Acute rapamycin treatment reveals novel mechanisms of behavioral, physiological, and functional dysfunction in a maternal inflammation mouse model of autism and sensory over-responsivity.

Maternal inflammatory response (MIR) during early gestation in mice induces a cascade of physiological and behavioral changes that have been associated with autism spectrum disorder (ASD). In a prior study and the current one, we find that mild MIR results in chronic systemic and neuro-inflammation, mTOR pathway activation, mild brain overgrowth followed by regionally specific volumetric changes, sensory processing dysregulation, and social and repetitive behavior abnormalities. Prior studies of rapamycin treatment in autism models have focused on chronic treatments that might be expected to alter or prevent physical brain changes. Here, we have focused on the acute effects of rapamycin to uncover novel mechanisms of dysfunction and related to mTOR pathway signaling. We find that within 2 hours, rapamycin treatment could rapidly rescue neuronal hyper-excitability, seizure susceptibility, functional network connectivity and brain community structure, and repetitive behaviors and sensory over-responsivity in adult offspring with persistent brain overgrowth. These CNS-mediated effects are also associated with alteration of the expression of several ASD-,ion channel-, and epilepsy-associated genes, in the same time frame. Our findings suggest that mTOR dysregulation in MIR offspring is a key contributor to various levels of brain dysfunction, including neuronal excitability, altered gene expression in multiple cell types, sensory functional network connectivity, and modulation of information flow. However, we demonstrate that the adult MIR brain is also amenable to rapid normalization of these functional changes which results in the rescue of both core and comorbid ASD behaviors in adult animals without requiring long-term physical alterations to the brain. Thus, restoring excitatory/inhibitory imbalance and sensory functional network modularity may be important targets for therapeutically addressing both primary sensory and social behavior phenotypes, and compensatory repetitive behavior phenotypes.

Brown carbon absorption and radiative effects under intense residential wood burning conditions in Southeastern Europe: New insights into the abundance and absorptivity of methanol-soluble organic aerosols.

Biomass burning is a major source of Brown Carbon (BrC), strongly contributing to radiative forcing. In urban areas of the climate-sensitive Southeastern European region, where strong emissions from residential wood burning (RWB) are reported, radiative impacts of carbonaceous aerosols remain largely unknown. This study examines the absorption properties of water- and methanol-soluble organic carbon (WSOC, MeS_OC) in a city (Ioannina, Greece) heavily impacted by RWB. Measurements were performed during winter (December 2019 - February 2020) and summer (July - August 2019) periods, characterized by RWB and photochemical processing of organic aerosol (OA), respectively. PM2.5 filter extracts were analyzed spectrophotometrically for water- and methanol-soluble BrC (WS_BrC, MeS_BrC) absorption. WSOC concentrations were quantified using TOC analysis, while those of MeS_OC were determined using a newly developed direct quantification protocol, applied for the first time to an extended series of ambient samples. The direct method led to a mean MeS_OC/OC of 0.68 and a more accurate subsequent estimation of absorption efficiencies. The mean winter WS_BrC and MeS_BrC absorptions at 365 nm were 13.9 Mm-1 and 21.9 Mm-1, respectively, suggesting an important fraction of water-insoluble OA. Mean winter WS_BrC and MeS_BrC absorptions were over 10 times those observed in summer. MeS_OC was more absorptive than WSOC in winter (mean mass absorption efficiencies - MAE365: 1.81 vs 1.15 m2 gC-1) and especially in summer (MAE: 1.12 vs 0.27 m2 gC-1) due to photo-dissociation and volatilization of BrC chromophores. The winter radiative forcing (RF) of WS_BrC and MeS_BrC relative to elemental carbon (EC) was estimated at 8.7 % and 16.7 %, respectively, in the 300-2500 nm band. However, those values increased to 48.5 % and 60.2 % at 300-400 nm, indicating that, under intense RWB, BrC forcing becomes comparable to that of soot. The results highlight the consideration of urban BrC emissions in radiative transfer models, as a considerable climate forcing factor.

Thalamocortical Projections Are Significantly Impaired in the R6/2 Mouse Model of Huntington's Disease.

As Huntington's disease (HD) progresses, there is a significant loss of neurons in the striatum in addition to a distinct thinning of the cerebral cortex. Despite an early presence of sensorimotor deficits in patients with HD, electrophysiological studies designed to assess the integrity of thalamocortical circuits are sparse. Using the R6/2 mouse model of HD, we provide evidence of reduced connectivity between thalamic cells and their targeted cortical regions. Whole-cell patch clamp recordings from ventral anterolateral nucleus (VAL; motor) and ventral posteromedial nucleus (VPM; somatosensory) thalamic neurons in ex vivo brain slices of R6/2 and wild-type (WT) mice revealed that cells in both thalamic nuclei of R6/2 mice exhibited significant differences in passive and active cell membrane properties (smaller cell membrane capacitances, faster decay time constants and increased input resistances) compared with WT cells. Although only cells in the VPM of symptomatic R6/2 mice had more depolarized resting membrane potentials compared with WTs, cells in both nuclei displayed increased excitability in symptomatic, but not presymptomatic, R6/2 mice. Optical activation of VAL and VPM terminals elicited smaller magnitude current responses in cortical pyramidal neurons (CPNs) in both motor cortex (M1CTX) and somatosensory barrel cortex (BCTX) of symptomatic R6/2 mice compared with CPNs in WT mice. Furthermore, we observed a decrease in the frequency of thalamocortical excitatory quantal events in R6/2 BCTX CPNs, with no genotype-dependent differences in AMPA:NMDA response amplitude ratios. These data suggest there is a decrease in the transmission of thalamocortical information that is likely because of impaired neurotransmitter release.

Mid-Term Outcomes of a Hybrid Approach Involving Open Surgery Plus TEVAR of the Descending Aorta in the Treatment of Complex Type A Dissection.

OBJECTIVES: Type A aortic dissection with true lumen collapse and malperfusion downstream is associated with a devastating prognosis. This study compares the clinical outcomes of two operative strategies for this disease: hybrid approach of ascending aorta (and hemiarch replacement) supplemented with retrograde stenting of the descending aorta (thoracic endovascular aortic repair [TEVAR]) and standard ascending aorta (and hemiarch) replacement without stent placement. METHODS: From January 1, 2016 to December 31, 2019, 81 patients with type A aortic dissection were studied. The hybrid technique was applied in 30 patients (group 1), while 51 patients received standard surgical repair (group 2). Patient demographics, clinical and operative findings, postoperative outcome, follow-up interventions, and mid-term survival were analyzed. RESULTS: Baseline characteristics were similar among the groups, except that more preoperative malperfusion was evident in group 1. The postoperative incidence of visceral malperfusion (0 vs. 15.7%, p = 0.02) and low cardiac output syndrome requiring extracorporeal membrane oxygenation support (3.3 vs. 19.6%, p = 0.04) was significantly less in group 1. In-hospital mortality was also significantly lower in group 1 as in group 2 (13.3 vs. 33.3%, p = 0.04). At follow-up, the need for secondary endovascular stenting (3.3 vs. 7.8%, p = 0.65) and surgical aortic reintervention (6.7 vs. 2.0%, p = 0.55) was comparable. One-year, 2-year, and 3-year survival rates were 83.3, 83.3, and 62.5% in group 1, and 58.7, 58.7, and 52.6% in group 2 (p = 0.05), respectively. CONCLUSION: The combination of open surgical replacement of the ascending aorta (and hemiarch) with TEVAR of the descending aorta for true lumen compromise is a feasible treatment option for patients with type A aortic dissection and is associated with a better perioperative outcome and improved mid-term survival rate.

Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study.

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.

Outcome after Interruption or Preservation of Internal Iliac Artery Flow During Endovascular Repair of Abdominal Aorto-iliac Aneurysms.

AIM: The aim was to conduct a systematic review of the literature investigating outcomes after interruption or preservation of the internal iliac artery (IIA) during endovascular aneurysm repair (EVAR). METHODS: A systematic review was undertaken using the MEDLINE and EMBASE databases to identify studies reporting IIA management during EVAR. The search identified 57 articles: 30 reported on IIA interruption (1468 patients) and 27 on IIA preservation (816 patients). RESULTS: The pooled 30 day buttock claudication (BC) rate was 29.2% (95% CI 24.2-34.7). Patients undergoing bilateral IIA interruption had a higher incidence of BC than patients with unilateral IIA interruption (36.5% vs. 27.2%, OR 1.7, 95% CI 1.11-2.6, p = .01). During a median follow up of 17 months, the pooled rate of persistent BC was 20.5% (95% CI 15.7-26.2). Of the patients, 93.9% underwent an endovascular revascularization procedure for IIA preservation. Most patients (87.6%) had an iliac branched device, and technical success was 96.2%. Within 30 days of EVAR, 4.3% of internal iliac branches occluded. During a median follow up of 15 months, the pooled occlusion rate at the site of IIA revascularization was 8.8% (95% CI 6.8-11.3). In patients treated with an iliac-branched device, 5.2% of internal iliac branches and 1.7% of external iliac arteries occluded. The pooled BC rate on the side of the IIA revascularization during follow up was 4.1% (95% CI 2.9-5.9). Pooled rates of late device related endoleak type I or III and secondary procedures on the side of the previous IIA revascularization were 4.6% (95% CI 3.2-6.5) and 7.8% (95% CI 5.7-10.7) respectively. CONCLUSION: Unilateral or bilateral IIA occlusion during EVAR seems to carry a substantial risk of significant ischemic complications in nearly one quarter of patients. Bilateral IIA occlusion was related to a significantly higher rate of BC. IIA preservation techniques represent a significant improvement in the treatment of aorto-iliac aneurysms and have been associated with high technical success and low morbidity.

Fenestrated Endovascular Aortic Aneurysm Repair as a First Line Treatment Option to Treat Short Necked, Juxtarenal, and Suprarenal Aneurysms.

OBJECTIVES: The outcomes of fenestrated endovascular aneurysm repair (FEVAR) as a first line strategy is reported. METHODS: All consecutive patients treated with FEVAR for short neck, juxtarenal, or suprarenal aortic aneurysms under the guidance of the senior author within the period January 2010 to December 2014 were included. Data were collected from a prospectively maintained database. Analyzed outcomes included technical success, defined by successful stent graft implantation with patent stented target vessels and no Type I/III endoleak, operative mortality and morbidity, target vessel patency, endoleak, re-intervention, and death. Survival, target vessel stent patency, and re-intervention during follow up were calculated by Kaplan-Meier analysis. RESULTS: A total of 281 patients (245 male, mean age 72.1 ± 7.7 years) were treated. The mean aneurysm diameter was 60.2 ± 9.3 mm and median proximal neck length 2 mm (range 0-10 mm). Technical success was 96.8% (272/281). Technical failure included one intra-operative death due to embolization and cardiac arrest, one open conversion due to iliac rupture, and seven target vessel complications. The thirty day mortality was 0.7% (2/281). Mean follow up was 21 ± 15.9 months. Estimated survival at 1 and 3 years was 94.7% ± 1.6% and 84.6% ± 3.0%, respectively. Estimated freedom from re-intervention at 1 and 3 years was 96.1% ± 1.4%, and 90% ± 2.7%. Estimated target vessel stent patency at 1 and 3 years was 98.6% ± 0.5%, and 98.1% ± 0.6%, respectively. Mean aneurysm sac diameter decreased from 60.2 ± 9.3 mm pre-operatively to 53.2 ± 12.8 mm (p < .001). CONCLUSIONS: FEVAR as a first line strategy was associated with high technical success and a low operative mortality rate. Efficacy and durability in the mid-term appear very good, with significant regression of aneurysm sac diameter, high target vessel patency, and acceptable rate of re-intervention.

Stent Graft Dislocation after EVAR Treated with an Endostapling Fixation System.

Stent-graft migration and type I endoleak are major complications after endovascular aneurysm repair (EVAR). We present a case of an 88-year-old female patient with a 56-mm-diameter progredient infrarenal AAA, with severely angulated proximal aneurysm neck and iliac arteries. EVAR was performed using a Gore Excluder stent-graft. -Computed tomography angiography (CTA) at one week postoperatively demonstrated a dislocation of the stent-graft and a proximal Type I endoleak. Placement of a proximal cuff with the use of 6 endostaples resulted in proximal neck seal and exclusion of the endoleak. CTA 2 years postoperatively showed no signs of a proximal type I endoleak. Use of an endostapling fixation system is a viable treatment option in cases of stent-graft dislocation resulting from angulation of the proximal neck.

Editor's Choice - Ten-year Experience with Endovascular Repair of Thoracoabdominal Aortic Aneurysms: Results from 166 Consecutive Patients.

OBJECTIVE: To present a 10 year experience with endovascular thoracoabdominal aortic aneurysm (TAAA) repair using fenestrated and branched stent grafts. MATERIALS AND METHODS: Consecutive patients with TAAA treated with fenestrated and branched stent grafts within the period January 2004-December 2013. Data were collected prospectively. RESULTS: 166 patients (125 male, 41 female, mean age 68.8 ± 7.6 years) were treated. The mean TAAA diameter was 71 ± 9.3 mm. Types of TAAA were: type I, n = 12 (7.2%), type II, n = 50 (30.1%), type III, n = 53 (31.9%), type IV, n = 41 (24.8%), and type V, n = 10 (6%). Fifteen (9%) patients had an acute TAAA (11 contained rupture, 4 symptomatic). One hundred and eight (65%) patients were refused for open surgery earlier. Seventy eight (47%) patients had previously undergone one or more open/endovascular aortic procedures. Technical success was 95% (157/166). Thirty day operative mortality was 7.8% (13/166), with an in hospital mortality of 9% (15/166). Peri-operative spinal cord ischemia (SCI) was observed in 15 patients (9%), including permanent paraplegia in two (1.2%). Mean follow up was 29.2 ± 21 months. During follow up 40 patients died, two of them probably from aneurysm related cause. Re-intervention, mostly by endovascular means, was needed in 40 (24%) patients. Estimated survival at 1, 2, and 5 years was 83% ± 3%, 78% ± 3.5%, and 66.6% ± 6.1%, respectively. Estimated target vessel stent patency at 1, 2, and 5 years was 98% ± 0.6%, 97% ± 0.8%, and 94.2% ± 1.5%, respectively. Estimated freedom from re-intervention at 1 and 3 years was 88.3% ± 2.7%, and 78.4% ± 4.5%, respectively. CONCLUSIONS: Endovascular repair of TAAA with fenestrated and branched stent grafts in high volume centers appears safe and effective in the mid-term in a high risk patient cohort. A considerable reintervention rate should be acknowledged, however.

Endostaples: are they the solution to graft migration and Type I endoleaks?

Effective proximal sealing, especially in the long-term, remains a limitation of contemporary endovascular aortic aneurysm repair (EVAR). Endostaples that fixate the proximal stent-graft to the aortic neck wall, aiming for better apposition and proximal sealing have been recently introduced in clinical practice to address this problem. Initial experimental studies have shown that endostaples can increase proximal stent-graft fixation to levels equivalent or superior to that of a hand-sewn anastomosis. Further clinical studies aimed to investigate whether this increased proximal fixation results in reduced migration and better sealing with lower rates of type I endoleak. The present chapter discusses the efficacy of endostaples in reducing migration and type I endoleak after EVAR, based on published clinical data.

Common iliac and hypogastric aneurysms: open and endovascular repair.

Currently, there are a variety of open surgical, endovascular, and hybrid options to treat iliac artery aneurysms (IAA). Anatomy of the common iliac artery (CIA) with regard to proximal and distal neck, involvement of the iliac bifurcation, and choice to preserve the ipsilateral internal iliac artery (IIA) all play a role in the decision process towards the preferred treatment method. This manuscript describes the available open surgical and endovascular techniques for the treatment of IAA. Indications, advantages and limitations, and outcomes of each technique are discussed.

Outcomes of fenestrated/branched endografting in post-dissection thoracoabdominal aortic aneurysms.

OBJECTIVES: Fenestrated/branched thoracic endovascular repair (F/Br-TEVAR) is increasingly applied for atherosclerotic thoracoabdominal aortic aneurysm (TAAA); however, use in post-dissection TAAAs is still very limited. Experience with F/Br-TEVAR in the treatment of post-dissection TAAA is presented. METHODS: Data were analysed from prospectively maintained databases including all patients with post-dissection TAAAs that underwent F/Br-TEVAR within the period January 2010 to July 2013 in two vascular institutions. Evaluated outcomes included initial technical success, operative mortality and morbidity, late survival, endoleak, aneurysm diameter regression, renal function, and reintervention during follow-up (FU). RESULTS: A total of 31 patients (25 male, mean age 65 ± 11.4 years) were treated. Technical success was 93.5% and 30-day mortality 9.6%. Temporary spinal cord ischaemia occurred in four (12.6%) patients, with no case of permanent paraplegia. Mean FU was 17.0 ± 10 months. There were seven late deaths, all aneurysm unrelated. Estimated overall survival rates were 83.9 ± 6.7, 76.4 ± 7.9 and 71.6 ± 8.7% at 6, 12, and 18 months, respectively. Impairment of renal function occurred in two (6.4%) patients. Endoleaks were diagnosed in 12 patients during FU, including six type IB endoleaks and six type II endoleaks. Reintervention was required in seven (22.5%) patients. Mean aneurysm sac regression was 9.3 ± 8.7 mm, with a false lumen thrombosis rate of 66.7% and 88.2% for patients with a FU longer than 6 and 12 months respectively. CONCLUSIONS: F/Br-EVAR is feasible for patients with a post-dissection TAAA. Although associated with additional technical challenges, and a significant need for reintervention, it leads to favourable aneurysm morphologic changes, and may play a more prominent role in the future for this type of pathology if long-term results confirm the good initial outcome.

Fenestrated and branched stent-grafting after previous open or endovascular aortic surgery.

AIM: Aim of the study was to review our experience with fenestrated and branched stent-grafts to treat juxtarenal (JAA) and thoracoabdominal (TAAA) aortic aneurysms after previous open or endovascular aortic surgery. METHODS: A prospectively maintained database including all consecutive patients with JAA or TAAA treated with fenestrated/branched stent-grafts after previous open or endovascular aortic surgery within the period March 2002-November 2013 was analyzed. Evaluated outcomes included initial technical success, operative mortality and morbidity and late procedure-related events with regard to survival, target vessel patency, and re-intervention. RESULTS: A total of 122 patients (110 male, 12 female; mean age mean age 70±9.5 years) were treated. Median time interval from previous aortic surgery to current fenestrated/branched stent-grafting was 80 months (range 3-261 months). Seventy-seven (63.1%) patients had previous open infrarenal aortic surgery, 33 (27%) had previous endovascular abdominal aortic aneurysm repair (EVAR), nine (7.4%) had previous open thoracic aortic surgery, and three (2.5%) had previous endovascular thoracic aortic repair (TEVAR). Indication for current treatment was a JAA in 65 (53.3%) patients and a TAAA in 57 (46.7%) patients. Technical success was achieved in 115 (94.3%) patients. Seven patients were considered as technical failure (open conversion; N.=1, target vessel loss; N.=6). Operative target vessel perfusion success rate with endovascular means was 98.5% (391/397). Intraoperative technical difficulties due to pre-existing stent-graft/surgical graft were encountered in 28 (23%) patients (access, N.=12; target vessel catheterisation, N.=16). Thirty-day operative mortality was 4.1% (5/122), with zero mortality in 65 JAA, and 8.8% (5/57) in TAAA, respectively. Cause of death was multiple organ failure (N.=3), acute gastrointestinal bleeding (N.=1), and subdural hematoma (N.=1). Major complications occurred in 20 (16.4%) patients. Median hospital stay was 7 days (range 3-50 days), and mean ICU stay 1.5±3.2 days. Mean follow-up was 22.5±21 months. All-cause late mortality was encountered in 23 patients, including one aneurysm-related mortality. Estimated survival was 91.2±3%, 83.3±4.2% and 81.1±4.6% at one, two and three years, respectively. During follow-up, eight target vessels occluded. Estimated target vessel patency was 97.2±1.1%, and 96.3±1.2% at one and three years, respectively. Reintervention during follow-up was required in 13 (10.6%) cases accounting for an estimated freedom from reintervention of 91.6±3.1%, and 82.1±5.4% at one and three years, respectively. CONCLUSION: Fenestrated and branched stent-grafting represents a feasible option for the repair of JAA and TAAA after prior endovascular or open aortic surgery. Despite increased technical difficulties it is associated with high technical success rate and is advantageous in terms of mortality and morbidity compared to redo open aortic surgery.

The new C3 Gore Excluder stent-graft: single-center experience with 100 patients.

OBJECTIVES: To present results from the first 100 patients treated with the new C3 Gore Excluder stent-graft in a single institution. METHODS: All patients treated with the C3 Excluder stent-graft between August 2010 and July 2013 in our institution were included. Patient demographics, treatment indication, need for intraoperative stent-graft repositioning, immediate technical success, survival, endoleak and migration rate, and need for reintervention during follow-up were analyzed. RESULTS: A total of 100 patients (86% male, mean age 71.1 ± 9.3 years) were enrolled. Elective abdominal aortic aneurysm (AAA) was the most common indication for treatment (n = 90), followed by common iliac artery aneurysm (n = 5), ruptured AAA (n = 2), type Ia endoleak (n = 1), and type IV endoleak (n = 1) after prior EVAR, and penetrating aortic ulcer (n = 1). Technical success was achieved in 98 patients. In two patients a small type I endoleak persisted at completion angiography, but had disappeared at the first control computed tomography angiogram. Stent-graft repositioning after initial deployment was required in 49 patients, almost equally distributed for level and contralateral gate reorientation. Exact positioning of the proximal trunk was achieved in 98 patients, with the remaining two cases within 5 mm of the intended location. Adverse events related to repositioning maneuvers were noticed in two cases. Mean follow-up duration was 12.2 ± 9.4 months (range 0-36 months). Eight patients died, none from aneurysm related causes. Cumulative patient survival was 96.2 ± 2.1% at 1 year, and 84 ± 6.1% at 2 years, respectively. No migration, or type I or III endoleak was detected during follow-up. Estimated freedom from reintervention was 96 ± 2.4% at 1 year, and 91 ± 5.2% at 2 years, respectively. CONCLUSIONS: The new C3 Excluder stent-graft provides excellent short-term outcomes and offers important advantages in terms of stent-graft repositioning to achieve high proximal deployment accuracy. Longer follow-up is required to confirm improved long-term outcome compared with the previous generation Excluder stent-graft.

Fenestrated stent-grafts for salvage of prior endovascular abdominal aortic aneurysm repair.

OBJECTIVES: To review our experience with fenestrated endovascular aneurysm repair (F-EVAR) to treat complications after previous standard infrarenal endovascular aneurysm repair (EVAR). METHODS: A prospectively maintained database including all consecutive patients with juxtarenal abdominal aortic aneurysm that were treated with F-EVAR after failed previous EVAR within the period March 2002 to November 2012 at the University Medical Center of Groningen, Netherlands (up to October 2009), and the Klinikum Nürnberg Süd, Germany (from November 2009) was analyzed. Evaluated outcomes included initial technical success, operative mortality and morbidity, and late procedure-related events with regard to survival, target vessel patency, endoleak, renal function, and reintervention. RESULTS: A total of 26 patients (24 male, mean age 73.2 ± 6.5 years) were treated. All patients had proximal anatomies precluding endovascular reintervention with standard techniques. In 23 patients a fenestrated proximal cuff was used, and in three patients a bifurcated fenestrated stent graft. Technical success was achieved in 24 (92.3%) patients. One patient required on-table open conversion because of impossibility to retrieve the top cap as a result of twist of the ipsilateral limb. In the second patient the right kidney was lost due to inadvertent stenting in a smaller branch of the renal artery. Catheterization difficulties, all related to the passage through the limbs or struts of the previous stent graft, were encountered in 11 (42.3%) cases, including five (19.2%) patients with iliac access problems and six (23.1%) with challenging renal catheterization. Operative target vessel perfusion success rate was 94.6% (70/74). Operative mortality was 0%. Mean follow-up was 26.8 ± 28.5 months. No proximal type I endoleak was present on first postoperative CTA. The mean aneurysm maximal diameter decreased from 73 ± 20 mm to 66.7 ± 21 mm (p < .05). There were six late deaths, one of them aneurysm related. Estimated survival rates at 1 and 2 years were 94.1 ± 5.7% and 87.4 ± 8.4%, respectively. Patency during follow-up for the target vessels treated successfully with a fenestrated stent graft was 100% (70/70). Reintervention was required in four cases, including one acute conversion due to rupture, one for iliac limb occlusion and two for type Ib and II endoleak. Renal function deterioration was observed solely in the two cases of primary technical failure. CONCLUSIONS: F-EVAR represents a feasible option for the repair of juxtarenal abdominal aortic aneurysm after prior EVAR failure. It is advantageous in terms of mortality and less morbid than open surgery, but is associated with increased technical challenges because of the previously placed stent graft. Outcome seems related to initial technical success.

Short-term outcome and attainment of secondary prevention goals in patients with acute coronary syndrome--results from the countrywide TARGET study.

BACKGROUND/OBJECTIVES: Acute coronary syndromes (ACS) continue to pose a significant medical and socioeconomic burden worldwide. Optimal management strategy aims to improve short and long-term outcome. The present study aims to assess short-term outcome of real-world ACS patients and evaluate the achievement rate of secondary prevention goals. METHODS: The TARGET study is an observational study enrolling 418 consecutive ACS patients from 17 centers countrywide (78.0% males, 63.9 ± 12.9 years). After the in-hospital phase, patients were followed for 6 months. In total, 366 patients were included in the prospective phase of the study. At the end of the follow-up, mortality, major adverse cardiovascular events (MACE), prescription pattern of cardiovascular medications, lipid levels, adherence rate to treatment and behavioral recommendations were measured. RESULTS: The overall mortality was 4.8% and the rate of MACE was 17.5%. At 6 months, a significantly lower proportion of patients received antiplatelet agents and statins as compared to hospital discharge. At the end of the follow-up, 87.7% of patients remained on statin treatment, yet only 18.2% of patients had LDL cholesterol levels less than 70 mg/dL. The adherence pattern to lifestyle and dietary recommendations remained low (66.2% quit smoking, 55.8% and 81.3% followed physical activity and dietary recommendations respectively). CONCLUSION: Despite the low rate of mortality and MACE occurrence rate in this countrywide observational study, the attainment rate of secondary prevention goals is relatively poor. Improvement interventions focusing in these gaps of optimal care provision are expected to have a favorable impact on the prognosis of real world ACS patients.

Neutrophil gelatinase-associated lipocalin (NGAL) in inflammatory bowel disease: association with pathophysiology of inflammation, established markers, and disease activity.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a multi-potent 25-kDa protein mainly secreted by neutrophils. In inflammatory bowel disease (IBD), overexpression of NGAL in colon epithelium has been previously shown. This is the first study analyzing serum and urinary NGAL levels in IBD patients, with regard to specific characteristics of patients and disease. METHODS: Serum and urinary NGAL levels were determined in 181 patients with IBD, 93 with ulcerative colitis (UC), and 88 with Crohn's disease (CD), 82 healthy controls (HC), and 41 patients with irritable bowel syndrome (IBS). RESULTS: Serum NGAL levels were elevated in IBD patients (88.19 ± 40.75 ng/mL) compared with either HC (60.06 ± 24.18 ng/mL) or IBS patients (60.80 ± 20.30 ng/mL), P < 0.0001. No significant difference was shown between UC (86.62 ± 35.40 ng/mL) and CD (89.92 ± 46.05 ng/mL). Significantly higher levels of serum NGAL were observed in patients with active (120.1 ± 38.46) versus inactive IBD (61.58 ± 15.98), P < 0.0001. Serum NGAL displayed a strong ability to distinguish active IBD from inactive disease, healthy controls, or IBS patients with a sensitivity of 100, 95, and 95% and a specificity of 68, 83, and 79%, respectively, performing better than erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the assessment of disease activity in both UC and CD. Urinary NGAL levels showed neither significant difference among patients and controls nor correlation with disease activity. CONCLUSIONS: Serum NGAL is elevated particularly in active IBD and correlates with established markers of inflammation and disease activity, implicating its role in the pathophysiology of IBD.

Anti-α actinin antibodies as new predictors of response to treatment in autoimmune hepatitis type 1.

BACKGROUND: We reported that combined presence of autoantibodies (Abs) against filamentous-actin (AFA) and α-actinin are specific for autoimmune hepatitis type 1 (AIH-1) diagnosis. AIM: To explore our data and assess whether anti-α-actinin and AFA Abs could be used as indicators of response to treatment and predictors of AIH-1 flares in a large cohort of AIH-1 patients. METHODS: Seven hundred and sixty-four serial serum samples of 86 consecutive AIH-1 patients, 509 pathological and 110 normal controls were tested for the presence of anti-α-actinin and AFA Abs by an in-house IgG-specific ELISA and a standardised commercially available ELISA respectively. Patients sera were divided into baseline group (active disease before treatment initiation, n = 86) and then according to treatment response into group A-responders (n = 40 patients), group B-relapsers/incomplete responders (n = 37 patients) and group C-not-treated (n = 9 patients). RESULTS: Anti-α-actinin and AFA levels were significantly higher at baseline. Double reactivity against α-actinin and AFA was associated with disease activity (OR 4.9; 95% CI: 2.7-9). Anti-α-actinin optical densities (ODs) before treatment decreased significantly at first remission (P < 0.05). Treatment response was associated with anti-α-actinin Abs negativity before treatment (OR 3.4; 95% CI: 1.3-8.9) and absence of double positivity for anti-α-actinin and AFA Abs before treatment (OR 3.8; 95% CI: 1.4-10.4). Responders had lower baseline levels of anti-α-actinin than relapsers and/or incomplete responders (P = 0.002). Binary logistic regression revealed lower levels of anti-α-actinin as the only independent predictors of response (P = 0.05). CONCLUSIONS: Anti-α-actinin Abs at baseline appear to predict treatment response and therefore they might be used for monitoring treatment outcome in AIH-1.

First experience with the new repositionable C3 excluder stent-graft.

AIM: The Gore Excluder device is a modern third generation device that performs well. Nevertheless, the proximal deployment was not as accurate and controlled as with some other modern devices. Therefore a new deployment system was developed. This system allows to reconstrain the graft after initial deployment, with the purpose to reposition the graft for both level or orientation. METHODS: The new system was used in 25 patients with an infrarenal abdominal aortic aneurysm. In 72% of cases the system was used to achieve a better proximal position or to facilitate catheterization of the contralateral limb. Surprisingly, the option to orientate the graft was used most. RESULTS: The new deployment system worked well, and all grafts were easily repositioned to the intended final position. Additional cuffs were not required in any of the patients. Surgical mortality was nil. All patients left the hospital in good condition. There were no type I endoleaks at completion angiography neither at first computed tomography scanning. CONCLUSION: With the new deployment system it is possible to reposition the Excluder to achieve optimal fixation and sealing. A global registry has been set into place to report real life results including longer term performance of the graft.

Is it time to eliminate CT after EVAR as routine follow-up?

Growing concerns regarding radiation exposure, contrast induced nephropathy and increasing costs lead us to reconsider the necessity of CTA for all EVAR patients. The purpose of this study is to compare the results of different follow-up imaging modalities with the aim of finding a rationale to the optimal follow-up imaging protocol. We reviewed recent literature regarding post EVAR imaging modalities and compared it to our experience with different follow-up protocols. Modalities compared were CTA, DUS, CEUS, and plain abdominal X-ray with regard to detection of complications, cost, overall impact to the patient, and on decision making regarding reintervention. CTA is related to increased follow-up costs and a much higher exposure to radiation compared to other modalities. The cumulative radiation dose can have a significant impact on the attributable lifetime cancer risk of patients. Renal function deterioration during post EVAR follow-up is higher compared to open repair. Plain abdominal X-ray is the best manageable modality and a well established tool in documenting migration kinking and stent fracture. Plain X-Ray cannot be used as a standalone imaging modality since it doesn't allow direct detection of endoleaks. As far as detection of endoleaks is concerned recent meta-analyses show a sensitivity of 66-77% for DUS and 81-98% for CEUS, respectively. Most endoleaks missed by DUS and CEUS are type II endoleaks with no need for reintervention. Our data in a cohort of 62 patients do show a sensitivity of 66.7% for DUS, and do correlate with current literature. No endoleaks requiring reintervention were missed. A follow-up protocol comprising of DUS/CEUS and plain abdominal X-ray gives a wide range of information covering EVAR related risks and is associated with less radiation exposure, avoidance of renal function deterioration due to repeated contrast agent application and an important decrease in the cost of EVAR follow-up. CTA should be reserved for cases of inconclusive ultrasound, signs of complications and unfavourable anatomy.