A systematic review and meta-analysis of combined carotid endarterectomy with ipsilateral proximal intervention (hybrid approach) for tandem carotid artery lesions.

OBJECTIVE: The safety and effectiveness of using the hybrid approach to treat tandem carotid lesions is controversial, and the clinical significance of the technical variants on the perioperative outcomes has not been evaluated. The present meta-analysis was performed to evaluate the technique, safety, effectiveness, and long-term outcomes of the hybrid approach. METHODS: The PubMed, Embase, and Cochrane Library databases were searched to identify studies from January 1, 1996 to January 11, 2020. The baseline patient characteristics, comorbidities, procedural details, and perioperative and long-term outcomes were collected and analyzed. A pooled overall survival curve was drawn. Univariate analysis was performed to compare the perioperative stroke risk between subgroups. RESULTS: Overall, 275 patients (mean age, 66.94 years) from 15 studies were included. All the patients had presented with tandem stenosis of ≥50%, and 67.2% were symptomatic. The overall technical success rate was 99.8% (95% confidence interval [CI], 98.0%-100.0%). The pooled perioperative complications rates were as follows: death, 1.5% (95% CI, 0.0%-2.9%); stroke, 2.6% (95% CI, 0.7%-4.4%); combined stroke/death, 3.3% (95% CI, 1.2%-5.4%); and myocardial infarction, 3.2% (95% CI, 0.7%-9.1%). The overall primary patency rates were 99.2% (95% CI, 96.0%-100.0%) and 88.2% (95% CI, 78.8%-95.4%) at 1 and 2 years, respectively. Reintervention was performed in 6.6% of the patients (95% CI, 3.0%-11.2%). The pooled overall survival rates were 89.9% (95% CI, 83.7%-96.7%), 83.7% (95% CI, 75.9%-92.2%), and 75.9% (95% CI, 66.5%-86.7%) at 1, 3, and 5 years, respectively. Operations in which carotid endarterectomy was performed first carried a significantly greater risk of perioperative stroke compared with those in which proximal intervention had been performed first (5.7% vs 0.0%; P = .01). No difference was found in perioperative stroke risk between the subgroups of baseline symptomatic status (asymptomatic, 5.1%; symptomatic, 1.9%; P = .32), preoperative antiplatelet therapy (dual, 3.6%; single, 5.8%; P = .79), and carotid clamping during intervention (clamping, 2.8%; unclamping, 6.3%; P = .40). CONCLUSIONS: For patients with a presumed high risk of neurologic events because of carotid tandem lesions, the hybrid approach could be considered a reasonable option with high technical success and acceptable perioperative and long-term results. Performing carotid artery stenting before carotid endarterectomy and administering perioperative dual antiplatelet therapy should be considered to promote technical success and better outcomes. Prospective and randomized controlled studies are needed to confirm the results and provide recommendations on patient selection for the hybrid approach.

Treatment Approaches and Outcomes for Acute Anterior Circulation Stroke Patients with Tandem Lesions.

OBJECTIVES: Endovascular thrombectomy (EVT) has revolutionized stroke care for large vessel occlusions (LVOs). However, over half treated remain functionally disabled or die. Patients with tandem lesions, or severe stenosis/occlusion of the cervical internal carotid artery (ICA) with intracranial LVO, may have technical EVT challenges and worse outcomes. We sought to compare treatments and outcomes for patients with anterior circulation tandem lesions versus isolated LVOs. MATERIALS AND METHODS: Consecutive tandem lesion and isolated intracranial LVO patients were identified at a single center. Demographics, medical history, presentations, treatments, and outcomes were collected and analyzed. RESULTS: From 381 EVT patients, 62 had tandem lesions related to atherosclerosis (74%) or dissection (26%). Compared to isolated intracranial LVOs, they were younger (63 vs 70, p = 0.003), had less atrial fibrillation (13% vs 40%, p < 0.0001), less adequate reperfusion (TICI 2b-3, 58% vs 82%, p < 0.0001), more intracranial hemorrhage (ICH, 13% vs 5%, p = 0.037), but similar 90-day functional independence (mRS 0-2, 34% vs 43%, p = 0.181). The cervical ICA was treated before intracranial EVT (57%), after (13%), not acutely (22%), or was inaccessible (8%). Acute cervical ICA treatments were stenting (57%) or angioplasty alone (13%). Neither acute stenting nor order of treatment was associated with outcomes (TICI 2b-3, ICH, or 90-day mRS 0-2). Among acutely stented, neither alteplase nor antiplatelets were associated with outcomes or stent patency. CONCLUSIONS: Tandem lesions were associated with less reperfusion, more ICH, but similar 90-day functional independence. No treatment approach was associated with outcomes. These data illustrate the technical challenges of tandem lesion treatment and underscore the importance of developing new approaches.

The Influence of 5'R and 5'S cdA and cdG on the Activity of BsmAI and SspI Restriction Enzymes.

Restriction endonucleases (REs) are intra-bacterial scissors that are considered tools in the fight against foreign genetic material. SspI and BsmAI, examined in this study, cleave dsDNA at their site of recognition or within a short distance of it. Both enzymes are representatives of type II REs, which have played an extremely important role in research on the genetics of organisms and molecular biology. Therefore, the study of agents affecting their activity has become highly important. Ionizing radiation may damage basic cellular mechanisms by inducing lesions in the genome, with 5',8-cyclo-2'-deoxypurines (cdPus) as a model example. Since cdPus may become components of clustered DNA lesions (CDLs), which are unfavorable for DNA repair pathways, their impact on other cellular mechanisms is worthy of attention. This study investigated the influence of cdPus on the elements of the bacterial restriction-modification system. In this study, it was shown that cdPus present in DNA affect the activity of REs. SspI was blocked by any cdPu lesion present at the enzyme's recognition site. When lesions were placed near the recognition sequence, the SspI was inhibited up to 46%. Moreover, (5'S)-5',8-cyclo-2'-deoxyadenosine (ScdA) present in the oligonucleotide sequence lowered BsmAI activity more than (5'R)-5',8-cyclo-2'-deoxyadenosine (RcdA). Interestingly, in the case of 5',8-cyclo-2'-deoxyguanosine (cdG), both 5'S and 5'R diastereomers inhibited BsmAI activity (up to 55% more than cdA). The inhibition was weaker when cdG was present at the recognition site rather than the cleavage site.

When UDG and hAPE1 Meet Cyclopurines. How (5'R) and (5'S) 5',8-Cyclo-2'-deoxyadenosine and 5',8-Cyclo-2'-deoxyguanosine Affect UDG and hAPE1 Activity?

Ionizing radiation is a factor that seriously damages cellular mechanisms/macromolecules, e.g., by inducing damage in the human genome, such as 5',8-cyclo-2'-deoxypurines (cdPus). CdPus may become a component of clustered DNA lesions (CDL), which are notably unfavorable for the base excision repair system (BER). In this study, the influence of 5'S and 5'R diastereomers of 5',8-cyclo-2'-deoxyadenosine (cdA) and 5',8-cyclo-2'-deoxyguanosine (cdG) on the uracil-DNA glycosylase (UDG) and human AP site endonuclease 1 (hAPE1) activity has been taken under consideration. Synthetic oligonucleotides containing 2'-deoxyuridine (dU) and cdPu were used as a model of single-stranded CDL. The activity of the UDG and hAPE1 enzymes decreased in the presence of RcdG compared to ScdG. Contrary to the above, ScdA reduced enzyme activity more than RcdA. The presented results show the influence of cdPus lesions located within CDL on the activity of the initial stages of BER dependently on their position toward dU. Numerous studies have shown the biological importance of cdPus (e.g., as a risk of carcinogenesis). Due to that, it is important to understand how to recognize and eliminate this type of DNA damage from the genome.

Addition of proximal intervention to carotid endarterectomy increases risk of stroke and death.

OBJECTIVE: Adding ipsilateral, proximal endovascular (IPE) intervention to carotid endarterectomy (CEA) for the treatment of tandem bifurcation and supra-aortic trunk disease is controversial. Some suggest that this combined strategy (CEA + IPE) confers no risk over isolated CEA (ICEA). Others disagree, reserving CEA + IPE for symptomatic patients. Using the Vascular Quality Initiative (VQI), this study assessed the effect of adding IPE to CEA on stroke and death risk. We further weighed CEA + IPE outcomes in the context of symptomatic status and Society for Vascular Surgery guidelines. METHODS: All CEAs in the VQI database from 2003 to 2017 were reviewed. Urgent and redo CEAs were excluded. CEA + IPE procedures were identified. To isolate the effect of IPE, patients undergoing other concurrent procedures were removed, providing an ICEA cohort. Primary end points were perioperative (30-day) stroke and death. Univariate and logistic regression analyses were performed. RESULTS: After exclusion and identification of CEA + IPE, 66,519 procedures were available for analysis. Of these, 66,115 represented ICEA and 404 represented CEA + IPE. Most patients (60%) were male, 93% were white, and 41% were symptomatic. Average age was 70 ± 9 years. Those undergoing CEA + IPE were more likely to be female (50% vs 40%; P < .001) and smokers (87% vs 76%; P < .001), and they were more likely to have coronary artery disease (32% vs 27%; P = .04), congestive heart failure (14% vs 10%; P = .01), and chronic obstructive pulmonary disease (30% vs 22%; P < .001). ICEA patients were more likely to have severe ipsilateral stenosis (86% vs 80%; P = .002) and to undergo intraoperative shunting (53% vs 49%; P = .05). There was no difference in 30-day mortality between cohorts (1% vs 1%; P = .23). However, CEA + IPE had higher rates of perioperative stroke (3.0% vs 1.4%; P = .01) and combined 30-day stroke and death (3.5% vs 1.8%; P = .02). When patients were stratified by symptomatic status, there were no differences in primary end points between cohorts in asymptomatic patients. In symptomatic patients, CEA + IPE carried significantly higher stroke (4.9% vs 1.9%; P = .002) and stroke and death risk (6.0% vs 2.4%; P = .002). After risk adjustment, predictors of stroke and death were diabetes (odds ratio [OR], 1.2; P = .001), symptomatic status (OR, 1.7; P < .001), and CEA + IPE (OR, 1.9; P = .02). CONCLUSIONS: The addition of IPE to CEA confers increased stroke and death risk over ICEA. Risk is largely in symptomatic patients. Although CEA + IPE increases risk compared with ICEA, overall risk remains low. Based on this VQI analysis, CEA + IPE outcomes for asymptomatic patients fall within Society for Vascular Surgery guidelines for ICEA. Those for symptomatic patients do not, and consideration should be given to other surgical bypass, cerebral protection, and staged strategies.

Order of Treatment Matters in Ischemic Stroke: Mechanical Thrombectomy First, Then Carotid Artery Stenting for Tandem Lesions of the Anterior Circulation.

BACKGROUND: One endovascular treatment option of acute ischemic stroke due to tandem occlusion (TO) comprises intracranial thrombectomy and acute extracranial carotid artery stenting (CAS). In this setting, the order of treatment may impact the clinical outcome in this stroke subtype. METHODS: Retrospective analysis was performed on data prospectively collected in 4 international stroke centers between 2013 and 2017. One hundred sixty-five patients with anterior TO were treated by endovascular therapy. Clinical and procedural data were evaluated. Favorable clinical outcome was defined as modified Rankin Scale (mRS) ≤2 at 90 days. Propensity score matching was performed for different treatment strategies. RESULTS: Patients' mean age was 65 ± 11 years and 118 were male (69%). The median admission National Institutes of Health Stroke Scale was 15 (interquartile range 8). In 59% of the patients (n = 101), the antegrade strategy (first stenting, then thrombectomy) was -performed, in 41% (n = 70) retrograde treatment (first thrombectomy, then stenting). Successful reperfusion (mTICI ≥2b) was achieved in 128 patients (75%). Fifty-nine patients (39%) showed a favorable clinical outcome after 90 days. After propensity score matching, data of 100 patients could be analyzed. Analysis revealed that the retrograde strategy yielded a significantly higher rate of successful reperfusion compared to the antegrade strategy (92 vs. 56%; p < 0.001). The rate of favorable clinical outcome after 90 days (mRS ≤2) was consistently higher (44 vs. 30%; p < 0.05) in the retrograde strategy group. CONCLUSION: Mechanical thrombectomy prior to acute CAS in TO is a predictive factor for favorable clinical outcome at 90 days.

Hybrid Interventions in the Case of Combined Stenosis of the Carotid Bifurcations and Supra-Aortic Arteries.

OBJECTIVES: The purpose of our study is to describe the technique, safety, and efficacy of hybrid carotid revascularization for the treatment of combined occlusive lesions of the carotid bifurcations and supra-aortic arteries. MATERIALS AND METHODS: We monitored the results of hybrid surgical interventions including carotid endarterectomy (CEA) and stenting either the common carotid artery (CCA) or the brachiocephalic trunk (BCT) in 12 patients. Nine men and 3 women with occlusive atherosclerosis made up the cohort. All surgical interventions were performed with local anesthesia by means of standard operative access to the bifurcation of the carotid artery. After the correction of the proximal stenosis of the CCA or BCT with subsequent angiography, the CEA was performed. The mean follow-up was 33.5 months (range, 6-48). RESULT: Ten patients underwent left CCA stenting in combination with CEA. Among the 10 patients, CEA was performed using the eversion technique in 5 cases and patch angioplasty in the other 5 cases. In the remaining 2 cases, the patients underwent CEA with patch angioplasty of the right internal carotid artery in combination with stenting of the BCT critical stenosis. During the early postoperative period and follow-up to 48 months, a stroke was not registered. CONCLUSION: Hybrid interventions (CEA and stenting of the CCA or BCT) allow combination of the advantages of each method in the treatment of multilevel vascular disease. This study confirms the safety and efficacy of hybrid interventions in a small cohort of patients while emphasizing the need for future randomized controlled trials in larger populations.

Acute carotid stenting versus non-stenting treatment of acute ischemic stroke due to tandem lesions: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness and safety of acute carotid stenting (ACS) in comparison to non-stenting interventions for patients experiencing acute ischemic stroke (AIS) caused by tandem lesions (TL). METHODS: A systematic review of literature from PubMed, Embase, and Cochrane databases was conducted to identify relevant studies published up to October 10, 2023. The comparison between ACS and no stenting in patients with TL undergoing endovascular therapy (EVT) focused on outcomes, such as 90-day modified Rankin Scale (mRS) score, successful recanalization, symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. RESULTS: The final analysis encompassed a total of 3,187 patients from 21 studies, with 1,786 patients classified as ACS patients and 1,401 as non-stent patients. The overall treatment effect favored the ACS group, as evidenced by their association with improved functional independence at 90 days (mRS 0-2) [relative risk (RR) = 1.18; 95% confidence interval (CI) 1.05-1.34; P < 0.05; I2 = 44%] and a higher rate of successful recanalization [modified Thrombolysis in Cerebral Infarction (mTICI) ≥ 2b/3] (RR = 1.16; 95% CI 1.09-1.25; P < 0.05; I2 = 40%). The risk of sICH was not significantly different between the two groups (RR = 1.28; 95% CI 0.98-1.68; P > 0.05; I2 = 0%). Additionally, there was no significant difference in 90-day mortality between the two groups (RR = 0.78; 95% CI 0.58-1.07; P > 0.05; I2 = 45%). CONCLUSION: Among TL patients undergoing EVT, ACS may be associated with better functional outcomes at 90 days compared with no stenting.

Timing of acute carotid artery stenting for tandem lesions in patients with acute ischemic stroke: A Maastricht Stroke Quality Registry (MaSQ-Registry) study.

BACKGROUND: To better understand the influence of treatment strategies on outcomes for patients with tandem lesions undergoing acute internal carotid artery (ICA) stenting during endovascular treatment (EVT), this study compared clinical, technical, and safety outcomes in patients with acute ischemic stroke due to a large vessel occlusion (LVO) who underwent ICA stenting before versus after intracranial thrombectomy. METHODS: This single-center retrospective cohort study included patients who underwent EVT due to a LVO and periprocedural ICA stenting for significant ICA stenosis or occlusion between September 2020 and January 2023. Data were extracted from the Maastricht Stroke Quality Registry (MaSQ-Registry). Primary outcome was the modified Rankin Scale (mRS) at 3 months. Secondary outcomes included procedure times, number of total thrombectomy attempts, first-attempt excellent recanalization rates (extended Thrombolysis In Cerebral Infarction (eTICI) ≥ 2C after one thrombectomy attempt), and safety outcomes. RESULTS: This study included 50 patients. Thirty-one patients (62%) underwent ICA stenting before intracranial thrombectomy. No significant differences between both groups were found regarding mRS, total procedure time, number of total thrombectomy attempts, first-attempt excellent recanalization, or complications. Time between groin puncture and recanalization (reperfusion time) was significantly longer in patients who had ICA stenting before intracranial thrombectomy versus after intracranial thrombectomy (45 min versus 28 min, P = 0.004). CONCLUSION: ICA stenting after intracranial thrombectomy in patients with tandem lesions undergoing EVT did not lead to better patient outcomes compared to stenting before intracranial thrombectomy, despite shorter reperfusion times.

Endovascular treatment of acute ischemic stroke patients with tandem lesions: antegrade versus retrograde approach.

OBJECTIVE: The optimal technique for treating tandem lesions (TLs) with endovascular therapy is debatable. The authors evaluated the functional, safety, and procedural outcomes of different approaches in a multicenter study. METHODS: Anterior circulation TL patients treated from January 2015 to December 2020 were divided on the basis of antegrade versus retrograde approach and included. The evaluated outcomes were favorable modified Rankin Scale (mRS) score (mRS score 0-2) at 3 months, ordinal shift in mRS score, successful recanalization, excellent recanalization, first-pass effect (FPE), time from groin puncture to successful recanalization, symptomatic intracranial hemorrhage (sICH), and 90-day mortality. RESULTS: Among 691 patients treated at 16 centers, 286 patients (174 antegrade and 112 retrograde approach patients) with acute stenting were included in the final analysis. There were no significant differences in mRS score 0-2 at 90 days (52.2% vs 50.0%, adjusted odds ratio [aOR] 0.83, 95% CI 0.42-1.56, p = 0.54), favorable shift in 90-day mRS score (aOR 1.03, 95% CI 0.66-1.29, p = 0.11), sICH (4.0% vs 4.5%, aOR 0.64, 95% CI 0.24-1.51, p = 0.45), successful recanalization (89.4% vs 93%, aOR 0.49, 95% CI 0.19-1.28, p = 0.19), excellent recanalization (51.4% vs 58.9%, aOR 0.59, 95% CI 0.40-1.07, p = 0.09), FPE (58.3% vs 69.7%, aOR 0.62, 95% CI 0.44-1.15, p = 0.21), and mortality at 90 days (16.6% vs 14.0%, aOR 0.94, 95% CI 0.35-2.44, p = 0.81) between the groups. The median (interquartile range) groin puncture to recanalization time was significantly longer in the antegrade group (59 [43-90] minutes vs 49 [35-73] minutes, p = 0.036). CONCLUSIONS: The retrograde approach was associated with faster recanalization times with a similar functional and safety profile when compared with the antegrade approach in patients with acute ischemic stroke with TL.

Efficacy and safety of bridging therapy versus direct thrombectomy for tandem lesions in acute stroke: A systematic review and meta-analysis.

BACKGROUND: Current studies have concluded that MT (Mechanical Thrombectomy) is safe and effective for tandem lesions (TL). However, The benefit of bridging therapy for TL is controversial. OBJECTIVE: To compare efficacy and safety between bridging therapy and direct thrombectomy of tandem lesions. METHOD: We conducted a systematic review and meta-analysis of studies comparing bridging therapy versus direct thrombectomy among TL patients with regards to symptomatic intracerebral hemorrhage(sICH), Parenchymal hemorrhage (PH), 3-month mortality, modified Rankin Scale (mRS) score within 3 months, successful reperfusion, and excellent reperfusion. The meta-analysis of proportions was conducted with a common effects model. RESULT: Five studies (n = 1198 patients) were identified for the systematic review. For safety outcomes, the bridging group had no significant difference in the rate of symptomatic intracranial hemorrhage (OR = 0.78, 95% CI = 0.49-1.25, P = 0.31) and the rate of PH (OR = 0.67, 95% CI = 0.39-1.13, P = 0.13) but significantly lower rate of 3-month mortality (OR = 0.53, 95% CI = 0.37-0.75, P = 0.0004) compared to the direct thrombectomy group. In terms of efficacy outcomes, the bridging therapy group had a significantly higher rate of 3- month good functional outcome (mRS 0-2) (OR = 1.76, 95% CI = 1.38-2.24, P < 0.00001) and successful recanalization (OR = 1.69, 95% CI = 1.27-2.25, P = 0.0003) but no significant difference in the rate of excellent recanalization(OR = 1.21, 95% CI = 0.91-1.59, P = 0.19) in patients with TL compared to direct thrombectomy group. CONCLUSION: Bridging therapy is effective in improving the 3-month functional prognosis and increasing the rate of arterial recanalization without increasing the risk of intracranial hemorrhage in patients with TL compared to direct thrombectomy. A large multicentre clinical RCT is expected, as are advanced intravenous thrombolysis and endovascular thrombectomy techniques.

Safety Outcomes of Antiplatelet Therapy During Endovascular Treatment of Tandem Lesions in Acute Ischemic Stroke Patients.

Risk of hemorrhage remains with antiplatelet medications required with carotid stenting during endovascular therapy (EVT) for tandem lesion (TLs). We evaluated the safety of antiplatelet regimens in EVT of TLs. This multicenter study included anterior circulation TL patients from 2015 to 2020, stratified by periprocedural EVT antiplatelet strategy: (1) no antiplatelets, (2) single oral, (3) dual oral, and (4) intravenous IV (in combination with single or dual oral). Primary outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were any hemorrhage, favorable functional status (mRS 0-2) at 90 days, successful reperfusion (mTICI score ≥ 2b), in-stent thrombosis, and mortality at 90 days. Of the total 691 patients, 595 were included in the final analysis. One hundred and nineteen (20%) received no antiplatelets, 134 (22.5%) received single oral, 152 (25.5%) dual oral, and 196 (31.9%) IV combination. No significant association was found for sICH (ref: no antiplatelet: 5.7%; single:4.2%; aOR 0.64, CI 0.20-2.06, p = 0.45, dual:1.9%; aOR 0.35, CI 0.09-1.43, p = 0.15, IV combination: 6.1%; aOR 1.05, CI 0.39-2.85, p = 0.92). No association was found for parenchymal or petechial hemorrhage. Odds of successful reperfusion were significantly higher with dual oral (aOR 5.85, CI 2.12-16.14, p = 0.001) and IV combination (aOR 2.35, CI 1.07-5.18, p = 0.035) compared with no antiplatelets. Odds of excellent reperfusion (mTICI 2c/3) were significantly higher for cangrelor (aOR 4.41; CI 1.2-16.28; p = 0.026). No differences were noted for mRS 0-2 at 90 days, in-stent thrombosis, and mortality rates. Administration of dual oral and IV (in combination with single or dual oral) antiplatelets during EVT was associated with significantly increased odds of successful reperfusion without an increased rate of symptomatic hemorrhage or mortality in patients with anterior circulation TLs.

Safety and efficacy of tirofiban in acute ischemic stroke due to tandem lesions undergoing mechanical thrombectomy: A multicenter randomized clinical trial (ATILA) protocol.

Background: In-stent thrombosis after mechanical thrombectomy (MT) worsen outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Although an optimal antiplatelet therapy is needed, the best approach to avoid in-stent thrombosis is yet to be elucidated. Hypothesis: Low-dose intravenous tirofiban is superior to intravenous aspirin in avoiding in-stent thrombosis in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. Methods: The ATILA-trial is a multicenter, prospective, phase IV, randomized, controlled (aspirin group as control), assessor-blinded clinical trial. Patients fulfilling inclusion criteria (AIS due to TL, ASPECTS ⩾ 6, pre-stroke modified Rankin Scale ⩽2 and onset <24 h) will be randomized (1:1) at MT onset to experimental (intravenous tirofiban) or control group (intravenous aspirin). Intravenous aspirin will be administered at a 500 mg single dose and tirofiban at a 500 µg bolus followed by a 200 µg/h infusion during first 22 h. All patients will be followed up to 3 months. Sample size estimated is 240 patients. Outcomes: The primary efficacy outcome is the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. The primary safety outcome is the rate of symptomatic intracranial hemorrhage. Secondary outcomes include functional independence defined as modified Rankin Scale 0-2, proportion of patients undergoing rescue therapy due to in-stent aggregation during MT and carotid reocclusion at 30 days. Discussion: ATILA-trial will be the first clinical trial regarding the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. Trial registration: NCT0522596.

Clinical and Safety Outcomes of Endovascular Therapy 6 to 24 Hours After Large Vessel Occlusion Ischemic Stroke With Tandem Lesions.

BACKGROUND AND PURPOSE: Effect of endovascular therapy (EVT) in acute large vessel occlusion (LVO) patients with tandem lesions (TLs) within 6-24 hours after last known well (LKW) remains unclear. We evaluated the clinical and safety outcomes among TL-LVO patients treated within 6-24 hours. METHODS: This multicenter cohort was divided into two groups, based on LKW to puncture time: early window (<6 hours), and late window (6-24 hours). Primary clinical and safety outcomes were 90-day functional independence measured by the modified Rankin Scale (mRS: 0-2) and symptomatic intracranial hemorrhage (sICH). Secondary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction score ≥2b), first-pass effect, early neurological improvement, ordinal mRS, and in-hospital and 90-day mortality. RESULTS: Of 579 patients (median age 68, 32.1% females), 268 (46.3%) were treated in the late window and 311 (53.7%) in the early window. Late window group had lower median National Institutes of Health Stroke Scale score at admission, Alberta Stroke Program Early Computed Tomography Score, rates of intravenous thrombolysis, and higher rates for perfusion imaging. After adjusting for confounders, the odds of 90-day mRS 0-2 (47.7% vs. 45.0%, adjusted odds ratio [aOR] 0.71, 95% confidence interval [CI] 0.49-1.02), favorable shift in mRS (aOR 0.88, 95% CI 0.44-1.76), and sICH (3.7% vs. 5.2%, aOR 0.56, 95% CI 0.20-1.56) were similar in both groups. There was no difference in secondary outcomes. Increased time from LKW to puncture did not predicted the probability of 90-day mRS 0-2 (aOR 0.99, 95% CI 0.96-1.01, for each hour delay) among patients presenting <24 hours. CONCLUSION: EVT for acute TL-LVO treated within 6-24 hours after LKW was associated with similar rates of clinical and safety outcomes, compared to patients treated within 6 hours.

Oxidatively generated tandem DNA modifications by pyrimidinyl and 2-deoxyribosyl peroxyl radicals.

Molecular oxygen sensitizes DNA to damage induced by ionizing radiation, Fenton-like reactions, and other free radical-mediated reactions. It rapidly converts carbon-centered radicals within DNA into peroxyl radicals, giving rise to a plethora of oxidized products consisting of nucleobase and 2-deoxyribose modifications, strand breaks and abasic sites. The mechanism of formation of single oxidation products has been extensively studied and reviewed. However, much evidence shows that reactive peroxyl radicals can propagate damage to vicinal components in DNA strands. These intramolecular reactions lead to the dual alteration of two adjacent nucleotides, designated as tandem or double lesions. Herein, current knowledge about the formation and biological implications of oxidatively generated DNA tandem lesions is reviewed. Thus far, most reported tandem lesions have been shown to arise from peroxyl radicals initially generated at pyrimidine bases, notably thymine, followed by reaction with 5'-flanking bases, especially guanine, although contiguous thymine lesions have also been characterized. Proper biomolecular processing is impaired by several tandem lesions making them refractory to base excision repair and potentially more mutagenic.

Tandem Lesions of the Vertebrobasilar System Treated by Thrombectomy and Vertebral Artery Stenting: A Case Report.

Objective: There are few reports on endovascular treatment of tandem lesions in the posterior circulation and no consensus on treatment strategies has been reached. We report a case of tandem lesions of basilar artery occlusion and vertebral artery stenosis treated by thrombectomy and vertebral artery stenting. Case Presentation: We present the case of a 73-year-old man who developed consciousness disorder and tetraplegia. Head and neck CTA revealed tandem left vertebral artery stenosis and basilar artery occlusion. The patient was treated using a reverse technique, which involves performing thrombectomy first and then vertebral artery stenting, along with Carotid Guardwire PS. Postoperative impairment of consciousness and improvement of tetraplegia were achieved. Conclusion: The reverse technique combined with Carotid Guardwire PS may be a useful treatment strategy for tandem lesions in the posterior circulation.

Impact of Serial Coronary Stenoses on Various Coronary Physiologic Indices.

BACKGROUND: Determining the functional significance of each individual coronary lesion in patients with serial coronary stenoses is challenging. It has been proposed that nonhyperemic pressure ratios, such as the instantaneous wave free ratio (iFR) and the ratio of resting distal to proximal coronary pressure (Pd/Pa) are more accurate than fractional flow reserve (FFR) because autoregulation should maintain stable resting coronary flow and avoid hemodynamic interdependence (cross-talk) that occurs during hyperemia. This study aimed to measure the degree of hemodynamic interdependence of iFR, resting Pd/Pa, and FFR in a porcine model of serial coronary stenosis. METHODS: In 6 anesthetized female swine, 381 serial coronary stenoses were created in the left anterior descending artery using 2 balloon catheters. The degree of hemodynamic interdependence was calculated by measuring the absolute changes in iFR, resting Pd/Pa, and FFR across the fixed stenosis as the severity of the other stenosis varied. RESULTS: The hemodynamic interdependence of iFR, resting Pd/Pa, and FFR was 0.039±0.048, 0.021±0.026, and 0.034±0.034, respectively (all P<0.001). When the functional significance of serial stenoses was less severe (0.70-0.90 for each index), the hemodynamic interdependence was 0.009±0.020, 0.007±0.013, and 0.017±0.022 for iFR, resting Pd/Pa, and FFR, respectively (all P<0.001). However, in more severe serial coronary stenoses (<0.60 for each index), hemodynamic interdependence was 0.060±0.050, 0.037±0.030, and 0.051±0.037 for iFR, resting Pd/Pa, and FFR, respectively (all P<0.001). CONCLUSIONS: When assessing serial coronary stenoses, nonhyperemic pressure ratios are affected by hemodynamic interdependence. When the functional significance of serial coronary stenoses is severe, the effect is similar to that which is seen with FFR.

A Case Series and Literature Review of Vertebral Artery Stump Syndrome.

PURPOSE: Stump syndrome refers to cerebral ischaemic symptoms caused by an embolus from a previously occluded ipsilateral artery that occludes a down-stream artery. It can be divided into two types: carotid stump syndrome and vertebral artery stump syndrome (VASS). At present, there is limited clinical experience with VASS. We aimed to propose a more precise diagnostic standard for VASS, and to share our experience with handling this condition. MATERIALS AND METHODS: We retrospectively collected data of patients who were treated with endovascular thrombectomy in the stroke centre of the First Hospital of Jilin University from January 2016 to March 2020. After screening patients with posterior-circulation acute ischaemic stroke, we selected patients who had an acute occlusion of an intracranial artery in the context of a previously occluded ipsilateral vertebral artery origin, as confirmed by digital subtraction angiography. RESULTS: Eleven patients met our inclusion criteria. Nine patients achieved recanalization of both extracranial and intracranial occluded arteries, one patient had modified thrombolysis in cerebral infarction grade 3, and eight patients had grade 2b. Residual stenosis of recanalized intracranial arteries was less than 30% in all cases, while three patients had embolism of distal arteries. No dissection or subarachnoid haemorrhage occurred. Two patients didn't reach vascular recanalization. Among the nine patients with recanalized artery, four had a 90-day modified Rankin Scale score ≤ 3 (favourable outcome), and four patients died; As for the two non-recanalized patients, one had a mRS score of 5 and one died. CONCLUSION: VASS is a clinical syndrome caused by embolic occlusion of a distal intracranial artery occluded ipsilateral extracranial vertebral artery. Antegrade blood flow from the collateral vessels, distal embolic occlusion and mild or no residual stenosis of the occluded intracranial artery after recanalization are notable features of this clinical event. Endovascular thrombectomy may be effective for treating VASS.

Preliminary Experience Using a Covered Stent Graft in Patients with Acute Ischemic Stroke and Carotid Tandem Lesion.

INTRODUCTION: Endovascular treatment with a covered heparin-bonded stent graft has been shown to be feasible and safe for treatment of peripheral artery disease, but its role in carotid disease remains unclear. The purpose of this study was to determine the feasibility and safety of a covered stent graft in treating cervical carotid artery disease in a consecutive series of patients with acute ischemic stroke (AIS) due to tandem lesion in a single high-volume Comprehensive Stroke Center. METHODS: A retrospective review of all patients that underwent carotid endovascular interventions during mechanical thrombectomy for AIS using a self-expanding covered stent graft at Vall d'Hebron University Hospital between 2016 and 2018 was conducted. Patient clinical and angiographical characteristics as well as postoperative outcome and follow-up were recorded. RESULTS: A total of eight patients were treated with the covered stents, and we observed significant improvement in stroke severity at 24 h in 5/8 patients (mean NIHSS 18 ± 5 vs 12 ± 8, p = 0.02). Successful recanalization (TICI 2b-3) after thrombectomy was achieved in 5/8 (62.5%) patients. One stent occluded during the procedure. At 3-month follow-up, stents were patent in three (37.5%) patients (two with mRS 3 and one with mRS 1). The stents of the remaining four patients (62.5%) were occluded (one with mRS 2 and three with mRS 4), although the patients did not show signs of stroke recurrence. CONCLUSION: The preliminary results of our study show that the self-expanding covered stent graft did not achieve satisfactory patency at 90-days among patients with AIS and tandem lesions, suggesting that its use in the carotid circulation may not be recommended in the context of AIS.

Simultaneous revascularization of the occluded internal carotid artery using the Solitaire as a workhorse wire during acute ischemic stroke intervention.

INTRODUCTION: Tandem lesions involving a large vessel occlusion intracranially with concomitant cervical carotid critical stenosis or occlusion are a common presentation of acute ischemic stroke. These lesions are both challenging and time-consuming but can be extremely beneficial for patients when successful. We present a technique utilizing the pusher wire of the stent retriever used for intracranial thrombectomy as the workhorse wire for carotid intervention using a monorail system to perform cervical carotid angioplasty. METHODS: We reviewed four successive patients who presented with a tandem occlusion and underwent thrombectomy and simultaneous carotid artery intervention using this technique. RESULTS: All four patients had radiographically successful intracranial thrombectomy and cervical carotid revascularization. Time from groin puncture to intracranial stent retriever deployment was 63 min on average. Then, using the pusher wire as a monorail workhorse, time from stent retriever deployment to carotid angioplasty was on average 6 min. DISCUSSION: This technique allows for cervical carotid revascularization to begin during the recommended 5-min wait time after stent retriever deployment, allowing for rapid near-simultaneous revascularization across both lesions. This technique has been reported briefly in the past for management of a cervical dissection. There is continued debate regarding the management of tandem occlusions, as to which lesion should be managed first. CONCLUSION: As the management paradigms of tandem occlusions continue to evolve, this technique may improve outcomes by expediting endovascular intervention. Using the stent retriever wire provides a method of expediting the management of the proximal lesion after addressing the more distal intracranial occlusion first.