Experimental and Numerical Integrated Strategy for the Optimization of Microfluidic Parameters for Eudragit L100 Nanoparticles and Microparticles.

Oral immunization offers a minimally invasive administration, inducing local and systemic immune responses and facilitating mass immunization without needle-related risks. However, the gastrointestinal environment poses challenges, compromising vaccine effectiveness through enzymatic degradation and poor absorption by Peyer's patches. Advances in nanoparticle and microparticle (NP/MP) technology protect vaccines from degradation and enhance targeted release. The aim of this study was to develop pH-controlled polymeric carriers for the oral delivery of protein vaccines in order to target the antigen-presenting cells and M cells in the region of Peyer's patches. Here, myoglobin was chosen as a model protein vaccine. This study focuses on Eudragit L100, a pH-responsive polymer stable in acidic conditions and dissolving at higher pH, to develop carriers for controlled myoglobin release in the intestinal tract. A microfluidic-based manufacturing process for Eudragit L100 NPs and MPs is optimized using a comprehensive experimental and computational approach to obtain NPs and MPs through the same setup. Integrating in silico and experimental methods highlights the potential of numerical simulations to streamline final product development. This approach improves the efficiency and cost-effectiveness of NP/MP production, demonstrating how the combination of design of experiment and numerical simulations can optimize production parameters and refine manufacturing processes for advanced drug delivery systems.

Impact of Nodular Calcifications in the Aortic Annulus and Left Ventricular Outflow Tract on TAVI Outcome with New-Generation Devices.

Background: The impact of nodular calcifications in left ventricular outlow tract (LVOT) and aortic annulus on the procedural outcome of transcatheter aortic valve implantation (TAVI) with new-generation devices is yet to be elucidated. Similarly, computational simulations may provide a novel insight into the biomechanical features of TAVI devices and their interaction with nodular calcifications. Methods: This retrospective single-center study included 232 patients submitted to TAVI with Evolut-R (53.4%), Portico (33.6%) and Lotus (13.0%) devices with available preoperative computed tomography (CT) angiography and evidence of nodular calcifications in aortic annulus and/or LVOT. Calcification severity was defined ≥ moderate in presence of at least two nodules or one nodule ≤ 5 mm. Three virtual simulation models of aortic root presenting a nodular calcification of increasing size were implemented. Stress distribution, stent-root contact area and paravalvular orifice area were computed. Results: At least moderate calcifications were found in 123 (53.0%) patients, with no sex differences. Among the ≥ moderate calcification group, lower device success rate was evident (87.8% vs. 95.4%; p = 0.039). Higher rates of ≥ moderate paravalvular leak (PVL) (11.4% vs. 3.7%; p = 0.028) and vascular complications (9.8% vs. 2.8%; p = 0.030) were also observed. Among the Evolut-R group, higher rates of at ≥ moderate PVL (12.1%) were observed compared to Portico (3.8%; p = 0.045) and Lotus (0.0%; p = 0.044) groups. Calcification of both annulus and LVOT (odds ratio [OR] 0.105; p = 0.023) were independent predictors of device success. On computational simulations, Portico exhibited homogeneous stress distribution by increasing calfications and overall a larger paravalvular orifice areas compared to Evolut-R and Lotus. Evolut-R showed higher values of average stress than Portico, although with a more dishomogeneous distribution leading to greater paravalvular orifice areas by severe calcifications. Lotus showed overall small paravalvular orifice areas, with no significant increase across the three models. Conclusions: At least moderate nodular calcifications in the annulus/LVOT region significantly affected TAVI outcome, as they were independent predictors of device success. Lotus and Portico seemed to perform better than Evolut-R as for device success and ≥ moderate PVL. Computational simulations revealed unique biomechanical features of the investigated devices in terms of stent compliance and radial force.

Modifications in Aortic Stiffness After Endovascular or Open Aortic Repair: A Systematic Review and Meta-Analysis.

OBJECTIVE: Increased aortic stiffness (AoS) has been recognised as a risk factor in the development of cardiovascular disease. The aim of this systematic review and meta-analysis was to assess the impact of aortic repair on AoS. DATA SOURCES: PubMed, Scopus, and Web of Science were searched systematically for relevant studies evaluating the consequences of endovascular and open aortic repair on AoS. REVIEW METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) statement was followed to perform the research process. Papers containing data on AoS before and after both thoracic (TEVAR) and abdominal (EVAR) endovascular repair, as well as open surgical repair (OSR), were included for detailed evaluation. A fixed effects model was used to perform analysis. The Newcastle-Ottawa Scale was calculated for each included study. RESULTS: The first article cluster comprised 367 papers. After removal of duplicates and the adoption of inclusion/exclusion criteria, 14 articles remained, 13 of which were selected for meta-analysis. Ten studies analysed EVAR and three analysed TEVAR. Five of the selected papers were case control studies, with OSR adopted in four of these as the EVAR comparator. Several graft types were used in the endovascular group. AoS increased after TEVAR and EVAR, in terms of pulse wave velocity (PWV), even though several spatial levels and measurement modalities were adopted. No differences were described after OSR, although no pooled data could be analysed. CONCLUSION: EVAR and TEVAR both demonstrated a significant increase in AoS measurement (PWV). Although the heterogeneity and the low number of available studies limit the strength of the results, this review highlights the potential deleterious endograft role in the cardiovascular system although further studies are needed to achieve robust evidence. Further studies are needed to improve the mutual interaction between aorta and endograft, minimising their impact on the native aortic wall properties.

Three-D-printed simulator for kidney transplantation.

BACKGROUND: Three-Dimensional (3D) printing technology can be used to manufacture training platforms for surgeons. Kidney transplantation offers a suitable model, since it mostly entails vascular and ureteric anastomoses. METHODS: A new simulation platform for surgical training in kidney transplantation was realized and validated in this study. A combination of different 3-D printing technology was used to reproduce the key anatomy of lower abdomen, of pelvis, and of a kidney graft, including their mechanical properties. RESULTS: Thirty transplantations were performed by two junior trainees with no previous experience in the area. Analysis of the times required to perform the simulated transplantation showed that proficiency was reached after about ten cases, as indicated by a flattening of the respective curves that corresponded to a shortening of about 40% and 47%, respectively, of the total time initially needed to perform the whole simulated transplantation. Although an objective assessment of the technical quality of the anastomoses failed to show a significant improvement throughout the study, a growth in self-confidence with the procedure was reported by both trainees. CONCLUSION: The quality of the presented simulation platform aimed at reproducing in the highest possible way a realistic model of the operative setting and proved effective in providing an integrated training environment where technical skills are enhanced together with a team-training experience. As a result the trainees' self-confidence with the procedure resulted enforced. Three-D--printed models can also offer pre-operative patient-specific training when anatomical variants are anticipated by medical imaging. An analysis of the costs related to the use of this platform is also provided and discussed.

Drag Forces after Thoracic Endovascular Aortic Repair. General Review of the Literature.

BACKGROUND: Despite the great evolution of endograft devices for thoracic endovascular aortic repair (TEVAR), threatening related complication such as graft migration and endoleaks still occur during follow up. The Drag Forces (DF), that is the displacement forces that play a role in graft migration and endoleaks caused by the blood flow against the thoracic graft, can be studied by means of Computational Fluid Dynamics (CFD). METHOD: A general review of papers found in current literature was performed. CFD studies available on the topic of thoracic aortic diseases and DF were analyzed. All anatomic, hemodynamics or graft related factors which could have an impact on DF were reported. RESULTS: Different factors deeply influence DF magnitude in the different site of the Ishimaru's zones classification: angulation, tortuosity and length of the landing zone, graft diameter, length and deployment position, blood pressure, pulse waveform, blood viscosity and patient heart rate have been related to the magnitude of DF. Moreover, also the three-dimensional orientation of DF is emerging as a fundamental issue from CFD studies. DF can be divided in sideways and upward components. The former, even of higher magnitude in zone 0, maintain always an orthogonal orientation and does not change in any type of aortic arch; the latter result strictly related to the anatomic complexity of the aortic arch with values up to four times higher in zone 3. CONCLUSION: Different DF magnitude and orientation could explain how TEVAR have higher rate of migration and endoleaks when we face with more complex aortic anatomies. All these aspects should be foreseen during the planning of TEVAR procedure. In this field, collaboration between physicians and engineers is crucial, as both parts have a primary role in understanding and describing hidden aspects involved in TEVAR procedures.

Simulating the spread of COVID-19 via a spatially-resolved susceptible-exposed-infected-recovered-deceased (SEIRD) model with heterogeneous diffusion.

We present an early version of a Susceptible-Exposed-Infected-Recovered-Deceased (SEIRD) mathematical model based on partial differential equations coupled with a heterogeneous diffusion model. The model describes the spatio-temporal spread of the COVID-19 pandemic, and aims to capture dynamics also based on human habits and geographical features. To test the model, we compare the outputs generated by a finite-element solver with measured data over the Italian region of Lombardy, which has been heavily impacted by this crisis between February and April 2020. Our results show a strong qualitative agreement between the simulated forecast of the spatio-temporal COVID-19 spread in Lombardy and epidemiological data collected at the municipality level. Additional simulations exploring alternative scenarios for the relaxation of lockdown restrictions suggest that reopening strategies should account for local population densities and the specific dynamics of the contagion. Thus, we argue that data-driven simulations of our model could ultimately inform health authorities to design effective pandemic-arresting measures and anticipate the geographical allocation of crucial medical resources.

Impact of Aortic Tortuosity on Displacement Forces in Descending Thoracic Aortic Aneurysms.

OBJECTIVE: As elastin fibres in the aorta deteriorate with age, the descending thoracic aorta (DTA) becomes longer and more tortuous. In patients with DTA aneurysms, this increased tortuosity may result in a hostile haemodynamic environment for thoracic endovascular aortic repair (TEVAR). The objective of this study was to analyse how increased tortuosity affects haemodynamic displacement forces (DFs) in different segments of the DTA in patients with DTA aneurysms (DTAAs). METHODS: Thirty patients with DTAAs were selected to form three equal groups based on the maximum tortuosity of their DTA: low < 30°, moderate 30°-60°, and high > 60°. Computational fluid dynamics simulations were performed to calculate DFs in all patients. Image based segmentations were carried out to create patient specific models of the aortic geometry. When physiological simulation results were obtained, the haemodynamic DFs on the aortic wall were calculated in four segments of the DTA (zones 4A - D). To enable comparison of DFs in different segments, the DF was normalised by the aortic wall surface area, the equivalent surface traction (EST). RESULTS: The mean age was 73 years, with 67% male. In zone 4C, where most tortuosity occurs, the EST in patients with high tortuosity was more than three times higher, than those with low tortuosity (low, 743 N/m2; moderate, 956 N/m2; high, 2294 N/m2; p = .004). These differences could be attributed to the higher sideways components of the DF vectors, which were more than two times greater in patients with high tortuosity than in patients with low or moderate tortuosity (low, 5.01 N; moderate, 5.50 N; high, 13.21 N; p = .009). CONCLUSION: High tortuosity results in increased displacement forces in the distal segments of the DTA. These forces should be taken into account when planning for TEVAR, as potentially they increase the risk of stent graft related complications, such as migration and endoleak.

An overview on 3D printing for abdominal surgery.

BACKGROUND: Three-dimensional (3D) printing is a disruptive technology that is quickly spreading to many fields, including healthcare. In this context, it allows the creation of graspable, patient-specific, anatomical models generated from medical images. The ability to hold and show a physical object speeds up and facilitates the understanding of anatomical details, eases patient counseling and contributes to the education and training of students and residents. Several medical specialties are currently exploring the potential of this technology, including general surgery. METHODS: In this review, we provide an overview on the available 3D printing technologies, together with a systematic analysis of the medical literature dedicated to its application for abdominal surgery. Our experience with the first clinical laboratory for 3D printing in Italy is also reported. RESULTS: There was a tenfold increase in the number of publications per year over the last decade. About 70% of these papers focused on kidney and liver models, produced primarily for pre-interventional planning, as well as for educational and training purposes. The most used printing technologies are material jetting and material extrusion. Seventy-three percent of publications reported on fewer than ten clinical cases. CONCLUSION: The increasing application of 3D printing in abdominal surgery reflects the dawn of a new technology, although it is still in its infancy. The potential benefit of this technology is clear, however, and it may soon lead to the development of new hospital facilities to improve surgical training, research, and patient care.

Geometrical Evaluation of Aortic Sac Remodeling During Two-Step Thoracoabdominal Aortic Aneurysm Endovascular Repair.

BACKGROUND: The present study evaluates aneurysmal sac remodeling and the loss of the intercostal arteries after the first step of staged treatment of thoracoabdominal aortic aneurysms (TAAAs). The purpose of this approach is to keep the aneurysmal sac temporarily perfused to induce progressive thrombosis of the aneurysm while simultaneously allowing the spinal cord to establish adequate perfusion thereby promoting the development of collateral circulation. METHODS: All patients with type II or type III TAAAs, having undergone 2-step endovascular treatment with at least a 2-branch endoprosthesis at our institution between April 2017 and May 2019, were retrospectively evaluated. Thirty-day mortality and spinal cord ischemia was assessed. The mean number of the intercostal and lumbar arteries, coverage length between the left subclavian artery and the stent graft proximal landing zone, total volume of the aneurysmal sac, lumen volume, and thrombosis volume were measured by preoperative and first-step postoperative computed tomography angiography. Patients were also grouped based on the chosen endoprosthesis (group A: double-branch aneurysmal sac reperfusion; group B: single-branch aneurysmal sac reperfusion). RESULTS: Eleven patients (mean age: 76.5 years; range: 61-86) were considered. No 30-day mortality was observed after the first-step procedure, and 1 patient died after second-step treatment. No permanent paraplegia was observed after either the first or second endovascular steps. The lumen volume significantly decreased (27%; P < 0.001) after first-step endovascular treatment although there was a significant increase in aneurysm thrombosis (34% to 54%). The mean number of the intercostal arteries decreased from 19.7 to 9.3 (P < 0.001) after first-step endovascular treatment. Volume variations and percentage of intercostal loss did not significantly differ between the 2 groups. CONCLUSIONS: Although aneurysm volume continued to increase after first-step treatment, two-step endovascular treatment is a feasible alternative to reduce the risk of severe ischemia in patients with extended TAAAs.

Multidisciplinary preoperative simulations to optimize surgical outcomes in a challenging case of the complete double aortic arch in the adult.

BACKGROUND: Challenging surgical cases are becoming more and more frequent, making the optimization of decision making process and an accurate preoperative planning mandatory in order to improve postoperative outcomes. AIMS: Here we present an original multidisciplinary approach aimed at optimizing decision making in a peculiar case of double aortic arch (DAA) presenting in an adult patient. MATERIALS AND METHODS: Following the diagnosis of DAA, based on conventional exams, a three steps engineering simulation was adopted including: a) three-dimensional (3D) rapid prototype simulation; b) computational fluid-dynamic analysis; c) 3D virtual simulation of surgical exposure. RESULTS: Based on careful evaluation of such simulations we were able to identify optimal anatomical and functional surgical options, along with the optimal surgical approach. DISCUSSION: In peculiar clinical case, a significant step forward to optimize preoperative surgical planning could be obtained applying current available engineering techniques. CONCLUSION: We do believe that a multidisciplinary approach could become mandatory, in challenging cases, to optimize preoperative planning and outcomes.

Feasibility of 3D printed salivary duct models for sialendoscopic skills training: preliminary report.

PURPOSES: To explore the feasibility of 3D printed salivary duct models for the sialendoscopic skills training. METHODS: Healthy volunteers and patients affected by obstructive salivary gland disorders were submitted to 3 Tesla MR sialography. The MR data underwent an image segmentation process to produce the 3D printed salivary duct prototypes. Sialendoscopies were carried out by three groups of investigators with different levels of endoscopic experience. Realism, usefulness of the training process and potential advantages of the 3D printed models in the preoperative surgical planning were evaluated by means of a specific survey. RESULTS: Four cases were included in our study: one healthy parotid, one submandibular gland, one case of lithiasis and one of stenosis involving the parotid gland. In all cases, the three groups of investigators successfully explored the salivary ducts up to the tertiary branches, detected the cause of obstruction and correctly treated it. Seven untoward events occurred during the operative sialendoscopies. Overall, the questionnaire score was about 79.3%, reflecting a positive impression regarding the models on behalf of all the investigators. CONCLUSIONS: 3D printed salivary duct models resulted feasible for the sialendoscopic skills training. The opportunity to reproduce the patient-specific anatomy may add further information useful in the preoperative decision making. These positive results should be verified by further researches and experiences.

In Vivo Morphological Changes of the Femoropopliteal Arteries due to Knee Flexion After Endovascular Treatment of Popliteal Aneurysm.

Purpose: To evaluate morphological changes of the femoropopliteal (FP) arteries due to limb flexion in patients undergoing endovascular treatment of popliteal artery aneurysms (PAAs). Materials and Methods: Seven male patients (mean age 68 years) underwent endovascular treatment of PAA with a Viabahn stent-graft between January 2013 and December 2017. During follow-up, one contrast-enhanced computed tomography angiography (CTA) scan of the lower limbs was acquired for each recruited patient. A standardized CTA protocol for acquisitions in both straight-leg and bent-leg positions was used to visualize changes in artery shape due to limb flexion. Three-dimensional reconstruction of the FP segment was performed to compute mean diameter and eccentricity of the vascular lumen and to measure length, tortuosity, and curvature of the vessel centerline in 3 arterial zones: (A) between the origin of the superficial femoral artery and the proximal end of the stent-graft, (B) within the stent-graft, and (C) from the distal end of the stent-graft to the origin of the anterior tibial artery. Results: After limb flexion, all zones of the FP segment foreshortened: 6% in zone A (p=0.001), 4% in zone B (p=0.001), and 8% in zone C (p=0.07), which was the shortest (mean 4.5±3.6 cm compared with 23.8±5.7 cm in zone A and 23.6±7.4 cm in zone B). Tortuosity increased in zone A (mean 0.03 to 0.05, p=0.03), in zone B (0.06 to 0.15, p=0.005), and in zone C (0.027 to 0.031, p=0.1). Mean curvature increased 15% (p=0.05) in zone A, 27% (p=0.005) in zone B, and 95% (p=0.06) in zone C. In all zones, the mean artery diameter and eccentricity were not significantly affected by limb flexion. Conclusion: Limb flexion induces vessel foreshortening and increases mean curvature and tortuosity of the FP segment both within and outside the area of the stent-graft.

Twelve-year Follow-up Post-Thoracic Endovascular Repair in Type B Aortic Dissection Shown by Three-dimensional Printing.

BACKGROUND: Thoracic endovascular repair (TEVAR) is currently considered the therapy of choice for complicated type B acute aortic dissection (TBAAD). Although several papers have reported good outcomes at short- and medium-term follow-up, some questions still remain regarding the long-term durability and re-intervention rate during follow-up. METHODS: We describe a case of a patient originally treated with TEVAR for TBAAD complicated by impending aortic rupture. RESULTS: Endovascular repair successfully excluded the flow through the primary entry tear but during the 12-year follow-up period the patient experienced several complications and re-interventions. Various full-size three-dimensional (3D) models of the patient-specific vasculature were printed to better explain the different interventional interventions over the 12 years of follow-up and as a hands-on tool for medical education. CONCLUSIONS: The present case report, involving long-term follow-up, provides an example of the effectiveness and the safety of TEVAR for the treatment of complicated TBAAD shown at short and medium-term follow-up. However, the long-term complications that were observed in this patient during follow-up support the importance of lifelong CTA surveillance. Furthermore, this study confirms the capability of 3D printing technology as a powerful tool to support communication with patients and residents' education through the physical analysis of the real cases.

Spatiotemporal Image Correlation Analysis for 3D Flow Field Mapping in Microfluidic Devices.

Microfluidic devices reproducing 3D networks are particularly valuable for nanomedicine applications such as tissue engineering and active cell sorting. There is however a gap in the possibility to measure how the flow evolves in such 3D structures. We show here that it is possible to map 3D flows in complex microchannel networks by combining wide field illumination to image correlation approaches. For this purpose, we have derived the spatiotemporal image correlation analysis of time stacks of single-plane illumination microscopy images. From the detailed analytical and numerical analysis of the resulting model, we developed a fitting method that allows us to measure, besides the in-plane velocity, the out-of-plane velocity component down to vz ≅ 65 µm/s. We have applied this method successfully to the 3D reconstruction of flows in microchannel networks with planar and 3D ramifications. These different network architectures have been realized by exploiting the great prototyping ability of a 3D printer, whose precision can reach few tens of micrometers, coupled to poly dimethyl-siloxane soft-printing lithography.

Extranuclear partners of androgen receptor: at the crossroads of proliferation, migration, and neuritogenesis.

In this review, we focus on the role played by the protein partners of ligand-activated extranuclear androgen receptor (AR) in the final effects of hormone action, such as proliferation, migration, and neuritogenesis. The choice of AR partner, at least in part, depends on cell type. Androgen-activated receptor directly associates with cytoplasmic Src tyrosine kinase in epithelial cells, whereas in mesenchymal and neuronal cells, it prevalently interacts with filamin A. In the former, proliferation represents the final hormonal outcome, whereas in the latter, either migration or neuritogenesis, respectively, occurs. Furthermore, AR partner filamin A is replaced with Src when mesenchymal cells are stimulated with very low androgen concentrations. Consequently, the migratory effect is replaced by mitogenesis. Use of peptides that prevent receptor/partner assembly abolishes the effects that are dependent on their association and offers new therapeutic approaches to AR-related diseases. Perturbation of migration is often associated with metastatic spreading in cancer. In turn, cell cycle aberration causes tumors to grow faster, whereas toxic signaling triggers neurodegenerative events in the CNS. Here, we provide examples of new tools that interfere in rapid androgen effects, including migration, proliferation, and neuronal differentiation, together with their potential therapeutic applications in AR-dependent diseases-mainly prostate cancer and neurodegenerative disorders.-Castoria, G., Auricchio, F., Migliaccio, A. Extranuclear partners of androgen receptor: at the crossroads of proliferation, migration, and neuritogenesis.

The Modified Arch Landing Areas Nomenclature (MALAN) Improves Prediction of Stent Graft Displacement Forces: Proof of Concept by Computational Fluid Dynamics Modelling.

OBJECTIVE: To assess whether the Modified Arch Landing Areas Nomenclature (MALAN), which merges Ishimaru's map with the Aortic Arch Classification, predicts the magnitude of displacement forces and their orientation in proximal landing zones for TEVAR. METHODS: Computational fluid dynamic (CFD) modelling was employed to prove the hypothesis. Healthy aorta CT angiography scans were selected based on aortic arch geometry to reflect Types I to III arches equally (each n = 5). CFDs were used to compute pulsatile displacement forces along the Ishimaru's landing zones in each aorta including their three dimensional orientation along the upward component and sideways component. Values were normalised to the corresponding aortic wall area to calculate equivalent surface traction (EST). RESULTS: In Types I and II arches, EST did not change across proximal landing zones (p = .297 and p = .054, respectively), whereas in Type III, EST increased towards more distal landing zones (p = .019). Comparison of EST between adjacent zones, however, showed that EST was greater in 3/II than in 2/II (p = .016), and in 3/III than in 2/III (p = .016). Notably, these differences were related to the upward component, that was four times greater in 3/II compared with 2/II (p < .001), and five times greater in 3/III compared with 2/III (p < .001). CONCLUSION: CFD modelling suggests that MALAN improves discrimination of expected displacement forces in proximal landing zones for TEVAR, which might influence clinical outcomes. The clinical relevance of the finding, however, remains to be validated in a dedicated post-operative outcome analysis of patients treated by TEVAR of the arch.

Comparative Analysis of Porcine and Human Thoracic Aortic Stiffness.

OBJECTIVES: To compare porcine and human thoracic aortic stiffness using the available literature. METHODS: The available literature was searched for studies reporting data on porcine or human thoracic aortic mechanical behaviour. A four fibre constitutive model was used to transform the data from included studies. Thus, equi-biaxial stress stretch curves were generated to calculate circumferential and longitudinal aortic stiffness. Analysis was performed separately for the ascending and descending thoracic aorta. Data on human aortic stiffness were divided by age <60 or ≥60 years. Porcine and human aortic stiffness were compared. RESULTS: Eleven studies were included, six reported on young porcine aortas, four on human aortas of various ages, and one reported on both. In the ascending aorta, circumferential and longitudinal stiffness were 0.42±0.08 MPa and 0.37±0.06 MPa for porcine aortas (4-9 months) versus 0.55±0.15 MPa and 0.45±0.08 MPa for humans <60 years, and 1.02±0.59 MPa and 1.03±0.54 MPa for humans ≥60 years. In the descending aorta, circumferential and longitudinal stiffness were 0.46±0.03 MPa and 0.44±0.01 MPa for porcine aortas (4-10 months) versus 1.04±0.70 MPa and 1.24±0.76 MPa for humans <60 years, and 3.15±3.31 MPa and 1.17±0.31 MPa for humans ≥60 years. CONCLUSIONS: The stiffness of young porcine aortic tissue shows good correspondence with human tissue aged <60 years, especially in the ascending aorta. Young porcine aortic tissue is less stiff than human aortic tissue aged ≥60 years.

Midterm Follow-up Geometrical Analysis of Thoracoabdominal Aortic Aneurysms Treated with Multilayer Flow Modulator.

BACKGROUND: Aim of our study is the analysis of clinical results and aneurysmal sac evolution after multilayer flow modulator (MFM) placement, in patients with thoracoabdominal aortic aneurysms (TAAs). METHODS: All patients with asymptomatic TAA treated at our institution between 2012 and 2014 with MFM were retrospectively analyzed. Thirty-day evaluated outcomes were mortality and complications. Follow-up evaluated outcomes were mortality, aneurysm collateral branches patency, and reintervention. A geometrical analysis of 2-year follow-up computed tomography scans was carried out to evaluate the total aneurysm volume, the percentage of aneurysm growth, and the evolution of maximum aneurysm diameter. RESULTS: Seven patients (mean age: 71.8 years, range: 63-85 years) were considered in the study. Mean preoperative aneurysm diameter was 6.8 cm (range 6-8.3 cm). No 30-day mortality or complications were observed. Mean follow-up was 29.4 months. During follow-up, 3 deaths (42.8%) were observed, not related to MFM complications. Reintervention rate was 42.8%, occurred in all cases after 2-year follow-up; in 2 cases, the reintervention was necessary due to an excessive increase of the aneurysmal sac. During the follow-up, a mean growth rate of 6 mm/year (4 patients) for the diameter of the aneurysm external wall and a total aneurysm volume increase from 2.45 × 105 mm3 to 3.50 × 105 mm3 (4 patients) was evaluated. CONCLUSIONS: Our results have shown no mortality related to aneurysm rupture during the follow-up and high rate of reinterventions after MFM placement. Further geometrical analyses, based on the proposed approach, regarding a larger group of patients with long-term follow-up are required to draw indications about the MFM use.

Aortic Expansion Induces Lumen Narrowing in Anomalous Coronary Arteries: A Parametric Structural Finite Element Analysis.

Anomalous aortic origin of coronary arteries (AAOCA) is a congenital disease that can lead to cardiac ischemia during intense physical activity. Although AAOCA is responsible for sudden cardiac death (SCD) among young athletes and soldiers, the mechanisms underlying the coronary occlusion during physical effort still have to be clarified. The present study investigates the correlation between geometric features of the anomaly and coronary lumen narrowing under aortic root dilatations. Idealized parametric computer-aided designed (CAD) models of the aortic root with anomalous and normal coronaries are created and static finite element (FE) simulations of increasing aortic root expansions are carried out. Different coronary take-off angles and intramural penetrations are investigated to assess their role on coronary lumen narrowing. Results show that increasing aortic and coronary pressures lead to lumen expansion in normal coronaries, particularly in the proximal tract, while the expansion of the anomalous coronaries is impaired especially at the ostium. Concerning the geometric features of the anomaly, acute take-off angles cause elongated coronary ostia, with an eccentricity increasing with aortic expansion; the impact of the coronary intramural penetration on the lumen narrowing is limited. The present study provides a proof of concept of the biomechanical reasons underlying the lumen narrowing in AAOCA during aortic expansion, promoting the role of computational simulations as a tool to assess the mechanisms of this pathology.

Transcatheter Technologies for Valvular Replacement: an Update.

This report provides a brief overview of the basic principles, recent advances, and recommendations for the treatment of severe aortic stenosis with transcatheter aortic valve replacement (TAVR) in adults. Approaches that avoid neurological, cardiac and peripheral vascular complications have been developed. In addition, TAVR can be performed in intermediate- and low-risk patients. However, these procedures require specialized training and may not allow for complete resolution of the underlying issue. Even if cardiologists learn to perform the procedure and despite advancements in device technology, TAVR is still susceptible to structural valve degeneration, thrombosis and late cerebral embolization. To date, TAVR has shown no consistent advantage over surgical aortic valve replacement (SAVR) in intermediate- and low-risk patients.