Stricturing Crohn's Disease Single-Cell RNA Sequencing Reveals Fibroblast Heterogeneity and Intercellular Interactions.

BACKGROUND & AIMS: Fibroblasts play a key role in stricture formation in Crohn's disease (CD) but understanding its pathogenesis requires a systems-level investigation to uncover new treatment targets. We studied full-thickness CD tissues to characterize fibroblast heterogeneity and function by generating the first single-cell RNA sequencing (scRNAseq) atlas of strictured bowel and providing proof of principle for therapeutic target validation. METHODS: We performed scRNAseq of 13 fresh full-thickness CD resections containing noninvolved, inflamed nonstrictured, and strictured segments as well as 7 normal non-CD bowel segments. Each segment was separated into mucosa/submucosa or muscularis propria and analyzed separately for a total of 99 tissue samples and 409,001 cells. We validated cadherin-11 (CDH11) as a potential therapeutic target by using whole tissues, isolated intestinal cells, NanoString nCounter, next-generation sequencing, proteomics, and animal models. RESULTS: Our integrated dataset revealed fibroblast heterogeneity in strictured CD with the majority of stricture-selective changes detected in the mucosa/submucosa, but not the muscle layer. Cell-cell interaction modeling revealed CXCL14+ as well as MMP/WNT5A+ fibroblasts displaying a central signaling role in CD strictures. CDH11, a fibroblast cell-cell adhesion molecule, was broadly expressed and up-regulated, and its profibrotic function was validated using NanoString nCounter, RNA sequencing, tissue target expression, in vitro gain- and loss-of-function experiments, proteomics, and knock-out and antibody-mediated CDH11 blockade in experimental colitis. CONCLUSIONS: A full-thickness bowel scRNAseq atlas revealed previously unrecognized fibroblast heterogeneity and interactions in CD strictures and CDH11 was validated as a potential therapeutic target. These results provide a new resource for a better understanding of CD stricture formation and open potential therapeutic developments. This work has been posted as a preprint on Biorxiv under doi: 10.1101/2023.04.03.534781.

Molecular MR Imaging of Renal Fibrogenesis in Mice.

BACKGROUND: In most CKDs, lysyl oxidase oxidation of collagen forms allysine side chains, which then form stable crosslinks. We hypothesized that MRI with the allysine-targeted probe Gd-oxyamine (OA) could be used to measure this process and noninvasively detect renal fibrosis. METHODS: Two mouse models were used: hereditary nephritis in Col4a3-deficient mice (Alport model) and a glomerulonephritis model, nephrotoxic nephritis (NTN). MRI measured the difference in kidney relaxation rate, ΔR1, after intravenous Gd-OA administration. Renal tissue was collected for biochemical and histological analysis. RESULTS: ΔR1 was increased in the renal cortex of NTN mice and in both the cortex and the medulla of Alport mice. Ex vivo tissue analyses showed increased collagen and Gd-OA levels in fibrotic renal tissues and a high correlation between tissue collagen and ΔR1. CONCLUSIONS: Magnetic resonance imaging using Gd-OA is potentially a valuable tool for detecting and staging renal fibrogenesis.

Assessment of Thoracic Endovascular Aortic Repair Using Relay Proximal Scallop: Results of a French Prospective Multicentre Study.

OBJECTIVE: A proximal scallop design allows aortic arch repair without complex endovascular manipulation in the aortic arch. The aim was to assess the safety and efficacy at one year of the Relay proximal scallop stent graft. METHODS: A prospective multicentre study evaluated consecutive patients treated with the Relay proximal scallop stent graft in 10 French aortic centres. All consecutive patients eligible for elective thoracic endovascular repair with proximal scallop in the 10 participating centres between January 2015 and July 2018 were included. Primary endpoints were 30 day mortality, stroke, and spinal cord ischaemia (SCI) rates. Outcomes including safety and efficacy, technical and clinical success, all cause death, neurological events, vessel patency, and device specific complications were analysed. Survival and survival without severe complications were estimated using Kaplan-Meier estimates. RESULTS: Ten aortic centres treated 40 patients for thoracic aortic aneurysm (45%), penetrating atherosclerotic aneurysm (30%), and dissection (25%). Half of the procedures (50%) targeted zone 0 of the aortic arch (zone 0 in 17.5% and zones 0/1 in 32.5%), 37.5% targeted zone 2 (35% zone 2 alone; 2.5% zones 1/2), and 15% targeted zone 1 (12.5% zone 1 alone). Median follow up was one year. Thirty day mortality, stroke, and SCI rates were 10%, 5%, and 0% respectively. Primary technical success was 95%. Type Ia, Ib, and III endoleaks rates were 5.4%, 0%, and 0% respectively at one month. The overall mortality rate at one year was 17.5%. Aneurysm expansion was > 5 mm in one case at one year associated with type Ia endoleak (3%). There was no supra-aortic trunk thrombosis, one (2%) graft kink, and no migration. CONCLUSION: One year outcomes showed that the Relay proximal scallop stent graft is an acceptable answer to thoracic aortic disease to deal with short proximal landing zones.

Risk Factors for Incomplete Aortic Remodeling With Stent-Assisted Balloon-Induced Intimal Disruption and Relamination in Aortic Dissection Repair for Complicated Aortic Dissection: Results of a Multicenter Study.

PURPOSE: The STABILISE technique has extended the treatment of aortic dissection to the thoracoabdominal aorta to achieve complete aortic remodeling. The aim of this multicenter study was to analyze the short- and midterm anatomical results of the STABILISE technique. MATERIALS AND METHODS: We retrospectively analyzed patients treated with the STABILISE technique for complicated aortic dissection at 3 French academic centers. The aortic diameter at different levels was measured preoperatively, postoperatively, and at 1 year. RESULTS: Between 2018 and 2020, 58 patients, including 47 men (average patient age: 60±11 years), were treated for type B aortic dissection in 34 cases and residual aortic dissection after type A repair in 24 cases. Three (5.2%) patients died postoperatively. Complete aortic remodeling (false lumen thrombosis and complete reapposition of the intimal flap) was achieved in 45/55 patients (81.8%), and false lumen thrombosis in the thoracic aorta was achieved in 52/55 patients (94.5%). At 1 year, with a computed tomographic (CT) scan available for 98.2% (54/55) of patients, we observed a significant decrease in the maximal thoracic aortic diameter and a significant increase in the aortic diameter at the bare-stent level compared with the preoperative CT scan. Severe aortic angulation (p=0.024) was a risk factor for incomplete aortic remodeling and significantly increased the aortic diameter (p=0.032). Chronic aortic dissection was associated with an increased risk of incomplete aortic remodeling (p=0.002). CONCLUSIONS: STABILISE for complicated aortic dissection results in false lumen thrombosis, complete reapposition of the intimal flap, and a decrease in the maximum aortic diameter in most cases. Incomplete reapposition of the intimal flap, which is more frequent in cases of chronic aortic dissection and severe aortic angulation, is a risk factor for a significant increase in the aortic diameter at the bare-stent level, and this risk justifies close follow-up and better patient selection. CLINICAL IMPACT: STABILISE technique for complicated aortic dissection results in false lumen thrombosis, complete aortic remodeling and a decrease in the maximum aortic diameter in most cases. At the bare-stent level, incomplete reapposition of the intimal flap, more frequent in chronic aortic dissection and severe aortic angulation, is a risk factor for an increased aortic diameter. This finding justifies close follow-up and better patient selection; thus, the STABILISE technique should be used with care in chronic aortic dissection and severe aortic angulation.

Initial Study of the Extended STABILISE Technique for Complete Remodeling in Aortic Dissection.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) is the standard treatment for acute complicated type B aortic dissection (TBAD). However, long-term results reveal that TEVAR does not achieve a complete aortic remodeling and poses a risk of aneurysmal aortic degeneration. Distal re-entry treatment at the abdominal level seems to be necessary to obtain a complete remodeling in TBAD. Moreover, it is necessary to treat the aortoiliac bifurcation in patients with persistent true lumen collapse or limb ischemia. METHODS: Between January 2018 and October 2019, 11 patients with acute or sub-acute complicated TBAD or non-A non-B aortic dissection were treated in our institution in an endovascular fashion. We performed the stent-assisted, balloon-induced intimal disruption and relamination in aortic dissection repair (STABILISE) technique in all cases, but 2 cases required complementary treatment of the aortoiliac bifurcation with a bifurcated AFX endograft system for limb ischemia due to true lumen collapse. RESULTS: Technical success was obtained in all patients. No procedural complications occurred. No postoperative deaths, stroke, paraplegia, mesenteric, or renal ischemia were observed, and no secondary intervention was necessary. Satisfactory aortic re-modeling was obtained after the follow-up periods with a 57.5% mean true lumen expansion. CONCLUSIONS: Our initial experience using the extended STABILISE (e-STABILISE) technique using a bifurcated AFX endograft did not result in any postoperative mortality or complications. Without additional data, this technique should be reserved for specific patients who require revascularization of the aortoiliac bifurcation.

School Risk and Protective Factors of Suicide: A Cultural Model of Suicide Risk and Protective Factors in Schools.

There are known cultural variations in correlates of and symptoms related to suicide-related thoughts and behaviors; however, the majority of research that informs suicide prevention in school systems has focused on research based on Euro-American/White students. By exploring school-related risk and protective factors in ethnic-racial minoritized students, we expand existing multicultural models of suicide prevention for school settings. Specifically, this systematic literature review identified 33 studies conducted with American Indian and Alaskan Native, Hispanic and Latinx, Black and African American, and Asian American and Pacific Islander students. Findings underscore the importance of building relationships with the school community and fostering a sense of safety for students, the need to approach school-based suicide prevention and intervention with cultural considerations, and the importance of connecting students and families with providers in culturally sensitive and informed ways. Taken together, schools need to build school-family-community partnerships that promote culturally sensitive approaches to suicide prevention.

Advanced MRI of Liver Fibrosis and Treatment Response in a Rat Model of Nonalcoholic Steatohepatitis.

Background Liver biopsy is the reference standard to diagnose nonalcoholic steatohepatitis (NASH) but is invasive with potential complications. Purpose To evaluate molecular MRI with type 1 collagen-specific probe EP-3533 and allysine-targeted fibrogenesis probe Gd-Hyd, MR elastography, and native T1 to characterize fibrosis and to assess treatment response in a rat model of NASH. Materials and Methods MRI was performed prospectively (June-November 2018) in six groups of male Wistar rats (a) age- and (b) weight-matched animals received standard chow (n = 12 per group); (c) received choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD) for 6 weeks or (d) 9 weeks (n = 8 per group); (e) were fed 6 weeks of CDAHFD and switched to standard chow for 3 weeks (n = 12); (f) were fed CDAHFD for 9 weeks with daily treatment of elafibranor beginning at week 6 (n = 14). Differences in imaging measurements and tissue analyses among groups were tested with one-way analysis of variance. The ability of each imaging measurement to stage fibrosis was quantified by using area under the receiver operating characteristic curve (AUC) with quantitative digital pathology (collagen proportionate area [CPA]) as reference standard. Optimal cutoff values for distinguishing advanced fibrosis were used to assess treatment response. Results AUC for distinguishing fibrotic (CPA >4.8%) from nonfibrotic (CPA ≤4.8%) livers was 0.95 (95% confidence interval [CI]: 0.91, 1.00) for EP-3533, followed by native T1, Gd-Hyd, and MR elastography with AUCs of 0.90 (95% CI: 0.83, 0.98), 0.84 (95% CI: 0.74, 0.95), and 0.65 (95% CI: 0.51, 0.79), respectively. AUCs for discriminating advanced fibrosis (CPA >10.3%) were 0.86 (95% CI: 0.76, 0.97), 0.96 (95% CI: 0.90, 1.01), 0.84 (95% CI: 0.70, 0.98), and 0.74 (95% CI: 0.63, 0.86) for EP-3533, Gd-Hyd, MR elastography, and native T1, respectively. Gd-Hyd MRI had the highest accuracy (24 of 26, 92%; 95% CI: 75%, 99%) in identifying responders and nonresponders in the treated groups compared with MR elastography (23 of 26, 88%; 95% CI: 70%, 98%), EP-3533 (20 of 26, 77%; 95% CI: 56%, 91%), and native T1 (14 of 26, 54%; 95% CI: 33%, 73%). Conclusion Collagen-targeted molecular MRI most accurately detected early onset of fibrosis, whereas the fibrogenesis probe Gd-Hyd proved most accurate for detecting treatment response. © RSNA, 2020 Online supplemental material is available for this article.

Incidence, predictors, impact, and treatment of vascular complications after transcatheter aortic valve implantation in a modern prospective cohort under real conditions.

OBJECTIVE: Vascular complications (VCs) occurring in transcatheter aortic valve implantation (TAVI) procedures have frequently been reported in the past. Considering significant technical improvements in delivery systems and vascular closure devices, the goal of this study was to determine the incidence, impact, and prognostic factors of VCs in a recent real-world cohort. METHODS: We report a bicentric prospective analysis of 479 consecutive patients who underwent TAVI between January 2017 and December 2017. VCs were defined according to criteria set out by the Valve Academic Research Consortium (VARC)-2. RESULTS: The incidence of VCs was 26.1% (n = 125 patients), of which 2.9% were major (n = 14) and 23.2% were minor (n = 111). VCs were related to the primary puncture point in 69% of cases compared with 31% at the secondary puncture site. Treatments implemented were medical in 76% of cases and surgical in 24% of cases. The risk factors for VCs were as follows: iliac morphology score, sheath to iliofemoral artery ratio (SIFAR), and moderate-severe iliofemoral calcifications or tortuosity. In the case of major VCs, only sheath to iliofemoral artery ratio was a risk factor. Major VCs significantly increased intrahospital mortality (30.7% vs 1.1% for minor VCs and 1.3% for no VCs; log-rank, P < .0001) and 1-year mortality (40.6% vs 5.6% for minor VCs and 5.6% for no VCs; log-rank, P < .0001). CONCLUSIONS: Using strictly VARC-2 end point definitions, more than one-quarter of TAVI procedures were associated with VCs, primarily minor ones. Secondary puncture points were responsible for one-third of VCs and should therefore also be actively monitored. Major VCs have a significant impact on short-term and midterm survival.

Lower Rate of Restenosis and Reinterventions With Covered vs Bare Metal Stents Following Innominate Artery Stenting.

PURPOSE: To determine any difference between bare metal stents (BMS) and balloon-expandable covered stents in the treatment of innominate artery atheromatous lesions. MATERIALS AND METHODS: A multicenter retrospective study involving 13 university hospitals in France collected 93 patients (mean age 63.2±11.1 years; 57 men) treated over a 10-year period. All patients had systolic blood pressure asymmetry >15 mm Hg and were either asymptomatic (39, 42%) or had carotid (20, 22%), vertebrobasilar (24, 26%), and/or brachial (20, 22%) symptoms. Innominate artery stenosis ranged from 50% to 70% in 4 (4%) symptomatic cases and between 70% and 90% in 52 (56%) cases; 28 (30%) lesions were preocclusive and 8 (9%) were occluded. One (1%) severely symptomatic patient had a <50% stenosis. Demographic characteristics, operative indications, and procedure details were compared between the covered (36, 39%) and BMS (57, 61%) groups. Multivariate analysis was performed to determine relative risks of restenosis and reinterventions [reported with 95% confidence intervals (CI)]. RESULTS: The endovascular procedures were performed mainly via retrograde carotid access (75, 81%). Perioperative strokes occurred in 4 (4.3%) patients. During the mean 34.5±31.2-month follow-up, 30 (32%) restenoses were detected and 13 (20%) reinterventions were performed. Relative risks were 6.9 (95% CI 2.2 to 22.2, p=0.001) for restenosis and 14.6 (95% CI 1.8 to 120.8, p=0.004) for reinterventions between BMS and covered stents. The severity of the treated lesions had no influence on the results. CONCLUSION: Patients treated with BMS for innominate artery stenosis have more frequent restenoses and reinterventions than patients treated with covered stents.

Reduced skeletal muscle phosphocreatine concentration in type 2 diabetic patients: a quantitative image-based phosphorus-31 MR spectroscopy study.

Mitochondrial function has been examined in insulin-resistant (IR) states including type 2 diabetes mellitus (T2DM). Previous studies using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in T2DM reported results as relative concentrations of metabolite ratios, which could obscure differences in phosphocreatine ([PCr]) and adenosine triphosphate concentrations ([ATP]) between T2DM and normal glucose tolerance (NGT) individuals. We used an image-guided 31P-MRS method to quantitate [PCr], inorganic phosphate [Pi], phosphodiester [PDE], and [ATP] in vastus lateralis (VL) muscle in 11 T2DM and 14 NGT subjects. Subjects also received oral glucose tolerance test, euglycemic insulin clamp, 1H-MRS to measure intramyocellular lipids [IMCL], and VL muscle biopsy to evaluate mitochondrial density. T2DM subjects had lower absolute [PCr] and [ATP] than NGT subjects (PCr 28.6 ± 3.2 vs. 24.6 ± 2.4, P < 0.002, and ATP 7.18 ± 0.6 vs. 6.37 ± 1.1, P < 0.02) while [PDE] was higher, but not significantly. [PCr], obtained using the traditional ratio method, showed no significant difference between groups. [PCr] was negatively correlated with HbA1c ( r = -0.63, P < 0.01) and fasting plasma glucose ( r = -0.51, P = 0.01). [PDE] was negatively correlated with Matsuda index ( r = -0.43, P = 0.03) and M/I ( r = -0.46, P = 0.04), but was positively correlated with [IMCL] ( r = 0.64, P < 0.005), HbA1c, and FPG ( r = 0.60, P = 0.001). To summarize, using a modified, in vivo quantitative 31P-MRS method, skeletal muscle [PCr] and [ATP] are reduced in T2DM, while this difference was not observed with the traditional ratio method. The strong inverse correlation between [PCr] vs. HbA1c, FPG, and insulin sensitivity supports the concept that lower baseline skeletal muscle [PCr] is related to key determinants of glucose homeostasis.

Characterization of Tiki, a New Family of Wnt-specific Metalloproteases.

The Wnt family of secreted glycolipoproteins plays pivotal roles in development and human diseases. Tiki family proteins were identified as novel Wnt inhibitors that act by cleaving the Wnt amino-terminal region to inactivate specific Wnt ligands. Tiki represents a new metalloprotease family that is dependent on Mn(2+)/Co(2+) but lacks known metalloprotease motifs. The Tiki extracellular domain shares homology with bacterial TraB/PrgY proteins, known for their roles in the inhibition of mating pheromones. The TIKI/TraB fold is predicted to be distantly related to structures of additional bacterial proteins and may use a core ß-sheet within an α+ß-fold to coordinate conserved residues for catalysis. In this study, using assays for Wnt3a cleavage and signaling inhibition, we performed mutagenesis analyses of human TIKI2 to examine the structural prediction and identify the active site residues. We also established an in vitro assay for TIKI2 protease activity using FRET peptide substrates derived from the cleavage motifs of Wnt3a and Xenopus wnt8 (Xwnt8). We further identified two pairs of potential disulfide bonds that reside outside the ß-sheet catalytic core but likely assist the folding of the TIKI domain. Finally, we systematically analyzed TIKI2 cleavage of the 19 human WNT proteins, of which we identified 10 as potential TIKI2 substrates, revealing the hydrophobic nature of Tiki cleavage sites. Our study provides insights into the Tiki family of proteases and its Wnt substrates.

Results of the French Multicentric Study of ANACONDA™ Fenestrated Endografts in the Treatment of Complex Aortic Pathologies (EFEFA Registry).

BACKGROUND: Most of the experience on fenestrated endovascular aneurysm repair involves the custom-made Zenith® endograft (Cook). The fenestrated Anaconda® endograft (Vascutek) was introduced with the potential advantages of complete repositioning and lack of stent material on the main aortic body for more versatility. However, few data are available. Our objective was to assess its mid-term results in the treatment of complex aortic aneurysms. METHODS: Consecutive patients treated with the custom-made fenestrated Anaconda endograft in France and the Principality of Monaco, from December 2010 to October 2015, were included. RESULTS: Eighty-six patients were included over 16 centers (82 men, mean age 73.4 ± 8.1 years, 16 (18.6%) symptomatic aneurysms). The repositioning system was used in 68 cases (79.1%). Two hundred ninety-two visceral/renal vessels were targeted, with a mean number of 3.4 ± 0.6 target vessels/patient and a successful reconstruction in 99.3% of the cases (290/292 vessels). Perioperative technical success was achieved in 86.0% (74/86 patients). In-hospital and 30-day mortality rates were 3.5% (3 patients) and 7.0% (6 patients), respectively. At 12 and 24 months, estimated overall survival rate was 88.3% and 85.2%, target vessel's patency rate was 97.2% and 96.3%, and freedom from aneurysm-related reintervention rate was 96.3% and 88.0%, respectively. At 24 months, there were 7 type II endoleaks (12.7%) and a significant reduction in aneurysm maximum transverse diameter in 70.4%. Five limb occlusions occurred at 1-year and 1 at 2-year follow-up (7.0%). CONCLUSIONS: The fenestrated Anaconda stent-graft system offers acceptable technical success rates, mid-term efficacy, and durability with respect to aneurysm sac regression, target vessel patency, overall mortality, and reintervention rates. Long-term results are still awaited, until then, the rate of graft limb occlusion is of concern and should be further investigated, especially in case of particularly complex aortic anatomies.

Tolerance of rapid right ventricular pacing during thoracic endovascular aortic repair.

BACKGROUND: The objective of this retrospective study was to evaluate the tolerance of rapid right ventricular pacing (RRVP) compared with that of the traditional methods of hypotension used during thoracic endovascular aortic repair (TEVAR). METHODS: From January 2002 to December 2012, we retrospectively included all the patients treated with TEVAR by comparing the 2 groups: patients operated with RRVP (RRVP+) and those operated without RRVP (RRVP-). The characteristics of the population and the procedures were recorded. The rates of complications were compared up to 1 year. RESULTS: Sixty-one patients were operated. Treated pathologies were multiple with 19 aneurysms, 14 false aneurysms, 12 isthmic ruptures, 11 dissections, 3 coarctations, and 2 endoleaks. Twenty-four patients were RRVP+ and 37 patients were RRVP-. Mortality rates at 1 month in groups RRVP+ and RRVP- were of 0% and 2.7%, respectively (P = 1), and reintervention rates were 0% and 13.5%, respectively (P = 0.15). Three peroperative rhythm disorders (12.5%) were observed in the RRVP+ group including 2 ventricular fibrillations and 1 atrial fibrillation, both reduced without complications. One pacemaker was implanted for atrioventricular block in the RRVP- group. In the RRVP+ group, 83.3% of the patients presented a rise in troponin Ic (TnI) >0.04 ng/mL in 72 hours compared with 40.5% of the patients in the RRVP- group (P = 0.0013), with a spontaneously favorable evolution. No coronary syndrome was observed at 1 year with a mortality rate of 10.8% in the RRVP- group vs. 0% in the RRVP+ (P = 0.15). CONCLUSIONS: In spite of a frequent moderate rise of TnI at the time of RRVP, this technique does not present more complications at 1 year than the use of a chemical hypotension. It thus seems an interesting alternative for selected patients, in trained teams.

Utility of electrofusion for the femoral approach in vascular surgery: a randomized prospective study.

BACKGROUND: The local complications are frequent after a femoral approach in vascular surgery and are often the cause of a delay in healing. Electrofusion showed its effectiveness to decrease the complications in general surgery but was not tested in vascular surgery. The aim of our study was to evaluate if the use of electrofusion in the approach to femoral vessels improved healing at 1 month by decreasing the local complications. METHODS: This prospective randomized study was conducted in 2 centers from May 1, 2012 to April 30, 2013. All the patients requiring a surgical access of the femoral trigone were included in 2 French teaching hospitals. Femoral artery surgical exposure was carried out using electrofusion or according to the conventional technique (diathermy or cold scalpel) according to a protocol of randomization. The principle criterion of the study was a complete healing at 1 month. The secondary criteria were the appearance of cutaneous, infectious, or lymphatic local complications. RESULTS: Two hundred ninety-two femoral approaches were carried out in 221 consecutive patients. One hundred forty-eight approaches were carried out with electrofusion and 144 according to the conventional technique. The demographic and operative characteristics were similar between the 2 groups. At 1 month, 86.3% of the approaches were healed without statistically significant difference between the 2 groups (88.5% vs. 84%, P = 0.241). There were less local complications (P = 0.012) and seromas (P = 0.012) in the electrofusion group. This difference could be linked with the least quantities (P = 0.036) and durations (P = 0.014) of drainage observed after approaches carried out with electrofusion. On the other hand, the incidence of cutaneous or infectious complications was not different between the 2 groups. CONCLUSIONS: In our series, the use of electrofusion decreased the lymphatic complications after a femoral approach. However, the correction of this single parameter was not sufficient to improve the rate of healing at 1 month.

Follow-up of aortic stent grafts: comparison of the volumetric analysis of the aneurysm sac by ultrasound and CT.

BACKGROUND: The long-term follow-up of patients with endovascular aneurysm repair (EVAR) and a normal surgical risk was defined by the French National Authority for Health (Haute Autorité de Santé) in 2009. The monitoring of the volume of the aneurysm sac theoretically avoids the bias related to the measurement of its diameter alone. The objective of this study was to evaluate how reliable and reproducible the volumetric measurement of the aneurysm sac by ultrasound was compared with computerized tomography angiography (CTA). METHODS: We carried out a retrospective diagnosis study of 75 consecutive patients treated with EVAR in our institution who were monitored with 3-dimensional ultrasonography (3DU) and CTA between January 2010 and December 2012. The measurement of the volume (cm(3)) of the aneurysm sac with a Toshiba Aplio XG ultrasound system equipped with a 3-MHz 3-dimensional probe was compared with the volume obtained by CTA. Interoperator reproducibility was studied in the last 45 enrolled patients; 2 different blinded operators made 2 volumetric measurements on the same patients, on the same day. An analysis of a 48-patient subgroup in which at least two 3DU were performed during follow-up was also carried out to determine the threshold value of the increase in the volume of the aneurysm sac, making it possible to suspect the presence of an endoleak. RESULTS: A total of 116 pairs of examinations were compared (the patients who had the longest postoperative follow-up had 4 pairs of compared examinations). The correlation between volumetric ultrasound and CTA measurements was excellent (r = 0.931; P < 0.0001) in the 116 pairs of examinations, and so was the reproducibility of volumetric echography (r = 0.949; P < 0.0001) in 45 patients. The subgroup study highlighted the fact that a 6.5-cm(3) increase of the aneurysm sac made it possible to suspect the presence of an endoleak in comparison with CTA as the gold standard (sensitivity and specificity were 85.7% and 85.3%, respectively). The area under the curve was 0.854 (95% confidence interval, 0.793-0.915). In the 116 examinations, a good correlation between volume and diameter was calculated with CTA (r = 0.733; P < 0.0001) and between ultrasound volumetric and CTA diameter (r = 0.660; P < 0.0001). CONCLUSIONS: Volumetric echography is comparable with CTA for the evaluation of the aneurysm sac after EVAR, reproducible and inexpensive. When a significant increase of the volume of the sac is detected by ultrasound, the examination can be supplemented by an injection of ultrasound contrast agent or by CTA to visualize an endoleak.

Successful hybrid management of a left vertebral artery aneurysm secondary to type-1 neurofibromatosis.

A 32-year-old man with type-1 neurofibromatosis (NF1) was diagnosed with a left vertebral artery aneurysm of 4 cm maximal diameter. A hybrid procedure was conducted associating the exclusion of the origin of the left vertebral artery with a covered stent in the left subclavian artery and a cervical incision for ligation of the vertebral artery to completely exclude the aneurysm and perform the aneurysm resection. The histologic findings confirmed the diagnosis of NF1 with a vascular localization in the aneurysm. The postoperative course was uneventful. The 1-year clinical and morphologic results were satisfactory.

Carotid artery stenting using a transapical approach for the treatment of radiation-induced carotid stenosis.

Radiation-induced stenosis of the carotid artery is considered a challenging entity for direct revascularization. We performed a carotid artery stenting for a radiation-induced stenosis using a transapical approach on an asymptomatic 63-year-old male patient. Transapical approach, which is often used for cardiac surgery, was not yet described for the endovascular treatment of carotid stenosis. The transapical approach could be an attractive alternative path for patients presenting significant supra-aortic trunks lesions and unfit for direct approach or peripheral access. This case reports the feasibility and the safety of carotid artery stenting using the transapical approach in well-trained teams.

Is early surgical revascularization of symptomatic carotid stenoses safe?

BACKGROUND: The objective of this exploratory study was to determine the rate of the complications of early surgery for symptomatic carotid stenosis, in 2 centers of Western France. METHODS: Between January 2011 and January 2013, we prospectively enrolled all the patients admitted for transient ischemic accident (TIA) or minor stroke (Rankin ≤ 3) associated with an ipsilateral carotid stenosis >50% (North American Symptomatic Carotid Endarterectomy Trial) and operated before the 14th day following the neurologic event at the University hospitals of Angers and Tours. The demographic data (gender, age, and medical history) and the characteristics of the procedures were recorded. The rates of stroke, TIA, and postoperative deaths defined the cumulative morbidity and mortality rate (CMMR) of the study. RESULTS: Ninety-one patients were included in the study. They presented 27 TIAs and 64 strokes. The average elapsed time between the neurologic event and surgery was 9.8 days. During this time, 10 patients, that is, 11% of the operated cohort, presented a new ischemic neurologic event while waiting for surgery. Surgical operations consisted of 56 eversions (61.5%), 32 endarterectomies with patch (35.1%), 2 bypasses, and 1 direct closure. The CMMR reached 3.3%. Two patients presented with a stroke and 1 patient died of a cardiologic cause during the postoperative period. CONCLUSIONS: This study confirms the interest of an early surgery for symptomatic carotid stenoses with a Rankin score of ≤3. The risk of recurrence of a cerebral ischemic accident during the preoperative period remains high.

Role of Histone Deacetylase Inhibitor in Diabetic Painful Neuropathy.

Diabetic painful neuropathy (DPN) is one of the most detrimental complications of diabetes. Alterations in neuroinflammatory mediators play significant roles in the development of DPN. Infiltration of the neutrophils and monocyte/macrophages contributes substantial role in the degenerative process of the distal sciatic nerve by forming neutrophil extracellular traps (NETs) under diabetic condition. Citrullination of histones due to increase in protein arginine deiminase (PAD) enzyme activity under hyperglycemia may promote NET formation, which can further increase the cytokine production by activating macrophages and proliferation of neutrophils. This study reveals that the increase in histone deacetylases (HDAC) is crucial in DPN and inhibition of HDAC using HDAC inhibitor (HDACi) FK228 would suppress NETosis and alleviate diabetic nerve degeneration and pain. FK228, also known as romidepsin, is FDA approved for the treatment of cutaneous T-cell lymphoma yet the molecular mechanisms of this drug are not completely understood in DPN. In this study, type 2 diabetic (T2D) mice with pain were treated with HDACi, FK228 1 mg/kg; I.P. 2 × /week for 3 weeks. The results demonstrate that FK228 treatment can alleviate thermal hyperalgesia and mechanical allodynia significantly along with changes in the expression of HDACs in the dorsal root ganglia (DRG) and spinal cord dorsal horn neurons of diabetic animals. The results also indicate that FK228 treatment can alter the expression of neutrophil elastase (NE), extracellular or cell free DNA (cfDNA), citrullinated histone-3 (CitH3), PADI4, growth-associated protein (GAP)-43, and glucose transporter (GLUT)-4. Overall, this study suggests that FK228 could amend the expression of nerve regeneration markers and inflammatory mediators in diabetic animals and may offer an alternative treatment approach for DPN.