PrP.sup.Sc, a misfolded, aggregation-prone isoform of the cellular prion protein (PrP.sup.C), is the infectious prion agent responsible for incurable brain diseases such as scrapie of sheep, bovine ...spongiform encephalopathy, and its human counterpart, variant Creutzfeldt-Jakob disease. In these disorders, collectively known as prion diseases, exogenous PrP.sup.Sc propagates in the infected host by imprinting its aberrant conformation onto endogenous PrP.sup.C, eventually triggering a rapidly progressing neurodegenerative process that invariably leads to death. But what is the function of PrP.sup.C besides serving as a substrate for the generation of PrP.sup.Sc? And how does PrP.sup.C misfolding cause neurological disease?
Objective The aim of this study was to investigate outcomes of patients treated with endovascular repair (ER) with the use of fenestrated and branched stent grafts or open surgery (OS) for ...thoracoabdominal aortic aneurysm (TAAA) in a current series of patients. Methods All TAAA patients undergoing repair at three centers between January 2007 and December 2014 were included in a prospective database. Patients were stratified according to treatment by ER or OS, and outcomes were compared using propensity score matching (1:1). Covariates included age, sex, aneurysm extent, hypertension, coronary disease, chronic pulmonary disease, diabetes, and renal function. The primary end points were mortality and paraplegia. Secondary end points included any spinal cord ischemia (SCI), renal and respiratory insufficiency, and a composite of these complications or death at 30 days. All-cause survival and freedom from reintervention were compared in the two groups. Results Of 341 patients, 84 (25%) underwent ER and 257 underwent OS (75%). After propensity score matching (65 patients per group), no significant differences were observed in rates of 30-day mortality (7.7% in ER and 6.2% in OS; P = 1) and paraplegia (9.2% and 10.8%; P = 1). Any SCI, renal insufficiency, and respiratory insufficiency were 12.3% and 20% ( P = .34), 9.2% and 12.3% ( P = .78), and 0% and 12.3% ( P = .006) in ER and OS, respectively. The incidence of the composite end point was significantly lower in ER patients (18.5% in ER vs 36.0% in OS; P =.03). According to Kaplan-Meier estimates, all-cause survival at 24 months was 82.8% in ER and 84.9% in OS, with rates unchanged at 42 months ( P = .9). Rates of freedom from reintervention were 91.0% vs 89.7% at 24 months and 80.0% vs 79.9% at 42 months in ER vs OS, respectively ( P = .3). Conclusions A propensity score analysis in patients with TAAA undergoing repair suggests an early benefit from ER compared with OS with regard to the composite end point because of reduced 30-day respiratory complications. No significant differences were found in SCI and renal insufficiency at 30 days and in survival and reintervention rates at midterm.
Objective This study evaluates the safety and effectiveness of a unique composite thoracic endovascular aneurysm repair (TEVAR) construct (proximal stent graft and distal bare metal stent) for the ...treatment of patients with complicated type B aortic dissection (cTBAD). Methods In this prospective, single-arm, multicenter study, patients with cTBAD were treated with an endovascular system consisting of proximal TX2 thoracic stent grafts and distal bare metal dissection stents (Zenith Dissection Endovascular System; Cook Medical, Bloomington, Ind). Indications for enrollment were branch vessel malperfusion, impending rupture, aortic diameter ≥40 mm, rapid aortic expansion, and persistent pain or hypertension despite maximum medical therapy. One-year follow-up results, including clinical and radiographic (computerized tomography CT and X-ray) evaluation, were available for this report. Results Ten centers enrolled 40 patients (70% men; mean age 58 years old) between December 2007 and August 2009. The onset of symptoms was acute (≤14 days) in 24 patients (60%), subacute (15-30 days) in six patients (15%), and chronic (31-90 days) in 10 patients (25%); the overall mean time from symptom onset to treatment was 20 days (range, 0-78 days). A majority of patients (77.5%; 31 of 40 patients) presented with impending aortic rupture (indicated by periaortic effusion/hematoma) or branch vessel malperfusion. Seven combinations of stent grafts and dissection stents were used, and all devices were successfully deployed and patent. The 30-day mortality rate was 5% (2 of 40); two deaths occurred after 30 days, leading to a 1-year survival rate of 90%. Two deaths, occurring at 11 and 81 days postprocedure, respectively, were secondary to aortic rupture. Morbidity occurring within 30 days included stroke (7.5%), transient ischemic attack (2.5%), paraplegia (2.5%), retrograde progression of dissection (5%), and renal failure (12.5%). Additional morbidity after 30 days included one case of retrograde progression of dissection and one case of renal failure. None of the patients with renal failure became dialysis-dependent. Four patients (10%) underwent secondary interventions within 1 year. Favorable aortic remodeling was observed during the course of follow-up, indicated by an increase in the true lumen size and a concomitant decrease in the false lumen size along the dissected aorta, with completely thrombosed thoracic false lumen observed in 31% of patients at 12 months as compared to 0% at baseline. Conclusions Initial data with a composite TEVAR construct have demonstrated favorable clinical and anatomic results. Continued enrollment and long-term data are needed to assess the overall effectiveness of this treatment strategy.
Plasma electrolytic oxidation (PEO) is proven as a scalable method for surface treatment of titanium (Ti) providing a thick oxide layer with porous micro-nano morphology. Despite the lack of ...antibacterial performance, this modification has potential to improve the osseointegration properties of Ti-based implant. To address this limitation, we demonstrated a new concept, showing that partial incorporation of graphene oxide (GO) to porous-PEO Ti-surface can significantly improve its antibacterial performance. Our idea for partial coating compared with a full surface coverage of GO was motivated to create a mixed surface with porous PEO and GO to improve antibacterial ability, while maintaining the osseointegration properties. To achieve these goals, we combined PEO and electrophoretic deposition process (EPD) to deposit GO sheets over the titanium PEO-treated substrate. The SEM, EDS, optical profilometry, XRD and Raman spectroscopy confirmed the growth of unique multi-structured porous PEO structures decorated with GO patches. The bio-mineralization test provided the evidence of hydroxyapatite formation over the PEO-GO surface, indicating its good bioactivity. Finally, PEO-GO samples demonstrated a superior antibacterial rate of ~80% against E.coli and ~100% against S. aureus. These results indicate that PEO-GO modified titanium substrates are very promising for the development of advanced biomedical implants.
Display omitted
•Plasma Electrolytic Oxidation (PEO) and Electrophoretic Deposition (ED) are combined for Graphene Oxide deposition (GO).•Partial deposition of (GO) sheets on PEO anodized titanium as new antibacterial surface is demonstrated.•The optimized deposition with 60% GO surface coverage is found as the best performing.•Antibacterial activity ~80% against E.coli and ~100% against S. aureus bacteria is achieved.
Complex aortic aneurysms (juxtarenal aortic aneurysms JAAA, pararenal aortic aneurysms PAAAs, thoracoabdominal aortic aneurysms TAAAs) are treated with increasing frequency through fenestrated and ...branched endovascular repair (F/B-EVAR); however, the outcome of these procedures is usually reported separately by single experiences and wider overviews are not frequent. The aim of this study was therefore to report an Italian experience analyzing the results obtained in four academic centers to evaluate the predictors of outcomes.
Between 2008 and 2019, all consecutive patients undergoing F/B-EVAR in four Italian university centers were recorded prospectively and analyzed retrospectively. Preoperative comorbidities and postoperative complications were classified according with the Society for Vascular Surgery reporting standard. Postoperative complications and 30-day/in-hospital mortality were assessed as early outcomes. Survival, freedom from reinterventions and target visceral vessels patency were assessed as follow-up outcomes by Kaplan-Meier analysis. Risk factors for 30-day/in-hospital mortality and spinal cord ischemia (SCI) were determined by multivariate analysis. Risk factors for follow-up mortality and reinterventions were evaluated by Cox regression model.
Five hundred ninety-six patients underwent F/B-EVAR for 124 JAAAs (21%), 121 PAAAs (20%), and 351 TAAAs (59%). Elective and urgent procedures were performed in 520 (87%) and 76 (13%) cases, respectively. Postoperative cardiac, pulmonary, and renal complications were reported in 41 (7%), 50 (8%), and 80 (13%) patients, respectively. Seven bowel ischemia (1%) and 23 cerebrovascular complications (4%) occurred. Forty-seven (8%) patients suffered SCI with 17 cases (3%) of permanent paraplegia. Crawford's extent I-II-III TAAAs (odds ratio OR, 13.41; 95% confidence interval CI, 1.77-101.65; P = .012) and postoperative renal complications (OR, 3.84; 95% CI, 1.70-8.69; P = .001) independently predicted SCI. Thirty-two patients (5%) died in the perioperative period. Preoperative chronic renal failure (OR, 7.81; 95% CI, 7.81-26.31; P = .001), postoperative bowel ischemia (OR, 26.97; 95% CI, 3.37-215.5; P = .002), cardiac complications (OR, 5.77; 95% CI, 1.41-23.64; P ≤ .001), cerebrovascular complications (OR, 28.63; 95% CI, 5.20-157.5; P < .001), and SCI (OR, 5.99; 95% CI, 1.12-32.5; P = .036) were independently correlated with 30-day/in-hospital mortality. The mean follow-up was 25 ± 7 months. Freedom from target visceral vessels occlusion and freedom from reintervention were 96% and 92% at 1 year and 93% and 85% at 3 years, respectively. TAAAs (hazard ratio HR. 3.16; 95% CI, 1.68-5.92; P ≤ .001), postdissection TAAAs (HR, 2.20; 95% CI, 1.30-4.90; P = .05) and postoperative bowel ischemia (HR, 11.98; 95% CI, 1.53-93.31; P = .018) were independent predictors of reinterventions. Survival was 88% and 78% at 1 and 3 years, respectively. Preoperative chronic renal failure (HR, 2.39; 95% CI, 1.59-3.59; P ≤ .001), urgent repair (HR, 1.80; 95% CI, 1.03-3.20; P = .039), TAAAs (HR, 2.01; 95% CI, 1.13-3.56; P = .017), postoperative bowel ischemia (HR, 5.55; 95% CI, 2.11-14.59; P = .001), cardiac complications (HR, 3.89; 95% CI, 2.25-6.71; P ≤ .001), and pulmonary complications (HR, 1.97; 95% CI, 1.56-3.35; P = .013) were independent predictors of mortality during follow-up.
F/B-EVAR is associated with satisfactory midterm outcomes in a nationwide experience. A variety of risk factors should be considered in F/B-EVAR indications and postoperative patient management to decrease the risk of postoperative complications and improve midterm outcomes.
Display omitted
Background The PETTICOAT (Provisional ExTension to Induce COmplete ATtachment) technique may be employed during endovascular treatment of type B aortic dissection (TBD) using self-expandable bare ...stents distal to the covered stent graft placed over the proximal entry tear. The aim of this study is to evaluate the volume changes of the true (TL) and false lumen (FL) on computed tomography (CT) scans. Methods Since 2005, 25 selected patients received endovascular treatment for complicated TBD with the PETTICOAT technique employing the Zenith Dissection Endovascular System (William Cook Europe, Bjaerverskov, Denmark). Indications to the use of the PETTICOAT technique were the evidence of clinical manifest dynamic malperfusion in five cases (20%) and/or radiologic evidence of TL collapse in 20 cases (80%). Five patients were treated within 2 weeks from onset, 13 patients between 2 weeks and 3 months, and seven patients over 3 months after the initial acute event. The volumetric analysis of the changes of TL and FL obtained from CT scan performed before endovascular treatment of TBD, postoperatively and yearly thereafter were analyzed using the OsiriX software v 3.9 (Pixmeo sarl, Bernex, Switzerland). Results Initial clinical (30 days) and midterm clinical success was observed in 21 cases (84%) and in 23 cases (92%), respectively. The volumes of the aortic TL and FL were evaluated at 30 days and midterm follow-up (mean, 38 ± 17 months). The following TL volumes were recorded: baseline 84 ± 29 cm3 , postoperative 167 ± 31 cm3 (+98%), 1 year 193 ± 46 cm3 (+131%), and 2 years 216 ± 54 cm3 (+140%). The following FL volumes were recorded: baseline 332 ± 86 cm3 , postoperative 286 ± 85 cm3 (−14%), 1 year 233 ± 81 cm3 (−30%), and 2 years 248 ± 112 cm3 (−32%). Progressive remodeling of the TL was recorded over time in both thoracic and abdominal segments with shrinkage of the FL mainly in the thoracic segment. Conclusions These data provide insight into potential therapeutic benefit of the PETTICOAT technique. A significant immediate increase in TL could be achieved with resolution of all cases of dynamic malperfusion and TL collapse. A different behavior of volumes in the thoracic and abdominal segments was observed.
Inability to form new memories is an early clinical sign of Alzheimer's disease (AD). There is ample evidence that the amyloid-β (Aβ) peptide plays a key role in the pathogenesis of this disorder. ...Soluble, bio-derived oligomers of Aβ are proposed as the key mediators of synaptic and cognitive dysfunction, but more tractable models of Aβ-mediated cognitive impairment are needed. Here we report that, in mice, acute intracerebroventricular injections of synthetic Aβ₁₋₄₂ oligomers impaired consolidation of the long-term recognition memory, whereas mature Aβ₁₋₄₂ fibrils and freshly dissolved peptide did not. The deficit induced by oligomers was reversible and was prevented by an anti-Aβ antibody. It has been suggested that the cellular prion protein (PrPC) mediates the impairment of synaptic plasticity induced by Aβ. We confirmed that Aβ₁₋₄₂ oligomers interact with PrPC, with nanomolar affinity. However, PrP-expressing and PrP knock-out mice were equally susceptible to this impairment. These data suggest that Aβ₁₋₄₂ oligomers are responsible for cognitive impairment in AD and that PrPC is not required.
See Sastre et al. (doi:10.1093/brain/awy225) for a scientific commentary on this article.
Traumatic brain injury (TBI) is a risk factor for subsequent neurodegenerative disease. Zanier et al. report ...that single severe TBI induces tau pathology in humans and mice. Studies in the latter provide evidence that this pathology is self-propagating and can be transmitted between animals, causing brain dysfunction like a prion.
Abstract
Traumatic brain injury is a risk factor for subsequent neurodegenerative disease, including chronic traumatic encephalopathy, a tauopathy mostly associated with repetitive concussion and blast, but not well recognized as a consequence of severe traumatic brain injury. Here we show that a single severe brain trauma is associated with the emergence of widespread hyperphosphorylated tau pathology in a proportion of humans surviving late after injury. In parallel experimental studies, in a model of severe traumatic brain injury in wild-type mice, we found progressive and widespread tau pathology, replicating the findings in humans. Brain homogenates from these mice, when inoculated into the hippocampus and overlying cerebral cortex of naïve mice, induced widespread tau pathology, synaptic loss, and persistent memory deficits. These data provide evidence that experimental brain trauma induces a self-propagating tau pathology, which can be transmitted between mice, and call for future studies aimed at investigating the potential transmissibility of trauma associated tau pathology in humans.
PDF
