Sex Influence on Fenestrated and Branched Endovascular Aortic Aneurysm Repair: Outcomes From a National Multicenter Registry

Introduction: Women are generally underrepresented in trials focusing on aortic aneurysm. Nevertheless, sex-related differences have recently emerged from several studies and registries. The aim of this research was to assess whether sex-related anatomical disparities existed in fenestrated and branched aortic repair candidates and whether these discrepancies could influence endovascular repair outcomes. Methods: Data from all consecutive patients treated during the 2008–2019 period within the Italian Multicenter fenestrated or branched endovascular aortic repair (F/BEVAR) Registry were included in the present study. Propensity matching was performed using a logistic regression model adjusted for demographic data and comorbidities to obtain comparable male and female samples. The selection model led to a final study population of 176 patients (88 women and 88 men) among the total initial cohort of 596. Study endpoints were technical and clinical success, overall survival, aneurysm-related death, and reintervention rates evaluated at 30 days and during follow-up. Results: Twenty-eight patients (15.9%) received urgent/emergent repair. In most of the cases (71.6%), women received treatment for extensive thoracoabdominal pathology (Crawford type I, II, or III aneurysm rather than type IV or juxta-pararenal) versus 46.6% of men (p=0.001). Female patients presented with more challenging iliac accesses with at least one side considered hostile in 27.3% of the cases (vs 13.6% in male patients, p=0.039). Finally, women had significantly smaller visceral vessels. Women had significantly worse operative outcomes, with an 86.2% technical success rate versus 96.6% in the male population (p=0.016). No differences were recorded in terms of 30-day reinterventions between men and women. The 5-year estimate of freedom from late reintervention, according to Kaplan-Meier analysis, was 85.6% in men versus 81.6% in women (p=ns). No aneurysm-related death was recorded during follow-up (median observational time, 23 months [interquartile range, 7–45 months]). Conclusion: Women presented a significantly higher incidence of thoracoabdominal aneurysms, smaller visceral vessels, and more complex iliofemoral accesses, resulting in a significantly lower technical success after F/BEVAR. Further studies assessing sex-related differences are needed to properly determine the impact on outcomes and stratify procedural risks. Clinical Impact: Women are generally underrepresented in trials focusing on aortic aneurysms. Aiming to assess whether sex may affect outcomes after a complex endovascular aortic repair, a propensity score selection was applied to a total population of 596 patients receiving F/BEVAR aortic repair with the Cook platform, matching each treated female patient with a corresponding male patient. Women presented more frequently a thoracoabdominal aneurysm extent, smaller visceral vessels, and complex iliofemoral accesses, resulting in significantly worse operative outcomes, with an 86.2% technical success versus 96.6% (p=0.016). No differences were recorded in terms of short-term and mid-term reinterventions. According to these results, careful and critical assessment should be posed in case of female patients receiving complex aortic repair, especially regarding preoperative anatomical evaluation and clinical selection with appropriate surgical risk stratification

Folding mechanisms steer the amyloid fibril formation propensity of highly homologous proteins

Significant advances in the understanding of the molecular determinants of fibrillogenesis can be expected from comparative studies of the aggregation propensities of proteins with highly homologous structures but different folding pathways. Here, we fully characterize, by means of stopped-flow, T-jump, CD and DSC experiments, the unfolding mechanisms of three highly homologous proteins, zinc binding Ros87 and Ml153-149 and zinc-lacking Ml452-151. The results indicate that the three proteins significantly differ in terms of stability and (un)folding mechanisms. Particularly, Ros87 and Ml153-149 appear to be much more stable to guanidine denaturation and are characterized by folding mechanisms including the presence of an intermediate. On the other hand, metal lacking Ml452-151 folds according to a classic two-state model. Successively, we have monitored the capabilities of Ros87, Ml452-151 and Ml153-149 to form amyloid fibrils under native conditions. Particularly, we show, by CD, fluorescence, DLS, TEM and SEM experiments, that after 168 hours, amyloid formation of Ros87 has started, while Ml153-149 has formed only amorphous aggregates and Ml452-151 is still monomeric in solution. This study shows how metal binding can influence protein folding pathways and thereby control conformational accessibility to aggregation-prone states, which in turn changes aggregation kinetics, shedding light on the role of metal ions in the development of protein deposition diseases

Probing the Residual Structure in Avian Prion Hexarepeats by CD, NMR and MD Techniques

Many proteins perform essential biological functions by means of regions that lacking specific organized structure exist as an ensemble of interconverting transient conformers. The characterization of such regions, including the description of their structural propensities, number of conformations and relative populations can provide useful insights. Prion diseases result from the conversion of a normal glycoprotein into a misfolded pathogenic isoform. The structures of mammal and chicken prion proteins show a similar fold with a globular domain and a flexible N-terminal portion that contains different repeated regions: octarepeats (PHGGGWGQ) in mammals and hexarepeats (PHNPGY) in chickens. The higher number of prolines in the hexarepeat region suggests that this region may retain a significant amount of residual secondary structure. Here, we report the CD, NMR and MD characterization of a peptide (2-HexaPY) composed of two hexarepeats. We combine experimental NMR data and MD to investigate at atomic level its ensemble-averaged structural properties, demonstrating how each residue of both repeats has a different quantified PPII propensity that shows a periodicity along the sequence. This feature explains the absence of cooperativity to stabilize a PPII conformation. Nonetheless, such residual structure can play a role in nucleating local structural transitions as well as modulating intra-molecular or inter-molecular interactions

Field and Temperature Shaping for Microwave Hyperthermia: Recent Treatment Planning Tools to Enhance SAR-Based Procedures

The aim of the article is to provide a summary of the work carried out in the framework of a research project funded by the Italian Ministry of Research. The main goal of the activity was to introduce multiple tools for reliable, affordable, and high-performance microwave hyperthermia for cancer therapy. The proposed methodologies and approaches target microwave diagnostics, accurate in vivo electromagnetic parameters estimation, and improvement in treatment planning using a single device. This article provides an overview of the proposed and tested techniques and shows their complementarity and interconnection. To highlight the approach, we also present a novel combination of specific absorption rate optimization via convex programming with a temperature-based refinement method implemented to mitigate the effect of thermal boundary conditions on the final temperature map. To this purpose, numerical tests were carried out for both simple and anatomically detailed 3D scenarios for the head and neck region. These preliminary results show the potential of the combined technique and improvements in the temperature coverage of the tumor target with respect to the case wherein no refinement is adopted

Efficiency and Patient-Reported Outcome Measures From Clinic to Home: The Human Empowerment Aging and Disability Program for Digital-Health Rehabilitation

Background: The recent exponential growth of Digital Health (DH) in the healthcare system provides a crucial transformation in healthcare, answering to alarming threats related to the increasing number of Chronic Neurological Diseases (CNDs). New long-term integrated DH-care approaches, including rehabilitation, are warranted to address these concerns. Methods: The Human Empowerment Aging and Disability (HEAD) rehabilitation program, a new long-term integrated care including DH-care system, was evaluated in terms of efficiency and patient-reported outcome measures (PROMs) in 107 CND patients (30 with Parkinson's Disease, PD; 32 with Multiple Sclerosis, MS; 45 with stroke in chronic stage). All participants followed 1-month of HEAD rehabilitation in clinic (ClinicHEAD: 12 sessions, 3/week), then 1:3 patient was consecutively allocated to 3-months telerehabilitation at home (HomeHEAD: 60 sessions, 5/week). Efficiency (i.e., adherence, usability, and acceptability) and PROMs (i.e., perceived functioning in real-world) were analyzed. Results: The rate of adherence to HEAD treatment in clinic (≥90%) and at home (77%) was high. Usability of HEAD system was judged as good (System Usability Scale, median 70.00) in clinic and even more at home (median 80.00). Similarly, administering the Technology Acceptance Model 3 questionnaire we found high scores both in clinic/at home (Usefulness, mean 5.39 ± 1.41 SD/mean 5.33 ± 1.29 SD; Ease of use, mean 5.55 ± 1.05 SD/ mean 5.45 ± 1.17 SD, External Control, mean 4.94 ± 1.17 SD/mean 5.07 ± 1.01 SD, Relevance, mean 5.68 ± 1.29 SD/mean 5.70 ± 1.13 SD and Enjoyment, mean 5.70 ± 1.40 SD/mean 6.01 ± 1.08 SD). After ClinicHEAD, participation and autonomy in daily routine was maintained or even ameliorated (PD and stroke > MS). Whereas, increased functionality and participation in the MS group was found only after HomeHEAD intervention. Discussion: Our results suggest that a tele-health-based approach is both feasible and efficient in providing rehabilitation care to CNDs from clinic to home. Increasing and maintaining participation as well as autonomy in daily routine are promising findings that open up scenarios for the continuity of care at home through DH-care for CNDs

Telerehabilitation for Lee Silverman Voice Treatment (Tele-LSVT)-Loud on voice intensity and voice use in daily living in people with multiple sclerosis: A protocol for a feasibility and pilot randomized controlled study

Objective: Alterations in voice intensity and quality may constitute a social life limitation in people with multiple sclerosis (MS), but only 2% of cases receive speech therapy. Especially the Lee Silverman Voice Treatment (LSVT)-Loud is a highly effective intensive method for voice intensity, requiring subjects’ repeated attendance at the clinic. Telerehabilitation may represent a feasible solution to bypass potential barriers related to speech therapy attendance, scaling up the beneficial effects of the treatment to a broader population. The proposed protocol aims to test the feasibility and the pilot efficacy of the LSVT-Loud delivered in telerehabilitation (Tele-LSVT-Loud), compared to the same treatment delivered in the clinic (LSVT-Loud). Methods: A single-blinded, parallel, two-arm, pilot randomized (1:1 ratio) controlled trial will be performed involving 20 people with MS. Patients will be allocated to 4 weeks of Tele-LSVT-Loud by accessing a telerehabilitation platform at home or LSVT-Loud conventionally delivered in the clinic. Feasibility and pilot effectiveness will be evaluated three times: before (T0), after the treatment (T1), and 3-month follow-up (T2). Feasibility measures will include adherence, adverse events, user experience, motivation, engagement, and acceptability. Vocal intensity during a 1-minute monologue will be the primary outcome measure. Secondary outcome measures will be the vocal quality during a 1-minute monologue, sustained /a/ voice intensity, quality and stability, voice use in daily life, voice subjective perception in daily life, and quality of life. Results: Expected results will be (1) high feasibility of Tele-LSVT-Loud and (2) a non-inferiority effect of Tele-LSVT-Loud compared with face-to-face treatment delivery on voice intensity and quality outcomes. Conclusions: Tele-LSVT-Loud may be a feasible intervention for MS alteration in voice intensity and quality with a non-inferior effect compared to LSVT-Loud

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

A Non-Iterative Crosswords-Inspired Approach to the Recovery of 2-D Discrete Signals From Phaseless Fourier Transform Data

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