Systematic review and meta-analysis of outcomes after semi-conversion with graft preservation for failed endovascular aneurysm repair.

OBJECTIVE: The aim of this study was to evaluate the outcomes after semi-conversion (open conversion with graft preservation) after failed endovascular aneurysm repair (EVAR). The primary outcomes were 30-day mortality and semi-conversion failure. Secondary outcomes were 30-day major systemic complications, endoleak recurrence, reinterventions, and overall survival. METHODS: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol was prospectively registered on PROSPERO (CRD42023421153). All studies reporting the outcomes of semi-conversions for failed EVAR were eligible for inclusion. Quality assessment was performed using the Methodological Index for Non-Randomized Studies (MINORS) tool. A random effects meta-regression of proportions was conducted using the double arcsine-Tukey transformation, given the frequent zero event rate in the primary outcome. Heterogeneity was assessed with the I2 statistic. RESULTS: Eight studies were included in the review after full text screening. A total of 196 patients underwent semi-conversion at a mean time from EVAR of 47.4 months, 68.9% in an elective setting. Mean age at conversion was 78.1 years, and the main indication was isolated endoleak type II (70.1% of cases). Aortic clamping was not necessary in 92.3% of semi-conversions; the aortic sac was opened in 96.1% of cases; in 93.3% of cases, ligation/suture of one or more culprit arteries were performed; and aortic neck banding was executed in 29.2%. At 30 days from surgery, the pooled mortality and the major systemic complications rates were 5.3% (I2 = 24.9%) and 13.4% (I2 = 54.3%), respectively. At follow-up, endoleak recurred after 12.6% semi-conversions (I2 = 83.2%), and the rate of reinterventions was 7% (I2 = 50.1%); the semi-conversion failure rate was 5.5% (I2 = 54.1%), and the overall survival was 84.6% (I2 = 33.3%). CONCLUSIONS: Semi-conversions have acceptable 30-day mortality rates, but the early and mid-term risks of complications, reinterventions, ruptures, and infections are not negligible. This procedure might be an alternative to complete or partial graft explant in patients whom aortic cross-clamping is not ideal.

Cardiac risk after elective endovascular repair for infrarenal abdominal aortic aneurysm: Results from the Italian Collaborators for EVAR multicenter registry.

OBJECTIVE: Major adverse cardiac events (MACEs) were common complications after endovascular aortic repair (EVAR) causing significant postoperative morbidity and mortality. The aim of the study was to evaluate the cardiac risk after elective EVAR for uncomplicated noninfected infrarenal abdominal aortic aneurysm in a large multicenter cohort. METHODS: This is a multicenter, retrospective, financially unsupported physician-initiated observational cohort study conducted by four academic tertiary referral hospitals from January 2018 to March 2021. Baseline, perioperative, and postoperative information of elective EVARs was evaluated. The primary outcome was the incidence of MACEs after EVAR, which was defined as acute coronary syndrome, non-ST-elevation myocardial infarction, unstable angina pectoris, de novo atrial fibrillation, hospitalization for heart failure, and revascularization as well as cardiovascular death. Secondary outcomes were 1-year overall survival (all-cause mortality) and freedom from aorta-related mortality. Comparative analysis was conducted between MACE and overall population, and univariate and multivariate logistic regression analyses were used to analyze factors associated with the risk of the MACE occurrence and early 1-year mortality. RESULTS: The study has enrolled 497 patients (35 females, 7%) with a mean age of 75.3 ± 7.8 years. The MACE rate was 6.4% (32/497, events/patients), and the majority of the events were recorded in the postoperative period (24/32, 75%; overall 24/497, 4.8%). One-year survival from all-cause mortality was 94% (95% confidence interval [CI]: 91-96), and the MACE population showed a significantly lower survival estimation rate (Overall - MACEs, 95.8% [95% CI: 93-97] - 67.9% [95% CI: 47-82], log-rank 41.950, P = .0001). Freedom from aorta-related mortality was 99.3% (95% CI: 98-100). The perioperative need for red blood cell transfusions was strongly related to the MACE occurrence (odds ratio: 2.67, 95% CI: 1.52-4.68, P = .001) and 1-year mortality (hazard ratio: 2.14, 95% CI: 1.48-3.09, P = .0001). CONCLUSIONS: MACEs represent a common complication in the postoperative and early period after elective EVAR. Blood loss requiring red blood cell transfusions is associated with increased postoperative MACEs and early mortality, suggesting that all the efforts should be carried out to reduce the bleeding during and after elective interventions.

Results of the Italian Collaborators for Evar Registry on Acute Kidney Injury After Elective Endovascular Aortic Repair of Infrarenal Abdominal Aortic Aneurysm.

OBJECTIVES: To analyze the incidence and predictive factors of postoperative acute kidney injury (AKI) after elective standard endovascular aortic repair (EVAR) in a large recent, multicenter cohort. MATERIALS AND METHODS: This is a multicenter, retrospective, financially unsupported physician-initiated observational cohort study. Between January 2018 and March 2021, only patients treated with elective standard EVAR for infrarenal non-infected abdominal aortic aneurysm were analyzed. Patients already on hemodialysis (HD) were excluded. AKI was defined as an increase in serum creatinine (sCr) ≥0.3 mg/dL within 48 hours or an increase in sCr to ≥1.5 times baseline known or presumed to have occurred within 7 days, or a urine volume of <0.5 mL/kg/h for 6 hours. Primary outcomes of interest were AKI incidence at 30 days and freedom from HD at 1-year follow-up. Secondary outcomes were freedom from severe postoperative complication, and freedom from aorta-related mortality (ARM) at 1 year. RESULTS: The final cohort analyzed 526 (29.8%). There were 489 (93%) males and 37 (7%) females: the median age was 76 years (interquartile range [IQR], 71-81). Chronic kidney disease (CKD) was present in 86 (16.3%) patients. Early mortality was observed in 8 (1.5%) patients, none was aorta-related. Complication rate was 17.1% (n=89). AKI was observed in 17 (3.2%). Renal replacement therapy was needed in 4 (0.8%). HD was transitory in 2 cases and definitive in 1. Binary logistic regression analysis identified CKD (odds ratio [OR]: 4.68, 95% confidence interval [CI]: 2.10-10.45, p<0.001), and the presence of renal artery stenosis (OR: 3.80, 95% CI: 1.35-10.66, p=0.011) to be associated with an increased risk of postoperative AKI. Estimated freedom from ARM was 94.9% at 1 year. Estimated freedom from HD rate at 1 year was 94%: This was significantly different between patients with preoperative CKD and those who did not have preoperative CKD (log-rank, p=0.042). CONCLUSION: AKI after elective standard EVAR still occurs but with an acceptably low incidence rate. Preoperative CKD is the most important predictor for postoperative AKI, which was not associated with the need for HD at 1-year follow-up but with a higher propensity of mortality. CLINICAL IMPACT: This "real world" experience confirm that EVAR performed with standard contrats agent protocol remains safe for acute kidney injury development. Therefore, only patients presenting with preoperative borderline or ascertained chronic kidney disease will take the most advantage from the use of carbon dioxide contrast.

Three-Dimensional Geometric Analysis of Viabahn VBX Bridging Stent Grafts in Fenestrated Endovascular Aortic Repair: A Multicenter, Retrospective Cohort Study.

PURPOSE: The primary aim of this study was to assess the 3-dimensional flare geometry of the Gore Viabahn VBX balloon-expandable covered stent (BECS) after fenestrated endovascular aortic repair (FEVAR) and to determine and visualize BECS-associated complications. METHODS: This multicenter retrospective study included patients who underwent FEVAR between 2018 and 2022 in 3 vascular centers participating in the VBX Expand Registry. Patients with at least one visceral artery treated with the VBX and with availability of 2 post-FEVAR computed tomography angiography (CTA) scans (follow-up [FU] 1: 0-6 months; FU2: 9-24 months) were included. The flare geometry of the VBX, including flare-to-fenestration distance, flare-to-fenestration diameter ratio, flare angle, and apposition with the target artery were assessed using a vascular workstation and dedicated CTA applied software. RESULTS: In total, 90 VBX BECS were analyzed in 43 FEVAR patients. The median CTA FU for FU1 and FU2 was 35 days (interquartile range [IQR], 29-51 days) and 14 months (IQR, 13-15 months), respectively. The mean flare-to-fenestration distance was 5.6±2.0 mm on FU1 and remained unchanged at 5.7±2.0 mm on FU2 (p=.417). The flare-to-fenestration diameter ratio was 1.19±0.17 on FU1 and remained unchanged at 1.21±0.19 (p=.206). The mean apposition length was 18.6±5.3 mm on FU1 and remained 18.6±5.3 mm (p=.550). The flare angle was 31°±15° on FU1 and changed to 33°±16° (p=.009). On FU1, the BECS-associated complication rate was 1%, and the BECS-associated reintervention rate was 0%. On FU2, the BECS-associated complication rate was 3%, and the BECS-associated reintervention rate was 1%. CONCLUSIONS: The flare geometry of the VBX bridging stent did not change significantly during 14 months follow-up in this study. Three-dimensional geometric analysis of the flare may contribute to identify the origin of endoleaks and occlusions, but this should be confirmed in a larger study including enough patients and BECS to compare complicated and uncomplicated cases. CLINICAL IMPACT: The three-dimensional flare geometry of the Gore Viabahn VBX BECS was assessed on the first and second postoperative CTA scans, and geometrical changes during this period were identified. For BECS that were diagnosed with a type 3c endoleak or occlusion, the BECS geometry was analyzed to detect geometrical components that were related to the complication. Geometric analysis of the flare may help to better detect and identify the cause of such complications.

Systematic Review and Meta-Analysis of Elective Open Conversion versus Fenestrated and Branched Endovascular Repair for Previous Non-Infected Failed Endovascular Aneurysm Repair.

OBJECTIVE: To evaluate outcomes of patients electively undergoing fenestrated and branched endovascular repair (F/B-EVAR) or open conversion for failed previous non-infected endovascular aneurysm repair (EVAR). DATA SOURCES: Embase, MEDLINE, Cochrane Library. REVIEW METHOD: The protocol was prospectively registered on PROSPERO (CRD42023404091). The review followed the PRISMA guidelines; certainty was assessed through the GRADE and quality through MINORS tools. Outcomes data were pooled separately for F/B-EVAR and open conversion. A random effects meta-analysis of proportions was conducted; heterogeneity was assessed with the I2 statistic. RESULTS: Thirty eight studies were included, for a total of 1 645 patients of whom 1 001 (60.9%) underwent an open conversion and 644 (39.1%) a F/B-EVAR. The quality of evidence was generally limited. GRADE certainty was judged low for 30 day death (in both groups) and F/B-EVAR technical success, and very low for the other outcomes. Pooled 30 day death was 2.3% (I2 33%) in the open conversion group and 2.4% (I2 0%) in the F/B-EVAR conversion group (p = .36). Technical success for F/B-EVAR was 94.1% (I2 23%). The pooled 30 day major systemic complications rate was higher in the open conversion (21.3%; I2 74%) than in the F/B-EVAR (15.7%; I2 78%) group (p = .52). At 18 months follow up, the pooled re-intervention rate was 4.5% (I2 58%) in the open conversion and 26% (I2 0%) in the F/B-EVAR group (p < .001), and overall survival was 92.5% (I2 59%) and 81.6% (I2 68%), respectively (p = .005). CONCLUSION: In the elective setting, and excluding infections, the early results of both open conversion and F/B-EVAR after failed EVAR appear satisfactory. Although open conversion presented with higher complication rates in the first 30 days after surgery, at follow up it seemed to be associated with fewer re-interventions and better survival compared with F/B-EVAR.

CO2 is the contrast media to choose in patients with initial Chronic Kidney Disease undergoing endovascular aneurysm repair to prevent further renal function deterioration.

OBJECTIVE: Even low quantities of iodine contrast media (ICM) could be responsible for exacerbation of a chronic kidney disease (CKD). Aim of this study was to determine whether it is more reasonable to perform endovascular aneurysm repair (EVAR) procedures in patients with initial CKD using CO2 rather than ICM to prevent further kidney deterioration. METHODS: A retrospective analysis was performed at our institution to identify patients with preoperative CKD at initial stage (class G3a-G3b according to KDOQI-KDIGO classification) who underwent either CO2-EVAR or ICM-EVAR. Primary endpoint was renal function evaluation; secondary endpoints were technical success, perioperative complications, hospital stay, and reinterventions and overall mortality at follow-up. RESULTS: Both CO2-EVAR and ICM-EVAR groups were composed of 21 patients. There were no differences in demographics, anatomy, and comorbidities, apart from worse ASA score in CO2-EVAR group (100% vs 57.1%, p = .001). Preoperative serum creatinine and glomerular filtration rates (GFR) were comparable (1.73 vs 1.6 mg/dl, p = .082 and 39.71 vs 43.04 mL/min/1.73 m2, p = .935). At follow-up (16.7 ± 18.1 months), CO2-EVAR was not associated with significant changes in creatinine and GFR, whereas ICM-EVAR determined a significant increase in creatinine (1.6 mg/dl vs 1.91 mg/dl, p = .04) and decrease in GFR values (43 vs 37.9 mL/min/1.73 m2, p = .04), determining the need for dialysis in one patient. CONCLUSIONS: ICM seems to be a determining factor in worsening renal function; therefore, an effort should be made to standardize the use of CO2 as the contrast medium of choice in patients with initial renal insufficiency undergoing EVAR.

Results of current endovascular treatments for visceral artery aneurysms.

OBJECTIVE: This single-center retrospective cohort study aimed to analyze the early and long-term results of endovascular treatment for true visceral artery aneurysms (VAAs). Moreover, a comparison with the results of our previously published historical series of open surgical procedures was performed. METHODS: From January 2008 to December 2021, 78 consecutive patients were treated at our institution for true VAAs. All demographic data, procedural details, perioperative outcomes, and follow-up data were collected prospectively from a dedicated database. A retrospective analysis identified 72 patients who underwent endovascular surgery. Early results were analyzed in terms of technical success, conversion to open surgery, mortality, and local and systemic morbidities. Follow-up results were analyzed in terms of survival, need for open or endovascular reintervention, and freedom from complications at the level of the treated visceral artery. These results were then compared with those of our historical open surgical group (1982-2007), which included 54 interventions. RESULTS: In four cases, the planned endovascular procedure could not be completed, and the overall technical success rate was 94.5%. No deaths occurred during the hospital stay or within 30 days after surgery. Overall, the 30-day perioperative complication rate was 5.8%, with an early reintervention rate of 2.9%. The median follow-up time was 29 months (range, 1-132 months). The estimated 7-year survival rate was 88% (standard error [SE]. 0.05). The estimated 7-year aneurysm-related complication-free rate was 85.5% (SE, 0.06), with reintervention-free and aneurysm-related complication-free survival rates of 93.3% (SE, 0.04) and 75.6% (SE, 0.07), respectively. At the 7-year follow-up, the survival rate was similar between the endovascular and open groups. There was a trend toward a higher aneurysm-related complication rate in the endovascular group than in the open group (14.5% vs 6.4%; P = .07). However, no significant differences in reintervention-free and overall estimated aneurysm-related complication-free survival rates were found between the two groups. CONCLUSIONS: Endovascular repair is safe and effective in patients with VAAs, with low perioperative complication rates. The long-term outcomes were satisfactory and comparable with those of the historical series of open surgical repairs. Even if there is a trend toward a higher risk of late aneurysm-related complications among endovascular patients, it does not imply an increased need for late reinterventions.

Fate of target visceral vessels in fenestrated and branched complex endovascular aortic repair.

OBJECTIVE: To assess branch vessel outcomes after endovascular repair of complex aortic aneurysms analyzing possible factors influencing early and long-term results. METHODS: The Italian Multicentre Fenestrated and Branched registry enrolled 596 consecutive patients treated with fenestrated and branched endografts for complex aortic disease from January 2008 to December 2019 by four Italian academic centers. The primary end points of the study were technical success (defined as target visceral vessel [TVV] patency and absence of bridging device-related endoleak at final intraoperative control), and freedom from TVV instability (defined as the combined results of type IC/IIIC endoleaks and patency loss) during follow-up. Secondary end points were overall survival and TVV-related reinterventions. RESULTS: We excluded 591 patients (3 patients with a surgical debranching and 2 patients who died before completion from the study cohort) were treated for a total of 1991 visceral vessels targeted by either a directional branch or a fenestration. The overall technical success rate was 98.4%. Failure was related to the use of an off-the-shelf (OTS) device (custom-made device vs OTS, HR, 0.220; P = .007) and a preoperative TVV stenosis of >50% (HR, 12.460; P < .001). The mean follow-up time was 25.1 months (interquartile range, 3-39 months). The overall estimated survival rates were 87%, 77.4%, and 67.8% at 1, 3, and 5 years, respectively (standard error [SE], 0.015, 0.022, and 0.032). During follow-up, TVV branch instability was observed in 91 vessels (5%): 48 type IC/IIIC endoleaks (2.6%) and 43 stenoses-thromboses (2.4%). The extent of aneurysm disease (thoracoabdominal aortic aneurysm [TAAA] types I-III vs TAAA type IV/juxtarenal aortic aneurysm/pararenal aortic aneurysm) was the only independent predictor for developing a TVV-related type IC/IIIC endoleak (HR, 3.899; 95% confidence interval [CI]:, 1.924-7.900; P < .001). Risk of patency loss was independently associated with branch configuration (HR, 8.883; P < .001; 95% CI, 3.750-21.043) and renal arteries (HR, 2.848; P = .030; 95% CI, 1.108-7.319). Estimated rates at 1, 3, and 5 years of freedom from TVV instability and freedom from TVV-related reintervention were 96.6%, 93.8%, and 90% (SE, 0.005, 0.007, and 0.014) and 97.4%, 95.0%, and 91.6% (SE, 0.004, 0.007, and 0.013), respectively. CONCLUSIONS: Intraoperative failure to bridge a TVV was associated with a preoperative TVV stenosis of >50% and the use of OTS devices. Midterm outcomes were satisfying, with an estimated 5-year freedom from TVV instability and reintervention of 90.0% and 91.6%, respectively. During follow-up, the larger extent of aneurysm disease was associated with an increased risk of TVV-related endoleaks, whereas a branch configuration and renal arteries were more prone to patency loss.

Total Iodine Contrast-free Strategy for the Endovascular Management of Abdominal Aortic Aneurysms in Chronic Kidney Disease Patients: A Pilot Study.

BACKGROUND: To retrospectively evaluate the feasibility and effectiveness of the endovascular treatment of patients with abdominal aortic aneurysm and chronic kidney disease (CKD) without the need for using iodinated contrast media throughout the diagnostic, therapeutic, and follow-up pathway. METHODS: A retrospective review of prospectively collected data concerning 251 consecutive patients presenting an abdominal aortic or aorto-iliac aneurysm who underwent endovascular aneurysm repair (EVAR) from January 2019 to November 2022 at our academic institution was performed in order to identify patients with feasible anatomy with respect to manufacturer's instructions for use and with CKD. Patients whose preoperative workout included duplex ultrasound and plain computed tomography for preprocedural planning were extracted from a dedicated EVAR database. EVAR was performed with the use of carbon dioxide (CO2) as the contrast media of choice, whereas follow-up examinations consisted of either duplex ultrasound, plain computed tomography, or contrast-enhanced ultrasound. Primary endpoints were technical success, perioperative mortality, and early renal function variations. Secondary endpoints were all-type endoleaks and reinterventions, midterm aneurysm-related and kidney-related mortality. RESULTS: Forty-five patients had CKD and were treated electively (45/251, 17.9%). Of them, 17 patients were managed with a total iodinated contrast media-free strategy and constituted the object of the present study (17/45, 37.8%; 17/251, 6.8%). In 7 cases, an adjunctive planned procedure was performed (7/17, 41.2%). No intraoperative bail-out procedures were needed. This extracted cohort of patients presented similar mean preoperative and postoperative (at discharge) glomerular filtration rate values, 28.14 (SD 13.09; median 28.06, interquartile range (IQR) 20.25) ml/min/1.73 m2 and 29.33 (SD 14.61; median 27.35, IQR 22) ml/min/1.73 m2, respectively (P = 0.210). Mean follow-up was 16.4 months (SD 11.89; median 18, IQR 23). During follow-up, no graft-related complications occurred in terms of either thrombosis, type I or III endoleaks, aneurysm rupture, or conversion. The mean glomerular filtration rate at follow-up was 30.39 ml/min/1.73 m2 (SD 14.45; median 30.75, IQR 21.93), with no significant worsening in comparison with preoperative and postoperative values (P = 0.327 and P = 0.856 respectively). No aneurysm- or kidney-related deaths occurred during follow-up. CONCLUSIONS: Our initial experience shows that total iodine contrast-free abdominal aortic aneurysm endovascular management in patients with CKD may be feasible and safe. Such an approach seems to guarantee the preservation of residual kidney function without increasing the risks of aneurysm-related complications in the early and midterm postoperative periods, and it could be considered even in the case of complex endovascular procedures.

The Suite for the Assessment of Low-Level cues on Orientation (SALLO): The psychophysics of spatial orientation in virtual reality.

Spatial orientation is a complex ability that emerges from the interaction of several systems in a way that is still unclear. One of the reasons limiting the research on the topic is the lack of methodologies aimed at studying multimodal psychophysics in an ecological manner and with affordable settings. Virtual reality can provide a workaround to this impasse by using virtual stimuli rather than real ones. However, the available virtual reality development platforms are not meant for psychophysical testing; therefore, using them as such can be very difficult for newcomers, especially the ones new to coding. For this reason, we developed SALLO, the Suite for the Assessment of Low-Level cues on Orientation, which is a suite of utilities that simplifies assessing the psychophysics of multimodal spatial orientation in virtual reality. The tools in it cover all the fundamental steps to design a psychophysical experiment. Plus, dedicated tracks guide the users in extending the suite components to simplify developing new experiments. An experimental use-case used SALLO and virtual reality to show that the head posture affects both the egocentric and the allocentric mental representations of spatial orientation. Such a use-case demonstrated how SALLO and virtual reality can be used to accelerate hypothesis testing concerning the psychophysics of spatial orientation and, more broadly, how the community of researchers in the field may benefit from such a tool to carry out their investigations.

Hybrid Surgical Approach to a Giant Post-Coarctation Aortic Aneurysm.

PURPOSE: To report a rare case of giant aortic coarctation (CoA)-related descending thoracic aneurysmal degeneration, complicated by an acute aortic dissection. CASE REPORT: A 57-year-old man referred with acute chest pain to the emergency department. A computed tomography angiography (CTA) revealed a CoA with a giant post-stenotic descending thoracic aneurysm (14 cm) and a concomitant left subclavian artery (LSA) aneurysm, complicated by an acute type B aortic dissection. A single-stage hybrid procedure was planned in an urgent setting. Initially, a left common carotid-to-left subclavian artery (LCCA-LSA) bypass was performed to gain a suitable proximal landing zone, the procedure was then completed with 3 thoracic endografts and 1 aortic dissection stent through a percutaneous femoral approach. The patient was discharged in postoperative day 8th without complications; the CTA performed at 1 month demonstrated patency of supra-aortic and visceral vessels, dilation of CoA site and exclusion of the false lumen. CONCLUSIONS: CoA is a congenital malformation rarely found in adults that may represent a challenge for the surgeon, especially when combined with a complication like an acute aortic dissection. This case shows that a hybrid approach is a safe and feasible treatment option even in such complex anatomies.

Different mechanisms of magnitude and spatial representation for tactile and auditory modalities.

The human brain creates an external world representation based on magnitude judgments by estimating distance, numerosity, or size. The magnitude and spatial representation are hypothesized to rely on common mechanisms shared by different sensory modalities. We explored the relationship between magnitude and spatial representation using two different sensory systems. We hypothesize that the interaction between space and magnitude is combined differently depending on sensory modalities. Furthermore, we aimed to understand the role of the spatial reference frame in magnitude representation. We used stimulus-response compatibility (SRC) to investigate these processes assuming that performance is improved if stimulus and response share common features. We designed an auditory and tactile SRC task with conflicting spatial and magnitude mapping. Our results showed that sensory modality modulates the relationship between space and magnitude. A larger effect of magnitude over spatial congruency occurred in a tactile task. However, magnitude and space showed similar weight in the auditory task, with neither spatial congruency nor magnitude congruency having a significant effect. Moreover, we observed that the spatial frame activated during tasks was elicited by the sensory inputs. The participants' performance was reversed in the tactile task between uncrossed and crossed hands posture, suggesting an internal coordinate system. In contrast, crossing the hands did not alter performance (i.e., using an allocentric frame of reference). Overall, these results suggest that space and magnitude interaction differ in auditory and tactile modalities, supporting the idea that these sensory modalities use different magnitude and spatial representation mechanisms.

Crystal structure of the human carbonic anhydrase II adduct with 1-(4-sulfamoylphenyl-ethyl)-2,4,6-triphenylpyridinium perchlorate, a membrane-impermeant, isoform selective inhibitor.

Pyridinium containing sulfonamides have been largely investigated as carbonic anhydrase inhibitors (CAIs), showing interesting selectivity features. Nevertheless, only few structural studies are so far available on adducts that these compounds form with diverse CA isoforms. In this paper, we report the structural characterization of the adduct that a triphenylpyridinium derivative forms with hCA II, showing that the substitution of the pyridinium ring plays a key role in determining the conformation of the inhibitor in the active site and consequently the binding affinity to the enzyme. These findings open new perspectives on the basic structural requirements for designing sulfonamide CAIs with a selective inhibition profile.

Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations.

Sulphamate and sulphamide derivatives have been largely investigated as carbonic anhydrase inhibitors (CAIs) by means of different experimental techniques. However, the structural determinants responsible for their different binding mode to the enzyme active site were not clearly defined so far. In this paper, we report the X-ray crystal structure of hCA II in complex with a sulphamate inhibitor incorporating a nitroimidazole moiety. The comparison with the structure of hCA II in complex with its sulphamide analogue revealed that the two inhibitors adopt a completely different binding mode within the hCA II active site. Starting from these results, we performed a theoretical study on sulphamate and sulphamide derivatives, demonstrating that electrostatic interactions with residues within the enzyme active site play a key role in determining their binding conformation. These findings open new perspectives in the design of effective CAIs using the sulphamate and sulphamide zinc binding groups as lead compounds.

Redefining biorefinery: the search for unconventional building blocks for materials.

This review discusses different strategies for the upgrading of biomass into sustainable monomers and building blocks as scaffolds for the preparation of green polymers and materials.

Titanium nitride-nickel nanocomposite as heterogeneous catalyst for the hydrogenolysis of aryl ethers.

Lignin from biomass can become a sustainable source of aromatic compounds. Its depolymerization can be accomplished through hydrogenolysis, although the development of catalysts based on cheap and abundant metals is lacking. Herein, a sustainable composite based on titanium nitride and nickel is synthesized and employed as catalyst for the hydrogenolysis of aryl ethers as models for lignin. The catalytic activity of the new material during hydrogenation reactions is proven to be superior to that of either component alone. In particular, different aryl ethers could be efficiently converted under relatively mild conditions into aromatic compounds and cycloalkanes within minutes.

Endovascular aneurysm repair under local anesthesia through bilateral percutaneous femoral access is a safe strategy to improve early outcomes and reduce hospital stay.

BACKGROUND: To estimate the impact of anesthetic conduct, alone and in combination with the type of femoral access, on early results after endovascular aneurysm repair (EVAR). METHODS: A retrospective multicenter analysis on patients undergoing elective standard EVAR at four academic centers was performed. Patients undergoing the procedure through either local or general anesthesia were compared. Comparative subanalyses of the two groups were performed for the type of femoral access to evaluate further impact on outcomes. RESULTS: Five hundred twenty-four patients underwent elective standard EVAR, of which 207 (39.5%) under general anesthesia and 317 (60.5%) under local anesthesia. Patients who underwent general anesthesia had higher 30-day mortality rates (3.4% vs. 0.3%, P=0.005), as well as slightly worse 30-day major systemic complication rates (8.2% vs. 5.4%, P=0.195). There were no differences in terms of reinterventions (2.1% vs. 2.5%, P=0.768) and aneurysm-related mortality (0% vs. 0.4%, P=0.422) at one year. Total intervention times were significantly longer in the general anesthesia group (126 vs. 89 minutes, P=0.001), as well as the total length of hospital stay (7.6 vs. 5.3 days, P=0.007). At subanalyses, the combination of local anesthesia with bilateral percutaneous femoral access further improved 30-day outcomes and determined an additional reduction in total intervention times and ICU stays. CONCLUSIONS: EVAR performed under local anesthesia has a significantly better impact on early results when compared to general anesthesia. Combining percutaneous bilateral femoral access to local anesthesia reduced procedural times, ICU stays and consequently improved early results.

Guidelines on the diagnosis, treatment and management of visceral and renal arteries aneurysms: a joint assessment by the Italian Societies of Vascular and Endovascular Surgery (SICVE) and Medical and Interventional Radiology (SIRM).

The objective of these Guidelines is to provide recommendations for the classification, indication, treatment and management of patients suffering from aneurysmal pathology of the visceral and renal arteries. The methodology applied was the GRADE-SIGN version, and followed the instructions of the AGREE quality of reporting checklist. Clinical questions, structured according to the PICO (Population, Intervention, Comparator, Outcome) model, were formulated, and systematic literature reviews were carried out according to them. Selected articles were evaluated through specific methodological checklists. Considered Judgments were compiled for each clinical question in which the characteristics of the body of available evidence were evaluated in order to establish recommendations. Overall, 79 clinical practice recommendations were proposed. Indications for treatment and therapeutic options were discussed for each arterial district, as well as follow-up and medical management, in both candidate patients for conservative therapy and patients who underwent treatment. The recommendations provided by these guidelines simplify and improve decision-making processes and diagnostic-therapeutic pathways of patients with visceral and renal arteries aneurysms. Their widespread use is recommended.

Autoregulatory circuit of human rpL3 expression requires hnRNP H1, NPM and KHSRP.

Alternative pre-mRNA splicing (AS) is a major mechanism that allows proteomic variability in eukaryotic cells. However, many AS events result in mRNAs containing a premature termination codon, which are degraded by nonsense-mediated mRNA decay (NMD) pathway. We have previously demonstrated that human rpL3 autoregulates its expression through the association of AS with NMD. In fact, overexpression of rpL3 promotes downregulation of canonical splicing and upregulation of alternative splicing that produces an NMD-targeted mRNA isoform. The result of these events is a decreased production of rpL3. We have also identified heterogeneous nuclear ribonucleoprotein (hnRNP) H1 as a splicing factor involved in the regulation of rpL3 alternative splicing and identified its regulatory cis-elements within intron 3 transcript. Here, we report that NPM and KHSRP are two newly identified proteins involved in the regulation of rpL3 gene expression via AS-NMD. We demonstrate that hnRNP H1, KHSRP and NPM can be found associated, and present also in ribonucleoproteins (RNPs) including rpL3 and intron 3 RNA in vivo, and describe protein-protein and RNA-protein interactions. Moreover, our data provide an insight on the crucial role of hnRNP H1 in the regulation of the alternative splicing of the rpL3 gene.