Co-expression of functional human Heme Oxygenase 1, Ecto-5'-Nucleotidase and ecto-nucleoside triphosphate diphosphohydrolase-1 by "self-cleaving" 2A peptide system

We developed an F2A-based multicistronic system to evaluate functional effects of co-expression of three proteins important for xenotransplantation: heme oxygenase 1 (HO1), ecto-5'-nucleotidase (E5NT) and ecto-nucleoside triphosphate diphosphohydrolase-1 (ENTPD1). The tricistronic p2A plasmid that we constructed was able to efficiently drive concurrent expression of HO1, E5NT and ENTPD1 in HEK293T cells. All three overexpressed proteins possessed relevant enzymatic activities, while addition of furin site interfered with protein expression and activity. We conclude that our tricistronic p2A construct is effective and optimal to test the combined protective effects of HO1, E5NT and ENTPD1 against xeno-rejection mechanisms

Development of a navigation algorithm for autonomous underwater vehicles

In this paper, the authors present an underwater navigation system for Autonomous Underwater Vehicles (AUVs) which exploits measurements from an Inertial Measurement Unit (IMU), a Pressure Sensor (PS) for depth and the Global Positioning System (GPS, used during periodic and dedicated resurfacings) and relies on either the Extended Kalman Filter (EKF) or the Unscented Kalman Filter (UKF) for the state estimation. Both (EKF and UKF) navigation algorithms have been validated through experimental navigation data related to some sea tests performed in La Spezia (Italy) with one of Typhoon class vehicles during the NATO CommsNet13 experiment (held in September 2013) and through Ultra-Short BaseLine (USBL) fixes used as a reference (ground truth). Typhoon is an AUV designed by the Department of Industrial Engineering of the Florence University for exploration and surveillance of underwater archaeological sites in the framework of the Italian THESAURUS project and the European ARROWS project. The obtained results have demonstrated the effectiveness of both navigation algorithms and the superiority of the UKF (very suitable for AUV navigation and, up to now, still not used much in this field) without increasing the computational load (affordable for on-line on-board AUV implementation)

The new educational project Televascular Games during the Coronavirus Disease 2019 pandemic

Objective: To report methodology and first-year results of a new educational project called Televascular Games,” which took place during coronavirus disease 2019 pandemic. Methods: Complex aneurysmal aortic disease was discussed during a 2-hour competition webinar, according to three modalities. (1) Planning case competition (PCC): Two to four preoperative computed tomography angiography (CTA) scans of an already performed selected case were submitted for the competition. CTA scans were uploaded anonymously, without any reference to the center or the surgeon who performed the case. The competitor had to prepare a presentation of how he or she would have diagnosed, sized, planned, treated, and followed up the case, of the medical therapy and of the bail-out maneuvers. (2) Challenging case competition (CCC): The competitor elaborates a presentation of an already treated case concerning an aortic topic and discusses sizing, planning, treatment, possible bail-out maneuvers and obtained results. For the CCC and PCC, the competitors with the best score were preselected to present and discuss their plan during the webinars. (3) Quiz competition: Two to six CTA scans of already performed selected aortic cases were submitted for the competition. A quiz with multiple choice questions was answered by the competitors. The top four competitors were selected for the webinars and then they discussed the cases during the webinar. Finally, at the end of the case discussion, the effective case resolution and follow-up were shown. A final winner was voted via televoting, based on six preestablished criteria. The project was endorsed by different national and international societies. Results: Between October 2020 and December 2021, there were 12 Italian and 1 international webinars with 1695 participants overall (mean, 130; range, 86-177). Competitors were 54 years of age (mean, 27 years; range, 22-38 years). Two editions were CCCs, two quiz competitions, and nine PCCs. The reliability of the interobserver sizing of competitors was κ = 0.43 and κ = 0.62 for the proximal and distal sealing measurements respectively and very good (κ = 0.88-0.95) in the evaluation of orientation of the vessels, presence of angulations, calcifications, and thrombus. The sizing discrepancy resulted in a significant variability of the planning (κ = 0.45). The project ranked 9.6 on a 10-point rating scale by all the participants and competitors. Conclusions: The formula of gaming and collegial discussion of aortic cases herein reported has proved valid and attractive during coronavirus disease 2019 pandemic period. The variability of the results on sizing and planning suggested to confer with a second opinion, especially for less experienced surgeons

Surveillance imaging modality does not affect detection rate of asymptomatic secondary interventions following EVAR.

OBJECTIVES: Literature reports that surveillance imaging following endovascular aortic aneurysm repair (EVAR) gives rise to asymptomatic secondary interventions (SI) in 1.4-9% of cases. This retrospective study aimed to evaluate whether the modality of surveillance imaging influences the detection rate of asymptomatic SI. MATERIALS AND METHODS: Two EVAR surveillance protocols were compared at the same vascular centre. Protocol I, performed from January 2003 to December 2006, consisted of colour duplex ultrasound scan (CDU) plus CT angiography (CTA) 1 month after procedure and every 6 months thereafter. Protocol II, performed from January 2007 to June 2010, consisted of CDU plus CTA 1 month after operation and CDU plus plain abdominal films (XR) every 6 months thereafter. In the second protocol, CTA was carried out only during follow-up in specific conditions. The term 'asymptomatic SI' was used when the necessity for SI was detected by imaging alone on an elective basis, prior to development of any symptoms. RESULTS: Enrolment included 376 and 341 consecutive patients with a mean follow-up of 1148 days (range 1-3204 days) and 942 days (range1-1512 days) in Protocols I and II, respectively (p < 0.001). Freedom rates from aneurysmal rupture, freedom from SI and detection rate for asymptomatic SI at 3 years were 98.3% and 98.7% (p = 0.456), 82% and 83.5%(p = 0.876) and 8.8% (n = 33/376) and 8.5%(n = 25/341) (p = 0.49) in Protocols I and II, respectively. Estimated comparison of the costs, radiation exposure and contrast used at 3 years in Protocol I versus Protocol II showed that Protocol II allowed for a three-, four- and six fold reduction in overall costs, radiation exposure and contrast used, respectively (p < 0.0001). CONCLUSIONS: The detection rate of asymptomatic SI following EVAR is not affected by the type of surveillance imaging. A surveillance schedule based primarily on CDU and XR appears to be justified

Endovascular Abdominal Aortic Aneurysm Repair With Ovation Alto Stent Graft: Protocol for the ALTAIR (ALTo endogrAft Italian Registry) Study

Background: Since 2010, the Ovation Abdominal Stent Graft System has offered an innovative sealing option for abdominal aortic aneurysm (AAA) by including a sealing ring filled with polymer 13 mm from the renal arteries. In August 2020, the redesigned Ovation Alto, with a sealing ring 6 mm closer to the top of the fabric, received CE Mark approval. Objective: This registry study aims to evaluate intraoperative, perioperative, and postoperative results in patients treated by the Alto stent graft (Endologix Inc.) for elective AAA repair in a multicentric consecutive experience. Methods: All consecutive eligible patients submitted to endovascular aneurysm repair (EVAR) by Alto Endovascular AAA implantation will be included in this analysis. Patients will be submitted to EVAR procedures based on their own preferences, anatomical features, and operators experience. An estimated number of 300 patients submitted to EVAR with Alto stent graft should be enrolled. It is estimated that the inclusion period will be 24 months. The follow-up period is set to be 5 years. Full data sets and cross-sectional images of contrast-enhanced computed tomography scan performed before EVAR, at the first postoperative month, at 24 or 36 months, and at 5-year follow-up interval will be reported in the central database for a centralized core laboratory review of morphological changes. The primary endpoint of the study is to evaluate the technical and clinical success of EVAR with the Alto stent graft in short- (90-day), mid- (1-year), and long-term (5-year) follow-up periods. The following secondary endpoints will be also addressed: operative time; intraoperative radiation exposure; contrast medium usage; AAA sac shrinkage at 12-month and 5-year follow-up; any potential role of patients' baseline characteristics, valuated on preoperative computed tomography angiographic study, and of device configuration (number of component) in the primary endpoint. Results: The study is currently in the recruitment phase and the final patient is expected to be treated by the end of 2023 and then followed up for 5 years. A total of 300 patients will be recruited. Analyses will focus on primary and secondary endpoints. Updated results will be shared at 1- and 3-5-year follow-ups. Conclusions: The results from this registry study could validate the safety and effectiveness of the new design of the Ovation Alto Stent Graft. The technical modifications to the endograft could allow for accommodation of a more comprehensive range of anatomies on-label

An artificial neural network stratifies the risks of reintervention and mortality after endovascular aneurysm repair:a retrospective observational study

Background Lifelong surveillance after endovascular repair (EVAR) of abdominal aortic aneurysms (AAA) is considered mandatory to detect potentially life-threatening endograft complications. A minority of patients require reintervention but cannot be predictively identified by existing methods. This study aimed to improve the prediction of endograft complications and mortality, through the application of machine-learning techniques. Methods Patients undergoing EVAR at 2 centres were studied from 2004-2010. Pre-operative aneurysm morphology was quantified and endograft complications were recorded up to 5 years following surgery. An artificial neural networks (ANN) approach was used to predict whether patients would be at low- or high-risk of endograft complications (aortic/limb) or mortality. Centre 1 data were used for training and centre 2 data for validation. ANN performance was assessed by Kaplan-Meier analysis to compare the incidence of aortic complications, limb complications, and mortality; in patients predicted to be low-risk, versus those predicted to be high-risk. Results 761 patients aged 75 +/- 7 years underwent EVAR. Mean follow-up was 36+/- 20 months. An ANN was created from morphological features including angulation/length/areas/diameters/ volume/tortuosity of the aneurysm neck/sac/iliac segments. ANN models predicted endograft complications and mortality with excellent discrimination between a low-risk and high-risk group. In external validation, the 5-year rates of freedom from aortic complications, limb complications and mortality were 95.9% vs 67.9%; 99.3% vs 92.0%; and 87.9% vs 79.3% respectively (p0.001) Conclusion This study presents ANN models that stratify the 5-year risk of endograft complications or mortality using routinely available pre-operative data

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Socket Preservation after Tooth Extraction: Particulate Autologous Bone vs. Deproteinized Bovine Bone

Background: The technique of socket preservation after tooth extraction allows for less volumetric decrease after tooth extraction. The aim of this retrospective study was to evaluate differences between alveolar socket preservation performed with deproteinized bovine bone graft and autologous particulate bone graft taken from the mandibular ramus. Materials and Methods: This retrospective study enrolled a total of 21 consecutive patients. A total of 11 patients underwent socket preservation with deproteinized bovine bone graft and collagen matrix (group A), and 10 patients underwent socket preservation performed with particulate autologous bone taken from the mandibular ramus and collagen matrix (group B). All patients received cone beam computed tomography (CBCT) before socket preservation and after four months. Alveolar bone width (ABW) values and alveolar bone height (ABH) values were measured at the first and second CBCT, and the reduction of the values in the two groups was compared. Statistical analysis was performed using Student’s t-test for independent variables, and p values &lt; 0.05 were considered statistically significant. Results: There were no statistically significant differences between ABW reduction of group A and ABW reduction of group B (t-test value p = 0.28). There were no statistically significant differences between ABH reduction of group A and ABH reduction of group B (t-test value p = 0.10). Conclusions: In this retrospective study, no statistical differences were found between the group that received autologous particulate bone compared to the group that received deproteinized bovine bone in socket preservation