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In the contemporary world, human and natural calamities are challenging our capabilities to preserve heritage and develop innovative safeguard strategies that also address the requirement of sustainability for restoration purposes, still considering the connection between tradition and innovation. This work introduces non-invasive diagnostic practices that offer a new insight of the built environment by studying two different elements of the same architecture of San Bevignate Templar church: a thermographic mapping obtained with special post-processing procedures provided interesting information about the hidden wall pattern, while a prototypal laser scanner, called RGB-ITR, and a UAV survey supplied new insights on the precious paintings. The assessment of the masonry quality constitutes an a priori condition for a reliable estimation of its seismic vulnerability and for the planning of effective yet conservative interventions. The access keys to 'sustainability' therefore consist in the improvement of these contactless investigations, which can be performed both in passive conditions, in the case of thermography surveys, and in active ones, such as for the RGB-ITR scanner, as necessary substitutes for destructive or partial-destructive tests. The research achieved promising results for the characterisation of the architectural structure and the paintings, with the aim of a long-term monitoring of the structure and the decorative apparatus of a monumental heritage located in an area vulnerable to seismic and environmental events.

Background: The impact of prosthesis-patient mismatch (PPM) on major endpoints after transcatheter aortic valve replacement (TAVR) is controversial and the effects on progression of heart damage are poorly investigated. Therefore, our study aims to evaluate the prevalence and predictors of PPM in a "real world" cohort of patients at intermediate and low surgical risk, its impact on mortality and the clinical-echocardiographic progression of heart damage., Methods: 963 patients who underwent TAVR procedure between 2017 and 2021, from the RECOVERY-TAVR international multicenter observational registry, were included in this analysis. Multiparametric echocardiographic data of these patients were analyzed at 1-year follow-up (FU). Clinical and echocardiographic features were stratified by presence of PPM and PPM severity, as per the most current international recommendations, using VARC-3 criteria., Results: 18% of patients developed post-TAVR. PPM, and 7.7% of the whole cohort had severe PPM. At baseline, 50.3% of patients with PPM were male (vs 46.2% in the cohort without PPM, P = .33), aged 82 (IQR 79-85y) years vs 82 (IQR 78-86 P = .46), and 55.6% had Balloon-Expandable valves implanted (vs 46.8% of patients without PPM, P = .04); they had smaller left ventricular outflow tract (LVOT) diameter (20 mm, IQR 19-21 vs 20 mm, IQR 20-22, P = .02), reduced SVi (34.2 vs 38 mL/m 2 , P < .01) and transaortic flow rate (190.6 vs 211 mL/s, P < .01). At predischarge FU patients with PPM had more paravalvular aortic regurgitation (moderate-severe AR 15.8% vs 9.2%, P < .01). At 1-year FU, maladaptive alterations of left ventricular parameters were found in patients with PPM, with a significant increase in end-systolic diameter (33 mm vs 28 mm, P = .03) and a significant increase in left ventricle end systolic indexed volume in those with moderate and severe PPM (52 IQR 42-64 and 52, IQR 41-64 vs 44 IQR 35-59 in those without, P = .02)). No evidence of a significant impact of PPM on overall (P = .71) and CV (P = .70) mortality was observed. Patients with moderate/severe PPM had worse NYHA functional class at 1 year (NYHA III-IV 13% vs 7.8%, P = .03). Prosthesis size≤23 mm (OR 11.6, 1.68-80.1) was an independent predictor of PPM, while SVi (OR 0.87, 0.83-0.91, P < .001) and LVOT diameter (OR 0.79, 0.65-0.95, P = .01) had protective effect., Conclusions: PPM was observed in 18% of patients undergoing TAVR. Echocardiographic evaluations demonstrated a PPM-related pattern of early ventricular maladaptive alterations, possibly precursor to a reduction in cardiac function, associated with a significant deterioration in NYHA class at 1 year. These findings emphasize the importance of prevention of PPM of any grade in patients undergoing TAVR procedure, especially in populations at risk., Competing Interests: Declaration of competing interest The authors have no conflict of interest to report related to this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The endosomal sorting complex required for transport (ESCRT) machinery is composed of an articulated architecture of proteins that assemble at multiple cellular sites. The ESCRT machinery is involved in pathways that are pivotal for the physiology of the cell, including vesicle transport, cell division, and membrane repair. The subunits of the ESCRT I complex are mainly responsible for anchoring the machinery to the action site. The ESCRT II subunits function to bridge and recruit the ESCRT III subunits. The latter are responsible for finalizing operations that, independently of the action site, involve the repair and fusion of membrane edges. In this review, we report on the data related to the activity of the ESCRT machinery at two sites: the nuclear membrane and the midbody and the bridge linking cells in the final stages of cytokinesis. In these contexts, the machinery plays a significant role for the protection of genome integrity by contributing to the control of the abscission checkpoint and to nuclear envelope reorganization and correlated resilience. Consistently, several studies show how the dysfunction of the ESCRT machinery causes genome damage and is a codriver of pathologies, such as laminopathies and cancer.

Background: Destructive aortic prosthetic valve endocarditis portends a high morbidity and mortality, and requires complex high-risk surgery. Homograft root replacement is the most radical and biocompatible operation and, thus, the preferred option. Methods: A retrospective analysis was conducted on 61 consecutive patients who underwent a cardiac reoperation comprising homograft aortic root replacement since 2010. The probabilities of survival were calculated with the Kaplan-Meier method, whereas multivariable regression served to outline the predictors of adverse events. The endpoints were operative/late death, perioperative low cardiac output and renal failure, and reoperations. Results: The operative (cumulative hospital and 30-day) mortality was 13%. The baseline aspartate transaminase (AST) and associated mitral procedures were predictive of operative death ( p = 0.048, OR [95% CIs] = 1.03 [1-1.06]) and perioperative low cardiac output, respectively ( p = 0.04, OR [95% CIs] = 21.3 [2.7-168.9] for valve replacement). The latter occurred in 12 (20%) patients, despite a normal ejection fraction. Survival estimates (±SE) at 3 months, 6 months, 1 year, and 3 years after surgery were 86.3 ± 4.7%, 82.0 ± 4.9%, 75.2 ± 5.6, and 70.0 ± 6.3%, respectively. Survival was significantly lower in the case of AST ≥ 40 IU/L ( p = 0.04) and aortic cross-clamp time ≥ 180 min ( p = 0.01), but not when excluding operative survivors. Five patients required early (two out of the five, within 3 months) or late (three out of the five) reoperation. Conclusions : Homograft aortic root replacement for destructive prosthetic valve endocarditis can currently be performed with a near 90% operative survival and reasonable 3-year mortality and reoperation rate. AST might serve to additionally stratify the operative risk.

Objective: Bleeding is frequent during transcatheter aortic valve implantation (TAVI), especially when performed through a transapical approach (TA), and is associated with a worse prognosis. The present study aims to test the implication of red blood cell (RBC) transfusion and the optimal transfusion strategy in this context., Methods: Among 11,265 participants in the multicenter TRITAVI (Transfusion Requirements in Transcatheter Aortic Valve Implantation) registry, 548 patients (4.9%) who received TA-TAVI at 19 European centers were included. One-to-one propensity score matching was performed to reduce treatment selection bias and potential confounding among transfused versus non-transfused patients. The primary endpoint of the study was the 30-day occurrence of all-cause mortality., Results: 209 patients (38 %) received RBC transfusions. The primary endpoint occurred in 47 (8.6 %) patients. Propensity score matching identified 188 pairs of patients with and without RBC transfusion. In the propensity score-matched analysis, RBC transfusion was associated with increased 30-day mortality (HR 3.35, 95 % CI 1.51 - 7.39; p = 0.002). At multivariable cox regression analysis, RBC transfusion was an independent predictor of 30-day mortality (HR 3.07, 95 % CI 1.01-9.41, p = 0.048), as well as baseline ejection fraction (HR 0.96, 95 % CI 0.92-0.99, p = 0.043), and acute kidney injury (HR 3.95, 95 % CI 1.11-14.05, p = 0.034)., Conclusions: RBC transfusion is an independent predictor of short-term mortality in patients undergoing TA-TAVI, regardless of major bleeding.Clinical trial registration: https://www.clinicaltrials.gov Unique identifier: NCT03740425., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: Dialysis is a rare but serious complication after transcatheter aortic valve replacement. We analyzed the large multicenter TRITAVI (transfusion requirements in transcatheter aortic valve implantation) registry in order to develop and validate a clinical score assessing this risk., Methods and Results: A total of 10 071 consecutive patients were enrolled in 19 European centers. Patients were randomly assigned (2:1) to a derivation and validation cohort. Two scores were developed, 1 including only preprocedural variables (TRITAVIpre) and 1 also including procedural variables (TRITAVIpost). In the 6714 patients of the derivation cohort (age 82±6 years, 48% men), preprocedural factors independently associated with dialysis and included in the TRITAVIpre score were male sex, diabetes, prior coronary artery bypass graft, anemia, nonfemoral access, and creatinine clearance <30 mL/min per m 2 . Additional independent predictors among procedural features were volume of contrast, need for transfusion, and major vascular complications. Both scores showed a good discrimination power for identifying risk for dialysis with C-statistic 0.78 for TRITAVIpre and C-statistic 0.88 for TRITAVIpost score. Need for dialysis increased from the lowest to the highest of 3 risk score groups (from 0.3% to 3.9% for TRITAVIpre score and from 0.1% to 6.2% for TRITAVIpost score). Analysis of the 3357 patients of the validation cohort (age 82±7 years, 48% men) confirmed the good discrimination power of both scores (C-statistic 0.80 for TRITAVIpre and 0.81 for TRITAVIpost score). Need for dialysis was associated with a significant increase in 1-year mortality (from 6.9% to 54.4%; P =0.0001)., Conclusions: A simple preprocedural clinical score can help predict the risk of dialysis after transcatheter aortic valve replacement.

The present study was conceived to examine the effects of inhibition of BMS-345541 mediated IKK kinase phosphorylation on the cellular defence system as well as on anti-inflammatory response and HSP90 activity. The analysis was conducted in A549 cell line, since such cells carry a homozygous Keap1 mutation (G333C) that alters its interaction with Nrf2. Recent data have highlighted that Keap1, HSP90 protein and IKK kinase interact reciprocally and particularly Keap1 protein is involved in HSP90 and anti-oxidative pathway regulation. The activities of COX2 and HO1 were investigated by real time and immunoblot analysis along with the synthesis and activity of inducible forms of heat shock protein HSP90. Pre-treatment with IKK kinase inhibitor proved to be a protective means to lower the activity of inflammatory cascade, so preventing the formation of excessive amounts of pro-inflammatory molecules. The inhibitor of IKK kinase BMS-345541 was added to cultured A549 cells before the Escherichia coli lipopolysaccharide (LPS) addition. The viability of the cells was determined after 1-24 h incubation with BMS-345541 at concentrations ranging from 1,25-5 µM. It was found that 1 µM concentration does not significantly affected cell viability (data not shown). As a result, the treatment with 1 μM of BMS-345541 induces the inhibition of IKK phosphorylation. In the A549 cells treated with BMS-345541 and LPS, COX2 activity is not induced: mRNA and protein levels have not increased, while there is an increase in the level of HSP90, HO1 proteins and mRNA. The results suggest that the IKK inhibition is effective in the reduction of the inflammatory response thanks to mechanisms involving both the heat shock cellular defense system and the antioxidative pathway., (© 2023. The Author(s).)

Competing Interests: Funding Support and Author Disclosures Prof Vola is a clinical consultant for Affluent Medical. Prof Salizzoni is a surgical proctor for Epygon. Dr Vairo is an echocardiography proctor for Epygon. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

DNA damage is emerging as a driver of heart disease, although the cascade of events, its timing, and the cell types involved are yet to be fully clarified. In this context, the implication of cardiomyocytes has been highlighted, while that of vasculature smooth muscle cells has been implicated but not explored exhaustively. In our previous work we characterized a factor called Ft1 in mice and AKTIP in humans whose depletion generates telomere instability and DNA damage. Herein, we explored the effect of the reduction of Ft1 on the heart with the goal of comparatively defining the impact of DNA damage targeted to vasculature smooth muscle cells to that of diffuse damage. Using two newly generated mouse models, Ft1 constitutively knocked out (Ft1ko) mice, and mice in which we targeted the Ft1 depletion to the smooth muscle cells (Ft1sm22ko), it is shown that both genetic models display cardiac defects but with differences. Both Ft1ko and Ft1sm22ko mice display hypertrophy, fibrosis, and functional heart defects. Interestingly, Ft1sm22ko mice have early milder pathological traits that become manifest with age. Significantly, the defects of Ft1ko mice, including the alteration of the left ventricle and functional heart defects, are rescued by depletion of the DNA damage sensor p53. These results point to Ft1 deficiency as a driver of cardiac disease and show that Ft1 deficiency targeted to vasculature smooth muscle cells generates a pre-pathological profile exacerbated by age., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Research on the topic of knowledge risks and their management in organizations is still very scarce, this also applies to empirical studies. However, to avoid the uncritical acceptance of empirical results, replication studies play a crucial role in science. Therefore, this study represents a replication study of the type of empirical generalization of the paper by Durst et al. (2019) which studied knowledge risk management (KRM) in private and public organizations. Considering the KRM and performance assumptions underlying the original study and the methodology used, the results at that time are reviewed using new data from 103 Italian cooperative banks. This paper contributes to the study of risks related to knowledge and its theoretical development by providing new empirical evidence from a different cultural, geographical and institutional context. Furthermore, it emphasizes the importance of replication studies for knowledge accumulation and theory development in management science., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Aim: Complex anal fistula represents a burden for patients, and its management is a challenge for surgeons. Video-assisted anal fistula treatment (VAAFT) is one sphincter-sparing technique. However, data on its long-term effectiveness are scant. We aimed to explore the outcomes of VAAFT in a retrospective cohort of patients referred to a tertiary centre., Method: Consecutive adult patients with a minimum of 2 years' follow-up after VAAFT were reviewed. Patients were followed up to 5 years postoperatively. Failure was defined as incomplete healing of the external orifice(s) during the first 6 months. Recurrence was defined as new radiologically and/or clinically confirmed onset of the fistula after primary healing. A generalized linear model was fitted to evaluate the association between failure and sociodemographic characteristics. Predictors of recurrence were determined in a subgroup analysis of patients found to be free from disease at 6 months postoperatively., Results: Overall, 106 patients (70% male; mean age 41 years) were reviewed. Of these 86% had a previous seton placement. Fistulas were either high trans-sphincteric (74%), suprasphincteric (12%) or extrasphincteric (13%). Eight (7%) patients experienced postoperative complications, none of which required reintervention. Mean follow-up was 53 ± 13.2 months. VAAFT failed in 14 (13%) patients. The overall recurrence rate ranged from 29% at 1 year to 63% at 5 years. Multiple external orifices, suprasphincteric fistula, younger age, previous surgery and higher complexity of the fistulous tract were independent risk factors for recurrence., Conclusion: VAAFT is a safe sphincter-sparing technique. The initially high success rate decreases over time and relates to a higher degree of complexity., (© 2023 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Purpose: The aim of this study was to evaluate the 5-year recurrence rate of pilonidal sinus disease (PSD) after endoscopic sinusectomy and identify risk factors for recurrence., Methods: All consecutive patients from September 2011 through December 2017 who underwent endoscopic sinusectomy at seven referral centres for pilonidal sinus treatment were retrospectively analysed from a prospectively maintained database., Results: Out of 290 patients (185 males versus 105 female, with a mean age of 25.5±6.9), 73 presented recurrence at 5-year follow-up with a recurrence rate of 25.2%. The number of pilonidal sinus with pits off the midline (p = 0.001) and the mean (SD) distance from the most lateral orifice to the midline (p = 0.001) were higher in the group of patients with recurrence at 5-year follow-up. Multivariate analysis demonstrated that the position of the pits off the midline (p = 0.001) and the distance of the most lateral orifice from the midline (p = 0.001) were independent risk factors for recurrence at 5-year follow-up. Receiver operating characteristic (ROC) curve analysis showed that the distance of lateral orifice from midline predicted an 82.2% possibility of recurrence at 5-year follow-up and Youden's test identified the best cut-off as 2 cm for this variable. Out of 195 cases with the most lateral orifice less than 2 cm from the midline, 13 presented recurrence at 5-year follow-up with a recurrence rate of 6.7%. Out of 95 cases with the most lateral orifice more than 2 cm from midline, 60 showed recurrence at 5-year follow-up with a recurrence rate of 63.2%., Conclusions: This data may help guide which disease characteristics predict the optimal use of an endoscopic pilonidal sinus technique., (© 2023. Springer Nature Switzerland AG.)

Complex anal fistulas (CAF) present a challenge in achieving healing while preserving anal sphincter function. This study aims to introduce a novel staged approach for CAF treatment, combining video-assisted anal fistula treatment (VAAFT), seton placement, and other staged approaches. Consecutive patients with CAF underwent the staged approach involving VAAFT and seton placement. Data on patient demographics, fistula characteristics, and operative findings were collected. Pre-operative work-up included clinical evaluation, endoanal ultrasonography (EAUS), and magnetic resonance imaging (MRI). Surgical techniques and outcomes were evaluated. Eighteen patients (median age 38 years) were included. Misplacement of a previously placed seton was observed in 64% of cases. VAAFT combined with seton placement achieved simplification and healing of secondary tracts in 66% of cases. Operative times significantly decreased across interventions. At a median follow-up of 14 months, complete healing was achieved in 2 patients, with 1 patient demonstrating persistence of the fistula. Post-operative complications were observed in 11% of patients, with no deterioration in continence. The staged approach combining VAAFT, seton placement, and staged procedures offers a potential solution for treating CAF. VAAFT provides diagnostic and therapeutic benefits, simplifying the fistula anatomy and optimizing seton placement. The approach allows subsequent procedures based on individual fistula characteristics., (© 2023. The Author(s).)

Aim: Chronic anal fissure (CAF) is an extremely frequent finding in clinical practice. Several topical agents have been proposed for its treatment with the common goal of increasing anodermal blood flow to promote healing. The aim of this study was to compare the efficacy and safety of a Propionibacterium extract gel (PeG) and 0.4% glyceryl trinitrate ointment (GTN) in patients with CAF., Method: Patients were randomly allocated to a PeG or GTN group and medication was administered every 12 h for 40 days. The primary outcome was the success rate, as measured by a decrease in the REALISE scoring system for anal fissure at 10, 20 and 40 days after initiating either treatment. The secondary outcomes recorded at the same time points were healing rate, visual analogue scales for itching and burning, rate of complications and adverse events, patient quality of life and satisfaction, and cost analysis., Results: A total of 120 patients were enrolled, and 96 patients (PeG, n = 53; GTN, n = 43) completed the primary outcomes. A significant decrease over time in the REALISE score was observed in both groups. Adverse events occurred more frequently in the GTN group than in the PeG group, peaking at visit 1 [37 (63.8%) vs. 2 (3.4%), respectively], with headache being the most prevalent. The between-treatment cumulative average costs per patient were significantly higher for GTN than that for PeG at each follow-up visit. There were no other significant differences between the two groups for any of the other outcomes., Conclusion: While there was no difference in healing rates between the two treatments, PeG was more cost-effective and associated with fewer adverse events., (© 2023 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Background: Long-term right ventricular pacing (VP) has been related to negative left ventricular remodeling and heart failure (HF), but there is a lack of evidence regarding the prognostic impact on transcatheter aortic valve replacement (TAVR) patients., Objectives: The aim of the PACE-TAVI registry is to evaluate the association of high percentage of VP with adverse outcomes in patients with pacemaker implantation after TAVR., Methods: PACE-TAVI is an international multicenter registry of all consecutive TAVR patients who underwent permanent pacemaker implantation for conduction disturbances in the first 30 days after the procedure. Patients were divided into 2 subgroups according to the percentage of VP (<40% vs ≥40%) at pacemaker interrogation. The primary endpoint was the composite of cardiovascular mortality or hospitalization for HF., Results: A total of 377 patients were enrolled, 158 with VP <40% and 219 with VP ≥40%. After multivariable adjustment, VP ≥40% was associated with a higher incidence of the primary endpoint (HR: 2.76; 95% CI: 1.39-5.51; P = 0.004), first HF hospitalization (HR: 3.37; 95% CI: 1.50-7.54; P = 0.003), and cardiovascular death (HR: 3.77; 95% CI: 1.02-13.88; P = 0.04), while the incidence of all-cause death was not significantly different (HR: 2.17; 95% CI: 0.80-5.90; P = 0.13). Patients with VP ≥ 40% showed a higher New York Heart Association functional class both at 1 year (P = 0.009) and at last available follow-up (P = 0.04) and a nonsignificant reduction of left ventricular ejection fraction (P = 0.18) on 1-year echocardiography, while patients with VP <40% showed significant improvement (P = 0.009)., Conclusions: In TAVR patients undergoing permanent pacemaker implantation, a high percentage of right VP at follow-up is associated with an increased risk for cardiovascular death and HF hospitalization. These findings suggest the opportunity to minimize right VP through dedicated algorithms in post-TAVR patients without complete atrioventricular block and to evaluate a more physiological VP modality in patients with persistent complete atrioventricular block., Competing Interests: Funding Support and Author Disclosures Dr Ziacchi has received speaker fees from Abbott, Biotronik, and Boston Scientific. Prof Rordorf has received modest speaker fees from Abbott and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Strawberry cultivation is an important source of income for Brazilian farmers. Cultivation can be done using the traditional model, in which producers must flex their trunk to handle seedlings, or using the hydroponic model, which involves an upright posture., Objectives: To verify the influence of cultivation model on posture and back pain prevalence among strawberry producers., Methods: A total of 26 strawberry producers who used traditional or hydroponic methods participated in the study. The angular values of the curvatures of the thoracic and lumbar spine in the sagittal plane were obtained using the "flexicurve" method, while pain prevalence was determined with Souza & Krieger's back pain questionnaire. The t -test for independent samples and the chi-square test were used to compare group results., Results: Growers using the traditional model had greater thoracic spine curvature (45.5 [SD, 26.2 ]) than those who used the hydroponic model (24.4 [SD, 10.3 ]). There was an association between thoracic spine classification and cervical pain, with a higher prevalence of thoracic kyphosis and cervical pain in the traditional model and a higher prevalence of normal curvature in the hydroponic model. Both groups reported a higher prevalence of pain in the lower back than in other locations., Conclusions: The cultivation model influenced posture and back pain prevalence in strawberry producers. Producers who use the traditional model have greater angulations of the thoracic spine, hyperkyphosis, lumbar straightening, and cervical pain than those who use the hydroponic model., Competing Interests: Conflicts of interest: None

Aim: Pilonidal sinus or Pilonidal Disease (PD) is a relatively common, benign but challenging condition. Although commonly encountered in practice, its ideal treatment is controversial. One of the most validated treatments is video-assisted surgery. In this context, very similar endoscopic techniques have been published under different names. The aim of this systematic review is to assess the differences among these proposed techniques and their outcomes., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed during all stages of this systematic review. A systematic search of the English literature was performed on multiple databases from 1 January 2014 to 3 April 2022. The primary outcome measure was the IDEAL framework stage of innovation. The key secondary outcome measures were the adherence to the IDEAL reporting guidelines, the Blencowe framework and the core outcome set (COS) for studies evaluating the introduction and evaluation of novel surgical techniques, the qualitative assessment using appropriate tools, the procedural variations and outcomes of each technique., Results: A total of 38 articles were included reporting a very similar technique under eight different acronyms. The number of patients varied from 9 to 250. Mean follow-up ranged from 1 to 60 months. There was only one published study of IDEAL 3. The majority (58%) were IDEAL 2a studies. Reporting of domains in the IDEAL reporting guidelines and Blencowe framework was poor, with most studies not reporting the component steps of procedures or efforts to standardize them. Half of COS domains were markedly underreported. The quality of the evidence was categorized as having a risk of bias from moderate to critical level in all nine comparative non-randomized series. Postoperative complications occurred in 0%-6% of cases, including surgical site infection, poor or failed wound healing bleeding, granuloma, haematoma, and pain requiring intervention. The recurrence rate varied from 0% to 22%., Conclusion: The study demonstrates that reporting on technical aspects of interventions for PD is poor, thus warranting a better-quality control of surgical techniques. It is advisable to group all endoscopic procedures under the umbrella term of 'endoscopic sinusectomy', thus embracing the two main principles of this technique, that is, video assistance and PD ablation., (© 2022 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Background: Lamins, key nuclear lamina components, have been proposed as candidate risk biomarkers in different types of cancer but their accuracy is still debated. AKTIP is a telomeric protein with the property of being enriched at the nuclear lamina. AKTIP has similarity with the tumor susceptibility gene TSG101. AKTIP deficiency generates genome instability and, in p53 -/- mice, the reduction of the mouse counterpart of AKTIP induces the exacerbation of lymphomas. Here, we asked whether the distribution of AKTIP is altered in cancer cells and whether this is associated with alterations of lamins., Methods: We performed super-resolution imaging, quantification of lamin expression and nuclear morphology on HeLa, MCF7, and A549 tumor cells, and on non-transformed fibroblasts from healthy donor and HGPS (LMNA c.1824C > T p.Gly608Gly) and EDMD2 (LMNA c.775 T > G) patients. As proof of principle model combining a defined lamin alteration with a tumor cell setting, we produced HeLa cells exogenously expressing the HGPS lamin mutant progerin that alters nuclear morphology., Results: In HeLa cells, AKTIP locates at less than 0.5 µm from the nuclear rim and co-localizes with lamin A/C. As compared to HeLa, there is a reduced co-localization of AKTIP with lamin A/C in both MCF7 and A549. Additionally, MCF7 display lower amounts of AKTIP at the rim. The analyses in non-transformed fibroblasts show that AKTIP mislocalizes in HGPS cells but not in EDMD2. The integrated analysis of lamin expression, nuclear morphology, and AKTIP topology shows that positioning of AKTIP is influenced not only by lamin expression, but also by nuclear morphology. This conclusion is validated by progerin-expressing HeLa cells in which nuclei are morphologically altered and AKTIP is mislocalized., Conclusions: Our data show that the combined alteration of lamin and nuclear morphology influences the localization of the tumor-associated factor AKTIP. The results also point to the fact that lamin alterations per se are not predictive of AKTIP mislocalization, in both non-transformed and tumor cells. In more general terms, this study supports the thesis that a combined analytical approach should be preferred to predict lamin-associated changes in tumor cells. This paves the way of next translational evaluation to validate the use of this combined analytical approach as risk biomarker., (© 2022. The Author(s).)

Introduction: Despite limited to short and midterm outcomes, valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) has emerged as a valid alternative to re-surgical aortic valve replacement (re-SAVR) for high- and intermediate-risk patients with degenerated surgical bioprosthesis., Methods: All studies comparing multivariate adjustment between ViV TAVI and re-SAVR were screened. The primary end-points were all-cause and cardiovascular (CV) mortality at 30 days and at Midterm follow-up. Short-term complications were the secondary endpoints., Results: We obtained data from 11 studies, encompassing 8570 patients, 4224 undergoing ViV TAVI, and 4346 re-SAVR. Four studies included intermediate-risk patients and seven high-risk patients. 30-day all-cause and CV mortality were significantly lower in ViV (odds ratio [OR] 0.43, 95% confidence intervals [CIs] 0.29-0.64 and OR 0.44, 0.26-0.73 respectively), while after a mean follow-up of 717 (180-1825) days, there was no difference between the two groups (OR 1.04, 0.87-1.25 and OR 1.05, 0.78-1.43, respectively). The risk of stroke (OR 1.03, 0.59-1.82), MI (OR 0.70, 0.34-1.44), major vascular complications (OR 0.92, 0.50-1.67), and permanent pacemaker implantation (OR 0.67, 0.36-1.25) at 30 days did not differ, while major bleedings and new-onset atrial fibrillation were significantly lower in ViV patients (OR 0.41, 0.25-0.67 and OR 0.23, 0.12-0.42, respectively, all 95% CIs)., Conclusions: In high- and intermediate-risk patients with degenerated surgical bioprostheses, ViV TAVI is associated with reduced short-term mortality, compared with re-SAVR. Nevertheless, no differences were found in all-cause and CV mortality at midterm follow-up. PROSPERO CRD42021226488., (© 2022 Wiley Periodicals LLC.)

Membrane-enclosed organelle compartmentalization is not the only way by which cell processes are spatially organized. Phase separation is emerging as a new driver in the organization of membrane-less compartments and biological processes. Liquid-liquid phase separation has been indicated as a new way to control the kinetics of molecular reactions and is based on weak multivalent interactions affecting the stoichiometry of the molecules involved. In the nucleus, liquid-liquid phase separation may represent an ancestral means of controlling genomic activity by forming discrete chromatin regions, regulating transcriptional activity, contributing to the assembly of DNA damage response foci, and controlling the organization of chromosomes. Liquid-liquid phase separation also contributes to chromatin function through its role in the reorganization of the nuclear periphery in the post-mitotic phase. Herein, we describe the basic principles regulating liquid-liquid phase separation, analyze examples of phase separation occurring in the nucleus, and dedicate attention to the implication of liquid-liquid phase separation in the reorganization of the nuclear periphery by the endosomal sorting complexes required for transport (ESCRT) machinery. Although some caution is warranted, current scientific knowledge allows for the hypothesis that many factors and processes in the cell are yet to be discovered which are functionally associated with phase separation.

Background: The adoption of Computed tomography (CT)-defined sarcopenia to risk stratify transcatheter aortic valve implantation (TAVI) candidates remains limited by a lack of both standardized definition and evidence of independent value over currently adopted mortality prediction tools., Methods: 391 consecutive TAVI patients with pre-procedural CT scan were included (81 ​± ​6 years, 57.5% male, STS-PROM score 4.4 ​± ​3.6%) and abdominal muscle retrospectively quantified. The two definitions of radiologic sarcopenia previously adopted in TAVI studies were compared (psoas muscle area [PMA] at the L4 vertebra level: "PMA-sarcopenia"; indexed skeletal muscle area at the L3 vertebra level: "SMI-sarcopenia"). The primary endpoint was longer available-term all-cause mortality. Secondary endpoints were Valve Academic Research Consortium-2-defined in-hospital and 30-day outcomes., Results: SMI- and PMA-sarcopenia were present in 192 (49.1%) and 117 (29.9%) patients, respectively. After a median of 24 (12-30) months follow-up, 83 (21.2%) patients died. PMA-(adj-HR 1.81, 95%CI 1.12-2.93, p ​= ​0.015), but not SMI-sarcopenia (adj-HR 1.23, 95%CI 0.76-2.00, p ​= ​0.391), was associated with all-cause mortality independently of age, sex and in-study outcome predictors (atrial fibrillation, hemoglobin, history of peripheral artery disease, cancer and subcutaneous adipose tissue). PMA-defined sarcopenia provided additive prognostic value over current post-TAVI mortality risk estimators including STS-PROM (p ​= ​0.001), Euroscore II (p ​= ​0.025), Charlson index (p ​= ​0.025) and TAVI2-score (p ​= ​0.020). Device success, early safety, clinical efficacy and 30-day all-cause death were unaffected by sarcopenia status regardless of definition., Conclusions: PMA-sarcopenia (but not SMI-sarcopenia) is predictive of 2 year mortality among TAVI patients. The prognostic information provided by PMA-sarcopenia is independent of the tools currently adopted to predict post-TAVI mortality in clinical practice., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2021 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

The prevalence of chronic wounds is increasing due to the population aging and associated pathologies, such as diabetes. These ulcers have an important socio-economic impact. Thus, it is necessary to design new products for their treatment with an adequate cost/effectiveness ratio. Among these products are amorphous hydrogels. Their composition can be manipulated to provide a favorable environment for ulcer healing. The aim of this study was to evaluate a novel multifunctional amorphous hydrogel (EHO-85), containing Olea europaea leaf extract, designed to enhance the wound healing process. For this purpose, its moistening ability, antioxidant capacity, effect on pH in the wound bed of experimental rats, and the effect on wound healing in a murine model of impaired wound healing were assessed. EHO-85 proved to be a remarkable moisturizer and its application in a rat skin wound model showed a significant antioxidant effect, decreasing lipid peroxidation in the wound bed. EHO-85 also decreased the pH of the ulcer bed from day 1. In addition, in mice (BKS. Cg-m +/+ Leprdb) EHO-85 treatment showed superior wound healing rates compared to hydrocolloid dressing. In conclusion, EHO-85 can speed up the closure of hard-to-heal wounds due to its multifunctional properties that are able to modulate the wound microenvironment, mainly through its remarkable effect on reactive oxygen species, pH, and moistening regulation.

Aims: To evaluate the impact of systematic predilation with balloon aortic valvuloplasty (BAV) on transcatheter aortic valve implantation (TAVI)., Methods and Results: We performed a systematic meta-analysis investigating patients undergoing TAVI with systematic BAV vs no BAV in RCT or in adjusted studies. Device success was the primary endpoint, while all-cause mortality, 30-day moderate/severe aortic regurgitation (AR), stroke, permanent pacemaker implantation (PPI) and acute kidney injury (AKI) were the secondary endpoints. Subanalysis according to design of the study (RCT and adjusted analysis) and to the type of valve (balloon-expandable [BE] vs self-expanding [SE]) were conducted. We obtained data from 15 studies, comprising 16,408 patients: 10,364 undergoing BAV prior to TAVI and 6,044 in which direct TAVI has been performed. At 30-day follow-up, BAV did not improve the rate of device success in the overall population (OR, 1.09; 95% CI, 0.90-1.31), both in SE (OR, 0.93; 95% CI, 0.60-1.45) and in BE (OR, 1.16; 95% CI, 0.88-1.52) valves. Between BAV and direct TAVI, no differences in secondary outcomes were observed neither in overall population nor according to valve type between BAV and direct TAVI strategies. All endpoints results were consistent between RCTs and adjusted studies except for postdilation rate that did not differ in observational studies (OR, 0.70; 95% CI, 0.47-1.04), while it was lower in BAV when only RCTs were included in the analysis (OR, 0.48; 95% CI, 0.24-0.97)., Conclusions: Direct TAVI is feasible and safe compared to predilation approach with similar device success rates and clinical outcomes. Direct TAVI could represent a first-choice approach in contemporary TAVI procedures.

The excess of free radicals in the wound environment contributes to its stagnation during the inflammatory phase, favoring hard-to-heal wounds. Oxidative stress negatively affects cells and the extracellular matrix, hindering the healing process. In this study, we evaluated the antioxidant and wound-healing properties of a novel multifunctional amorphous hydrogel-containing Olea europaea leaf extract (OELE). Five assessments were performed: (i) phenolic compounds characterization in OELE; (ii) absolute antioxidant activity determination in OELE and hydrogel (EHO-85); (iii) antioxidant activity measurement of OELE and (iv) its protective effect on cell viability on human dermal fibroblasts (HDFs) and keratinocytes (HaCaT); and (v) EHO-85 wound-healing-capacity analysis on diabetic mice (db/db; BKS.Cg-m+/+Leprdb). The antioxidant activity of OELE was prominent: 2220, 1558, and 1969 µmol TE/g by DPPH, ABTS, and FRAP assays, respectively. Oxidative stress induced with H 2 O 2 in HDFs and HaCaT was normalized, and their viability increased with OELE co-treatment, thus evidencing a protective role. EHO-85 produced an early and sustained wound-healing stimulating effect superior to controls in diabetic mice. This novel amorphous hydrogel presents an important ROS scavenger capacity due to the high phenolic content of OELE, which protects skin cells from oxidative stress and contributes to the physiological process of wound healing.

Pilonidal disease (PD) is a relatively common, benign but challenging condition of the natal cleft. This consensus statement was drawn up by a panel of surgeons, identified by the Italian Society of Colorectal Surgery (SICCR) as having a "special interest" in PD, with the aim of recommending the best therapeutic options according to currently available scientific evidence. A three-step modified-Delphi process was adopted, implying: (1) choice of the panelists; (2) development of a discussion outline and of target issues; and (3) a detailed systematic review of the current literature. The agreement/disagreement level was scored on a five-point Likert scale as follows: "A + : strongly agree; A-: agree; N: unsure/no opinion; D-: disagree; D + : strongly disagree. Each panelist contributed to the production of this manuscript, and the final recommendations were reviewed by the Clinical Practice Guidelines Committee., (© 2021. The Author(s).)

Background: Surgical treatment of anal fistulas is still a challenge. The aims of this study were to evaluate the adoption and healing rates for the different surgical techniques used in Italy over the past 15 years., Methods: This was a multicenter retrospective observational study of patients affected by simple and complex anal fistulas of cryptoglandular origin who were surgically treated in the period 2003-2017. Surgical techniques were grouped as sphincter-cutting or sphincter-sparing and as technology-assisted or techno-free. All patients included in the study were followed for at least 12 months., Results: A total of 9,536 patients (5,520 simple; 4,016 complex fistulas) entered the study. For simple fistulas, fistulotomy was the most frequently used procedure, although its adoption significantly decreased over the years (P < .0005), with an increase in sphincter-sparing approaches; the overall healing rate in simple fistulas was 81.1%, with a significant difference between sphincter-cutting (91.9%) and sphincter-sparing (65.1%) techniques (P = .001). For complex fistulas, the adoption of sphincter-cutting approaches decreased, while sphincter-sparing techniques were mildly preferred (P < .0005). Moreover, there was a significant trend toward the use of technology-assisted procedures. The overall healing rate for complex fistulas was 69.0%, with a measurable difference between sphincter-cutting (81.1%) and sphincter-sparing (61.4%; P = .001) techniques and between techno-free and technology-assisted techniques (72.5% and 55.0%, respectively; P = .001)., Conclusion: Surgical treatment of anal fistulas has changed, with a trend toward the use of sphincter-sparing techniques. The overall cure rate has remained stable, even if the most innovative procedures have achieved a lower success rate., (Copyright © 2021 Elsevier Inc. All rights reserved.)

To complete mitosis, the bridge that links the two daughter cells needs to be cleaved. This step is carried out by the endosomal sorting complex required for transport (ESCRT) machinery. AKTIP, a protein discovered to be associated with telomeres and the nuclear membrane in interphase cells, shares sequence similarities with the ESCRT I component TSG101. Here we present evidence that during mitosis AKTIP is part of the ESCRT machinery at the midbody. AKTIP interacts with the ESCRT I subunit VPS28 and forms a circular supra-structure at the midbody, in close proximity with TSG101 and VPS28 and adjacent to the members of the ESCRT III module CHMP2A, CHMP4B and IST1. Mechanistically, the recruitment of AKTIP is dependent on MKLP1 and independent of CEP55. AKTIP and TSG101 are needed together for the recruitment of the ESCRT III subunit CHMP4B and in parallel for the recruitment of IST1. Alone, the reduction of AKTIP impinges on IST1 and causes multinucleation. Our data altogether reveal that AKTIP is a component of the ESCRT I module and functions in the recruitment of ESCRT III components required for abscission., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Recently, observational data have raised concerns about safety of selfexpandable (SE) compared to balloon-expandable (BE) valves in TAVI, although potentially limited by patient selection bias., Methods: All Randomized Controlled Trials (RCTs) comparing BE vs. SE TAVI or/and vs. aortic valve replacement (AVR) were included and compared through Network Meta Analysis (NMA). All-cause and cardiovascular (CV) mortality were the primary endpoints, stroke, rates of permanent pacemaker implantation (PPI), moderate/severe paravalvular leak (PVL) and reintervention were the secondary endpoints. Results We obtained data from 11 RCTs, encompassing 9752 patients. After one and two years, no significant differences for allcause and CV mortality were observed. Compared to surgical bioprostheses, both BE and SE TAVI reduced the risk of acute kidney injury (OR 0.42; CI 95% 0.30-0.60 and OR 0.44; CI 95% 0.32-0.60), new-onset atrial fibrillation (OR 0.24; CI 95% 0.14-0.42 and OR 0.21; CI 95% 0.13-0.34) and major bleedings (OR 0.32; CI 95% 0.16-0.65 and OR 0.47; CI 95% 0.25-0.89). The BE prostheses reduced the risk of moderate/severe PVL at 30-day (OR 0.31; CI 95% 0.17-0.55) and of PPI both at 30-day (OR 0.51; CI 95% 0.33-0.79) and 1 year (OR 0.40; CI 95% 0.30-0.55) as compared to SE TAVI. Conclusions A TAVI strategy, independently from BE or SE prostheses, offers a midterm survival comparable to AVR. The BE prostheses are associated with a reduction of PPI and PVL compared to SE prostheses without any differences in all-cause and CV mortality during two years of follow up. PROSPERO ID CRD42020182407., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: Accurate detection of SARS-CoV-2 RNA is essential to stopping the spread of SARS-CoV-2. The aim of this study was to evaluate the performance of the recently introduced MassARRAY ® SARS-CoV-2 Panel and to compare it to the cobas ® SARS-CoV-2 Test., Methods: The MassARRAY ® SARS-CoV-2 Panel consists of five assays targeting different sequences of the SARS-CoV-2 genome. Accuracy was determined using national and international proficiency panels including 27 samples. For clinical evaluation, 101 residual clinical samples were analyzed and results compared. Samples had been tested for SARS-CoV-2 RNA with the cobas ® SARS-CoV-2 Test., Results: When accuracy was tested with the MassARRAY ® SARS-CoV-2 Panel, 25 of 27 (92.6%) samples revealed correct results. When clinical samples were analyzed with the MassARRAY ® SARS-CoV-2 Panel and compared to the cobas ® SARS-CoV-2 Test, 100 samples showed concordant results. One sample was found to be inconclusive with the MassARRAY ® SARS-CoV-2 Panel. When time-to-results were compared, the new assay showed longer total and hands-on times., Conclusions: The MassARRAY ® SARS-CoV-2 Panel showed a good performance and proved to be suitable for use in the routine diagnostic laboratory. Especially during phases of shortage of reagents and/or disposables, the new test system appears as beneficial alternative to standard assays used for detection of SARS-CoV-2 RNA., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: To investigate the effects of myofascial release on the flexibility and electromyographic activity of the lumbar erector spinae muscle in healthy individuals., Methods: Ten healthy subjects were recruited to an intervention protocol of myofascial release techniques: (1) superficial myofascial release; (2) deep myofascial release apply along 10 sessions, twice a week, with 40 min per sessions. The outcomes evaluated were flexibility (Toe-Touch Test) and electromyography activity (EMG) of the lumbar erector spinae muscle (Iliocostalis and Longissimus bilaterally) during the movement of extension-flexion of the trunk. Paired t-test was used to compare the electromyographic outcomes, while the Wilcoxon test was used to compare the flexibility outcomes., Results: The myofascial release techniques increased the flexibility (p = 0.005; r = 0.88) and have no influence over the electromyographic activity of the right iliocostalis (p = 0.179; r = 0.43), right longissimus (p = 0.877; r = 0.05), left iliocostalis (p = 0.386; r = 0.29) and left longissimus (p = 0.418; r = 0.27)., Conclusions: The application of myofascial release techniques increase flexibility and did not influence over the electromyographic activity of the lumbar erector spinae muscles in healthy individuals. Further studies should include a larger sample with a sham group and/or compare EMG activity of the lumbar erector spinae muscles with patients with low back pain during the movement of extension-flexion of the trunk., Competing Interests: Declaration of competing interest We state that all authors (Laura Rodrigues, Patricia Cilene Freitas Sant’Anna, Marcelo La Torre and William Dhein) have made substantial contributions to the article, either in its conception and design or in the acquisition of data and analysis and interpretation of it. Also, all authors participated in the drafting of the article and in its reviews until was considered for submitting. We hereby state that each of the authors has read and concurs with the content in the manuscript. Also, we declare that this paper has not been published elsewhere and the authors declare that was no conflict of interest in this study., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims: Permanent pacemaker implantation (PPI) may be required after transcatheter aortic valve implantation (TAVI). Evidence on PPI prediction has largely been gathered from high-risk patients receiving first-generation valve implants. We undertook a meta-analysis of the existing literature to examine the incidence and predictors of PPI after TAVI according to generation of valve, valve type, and surgical risk., Methods and Results: We made a systematic literature search for studies with ≥100 patients reporting the incidence and adjusted predictors of PPI after TAVI. Subgroup analyses examined these features according to generation of valve, specific valve type, and surgical risk. We obtained data from 43 studies, encompassing 29 113 patients. Permanent pacemaker implantation rates ranged from 6.7% to 39.2% in individual studies with a pooled incidence of 19% (95% CI 16-21). Independent predictors for PPI were age [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01-1.09], left bundle branch block (LBBB) (OR 1.45, 95% CI 1.12-1.77), right bundle branch block (RBBB) (OR 4.15, 95% CI 3.23-4.88), implantation depth (OR 1.18, 95% CI 1.11-1.26), and self-expanding valve prosthesis (OR 2.99, 95% CI 1.39-4.59). Among subgroups analysed according to valve type, valve generation and surgical risk, independent predictors were RBBB, self-expanding valve type, first-degree atrioventricular block, and implantation depth., Conclusions: The principle independent predictors for PPI following TAVI are age, RBBB, LBBB, self-expanding valve type, and valve implantation depth. These characteristics should be taken into account in pre-procedural assessment to reduce PPI rates. PROSPERO ID CRD42020164043., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

The COVID-19 pandemic changed expectations for information dissemination and use around the globe, challenging accepted models of communications, leadership, and social systems. We explore how social media discourse about COVID-19 in Italy was affected by the rapid spread of the virus, and how themes in postings changed with the adoption of social distancing measures and non-pharmaceutical interventions (NPI). We used topic modeling and social network analysis to highlight critical dimensions of conversations around COVID-19: 1) topics in social media postings about the Coronavirus; 2) the scope and reach of social networks; and 3) changes in social media content as the nation moved from partial to full social distancing. Twitter messages sent in Italy between February 11th and March 10th, 2020. 74,306 Tweets sent by institutions, news sources, elected officials, scientists and social media influencers. Messages were retweeted more than 1.2 million times globally. Non-parametric chi-square statistic with residual analysis to identify categories, chi-square test for linear trend, and Social Network Graphing. The first phase of the pandemic was dominated by social media influencers, followed by a focus on the economic consequences of the virus and placing blame on immigrants. As the crisis deepened, science-based themes began to predominate, with a focus on reducing the spread of the virus through physical distancing and business closures Our findings highlight the importance of messaging in social media in gaining the public's trust and engagement during a pandemic. This requires credible scientific voices to garner public support for effective mitigation. Fighting the spread of an infectious disease goes hand in hand with stemming the dissemination of lies, bad science, and misdirection.