An international, multispecialty, expert-based Delphi Consensus document on controversial issues in the management of patients with asymptomatic and symptomatic carotid stenosis.

OBJECTIVE: Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear. METHODS: Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response. RESULTS: Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence. CONCLUSIONS: The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research.

Exploring vertebral artery stump syndrome: An overlooked cause of posterior ischemic strokes. A narrative review of current management options.

INTRODUCTION: Stump syndrome is defined as a clinical syndrome resulting from a distal intracranial vessel embolic stroke due to an extracranial vessel occlusion. Similar to the anterior circulation, the recurrence of ischemic strokes in territories supplied by the posterior circulation in the presence of vertebral artery occlusion is termed Vertebral Artery Stump Syndrome (VASS). MATERIAL AND METHODS: We conducted a literature review, identifying 72 patients with transient ischemic attacks (TIAs) or ischemic strokes attributed to VASS, according to Kawano criteria. We categorized all patients in two groups focusing on the therapeutic management those who underwent primary medical treatment and those who received endovascular or surgical treatment either in acute or chronic phase. RESULTS: In the anticoagulant therapy group, only 1 patient had a stroke recurrence. Among the 4 on antiplatelets, all had recurrences, but 3 benefited from switching to anticoagulants or endovascular therapy. In the endovascular therapy group, worse outcomes were linked to acute large vessel occlusion. Endovascular treatment of the vertebral artery, in a chronic phase, was explored in literature for recurrent TIAs or minor strokes suggesting that this could be a viable therapeutic alternative when medical treatment failed in preventing recurrence of ischemic stroke. CONCLUSIONS: Some studies suggest that anticoagulant medical therapy may be beneficial for VASS and endovascular therapy has also been reported for selected patients. However, data on treatment outcomes and prognosis are still underreported, making treatment decisions challenging. Randomized Controlled Trials are needed to establish the optimal treatment approach.

Red and Blue Light Differently Influence Actinidia chinensis Performance and Its Interaction with Pseudomonas syringae pv. Actinidiae.

Light composition modulates plant growth and defenses, thus influencing plant-pathogen interactions. We investigated the effects of different light-emitting diode (LED) red (R) (665 nm) and blue (B) (470 nm) light combinations on Actinidia chinensis performance by evaluating biometric parameters, chlorophyll a fluorescence, gas exchange and photosynthesis-related gene expression. Moreover, the influence of light on the infection by Pseudomonas syringae pv. actinidiae (Psa), the etiological agent of bacterial canker of kiwifruit, was investigated. Our study shows that 50%R-50%B (50R) and 25%R-75%B (25R) lead to the highest PSII efficiency and photosynthetic rate, but are the least effective in controlling the endophytic colonization of the host by Psa. Monochromatic red light severely reduced ΦPSII, ETR, Pn, TSS and photosynthesis-related genes expression, and both monochromatic lights lead to a reduction of DW and pigments content. Monochromatic blue light was the only treatment significantly reducing disease symptoms but did not reduce bacterial endophytic population. Our results suggest that monochromatic blue light reduces infection primarily by modulating Psa virulence more than host plant defenses.

Optimal Management of Asymptomatic Carotid Stenosis in 2021: The Jury is Still Out. An International, Multispecialty, Expert Review and Position Statement.

OBJECTIVES: The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement is to reconcile the conflicting views on the topic. MATERIALS AND METHODS: A literature review was performed with a focus on data from recent studies. RESULTS: Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients < 75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses. CONCLUSIONS: Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients.

Inframalleolar bypass for chronic limb-threatening ischemia.

The aims of this study were to analyze the results of inframalleolar bypass for chronic limb-threatening ischemia (CLTI) and to identify outcome-predicting factors. All consecutive patients undergoing inframalleolar bypass for CLTI between 2015 and 2018 were included in this retrospective, single-center study. Outflow artery was the most proximal patent vessel segment in continuity with inframalleolar arteries. Bypasses originating from the popliteal artery were defined as 'short bypasses'. Sixty patients underwent inframalleolar bypass, with four patients undergoing bilateral procedures, making a total of 64 limbs included. The mean age was 73 ± 14 and 52 (81%) were male. The great saphenous vein was the preferred conduit (n = 58, 91%), in a devalvulated fashion (n = 56, 88%). Superficial femoral artery was the most common inflow artery for 'long' grafts (n = 22, 34%), while popliteal artery was the inflow artery for all 'short' grafts (n = 25, 39%). Dorsalis pedis artery was chosen as an outflow artery in 41 patients (63%). Median follow-up was 21 months. Two-year primary and secondary patency, limb salvage, amputation-free survival, and overall survival rates were 67 ± 6%, 88 ± 4%, 84 ± 4%, 72 ± 6%, and 85 ± 4%, respectively. At multivariate analysis, dialysis was an independent predictor for poor primary patency (HR, 4.6; 95% CI, 1.62-13.05; p = 0.004), whereas a short bypass was independently associated with an increased primary patency (HR, 0.3; 95% CI, 0.10-0.89; p = 0.03). In conclusion, bypass grafting to the inframalleolar arteries resulted in good patency rates, limb salvage and overall survival. Dialysis patients had lower primary patency but still had good limb salvage and survival. Short bypass was a predictor of improved primary patency.

Comparison of Outcomes Following EVAR Based on Aneurysm Diameter and Volume and Their Postoperative Variations.

PURPOSE: to evaluate the impact of bi- and 3-dimensional preoperative aortic morphological features and their immediate postoperative variations on the outcome of abdominal aortic aneurysms (AAA) treated by endovascular exclusion with standard devices (EVAR). MATERIALS AND METHODS: Double centre retrospective analysis of prospectively collected registry data of EVAR patients. For all patients, preoperative and 30-day computed tomographic angiography images (CTA) were reviewed. Preoperative maximum AAA diameter >59 mm and volume >159 cm3, and any 30-day postoperative increasing at CTA, were considered as potentially influencing the outcome. The outcome measures were: primary technical success; 30-day, 1-year, and mean follow-up reintervention, all-cause and AAA-related mortality rates, and also endoleak-related reinterventions. RESULTS: Three hundred and thrity-three patients were enrolled. Mean preoperative and 30-day AAA diameter and volume were 50.4 mm ± 11.8 vs. 49.1 mm ± 12.1, and 112.9 cm3 ± 79.5 vs. 112.1 cm3 ± 80.5, respectively. Primary technical success was achieved in all cases. At 34.9 months follow-up, cumulative reintervention rate was 12.0%, mortality rates 7.2%, without AAA-related deaths. Endoleak-related reintervention rate was 7.5%. At uni- and multi-variate analysis, preoperative AAA diameter >59 mm, and AAA volume >159 cm3 were significantly associated to reintervention (P = 0.012; P = 0.002), and reintervention and death (P = 0.002; P = 0.001) during follow-up. Additionally, any increase in postoperative AAA diameter or volume was significantly associated with reintervention (P = 0.001, P = 0.001) and reintervention and death (P = 0.006, P = 0.001). Endoleak-related reintervention were also significantly associated with all of the analysed morphological parameters (P = 0.019, P = 0.005, P = 0.005, and P = 0.002, respectively). CONCLUSIONS: Patients with larger baseline AAA size and volume as well as unfavourable early remodelling of the sac are associated to worse long-term EVAR outcome.

3D Printing in Cardiovascular Disease: Current Applications and Future Perspectives.

Three-dimensional (3D) printing is emerging as an innovative tool for a tailored approach to endovascular or open procedures. The efforts of different specialists and data analysis can be used to fabricate patient-specific implants, which might have significant impact even in life-saving procedures such as aortic dissections or aortic arch aneurysm. 3D printing is gradually changing the traditional pattern of diagnosis and treatment. This innovative approach allows a perfect match between the patient's anatomy and the prosthetic graft, ideally resulting in better hemodynamics and improved long-term patency related to reduced turbulent flow. Future applications of 3D printing in the cardiovascular field combined with tissue engineering will enhance the therapeutic features of bioprinted tissues and scaffolds for regenerative medicine. This review will summarize the clinical significance of 3D printing in cardiovascular disease, exploring current applications, translational outlooks and future perspectives.

A Breach in Plant Defences: Pseudomonas syringae pv. actinidiae Targets Ethylene Signalling to Overcome Actinidia chinensis Pathogen Responses.

Ethylene interacts with other plant hormones to modulate many aspects of plant metabolism, including defence and stomata regulation. Therefore, its manipulation may allow plant pathogens to overcome the host's immune responses. This work investigates the role of ethylene as a virulence factor for Pseudomonas syringae pv. actinidiae (Psa), the aetiological agent of the bacterial canker of kiwifruit. The pandemic, highly virulent biovar of this pathogen produces ethylene, whereas the biovars isolated in Japan and Korea do not. Ethylene production is modulated in planta by light/dark cycle. Exogenous ethylene application stimulates bacterial virulence, and restricts or increases host colonisation if performed before or after inoculation, respectively. The deletion of a gene, unrelated to known bacterial biosynthetic pathways and putatively encoding for an oxidoreductase, abolishes ethylene production and reduces the pathogen growth rate in planta. Ethylene production by Psa may be a recently and independently evolved virulence trait in the arms race against the host. Plant- and pathogen-derived ethylene may concur in the activation/suppression of immune responses, in the chemotaxis toward a suitable entry point, or in the endophytic colonisation.

Pseudomonas syringae pv. actinidiae: Ecology, Infection Dynamics and Disease Epidemiology.

Since 2008, the kiwifruit industry has been devastated by a pandemic outbreak of Pseudomonas syringae pv. actinidiae (Psa), the causal agent of bacterial canker. This disease has become the most significant limiting factor in kiwifruit production. Psa colonizes different organs of the host plant, causing a specific symptomatology on each of them. In addition, the systemic invasion of the plant may quickly lead to plant death. Despite the massive risk that this disease poses to the kiwifruit industry, studies focusing on Psa ecology have been sporadic, and a comprehensive description of the disease epidemiology is still missing. Optimal environmental conditions for infection, dispersal and survival in the environment, or the mechanisms of penetration and colonization of host tissues have not been fully elucidated yet. The present work aims to provide a synthesis of the current knowledge, and a deeper understanding of the epidemiology of kiwifruit bacterial canker based on new experimental data. The pathogen may survive in the environment or overwinter in dormant tissues and be dispersed by wind or rain. Psa was observed in association with several plant structures (stomata, trichomes, lenticels) and wounds, which could represent entry points for apoplast infection. Environmental conditions also affect the bacterial colonization, with lower optimum values of temperature and humidity for epiphytic than for endophytic growth, and disease incidence requiring a combination of mild temperature and leaf wetness. By providing information on Psa ecology, these data sets may contribute to plan efficient control strategies for kiwifruit bacterial canker.

N-Acyl Homoserine Lactones and Lux Solos Regulate Social Behaviour and Virulence of Pseudomonas syringae pv. actinidiae.

The phyllosphere is a complex environment where microbes communicate through signalling molecules in a system, generally known as quorum sensing (QS). One of the most common QS systems in Gram-negative proteobacteria is based on the production of N-acyl homoserine lactones (AHLs) by a LuxI synthase and their perception by a LuxR sensor. Pseudomonas syringae pv. actinidiae (Psa), the aetiological agent of the bacterial canker of kiwifruit, colonises plant phyllosphere before penetrating via wounds and natural openings. Since Psa genome encodes three LuxR solos without a cognate LuxI, this bacterium may perceive diffusible signals, but it cannot produce AHLs, displaying a non-canonical QS system. The elucidation of the mechanisms underlying the perception of environmental cues in the phyllosphere by this pathogen and their influence on the onset of pathogenesis are of crucial importance for a long-lasting and sustainable management of the bacterial canker of kiwifruit. Here, we report the ability of Psa to sense its own population density and the presence of surrounding bacteria. Moreover, we show that Psa can perceive AHLs, indicating that AHL-producing neighbouring bacteria may regulate Psa virulence in the host. Our results suggest that the ecological environment is important in determining Psa fitness and pathogenic potential. This opens new perspectives in the use of more advanced biochemical and microbiological tools for the control of bacterial canker of kiwifruit.

Minimally Invasive Open Conversion for Late EVAR Failure.

OBJECTIVE: With the increasing use of endovascular aortic aneurysm repair (EVAR), open repair after aortic stent grafting is of growing interest. The surgical conversion treatment may be a very challenging process with high mortality and in-hospital complication rates. The aim of this article is to present our experience in patients with EVAR failure treated by minimally invasive open conversion (MOC) and its technical aspects. METHODS: A retrospective study was conducted on a prospectively compiled computerized database of consecutive patients treated by MOC at our institution between May 2014 and June 2018. Indications for treatment were endoleaks with sac growth at least >5 mm in the last 6 months and failure of previous endovascular tentative for aneurysm sealing. Demographics of the patients, reason for conversion, previous endovascular procedures, surgical outcomes, and survival were reviewed. MOC was performed by a small abdominal incision, infrarenal clamping, and partial explantation of the endograft in all patients. RESULTS: A total of 10 patients were treated during the study period. The mean interval to MOC after EVAR was 45.1 months (range, 14-128). Indications for MOC included type Ia endoleak in three patients (30%), persistent type II EL in four (40%), and type III EL in one patient (10%), indeterminate or type V EL in two (20%). At 30 days, no deaths or reinterventions were reported, and major complication rate was 10% (one postoperative pneumonia). At mean follow-up of 22.9 ± 15.9 months, no reinterventions were described. Death rate was (20%) with one aneurysm-related death (10%) for graft infection 32 months after MOC and one (10%) cardiac event at 18 months. CONCLUSIONS: Despite the potential high risk of open conversion, MOC appears to be a safe surgical solution for EVAR failure. This potentially challenging operation may be improved with minimally invasive techniques that are presented.

Externally Supported Extra-anatomical Venous Bypass to Treat Upper Limb Ischemia with Shoulder Prosthetic Infection.

To report a case of acute arm ischemia and prosthetic shoulder infection treated by extra-anatomical great saphenous vein graft with external vascular scaffolding. A 65 year-old man with multiple surgical interventions for soft tissue sarcoma of the right shoulder, local radiotherapy with residual brachial plexus neuropraxia, was referred to our attention for signs of arm ischemia. Two weeks before, the patient was submitted to prosthetic shoulder replacement complicated with prosthetic infection. Considering the mechanism of vascular injury, an open surgical revascularization was planned with a deliberate avoidance of the natural anatomic pathway to reduce the risk of graft infection. Consequently, after the complete removal of infected shoulder prosthesis and placement of antibiotic spacer, an axillarbrachial artery bypass using great saphenous vein was performed using a new braided cobalt chrome kink resistant external vascular support to prevent compression, also considering the extra-anatomical position of the graft. At 12 months' follow-up, patient was in good clinical condition with complete resolution of arm ischemia; computed tomographic angiography and duplex scan revealed patency of the graft with excellent distal perfusion. The new external vascular support seems to be useful and feasible for preventing compression of extra-anatomical venous bypass.

Simultaneous Superficial Femoral Artery Angioplasty/Stent Plus Popliteal Distal Bypass for Limb Salvage.

BACKGROUND: Treatment of severe critical limb ischemia (CLI) due to superficial femoral artery (SFA) and below-the-knee (BTK) vessels' involvement could be compromised by the lack of a great saphenous vein (GSV) suitable in its entire length. The purpose of this study is to assess the efficacy of a hybrid endovascular and open lower limbs arterial reconstruction in these patients with multilevel, advanced CLI. METHODS: From 2005 to 2019, we performed hybrid endovascular and surgical treatment for limb salvage in SFA-BTK CLI. This consisted of percutaneous transluminal angioplasty (PTA) with or without stenting of the SFA, along with distal origin vein graft bypass. Inclusion criteria were Rutherford category 5 or 6, lack of a suitable GSV, patency of the popliteal artery, steno-obstructive lesions of the SFA, lesions of the 3 crural vessels >5 cm in length each. The follow-up was performed with duplex scan surveillance of both the bypass graft and PTA sites. RESULTS: The hybrid treatment could be performed in 34 patients. Fifty-six percent of the SFA steno-obstructive lesions were treated with simple PTA, except for the application of a bare metal stent in one patient (3%), while in all the SFA occlusions PTA was completed with covered stents (41%). Thirty-four popliteal-to-distal vein bypass grafts bypass grafts have been performed. There were no perioperative PTA or bypass graft failures. Clinical improvement was achieved in 26 (76%) patients. Overall, primary and secondary patency, limb salvage, and survival rates were 65%, 68%, 75%, and 75% at 5 years, respectively. CONCLUSIONS: A hybrid strategy in multilevel SFA-BTK CLI is a well-established approach. Additional studies are warranted to validate these results.

Reinnervation of the Diaphragm After Bilateral Phrenic Nerve Resection and Immediate Reconstruction Using a Contralateral Phrenic Nerve Autograft.

A patient affected by a voluminous synovial sarcoma of mediastinum received radical surgery, resulting in injury of both phrenic nerves. Because of the cancer location, reconstruction of the left phrenic nerve was not possible, so to prevent the patient's ventilator dependence, the right phrenic nerve was reconstructed via an autograft from the residual proximal stump of the contralateral one. In 3 months, the right hemidiaphragm function showed a full recovery, documented by ultrasonographic and radiographic assessment of diaphragmatic excursion, and the patient was weaned from mechanical ventilation. When a nerve autograft is indicated, the sural nerve still remains the criterion standard, because of the low morbidity of the donor site and ease of harvesting; however, in particular situations, such as in this unique case, the choice of an orthotopic graft may offer promising results.

Apple fruit superficial scald resistance mediated by ethylene inhibition is associated with diverse metabolic processes.

Fruits stored at low temperature can exhibit different types of chilling injury. In apple, one of the most serious physiological disorders is superficial scald, which is characterized by discoloration and brown necrotic patches on the fruit exocarp. Although this phenomenon is widely ascribed to the oxidation of α-farnesene, its physiology is not yet fully understood. To elucidate the mechanism of superficial scald development and possible means of prevention, we performed an integrated metabolite screen, including an analysis of volatiles, phenols and lipids, together with a large-scale transcriptome study. We also determined that prevention of superficial scald, through the use of an ethylene action inhibitor, is associated with the triggering of cold acclimation-related processes. Specifically, the inhibition of ethylene perception stimulated the production of antioxidant compounds to scavenge reactive oxygen species, the synthesis of fatty acids to stabilize plastid and vacuole membranes against cold temperature, and the accumulation of the sorbitol, which can act as a cryoprotectant. The pattern of sorbitol accumulation was consistent with the expression profile of a sorbitol 6-phosphate dehydrogenase, MdS6PDH, the overexpression of which in transgenic Arabidopsis thaliana plants confirmed its involvement in the cold acclimation and freezing tolerance.

Biological control of bacterial plant diseases with Lactobacillus plantarum strains selected for their broad-spectrum activity.

The use of lactic acid bacteria (LAB) to control multiple pathogens that affect different crops was studied, namely, Pseudomonas syringae pv. actinidiae in kiwifruit, Xanthomonas arboricola pv. pruni in Prunus and Xanthomonas fragariae in strawberry. A screening procedure based on in vitro and in planta assays of the three bacterial pathogens was successful in selecting potential LAB strains as biological control agents. The antagonistic activity of 55 strains was first tested in vitro and the strains Lactobacillus plantarum CC100, PM411 and TC92, and Leuconostoc mesenteroides CM160 and CM209 were selected because of their broad-spectrum activity. The biocontrol efficacy of the selected strains was assessed using a multiple-pathosystem approach in greenhouse conditions. L. plantarum PM411 and TC92 prevented all three pathogens from infecting their corresponding plant hosts. In addition, the biocontrol performance of PM411 and TC92 was comparable to the reference products (Bacillus amyloliquefaciens D747, Bacillus subtilis QST713, chitosan, acibenzolar-S-methyl, copper and kasugamycin) in semi-field and field experiments. The in vitro inhibitory mechanism of PM411 and TC92 is based, at least in part, on a pH lowering effect and the production of lactic acid. Moreover, both strains showed similar survival rates on leaf surfaces. PM411 and TC92 can easily be distinguished because of their different multilocus sequence typing and random amplified polymorphic DNA profiles.

Comparative transcriptome analysis of the interaction between Actinidia chinensis var. chinensis and Pseudomonas syringae pv. actinidiae in absence and presence of acibenzolar-S-methyl.

BACKGROUND: Since 2007, bacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa) has become a pandemic disease leading to important economic losses in every country where kiwifruit is widely cultivated. Options for controlling this disease are very limited and rely primarily on the use of bactericidal compounds, such as copper, and resistance inducers. Among the latter, the most widely studied is acibenzolar-S-methyl. To elucidate the early molecular reaction of kiwifruit plants (Actinidia chinensis var. chinensis) to Psa infection and acibenzolar-S-methyl treatment, a RNA seq analysis was performed at different phases of the infection process, from the epiphytic phase to the endophytic invasion on acibenzolar-S-methyl treated and on non-treated plants. The infection process was monitored in vivo by confocal laser scanning microscopy. RESULTS: De novo assembly of kiwifruit transcriptome revealed a total of 39,607 transcripts, of which 3360 were differentially expressed during the infection process, primarily 3 h post inoculation. The study revealed the coordinated changes of important gene functional categories such as signaling, hormonal balance and transcriptional regulation. Among the transcription factor families, AP2/ERF, MYB, Myc, bHLH, GATA, NAC, WRKY and GRAS were found differentially expressed in response to Psa infection and acibenzolar-S-methyl treatment. Finally, in plants treated with acibenzolar-S-methyl, a number of gene functions related to plant resistance, such as PR proteins, were modulated, suggesting the set-up of a more effective defense response against the pathogen. Weighted-gene coexpression network analysis confirmed these results. CONCLUSIONS: Our work provides an in-depth description of the plant molecular reactions to Psa, it highlights the metabolic pathway related to acibenzolar-S-methyl-induced resistance and it contributes to the development of effective control strategies in open field.

The Pivotal Role of Copper in Neurodegeneration: A New Strategy for the Therapy of Neurodegenerative Disorders.

Copper is an essential trace element for the human body since it is a cofactor of several enzymes and proteins and plays a pivotal role in several biological functions (e.g., respiration, protection from oxidative damage, iron metabolism, etc.), also including the central nervous system development and functioning (e.g., synthesis of neurotransmitters, myelination, activation of neuropeptides, etc.). Therefore, copper dysmetabolism is associated with different toxic effects, mainly represented by oxidative stress, and it has been reported in many neurodegenerative disorders, such as Wilson's disease, Menkes disease, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This paper shows a detailed report of how copper is involved in the pathophysiology of these diseases. Moreover, a hint on novel therapeutic approaches based on restoring copper homeostasis through metal chelators will be pointed out.

Radioligands for positron emission tomography imaging of cannabinoid type 2 receptor.

The cannabinoid type 2 (CB2) receptor is an immunomodulatory receptor mainly expressed in peripheral cells and organs of the immune system. The expression level of CB2 in the central nervous system under physiological conditions is negligible, however under neuroinflammatory conditions an upregulation of CB2 protein or mRNA mainly colocalized with activated microglial cells has been reported. Consequently, CB2 agonists have been confirmed to play a role in neuroprotective and anti-inflammatory processes. A suitable positron emission tomography radioligand for imaging CB2 would provide an invaluable research tool to explore the role of CB2 receptor expression in inflammatory disorders. In this review, we provide a summary of so far published CB2 radioligands as well as their in vitro and in vivo binding characteristics.

Initial clinical experience with a polytetrafluoroethylene vascular dialysis graft reinforced with nitinol at the venous end.

OBJECTIVE: The purpose of this study was to examine the outcomes of a vascular hybrid polytetrafluoroethylene (PTFE) graft, provided with a nitinol-reinforced section (NRS) on one end, in hemodialysis vascular access placement. METHODS: A retrospective study was conducted including all the consecutive patients who underwent Gore Hybrid Vascular Graft (GHVG; W. L. Gore & Associates, Flagstaff, Ariz) implantation for hemodialysis access placement between October 2013 and November 2015. A propensity-matched control group was obtained from consecutive patients who underwent standard PTFE arteriovenous graft implantation between January 2010 and July 2013. The selection criteria were inadequate venous material for autogenous arteriovenous fistula placement, patent deep venous circulation, and vein diameter of 4 to 8.5 mm. The implantation technique involves the insertion of the NRS some centimeters into the target vein. Fluoroscopic guidance helps deploy the device in the desired landing zone (ie, position of the proximal end of the NRS), based on anatomic landmarks. Survival, functional patency rates, and complications were compared with a propensity-matched historical control group. Vein diameter, previous vascular access placement, and diabetes were tested as predictors of reintervention with a logistic regression analysis. RESULTS: There were 32 patients (14 men; mean age, 69 ± 14 years) who received the GHVG graft. The historical control group included 43 patients. Technical success was 100%. The graft configuration was brachial-axillary (n = 22 [69%]), brachial-basilic loop (n = 5 [16%]), brachial-antecubital loop (n = 3 [9%]), axilloaxillary loop (n = 1 [3%]), and femoral-femoral loop (n = 1 [3%]). Mean NRS oversize was 20% ± 7% (range, 3%-34%; median, 19%). Perioperative complications requiring revision included acute limb ischemia treated with thrombectomy (n = 1 [3%]) and graft infection requiring explantation (n = 2 [6%]). Two patients (6%) died in the hospital of unrelated causes. The mean follow-up was 15 ± 11 months (range, 0-33 months; median, 15.5). The propensity-matched groups included 25 patients each. Survival estimates at 24 months for the GHVG and standard PTFE groups were 91% ± 6% and 82% ± 9% (P > .05), respectively. The 12-month patency estimates were as follows: functional primary patency, 66% ± 10% vs 51% ± 10% (P > .05); functional assisted primary patency, 75% ± 9% vs 51% ± 10% (P > .05); and functional secondary patency, 79% ± 9% vs 67% ± 10% (P > .05). Reduction in vein diameter was associated with reintervention. CONCLUSIONS: The GHVG is a safe and effective alternative to standard PTFE in hemodialysis access surgery. Careful planning for the landing zone is advisable, especially for small outflow veins. Larger studies and randomized trials are needed to define the role for this device. A study including a greater number of centers experienced with this device is currently under way.