Vascular Tissue Engineering: Recent Advances in Small Diameter Blood Vessel Regeneration

Cardiovascular diseases are the leading cause of mortality around the globe. The development of a functional and appropriate substitute for small diameter blood vessel replacement is still a challenge to overcome the main drawbacks of autografts and the inadequate performances of synthetic prostheses made of polyethylene terephthalate (PET, Dacron) and expanded polytetrafluoroethylene (ePTFE, Goretex). Therefore, vascular tissue engineering has become a promising approach for small diameter blood vessel regeneration as demonstrated by the increasing interest dedicated to this field. This review is focused on the most relevant and recent studies concerning vascular tissue engineering for small diameter blood vessel applications. Specifically, the present work reviews research on the development of tissue-engineered vascular grafts made of decellularized matrices and natural and/or biodegradable synthetic polymers and their realization without scaffold

Characteristics that matter in a climate façade: A sensitivity analysis with building energy simulation tools

Double skin façades (DSFs) are considered façade technologies that can reduce energy use and improve occupant comfort due to their advanced features. Their design requires reliable simulations due to their complex thermophysical behaviour, which are often carried out by practitioners using building energy software (BES) tools. Using an exhaust-air façade (also called climate façade) case study, the paper analyses the sensitivity of in-built DSF models in two popular BES tools (EnergyPlus and IDA ICE) for different orientations and climates. Small variations in input variables were considered to identify the parameters that the designer should pay most attention to during the design of the DSF according to different performance indicators. The results show that, regardless of the climate or orientation, the optical properties of the system (glazing and shading) were the most important in determining its performance, followed by the thermal properties of the glazing, while the geometrical, airflow and frame characteristics were less relevant. The model validation process also showed how differences in the in-built models (i.e. the use of a capacitance node for the glazed layers) lead to a difference in the reliability of the two BES tools. This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Comparison between First- and Second-Generation Cryoballoon for Paroxysmal Atrial Fibrillation Ablation

Introduction. Cryoballoon (CB) ablation has emerged as a novel treatment for pulmonary vein isolation (PVI) for patients with paroxysmal atrial fibrillation (PAF). The second-generation Arctic Front Advance (ADV) was redesigned with technical modifications aiming at procedural and outcome improvements. We aimed to compare the efficacy of the two different technologies over a long-term follow-up. Methods. A total of 120 patients with PAF were enrolled. Sixty patients underwent PVI using the first-generation CB and 60 patients with the ADV catheter. All patients were evaluated over a follow-up period of 2 years. Results. There were no significant differences between the two groups of patients. Procedures performed with the first-generation CB showed longer fluoroscopy time (36.3±16.8 versus 14.2±13.5 min, resp.; p=0.00016) and longer procedure times as well (153.1±32 versus 102±24.8 min, resp.; p=0.019). The overall long-term success was significantly different between the two groups (68.3 versus 86.7%, resp.; p=0.017). No differences were found in the lesion areas of left and right PV between the two groups (resp., p=0.61 and 0.57). There were no significant differences in procedural-related complications. Conclusion. The ADV catheter compared to the first-generation balloon allows obtaining a significantly higher success rate after a single PVI procedure during the long-term follow-up. Fluoroscopy and procedural times were significantly shortened using the ADV catheter

Ca2+ dysregulation in cardiac stromal cells sustains fibro-adipose remodeling in Arrhythmogenic Cardiomyopathy and can be modulated by flecainide

BACKGROUND: Cardiac mesenchymal stromal cells (C-MSC) were recently shown to differentiate into adipocytes and myofibroblasts to promote the aberrant remodeling of cardiac tissue that characterizes arrhythmogenic cardiomyopathy (ACM). A calcium (Ca(2+)) signaling dysfunction, mainly demonstrated in mouse models, is recognized as a mechanism impacting arrhythmic risk in ACM cardiomyocytes. Whether similar mechanisms influence ACM C-MSC fate is still unknown. Thus, we aim to ascertain whether intracellular Ca(2+) oscillations and the Ca(2+) toolkit are altered in human C-MSC obtained from ACM patients, and to assess their link with C-MSC-specific ACM phenotypes. METHODS AND RESULTS: ACM C-MSC show enhanced spontaneous Ca(2+) oscillations and concomitant increased Ca(2+)/Calmodulin dependent kinase II (CaMKII) activation compared to control cells. This is manly linked to a constitutive activation of Store-Operated Ca(2+) Entry (SOCE), which leads to enhanced Ca(2+) release from the endoplasmic reticulum through inositol-1,4,5-trisphosphate receptors. By targeting the Ca(2+) handling machinery or CaMKII activity, we demonstrated a causative link between Ca(2+) oscillations and fibro-adipogenic differentiation of ACM C-MSC. Genetic silencing of the desmosomal gene PKP2 mimics the remodelling of the Ca(2+) signalling machinery occurring in ACM C-MSC. The anti-arrhythmic drug flecainide inhibits intracellular Ca(2+) oscillations and fibro-adipogenic differentiation by selectively targeting SOCE. CONCLUSIONS: Altogether, our results extend the knowledge of Ca(2+) dysregulation in ACM to the stromal compartment, as an etiologic mechanism of C-MSC-related ACM phenotypes. A new mode of action of flecainide on a novel mechanistic target is unveiled against the fibro-adipose accumulation in ACM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03742-8

Erdafitinib in BCG-treated high risk non-muscle invasive bladder cancer

© 2023 The Author(s). Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Background: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette–Guérin (BCG) treatment and who are ineligible for/refuse radical cystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, a selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy in patients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment. Patients and methods: Patients aged ≥18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oral erdafitinib or investigator's choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpoint was recurrence-free survival (RFS). The key secondary endpoint was safety. Results: Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2: 1 to erdafitinib (n = 49) and chemotherapy (n = 24). Median follow-up for RFS was 13.4 months for both groups. Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6 months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6; nominal P value = 0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy. Conclusions: Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy.Peer reviewe

Comparison between First-and Second-Generation Cryoballoon for Paroxysmal Atrial Fibrillation Ablation

Introduction. Cryoballoon (CB) ablation has emerged as a novel treatment for pulmonary vein isolation (PVI) for patients with paroxysmal atrial fibrillation (PAF). The second-generation Arctic Front Advance (ADV) was redesigned with technical modifications aiming at procedural and outcome improvements. We aimed to compare the efficacy of the two different technologies over a long-term follow-up. Methods. A total of 120 patients with PAF were enrolled. Sixty patients underwent PVI using the firstgeneration CB and 60 patients with the ADV catheter. All patients were evaluated over a follow-up period of 2 years. Results. There were no significant differences between the two groups of patients. Procedures performed with the first-generation CB showed longer fluoroscopy time (36.3 ± 16.8 versus 14.2 ± 13.5 min, resp.; = 0.00016) and longer procedure times as well (153.1 ± 32 versus 102±24.8 min, resp.; = 0.019). The overall long-term success was significantly different between the two groups (68.3 versus 86.7%, resp.; = 0.017). No differences were found in the lesion areas of left and right PV between the two groups (resp., = 0.61 and 0.57). There were no significant differences in procedural-related complications. Conclusion. The ADV catheter compared to the first-generation balloon allows obtaining a significantly higher success rate after a single PVI procedure during the long-term follow-up. Fluoroscopy and procedural times were significantly shortened using the ADV catheter

MiR-320a as a Potential Novel Circulating Biomarker of Arrhythmogenic CardioMyopathy

Diagnosis of Arrhythmogenic CardioMyopathy (ACM) is challenging and often late after disease onset. No circulating biomarkers are available to date. Given their involvement in several cardiovascular diseases, plasma microRNAs warranted investigation as potential non-invasive diagnostic tools in ACM. We sought to identify circulating microRNAs differentially expressed in ACM with respect to Healthy Controls (HC) and Idiopathic Ventricular Tachycardia patients (IVT), often in differential diagnosis. ACM and HC subjects were screened for plasmatic expression of 377 microRNAs and validation was performed in 36 ACM, 53 HC, 21 IVT. Variable importance in data partition was estimated through Random Forest analysis and accuracy by Receiver Operating Curves. Plasmatic miR-320a showed 0.53\u2009\ub1\u20090.04 fold expression difference in ACM vs. HC (p\u2009<\u20090.01). A similar trend was observed when comparing ACM (n\u2009=\u200913) and HC (n\u2009=\u200917) with athletic lifestyle, a ACM precipitating factor. Importantly, ACM patients miR-320a showed 0.78\u2009\ub1\u20090.05 fold expression change vs. IVT (p\u2009=\u20090.03). When compared to non-invasive ACM diagnostic parameters, miR-320a ranked highly in discriminating ACM vs. IVT and it increased their accuracy. Finally, miR-320a expression did not correlate with ACM severity. Our data suggest that miR-320a may be considered a novel potential biomarker of ACM, specifically useful in ACM vs. IVT differentiation

Vascular Tissue Engineering: Recent Advances in Small Diameter Blood Vessel Regeneration

Cardiovascular diseases are the leading cause of mortality around the globe. The development of a functional and appropriate substitute for small diameter blood vessel replacement is still a challenge to overcome the main drawbacks of autografts and the inadequate performances of synthetic prostheses made of polyethylene terephthalate (PET, Dacron) and expanded polytetrafluoroethylene (ePTFE, Goretex). Therefore, vascular tissue engineering has become a promising approach for small diameter blood vessel regeneration as demonstrated by the increasing interest dedicated to this field. This review is focused on the most relevant and recent studies concerning vascular tissue engineering for small diameter blood vessel applications. Specifically, the present work reviews research on the development of tissue-engineered vascular grafts made of decellularized matrices and natural and/or biodegradable synthetic polymers and their realization without scaffold