Publications by authors named "S Pirola"

39 Publications

Geometry and flow in ascending aortic aneurysms are influenced by left ventricular outflow tract orientation: Detecting increased wall shear stress on the outer curve of proximal aortic aneurysms.

J Thorac Cardiovasc Surg 2021 Jun 16. Epub 2021 Jun 16.

Department of Surgery, Imperial College London, London, United Kingdom.

Background: The geometrical characterization of ascending thoracic aortic aneurysms in clinical practice is limited to diameter measurements. Despite growing interest in hemodynamic assessment, its relationship with ascending thoracic aortic aneurysm pathogenesis is poorly understood. This study examines the relationship between geometry of the ventriculo-aortic junction and blood flow patterns in ascending thoracic aortic aneurysm disease.

Methods: Thirty-three patients with ascending thoracic aortic aneurysms (exclusions: bicuspid aortic valves, connective tissue disease) underwent 4-dimensional flow magnetic resonance imaging. After image segmentation, geometrical parameters were measured, including aortic curvature, tortuosity, length, and diameter. A unique angular measurement made by the trajectory of the left ventricular outflow tract axis and the proximal aorta was also conducted. Velocity profiles were quantitatively and qualitatively analyzed. In addition, 11 patients (33%) underwent wall shear stress mapping of the ascending thoracic aortic aneurysm region using computational fluid dynamics simulation.

Results: Greater left ventricular outflow tract aortic angles were associated with larger aortic diameters at the levels of the sinus (coefficient = 0.387, P = .014) and ascending aorta (coefficient = 0.284, P = .031). Patients with left ventricular outflow tract aortic angles greater than 60° had marked asymmetric flow acceleration on the outer curvature in the proximal aorta, ascertained from 4-dimensional flow analysis. For patients undergoing computational fluid dynamics assessment, regression analysis found that higher left ventricular outflow tract aortic angles were associated with significantly higher wall shear stress values in the outer curve of the aorta (coefficient 0.07, 95% confidence interval 0.04-0.11, P = .002): Angles greater than 50° yielded time-averaged wall shear stress values greater than 2.5 Pa, exhibiting a linear relationship.

Conclusions: Our findings strengthen the hypothesis of flow-mediated ascending thoracic aortic aneurysm disease progression and that left ventricular outflow tract aortic angle may be a predictor of disease severity.
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http://dx.doi.org/10.1016/j.jtcvs.2021.06.014DOI Listing
June 2021

Thymic carcinoma with Lynch syndrome or microsatellite instability, a rare entity responsive to immunotherapy.

Eur J Cancer 2021 Jun 20;153:162-167. Epub 2021 Jun 20.

Division of Medical Oncology for Melanoma & Sarcoma, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Importance: Thymic carcinoma (TC) is a rare aggressive tumour occurring in adults characterised by one of the lowest tumor mutational burdens (TMB). Microsatellite instability (MSI) is a mutational signature, caused by defects in the DNA MisMatch Repair (MMR) system, that predicts benefit from immunotherapy and causes high TMB. Fragmentary and unstructured evidence of these conditions co-occurring are reported in literature.

Objective: Review available data on the co-occurrence of these two conditions and determine its frequency in our institute case series.

Design: We performed a systematic analysis of literature and a retrospective evaluation of all the cases of TET treated at our institution from 2000 to 2020, selecting patients with a medical history of multiple tumours to enhance a priori probability of identifying cases with underlying predisposition.

Results: Literature yielded 3 cases of patients with MSI TC, for which MMR gene alteration was reported. None of them received immunotherapy. Of 366 patients with TETs treated in our institute, 32 had a medical history of multiple tumours and 25 of 32 (19 thymomas and 6 TCs) had available tissue for MMR analysis. One patient with TC showed a high TMB, and MSI due to MLH1 mutation and was treated in a phase II study with avelumab and axitinib combination obtaining a long-lasting partial response. MLH1 alterations are shared across MSI TC cases.

Conclusions And Relevance: This analysis highlights the usefulness of MSI testing in patients with TC. The observation of cases of TC occurring in patients with Lynch syndrome and the unexpected homogeneity of gene alterations support further investigation.
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http://dx.doi.org/10.1016/j.ejca.2021.05.029DOI Listing
June 2021

Involvement of matrix metalloproteinases and their inhibitors in Staphylococcus aureus chronically infected bovine mammary glands during active involution.

Res Vet Sci 2021 Jul 16;137:30-39. Epub 2021 Apr 16.

Laboratorio de Biología Celular y Molecular Aplicada, Instituto de Ciencias Veterinarias del Litoral (ICIVET-Litoral), Universidad Nacional del Litoral (UNL)/Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Esperanza, Santa Fe, Argentina; Facultad de Ciencias Veterinarias, Universidad Nacional del Litoral (UNL), Esperanza, Santa Fe, Argentina. Electronic address:

The aim of this study was to characterize the protein expression of matrix metalloproteinase-2 (MMP-2) and -- 9 and their inhibitors (TIMP-1 and -2) in mammary tissue of dairy cows with naturally occurring chronic S. aureus intramammary infections (IMI) during active involution. Moreover, the gelatinolytic activity of MMP-2 and -9 in mammary secretions was evaluated. Cows in late lactation that were either uninfected or with chronic naturally acquired S. aureus IMI were included in this study. Protein expression of MMP-2 and -9 in mammary tissues was significantly higher in S. aureus-infected than uninfected quarters at day 14 and 21 of involution. Protein expression of TIMP-1 and -2 was significantly higher in S. aureus-infected than uninfected quarters at day 7, 14 and 21 of involution. The MMP-2/TIMP-1, MMP-2/TIMP-2, MMP-9/TIMP-1 and MMP-9/TIMP-2 ratios were significantly higher in S. aureus-infected compared with uninfected quarters at day 14 of involution. The MMP-2 activity was significantly higher in mammary secretions from S. aureus-infected compared with uninfected quarters at day 1, 2, 7 and 14 of involution. The MMP-9 activity was significantly higher in mammary secretions from infected quarters compared with uninfected quarters at day 7, 14 and 21 of involution. The increased expression of MMP-2 and -9 in mammary tissue as well as the high levels of activity observed in mammary secretion from infected quarters compared with uninfected quarters during active involution, strongly suggests that these gelatinases could contribute to degradation of mammary tissue components during chronic S. aureus IMI. The MMPs/TIMPs imbalance could lead to greater proteolysis and potentially more damage to mammary tissue in S. aureus-infected quarters.
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http://dx.doi.org/10.1016/j.rvsc.2021.04.019DOI Listing
July 2021

Analysis of Turbulence Effects in a Patient-Specific Aorta with Aortic Valve Stenosis.

Cardiovasc Eng Technol 2021 Apr 7. Epub 2021 Apr 7.

Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.

Blood flow in the aorta is often assumed laminar, however aortic valve pathologies may induce transition to turbulence and our understanding of turbulence effects is incomplete. The aim of the study was to provide a detailed analysis of turbulence effects in aortic valve stenosis (AVS).

Methods: Large-eddy simulation (LES) of flow through a patient-specific aorta with AVS was conducted. Magnetic resonance imaging (MRI) was performed and used for geometric reconstruction and patient-specific boundary conditions. Computed velocity field was compared with 4D flow MRI to check qualitative and quantitative consistency. The effect of turbulence was evaluated in terms of fluctuating kinetic energy, turbulence-related wall shear stress (WSS) and energy loss.

Results: Our analysis suggested that turbulence was induced by a combination of a high velocity jet impinging on the arterial wall and a dilated ascending aorta which provided sufficient space for turbulence to develop. Turbulent WSS contributed to 40% of the total WSS in the ascending aorta and 38% in the entire aorta. Viscous and turbulent irreversible energy losses accounted for 3.9 and 2.7% of the total stroke work, respectively.

Conclusions: This study demonstrates the importance of turbulence in assessing aortic haemodynamics in a patient with AVS. Neglecting the turbulent contribution to WSS could potentially result in a significant underestimation of the total WSS. Further work is warranted to extend the analysis to more AVS cases and patients with other aortic valve diseases.
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http://dx.doi.org/10.1007/s13239-021-00536-9DOI Listing
April 2021

The Importance of Heart Team in Minimally Invasive Direct Coronary Artery Bypass.

Ann Thorac Surg 2021 Mar 29. Epub 2021 Mar 29.

Department of Cardiac Surgery, Centro CardiologicoMonzino, IRCCS, Milan, Italy.

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http://dx.doi.org/10.1016/j.athoracsur.2021.03.057DOI Listing
March 2021