Search

Background: The aim of this work was to optimize a three-dimensional (3D) turbo-spin-echo (TSE) sequence using a small field-of-view (FOV) technique for the study of the cerebellopontine angle and to compare it with a constructive interference steady-state (CISS) sequence., Methods: A total of 30 consecutive patients underwent magnetic resonance imaging with a 3Tesla (T) scanner, including 3D CISS and the optimized 3D small FOV technique turbo spin echo (3D SFT-TSE) T2-weighted sequences for the study of the cerebellopontine angle. The 3D SFT-TSE sequence was optimized after three different steps, and a quantitative evaluation of the signal-to-noise ratio (SNR) was obtained according to the National Electrical Manufacturers Association (NEMA) method. Three neuroradiologists made a blind comparative qualitative evaluation of the images between the 3D CISS and the 3D SFT-TSE obtained after the third optimization step, based on spatial resolution, contrast resolution, and presence of artifacts and noise., Results: The calculation of SNR using the NEMA method confirmed the superiority of the third optimization step over the others. For both spatial and contrast resolution, the optimized SFT-TSE was considered better (p < 0.001) than the CISS, while image artifacts and noise were considered worse in the CISS sequence (p < 0.001). Intraobserver analysis showed that all neuroradiologists preferred the 3D SFT-TSE sequence in terms of both spatial resolution and contrast resolution and found more noise and artifact disruption in the CISS sequence., Conclusions: The use of the 2D radiofrequency pulse technique with a 3D SFT-TSE T2 sequence was significantly more efficient than the 3D CISS sequence for the study of the cerebellopontine angle and inner ear structures., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Natural and human-provoked disasters pose serious health risks to children, particularly children and youth with special healthcare needs, including many cardiology patients. The American Academy of Pediatrics (AAP) provides preparedness recommendations for families, but little is known about recommendation adherence. Caregivers of children seen in a pediatric cardiology clinic network were recruited to complete an electronic survey. Participants self-reported child medical history and their household's implementation of AAP recommended disaster preparedness items. Families received a link to AAP resources and a child ID card. Data were analyzed using descriptive statistics with Fisher's exact and Wilcoxon rank sum tests. 320 caregivers participated in the study, of whom 124 (38.8%) indicated that their child has a diagnosed cardiac condition, and 150 (46.9%) indicated that their child had special healthcare needs. The average preparedness item completion rate was 70.7% for household preparedness, 40.1% for reunification preparedness, and 26.3% for community preparedness. Households of children with medical needs had similar rates of preparedness compared to overall rates. Of all respondents, 27.8% previously received disaster preparedness resources, 67.7% would like resources on discussing disaster preparedness, and 93.0% intend to talk with their household about disaster preparedness after completing the survey. These results demonstrate a gap between AAP recommendations and household-level disaster preparedness, including patients with cardiac conditions and those with special healthcare needs. Families expressed that they were interested in getting resources for disaster preparedness. Pediatric cardiologists may consider asking about disaster preparedness and providing disaster preparedness resources tailored to the needs of their patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Covid-19 infection is characterized by several acute complications, as well long-term sequelae, mostly sustained by endothelial dysfunction; several studies show that complications as pulmonary embolism (PE) are described both in the acute phase and after negativization. Aim of research was to evaluate anthropometric, bio-humoral, instrumental parameters in a group of patients affected by PE after recent Covid-19 infection compared to PE patients without previous Covid-19 infection. We enrolled 72 consecutive patients (35M, 37F) with acute PE, distinguished in relation to previous acute Covid-19 infection: 54 pts without previous acute Covid-19 infection and 18 pts with previous Covid-19 infection within negativity at least 2 months before PE diagnosis; 44 healthy subjects (21M, 23F) were recruited as control group. Patients who had previously developed Covid-19 needed hospitalization in high percentage (84%); this group showed significantly higher prevalence of diabetes mellitus than Covid-19-free PE patients, reduced serum levels of C-reactive protein, sST2 and PESI score. In post-Covid-19 PE group, we observed higher mean IMPROVE risk score, whereas in Covid-19-free group lower P/F ratio, higher radiological severity, and worse PESI score and severity index. Covid-19 infection affects not just the lung parenchyma but also other organs; endothelial damage plays pivotal role in long-term alterations; in high thrombotic risk group (recent hospitalization due to acute Covid-19 infection), we have described thrombotic complications characterized by persistent prothrombotic state after recovery, highlighted by well-known markers as PCR and D-Dimer as well as novel vascular marker (sST2)., (© 2023. The Author(s).)

Pulmonary embolism (PE) is a potentially life-threatening disorder. Beyond its usefulness in the prognostic stratification of heart failure, sST2 can represent a biomarker with high utility in several acute conditions. Our study was aimed to investigate whether sST2 can be used as a clinical marker of severity and prognostic outcome in acute PE. We enrolled 72 patients with documented PE and 38 healthy subjects; we measured the plasma concentrations of sST2 to evaluate the prognostic and severity performance of different levels of sST2 according to its association with the pulmonary embolism severity index (PESI) score and several parameters of respiratory function. PE patients had significantly higher levels of sST2 compared with healthy subjects (87.74 ± 17.1 vs. 17.1 ± 0.4 ng/mL, p < 0.001); we found higher PESI scores and serum lactate values in the group of patients with sST2 > 35 ng/mL compared with patients with sST2 < 35 ng/mL (138.7 ± 14.9 vs. 103.7 ± 15.1 and 2.43 ± 0.69 vs. 1.025 ± 0.05 mmol/L, respectively; p < 0.05). Patients with sST2 > 35 ng/mL showed higher radiological severity of PE compared with patients with sST2 < 35 ng/mL. Moreover, sST2 was the strongest parameter with a discriminative capacity for the development of acute respiratory failure and a PESI score >106 with respect to C reactive protein (CRP), creatinine, d-dimer, and serum lactate. We clearly demonstrated that sST2 significantly increased in PE and that its elevation was associated with disease severity. Therefore, sST2 may be used as a clinical marker in the evaluation of PE severity. However, further studies with larger patient populations are required to confirm these findings.

We report the successful treatment of multiple ruptured fusiform middle cerebral artery (MCA) aneurysms in a 10-month-old girl. This previously healthy infant presented with subarachnoid hemorrhage and was found to have multiple irregular dilatations of the superior division branch of the right MCA. Cerebral angiography was performed and confirmed the presence of multiple fusiform aneurysms of the MCA. After discussion with the multidisciplinary team, it was decided to treat the aneurysms with a endovascular approach, using a flow diverter. Microsurgical clipping was deemed risky because of the high likelihood of parent artery occlusion, and expectant management was also considered inappropriate because of the risk of rebleeding. Dual antiplatelet therapy was started, and a flow diverter was successfully delivered in the superior division branch of the right MCA. The postoperative course was uneventful, MRI at 12 months did not show any sign of recurrence, and at 3 years of age the patient had a normal neurological examination., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Aldosterone plays important role in cardiovascular damage. Aim was to evaluate arterial subclinical damage through arterial stiffness parameters in patients with Essential Hypertension (EH) and Primary Aldosteronism (PA)., Methods: From 2018 to 2019 we consecutively enrolled 82 subjects (37 males and 45 women), distinguished in two groups: 60 EH [systolic blood pressure (SBP) 143.4 ± 16.7 mmHg, diastolic blood pressure (DBP) 89.5 ± 12.1 mmHg] and 22 PA (SBP 149 ± 19.5 mmHg, DBP 92.7 ± 12.4 mmHg) [5 with aldosterone-secreting adrenal adenoma(APA), 17 with idiopathic aldosteronism(IHA)]; 40 matched normotensive subjects (NS) were enrolled (SBP 109.7 ± 6.2 mmHg, DBP 71.3 ± 9.7 mmHg). We used non-invasive applanation tonometer to acquire pressure waveform., Results: PA patients showed higher μ-Albuminuria (UAE) (65.7 ± 11.0mg/24 h) than EH and NS (21.5 ± 7.0 mg/24 h and 21.5 ± 7.0 mg/24 h, respectively); APA group showed increased levels of arterial stiffness index (11.7 ± 4.8 m/s; p < 0.02) compared to EH subjects (8.3 ± 3 m/s) and NS subjects (7.2 ± 1.7 m/s) as well as higher carotid intima-media thickness (c-IMT); APA patients showed significant reduction of subendocardial viability ratio (SEVR) and travel time of the reflected waves (TI) respect EH and NS. PA groups showed high percentage of augmented "worsening age" (60%), compared to EH (38%) and NS (37%). PAC was positively correlated with Arterial Stiffness Index. Performing multiple linear regression analysis (evaluating anthropometric and biochemical parameters), we found UAE as predictor of Augmentation Index, Arterial Stiffness Index and Travel Time of reflected waves in the enrolled population., Conclusion: PA patients showed higher cardiovascular subclinical damage respect to EH; UAE excretion had significant correlation with aldosterone, resulting best marker of subclinical vascular remodeling., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Infantile Hemangiomas (IH) are the most common benign tumor of infancy, occurring in over 10% of newborns. The head and neck is the most frequently affected area (60%), and the scalp is a typical site for such large lesions. Scalp-IHs are usually focal lesions that can be both disfiguring and may lead to complications such as ulceration and bleeding. We describe a case of a 30-months old female who presented a large scalp-IH at birth that rapidly grew in the first year of life. Topical and systemic treatments (with timolol ointment and oral propranolol, respectively) were not effective in reducing dimensions of the hemangioma. After vascular imaging study, the patient underwent surgical resection of the IH and primary closure with excellent cosmetic outcome. When medical therapy is ineffective or cosmetic and functional integrity is threatened, early surgery allows to completely removing large scalp-IHs, with good cosmetic results.

Intorduction: Aldosterone is known to play important role in developing cardiovascular, metabolic, renal damage in hypertensive patients., Aim: Aim of study was to evaluate parameters obtained by eco-color Doppler study, as non-invasive and easly performed method in asyntomatic patients with Essential Hypertension (EH) and Primary Aldosteronism (PA), without overt organ damage., Methods: From April 2019 to March 2020 we consecutively enrolled 73 hypertensive subjects (48 males, 25 women), distinguished in two groups: 30 EH patients (mean age 49.5 ± 18.7 years) and 43 PA patients (mean age 53.1 ± 11.6 years)] [23 with aldosterone-secreting adrenal adenoma (APA), 20 with idiopathic aldosteronism (IHA)]., Results: PA group showed higher renal filtration rate and 24-h urinary excretion of albumin respect to EH; moreover, in PA we found higher Pulsatility Index, altered percentage of Renale Resistance Index, Atrophy Index, and reducted parietal thickness than EH. The correlation study showed that plasma aldosterone were positively correlated with pulsatility index in PA group (right r = 0.35; p < 0.05; left r = 0.36; p < 0.05)., Conclusion: parameters obtained through the intra-renal eco-color Doppler examination, easly performed and non-invasive, can be useful in the early-stage identification of subclinical microvascular alterations, especially in PA, condition characterized by increased risk of cardio-vascular remodelling and metabolic alterations., (© 2021. Italian Society of Hypertension.)

Although several innovations in techniques and implantable devices were reported over the last decades, a consensus on the best endovascular treatment for intracranial aneurysms originating from the posterior communicating artery is still missing. This work investigates radiological outcomes of different endovascular techniques for posterior communicating artery aneurysms treatment in a retrospective multi-centric cohort. We included patients endovascularly treated for posterior communicating artery aneurysms from 2015 through 2020 in six tertiary referral hospitals. We evaluated the relationship between patients and aneurysms characteristics, baseline neurological status, radiological outcomes, and the different endovascular techniques. Overall, 250 patients were included in this study. Simple coiling was the most frequent treatment in 171 patients (68%), followed by flow-diverter stenting in 32 cases (13%). Complete occlusion was reported in 163 patients (65%), near-complete occlusion in 43 (17%), and incomplete occlusion in 44 (18%). Radiological follow-up was available for 247 (98%) patients. The occlusion rate was stable in 149 (60%), improved in 49 (19%), and worsened in 51 (21%). No significant difference in exclusion rate was seen between ruptured and unruptured aneurysms at the last follow-up (p = 0.4). Posterior communicating artery thrombosis was reported in 25 patients (9%), transient ischemic attack in 6 (2%), and in 38 patients (15%), subsequent procedures were needed due to incomplete occlusion or reperfusion. Endovascular strategies for posterior communicating artery aneurysms represent effective and relatively safe treatments. Simple coiling provides a higher immediate occlusion rate, although recanalization has been frequently reported, conversely, flow-diversion devices provide good long-term radiological outcomes., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Introduction: Progressive multifocal leukoencephalopathy (PML) is caused by JC virus opportunistic infection in the setting of immunodeficiency. Typical imaging features are multifocal and asymmetric lesions within supratentorial subcortical white matter in parieto-occipital regions., Case Description: A 47-year-old patient experienced a relapse of acute myeloid leukemia 21 months after hematopoietic stem cell transplantation. He also had visual impairment and magnetic resonance imaging showed an isolated cerebellar lesion without mass effect or enhancement. Common opportunistic infections and leukemic central nervous system involvement were excluded by cerebrospinal fluid (CSF) analysis. Given the worsening clinical and radiologic scenario, PML was suspected, and CSF protein chain reaction analysis was positive for JC virus., Conclusions: Given its potential curability, PML should be thoroughly investigated in patients with hematologic neoplasms and atypical isolated cerebellar presentation.

Objective: To determine whether racial/ethnic differences exist for the treatment of Marfan syndrome aortopathy. The 2014 Pediatric Heart Network randomised trial of losartan versus atenolol in Marfan syndrome paediatric and young adult patients showed no treatment differences in the rate of aortic root growth over 3 years; however, they did not examine racial/ethnic differences, and recent data suggest that angiotensin receptor blockers may have different pharmacologic effects in different racial/ethnic populations., Methods: We performed a secondary analysis of public-use data from the Pediatric Heart Network randomised trial comparing the differences by race/ethnicity (non-Hispanic White, non-Hispanic Black, and Hispanic patients) amongst the treatment groups for the primary outcome of rate of aortic root enlargement by z score and secondary outcome of rate of change of absolute diameter of aortic root, z score and absolute diameter of ascending aorta, and blood pressure changes., Results: For aortic root enlargement by z score amongst non-Hispanic White patients, patients on losartan exhibited an annual z score change of -0.090 ± 0.016, compared to -0.146 ± 0.015 for those on atenolol (p = 0.01), favouring atenolol. For Hispanic and non-Hispanic Black patients, there was no difference in primary or secondary outcomes between treatment groups., Conclusion: Non-Hispanic White patients had a small, but statistically significantly greater decrease in aortic root z score favouring atenolol over losartan. There were no significant differences amongst Hispanic or non-Hispanic Black patients, which may be due to relatively small size numbers. These findings may have important implications for medication selection by race/ethnicity in Marfan syndrome patients, which has not previously been evaluated in studies.

Purpose: To assess efficacy, safety and to discuss optimal medical therapy of stent-assisted coiling of ruptured intracranial aneurysms., Methods: Ruptured intracranial aneurysms treated with stent-assisted coiling in eight different institutions were retrospectively reviewed. Medical treatment regimens varied among the centers, mainly regarding heparin administration and post-procedural single or double antiplatelet therapy. Clinical and angiographic results, including complications and outcomes were analyzed and related to the different therapies., Results: Sixty-one consecutive patients (male/female 23/38), aged 59.1 years (36-86) underwent stent-assisted coiling for ruptured intracranial aneurysm without antiplatelet pre-medication. Intravenous acetylsalicylic acid (ASA) 500mg was administered to all patients immediately after stent deployment. At the same time heparin was given as bolus in 15 patients (24.6%) as part of local protocol. Intravenous glycoprotein 2b/3a inhibitors (antiGP2b3a) were used as bail-out therapy for stent thrombosis. Stent thrombosis occurred in 22 patients (36.1%), of which 4 (6.5%) lead to incomplete and 18 (29.6) to complete occlusion of the stent. Heparin administration had no effect on thrombosis rate. Thrombosis resolution occurred in all cases with intravenous antiGP2b3a (7 tirofiban, 15 abciximab), without increasing overall complication rate. Single antiplatelet therapy with ASA (28 patients, 45.9%) or double antiplatelet therapy including ASA and clopidogrel (33 patients, 54.1%) were administered after procedure, depending on local protocols and on neurointerventionists' experience. Overall complication rate, including ischemia and hemorrhage was higher in patients in which only ASA was administered (21.4% vs. 12.1%). No late stent thrombosis was seen, regardless of whether a single or double antiplatelet regimen was used. Nevertheless, the small sample size suggests caution in interpreting these results. Moreover, a possible bias may arise from the decision whether to modify the maintenance therapy or not depending on the severity of the intracranial hemorrhage in a case-by-case assessment. At three months, 34 out of 38 patients with HH grade 1-2 (89.4%), and 11 out of 23 with Hunt-Hess grade of 3-4 (47.8%) were independent (Modified Ranking Scale 0-2)., Conclusion: Stent assisted coiling of ruptured intracranial aneurysms is a feasible option when simple coiling is not possible. Optimal medical treatment is still controversial because balance between hemorrhagic and ischemic risks is difficult to evaluate. In our series, heparin bolus had no effect on subsequent stent thrombosis. In all cases peri-operative stent thrombosis was successfully managed using bail-out intravenous antiGP2b3a, which did not increase post-procedural hemorrhage rates. A non-significant trend towards increased complications rate was noticed in patients treated with single antiplatelet therapy versus double antiplatelet therapy., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Scalar-valued failure metrics are commonly used to assess the risk of aortic aneurysm rupture and dissection, which occurs under hypertensive blood pressures brought on by extreme emotional or physical stress. To compute failure metrics under an elevated blood pressure, a classical patient-specific computer model consists of multiple computation steps involving inverse and forward analyses. These classical procedures may be impractical for time-sensitive clinical applications that require prompt feedback to clinicians. In this study, we developed a machine learning-based surrogate model to directly predict a probabilistic and anisotropic failure metric, namely failure probability (FP), on the aortic wall using aorta geometries at the systolic and diastolic phases. Ascending thoracic aortic aneurysm (ATAA) geometries of 60 patients were obtained from their CT scans, and biaxial mechanical testing data of ATAA tissues from 79 patients were collected. Finite element simulations were used to generate datasets for training, validation, and testing of the ML-surrogate model. The testing results demonstrated that the ML-surrogate can compute the maximum FP failure metric, with 0.42% normalized mean absolute error, in 1 s. To compare the performance of the ML-predicted probabilistic FP metric with other isotropic or deterministic metrics, a numerical case study was performed using synthetic "baseline" data. Our results showed that the probabilistic FP metric had more discriminative power than the deterministic Tsai-Hill metric, isotropic maximum principal stress, and aortic diameter criterion., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We report the successful treatment of multiple ruptured fusiform middle cerebral artery (MCA) aneurysms in a 10-month-old girl. This previously healthy infant presented with subarachnoid haemorrhage and was found to have multiple irregular dilatations of the superior division branch of the right MCA. Cerebral angiography was performed and confirmed the presence of multiple fusiform aneurysms of the MCA. After multidisciplinary team discussion, it was decided to treat the aneurysms with endovascular approach, using a flow-diverter. Microsurgical clipping was deemed risky because of the high likelihood of parent artery occlusion and expectant management was also considered inappropriate because of the risk of re-bleeding. Dual antiplatelet therapy was started, and a flow-diverter was successfully delivered in the superior division branch of the right MCA. The post-operative course was uneventful, MRI at 12 months did not show any sign of recurrence and at 3 years of age the patient had a normal neurological examination., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: We performed a pilot study to evaluate the feasibility of future research about the presence of subclinical kidney damage after Gadolinium-based contrast media exposure. The future study aims to understand which are the behaviors of two markers of kidney damage, such as urinary NephroCheck (NC) and/or neutrophil gelatinase-associated lipocalin (NGAL). Specifically, after GBCM exposure, NC urinary detection should identify proximal tubule damage while NGAL urinary detection should be related to distal tubule damage., Methods: We performed a pilot study in patients who had Gadolinium exposure. The feasibility of future study is reached when at least 90% of candidates completed the pilot study. In each patient, we tested urinary NC and NGAL levels 24 h before magnetic resonance imaging (MRI) and 12-24 h after the exposure. Furthermore, we evaluated the administration of other nephrotoxic agents, the presence of comorbidity, and kidney function by S-creatinine and urine protein before the MRI., Results: We enrolled 35 candidates of whom 33 patients completed all study procedures. Our population had a mean age of 60.7 ± 14.8 years with normal kidney function with a median S-creatinine equal to 0.7 mg/dl (Interquartile range [IQR] 0.6-0.91). Urinary NC levels increased from 0.21 ng 2 /ml 2 (IQR 0.11-0.4) before MRI to 0.34 ng 2 /ml 2 (IQR 0.16-0.86) (p = 0.005). Conversely, we did not appreciate any significant modification in urinary NGAL (p = 0.53)., Conclusion: Our pilot study seems adequate in terms of feasibility and encourages us to focus our future research on renal proximal tubule, as the principal site of subclinical kidney damage after Gadolinium exposure., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.)

Background: The flow-diverter devices (FDDs) safety and effectiveness have been demonstrated by large series and meta-analyses. Due to the high occlusion rates and the acceptable morbidity rates of FDDs, the indications for their use are continuously expanding. We presented our Italian multicentric experience using the second generation of DERIVO® Embolization Device (DED ® ; Acandis, Pforzheim, Germany) to cure cerebral aneurysms, evaluating both middle and long-term safety and efficacy of this device., Methods: Between July 2016 and September 2017 we collected 109 consecutive aneurysms in 108 patients treated using DED ® during 109 endovascular procedures in 34 Italian centers (100/109 aneurysms were unruptured, 9/109 were ruptured). The collected data included patient demographics, aneurysm location and characteristics, baseline angiography, adverse event and serious adverse event information, morbidity and mortality rates, and pre- and post-treatment modified Rankin Scale scores. Midterm and long-term clinical, angiographic and cross-sectional CT/MR follow-up were recorded and collected until December 2018., Results: In 2/109 cases, DED ® placement was classified as technical failures. The overall mortality and morbidity rates were respectively 6.5% and 5.5%. Overall DERIVO® related mortality and morbidity rates were respectively 0% and 4.6% (5 out of 108 patients). Midterm neuroimaging follow-up showed the complete or nearly complete occlusion of the aneurysm in 90% cases, which became 93% at long-term follow-up. Aneurysmal sac shrinking was observed in 65% of assessable aneurysms., Conclusions: Our multicentric experience using DED ® for endovascular treatment of unruptured and ruptured aneurysms showed a high safety and efficacy profile, substantially equivalent or better compared to the other FDDs.

Background: Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established., Objective: We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF., Methods: An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users., Results: The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52-0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74-0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52-0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50-0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47-0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78-1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78-1.06; p 0.24)., Conclusions: In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

The aim of our cross-sectional study was to evaluate skin microvascular alterations in patients with hypertension secondary to primary aldosteronism (PA) and in subjects with essential hypertension (EH). Skin microcirculation was detected by nailfold videocapillaroscopy (NVC) and laser Doppler perfusion imaging (LDPI), both noninvasive techniques for the evaluation of digital capillaroscopic damage and hand skin blood perfusion. From September 2018 to April 2019, we consecutively enrolled 80 patients, of whom 42 had PA and 38 had EH. A morphological and structural study of cutaneous microcirculation was carried out through NVC, while functional evaluation of the peripheral microcirculation was carried out with LDPI. Using LDPI indices, dermal perfusion gradients were calculated in various regions of interest at the level of the back of the hand (ROI1 and ROI2). No differences between the two groups in NVC parameters were found. In contrast, LDPI showed worse skin perfusion parameters in patients with PA compared with patients with EH (ROI1: 143.9 ± 29.9 pU vs 163.3 ± 35.2 pU, p = 0.01; perfusion gradient ROI1-ROI2: 62.4 ± 28.8 pU vs 79.3 ± 33.5 pU, p = 0.019). Furthermore, the ROI1-ROI2 (proximal-distal) perfusion gradient was negatively correlated with aldosterone plasma levels (r -0.269; p = 0.017). Multivariate analysis showed that aldosterone was significantly associated with the ROI1-ROI2 perfusion gradient (b -0.220; p = 0.044). Patients with PA showed altered skin perfusion and greater microvascular dysfunction compared with the EH group. Our results are consistent with the hypothesis that aldosterone may have a pathophysiological role in microvascular remodeling in patients with PA, with predominant functional dysfunction.

Introduction: Remote monitoring (RM) has significantly transformed the standard of care for patients with cardiac electronic implantable devices. It provides easy access to valuable information, such as arrhythmic events, acute decompensation manifestations and device-related issues, without the need of in-person visits., Methods: Starting March 1st, 332 patients were introduced to an RM program during the Italian lockdown to limit the risk of in-hospital exposure to severe acute respiratory syndrome-coronavirus-2. Patients were categorized into two groups based on the modality of RM delivery (home [n = 229] vs. office [n = 103] delivered). The study aimed at assessing the efficacy of the new follow-up protocol, assessed as mean RM activation time (AT), and the need for technical support. In addition, patients' acceptance and anxiety status were quantified via the Home Monitoring Acceptance and Satisfaction Questionnaire and the Generalized Anxiety Disorder 7-item scale., Results: AT time was less than 48 h in 93% of patients and 7% of them required further technical support. Despite a higher number of trans-telephonic technical support in the home-delivered RM group, mean AT was similar between groups (1.33 ± 0.83 days in home-delivered vs 1.28 ± 0.81 days in office-delivered patients; p = .60). A total of 28 (2.5%) urgent/emergent in-person examinations were required. A high degree of patient satisfaction was reached in both groups whereas anxiety status was higher in the office-delivered group., Conclusions: The adoption of RM resulted in high patient satisfaction, regardless of the modality of modem delivery; nonetheless, in-office modem delivery was associated with a higher prevalence of anxiety symptoms., (© 2020 Wiley Periodicals LLC.)

Accurate failure criteria play a fundamental role in biomechanical analyses of aortic wall rupture and dissection. Experimental investigations have demonstrated a significant difference of aortic wall strengths in the circumferential and axial directions. Therefore, the isotropic von Mises stress and maximum principal stress, commonly used in computational analysis of the aortic wall, are inadequate for modeling of anisotropic failure properties. In this study, we propose a novel stress-based anisotropic failure criterion with dispersed fiber orientations. In the new failure criterion, the overall failure metric is computed by using angular integration (AI) of failure metrics in all directions. Affine rotations of fiber orientations due to finite deformation are taken into account in an anisotropic hyperelastic constitutive model. To examine fitting capability of the failure criterion, a set of off-axis uniaxial tension tests were performed on aortic tissues of four porcine individuals and 18 human ascending thoracic aortic aneurysm (ATAA) patients. The dispersed fiber failure criterion demonstrates a good fitting capability with the off-axis testing data. Under simulated biaxial stress conditions, the dispersed fiber failure criterion predicts a smaller failure envelope comparing to those predicted by the traditional anisotropic criteria without fiber dispersion, which highlights the potentially important role of fiber dispersion in the failure of the aortic wall. Our results suggest that the deformation-dependent fiber orientations need to be considered when wall strength determined from uniaxial tests are used for in vivo biomechanical analysis. More investigations are needed to determine biaxial failure properties of the aortic wall., (Copyright © 2020 by ASME.)

Purpose: Adrenal incidentalomas (AI) are discovered after work-up unrelated to adrenal gland diseases; up to 30% of AI show subclinical endogenous cortisol excess (SH), frequently associated to hypertension, obesity, metabolic disorders and increased incidence of cardiovascular events (CVEs)., Methods: We analysed 628 AI patients divided into two groups: 471 non-functional adrenal adenoma (NFA) and 157 SH. All patients underwent complete examinations, 24-h ambulatory blood pressure monitoring, biohumoral parameters and vascular damage markers, such as c-IMT and ankle brachial index. After long-term follow-up, we registered newly onset of CVEs such as myocardial infarction (MI), percutaneous stenting and surgical bypass (PTA/CABG), stroke, overall/cardiovascular mortality. Moreover, SH patients underwent to surgical (SSH) or pharmacological treatment (MSH)., Results: SH patients showed higher prevalence of metabolic syndrome, diabetes mellitus, and previous CVEs respect NFA at baseline. After follow-up MSH group showed higher recurrence of major CV events compared with NFA and SSH (RR 2.27 MSH vs NFA for MI; RR 2.30 MSH vs NFA for PTA/CABG; RR 2.41 MSH vs NFA for stroke). In SSH there was a significant reduction of the number of antihypertensive medications needed to reach target blood pressure levels (2.3 ± 1.0 to 1.5 ± 0.4 drugs). None differences were found in SH patients, distinguished in relation to cortisol plasma levels after dexamethasone suppression test (1.8-5 µg/dL, above 5 µg/dL)., Conclusions: SH is linked to relevant cardiovascular and metabolic alterations, leading to worsen clinical outcomes. In eligible patients, adrenalectomy is valid and safe option to treat SH, reducing cardiometabolic abnormalities.

Anorexia nervosa is a psychiatric eating disorder related to malnutrition and consequent altered metabolism. A 48-year-old female with a history of anorexia in the last 2 years referred to our hospital with spinal pain. She underwent spinal X-ray and magnetic resonance imaging (MRI) showing multiple vertebral collapses in dorsal and lumbar spine with inversion of normal bone marrow and soft tissue signal in T1-weighted and STIR images. We describe this case of spinal 'flip-flop' phenomenon, underlining how what seems a technical failure is actually a specific imaging pattern related to the clinical context., (© 2020 The Royal Australian and New Zealand College of Radiologists.)

Neutrophils or PolyMorphonuclear Neutrophils (PMNs) are key effector cells of the innate immune system and thanks to their remarkable plasticity, establish a cross talk with T cells modulating their survival and effector functions. During Nonalcoholic Steatohepatitis (NASH), the advanced form of hepatic steatosis or NAFL, PMNs infiltrate liver tissue, becoming a histological feature of NASH. Our aim was to evaluate the frequency of PMNs in NAFL and NASH patients in order to understand how they modulate the activity of circulating CD4 + and CD8 + T cells. In our cohort of patients, NASH patients displayed a higher frequency of circulating PMNs that was strongly correlated to liver enzymes, grade of steatosis, inflammation and fibrosis, the hepatocellular ballooning, and NAFLD Activity Score (NAS). Furthermore, even if ex vivo , in both groups of patients, PMNs shared the same phenotype of resting cells, after 24 hours of coculture with autologous CD4+ and CD8+ T cells, PMNs of NASH patients acquired a more active phenotype, becoming able to strongly inhibit proliferation and activation of CD4 + and CD8 + T cells. The higher ability of PMNs of NASH patients in suppressing CD4 + and CD8 + T cells, over time, might contribute in reducing the immunological defense of liver tissue against damages thus taking part in the progression of the NAFL disease toward NASH., Competing Interests: The research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Laura Antonucci et al.)

Introduction: The nephrotoxicity of modern contrast media remains controversial. Novel biomarkers of kidney damage may help in identifying a subclinical structural renal injury not revealed by widely used markers of kidney function., Objective: The aim of this study was to investigate clinical (contrast-induced acute kidney injury [CI-AKI]) and subclinical CI-AKI (SCI-AKI) after intra-arterial administration of Iodixanol and Iopamidol in patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2., Methods: This is a prospective observational monocentric study. Urinary sample was collected at 4-8 h after contrast medium exposure to measure neutrophil gelatinase associated lipocalin (NGAL) and the product tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2] × [IGFBP7]), while blood samples were collected at 24 and 48 h after exposure to measure serum creatinine., Results: One hundred patients were enrolled, of whom 53 were exposed to Iodixanol and 47 to Iopamidol. Patients in Iodixanol and Iopamidol groups were comparable in terms of demographics, pre-procedural and procedural data. No patient developed CI-AKI according KDIGO criteria, while 13 patients reported SCI-AKI after exposure to iodine-based medium contrast (3 patients in Iodixanol group and 10 patients in Iopamidol group), defined by positive results of NGAL and/or [TIMP-2] × [IGFBP7]. A positive correlation was found between NGAL and [TIMP-2] × [IGFBP7] in the analysed population (Spearman's rho 0.49, p < 0.001). In logistic regression analysis, Iopamidol exposure showed higher risk for SCI-AKI compared to Iodixanol (OR 4.5 [95% CI 1.16-17.52], p = 0.030), even after controlling for eGFR and volume of contrast medium used., Conclusions: This study showed that intra-arterial modern contrast media administration may have a nephrotoxic effect in a population without pre-existing chronic kidney disease. Further investigations on larger scale are warranted to confirm if Iopamidol exposed patients to increased risk of SCI-AKI compared to Iodixanol., (© 2020 S. Karger AG, Basel.)

A 14-year-old female with no significant medical history presented with hypertensive urgency, in the setting of 4 to 6 weeks of diarrhea, abdominal pain, headaches, anemia, weight loss, and high blood pressures. Her evaluation revealed signs of a systemic inflammatory process that was most suspicious for inflammatory bowel disease. However, when her hypertension was evaluated with a renal Doppler ultrasound, there were signs of narrowing, stenosis, and hypoplasia that led to a diagnostic angiogram of the abdominal aorta. Full body positron emission tomography scan revealed multiple areas of stenosis and aortic thickening with enhancement compatible with Takayasu arteritis. She received prednisone, methotrexate, and infliximab with marked improvement in her clinical symptoms and inflammatory markers.

Background and Aims: The adrenal mineralocorticoid system plays a key role in cardiovascular, metabolic and renal damage. This study aimed to assess the relationship between plasma aldosterone concentration (PAC) and some surrogate markers of subclinical atherosclerosis, such as carotid intima-media thickness (cIMT), ankle-brachial index (ABI) and biochemical parameters in patients with essential hypertension., Methods and Results: From January 2014 to December 2017, we consecutively enrolled 804 essential hypertensive patients (407 men and 397 women, mean age 50 ± 14 years) without cardiovascular complications, distinguishing patients in quartiles according to PAC. Compared with the first quartile, the highest PAC quartile was associated with the highest levels of serum uric acid (SUA) (5.3 ± 1.3 vs. 5.0 ± 1.0 mg/dl; P = 0.01), triglycerides (117.5 ± 15.7 vs. 106.8 ± 10.5 mg/dl; P < 0.05), 24-h urinary albumin excretion (UAE) (38.8 ±  vs. 7.6 ± mg/24 h; P < 0.05), cIMT (0.87 ± 0.22 vs. 0.80 ± 0.21 mm; P = 0.001) and increased prevalence of carotid plaques (26 vs. 16%; P < 0.005). Moreover, we found that in patients with PAC more than 150 pg/ml, the ABI was significantly lower than those with PAC < 150 pg/ml (1.01 ± 0.09 vs. 1.10 ± 0.09; P < 0.022). PAC was also found to be an independent predictor of the presence of carotid plaques and pathological ABI (<0.9) in essential hypertensive individuals., Conclusion: Our results revealed that higher PAC values are strongly associated with some metabolic variables, as triglycerides, UAE, cIMT, worse ABI and major prevalence of carotid plaques that, together with elevated blood pressure values, are strictly correlated with higher risk of atherosclerosis and cardiovascular complications.

Accurate identification of in vivo nonlinear, anisotropic mechanical properties of the aortic wall of individual patients remains to be one of the critical challenges in the field of cardiovascular biomechanics. Since only the physiologically loaded states of the aorta are given from in vivo clinical images, inverse approaches, which take into account of the unloaded configuration, are needed for in vivo material parameter identification. Existing inverse methods are computationally expensive, which take days to weeks to complete for a single patient, inhibiting fast feedback for clinicians. Moreover, the current inverse methods have only been evaluated using synthetic data. In this study, we improved our recently developed multi-resolution direct search (MRDS) approach and the computation time cost was reduced to 1~2 hours. Using the improved MRDS approach, we estimated in vivo aortic tissue elastic properties of two ascending thoracic aortic aneurysm (ATAA) patients from pre-operative gated CT scans. For comparison, corresponding surgically-resected aortic wall tissue samples were obtained and subjected to planar biaxial tests. Relatively close matches were achieved for the in vivo-identified and ex vivo-fitted stress-stretch responses. It is hoped that further development of this inverse approach can enable an accurate identification of the in vivo material parameters from in vivo image data.

Myocarditis has a variable clinical presentation and there is still debate regarding accurate diagnostic criteria. Adding to the controversy surrounding this diagnosis, there is no clear consensus for the treatment or ongoing follow-up of patients with myocarditis. All of this makes the diagnosis and management of myocarditis a particular challenge in the pediatric population. Furthermore, the literature with respect to this topic is dynamic and ever-changing. In this review article, we aim to review and summarize the common clinical presentations of myocarditis, along with the latest recommendations for diagnostic criteria, treatment, and follow-up of patients with myocarditis., (© 2019 Wiley Periodicals, Inc.)

Accumulating evidence suggests a potential role of dietary protein among nutritional factors interfering with the regulation of blood pressure. Dietary protein source (plant versus animal protein), and especially, protein composition in terms of amino acids has been postulated to interfere with mechanisms underlying the development of hypertension. Recently, mounting interest has been directed at amino acids in hypertension focusing on habitual dietary intake and their circulating levels regardless of single amino acid dietary supplementation. The aim of the present review was to summarize epidemiological evidence concerning the connection between amino acids and hypertension. Due to the large variability in methodologies used for assessing amino acid levels and heterogeneity in the results obtained, it was not possible to draw robust conclusions. Indeed, some classes of amino acids or individual amino acids showed non-causative association with blood pressure as well as the incidence of hypertension, but the evidence was far from being conclusive. Further research should be prompted for a thorough understanding of amino acid effects and synergistic actions of different amino acid classes on blood pressure regulation.

Objective: Intra-arterial embolization of jugular paragangliomas is an established endovascular technique. Intratumoral embolization by direct puncture has been proposed, prior to surgical treatment or radiosurgery to reduce the risk of cranial nerve deficits. Methods: We examined the technical aspects of two patients with jugular paragangliomas embolized with liquid embolic agent by direct puncture of the lesion, as sole treatment. Results: Two patients with jugular paragangliomas presented with lower cranial nerve deficits. The first patient showed an extended lesion (55-mm) and was treated with partial intra-arterial embolization plus direct puncture and injection of Squid 18 and a second staged embolization by direct puncture and filling of the remainder of the lesion. The second patient with a smaller jugular paraganglioma (33-mm) was treated by single embolization by direct puncture of the tumor and injection of Squid 12 and Squid 18 obtaining complete filling of the lesion. No procedural complications were observed. Both patients showed no residual and initial improvement of the neurological deficits. Conclusion: The intratumoral embolization by direct puncture of jugular paragangliomas, under accurate radiological control is a safe procedure, and complete exclusion of the lesion can be obtained in selected cases. A staged particle embolization of the lesion by direct puncture can be proposed for large lesions. Only further studies with larger series and long-term follow-up will be able to define, if this strategy can be curative avoiding additional surgical or radio-surgical treatment.

Data on short-term blood pressure variability (BPV), which is a well-established cardiovascular prognostic tool, in pheochromocytoma and paraganglioma (PPGL) patients is still lack and conflicting. We retrospectively evaluated 23 PPGL patients referred to our unit from 2010 to 2019 to analyze 24 h ambulatory blood pressure monitoring (24-h ABPM)-derived markers of short-term BPV, before and after surgical treatment. PPGL diagnosis was assessed according to guidelines and confirmed by histologic examination. The 24-h ABPM-derived markers of short-term BPV included: circadian pressure rhythm; standard deviation (SD) and weighted SD (wSD) of 24-h, daytime, and night-time systolic and diastolic blood pressure (BP); average real variability (ARV) of 24-h, daytime, and night-time systolic and diastolic BP. 7 males and 16 females of 53 ± 18 years old were evaluated. After surgical resection of PPGL we found a significant decrease in 24-h systolic BP ARV (8.8 ± 1.6 vs. 7.6 ± 1.3 mmHg, p < 0.001), in 24-h diastolic BP ARV (7.5 ± 1.6 vs. 6.9 ± 1.4 mmHg, p = 0.031), and in wSD of 24-h diastolic BP (9.7 ± 2.0 vs 8.8 ± 2.1 mmHg, p = 0.050) comparing to baseline measurements. Moreover, baseline 24-h urinary metanephrines significantly correlated with wSD of both 24-h systolic and diastolic BP. Our study highlights as PPGL patients, after proper treatment, show a significant decrease in some short-term BPV markers, which might represent a further cardiovascular risk factor.

Distal, dissecting, middle cerebral artery (MCA) aneurysms are changing surgically and endovascularly. Endovascular treatment requires flow diverter stenting. A good vessel visualization is crucial for safe navigation. Three-dimensional rotational digital subtraction angiography (3D-DSA) is used routinely in diagnostic imaging. The utilization of the 3D-DSA road map in vessel navigation and stent deployment is novel. An illustrative video of a distal, dissecting left MCA aneurysm treated with flow diverter stenting is presented. The technical issues were distal location, dissecting nature with double lumen, proximal stenosis, and vessel curves. The 3D-DSA road map helped to enhance visualization with a safer procedure.The video can be found here: https://youtu.be/sS3o1Z0P8WE.

Introduction: Cushing's syndrome (CS) is a clinical condition characterized by excessive cortisol production, associated with metabolic complications, such as diabetes mellitus, dyslipidemia, metabolic syndrome, hypertension, and cardiovascular diseases. Nowadays, the occurrence of autoimmune diseases in CS have not been completely evaluated in the previous studies., Objective: The aim of this study was to evaluate the occurrence of autoimmune diseases in CS patients after successfully treated., Materials and Methods: From January 2001 to December 2017, in our Secondary Hypertension Unit, we evaluated 147 CS patients (91 with ACTH-independent disease, 54 with ACTH-dependent disease, and 2 patients with ectopic ACTH production., Results: 109 CS patients (74.1%) were surgically treated (67 ACTH-independent CS patients (61.5%) undergone adrenalectomy and 42 ACTH-dependent CS (38.5%) undergone transsphenoidal surgery) and evaluated after 6, 12, and 24 months after clinical and biochemical remission of disease. In 9 (8.3%) of overall treated CS patients (8.3%), during follow-up, we observed the onset of some manifestations of autoimmune diseases. In particular, one patient had a systemic lupus erythematosus, one patient had rheumatoid arthritis, 4 patients reported autoimmune thyroiditis (Basedow-Graves' disease and Hashimoto's thyroiditis), one patient had clinical features of psoriasis, one patient showed myasthenia gravis, and one patient had giant cell arteritis., Conclusions: Our results demonstrate that patients successfully treated for CS could develop autoimmune diseases. Therefore, after treatment, CS patients need to be strictly monitored in order to evaluate the possible onset of autoimmune diseases.

Rationale: Catecholamine-producing tumors are rare, occurring in less than 0.2% of patients with hypertension, but can have relevant cardiovascular morbidity and mortality., Patient Concerns: A 37-year-old woman presented with a history of dyspnea, chest pain, palpitations, and paroxysmal hypertension. Electrocardiogram, echocardiogram, and cardiac magnetic resonance showed severe LVH with a prevalent involvement of the anterior portion of interventricular septum. Endomyocardial biopsy found severe hypertrophy with disarray of cardiomyocytes and ultrastructural evidence of contraction and necrosis of myocytes. Hormone investigations revealed high values of 24-hours urinary metanephrines. Abdominal computed tomography (CT) showed an enlarged left adrenal gland with a strong uptake of I-metaiodobenzylguanidine at scintigraphy scan., Interventions: Thus, the adrenal tumor was surgically removed., Outcomes: At follow-up examination, the patient's metanephrines levels were normalized and the transthoracic echocardiogram showed a reduction of LVH., Diagnosis and Lessons: We report a rare case of catecholamine-induced cardiomyopathy due to an adrenal adenoma mixed with nodules enriched in epinephrine-types secreting granules.

Purpose: Smooth muscle dysfunction syndrome (SMDS) due to heterozygous ACTA2 arginine 179 alterations is characterized by patent ductus arteriosus, vasculopathy (aneurysm and occlusive lesions), pulmonary arterial hypertension, and other complications in smooth muscle-dependent organs. We sought to define the clinical history of SMDS to develop recommendations for evaluation and management., Methods: Medical records of 33 patients with SMDS (median age 12 years) were abstracted and analyzed., Results: All patients had congenital mydriasis and related pupillary abnormalities at birth and presented in infancy with a patent ductus arteriosus or aortopulmonary window. Patients had cerebrovascular disease characterized by small vessel disease (hyperintense periventricular white matter lesions; 95%), intracranial artery stenosis (77%), ischemic strokes (27%), and seizures (18%). Twelve (36%) patients had thoracic aortic aneurysm repair or dissection at median age of 14 years and aortic disease was fully penetrant by the age of 25 years. Three (9%) patients had axillary artery aneurysms complicated by thromboembolic episodes. Nine patients died between the ages of 0.5 and 32 years due to aortic, pulmonary, or stroke complications, or unknown causes., Conclusion: Based on these data, recommendations are provided for the surveillance and management of SMDS to help prevent early-onset life-threatening complications.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is associated with early organ damage such as left ventricular hypertrophy and higher cardiovascular risk when compared to essential hypertension (EH). Epicardial adipose tissue (EAT) is a new cardiovascular risk factor, but its role and correlation with left ventricular mass (LVM) in ADPKD is unknown., Aims: we sought to investigate whether EAT is higher and related to LVM indexed by body surface area (LVMi) in hypertensive patients with ADPKD compared to those with EH., Methods: We performed ultrasound measurement of EAT thickness, LVM, LVMi, and left atrium size (left atrial volume indexed for body surface, LAVI) in 41 consecutive hypertensive patients with ADPKD, compared to 89 EH patients., Results: EAT was significantly higher in the ADPKD group in comparison to EH subjects (9.2 ± 2.9 mm vs. 7.8 ± 1.6 mm, p < 0.001), and significantly correlated with LVM, LVMi, and LAVI in the ADPKD group (r = 0.56, p = 0.005; r = 0.424, p = 0.022; and r = 0.48, p = < 0.001, respectively). Comparing EAT against body mass index, systolic blood pressure, and age, we found that EAT was the strongest predictor of LVMi (β = 0.42, p = 0.007)., Conclusion: Our data showed that EAT was higher in ADPKD patients than in EH subjects and independently correlated with LVMi. EAT measurement can be a useful marker for the cardiovascular risk stratification in ADPKD., (© 2018 S. Karger AG, Basel.)

Ambulatory blood pressure monitoring (ABPM) is a helpful tool to comprehensively identify and diagnose arterial hypertension. Moreover, it allows to better identify alterations in the circadian BP profile, as the nocturnal "nondipping" status, characterized by a lack of the physiological 10% night BP reduction and associated with a greater risk of target organ damage. However, ABPM has some limitations such as restricted availability, discomfort, particularly at night, cost implications, and reproducibility.Aim of the study was evaluate if the "nondipping" phenomenon may be related to low degree of tolerance to ABPM. Additionally, to determine whether self-reported events of sleep disorders and nighttime urinations may affect the "nondipping" status.From January 2013 to December 2015, we consecutively evaluated 1046 patients with arterial hypertension, performing ABPM, considering a tolerance index calculated on the basis of the patients' responses to a questionnaire.Thirty-eight out of 1046 patients showed complete lack of tolerance to the instrument during the day, whilst 126 during the night. There were no statistically significant differences in daytime and nighttime values of tolerance to the instrument between "dippers" and "nondippers," between "extreme-dippers" and the remaining patients or between "reverse-dippers" and the remaining patients. There were no statistically significant differences in the number of nocturnal awakenings between the groups. However, we found that the number of awakenings followed by urination was higher in "nondipping" patients and in "reverse-dipping" patients compared to the other groups.We found that the poor tolerance to the instrument does not seem to influence the BP "dipping" phenomenon among hypertensive individuals. Moreover, we think that in the evaluation of the ABPM data, factors, such as nocturnal urination and sleep disorders, need to be carefully taken into account, since may lead to a higher incidence of "nondipping" pattern., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Marfan syndrome (MFS), a genetic disorder of the connective tissue, has been strongly linked to dilation of the thoracic aorta, among other cardiovascular complications. As a result, MFS patients frequently suffer from aortic dissection and rupture, contributing to the high rate of mortality and morbidity among MFS patients. Despite the significant effort devoted to the investigation of mechanical and structural properties of aneurysmal tissue, studies on Marfan aneurysmal biomechanics are scarce. Ex vivo mechanical characterization of MFS aneurysmal tissue can provide a better insight into tissue strength outside the physiologic loading range and serve as a basis for improved risk assessment and failure prediction., Methods: The mechanical and microstructural properties of MFS aneurysmal thoracic aorta (MFS, n=15, 39.5±3.91 years), non-MFS aneurysmal thoracic aorta (TAA, n=8, 52.8±4.9 years), healthy human thoracic aorta (HH, n=8, 75.4±6.1 years), and porcine thoracic aorta (n=10) are investigated. Planar biaxial tensile testing and uniaxial failure testing were utilized to characterize the mechanical and failure properties of the tissue, respectively. Verhoeff-Van Gieson (VVG) and PicroSirius Red stains were utilized to visualize the elastin and collagen fiber architecture, respectively., Results: MFS tissue was found to have age-dependent but diameter-independent mechanical, structural, and morphological properties, also showing extensive elastin fiber degradation. Non-MFS thoracic aneurysmal aorta was thicker and stiffer than age-matched MFS tissue. Moreover, non-MFS thoracic aneurysmal mechanics resembled closely the mechanics of older healthy human tissue. Younger MFS tissue (<40 years) exhibited similar mechanical and structural properties to aged porcine tissue., Conclusions: Both age and aneurysmal presence were found to be factors associated with increased stiffness in aortic tissue, and aortic diameter was not a significant determinant of mechanical property deterioration. Additionally, the presence of MFS was found to induce stiffening of the thoracic aorta, although not to the extent of the non-MFS aneurysm., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Non-alcoholic fatty liver disease (NAFLD) is characterized by excess lipids in hepatocytes, due to excessive fatty acid influx from adipose tissue, de novo hepatic lipogenesis, in addition to excessive dietary fat and carbohydrate intake. Chronic hepatic lipid overload induces mitochondrial oxidative stress and cellular damage leading the development of NAFLD into a more severe liver disease condition, non-alcoholic steato-hepatitis (NASH). In turn, this can progress to cirrhosis and hepatocellular carcinoma (HCC). Among others, copper is one of the main bio-metals required for the preponderance of the enzymes involved in physiological redox reactions, which primarily occurs during mitochondrial respiration. Thus, copper homeostasis could be considered a target point for counteracting the progression of NAFLD. Accordingly, many diseases are correlated to unbalanced copper levels and, actually, some clinical trials are examining the use of copper chelating agents. Currently, no pharmacological interventions are approved for NAFLD, but nutritional and lifestyle modifications are always recommended. Fittingly, antioxidant food agents recognized to improve NAFLD and its complications have been described in the literature to bind copper. Therefore, this review describes the role of nutrition in the development and progression of NAFLD with a particular focus on copper and copper-binding antioxidant compounds against NAFLD., Competing Interests: The authors declare no conflicts of interest.

Introduction: Pheochromocytoma (PHEO) is a rare catecholamine-producing tumour arising from chromaffin cells in the sympatho-adrenal system, and can present as asymptomatic adrenal incidentaloma (AI)., Patient: We describe the case of a 61-year-old woman with a right adrenal mass incidentally discovered, who was biochemically characterized with subclinical hypercortisolism (SH). The patient was scheduled for adrenalectomy because of increasing seizure of the right adrenal gland with a haemorrhagic and focal pseudocystic appearance macroscopically, incidental histological and immunohistochemical PHEO, and micronodular cortico-adrenal hyperplasia., Discussion: This report describes a rare case of incidental non-functioning PHEO coexisting with corticomedullary hyperplasia and SH., Learning Points: Rare presentation of coexisting common (adrenal incidentaloma and subclinical Cushing's syndrome) and uncommon (pheochromocytoma) endocrinological conditions., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests.

Introduction: Resistant arterial hypertension (RHT) is defined as poor controlled blood pressure (BP) despite optimal doses of three or more antihypertensive agents, including a diuretic. In the development of RHT, hyperactivity of sympathetic (SNS) and renin-angiotensin-aldosterone (SRAA) systems are involved, and SNS is a potent stimulator of vasoactive endothelin-1 (ET-1) peptide. Renal sympathetic denervation (RSD) through disrupting renal afferent and efferent nerves attenuates SNS activity., Material and Methods: We carried out pilot study investigating the effect of RSD on BP and plasma ET-1 levels in consecutive 9 RHT patients (7 male and 2 female, mean age of 56 ± 13.3)., Results: After 12 months of the RSD, we observed a significant reduction of BP office, 24-h ambulatory BP monitoring (ABPM) (p < 0.05, respectively), and "non-dipping" pattern (from 55% to 35%) (p < 0.05). Moreover, RSD significantly decreased plasma ET-1 levels in both renal artery (at right from 21.8 ± 4.1 to 16.8 ± 2.9 pg/ml; p = 0.004; at left from 22.1 ± 3.7 to 18.9 ± 3.3 pg/ml; p = 0.02). We observed positive correlations between plasma renal arteries ET-1 levels and systolic BP values at ABPM [Global-SBP (r = 0.58; p < 0.01), Diurnal-SBP (r = 0.51; p < 0.03) and Nocturnal-SBP (r = 0.58; p < 0.01), respectively]., Discussion: Our data confirmed the positive effects of RSD on BP values in patients with RHT, and showed a possible physio-pathological role of ET-1. KEY MESSAGES RSD is associated to a significant reduction of plasma ET-1 levels, representing an useful tool into reduction of BP in RHT patients.

Introduction: This study was designed to evaluate the results of unilateral laparoscopic adrenalectomy in patients with subclinical hypercortisolism (SH) due to adrenal incidentaloma (AI) concerning the main cardiometabolic disorders., Methods: We have studied between January 2000 to December 2015, 645 patients with AI (283 males and 362 females; mean age 61.9 ± 10 years) and we found 70 patients with SH (27 males and 43 females; mean age 61.9 ± 8.4 years). Twenty-six (37%) SH patients (6 males and 20 females; mean age 58.7 ± 7.1 years) underwent unilateral laparoscopic adrenalectomy, whereas 44 SH patients (21 males and 23 females; mean age 63.9 ± 9.9 years) performed a conservative treatment. All SH patients were evaluated at diagnosis and after follow-up (mean 12 months; range 9-15 months)., Results: In only SH patients undergoing unilateral adrenalectomy we found a statistical significant reduction of the arterial hypertension and metabolic syndrome (p < 0.05, respectively). In particular we observed a reduction of 24-h systolic blood pressure and "non-dipper" pattern (p < 0.05, respectively) evaluated with ambulatory blood pressure monitoring (ABPM)., Conclusions: Our study confirm the high prevalence of SH in AI, and the unilateral laparoscopic adrenalectomy seemed to have a beneficial effect on some cardiometabolic disorders.

Objective: To assess vitreous and plasma changes of vascular endothelial growth factor A (VEGF-A), adrenomedullin (ADM) and endothelin-1 (ET-1) in proliferative diabetic retinopathy (PDR)., Patients and Methods: 9 patients with PDR in type 2 diabetes (T2DM) and 11 age-matched non-diabetic patients were enrolled. The levels of VEGF-A, ADM and ET-1 were measured using an enzyme (ELISA) and a radioimmunoassay (RIA) both in vitreous and plasma samples., Results: Vitreous ADM and VEGF-A levels were significantly higher in PDR patients (p=0.04 and p=0.02), whereas no differences were found in ET-1 levels (p=0.29). Plasma ADM levels were significantly higher in the PDR group (p<0.01), whereas no significant differences were found in the plasma ET-1 and VEGF-A levels (p=0.30 and p=0.37). The ADM vitreous/plasma ratio was significantly reduced in PDR group., Conclusions: The role of ET-1 in advanced PDR is still controversial; it has been supposed a role limited to induce hypoxic state and promote angiogenesis in the early phases. Once the neo-angiogenic process starts, other mediators are mainly involved as VEGF and ADM. Our findings suggest that ADM is an important marker of advanced PDR as well as VEGF. Conversely, ET-1 is not significantly involved in the advanced stage of PDR.