Mathematical modeling of thrombus formation in idealized models of aortic dissection: Initial findings and potential applications

Aortic dissection is a major aortic catastrophe with a high morbidity and mortality risk caused by the formation of a tear in the aortic wall. The development of a second blood filled region defined as the “false lumen” causes highly disturbed flow patterns and creates local hemodynamic conditions likely to promote the formation of thrombus in the false lumen. Previous research has shown that patient prognosis is influenced by the level of thrombosis in the false lumen, with false lumen patency and partial thrombosis being associated with late complications and complete thrombosis of the false lumen having beneficial effects on patient outcomes. In this paper, a new hemodynamics-based model is proposed to predict the formation of thrombus in Type B dissection. Shear rates, fluid residence time, and platelet distribution are employed to evaluate the likelihood for thrombosis and to simulate the growth of thrombus and its effects on blood flow over time. The model is applied to different idealized aortic dissections to investigate the effect of geometric features on thrombus formation. Our results are in qualitative agreement with in-vivo observations, and show the potential applicability of such a modeling approach to predict the progression of aortic dissection in anatomically realistic geometries

Inter-firm trade finance in times of crisis

The paper discusses the main features that distinguish inter-firm international trade finance from alternative sources of financing. On the one hand, inter-firm trade finance could help overcome informational problems associated with other lending relationships; on the other, it may contribute to propagate shocks due to the interconnection among firms along credit chains. The paper evaluates the potential effects of a financial crisis on the use of trade credit for firms operating in developing countries. It argues that while the advantages of trade credit might remain largely unexploited due to poor legal institutions, the disadvantages might be exacerbated because of these firms’ greater exposure to a default chain. Based on these arguments, a menu of choices is identified for what policymakers can do to boost firms’ access to inter-firm trade finance in times of crisis.Debt Markets,Access to Finance,Bankruptcy and Resolution of Financial Distress,Economic Theory&Research,Emerging Markets

Predicting false lumen thrombosis in patient-specific models of aortic dissection

Aortic dissection causes splitting of the aortic wall layers, allowing blood to enter a ‘false lumen’ (FL). For type B dissection, a significant predictor of patient outcomes is patency or thrombosis of the FL. Yet, no methods are currently available to assess the chances of FL thrombosis. In this study, we present a new computational model that is capable of predicting thrombus formation, growth and its effects on blood flow under physiological conditions. Predictions of thrombus formation and growth are based on fluid shear rate, residence time and platelet distribution, which are evaluated through convection–diffusion–reaction transport equations. The model is applied to a patient-specific type B dissection for which multiple follow-up scans are available. The predicted thrombus formation and growth patterns are in good qualitative agreement with clinical data, demonstrating the potential applicability of the model in predicting FL thrombosis for individual patients. Our results show that the extent and location of thrombosis are strongly influenced by aortic dissection geometry that may change over time. The high computational efficiency of our model makes it feasible for clinical applications. By predicting which aortic dissection patient is more likely to develop FL thrombosis, the model has great potential to be used as part of a clinical decision-making tool to assess the need for early endovascular intervention for individual dissection patients

Computational modeling of low-density lipoprotein accumulation at the carotid artery bifurcation after stenting

Restenosis typically occurs in regions of low and oscillating wall shear stress, which also favor the accumulation of atherogenic macromolecules such as low-density lipoprotein (LDL). This study aims to evaluate LDL transport and accumulation at the carotid artery bifurcation following carotid artery stenting (CAS) by means of computational simulation. The computational model consists of coupled blood flow and LDL transport, with the latter being modeled as a dilute substance dissolved in the blood and transported by the flow through a convection-diffusion transport equation. The endothelial layer was assumed to be permeable to LDL, and the hydraulic conductivity of LDL was shear-dependent. Anatomically realistic geometric models of the carotid bifurcation were built based on pre- and post-stent computed tomography (CT) scans. The influence of stent design was investigated by virtually deploying two different types of stents (open- and closed-cell stents) into the same carotid bifurcation model. Predicted LDL concentrations were compared between the post-stent carotid models and the relatively normal contralateral model reconstructed from patient-specific CT images. Our results show elevated LDL concentration in the distal section of the stent in all post-stent models, where LDL concentration is 20 times higher than that in the contralateral carotid. Compared with the open-cell stents, the closed-cell stents have larger areas exposed to high LDL concentration, suggesting an increased risk of stent restenosis. This computational approach is readily applicable to multiple patient studies and, once fully validated against follow-up data, it can help elucidate the role of stent strut design in the development of in-stent restenosis after CAS

The location of re-entry tears affects false lumen thrombosis in aortic dissection following TEVAR

Purpose. Thoracic endovascular aortic repair (TEVAR) has been shown to be an effective treatment method for acute type B aortic dissection. However, it remains unclear which factors determine false lumen thrombosis (FLT) after TEVAR. In this study we assess the influence of the distance between the distal end of the stent graft and first re-entry tear (SG-FET)on the progression of FLT.Methods.Three post-operative patient-specific models were reconstructed from computed tomography scans. Two additional models were created byartificially changing the SG-FET distance in patient 1 and 2. In all five models, computational fluid dynamics simulations coupled with thrombus formation modelling were performed at physiological flow conditions.Predicted FLT was compared with follow-up scans.Results.Ourresults showed reduced false lumen flow and low time-averaged wall shear stress (TAWSS) inpatients withlarge SG-FET distances. Predicted thrombus formation and growth were consistent with follow-up scansfor all patients. Reducingthe SG-FET distanceby 30 mm in patient 1 increased flowandTAWSS in the upper abdominal false lumen, reducing the thrombus volume by 9.6%. Increasingthe SG-FET distance inpatient 2 resulted in fasterthoracic thrombosis and increased total thrombus volume.Conclusion.The location of re-entry tears can influencethe progression of FLT following TEVAR. The more distal the re-entry tear in the aorta the more likely FLTis. Hence, the distal landing zone of the stent graft should be chosen carefully to ensure a sufficient SG-FET distance

High wall stress may predict the formation of stent-graft-induced new entries after thoracic endovascular aortic repair

PURPOSE: To explore the potential role of morphological factors and wall stress in the formation of stent-graft-induced new entries (SINE) based on computed tomography (CT) images after thoracic endovascular aortic repair (TEVAR). CASE REPORT: Two female patients aged 59 years (patient 1) and 44 years (patient 2) underwent TEVAR for type B dissection in the chronic (patient 1) or subacute (patient 2) phase. CT scans at 3-month follow-up showed varying degrees of false lumen thrombosis in both patients. At 14-month follow-up, a SINE was observed in patient 1 while the dissected aorta in the other patient remained stable. Morphological and finite element analyses were performed based on the first follow-up CT images. The computational results showed that the SINE patient had higher stent-graft tortuosity than the non-SINE patient and much higher wall stress in the region close to the distal SINE. CONCLUSION: This case study suggests that high stent-graft tortuosity can lead to high wall stress, which is potentially linked to the formation of SINE. Further large population-based studies are needed to confirm this preliminary finding

Mode of Delivery in Women with Stillbirth: Results of an Area-Based Italian Prospective Cohort Study

Introduction: The choice of the mode of delivery, in case of stillbirth (SB) (fetus non-viable >22 weeks' gestation), should consider maternal preference, gestational age, bishop score, the clinical condition of the woman, and her previous obstetric history. However, despite these clear indications, data on the effective implementation of the latter are lacking. The aim of our study is to evaluate the different modes of delivery in an Italian population of SBs, according to gestational age, parity, causes of death, obstetric history, and maternal characteristics. Material and Methods: This is an area-based, prospective cohort study conducted in Emilia Romagna, Italy between January 2014 to December 2020. Data included all cases of SB (>22 weeks). Results: From 2014 to 2020, 783 SB occurred out of a total of 232.506 births, with a SB rate of 3.3 per 1000. Labor was spontaneous in 85 (11%). Of remnant, 567 (73.6%) were induced and 118 (15.3%) had no labor. The mode of delivery was vaginal in most of the cases (649/770, 84.3%) and by cesarean section in 121/770 (15.7%) of cases. Emergency CS was most frequent and performed in 89/121 (73.5%) of total CS, representing 11.5% of SB deliveries. Mode of induction did not differ in relation to gestational age at stillbirth, while vaginal delivery was significantly higher in women induced with prostaglandins (p = 0.000) respect to other methods. Nulliparous women had a significantly higher need for multiple methods of induction (p = 0.000) respect multiparous and obese women used more frequently prostaglandins (p = 0.03) than other methods. Women with a history of previous CS presented a significantly higher rate of repeated elective CS (p = 0.000). Moreover, emergency CS was performed more frequent in obese (p = 0.02), diabetic (p = 0.04) and hypertensive (p = 0.04) women and in SB caused by placenta disorders, namely in abruptio placentae (p = 0.000). In the case of chorioamnionitis and funisitis women significantly were induced with prostaglandin (p = 0.000) and delivered vaginally (p = 0.000). Conclusions: The method of induction of labor and the mode of delivery in case of SB did not depend on gestational age at the diagnosis of death, while they are related to placenta disorders representing a relevant condition leading to emergency CS also after diagnosis of fetal death. These data could help obstetric providers in managing the deliveries of stillborn infants

Stillbirth occurrence during COVID-19 pandemic: A population-based prospective study

Objectives: Data collected worldwide on stillbirth (SB) rates during the Covid-19 pandemic are contradictory. Variations may be due to methodological differences or population characteristics. The aim of the study is to assess the changes in SB rate, risk factors, causes of death and quality of antenatal care during the pandemic compared to the control periods. Methods: This prospective study is based on the information collected by the Emilia-Romagna Surveillance system database. We conducted a descriptive analysis of SB rate, risk factors, causes of death and quality of cares, comparing data of the pandemic (March 2020-June 2021) with the 16 months before. Results: During the pandemic, the SB rate was 3.45/1,000 births, a value in line with the rates of previous control periods. Neonatal weight >90th centile was the only risk factor for SB that significantly changed during the pandemic (2.2% vs. 8.0%; p-value: 0.024). No significant differences were found in the distribution of the causes of death groups. Concerning quality of antenatal cares, cases evaluated with suboptimal care (5.2%) did not change significantly compared to the control period (12.0%), as well as the cases with less than recommended obstetric (12.6% vs. 14%) and ultrasound evaluations (0% vs. 2.7%). Conclusions: During the COVID-19 pandemic, no significant differences in SB rates were found in an area that maintained an adequate level of antenatal care. Thus, eventual associations between SB rate and the COVID-19 infection are explained by an indirect impact of the virus, rather than its direct effect