Optimal Site for Proximal Optimization Technique in Complex Coronary Bifurcation Stenting: A Computational Fluid Dynamics Study

Background/purpose: The optimal position of the balloon distal radio-opaque marker during the post optimization technique (POT) remains debated. We analyzed three potential different balloon positions for the final POT in two different two-stenting techniques, to compare the hemodynamic effects in terms of wall shear stress (WSS) in patients with complex left main (LM) coronary bifurcation. Methods/materials: We reconstructed the patient-specific coronary bifurcation anatomy using the coronary computed tomography angiography (CCTA) data of 8 consecutive patients (6 males, mean age 68.2± 18.6 years) affected by complex LM bifurcation disease. Subsequently a virtual bench test was performed in each patient using two different double stenting techniques represented by the DK and Nano crush using the reconstruction of Orsiro stents (Biotronik IC, Bulack, Switzerland). Results: A significant reduction in the mean WSS values in all the lesion's sites was observed when the final POT was performed 1 mm distally the carina cut plane in both techniques. Moreover, a significant improvement in the mean WSS values of the entire SB (e.g. LCX) was obtained performing the POT 1 mm distally to the carina cut plane. The proximal POT resulted in larger area of lower WSS values at the carina using both the Nano crush and the DK crush techniques. Conclusions: In patients with complex LM bifurcation disease the use of a final POT performed 1 mm distally to the carina cut plane might results in more favorable WSS patterns (i.e. higher WSS values) along all stented segments and, especially, along the entire LCX lesions

Biomechanical Evaluation of Different Balloon Positions for Proximal Optimization Technique in Left Main Bifurcation Stenting

Background: Proximal optimization technique (POT) is a key step during left main (LM) bifurcation stenting. However, after crossover stenting, the ideal position of POT balloon is unclear. We sought to evaluate the biomechanical impact of different POT balloon positions during LM cross-over stenting procedure. Methods: We reconstructed the patient-specific LM bifurcation anatomy, using coronary computed tomography angiography data of 5 consecutive patients (3 males, mean age 66.3 ± 21.6 years) with complex LM bifurcation disease, defined as Medina 1,1,1, evaluated between 1st January 2018 to 1st June 2018 at our center. Finite element analyses were carried out to virtually perform the stenting procedure. POT was virtually performed in a mid (marker just at the carina cut plane), proximal (distal marker 1 mm before the carina) and distal (distal marker 1 mm after the carina) position in each investigated case. Final left circumflex obstruction (SBO%), strut malapposition, elliptical ratio and stent malapposition were evaluated. Results: The use of both proximal and distal POT resulted in a smaller LM diameter compared to the mid POT. SBO was significantly higher in both proximal and distal configurations compared to mid POT: 38.3 ± 5.1 and 29.3 ± 3.1 versus 18.3 ± 3.6%, respectively. Similarly stent malapposition was higher in both proximal and distal configurations compared to mid POT: 1.3 ± 0.4 and 0.82 ± 1.8 versus 0.78 ± 1.2, respectively. Conclusions: Mid POT offers the best results in terms of LCx opening maintaining slightly smaller but still acceptable LM and LAD diameters compared to alternative POT configuration

Designing high efficiency glow discharge cleaning systems

In this paper we present our studies about the choices of anode design and operational regime in order to get high efficiency glow discharge cleaning of the first wall of a fusion device. We analyzed a database of toroidal and poloidal profiles of the ion current density at the wall, measured by electrostatic probes embedded in RFX-mod first wall tiles, taken in different configurations. The ion current at the wall, both global and local, is in fact strictly connected to the cleaning efficiency, since during glow discharge the wall is physically sputtered by the ions. We found that small size anodes and high in-vessel pressure lead to the peaking of the current profile around the anodes locations, and we experimentally characterized this effect. Instead, we found that anode radial position in the poloidal section has negligible effect on current density profile, even when the anodes are placed at the first wall. Finally, the most convenient operational regime, in terms of pressure and current, has been proposed. Keywords: RFX-mod, Glow discharge, Wall cleaning, Ion current profile, Anode desig

Tryptophan Metabolism as Source of New Prognostic Biomarkers for FAP Patients

Familial adenomatous polyposis (FAP), a common inherited form of colorectal cancer (CRC), causes the development of hundreds to thousands of colonic adenomas in the colorectum beginning in early adolescence. In absence of a prophylactic surgery, FAP patients almost inevitably develop CRC by the age of 40 to 50. The lack of valuable prognostic biomarkers for FAP patients makes it difficult to predict when the progression from adenoma to malignant carcinoma occurs. Decreased tryptophan (TRP) plasma levels and increased indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan hydroxylase 1 (TPH1) enzymatic activities have been associated to tumour progression in CRC. In the present study, we aimed at investigating whether an altered TRP metabolism might also exist in FAP patients. Our results highlighted that plasma levels of TRP and its main catabolites are comparable between FAP patients and healthy subject. On the contrary, FAP patients presented significantly higher TRP levels with respect to high-grade adenoma (ADE) subjects and CRC patients. Obtained data lead us to evaluate IDO1 and TPH1 enzymes activity in the study groups. For both enzymes, it was possible to discriminate correctly between FAP subject and ADE/CRC patients with high sensitivities and specificities. By receiver operating characteristic (ROC) curve analysis, the cut-off values of IDO1 and TPH1 enzymatic activities associated to the presence of an active malignant transformation have been calculated as >38 and >5.5, respectively. When these cut-off values are employed, the area under the curve (AUC) is > 0.8 for both, indicating that TRP metabolism in patients with FAP may be used to monitor and predict the tumorigenic evolution

Efficacy of adalimumab as second-line therapy in a pediatric cohort of crohn’s disease patients who failed infliximab therapy: The Italian society of pediatric gastroenterology, hepatology, and nutrition experience

Background: Adalimumab (Ada) treatment is an available option for pediatric Crohn’s disease (CD) and the published experience as rescue therapy is limited. Objectives: We investigated Ada efficacy in a retrospective, pediatric CD cohort who had failed previous infliximab treatment, with a minimum follow-up of 6 months. Methods: In this multicenter study, data on demographics, clinical activity, growth, laboratory values (CRP) and adverse events were collected from CD patients during follow-up. Clinical remission (CR) and response were defined with Pediatric CD Activity Index (PCDAI) score ≤10 and a decrease in PCDAI score of ≥12.5 from baseline, respectively. Results: A total of 44 patients were consecutively recruited (mean age 14.8 years): 34 of 44 (77%) had active disease (mean PCDAI score 24.5) at the time of Ada administration, with a mean disease duration of 3.4 (range 0.3–11.2) years. At 6, 12, and 18 months, out of the total of the enrolled population, CR rates were 55%, 78%, and 52%, respectively, with a significant decrease in PCDAI scores (P<0.01) and mean CRP values (mean CRP 5.7 and 2.4 mL/dL, respectively; P<0.01) at the end of follow-up. Steroid-free remission rates, considered as the total number of patients in CR who were not using steroids at the end of this study, were 93%, 95%, and 96% in 44 patients at 6, 12, and 18 months, respectively. No significant differences in growth parameters were detected. In univariate analysis of variables related to Ada efficacy, we found that only a disease duration >2 years was negatively correlated with final PCDAI score (P<0.01). Two serious adverse events were recorded: 1 meningitis and 1 medulloblastoma. Conclusion: Our data confirm Ada efficacy in pediatric patients as second-line biological therapy after infliximab failure. Longer-term prospective data are warranted to define general effectiveness and safety in pediatric CD patients