Genetically predicted retinal vascular occlusion in relation to cardiovascular diseases: A bidirectional two-sample Mendelian randomization analysis.

INTRODUCTION: Increasing evidence implicates retinal vascular occlusions as a susceptibility factor for cardiovascular diseases (CVDs), whereas inconsistent results on the relationship were reported in previous observational studies. This research using a bidirectional two-sample Mendelian randomization (MR) analysis aimed to investigate the potential association between genetically determined central/branch retinal artery and retinal vein occlusions (CRAO/BRAO/RVO) and the risk of CVD. METHODS: Summary statistics of retinal vascular occlusions from the largest available genome-wide association study of European descent were used to investigate their relationship with CVDs, and vice versa. Primary analyses were conducted using the common inverse-variance weighted approach. Several complementary sensitivity analyses were performed to verify the reliability of our results. RESULTS: Inverse variance weighted method showed suggestive effects of genetically determined RVO on ischemic stroke (IS) (odds ratio [OR] = 1.021, 95% confidence [CI] = 1.004-1.037, p = 0.012), a genetic liability to CRAO increased the risk of myocardial infarction (MI) (OR = 1.014, 95% CI = 1.006-1.023, p = 7.0 × 10-4). In addition, genetic predisposition to BRAO had a positive effect on stroke (OR = 1.008, 95% CI = 1.002-1.013, p = 0.011), IS (OR = 1.007, 95% CI = 1.001-1.014, p = 0.022), and cardioembolic stroke (CES) (OR = 1.018, 95% CI = 1.006-1.031, p = 0.004). The point estimates from sensitivity analyses were in the same direction. Reverse MR analyses found no significant evidence for the effect of CVDs on retinal vascular occlusions. CONCLUSION: Our MR study provides potential evidence that retinal vascular occlusions are causally linked to increased risk of CVDs including IS, MI, stroke, and CES. This supports the need for clinical CVD screening in individuals with retinal vascular occlusions. Further investigations are warranted to clarify the effects of CVDs on ocular comorbidities.

DETOUR2 trial outcomes demonstrate clinical utility of percutaneous transmural bypass for the treatment of long segment, complex femoropopliteal disease.

OBJECTIVE: Percutaneous transmural arterial bypass (PTAB) using the DETOUR system aims to create a percutaneous, endovascular femoropopliteal bypass for the treatment of long segment, complex superficial femoral and proximal popliteal artery disease. The goal of the DETOUR2 study is to investigate the safety and effectiveness of the therapy in comparison with pre-established performance goals. METHODS: The DETOUR2 investigational device exemption study is a prospective, single-arm, multicenter, international trial of symptomatic peripheral arterial disease patients (Rutherford classes 3-5) undergoing the DETOUR procedure for long segment (>20 cm) superficial femoral artery disease. Prespecified end points included primary safety (composite of major adverse events) at 30 days, and effectiveness (primary patency defined as freedom from restenosis or clinically driven target lesion revascularization) at 1 year. RESULTS: We enrolled 202 patients at 32 sites with 200 treated with the DETOUR system. The mean lesion length was 32.7 cm, of which 96% were chronic total occlusions (CTO) and 70% were severely calcified. Technical success was achieved in 100% of treated patients. The primary safety end point was met with a 30-day freedom from major adverse event rate of 93.0%. The 1-year primary effectiveness end point was met with 72.1% primary patency at 12 months. Primary-assisted and secondary patency were 77.7% and 89.0%, respectively, at 12 months. The 12 month deep venous thrombosis incidence was 4.1% with no pulmonary emboli reported. Venous quality-of-life scores showed no significant changes from baseline. There was a Rutherford improvement of at least one class through 12 months in 97.2% of patients. The mean ankle-brachial index also improved from 0.61 to 0.95 during this period. There were marked improvements in quality-of-life and functional status measures. CONCLUSIONS: The DETOUR2 study met both the primary safety and effectiveness end points, demonstrating clinical usefulness of this novel therapeutic strategy in long femoropopliteal lesions.

Role of mRNA-binding proteins in retinal neovascularization.

Retinal neovascularization (RNV) is a pathological process that primarily occurs in diabetic retinopathy, retinopathy of prematurity, and retinal vein occlusion. It is a common yet debilitating clinical condition that culminates in blindness. Urgent efforts are required to explore more efficient and less limiting therapeutic strategies. Key RNA-binding proteins (RBPs), crucial for post-transcriptional regulation of gene expression by binding to RNAs, are closely correlated with RNV development. RBP-RNA interactions are altered during RNV. Here, we briefly review the characteristics and functions of RBPs, and the mechanism of RNV. Then, we present insights into the role of the regulatory network of RBPs in RNV. HuR, eIF4E, LIN28B, SRSF1, METTL3, YTHDF1, Gal-1, HIWI1, and ZFR accelerate RNV progression, whereas YTHDF2 and hnRNPA2B1 hinder it. The mechanisms elucidated in this review provide a reference to guide the design of therapeutic strategies to reverse abnormal processes.

Brain imaging prior to thrombectomy in the late window of large vessel occlusion ischemic stroke: a systematic review and meta-analysis.

PURPOSE: Optimal imaging modalities to select patients for endovascular thrombectomy (EVT) in the late window of acute ischemic stroke due to large vessel occlusions (AIS-LVO) are not known. We conducted a systematic review comparing outcomes of patients selected by non-contrast computed tomography (NCCT)/CT angiography (CTA) vs. those selected by CT perfusion (CTP) or magnetic resonance imaging (MRI) for EVT in these patients. METHODS: We searched PUBMED, EMBASE, and the Cochrane Library from January 1, 2000, to July 15, 2023, to identify studies comparing outcomes of patients selected for EVT by NCCT/CTA vs. CTP or MRI in the late time window for AIS-LVO. Primary outcome was independence (mRS 0-2) at 90 days or discharge. Secondary outcomes were symptomatic intracranial hemorrhage (sICH) and mortality. We pooled data across studies based on an inverse variance method. RESULTS: Six cohort studies with 4208 patients were included. Pooled results showed no significant difference in the rate of independence at 90 days or discharge (RR 0.96, 95% CI 0.88-1.03) and sICH (RR 1.26, 0.85-1.86) between patients selected by NCCT/CTA vs. CTP or MRI for EVT in the late window of AIS-LVO. However, patients selected by NCCT/CTA vs. CTP or MRI for EVT were associated with a higher risk of mortality (RR 1.21, 1.06-1.39). CONCLUSION: For AIS-LVO in the late window, patients selected by NCCT/CTA compared with those selected by CTP or MRI for EVT might have a comparable rate of functional independence and sICH. Baseline NCCT/CTA may triage AIS-LVO in the late window.

Current trends in antiplatelet strategies for emergent carotid stenting in acute tandem occlusions: a web-based, nationwide survey in the Italian neurovascular community.

BACKGROUND: Although a benefit from mechanical thrombectomy has been proven, the best treatment strategy for tandem occlusions (TOs) remains unclear. We conducted a survey that aimed to investigate the trends of pharmacological strategy in the setting of emergent carotid stenting for TOs in the Italian neuro-endovascular community. METHODS: We administered a 13-multiple choice-questions survey to the Chiefs of the centers participating to the Italian Registry of Endovascular Thrombectomy in Acute Stroke (IRETAS), focused on the technical aspects and on the management of the antiplatelet therapy for emergent carotid tenting in TOs. An internal coherence control was performed by the coordinating investigator. RESULTS: We obtained responses from 56/66 centers (84.8%). The main results of the survey showed that most of the center treat TOs using a retrograde approach, deploying a closed-cell stent. A single antiplatelet therapy is preferred at the moment of the deployment of the stent. CONCLUSIONS: This survey showed that the current practice regarding the acute management of TOs, in particular the antiplatelet therapy, remains heterogeneous in the Italian neurovascular community. Specific evidences are urgently needed in order to achieve a consensus on the acute management of TOs.

Intraluminal crossing of infrainguinal SFA chronic total occlusions may offer patency superiority compared to subintimal crossing.

OBJECTIVES: Patency for chronic total occlusions (CTO) of the superficial femoral artery (SFA) after endovascular interventions traditionally demonstrate a low 1-year patency ranging from 40%-60%. The optical coherence tomography (OCT) catheter (Avinger Inc., Redwood City, CA) uses light-based technology imaging to cross Trans-Atlantic Inter-Society Consensus D (TASC D) lesions intraluminally with direct intra-arterial visualization. Insufficient data exist evaluating intraluminal crossing with OCT imaging compared with traditional subintimal techniques. We evaluated outcomes for TASC D lesions crossed intraluminally. METHODS: A retrospective analysis of patients with SFA TASC D lesions crossed intra-arterially with the OCT catheter imaging. Descriptive statistics evaluated patient characteristics which included patient demographics, Rutherford scores, ABIs, CTA information, lesion categorization, as well as runoff score. Patency at baseline, 30-day, 6-month, and 1-year outcomes were compared using t-tests. Cumulative patency rates were evaluated using Kaplan-Meier analysis. RESULTS: 101 patients underwent elective intervention for SFA TASC D lesions with the OCT catheter. The crossing rate was 78.2%, mean lesion length was 16.2 cm, and runoff at the tibial level was 2.2 patent vessels. Mean age and BMI were 64 years and 29 kg/m2, respectively. Patient characteristics are male (57%); Caucasian (90%); ever smoking (85%); hypertension (82%), hyperlipidemia (70%), and diabetes (46%). Pre-operative computed tomography demonstrated SFA lesions were predominantly eccentric (91%) with mild to moderate calcification (90%). All underwent PTA, 87% were stented (mean stent length: 186.1 mm), mean crossing time was 13.4 min. Pre-operative, 30-day, 6-month, and 1-year post-operative mean Rutherford-Becker scores were 4, 1, 1, and 1, respectively (p < 0.0001). Mean pre-operative ABI was 0.49, compared to 0.84 at 30 days, 0.64 at 6 months, and 0.67 at 1 year (p < .0001). Duplex demonstrated 6- and 12-month primary patency of 89% and 75%; primary-assisted patency was 94% and 84%. CONCLUSIONS: The OCT imaging catheter successfully crossed long chronic total occlusions of the SFA using direct intra-arterial imaging. Compared to subintimal techniques, patients had high 1-year primary patency and prolonged symptom improvement with intraluminal crossing. These data suggest that intraluminal crossing of TASC D lesions may be superior to traditional subintimal crossing techniques.

Synergistic Effect of Hydroxyl and Carboxyl Groups on Promoting Nanoparticle Occlusion within Calcite.

Direct occlusion of guest nanoparticles into host crystals enables the straightforward preparation for various of nanocomposite materials with emerging properties. Therefore, it is highly desirable to elucidate the 'design rules' that govern efficient nanoparticle occlusion. Herein, a series of sterically-stabilized nanoparticles are rationally prepared, where the surface stabilizer chains of such nanoparticles are composed of either poly(methacrylic acid), or poly(glycerol monomethacrylate), or poly((2-hydroxy-3-(methacryloyloxy)propyl)serine). Systematic investigation reveals that hydroxyl groups and carboxyl groups play a synergistic role in driving nanoparticle incorporation into calcite crystals, where the hydroxyl groups enhance colloidal stability of the nanoparticles and the carboxyl groups provide binding sites for efficient occlusion. The generality of these findings is further validated by extending it to polymer-stabilized gold nanoparticles. This study demonstrates that precision synthesis of polymer stabilizers comprising of synergistic functional groups can significantly promote nanoparticle occlusion, thus enabling the efficient construction of organic-inorganic hybrid materials via nanoparticle occlusion strategy.

Intraplaque wiring enables drug-coated balloons to be utilized for percutaneous recanalization of chronically occluded coronary arteries.

OBJECTIVES: This study aimed to determine whether drug-coated balloon (DCB) angioplasty following intraplaque wiring and the use of modified balloons is safe and effective in the percutaneous treatment of coronary chronic total occlusions (CTOs). BACKGROUND: DCB is an alternative therapeutic option without the limitations of permanent vascular implants. However, its efficacy in CTOs has yet to be confirmed. The combination of modified balloons and DCB can be effectively applied when the intraplaque passage of the guidewire is achieved in CTOs. METHODS: Data from 124 consecutive CTO lesions (105 patients) treated at our hospital between February 2016 and December 2020 were screened for inclusion and retrospectively analyzed. Among the 118 lesions successfully recanalized, intraplaque wiring was achieved in 108, and 85 were treated by the DCB-only approach following cutting/scoring balloon dilatation. RESULTS: Follow-up data were available for 82 lesions (71 patients). The median occlusion length was 18.5 mm, and the J-CTO score was 1.7 ± 0.9. No in-hospital major adverse cardiac events occurred, including abrupt vessel closure. During the median 29-month follow-up period, target lesion revascularization was performed for 10 lesions. Follow-up coronary angiography (8.7 ± 3.9 months after the index procedure) was performed for 64 lesions, demonstrating late lumen loss of -0.15 mm (interquartile range -0.4 to 0.23 mm), binary restenosis (diameter stenosis ≥50%) in 12 lesions (18.8%), and late lumen enlargement in 37 (57.8%). CONCLUSION: The DCB-only approach following the use of modified balloons is a promising strategy for coronary CTOs when intraplaque wiring is achieved.

Stent expansion in calcified coronary chronic total occlusions: The impact of different stent platforms.

OBJECTIVES: To evaluate the stent expansion of the durable-polymer Zotarolimus-eluting stent (dp-ZES), the durable-polymer Everolimus-eluting stent (dp-EES), and the bioabsorbable-polymer Sirolimus-eluting stent (bp-SES) in calcified coronary chronic total occlusions (CTO). BACKGROUND: The newer generation stents with ultrathin struts might raise concerns regarding reduced radial strength and higher stent recoil (SR) when implanted in calcified CTOs. METHODS: Between January 2017 and June 2021 consecutive patients with CTO undergoing percutaneous coronary intervention with dp-ZES, dp-EES, or bp-SES were evaluated. The analysis was performed in calcific and in noncalcific CTOs. Quantitative coronary angiography analysis was used to assess diameter stenosis (DS), absolute and relative SR, absolute and relative focal SR, absolute and relative balloon deficit (BD), and absolute and relative focal BD. The primary endpoint was DS. RESULTS: A total of 213 CTOs were evaluated, 115 calcific CTOs (dp-ZES:25, dp-EES:29, bp-SES:61) and 98 non-calcific CTOs (dp-ZES:41, dp-EES:11, bp-SES:46). In calcific CTOs, residual DS was lower in dp-ZES than in dp-EES and bp-SES (-1.00% [-6.50-6.50] vs. 13.00% [7.0-19.00] vs. 15.00% [5.00-20.00]; p < 0.001). Dp-ZES was also an independent predictor of residual DS ≤ 10% (OR 11.34, 95% CI 2.6-49.43, p = 0.001). Absolute and relative focal SR and absolute and relative SR were similar between dp-ZES, dp-EES, and bp-SES (p = 0.913, p = 0.890, p = 0.518, p = 0.426, respectively). In noncalcified CTOs, the residual DS was similar in the three groups (p = 0.340). High relative focal SR was less frequent in dp-ZES than in dp-EES and in bp-SES (19.5% vs. 54.5% vs. 37.0%; p < 0.048). CONCLUSIONS: The three stent platforms demonstrated an overall low residual DS when implanted in CTOs. However, dp-ZES was associated with the lowest residual DS and identified as independent predictor of residual DS ≤ 10% in patients with calcific CTOs. Dp-ZES was associated with a lower incidence of high relative focal stent recoil, in noncalcific CTOs. Balloon deficit might be considerate as a surrogate for stent expansion in calcified CTOs.

Major Bleeding During Thrombolytic Therapy for Acute Lower Limb Ischaemia: Value of Laboratory Tests for Clinical Decision Making, 17 Years of Experience.

OBJECTIVE: Regular measurement of fibrinogen as dose guidance in catheter directed thrombolysis (CDT) for acute limb ischaemia (ALI) has recently been dropped from European guidelines based on inconsistent literature. This study aimed to determine whether low fibrinogen levels and high activated partial thromboplastin time (APTT) are associated with an increased major bleeding risk during CDT. METHODS: All consecutive patients treated with CDT for ALI in two Dutch hospitals between January 2004 and April 2021 were analysed retrospectively. Patients were treated with two dosing regimens (low dose: 50 000 IU/hour; high dose: 100 000 IU/hour) of urokinase and, after 2018, with a single low dose regimen of alteplase (rtPA) due to urokinase manufacturing problems. The incidence of major bleeding and associated APTT and fibrinogen levels were reviewed from patient charts. RESULTS: Of the 443 included cases, 277 underwent CDT with urokinase and 166 with rtPA. The incidence of major bleeding in the whole cohort was 7%. Patients with a fibrinogen levels < 1.0 g/L developed more major bleeding than those in whom the fibrinogen level did not drop below 1.0 g/L (15% vs. 6%; p = .041). Systemic heparinisation during CDT or high (> 80 seconds) APTT were not significantly associated with major bleeding. Angiographic success (47% vs. 72%; p = .003) and 30 day amputation free survival (53% vs. 82%; p < .001) were lower for cases with major bleeding. Older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02 - 1.11), cardiac history (OR 3.35, 95% CI 1.39 - 8.06), high dose regimens (≥ 75 000 IU/hour urokinase; OR 2.67, 95% CI 1.18 - 6.04), and fibrinogen values < 1.0 g/L (OR 5.59, 95% CI 1.98 - 15.77) were independent predictors for major bleeding during CDT. CONCLUSION: High dose thrombolytic regimens and fibrinogen levels of ≤ 1.0 g/L are associated with more major bleeding during thrombolytic therapy. Major bleeding significantly worsened the clinical outcome. A prospective comparative study is needed to assess the benefit of monitoring fibrinogen levels.

Catheter Directed Thrombolysis for Not Immediately Threatening Acute Limb Ischaemia: Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis reports the outcomes of catheter directed thrombolysis (CDT) in patients with not immediately threatening (Rutherford I) acute lower limb ischaemia (ALI). DATA SOURCES: PubMed, Embase, and the Cochrane Library. REVIEW METHODS: A systematic search of PubMed, Embase, and the Cochrane Library was performed to identify observational studies and trials published between 1990 and 2022 reporting on the results of CDT in patients with Rutherford I ALI. A meta-analysis was performed using a random effects model with 95% confidence intervals (CIs). The outcomes of interests were treatment duration, angiographic success, bleeding complications, amputation and mortality rates, primary and secondary patency, and functional outcome expressed as pain free walking distance. RESULTS: Thirty-nine studies were included, comprising 1 861 patients who received CDT for not immediately threatening ALI. Funnel plots showed an indication of publication bias, and heterogeneity was substantial. Data from 5 to 13 studies were included in the meta-analysis. The pooled treatment duration was 2 days (95% CI 1 - 2), with an angiographic success rate of 80% (95% CI 73 - 86) and a 30 day freedom of amputation rate of 98% (95% CI 92 - 100). The major bleeding rate was 5% (95% CI 2 - 14), with a 30 day mortality rate of 3% (95% CI 1 - 5). The amputation free survival rate was 71% (95% CI 62 - 80) at the one year and 63% (95% CI 51 - 73) at the three year follow up. Long term patency rates were retrieved from four studies: 48% at one year (95% CI 27 - 70). No data could be retrieved on patient walking distance. CONCLUSION: Although CDT in the treatment of not immediately threatening ALI showed high angiographic success, the long term outcomes were relatively poor, with low patency and a substantial risk of major amputation. Further research is required to interpret the outcome of CDT in the context of potential confounders such as age and comorbidities.

Predictors of outcome after endovascular treatment for tandem occlusions: a single center retrospective analysis.

BACKGROUND: The endovascular treatment procedure in tandem occlusions (TO) is complex compared to single occlusion (SO) and optimal management remains uncertain. The aim of this study was to identify clinical and procedural factors that may be associated to efficacy and safety in the management of TO and compare functional outcome in TO and SO stroke patients. METHODS: This is a retrospective single center study of medium (MeVO) and large vessel occlusion (LVO) of the anterior circulation. Clinical, imaging, and interventional data were analyzed to identify predictive factors for symptomatic intracranial hemorrhage (sICH) and functional outcome after endovascular treatment (EVT) in TO. Functional outcome in TO and SO patients was compared. RESULTS: Of 662 anterior circulation stroke patients with MeVO and LVO stroke, 90 (14%) had TO. Stenting was performed in 73 (81%) of TO patients. Stent thromboses occurred in 8 (11%) patients. Successful reperfusion with modified thrombolysis in cerebral infarction (mTICI) ≥ 2b was achieved in 82 (91%). SICH occurred in seven (8%). The strongest predictors for sICH were diabetes mellitus and number of stent retriever passes. Good functional clinical outcome (mRS ≤ 2) at 90-day follow up was similar in TO and SO patients (58% vs 59% respectively). General anesthesia (GA) was associated with good functional outcome whereas hemorrhage in the infarcted tissue, lower mTICI score and history of smoking were associated with poor outcome. CONCLUSIONS: The risk of sICH was increased in patients with diabetes mellitus and those with extra stent-retriever attempts. Functional clinical outcomes in patients with TO were comparable to patients with SO.

Application of checklist-based nursing care process in patients undergoing intervention for coronary chronic total occlusions: a quasi-randomized study.

BACKGROUND: Coronary chronic total occlusion (CTO) interventions are more complex than general percutaneous coronary intervention (PCI) procedures. However, only a few nursing methods are specifically applied to patients undergoing CTO interventions. And the conventional nursing effect is not ideal, urgent need to explore more effective nursing methods. The checklist is a simple and effective tool for error management and performance improvement that has been widely used in many fields. But there have been no reports of the checklist being used to improve care for CTO patients. OBJECTIVE: This study aimed to investigate the effectiveness of a checklist-based nursing care process in patients undergoing Coronary chronic total occlusion (CTO) interventions, including duration of care, patient anxiety, improved patient satisfaction, and occurrence of adverse events. METHODS: A total of 120 CTO patients undergoing percutaneous coronary intervention (PCI) were selected at our hospital and divided into an intervention group (n = 60, adopted the checklist-based nursing care process for patient care) and a control group (n = 60, adopted nursing care according to the existing workflow) according to different nursing interventions. After surgery, the nurse in charge of the patient completed the nursing according to the "List of postoperative care for CTO patients" filled in by the patient within 24 h after surgery, conducted a doctor satisfaction survey, recorded adverse events, and completed the postoperative Self-Rating Anxiety Scale (SAS) score and patient satisfaction survey before the patient was discharged. Subsequently, the Qc team checks the completion of the patient's checklist for safety and the completion of the questionnaire. Finally, the differences between the two groups in preoperative nursing time, incidence of adverse events caused by nurses' omission or inadequate guidance, patient anxiety, and doctor and patient satisfaction were compared. RESULTS: The intervention grouphad significantly shorter preoperative nursing care time and significantly lower the total number of adverse events than the control group (P < 0.05).The postoperative Self-Rating Anxiety Scale (SAS) score of the intervention group was significantly lower than that of the control group (P < 0.05).The satisfaction of doctors and patients in the intervention groupwas significantly higher than that in the control group (P < 0.05). CONCLUSION: The application of the checklist-based nursing care process in patients with CTO intervention can significantly reduce the preoperative nursing care time, reduce patient anxiety, improve patients' and doctors' satisfaction with nursing care, and effectively reduce the occurrence of adverse events caused by nurses' omissions or inadequate instructions. TRIAL REGISTRATION: The protocol of the trial was registered retrospectively of Chinese Clinical Trial Registry (registration number ChiCTR2200056804, reg date17/02/2022).

Folate and retinal vascular diseases.

Folate, a pteroylglutamic acid derivative, participates in fundamental cellular metabolism. Homocysteine, an amino acid, serves as an intermediate of the methionine cycle and can be converted back to methionine. Hyperhomocysteinemia is a recognized risk factor for atherosclerotic and cardiovascular diseases. In recent decades, elevated plasma homocysteine levels and low folate status have been observed in many patients with retinal vascular diseases, such as retinal vascular occlusions, diabetic retinopathy, and age-related degeneration. Homocysteine-induced toxicity toward vascular endothelial cells might participate in the formation of retinal vascular diseases. Folate is an important dietary determinant of homocysteine. Folate deficiency is the most common cause of hyperhomocysteinemia. Folate supplementation can eliminate excess homocysteine in plasma. In in vitro experiments, folic acid had a protective effect on vascular endothelial cells against high glucose. Many studies have explored the relationship between folate and various retinal vascular diseases. This review summarizes the most important findings that lead to the conclusion that folic acid supplementation might be a protective treatment in patients with retinal vascular diseases with high homocysteine or glucose status. More research is still needed to validate the effect of folate and its supplementation in retinal vascular diseases.

Best crossing of peripheral chronic total occlusions.

Together with colleagues from different disciplines, including cardiologists, interventional radiologists and vascular surgeons, committee members of the of the German Society of Angiology (Deutsche Gesellschaft für Angiologie [DGA]), developed a novel algorithm for the endovascular treatment of peripheral chronic total occlusive lesions (CTOs). Our aim is to improve patient and limb related outcomes, by increasing the success rate of endovascular procedures. This can be achieved by adherence to the proposed crossing algorithm, aiding the standardization of endovascular procedures. The following steps are proposed: (i) APPLY Duplex sonography and if required 3D techniques such as computed tomography or magnetic resonance angiography. This will help you to select the optimal access site. (ii) EVALUATE the CTO cap morphology and distal vessel refilling sites during diagnostic angiography, which are potential targets for a retrograde access. (iii) START with antegrade wiring strategies including guidewire (GW) and support catheter technology. Use GW escalation strategies to penetrate the proximal cap of the CTO, which may usually be fibrotic and calcified. (iv) STOP the antegrade attempt depending on patient specific parameters and the presence of retrograde options, as evaluated by pre-procedural imaging and during angiography. (v) In case of FAILURE, consider advanced bidirectional techniques and reentry devices. (vi) In case of SUCCESS, externalize the GW and treat the CTO. Manage the retrograde access at the end of the endovascular procedure. (vii) STOP the procedure if no progress can be obtained within 3 hours, in case of specific complications or when reaching maximum contrast administration based on individual patient's renal function. Consider radiation exposure both for patients and operators. In this manuscript we systematically follow and explain each of the steps (i)-(vi) based on practical examples from our daily routine. We strongly believe that the integration of this algorithm in the daily practice of endovascular specialists, can improve vessel and patient specific outcomes.

Emergent use of ticagrelor during endovascular reperfusion in large arterial occlusions.

OBJECTIVE: Given many emerging indications for endovascular interventions in ischemic strokes, a safe and effective adjuvant antiplatelet regimen for acute revascularization has become a subject of interest. Ticagrelor is a direct oral P2Y12 inhibitor that may achieve rapid platelet suppression than standard oral therapies. We report our experience of Ticagrelor use in revascularization of acute large arterial steno-occlusive disease, describing procedural post-procedure thrombotic events, major hemorrhages, and other clinical outcomes. METHODS: This was a single-center retrospective case series of large steno-occlusive disease requiring endovascular reperfusion with emergent adjuvant Ticagrelor, defined as 30 min of the procedure from skin puncture to closure of the arteriotomy. Major outcomes investigated were thromboembolism in the target artery, and symptomatic intracranial or extracranial major hemorrhages. Additional analyses were performed with respect to timing of the administration and use of rescue GPIIb/IIIa inhibitors if any. RESULTS: 73 consecutive patients were identified, presenting with severe ischemic stroke (median NIHSS 16) of large artery origin. 67% required stent placement (45% cervical carotid, 22% intracranial artery), 9.5% angioplasty and 23% mechanical thrombectomy only. Two experienced symptomatic in-stent occlusion, and 7 experienced major hemorrhages (9.5%) including 3 fatal symptomatic intracranial hemorrhages (4.1%). Among 19 subjects (26%) who received pretreatment with Ticagrelor, there were fewer GPIIb/IIIa administration, angioplasty and stenting, without yielding benefit in functional outcome or mortality. GPIIb/IIIa was administered as rescue therapy in 45 subjects (62%), which was found associated with increased bleeding compared to patients receiving Ticagrelor only, in whom no bleeding complications were recorded (16% vs. 0%; p = 0.03). CONCLUSION: We report our findings on Ticagrelor as an adjuvant antiplatelet therapy in ischemic stroke of large arterial origin requiring emergent revascularization. Effectiveness, safety, need for additional rescue treatment, and comparison to other commonly used oral antiplatelets should be investigated in future prospective studies.

Larger ischemic cores and poor collaterals among large vessel occlusions presenting in the late evening.

BACKGROUND: Components critical to cerebral perfusion have been noted to oscillate over a 24-h cycle. We previously reported that ischemic core volume has a diurnal relationship with stroke onset time when examined as dichotomized epochs (i.e. Day, Evening, Night) in a cohort of over 1,500 large vessel occlusion (LVO) patients. In this follow-up analysis, our goal was to explore if there is a sinusoidal relationship between ischemic core, collateral status (as measured by HIR), and stroke onset time. METHODS: We retrospectively examined collection of LVO patients with baseline perfusion imaging performed within 24 h of stroke onset from four international comprehensive stroke centers. Both ischemic core volume and HIR, were utilized as the primary radiographic parameters. To evaluate for differences in these parameters over a continuous 24-h cycle, we conducted a sinusoidal regression analysis after linearly regressing out the confounders age and time to imaging. RESULTS: A total of 1506 LVO cases were included, with a median ischemic core volume of 13.0 cc (IQR: 0.0-42.0) and median HIR of 0.4 (IQR: 0.2-0.6). Ischemic core volume varied by stroke onset time in the unadjusted (p = 0.001) and adjusted (p = 0.003) sinusoidal regression analysis with a peak in core volume around 7:45PM. HIR similarly varied by stroke onset time in the unadjusted (p = 0.004) and adjusted (p = 0.002) models with a peak in HIR values at around 8:18PM. CONCLUSION: The results suggest that critical factors to the development of the ischemic core vary by stroke onset time and peak around 8PM. When placed in the context of prior studies, strongly suggest a diurnal component to the development of the ischemic core.

Retrograde use of the Outback re-entry catheter in complex infrainguinal arterial recanalizations.

OBJECTIVE/BACKGROUND: Retrograde recanalizations gained increasing recognition in complex arterial occlusive disease. Re-entry devices are a well-described adjunct for antegrade recanalizations. We present our experience with retrograde, infrainguinal recanalizations using the Outback re-entry catheter in challenging chronic total occlusions. METHODS: We report data from a retrospective multicenter registry in complex retrograde recanalizations. Eligibility criteria included retrograde infrainguinal use of the Outback re-entry catheter where both conventional antegrade and retrograde recanalizations had been unsuccessful. Procedural outcomes included technical success (defined as successful wire passage and delivery of adjunctive therapy with <30% residual stenosis), safety (periprocedural complications, eg, bleeding, vessel injury, or occlusion of the artery at the re-entry site, and distal embolizations), and clinical outcome (amputation-free survival and freedom from clinically driven target lesion revascularization [cd-TLR]). RESULTS: Forty-five consecutive patients underwent retrograde, infrainguinal recanalization attempts with the Outback re-entry catheter between February 2015 and August 2020. Thirty (67%) patients had a history of open vascular surgery in the index limb. In four patients, recanalizations were even more challenging due to previous surgical removal and/or ligation of the proximal segment of the superficial femoral artery. The retrograde access site of the Outback catheter was the femoropopliteal segment in 31 (69%) patients and crural vessels in 14 (31%) patients. The re-entry target sites were as follows: common femoral artery in 31 (69%) patients, superficial femoral artery in 9 (20%) patients, popliteal artery in 1 patient, and below-the-knee arteries in 2 patients. In four patients, the needle of the re-entry device was targeted to an inflated balloon, inserted via the antegrade route. The Outback re-entry catheter was placed via a 6-French sheath in 19 (42%) cases and sheathless in 26 (58%) cases. Technical success was achieved in 41 (91%) patients There were two instances of distal embolizations and three bleeding episodes. Amputation-free survival was 100% at 30 days, and after 12 months, freedom from cd-TLR was 95% at 30 days and 75% at 12 months of follow-up. Female sex was an independent predictor for cd-TLR at 12 months of follow-up. CONCLUSIONS: Retrograde use of the Outback re-entry catheter in infrainguinal chronic total occlusions provides an effective and safe endovascular adjunct, when conventional antegrade and retrograde recanalization attempts have failed.

Multiphase CTA-derived tissue maps aid in detection of medium vessel occlusions.

PURPOSE: Medium vessel occlusions (MeVOs) can be challenging to detect on imaging. Multiphase computed tomography angiography (mCTA) has been shown to improve large vessel occlusion (LVO) detection and endovascular treatment (EVT) selection. The aims of this study were to determine if mCTA-derived tissue maps can (1) accurately detect MeVOs and (2) predict infarction on 24-h follow-up imaging with comparable accuracy to CT perfusion (CTP). METHODS: Two readers assessed mCTA tissue maps of 116 ischemic stroke patients (58 MeVOs, 58 non-MeVOs) and determined by consensus: (1) MeVO (yes/no) and (2) occlusion site, blinded to clinical or imaging data. Sensitivity, specificity, and area under the curve (AUC) for MeVO detection were estimated in comparison to reference standards of (1) expert readings of baseline mCTA and (2) CTP maps. Volumetric and spatial agreement between mCTA- and CTP-predicted infarcts was assessed using concordance/intraclass correlation and Dice coefficients. Interrater agreement for MeVO detection on mCTA tissue maps was estimated with Cohen's kappa. RESULTS: MeVO detection from mCTA-derived tissue maps had a sensitivity of 91% (95% CI: 80-97), specificity of 82% (95% CI: 70-90), and AUC of 0.87 (95% CI: 0.80-0.93) compared to expert reads of baseline mCTA. Interrater reliability was good (0.72, 95% CI: 0.60-0.85). Compared to CTP maps, sensitivity was 87% (95% CI: 75-95), specificity was 78% (95%CI: 65-88), and AUC was 0.83 (95% CI: 0.76-0.90). The mean difference between mCTA- and CTP-predicted final infarct volume was 4.8 mL (limits of agreement: - 58.5 to 68.1) with a Dice coefficient of 33.5%. CONCLUSION: mCTA tissue maps can be used to reliably detect MeVO stroke and predict tissue fate.

Susac Syndrome: an uncommon cause of impaired vision.

A 35-year-old Caucasian woman presented an abrupt onset of bilateral impaired vision, and arrived to our attention two weeks later. She had a previous episode of mild dizziness. She underwent a fluorescein angiography showing branch retinal artery occlusions and a brain magnetic resonance imaging (MRI) revealing several supraand infratentorial FLAIR-hyperintense white matter lesions, two with contrast enhancement. Thrombophilic, autoimmune and infective (including Human Immunodeficiency Virus, Borrelia burgdorferi, Hepatitis B Virus, Hepatitis C Virus, Herpes Simplex Virus 1-2, Varicella Zoster Virus) screening was negative. Cerebrospinal fluid analysis showed intrathecal IgG synthesis. We suspected a Primary Central Nervous System Vasculitis, and intravenous steroids were started. Three months later a second brain MRI showed seven new lesions without contrast enhancement, and she revealed a cognitive impairment and bilateral hearing loss. Reviewing the clinical history and MRI, she fulfilled diagnostic criteria for Susac syndrome. She had two cycles of cyclophosphamide, and recovered in 6 months and then remained stable with metotrexate.