Review: Protein misfolding diseases - the rare case of Marinesco-Sjögren syndrome.

Secretory and cell membrane proteins are synthesized in the endoplasmic reticulum (ER), where a network of molecular chaperones and folding factors ensure correct protein folding and export to post-ER compartments. Failure of this process leads to accumulation of unfolded/misfolded proteins, ER stress, and activation of the unfolded protein response (UPR), a complex signalling pathway aimed at restoring ER homeostasis, whose failure eventually leads to cell death. Suppressor of Ire1/Lhs1 double mutant (SIL1) is a nucleotide exchange factor for immunoglobulin binding protein, the main ER chaperone and primary sensor of ER stress. Loss of SIL1 function causes Marinesco-Sjögren syndrome (MSS), a rare multisystem disease of early infancy for which there is no cure. This review, examines the current understanding of SIL1 activities in the ER, and reviews experimental data describing the consequences of SIL1 deficiency in cell and animal models. We discuss the evidence supporting a role of the UPR - particularly the protein kinase RNA-like endoplasmic reticulum kinase branch - in the pathogenesis of MSS, and how this may be pharmacologically manipulated for treatment.

Review: PrP 106-126 - 25 years after.

A quarter of a century ago, we proposed an innovative approach to study the pathogenesis of prion disease, one of the most intriguing biomedical problems that remains unresolved. The synthesis of a peptide homologous to residues 106-126 of the human prion protein (PrP106-126), a sequence present in the PrP amyloid protein of Gerstmann-Sträussler-Scheinker syndrome patients, provided a tractable tool for investigating the mechanisms of neurotoxicity. Together with several other discoveries at the beginning of the 1990s, PrP106-126 contributed to underpin the role of amyloid in the pathogenesis of protein-misfolding neurodegenerative disorders. Later, the role of oligomers on one hand and of prion-like spreading of pathology on the other further clarified mechanisms shared by different neurodegenerative conditions. Our original report on PrP106-126 neurotoxicity also highlighted a role for programmed cell death in CNS diseases. In this review, we analyse the prion research context in which PrP106-126 first appeared and the advances in our understanding of prion disease pathogenesis and therapeutic perspectives 25 years later.

Bactericidal activity of gallium-doped chitosan coatings against staphylococcal infection.

AIMS: The aim of this study was to develop a new class of gallium (Ga)-doped chitosan (CS) coatings fabricated by electrophoretic deposition (EPD) in staphylococcal infection therapy. METHODS AND RESULTS: Biofilm formation on EPD CS/Ga coatings by Staphylococcus epidermidis and Staphylococcus aureus, which are the main strains involved in postarthroplasty infections, was assessed. The codeposition of an antibacterial agent was effective; Ga loaded into CS matrix reduces biofilm viability by up to 86% and 80% for S. epidermidis and S. aureus strains respectively. Lastly, the influence of pulsed electromagnetic field (PEMF) on the bactericidal activity of CS/Ga coatings was investigated in vitro. To this end, the coatings were incubated with S. epidermidis and S. aureus and exposed to the PEMF using two different frequencies and times. Biofilm viability for S. epidermidis was decreased by 35-40% in the presence of low-frequency (LF) and high-frequency (HF) PEMF respectively. Biofilm viability by S. aureus was not further reduced in the presence of LF PEMF, but decreased by 38% at HF PEMF. CONCLUSIONS: This study has established that a combination of PEMFs with the antibacterial agent improves bactericidal activity of Ga against S. epidermidis strain 14990 and S. aureus strain 12600. SIGNIFICANCE AND IMPACT OF THE STUDY: This new integrated approach could reduce the incidence of infection in orthopaedic implant applications. It also clearly demonstrates that the combination of Ga treatment with PEMF could aid biofilm-associated infection therapy due to improved Ga efficiency.

Predicting the Need for Intra-operative Large Volume Blood Transfusions During Thoraco-abdominal Aortic Aneurysm Repair.

OBJECTIVE: Thoraco-abdominal aortic aneurysm (TAAA) repair is a complex procedure performed in patients at high cardiovascular risk. High volume intra-operative bleeding is often recorded, and the amount of intra-operative blood product transfusion is associated with relevant morbidity and mortality. The aim of the study was to identify pre-operative predictors of intra-operative large volume blood transfusions (LVBT) to stratify patients pre-operatively. METHODS: This was a retrospective analysis of prospectively collected data of all patients who underwent open TAAA surgery at San Raffaele Scientific Institute from January 2009 to December 2015. Intra-operative red blood cell (RBC) transfusions were administered to maintain a hematocrit of at least 30%. A LVBT was defined as a transfusion of at least four RBC units, corresponding to 1000 mL. RESULTS: The study population included 428 patients: 260 (61%) received fewer than 4 RBC units, and 168 (39%) were transfused with at least 4 RBC units. In patients who underwent LVBT, higher mortality was observed after surgery (p=.003), longer intensive care unit admission (p=.004), and longer mechanical ventilation compared with less transfused patients (p=.0002). The patients who received fewer units were administered a higher dose of heparin during the surgical operation compared with patients of the LVBT group: 3400±1100 vs. 2900±1300 IU (international units) (p=.0004). Pre-operative chronic renal failure (OR 1.8), the pre-operative haemoglobin value (OR 0.8), and the need for urgent or emergent surgery (OR 3.15) were independent predictors of LVBT on multivariate analysis. CONCLUSIONS: The identification of patients at risk of intra-operative LVBT during TAAA surgery is critical as these patients experience a worse outcome. Nevertheless, only few independent predictors are available for clinical practice.

Definition of criteria and indicators for the prevention of Healthcare-Associated Infections (HAIs) in hospitals for the purposes of Italian institutional accreditation and performance monitoring.

BACKGROUND: Healthcare-associated infections (HAIs) are an important issue in terms of quality of care. HAIs impact patient safety by contributing to higher rates of preventable mortality and prolonged hospitalizations. In Italy, analysis of the currently available accreditation systems shows a substantial heterogeneity of approaches for the prevention and surveillance of HAIs in hospitals. The aim of the present study is to develop and propose the use of a synthetic assessment tool that could be implemented homogenously throughout the nation. METHODS: An analysis of nine international and of the 21 Italian regional accreditation systems was conducted in order to identify requirements and indicators implemented for HAI prevention and control. Two relevant reviews on this topic were further analyzed to identify additional evidence-based criteria. The project team evaluated all the requirements and indicators with consensus meeting methodology, then those applicable to the Italian context were grouped into a set of "focus areas". RESULTS: The analysis of international systems and Italian regional accreditation manuals led to the identification respectively of 19 and 14 main requirements, with relevant heterogeneity in their application. Additional evidence-based criteria were included from the reviews analysis. From the consensus among the project team members all the standards were compared and 20 different thematic areas were identified, with a total of 96 requirements and indicators for preventing and monitoring HAIs. CONCLUSIONS: The study reveals a great heterogeneity in the definition of accreditation criteria between the Italian regions. The introduction of a uniform, synthetic assessment instrument, based on the review of national and international standards, may serve as a self-assessment tool to evaluate the achievement of a minimum standards set for HAIs prevention and control in healthcare facilities. This may be used as an assessment tool by the Italian institutional accreditation system, also useful to reduce regional disparities.

Osteogenic response and osteoprotective effects in vivo of a nanostructured titanium surface with antibacterial properties.

In implantology, as an alternative approach to the use of antibiotics, direct surface modifications of the implant addressed to inhibit bacterial adhesion and to limit bacterial proliferation are a promising tactic. The present study evaluates in an in vivo normal model the osteogenic response and the osteointegration of an anodic spark deposition nanostructured titanium surface doped with gallium (ASD + Ga) in comparison with two other surface treatments of titanium: an anodic spark deposition treatment without gallium (ASD) and an acid etching treatment (CTR). Moreover the study assesses the osteoprotective potential and the antibacterial effect of the previously mentioned surface treatments in an experimentally-induced peri-implantitis model. The obtained data points out a more rapid primary fixation in ASD and ASD + Ga implants, compared with CTR surface. Regarding the antibacterial properties, the ASD + Ga surface shows osteoprotective action on bone peri-implant tissue in vivo as well as an antibacterial effect within the first considered time point.

Hemothorax Management After Endovascular Treatment For Thoracic Aortic Rupture.

OBJECTIVES: The aim was to describe and analyze the management of hemothorax (HTX) and the occurrence of respiratory complications after endovascular repair of thoracic aortic rupture (TEVAR). METHODS: This was a multicenter study with retrospective analysis. Between November 2000 and December 2012, all patients with confirmed HTX due to rupture of the descending thoracic aorta treated with TEVAR were included. Respiratory function (acid base status, Pao2, Paco2, lactate, and respiratory index) was monitored throughout hospitalization. Primary endpoints were survival and post-operative respiratory complications. RESULTS: Fifty-six patients were treated. The mean age was 62 ± 21 years (range 18-92 years). Etiology included traumatic rupture (n = 23, 41%), atherosclerotic aneurysm (n = 20, 36%), Debakey type IIIa dissection (n = 8, 14%), and penetrating aortic ulcer (n = 5, 9%). The primary technical success of TEVAR was 100%. The in hospital mortality rate was 12.5% (n = 7). Hemothorax was drained in 21 (37.5%) cases. In hospital respiratory complications occurred in 23 (41%) patients who required a longer intensive care unit stay (days 2.3 ± 0.7 vs. 1.9 ± 0.8, p = .017), and hospitalization (26 ± 17 vs. 19 ± 17, p = .021). Those who developed post-operative respiratory complications had lower pre-operative PO2 values (mmHg, 80 ± 24 vs. 91 ± 21, p = .012). Respiratory complications and in hospital mortality did not differ among aortic pathologies (p = .269 and p = 1.0, respectively), nor did in hospital mortality differ between patients with and without respiratory complications (13% vs. 12%; p = .990). CONCLUSIONS: Thoracic aortic rupture still has a high mortality rate. Respiratory complications have not been eliminated by endovascular repair. HTX evacuation may have had a positive influence on the survival in these patients. Although traumatic and degenerative ruptures are two significantly different scenarios, survival and respiratory outcomes were similar and were not affected by the underlying aortic disease.

Propofol and survival: a meta-analysis of randomized clinical trials.

BACKGROUND: One of the most commonly used hypnotics is propofol. Several studies performed in cardiac surgery suggested an increased mortality in patients receiving a propofol-based total intravenous anaesthesia. Furthermore, the possibility of infections and the 'propofol syndrome' have suggested that propofol might be dangerous. Nonetheless, propofol is widely used in different settings because of its characteristics: fast induction, rapid elimination, short duration of action, smooth recovery from anaesthesia, few adverse effects, no teratogenic effects, characteristics that have undoubtedly contributed to its popularity. The effect of propofol on survival is unknown. We decided to carry out a meta-analysis of all randomized controlled studies ever performed on propofol vs. any comparator in any clinical setting. METHODS: Pertinent studies were independently searched in BioMedCentral, PubMed, Embase, Clinicaltrial.gov, and Cochrane Central Register of Clinical Trials by expert investigators. The following inclusion criteria were used: random allocation to treatment, comparison between propofol and any comparator in any clinical setting. RESULTS: One hundred thirty-three studies randomizing 14,516 patients were included. No differences in mortality between patients receiving propofol [349/6957 (5.0%)] vs. any comparator [340/7559 (4.5%)] were observed in the overall population [risk ratio = 1.05, 95% confidence interval (0.93 to 1.18), P = 0.5] and in several sub-analyses. CONCLUSION: Inspite of theoretical concerns, propofol has no detrimental effect on survival according to the largest meta-analysis of randomized trials ever performed on hypnotic drug.

On-label use of commercially-available abdominal endografts for para-anastomotic aneurysms and pseudoaneurysms after infrarenal abdominal aortic aneurysm open repair.

OBJECTIVES: To analyze feasibility and outcomes of endovascular aortic repair (EVAR) with a strictly on-label use of abdominal aortic endografts (OnL-EVAR) to treat para-anastomotic aneurysms (PAAs) and pseudoaneurysms (PSAs) after infrarenal abdominal aortic aneurysm open repair (OR). METHODS: The data of all consecutive patients treated between 1999 and 2012 for non-infected abdominal PAAs and PSAs at our center were prospectively collected. All cases fit for EVAR based on the instructions for use of a series of abdominal aortic endografts commercially available during the study period were scheduled for OnL-EVAR regardless of patients' surgical risk. Any patients unfit for OnL-EVAR underwent OR or other complex endovascular techniques. RESULTS: One hundred and forty-three patients were collected; 78 underwent OR and 65 endovascular repair with different strategies. Coil embolization, hybrid, and chimney/periscope grafts techniques were limited to seven patients unfit both for OR and OnL-EVAR. Inclusion criteria for OnL-EVAR were reached in 58 patients for an overall OnL-EVAR feasibility of approximately 40% (21% for PAAs and 55% for PSAs). In particular, OnL-EVAR feasibility was 19% in case of involvement of proximal aortic anastomosis, 71% for distal aortic anastomosis, and 80% for iliac arteries. Overall, 25 aortouniiliac and 11 bifurcated implants were performed, single proximal aortic cuffs were used in 10 patients, and iliac extension in 12. Primary technical success was 98% without perioperative mortality. At a median follow-up of 67 months (range: 1-144 months), cumulative aneurysm-related mortality was 7%, endograft migration 7%, and reintervention was 17%. Life-table analysis showed actuarial survival and freedom from aneurysm-related death at 1, 3, and 5 years of 100%, 98%, and 95%, and of 100%, 98%, and 95%, respectively. Freedom from aortic reintervention or open conversion at 1, 3, and 5 years was 94%, 90%, and 85%. CONCLUSIONS: Feasibility of OnL-EVAR was limited for PAAs and PSAs, with a rate that was lower than 20% in case of involvement of proximal aortic anastomosis. Aortouniiliac configuration was the most commonly feasible implant and, despite strict on-label use of abdominal devices, the rate of late complications and reinterventions was high.

Delayed open conversion after endovascular abdominal aortic aneurysm: device-specific surgical approach.

OBJECTIVES: Despite several advances in endoluminal salvage for failed endovascular abdominal aortic repair (EVAR), in our experience an increasing number of cases necessitate delayed open conversion (dOC). METHODS: EVAR patients requiring delayed (>30 days) conversion were prospectively collected in a computerized database including demographics, details of aortoiliac anatomy, procedural and clinical success, and postoperative complications. RESULTS: Between 2005 and 2011, 54 patients were treated for aortic stent-graft explantation. Indications included 34 type I and III endoleaks, 13 type II endoleaks with aneurysm growth, 4 cases of material failures, and 3 stent-graft infections. All fit-for-surgery patients with type I/III endoleak underwent directly dOC. Different surgical approaches were used depending on the type of stent-graft. Overall 30-day mortality was 1.9%. Overall morbidity was 31% mainly due to acute renal failure (13 cases). Mean hospitalization was 6 days (range, 5-27 days). Overall survival at mean follow-up of 19 months was 78%. CONCLUSIONS: In recent years, the use of EVAR has increased dramatically, including in young patients regardless of their fitness for open repair. dOC after endovascular abdominal aortic aneurysm seems to be a lifesaving procedure with satisfactory initial and mid-term results.

Genotypes and haplotypes in the 3' untranslated region of the HLA-G gene and their association with clinical outcome of hematopoietic stem cell transplantation for beta-thalassemia.

Polymorphisms in the 3' untranslated region (3'UTR) of HLA-G, an important player in immunological tolerance, could be involved in post-transcriptional expression control, and their association with different clinical immune-related conditions including autoimmunity and transplantation is of mounting interest. Most studies have focused on a 14 base pair (bp) insertion/deletion (ins/del), while additional single-nucleotide polymorphisms (SNPs) in the HLA-G 3'UTR have been described but not extensively investigated for their clinical relevance. Here we have comparatively studied the association between 3'UTR haplotypes of HLA-G, or the 14 bp ins/del, with clinical outcome of HLA-identical sibling hematopoietic stem cell transplantation (HSCT) in 147 Middle Eastern beta-thalassemia patients. Sequence based typing of 3'UTR HLA-G polymorphisms in the patients and in 102 healthy Italian blood donors showed strong linkage disequilibrium between the 14 bp ins/del and five 3'UTR SNPs, which together could be arranged into eight distinct haplotypes based on expectation-maximization studies, with four predominant haplotypes (UTRs1-4). After HSCT, we found a moderate though not significant association between the presence of UTR-2 in double dose and protection from acute graft versus host disease (hazard ratio (HR) 0.45, 95% confidence intervals (CI): 0.14-1.45; P = 0.18), an effect that was also seen when the corresponding 14 bp ins/ins genotype was considered alone (HR 0.42, 95% CI: 0.16-1.06; P = 0.07). No association was found with rejection or survival. Taken together, our data show that there is no apparent added value of considering entire 3'UTR HLA-G haplotypes for risk prediction after allogeneic HSCT for beta-thalassemia.

Effect of a long-term oral l-arginine supplementation on glucose metabolism: a randomized, double-blind, placebo-controlled trial.

AIM: This study assessed the efficacy of long-term l-arginine (l-arg) therapy in preventing or delaying type 2 diabetes mellitus. METHODS: A mono-centre, randomized, double-blind, parallel-group, placebo-controlled, phase III trial (l-arg trial) was conducted on 144 individuals affected by impaired glucose tolerance (IGT) and metabolic syndrome (MS). l-Arg/placebo was administered (6.4 g/day) on a background structured lifestyle intervention for 18 months plus a 12-month extended follow-up period after study drug termination. Fasting glucose levels and glucose tolerance after oral glucose tolerance test were evaluated throughout the study. RESULTS: After 18 months, l-arg as compared with placebo did not reduce the cumulative incidence of diabetes [21.4 and 20.8%, respectively, hazard ratio (HR), 1.04; 95% confidence interval (CI), 0.58-1.86] while the cumulative probability to become normal glucose tolerant (NGT) increased (42.4 and 22.1%, respectively, HR, 2.60; 95% CI, 1.51-4.46, p < 0.001). The higher cumulative probability to become of NGT was maintained during the extended period in subjects previously treated with l-arg (HR, 3.21; 95% CI, 1.87-5.51; p < 0.001). At the end of the extended period, the cumulative incidence of diabetes in subjects previously treated with l-arg was reduced as compared with placebo (27.2 and 47.1%, respectively, HR, 0.42; 95% CI, 0.24-0.75, p < 0.05). During both periods, l-arg significantly improved insulin sensitivity and ß-cell function. CONCLUSION: Among persons with IGT and MS, the supplementation of l-arg for 18 months does not significantly reduce the incidence of diabetes but does significantly increase regression to NGT.

Analysis of stroke after TEVAR involving the aortic arch.

OBJECTIVE: To analyse the incidence of stroke after thoracic endovascular aortic repair (TEVAR) for aortic arch disease. METHODS: In the last decade, 393 patients received TEVAR at our Institution; in 143 cases the aortic arch was involved (32 zones '0', 35 zones '1' and 76 zone '2'). The left subclavian artery (LSA) was revascularised selectively in 75 cases; the proximal LSA was ligated or occluded with a plug in 55 cases before endograft (EG) deployment. RESULTS: Initial clinical success, perioperative mortality, spinal cord ischaemia and stroke in TEVAR patients with or without arch involvement were, respectively, 86.7% vs. 94.4%, 4.2% vs. 2.4%, 2.1% vs. 3.6% and 2.8% vs. 1.2%. The stroke rate was 9.4% (P < 0.02) in 'zone 0', 0% in 'zone 1' and 1.3% in 'zone 2' with scans showing severe atheroma and/or thrombus in all cases. Stroke was observed in patients with 2.6% or without 2.9% LSA revascularisation; however, it was never observed in patients in whom the LSA was occluded before EG deployment and in 4.5% of patients in whom it was patent at the time of EG deployment. CONCLUSIONS: Stroke after TEVAR is not infrequent especially when the arch is involved. Careful patient selection together with a strategy to reduce embolisation such as occlusion of supra-aortic trunks before EG deployment may play a beneficial role.

Diagnostic laparoscopy for early detection of acute mesenteric ischaemia in patients with aortic dissection.

INTRODUCTION: Recognition of acute mesenteric ischaemia (AMesI) in patients with aortic dissection (AoD) may be a challenge and exploratory laparotomy is often performed. METHODS: We retrospectively analysed our experience with the use of diagnostic laparoscopy (DL) for the early detection of AMesI in patients with AoD, either undergoing medical treatment or after open/endovascular interventions. RESULTS: Between 2004 and 2011, 202 consecutive AoDs were treated in our centre (71 acute type A AoD; 131 acute and chronic type B AoD). Among the 17 (8.4%) patients in which AMesI was suspected, nine (52.9%) were selected for DL. Three DLs were performed during medical treatment of patients with acute type B AoD, six after treatment of AoD (both surgical and endovascular). Three second-look DLs were also performed. Eight DLs were negative, three showed AMesI and the patients underwent successful emergent revascularisation. One DL was not conclusive and laparotomy was required. Among the eight patients not submitted to DL, one case of bowel infarction was recorded. CONCLUSIONS: In our series DL was feasible and safe. The low invasiveness and repeatability were the main advantages. Although additional experience is mandatory, DL seems a promising technique for the detection of AMesI in patients with AoD.

Enhanced biological performance of human adipose-derived stem cells cultured on titanium-based biomaterials and silicon carbide sheets for orthopaedic applications.

It is well known that the surface properties of biomaterials may affect bone-healing processes by modulating both cell viability and osteogenic differentiation. In this study we evaluated proliferation and osteogenic differentiation of human adipose-derived stem cells (hASCs) cultured on three prototypes of titanium disks and on thin layers of silicon carbide (SiC-PECVD), a material characterized by a high hardness and wear resistance. Our data indicated that all the tested surfaces supported cell growth, in particular, hASCs seeded on both titanium treated by a double-step etching process (TIT) and titanium modified by two Anodic Spark Deposition processes (TAA) grew better respect to the ones cultured on titanium obtained by KOH alkali etching process on TAA (TAAK). Furthermore, hASCs well colonized SiC-PECVD surface, showing a quite similar viability to cells cultured on plastic (PA). TIT and TAA better supported osteogenic differentiation of hASCs compared to PA, as shown by a marked increase of both alkaline phosphatase activity and calcified extracellular matrix deposition; in contrast TAAK did not positively affect hASCs differentiation. SiC-PECVD did not alter osteogenic differentiation of hASC cells: indeed, ALP and calcium deposition levels were comparable to those of cells cultured on plastic. Furthermore, we observed similar results testing hASCs either pre-differentiated for 14 days in osteogenic medium or directly differentiated on biomaterials. Our study suggests that modifications of titanium surface may improve osteo-integration of implant devices and that SiC-PECVD may represent a valid alternative for the coating of prosthetic devices to reduce wear and metallosis events.

Surface modification of Ti-6Al-4V alloy for biomineralization and specific biological response: Part I, inorganic modification.

Titanium and its alloys represent the gold standard for orthopaedic and dental prosthetic devices, because of their good mechanical properties and biocompatibility. Recent research has been focused on surface treatments designed to promote their rapid osteointegration also in case of poor bone quality. A new surface treatment has been investigated in this research work, in order to improve tissue integration of titanium based implants. The surface treatment is able to induce a bioactive behaviour, without the introduction of a coating, and preserving mechanical properties of Ti6Al4V substrates (fatigue resistance). The application of the proposed technique results in a complex surface topography, characterized by the combination of a micro-roughness and a nanotexture, which can be coupled with the conventional macro-roughness induced by blasting. Modified metallic surfaces are rich in hydroxyls groups: this feature is extremely important for inorganic bioactivity (in vitro and in vivo apatite precipitation) and also for further functionalization procedures (grafting of biomolecules). Modified Ti6Al4V induced hydroxyapatite precipitation after 15 days soaking in simulated body fluid (SBF). The process was optimised in order to not induce cracks or damages on the surface. The surface oxide layer presents high scratch resistance.

Angio-CT imaging of the spinal cord vascularisation: a pictorial essay.

Knowledge of the spinal cord (SC) vascular supply is important in patients undergoing procedures that involve the thoracic and thoraco-abdominal aorta; the SC vasculature, however, has a complex and highly variable anatomy. Recent breakthroughs in imaging methods have expanded the non-invasive diagnostic ability to determine a patient's spinal cord vascular pattern, particularly in detecting the presence and location of the artery of Adamkiewicz. CT is the imaging modality of choice for most patients with thoracic and thoraco-abdominal aortic disease for pre-operative planning of endovascular treatment: thus the data set required for our analysis of spinal cord vascular anatomy is already available. This paper provides examples of the SC vasculature imaging that can be obtained with 64 row scanners and appropriate postprocessing.

Aorto-oesophageal and aortobronchial fistulae following thoracic endovascular aortic repair: a national survey.

OBJECTIVE: We evaluated the incidence of aorto-oesophageal (AEF) and aortobronchial (ABF) fistulae after thoracic endovascular aortic repair (TEVAR), and investigated their clinical features, determinants, therapeutic options and results. METHODS: We conducted a voluntary national survey among Italian universities and hospital centres with a thoracic endovascular programme. RESULTS: Thirty-nine centres were contacted, and 17 participated. Of the patients who underwent TEVAR between 1998 and 2008, 19/1113 (1.7%) developed AEF/ABF. Among indications to TEVAR, aortic pseudo-aneurysm was associated with the development of late AEF/ABF (P = 0.009). Further, emergent and complicated procedures resulted in increased risk of AEF/ABF (P = 0.008 and P < 0.001, respectively). Eight patients were treated conservatively, all of whom died within 30 days. Eleven patients underwent AEF/ABF surgical treatment, with a perioperative mortality of 64% (7/11). At a mean follow-up of 17.7 +/- 12.5 months, overall survival was 16% (3/19). CONCLUSIONS: The incidence of AEF and ABF following TEVAR is not negligible, and is comparable to that following open repair. This finding warrants an ad hoc long-term follow-up after TEVAR, particularly in patients submitted to emergent and complicated procedures. Both surgical and endovascular treatment of AEF/ABF are associated with high mortality. However, conservative treatment does not appear to be a viable option.

Management of thoracic endograft infection.

Thoracic endovascular aortic repair (TEVAR) has emerged as a promising, less invasive alternative to conventional open surgery for the treatment of thoracic aortic pathology. Most surveillance after TEVAR concentrates on the technical aspects of the procedure, including endoleak, device migration and endograft rupture; so far, the knowledge on endograft infectious complications is limited to anecdotal reports. Several etiopathogenetic factors may play a role in thoracic endograft infections (TEIs), including perioperative contamination, hematogenous seeding, and local bacterial translocation. Moreover, fistulization with the esophagus or the bronchial tree is a common mechanism of secondary TEI, and it represents a dramatic event requiring a multidisciplinary management. Risk factors assessment and prevention have a key role in avoiding the development of new TEIs. When a TEI is established, treatment is demanding, and includes several medical therapies associated with various surgical options. Patients are usually severely compromised by sepsis, and in most cases they are considered unfit for surgery for general clinical conditions or local concerns. Thus, results of different therapeutic strategies for TEI are still burdened with very high morbidity and mortality. In this paper, we reviewed the English literature regarding the main strategies proposed for operative management of TEI, we reported and analyzed our personal series of 7 patients treated at our institution for TEI from 1999 to 2009, and we summarized results from the data collected during a recent Italian multicenter national survey, performed to investigate aortoesophageal and aortobronchial fistulae treated with TEVAR or developed following TEVAR.