Combining 4D Flow MRI and Complex Networks Theory to Characterize the Hemodynamic Heterogeneity in Dilated and Non-dilated Human Ascending Aortas

Dilatació aòrtica; Aneurisma de l'aorta ascendent; Anàlisi espai-temporalDilatación aórtica; Aneurisma de la aorta ascendente; Análisis espacio-temporalAortic dilation; Ascending aorta aneurysm; Spatiotemporal analysisMotivated by the evidence that the onset and progression of the aneurysm of the ascending aorta (AAo) is intertwined with an adverse hemodynamic environment, the present study characterized in vivo the hemodynamic spatiotemporal complexity and organization in human aortas, with and without dilated AAo, exploring the relations with clinically relevant hemodynamic and geometric parameters. The Complex Networks (CNs) theory was applied for the first time to 4D flow magnetic resonance imaging (MRI) velocity data of ten patients, five of them presenting with AAo dilation. The time-histories along the cardiac cycle of velocity-based quantities were used to build correlation-based CNs. The CNs approach succeeded in capturing large-scale coherent flow features, delimiting flow separation and recirculation regions. CNs metrics highlighted that an increasing AAo dilation (expressed in terms of the ratio between the maximum AAo and aortic root diameter) disrupts the correlation in forward flow reducing the correlation persistence length, while preserving the spatiotemporal homogeneity of secondary flows. The application of CNs to in vivo 4D MRI data holds promise for a mechanistic understanding of the spatiotemporal complexity and organization of aortic flows, opening possibilities for the integration of in vivo quantitative hemodynamic information into risk stratification and classification criteria.Open access funding provided by Politecnico di Torino within the CRUI-CARE Agreement

Spatiotemporal Hemodynamic Complexity in Carotid Arteries: An Integrated Computational Hemodynamics and Complex Networks-Based Approach

Objective: The study of the arterial hemodynamics is essential for a better understanding of the risks associated with the onset/progression of vascular disease. However, conventional quantification and visualization paradigms are not sufficient to fully capture the spatiotemporal evolution of correlated blood flow patterns and their “sphere of influence” in complex vascular geometries. In the attempt to bridge this knowledge gap, an integrated computational hemodynamics and complex networks-based approach is proposed to unveil organization principles of cardiovascular flows. Methods: The approach is applied to ten patient-specific hemodynamic models of carotid bifurcation, a vascular bed characterized by a complex hemodynamics and clinically-relevant disease. Correlation-based networks are built starting from time-histories of two fluid mechanics quantities of physiological significance, respectively (1) the blood velocity vector axial component locally aligned with the main flow direction, and (2) the kinetic helicity density. Results: Unlike conventional hemodynamic analyses, here the spatiotemporal similarity of dynamic intravascular flow structures is encoded in a distance function. In the case of the carotid bifurcation, this study measures for the first time to what extent flow similarity is disrupted by vascular geometric features. Conclusion: It emerges that a larger bifurcation expansion, a hallmark of vascular disease, significantly disrupts the network topological connections between axial flow structures, reducing also their anatomical persistence length. On the contrary, connections in helical flow patterns are overall less geometry-sensitive. Significance: The integrated approach proposed here, by exploiting the connections of hemodynamic patterns undergoing similar dynamical evolution, opens avenues for further comprehension of vascular physiopathology

Axillary Treatment Management in Breast Cancer during COVID-19 Pandemic (Association between ACOSOG Z0011 Criteria and OSNA Test)

The outbreak of the SARS-COVID-2 pandemic (COVID-19) had a significant effect on the organisation of healthcare systems. Surgical units saw a significant reduction in the volume of surgical procedures performed, with lengthening waiting lists as a consequence. We assessed the surgical activity in relation to breast cancer that took place at the University Hospital of Cagliari, Italy, from February 2018 to March 2022. Two phases were identified based on the epidemiological circumstances: Phase 1—February 2018 to February 2020; Phase 2—March 2020 to March 2022. The surgery performed in the two phases was then compared. All the patients in our sample underwent a breast surgical procedure involving a lymph node biopsy using OSNA associated with the ACOSOG Z0011 criteria. In the study period overall at our facility, there were 4214 procedures, 417 of which involved breast surgery. In Phase 2, 91 procedures were performed using the OSNA method and ACOSOG Z0011 criteria, enabling the intraoperative staging of axillary nodes. Axillary treatment in breast cancer using this approach resulted in a significant reduction in the number of reoperations for the radicalisation of metastatic sentinel lymph nodes

Cardiovascular disease risk in liver transplant recipients transplanted due to chronic viral hepatitis

Background: Cardiovascular disease (CVD) is a major cause of morbidity and mortality after liver transplantation, mostly in patients transplanted for nonalcoholic steatohepatitis, obesity and diabetes. Few data exist on cardiovascular diseases among patients transplanted for viral hepatitis. Objective: Our aim is to clarify the cardiovascular risk and subclinical vascular damage among liver transplant recipients for chronic viral hepatitis (i.e. hepatits C virus, hepatis B virus and hepatitis D virus infection). Methods: Adult patients (age ≥ 18 years) with orthotopic liver transplants (OLT) due to viral hepatitis who signed informed consent, and were admitted for a routine follow-up between June 2019 and September 2020 at the Infectious Disease outpatient clinic of the University of Campania Luigi Vanvitelli, Naples, Italy, were prospectively enrolled. An estimation of cardiovascular risk was assessed using three main risk charts, echocolor-Doppler of epiaortic vessels was performed to assess subclinical Intima-Media changes. Results: A total of 161 patients were evaluated; of these 15 were excluded because not affected by viral hepatitis. 146 patients were considered. 83 patients (56.8%) were considered at high cardiovascular risk according to Framingham, 54 patients (36.9%) to American Heart Association Arteriosclerotic Cardiovascular Disease (ASCVD) score and 19 (13.0%) to Heart Score. Only 8 patients (5.4%) showed a normal carotid ultrasound, while 52 patients (35.6%) had a carotid artery Intima-Media Thickness (IMT) and 86 (58.9%) an atherosclerotic plaque. Conclusions: Liver transplant recipients for virus-related associated liver disease are, in light of the high percentage of carotid lesions, at high risk of CVD. Risk charts compared to subclinical carotid lesions which represent damage already established and a real localization of the disease, seem to underestimate the cardiovascular risk. A chronic inflammatory status, could play a key role. It's important to raise the awareness of cardiovascular risk in liver transplant patients to prevent cardiovascular diseases and improve the timing of early diagnosis of premature vascular lesions

Overcoming the dichotomy between open and isolated populations using genomic data from a large European dataset

Human populations are often dichotomized into "isolated" and "open" categories using cultural and/or geographical barriers to gene flow as differential criteria. Although widespread, the use of these alternative categories could obscure further heterogeneity due to inter-population differences in effective size, growth rate, and timing or amount of gene flow. We compared intra and inter-population variation measures combining novel and literature data relative to 87,818 autosomal SNPs in 14 open populations and 10 geographic and/or linguistic European isolates. Patterns of intra-population diversity were found to vary considerably more among isolates, probably due to differential levels of drift and inbreeding. The relatively large effective size estimated for some population isolates challenges the generalized view that they originate from small founding groups. Principal component scores based on measures of intra-population variation of isolated and open populations were found to be distributed along a continuum, with an area of intersection between the two groups. Patterns of inter-population diversity were even closer, as we were able to detect some differences between population groups only for a few multidimensional scaling dimensions. Therefore, different lines of evidence suggest that dichotomizing human populations into open and isolated groups fails to capture the actual relations among their genomic features

Semi-quantitative risk assessment of African swine fever virus introduction in pig farms

A semi-quantitative risk assessment was developed to classify pig farms in terms of the probability of introduction of African swine fever virus (ASFV). Following on-farm data collection via a specific checklist, we applied a modified failure mode and effect analysis (FMEA) to calculate the risk priority codes (RPC's), indicating increasing risk levels ranging from 1 to 5. The importance of biosecurity measures was attributed by experts. To consider geographic risk factors, we classified pig farms based on local density of farmed pigs, and on the estimated wild boar population density. The combination of RPC's with geographical risk factors resulted into a final ranking of pig farms in terms of the risk of ASFV introduction. Furthermore, the estimation of frequency and levels of non-compliance with biosecurity measures was used to identify weak points in risk prevention at farm level. The outcome of the risk assessment was affected by choices in assigning non-compliance scores and importance to specific components of biosecurity. The method was applied in 60 commercial farms in major pig production areas in Italy. Furthermore, we applied a reduced version of our checklist in 12 non-commercial/small commercial (≤20 pigs) farms in the northern Apennines. In commercial farms, highest RPC's were obtained for biosecurity measures associated with personnel practices and farm buildings/planimetry. Intervention should be addressed to training of personnel on biosecurity and ASF, to avoid contacts with other pig herds, and to improve practices in the entrance into the farm. Sharing trucks with other farms, and loading/unloading of pigs were other weak points. Fencing was classified as insufficient in 70% of the commercial farms. Among these farms, breeding units were characterised by the lowest risk of ASFV introduction (although differences among median ranks were not statistically significant: P-value = 0.07; Kruskal–Wallis test), and increasing herd size was not significantly correlated with a higher risk (Kendall's τ = −0.13; P-value = 0.14). Density of farmed pig was greatest in the main pig production area in northern Italy. Conversely, exposure to wild boars was greatest for non-commercial/small commercial farms on the Apennines, which were also characterised by non-compliance with critical biosecurity measures

Non-Small Cell Lung Cancer Harboring Concurrent EGFR Genomic Alterations: A Systematic Review and Critical Appraisal of the Double Dilemma

The molecular pathways which promote lung cancer cell features have been broadly explored, leading to significant improvement in prognostic and diagnostic strategies. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have dramatically altered the treatment approach for patients with metastatic non-small cell lung cancer (NSCLC). Latest investigations by using next-generation sequencing (NGS) have shown that other oncogenic driver mutations, believed mutually exclusive for decades, could coexist in EGFR-mutated NSCLC patients. However, the exact clinical and pathological role of concomitant genomic aberrations needs to be investigated. In this systematic review, we aimed to summarize the recent data on the oncogenic role of concurrent genomic alterations, by specifically evaluating the characteristics, the pathological significance, and their potential impact on the treatment approach

Higher Frequencies of Lymphocytes Expressing the Natural Killer Group 2D Receptor in Patients With Behçet Disease

Behçet disease (BD) is an inflammatory systemic disease with a fluctuating course, which can affect the skin, eyes, central nervous system, musculoskeletal, gastrointestinal, and vascular systems. No laboratory tests are currently available for the diagnosis of BD and monitoring disease activity. Moreover there is a lack of knowledge on BD pathogenesis. This study focused on circulating Natural Killer (NK), NKT and T cells evaluated as CD3neg CD56pos, CD3pos CD56pos, and CD3pos CD56neg. Peripheral blood mononuclear cells (PBMCs) were collected from 38 BD patients and 20 healthy controls (HC). The frequencies of NK, NKT, and T cells expressing CD16, CD69, NKG2D, Nkp30, Nkp46, and NKG2A were assessed by flow cytometry. Cytotoxic potential of NK cells was evaluated by flow cytometry as the percentage of cells expressing the degranulation marker CD107a after incubation with K562 cells. The levels of 27 cytokines were determined in plasma with a multiplex bead-based assay. Higher percentages of NK, NKT, and T cells expressing NKG2D were detected in PBMCs of BD patients than HC. ROC curve analysis showed that the evaluation of NKG2Dpos NK, NKT, and T cell percentages discriminated between BD patients and HC. Moreover, there was a positive correlation between the BD Current Activity Form (BDCAF) scores and the frequencies of NKG2Dpos NK and NKT cells. A higher frequency of NK cells expressing CD107a was induced in PBMCs from BD patients than HC after incubation with K562 cells. Concentrations of IL-5, IL-6, IL-10, IL-13, IP-10, and MIP-1β were higher in plasma of BD patients than HC. Monitoring the frequencies of NKG2Dpos lymphocytes could help the clinicians in BD patients management. In addition, the increased expression of NKG2D in BD patients is likely involved in disease pathogenesis

Uniparental markers in Italy reveal a sex-biased genetic structure and different historical strata

University of Adelaide Genographic Consortium contributers: Christina J. Adler, Alan Cooper, Clio S. I. Der Sarkissian, Wolfgang Haak.Located in the center of the Mediterranean landscape and with an extensive coastal line, the territory of what is today Italy has played an important role in the history of human settlements and movements of Southern Europe and the Mediterranean Basin. Populated since Paleolithic times, the complexity of human movements during the Neolithic, the Metal Ages and the most recent history of the two last millennia (involving the overlapping of different cultural and demic strata) has shaped the pattern of the modern Italian genetic structure. With the aim of disentangling this pattern and understanding which processes more importantly shaped the distribution of diversity, we have analyzed the uniparentally-inherited markers in ~900 individuals from an extensive sampling across the Italian peninsula, Sardinia and Sicily. Spatial PCAs and DAPCs revealed a sex-biased pattern indicating different demographic histories for males and females. Besides the genetic outlier position of Sardinians, a North West–South East Y-chromosome structure is found in continental Italy. Such structure is in agreement with recent archeological syntheses indicating two independent and parallel processes of Neolithisation. In addition, date estimates pinpoint the importance of the cultural and demographic events during the late Neolithic and Metal Ages. On the other hand, mitochondrial diversity is distributed more homogeneously in agreement with older population events that might be related to the presence of an Italian Refugium during the last glacial period in Europe.Alessio Boattini, Begoña Martinez-Cruz, Stefania Sarno, Christine Harmant, Antonella Useli, Paula Sanz, Daniele Yang-Yao, Jeremy Manry, Graziella Ciani, Donata Luiselli, Lluis Quintana- Murci, David Comas, Davide Pettener, the Genographic Consortiu