External Scaffold for Venous Graft to Treat Chronic Limb-Threatening Ischemia: Results of the FRAME Vascular Support.

Background: The surgical treatment of chronic limb-threatening ischemia and optimal conduit choice are extensively debated. The presence of suboptimal autologous material, such as varicosities or venous aneurysms, might impair long-term outcomes. Therefore, kink-resistant external supports have been advocated in the recent literature to improve the conduit quality and outcomes. This study analyzes the FRAME external support in venous ectasic grafts in patients with chronic limb-threatening ischemia. Methods: From September 2017 to September 2023, a total of sixteen patients underwent CLTI surgery with FRAME external support for venous grafts. The inclusion criteria for FRAME applications were varicose or ectasic autologous material with a diameter ≥ 4.5 and ≤ 8 mm in an isolated segment or in the entire vein and a higher risk of bypass extrinsic compression (e.g., extra-anatomical venous bypass course). Results: Technical success and intraoperative patency were achieved in all cases. At 30 days, the limb salvage and survival rates were 100%. The primary bypass patency was 93.7% due to an early graft occlusion. No graft infection was registered. In one case, dehiscence of the surgical wound was treated by surgical debridement and antibiotic therapy. Minor amputation was required in four patients. Over a median follow-up of 32 months, two occlusions were observed; one was treated with reoperation and the other with major amputation. The primary patency was 68.7% and the assisted primary patency was 75%. Limb salvage rates observed during the entire follow-up period were 87.5%. No graft infections or dilatation of the reinforced veins were registered. Conclusions: For patients with CLTI undergoing infrainguinal bypass, satisfactory results in terms of patency and limb salvage rates were achieved using the autologous venous material, even if ectasic or varicose, with the vascular external support FRAME.

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.

Subclavian artery revascularization with subclavian-carotid transposition for TEVAR and non-TEVAR patients.

BACKGROUND: Subclavian artery revascularization (SAR) has become an increasingly performed technique in patients undergoing thoracic endovascular aortic aneurysm repair (TEVAR), in order to optimize the proximal landing zone, or in patients with significant atherosclerotic diseases. SAR was usually achieved through carotid-subclavian bypass (CSB) which is daunted by graft and patency-related issues, or through subclavian carotid transposition (SCT) which has recently been reconsidered as a potential solution. Nowadays, multiple endovascular strategies including parallel grafts, chimney graft and branch-fenestrated repair, are available in patients unfit for open SAR. However, there is no consensus on the preferable technique in both TEVAR- and non TEVAR-patients. The purpose of this study was to evaluate our experience with SCT in terms of overall postoperative adverse events and mid-term patency rate. METHODS: We performed a retrospective cohort study, including all patients who underwent SCT between June 2014 and March 2020 at our Division. Preoperative risk factors, symptoms, intraoperative details, postoperative outcomes and follow-up data were collected. RESULTS: A total of 27 patients were included in this study. Indications for SCT included aortic arch debranching for TEVAR for thoracic aortic aneurysm and type B dissection and symptomatic subclavian steal syndrome (SSS). There were no major perioperative adverse events or major neurological complications; five minor adverse events occurred (18.5%) (3 Horner' Syndrome, 1 hematoma requiring reoperation,1 pneumothorax). Peripheral nerve injuries and lymphatic lesions were not recorded. On a mean follow-up of 21±16 months, SCT patency was confirmed in all patients and no deaths occurred. Comparison of baseline and operative characteristics and intraoperative details between groups of patients with or without adverse events did not found differences. CONCLUSIONS: SCT should be considered a feasible, effective and safe technique for SAR, with low perioperative complications and optimal mid-term patency. This surgical technique appears to provide a lower risk of neurological events and mortality, particularly in TEVAR patients, reducing the complications caused by the coverage of the left subclavian artery.

Long-Term Results of Below-The-Knee Bypass Using a Prosthetic Graft with a Distal Arteriovenous Fistula Interposition.

Surgical bypass is the gold standard treatment in patients affected by chronic limb-threatening ischemia in advanced GLASS stages, according to the Global Vascular Guidelines. For patients in whom an autologous graft is not available, a prosthesis could be used with the adjunct of a distal arteriovenous fistula interposition. The aim of this study was to examine the long-term results of below-the-knee surgical revascularization using a prosthesis with the distal adjunct mentioned above. From 2010 to 2020, we performed 159 lower limb below-the-knee surgical revascularizations using a prosthesis with the creation of an arteriovenous fistula interposition on the distal anastomosis. The GLASS stage was 3 in 100% of patients. The primary patency rates were as follows: 86.7% at 1 year, 57.2% at 3 years, and 12.6% at 5 years. The graft thrombosis rates were 17.4% at 1 year, 42.1% at 3 years, and 64.5% at 5 years. The amputation-free survival rates were 79% at 1 year, 76% at 3 years, and 64% at 5 years. PTFE prosthetic bypass for below-the-knee arteries using an arteriovenous fistula interposition is a good solution in patients without an autologous conduit. This technique offers reasonable graft patency and limb salvage rates.

Tissue Engineering and Targeted Drug Delivery in Cardiovascular Disease: The Role of Polymer Nanocarrier for Statin Therapy.

Atherosclerosis-related coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide. This requires effective primary and secondary prevention in reducing the complications related to CAD; the regression or stabilization of the pathology remains the mainstay of treatment. Statins have proved to be the most effective treatment in reducing adverse effects, but there are limitations related to the administration and achievement of effective doses as well as side effects due to the lack of target-related molecular specificity. The implemented technological steps are polymers and nanoparticles for the administration of statins, as it has been seen how the conjugation of drug delivery systems (DDSs) with statins increases bioavailability by circumventing the hepatic-renal filter and increases the related target specificity, enhancing their action and decreasing side effects. Reduction of endothelial dysfunction, reduced intimal hyperplasia, reduced ischemia-reperfusion injury, cardiac regeneration, positive remodeling in the extracellular matrix, reduced neointimal growth, and increased reendothelialization are all drug-related effects of statins enhanced by binding with DDSs. Recent preclinical studies demonstrate how the effect of statins stimulates the differentiation of endogenous cardiac stem cells. Poly-lactic-co-glycolic acid (PLGA) seems to be the most promising DDS as it succeeds more than the others in enhancing the effect of the bound drug. This review intends to summarize the current evidence on polymers and nanoparticles for statin delivery in the field of cardiovascular disease, trying to shed light on this topic and identify new avenues for future studies.

Asymptomatic carotid stenosis and cognitive impairment.

INTRODUCTION: The aim of this review was to assess the evidence supporting an association between asymptomatic carotid stenosis (ACS) with impaired cognitive function due to chronic cerebral hypoperfusion and/or silent cerebral embolization. EVIDENCE ACQUISITION: PubMed/Medline, Embase and the Cochrane databases were searched up to December 1, 2022 to identify studies focusing on the association between ACS and cognitive function, as well as the mechanisms involved. EVIDENCE SYNTHESIS: A total of 49 studies were identified. The evidence supports an association between ACS and progressive cognitive deterioration. The mechanisms involved in the cognitive decline associated with ACS include cerebral hypoperfusion and silent cerebral embolization. Irrespective of the mechanism involved, severe ACS is associated with a progressive decline in several aspects of cognitive function, including global cognition, memory and executive function. CONCLUSIONS: Patients with ACS are at increased risk of developing a progressive decline in their cognitive function. The evidence from the present systematic review suggests that it may be inappropriate to consider ACS patients developing cognitive dysfunction as "asymptomatic". Besides stroke, myocardial infarction and death rates, future studies should include evaluation of cognitive function as part of their outcomes.

Why do guidelines recommend screening for abdominal aortic aneurysms, but not for asymptomatic carotid stenosis? A plea for a randomized controlled trial.

BACKGROUND: Current guidelines do not recommend screening for asymptomatic carotid artery stenosis (AsxCS). The rationale behind this recommendation is that detection of AsxCS may lead to an unnecessary carotid intervention. In contrast, screening for abdominal aortic aneurysms is strongly recommended. METHODS: A critical analysis of the literature was performed to evaluate the implications of detecting AsxCS. RESULTS: Patients with AsxCS are at high risk for future stroke, myocardial infarction and vascular death. Population-wide screening for AsxCS should not be recommended. Additionally, screening of high-risk individuals for AsxCS with the purpose of identifying candidates for a carotid intervention is inappropriate. Instead, selective screening for AsxCS should be considered and should be viewed as an opportunity to identify individuals at high risk for atherosclerotic cardiovascular disease and future cardiovascular events for the timely initiation of intensive medical therapy and risk factor modification. CONCLUSIONS: Although mass screening should not be recommended, there are several arguments suggesting that selective screening for AsxCS should be considered. The rationale supporting such selective screening is to optimize risk factor control and to initiate intensive medical therapy for prevention of future cardiovascular events, rather than to identify candidates for an intervention.

Duplex and Angiographic-Assisted Evaluation of Outcomes of Endovascular Embolization after Surgical Deep Vein Arterialization for the Treatment No-Option Critical Limb Ischemia Patients.

OBJECTIVE: To report early and mid-term outcomes of the arterialization of the deep venous system in no-option critical limb-threatening ischemia (CLTI) using duplex ultrasound and angiographic evaluation to improve limb perfusion. METHODS: A single-center prospective study of patients with no-option CLTI treated with hybrid surgical arterialization of the deep venous circulation and staged endovascular embolization of the venous collateral. Embolization was performed using a controlled-release spiral, within two weeks after bypass surgery. Patients were assessed for clinical status, wound healing, median transcutaneous partial pressure of O2 (TcPO2), and post-operative duplex ultrasound evaluating peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) to assess foot perfusion and bypass features. Primary endpoint analysis was primary technical success, limb salvage, patency rates, and clinical improvement. Secondary endpoints were 30-day and long-term mortality, major cardiovascular events (MACE), including myocardial infarction or stroke, and serious adverse events (SAE). RESULTS: Five patients with no-option CLTI were treated at our center using the hybrid deep vein arterialization technique. Clinical stage was grade 3 in one patient and grade 4 in the remaining four. Mean age was 65.8 years (range 49-76 years), and two patients were affected by Buerger's disease. Primary technical success was achieved in all patients, and all the bypasses were patent at the angiographic examination. At 30-day and at average follow-up of 9.8 months (range 2-24 months), mortality, major cardiovascular events (MACE), and serious adverse events (SAE) were not reported, with a primary patency and limb salvage rates of 100%. Three patients required minor amputation. Clinical improvement was demonstrated in all patients with granulation, resolution of rest pain, or both. Median TcPO2 values rose from 10 mm Hg (range 4-25) before the procedure to 35 (range 31-57) after surgery, and to 59 mm Hg (range 50-76) after the staged endovascular procedure. CONCLUSIONS: In our initial experience, the arterialization of the deep venous circulation, with subsequent selective embolization of the venous escape routes from the foot, seems a feasible and effective solution for limb salvage in patients with no-option CLTI and those in the advanced wound, ischemia, and foot infection (WIfI) clinical stage.

Taxonomical and functional composition of strawberry microbiome is genotype-dependent.

INTRODUCTION: Specific microbial communities are associated to host plants, influencing their phenotype and fitness.Despite the rising interest in plant microbiome, the role of microbial communities associated with perennial fruit plants remains overlooked. OBJECTIVES: This work provides the first comprehensive descriptionof the taxonomical and functional bacterial and fungal microbiota of below- and above-ground organsof three commercially important strawberry genotypes under cultural conditions. METHODS: Strawberry-associatedfungal and bacterial microbiomes were characterised by Next-Generation Sequencing and the potential functions expressed by the bacterial microbiome were analysed by both in silico and in vitro characterisation of plant growth-promoting abilities of native bacteria. Additionally, the association between the strawberry microbiome, plant disease tolerance, plant mineral nutrient content, and fruit quality was investigated. RESULTS: Results showed that thestrawberry core microbiome included 24 bacteria and 15 fungal operational taxonomicunits (OTUs).However, plant organ and genotype had a significant role in determining the taxonomical and functional composition of microbial communities. Interestingly, the cultivar with the highesttolerance against powdery mildew and leaf spot and the highest fruit productivity was the only one able to ubiquitously recruit the beneficial bacterium, Pseudomonasfluorescens, and to establish a mutualistic symbiosis with the arbuscular mycorrhizaRhizophagus irregularis. CONCLUSION: This work sheds light on the interaction of cultivated strawberry genotypes with a variety of microbes and highlights the importance of their applications to increase the sustainability of fruit crop production.

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.

Plant Signals Anticipate the Induction of the Type III Secretion System in Pseudomonas syringae pv. actinidiae, Facilitating Efficient Temperature-Dependent Effector Translocation.

Disease resistance in plants depends on a molecular dialogue with microbes that involves many known chemical effectors, but the time course of the interaction and the influence of the environment are largely unknown. The outcome of host-pathogen interactions is thought to reflect the offensive and defensive capabilities of both players. When plants interact with Pseudomonas syringae, several well-characterized virulence factors contribute to early bacterial pathogenicity, including the type III secretion system (T3SS), which must be activated by signals from the plant and environment to allow the secretion of virulence effectors. The manner in which these signals regulate T3SS activity is still unclear. Here, we strengthen the paradigm of the plant-pathogen molecular dialogue by addressing overlooked details concerning the timing of interactions, specifically the role of plant signals and temperature on the regulation of bacterial virulence during the first few hours of the interaction. Whole-genome expression profiling after 1 h revealed that the perception of plant signals from kiwifruit or tomato extracts anticipated T3SS expression in P. syringae pv. actinidiae compared to apoplast-like conditions, facilitating more efficient effector transport in planta, as revealed by the induction of a temperature-dependent hypersensitive response in the nonhost plant Arabidopsis thaliana Columbia-0 (Col-0). Our results show that in the arms race between plants and bacteria, the temperature-dependent timing of bacterial virulence versus the induction of plant defenses is probably one of the fundamental parameters governing the outcome of the interaction. IMPORTANCE Plant diseases-their occurrence and severity-result from the impact of three factors: the host, the pathogen, and the environmental conditions, interconnected in the disease triangle. Time was further included as a fourth factor accounting for plant disease, leading to a more realistic three-dimensional disease pyramid to represent the evolution of disease over time. However, this representation still considers time only as a parameter determining when and to what extent a disease will occur, at a scale from days to months. Here, we show that time is a factor regulating the arms race between plants and pathogens, at a scale from minutes to hours, and strictly depends on environmental factors. Thus, besides the arms possessed by pathogens and plants per se, the opportunity and the timing of arms mobilization make the difference in determining the outcome of an interaction and thus the occurrence of plant disease.

Optimal periprocedural antithrombotic treatment in carotid interventions: An international, multispecialty, expert review and position statement.

BACKGROUND: The optimal antithrombotic (antiplatelet or anticoagulant) treatment of patients undergoing extracranial carotid artery interventions is a subject of debate. The aim of this multidisciplinary document was to critically review the recommendations of current guidelines, taking into consideration the results of recently published studies. METHODS: The various antithrombotic strategies reported were evaluated for asymptomatic and symptomatic patients undergoing extracranial carotid artery interventions (endarterectomy, transfemoral carotid artery stenting [CAS] or transcarotid artery revascularization [TCAR]). Based on a critical review, a series of recommendations were formulated by an international expert panel. RESULTS: For asymptomatic patients, we recommend low-dose aspirin (75-100 mg/day) or clopidogrel (75 mg/day) with the primary goal to reduce the risk of myocardial infarction and cardiovascular event rates rather than to reduce the risk of stroke. For symptomatic patients, we recommend dual antiplatelet treatment (DAPT) initiated within 24 h of the index event to reduce the risk of recurrent events. We suggest that following transfemoral CAS or TCAR, patients continue DAPT for 1 month after which a single antiplatelet agent is used. High level of evidence to support anticoagulant treatment for patients with carotid artery disease is lacking. CONCLUSIONS: The antithrombotic treatment offered to carotid patients should be individualized, taking into account the presence of symptoms, the type of intervention and the goal of the treatment. The duration and type of DAPT (ticagrelor instead of clopidogrel) should be evaluated in future trials.

Evaluation of cannabinoid type 2 receptor expression and pyridine-based radiotracers in brains from a mouse model of Alzheimer's disease.

Neuroinflammation plays an important role in the pathophysiology of Alzheimer's disease. The cannabinoid type 2 receptor (CB2R) is an emerging target for neuroinflammation and therapeutics of Alzheimer's disease. Here, we aim to assess the alterations in brain CB2R levels and evaluate novel CB2R imaging tracers in the arcAß mouse model of Alzheimer's disease amyloidosis. Immunohistochemical staining for amyloid-ß deposits (6E10), microgliosis (anti-Iba1 and anti-CD68 antibodies), astrocytes (GFAP) and the anti-CB2R antibody was performed on brain slices from 17-month-old arcAß mice. Autoradiography using the CB2R imaging probes [18F]RoSMA-18-d6, [11C]RSR-056, and [11C]RS-028 and mRNA analysis were performed in brain tissue from arcAß and non-transgenic littermate (NTL) mice at 6, 17, and 24 months of age. Specific increased CB2R immunofluorescence intensities on the increased number of GFAP-positive astrocytes and Iba1-positive microglia were detected in the hippocampus and cortex of 17-month-old arcAß mice compared to NTL mice. CB2R immunofluorescence was higher in glial cells inside 6E10-positive amyloid-ß deposits than peri-plaque glial cells, which showed low background immunofluorescence in the hippocampus and cortex of 17-month-old arcAß mice. Ex vivo autoradiography showed that the specific binding of [18F]RoSMA-18-d6 and [11C]RSR-056 was comparable in arcAß and NTL mice at 6, 17, and 24 months of age. The level of Cnr2 mRNA expression in the brain was not significantly different between arcAß and NTL mice at 6, 17, or 24 months of age. In conclusion, we demonstrated pronounced specific increases in microglial and astroglial CB2R expression levels in a mouse model of AD-related cerebral amyloidosis, emphasizing CB2R as a suitable target for imaging neuroinflammation.

The Diagnostic Value of Circulating Biomarkers and Role of Drug-Coated Balloons for In-Stent Restenosis in Patients with Peripheral Arterial Disease.

Peripheral arterial disease (PAD) is an increasingly pathological condition that commonly affects the femoropopliteal arteries. The current fashionable treatment is percutaneous transluminal angioplasty (PTA), often with stenting. However, the in-stent restenosis (ISR) rate after the stenting of the femoropopliteal (FP) district remains high. Many techniques have been proposed for the treatment of femoropopliteal ISR, such as intravascular brachytherapy, laser atherectomy, second stenting and drug-coated balloons angioplasty (DCB). DCB showed a significantly lower rate of restenosis and target lesions revascularization (TLR) compared to conventional PTA. However, further studies and multi-center RCTs with dedicated long-term follow-up are needed to verify the true efficiency of this approach. Nowadays, the correlation between PAD and inflammation biomarkers is well known. Multiple studies have shown that proinflammatory markers (such as C-reactive proteins) and the high plasma levels of microRNA could predict the outcomes after stent placement. In particular, circulating microRNA-320a, microRNA-3937, microRNA-642a-3p and microRNA-572 appear to hold promise in diagnosing ISR in patients with PAD, but also as predictors of stent patency. This narrative review intends to summarize the current knowledge on the value of circulating biomarkers as predictors of ISR and to foster the scientific debate on the advantages of using DCB in the treatment of ISR in the FP district.

First case of aorto-bi-iliac endograft thrombotic infection by Listeria monocytogenes: A case report.

Listeria monocytogenes may cause serious vascular and graft infections. In the present case report, a 71-year-old man underwent partial prosthetic endograft replacement due to high-flow endoleak and limb occlusion. Following surgery, a multiple empiric antibiotic regime was initiated due to fever, malaise, abdominal tenderness and signs of an acute abdomen; however, in spite of this, the clinical condition of the patient worsened. An aorto-enteric fistula was discovered, and duodenal resection with duodeno-jejunal anastomosis packaging was performed. Gastrointestinal bleeding originating from this anastomosis both complicated and prolonged the clinical course, necessitating appropriate parenteral support and endoscopic hemostasis. The growth of Candida lusitanae in the drained abdominal and pleural effusion, and the isolation of L. monocytogenes from the thrombus inside the removed abdominal aorto-bi-iliac endograft allowed for establishment of a specific antibiotic treatment. After a suitable period of clinical improvement, the patient was transferred to a clinical rehabilitation center. At the present time, the patient maintains a good condition. To the best of our knowledge, the present study represents the first described case of thrombotic infection of an aorto-bi-iliac endograft by L. monocytogenes. In the event of graft thrombotic occlusion, L. monocytogenes infection should be considered as a potential cause. In case of complications requiring open conversion, even if not suspected from the medical history of the patient, the possibility of an underlying and occult infection should always be excluded with an in-depth preoperative work-up.

Benefits and drawbacks of statins and non-statin lipid lowering agents in carotid artery disease.

International guidelines strongly recommend statins alone or in combination with other lipid-lowering agents to lower low-density lipoprotein cholesterol (LDL-C) levels for patients with asymptomatic/symptomatic carotid stenosis (AsxCS/SCS). Lowering LDL-C levels is associated with significant reductions in transient ischemic attack, stroke, cardiovascular (CV) event and death rates. The aim of this multi-disciplinary overview is to summarize the benefits and risks associated with lowering LDL-C with statins or non-statin medications for Asx/SCS patients. The cerebrovascular and CV beneficial effects associated with statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and other non-statin lipid-lowering agents (e.g. fibrates, ezetimibe) are reviewed. The use of statins and PCSK9 inhibitors is associated with several beneficial effects for Asx/SCS patients, including carotid plaque stabilization and reduction of stroke rates. Ezetimibe and fibrates are associated with smaller reductions in stroke rates. The side-effects resulting from statin and PCSK9 inhibitor use are also highlighted. The benefits associated with lowering LDL-C with statins or non-statin lipid lowering agents (e.g. PCSK9 inhibitors) outweigh the risks and potential side-effects. Irrespective of their LDL-C levels, all Asx/SCS patients should receive high-dose statin treatment±ezetimibe or PCSK9 inhibitors for reduction not only of LDL-C levels, but also of stroke, cardiovascular mortality and coronary event rates.

Host-specific signal perception by PsaR2 LuxR solo induces Pseudomonas syringae pv. actinidiae virulence traits.

Plant-associated bacteria, including pathogens, recognise host-derived signals to activate specific responses. The genome of Pseudomonas syringae pv. actinidiae (Psa), the aetiological agent of bacterial canker of kiwifruit, encodes for three putative LuxR-like receptors. Proteins of this family are usually involved in the quorum sensing system, through the perception of autoinducers (AHLs) produced by a cognate LuxI. However, Psa does not produce AHLs according to the lack of LuxI-encoding gene. It has been proposed that the so-called LuxR solos may be involved in the perception of environmental stimuli. We thus hypothesised that Psa LuxR-like receptors could be involved in host-derived signal sensing. Psa virulence traits, i.e., biofilm formation, motility and endophytic colonisation, were stimulated by growing the pathogen in host plant extracts, but not in non-host plant extracts or rich medium. Moreover, the phenotypic analyses of Psa mutant strains lacking the LuxR solo-encoding genes, demonstrated that PsaR2 plays a major role in host recognition and induction of virulence responses. The heterologous expression of PsaR2, followed by affinity chromatography and fraction activity assessment, confirmed the specific recognition of plant-derived components by this sensor. Overall, these data provide a deeper understanding of the regulation of Psa virulence through interkingdom communication, which represents a interesting target for the development of tolerant/resistant genotypes or innovative control strategies.

Comparison of Recent Practice Guidelines for the Management of Patients With Asymptomatic Carotid Stenosis.

Despite the publication of several national/international guidelines, the optimal management of patients with asymptomatic carotid stenosis (AsxCS) remains controversial. This article compares 3 recently released guidelines (the 2020 German-Austrian, the 2021 European Stroke Organization [ESO], and the 2021 Society for Vascular Surgery [SVS] guidelines) vs the 2017 European Society for Vascular Surgery (ESVS) guidelines regarding the optimal management of AsxCS patients.The 2017 ESVS guidelines defined specific imaging/clinical parameters that may identify patient subgroups at high future stroke risk and recommended that carotid endarterectomy (CEA) should or carotid artery stenting (CAS) may be considered for these individuals. The 2020 German-Austrian guidelines provided similar recommendations with the 2017 ESVS Guidelines. The 2021 ESO Guidelines also recommended CEA for AsxCS patients at high risk for stroke on best medical treatment (BMT), but recommended against routine use of CAS in these patients. Finally, the SVS guidelines provided a strong recommendation for CEA+BMT vs BMT alone for low-surgical risk patients with >70% AsxCS. Thus, the ESVS, German-Austrian, and ESO guidelines concurred that all AsxCS patients should receive risk factor modification and BMT, but CEA should or CAS may also be considered for certain AsxCS patient subgroups at high risk for future ipsilateral ischemic stroke.