mm Hg; night-time ABP ≥120/70 mm Hg; 24 hour ABP ≥130/80 mm Hg), and will be randomised to a management strategy based on OBPM (group 1) or on ABPM (group 2). Patients in group 1 will have OBP measured at 0, 3, 6, 12, 18, 24, 30, 36, 42 and 48 months and taken as a guide for treatment; ABPM will be performed at randomisation and at 12, 24, 36 and 48 months but will not be used to take treatment decisions. Patients randomised to group 2 will have ABPM performed at randomisation and all scheduled visits as a guide to antihypertensive treatment. The effects of MUCH management strategy based on ABPM or on OBPM on CV and renal intermediate outcomes (changing left ventricular mass and microalbuminuria, coprimary outcomes) at 1 year and on CV events at 4 years and on changes in BP-related variables will be assessed.

Ethics And Dissemination: MASTER study protocol has received approval by the ethical review board of Istituto Auxologico Italiano. The procedures set out in this protocol are in accordance with principles of Declaration of Helsinki and Good Clinical Practice guidelines. Results will be published in accordance with the CONSORT statement in a peer-reviewed scientific journal.

Trial Registration Number: NCT02804074; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2017-021038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303603PMC
December 2018

Impact of Mutation Density and Heterogeneity on Papillary Thyroid Cancer Clinical Features and Remission Probability.

Thyroid 2019 02 16;29(2):237-251. Epub 2019 Jan 16.

1 Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy.

Background: The need to integrate the classification of cancer with information on the genetic pattern has emerged in recent years for several tumors.

Methods: The genomic background of a large series of 208 papillary thyroid cancers (PTC) followed at a single center was analyzed by a custom MassARRAY genotyping platform, which allows the simultaneous detection of 19 common genetic alterations, including point mutations and fusions.

Results: Of the PTCs investigated, 71% were found to have pathognomonic genetic findings, with BRAF and TERT promoter mutations being the most frequent monoallelic alterations (42% and 23.5%, respectively), followed by RET/PTC fusions. In 19.2% of cases, two or more point mutations were found, and the co-occurrence of a fusion with one or more point mutation(s) was also observed. Coexisting BRAF and TERT promoter mutations were detected in a subgroup of aggressive PTCs (12%). A correlation between several aggressive features and mutation density was found, regardless of the type of association (i.e., only point mutations, or point mutations and fusions). Importantly, Kaplan-Meier curves demonstrated that mutation density significantly correlated with a higher risk of persistent disease. In most cases, the evaluation of the allelic frequencies normalized for the cancer cell content indicated the presence of the monoallelic mutation in virtually all tumor cells. A minority of cases was found to harbor low allelic frequencies, consistent with the presence of the mutations in a small subset of cancer cells, thus indicating tumor heterogeneity. Consistently, the presence of coexisting genetic alterations with different allelic frequencies in some tumors suggests that PTC can be formed by clones/subclones with different mutational profiles.

Conclusions: A large mono-institutional series of PTCs was fully genotyped by means of a cost- and time-effective customized panel, revealing a strong impact of mutation density and genetic heterogeneity on the clinical features and on disease outcomes, indicating that an accurate risk stratification of thyroid cancer cannot rely on the analysis of a single genetic event. Finally, the heterogeneity found in some tumors warrants attention, since the occurrence of this phenomenon is likely to affect response to targeted therapies.
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http://dx.doi.org/10.1089/thy.2018.0339DOI Listing
February 2019

Predictors of the transition from metabolically healthy obesity to unhealthy obesity.

Eat Weight Disord 2018 Dec 29;23(6):739-744. Epub 2018 Oct 29.

Dipartimento di Scienza Mediche e Riabilitative, Istituto Auxologico Italiano, IRCCS, Via Ariosto 13, 20145, Milan, Italy.

Purpose: Evidence that metabolically healthy obesity (MHO) is a stable benign condition is unclear. The aim of this study was to estimate the transition of MHO subjects to unhealthy obesity (occurrence of cardio-metabolic events and/or risk factors) and its predictors.

Methods: We conducted an explorative follow-up study in a subset of MHO patients > 40 years without any cardio-metabolic risk factors and with normal LDL cholesterol (LDLc) levels, identified among 1530 obese patients. Due to the low sample size, a bootstrap approach was applied to identify the variables to be included in the final multivariate discrete-time logit model.

Results: The prevalence of MHO was 3.7%. During the follow-up (mean 6.1 years, SD 2.0), none of the MHO reported cardiovascular events, diabetes or prediabetes; 26 subjects developed risk factors (53% high LDLc and 50% hypertension). At the 6 and 12-year of follow-up, the cumulative incidence of transition to unhealthy obesity was 44% (95% CI 31-59%) and 62% (95% CI 45-79%), the incidence of high LDLc was 23% (95% CI 13-37%) and 40% (95% CI 25-59%) and that of hypertension was 20% (95% CI 11-33%) and 30% (95% CI 17-48%). LDLc and duration of follow-up were independent predictors of the transition from MHO to unhealthy obesity [OR 1.038 (1.005-1.072) and 1.360 (1.115-1.659)].

Conclusions: Results suggest that (a) MHO individuals do not move over time forward diabetes/prediabetes but develop risk factors, such as hypertension and higher LDL c that worsen the cardiovascular prognosis; (b) LDLc and the flow of time independently predict the transition to unhealthy status.

Level Of Evidence: Level III, cohort study.
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http://dx.doi.org/10.1007/s40519-018-0600-4DOI Listing
December 2018

Different effects of antihypertensive treatment on office and ambulatory blood pressure: a meta-analysis.

J Hypertens 2019 03;37(3):467-475

University of Milano-Bicocca.

Objective: Office and ambulatory blood pressure (BP) measurements are the main techniques to detect the effects of antihypertensive treatments in clinical trials, but the treatment-induced changes in these BP values can differ markedly. We performed a meta-analysis of clinical trials to quantify these differences and identified some of the associated factors.

Methods: We conducted a MEDLINE search for randomized clinical trials (RCTs) on hypertensive patients treated with at least one antihypertensive drug that reported changes in both office and 24-h BP. Random-effects models were fitted to estimate the summary of the difference between the changes as quantified by either technique. The I and Cochrane's Q statistics were calculated to evaluate the heterogeneity between studies.

Results: A total of 52 studies were included in our meta-analysis with about 9500 patients. The summary estimate Δ of SBP and DBP was -6.5 (95% confidence interval: -7.5 to -5.6) and -3.3 (95% confidence interval, -3.9 to -2.7), respectively. The difference was independent on the treatment duration and use of mono or combination treatment but for SBP it varied with the different treatment types in monotherapy, and it was greater in relation to baseline office BP and age. Allowing for the placebo effect also reduced the difference. Absolute on treatment BP values were at target for either pressure and the rate of controlled hypertensive individuals was similar (around one-third) for either measuring approach.

Conclusion: Our meta-analysis confirms that overall treatment-induced reduction is markedly greater for office BP than for 24-h BP, but it also shows that the quantitative relationship between these two measuring approaches varies with demographic, clinical and therapeutic conditions as well as in relation to placebo correction.
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http://dx.doi.org/10.1097/HJH.0000000000001914DOI Listing
March 2019

Analysis of Predictive Equations for Estimating Resting Energy Expenditure in a Large Cohort of Morbidly Obese Patients.

Front Endocrinol (Lausanne) 2018 25;9:367. Epub 2018 Jul 25.

Obesity Research Laboratory, IRCCS Istituto Auxologico Italiano, Milan, Italy.

The treatment of obesity requires creating an energy deficit through caloric restriction and physical activity. Energy needs are estimated assessing the resting energy expenditure (REE) that in the clinical practice is estimated using predictive equations. In the present cross sectional study, we compared, in a large cohort of morbidly obese patients, the accuracy of REE predictive equations recommended by current obesity guidelines [Harris-Benedict, WHO/FAO/ONU and Mifflin-St Jeor (MJ)] and/or developed for obese patients (Muller, Muller BC, Lazzer, Lazzer BC), focusing on the effect of comorbidities on the accuracy of the equations. Data on REE measured by indirect calorimetry and body composition were collected in 4,247 obese patients (69% women, mean age 48 ± 19 years, mean BMI 44 ± 7 Kg/m) admitted to the Istituto Auxologico Italiano from 1999 to 2014. The performance of the equations was assessed in the whole cohort, in 4 groups with 0, 1, 2, or ≥ 3 comorbidities and in a subgroup of 1,598 patients with 1 comorbidity (47.1% hypertension, 16.7% psychiatric disorders, 13.3% binge eating disorders, 6.1% endocrine disorders, 6.4% type 2 diabetes, 3.5% sleep apnoea, 3.1% dyslipidemia, 2.5% coronary disease). In the whole cohort of obese patients, as well as in each stratum of comorbidity number, the MJ equation had the highest performance for agreement measures and bias. The MJ equation had the best performance in obese patients with ≥3 comorbidities (accuracy of 61.1%, bias of -89.87) and in patients with type 2 diabetes and sleep apnoea (accuracy/bias 69%/-19.17 and 66%/-21.67 respectively), who also have the highest levels of measured REE. In conclusion, MJ equation should be preferred to other equations to estimate the energy needs of Caucasian morbidly obese patients when measurement of the REE cannot be performed. As even MJ equation does not precisely predict REE, it should be better to plan the diet intervention by measuring rather than estimating REE. Future studies focusing on the clinical differences that determine the high inter-individual variability of the precision of the REE predictive equations (e.g., on the organ-tissue metabolic rate), could help to develop predictive equations with a better performance.
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http://dx.doi.org/10.3389/fendo.2018.00367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068274PMC
July 2018

Haemodynamics to predict outcome in pulmonary hypertension due to left heart disease: a meta-analysis.

Eur Respir J 2018 04 4;51(4). Epub 2018 Apr 4.

Dept of Cardiology, Cliniques Universitaires de Bruxelles, Hôpital Académique Erasme, Brussels, Belgium.

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http://dx.doi.org/10.1183/13993003.02427-2017DOI Listing
April 2018
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