Whether endovascular thrombectomy (EVT) benefits medium vessel occlusion (MeVO) stroke remains uncertain. Brain frailty, reflecting chronic small-vessel disease and neurodegeneration, may indicate weaken collateral circulation and limit tissue salvage. We retrospectively studied 227 MeVO patients who achieved successful reperfusion (mTICI 2b-3). Baseline multimodal CT (NCCT + CTP) and follow-up MRI/CT were used to quantify the penumbral salvage index (PSI). Brain frailty was categorized on NCCT as absent (n = 66), mild (n = 88), or moderate-to-severe (n = 73) based on white matter hyperintensities, atrophy, and vascular lesions. Mediation analysis tested the indirect effect through collateral status. Greater frailty severity was associated with progressively lower PSI (0.81 vs 0.70 vs 0.63, p < 0.001). In multivariable models, higher frailty independently predicted lower PSI (β = -0.19, p = 0.003). Collateral dysfunction mediated 38% of the frailty-PSI association. Correspondingly, rates of excellent outcome (mRS 0-1) and functional independence (mRS 0-2) at 90 days declined with increasing frailty severity (both p < 0.001). These findings identify brain frailty as an independent predictor of impaired penumbral salvage for MeVO after EVT and links it to worse 90-day outcomes. The effect appears substantially mediated by collateral failure. Incorporating brain frailty into acute assessment may improve prognostic stratification among patients who achieve successful reperfusion.

INTRODUCTION:The lenticulostriate arteries (LSAs) demonstrate developmental variability that is linked to the A1 segment of the anterior cerebral artery (ACA) anatomy. In acute ischaemic stroke (AIS) with MCA occlusion, basal ganglia (BG) infarction extent and haemorrhagic transformation (HT) correlate with LSA involvement. This study aimed to assess whether ipsilateral A1-ACA variations influence BG infarction severity and thrombectomy outcomes. PATIENTS AND METHODS:A control cohort (n = 300) undergoing catheter angiography from September 2023 to November 2024 was used to define anatomical relationships between the A1-ACA and the medial LSA (mLSA). A thrombectomy cohort (n = 236; MCA occlusion) from January 2019 to November 2024 was stratified by A1-ACA status (normal vs hypoplastic/absent) on pre-intervention CTA. Final basal ganglia infarct volume (FIVBG) was quantified on 72-h post-procedure MRI/NCCT. Associations between A1-ACA status, FIVBG, HT and outcomes were analysed via multivariable regression. Mediation analysis evaluated FIVBG's role in A1-ACA anatomy and HT relationships. RESULTS:Hypoplastic/absent A1 segments occurred in 16.3% (49/300) of controls, who had a reduced mLSA presence (6.1% vs 20.7%, P = .016) and increased predominant lateral LSAs (71.4% vs 50.6%, P = .007) compared to those with a normal A1. Among thrombectomy patients, hypoplastic/absent A1 (15.3%, 36/236) predicted larger FIVBG (median: 29.01 cm3 [24.4-37.8] vs median: 25.80 cm3 [21.5-32.5], P = .004) and higher HT rates (66.67% vs 34%, P < .01). Multivariable analyses confirmed A1 hypoplasia/absence was independently associated with FIVBG (β = 5.714; 95% CI, 2.860-8.569; P < .01) and HT (aOR = 3.059; 95% CI, 1.284-7.288; P = .012). Furthermore, FIVBG mediated 44% of the indirect effect of A1 development on HT post-EVT. CONCLUSIONS:Hypoplastic/absent A1 segments correlate with impaired mLSA development, thereby exacerbating BG infarction and HT risk post-thrombectomy. As one of several predictors, A1 segment morphology on preprocedural CTA may help stratify patients at risk for larger BG infarcts and haemorrhagic complications.

BACKGROUND:Rapid local ischemic postconditioning may protect the brain after acute ischemic stroke, but its safety and optimal dosing in successfully reperfused patients after mechanical thrombectomy remain undefined. METHODS:This investigator-initiated, prospective, adaptive, multicenter phase I single-arm dose-finding trial employed a Bayesian Optimal Interval (Bayesian Optimal Interval Phase I/II) design. Patients with anterior circulation large-vessel occlusion and modified Thrombolysis in Cerebral Infarction 2b/3 reperfusion were enrolled without randomization. Within 5 minutes of recanalization, rapid local ischemic postconditioning was delivered via a balloon-guiding catheter positioned at the ipsilateral C1-intracranial internal carotid artery, alternating inflation/deflation to interrupt antegrade flow. Six dose levels were prespecified by inflation/deflation durations and cycles: 15/15s ×5; 1/1, 2/2, 3/3, 4/4, and 5/5 minutes ×4. The dose-limiting toxicity (including malignant infarction, procedure-related complications requiring treatment, or other procedure-attributable serious adverse events) threshold was 15%. The efficacy target (absence of infarct growth >10 mL at 72 hours) was 60%. Doses were eliminated if the posterior probability that toxicity exceeded 15% was ≥0.95 or efficacy <60% was ≥0.90. The dose with the highest utility meeting these criteria was selected. RESULTS:Five cohorts (n=25, 5 each) were enrolled. Four cohorts received 2/2 minutes×4 (n=20): 14 met the efficacy end point (posterior probability true efficacy <60%, ≈0.15), and 1 had a dose-limiting toxicity due to large infarction growth (probability true toxicity >15%, ≈0.16). One cohort received 3/3 minutes×4 (n=5): 3 met the efficacy end point (probability true efficacy <60%, ≈0.31) and 2 had dose-limiting toxicities due to large infarction growth (probability true toxicity >15%, ≈0.95). This triggered the predefined safety rule, preventing further testing at 3/3-minute and higher doses. Bayesian Optimal Interval Phase I/II selected 2/2 minutes×4 as the optimal regimen with a favorable efficacy-toxicity profile. CONCLUSIONS:Rapid local ischemic postconditioning initiated immediately after thrombectomy was feasible. The 2/2 minutes×4 regimen met prespecified safety and efficacy thresholds and warrants evaluation in a larger, definitive trial. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06526429.

BACKGROUND:The benefits of endovascular thrombectomy (EVT) over medical treatment for medium vessel occlusion (MeVO) remain uncertain. Understanding how vascular reperfusion leads to favorable outcomes is crucial. This study examines whether penumbra salvage and infarct volume reduction quantify EVT benefits in MeVO patients and assesses their impact on clinical improvement post-reperfusion. METHODS:We conducted a multicenter, observational study analyzing MeVO patients who underwent thrombectomy and received multimodal CT imaging from January 2020 to June 2024. EVT efficacy was evaluated by measuring follow-up infarct volume (FIV) on CT scans 24-48 h post-procedure and calculating the penumbra salvage index (PSI). PSI is the ratio of salvaged tissue volume (difference between baseline delay time (DT) >3 s volume and FIV) to baseline DT >3 s volume. Mediation analysis assessed PSI and FIV's contributions to successful reperfusion and functional outcomes. RESULTS:Of 338 patients, 241 (72%) achieved successful reperfusion. Median FIV was 21 mL (IQR 12-32 mL), and median PSI was 0.68 (IQR 0.50-0.82). Successful reperfusion was linked to a 0.10 increase in PSI (95% CI: 0.05-0.15, p < 0.001) and a 4.36 mL reduction in FIV (95% CI: 1.31-7.20, p = 0.005). Successful reperfusion predicted improved outcomes, with an adjusted odds ratio (aOR) of 1.92 (95% CI: 1.08-3.47, p = 0.020) for excellent outcomes (modified Rankin Scale (mRS) score 0-1) and an aOR of 1.70 (95% CI: 1.01-2.89, p = 0.024) for functional independence (mRS score 0-2). PSI and FIV accounted for 44% and 16%, respectively, of the effect of reperfusion on excellent outcomes. CONCLUSIONS:In acute MeVO patients, penumbra salvage significantly mediates the beneficial relationship between reperfusion and excellent clinical outcomes, more so than infarct volume reduction.

Esophageal fistulas (EFs) arising from esophageal cancer, trauma, or iatrogenic injury can lead to severe complications. While covered metal stents can effectively occlude EFs, their long-term implantation may result in migration, in-stent stenosis, and bleeding. Biodegradable covered stents offer temporary support followed by self-degradation to circumvent permanent implantation risks, therefore can act as local biotherapeutic platforms. We have developed a novel biodegradable, biomimetic stent composed of polydioxanone with a hydrogel coating and oriented, TGF-β1-loaded nanofiber membrane. It provides up to 6.92 N of radial support force and maintains integrity for 30 days. Employing microsol oriented electrospinning technology, TGF-β1-loaded nanofibers are applied to the stent's surface, not only occluding the EF but also creating a directional matrix for stem cell migration and tissue repair. Additionally, GelMA laden with autologous BMSCs encapsulates the PLGA nanofibers, with BMSCs showing oriented growth and differentiation into myoblasts upon TGF-β1 stimulation. In a rabbit EF model, this biomimetic esophageal stent significantly lowered fistula incidence. Esophagography and histopathological assessments revealed complete EF occlusion in 78 % of subjects. These findings suggest that our biomimetic esophageal stent not only supports and seals the esophagus but also promotes self-repair and tissue regeneration, advancing the application of biodegradable stents for EF treatment.

Purpose: To investigate the effectiveness of prophylactic embolization of the internal iliac artery (IIA) or superior gluteal artery (SGA) before open reduction and internal fixation (ORIF) in reducing intraoperative blood loss (IBL) in hemodynamically stable patients with complex acetabular fractures. Materials and Methods: A total of 136 patients with complex acetabular fractures were retrospectively included and divided into the prophylactic transcatheter arterial embolization (PTAE) group and non-PTAE group, depending on whether ipsilateral IIA or SGA was embolized using coils within 3 days before ORIF. Demographic characteristics, injury severity score, fracture classification, and intraoperative and postoperative data were compared between the 2 groups. Propensity score matching (PSM) was also performed to balance the baseline characteristics of the patients. The determinants of IBL were investigated using multivariate linear regression analysis. Results: The PTAE and non-PTAE groups consisted of 64 and 72 patients, respectively. PSM yielded 43 matched pairs. After matching, IBL in the PTAE group was less than that in the non-PTAE group (median [interquartile range], 800 [400-1,200] mL vs 1,300 [1,000-1,600] mL; P < .001). Furthermore, the PTAE group showed a shorter ORIF duration and lower intraoperative and 24-hour postoperative blood transfusion requirements (all P < .05). Multivariate analysis revealed that PTAE and the duration of surgery were associated with IBL (PTAE: beta = -0.407; P < .001; duration of surgery: beta = 0.237; P = .021). Conclusions: Prophylactic IIA or SGA embolization may be beneficial in reducing IBL during ORIF in hemodynamically stable patients with complex acetabular fractures.

Tirofiban is a nonpeptide antagonist of the glycoprotein IIb/IIIa receptor that inhibits platelet aggregation selectively. Despite widespread use in acute ischemic stroke in conjunction with endovascular treatment, the role of tirofiban is uncertain. To assess whether intravenous tirofiban initiated before endovascular thrombectomy improves thrombectomy outcomes by achieving first-pass recanalization without intracranial hemorrhagic risk. This was a multicenter, prospective, open-label, blinded, end point phase 2 randomized clinical trial that enrolled patients from 7 Chinese hospital stroke centers between April 30, 2021, and July 16, 2023. Eligible patients were aged 18 to 85 years with large vessel occlusion (internal carotid artery or M1 or M2 segment of middle cerebral artery) and were considered for endovascular thrombectomy within 24 hours of ischemic stroke onset or last known well time. Patients with a history of atrial fibrillation or treated with intravenous thrombolysis were excluded. Patients were randomly assigned (1:1) to intravenous tirofiban (10 μg/kg bolus plus 0.1 μg/kg per minute infusion for 24 hours) or standard care before endovascular thrombectomy using a web-based, computer-generated randomization procedure. The primary outcome was the proportion of patients achieving first-pass recanalization without symptomatic intracranial hemorrhage. First-pass recanalization was assessed by reviewers blinded to treatment allocation and predefined as successful recanalization of a targeted vessel after a single pass of thrombectomy. The primary outcome was analyzed by modified Poisson regression with robust error estimation, adjusting for time from onset or last known well time to randomization and vessel occlusion site. Among 200 patients randomized (median age, 66 years [IQR, 58-72 years]; 146 male [73%]), 102 were allocated to receive intravenous tirofiban, and 98 were allocated to receive standard care before endovascular thrombectomy. In the intention-to-treat analysis, 64 of 99 patients receiving tirofiban (65%) and 46 of 95 control patients (48%) achieved the primary outcome of first-pass recanalization without symptomatic intracranial hemorrhage (adjusted risk ratio, 1.34 [95% CI, 1.04-1.73]; P = .03). Incidence of symptomatic intracranial hemorrhage was 0% (0 of 101 patients) in the tirofiban group vs 6% (6 of 98 patients) in the control group (unadjusted risk difference, −0.06 [95% CI, −0.11 to −0.01]). In this randomized clinical trial of patients who had acute ischemic stroke with no history of atrial fibrillation and no prior intravenous thrombolysis, intravenous tirofiban administered before endovascular thrombectomy increased the likelihood of first-pass recanalization without symptomatic intracranial hemorrhage. These findings suggest that neurointerventionalists may consider this pre-procedure antiplatelet treatment to facilitate endovascular thrombectomy. ClinicalTrials.gov Identifier: NCT04851457

The purpose of this study is to investigate whether patients with symptomatic severe intracranial atherosclerotic stenosis (ICAS) and downstream perfusion deficit could benefit from adding percutaneous transluminal angioplasty and stenting (PTAS) to medical therapy. We retrospectively reviewed patients with symptomatic severe ICAS and an Alberta Stroke Program Early CT score of < 6 on mean transit time map who received either medical plus PTAS therapy (PTAS group) or medical therapy alone (medical group) between January 2016 and December 2019 at a single center. After 1:1 propensity score matching, we analyzed the primary outcome—cumulative event rate (defined as ischemic stroke in the qualifying artery)—along with four secondary outcomes (any intracranial hemorrhage within 30 days; disabling stroke or death; any stroke, transient ischemic attack, or cardiovascular events; and death by the end of follow-up). A total of 145 patients (79 in the PTAS group, 66 in the medical group) were included. After PSM, during a median follow-up of 43 months, the cumulative event rate was significantly lower in the PTAS group (11.6

The optimal neuroimaging modalities for differentiating intracranial atherosclerotic stenosis-related large vessel occlusion (ICAS-LVO) from embolism related LVO remain uncertain. This study aimed to address this question by directly comparing collateral circulation using either baseline CT perfusion (CTP) or multiphase CT angiogram (mCTA) to define collaterals. We retrospectively analyzed consecutive patients with acute large vessel occlusion from October 2021 to December 2023. All patients underwent CTP before endovascular therapy, and mCTA was reconstructed from CTP data. In-situ ICAS-LVO was confirmed by a neuro-interventional radiologist. Favorable collateral circulation was defined as a collateral index <0.4 on CTP or a collateral score ≥3 on mCTA. Of 377 patients, 72 (19%) had ICAS-LVO. Patients with only a collateral score ≥3 did not show significantly higher odds of ICAS-LVO ( P = 0.681). In contrast, those with a collateral index <0.4 but not favorable mCTA collateral had higher odds of ICAS-LVO (OR2.69, 95%CI [1.07–7.01], P = 0.037). Subgroup analysis showed that a collateral grading scale ≥3 may not predict ICAS-LVO within 6 hours, whereas CTP’s predictive performance remained consistently strong in both early and late windows. CTP defined favorable collaterals of collateral index <0.4 demonstrate greater predictive value for ICAS-LVO compared to mCTA, especially within an early time window.

BACKGROUND:The benefits of endovascular thrombectomy (EVT) over medical treatment for medium vessel occlusion (MeVO) remain uncertain. Understanding how vascular reperfusion leads to favorable outcomes is crucial. This study examines whether penumbra salvage and infarct volume reduction quantify EVT benefits in MeVO patients and assesses their impact on clinical improvement post-reperfusion. METHODS:We conducted a multicenter, observational study analyzing MeVO patients who underwent thrombectomy and received multimodal CT imaging from January 2020 to June 2024. EVT efficacy was evaluated by measuring follow-up infarct volume (FIV) on CT scans 24-48 h post-procedure and calculating the penumbra salvage index (PSI). PSI is the ratio of salvaged tissue volume (difference between baseline delay time (DT) >3 s volume and FIV) to baseline DT >3 s volume. Mediation analysis assessed PSI and FIV's contributions to successful reperfusion and functional outcomes. RESULTS:Of 338 patients, 241 (72%) achieved successful reperfusion. Median FIV was 21 mL (IQR 12-32 mL), and median PSI was 0.68 (IQR 0.50-0.82). Successful reperfusion was linked to a 0.10 increase in PSI (95% CI: 0.05-0.15, p < 0.001) and a 4.36 mL reduction in FIV (95% CI: 1.31-7.20, p = 0.005). Successful reperfusion predicted improved outcomes, with an adjusted odds ratio (aOR) of 1.92 (95% CI: 1.08-3.47, p = 0.020) for excellent outcomes (modified Rankin Scale (mRS) score 0-1) and an aOR of 1.70 (95% CI: 1.01-2.89, p = 0.024) for functional independence (mRS score 0-2). PSI and FIV accounted for 44% and 16%, respectively, of the effect of reperfusion on excellent outcomes. CONCLUSIONS:In acute MeVO patients, penumbra salvage significantly mediates the beneficial relationship between reperfusion and excellent clinical outcomes, more so than infarct volume reduction.

Background:A new diffusion-weighted imaging (DWI) technique, known as zoomed-field-of-view echo-planar DWI (z-DWI), has been developed to reduce geometric distortions and susceptibility artifacts and to achieve higher spatial resolution. However, it remains unclear whether z-DWI, compared with the traditional DWI technique, can enhance the diagnostic performance of deep-learning-based computer-aided diagnosis (DL-CAD) and radiologists using DL-CAD in detecting prostate cancer (PCa). This study aims to evaluate and compare the diagnostic performance and PI-RADS scores of DL-CAD in detecting PCa using conventional full-field-of-view single-shot echo-planar DWI (f-DWI) and advanced z-DWI and to extend this comparison to clinical practice, in which radiologists use DL-CAD. Methods:This study retrospectively included magnetic resonance imaging from 359 patients for suspected PCa. There were 496 prostate lesions included, with 253 (51%) being malignant. Using a DL-CAD system, images of f-DWI and z-DWI were uploaded separately to obtain the localizations and the prostate imaging reporting and data system (PI-RADS) scores of suspected malignant lesions. The results were compared to histopathologic results. The diagnostic performance of f-DWI and z-DWI were evaluated using the free-response receiver operating characteristics and the alternative free-response receiver operating characteristics curves. Discrepancies in PI-RADS scores were analyzed. Additionally, two radiologists participated in consensus reading images by using DL-CAD with different DWI techniques, and their performance and PI-RADS scores were compared. Lastly, the relationship between PI-RADS discrepancies and clinically significant prostate cancer (csPCa) risk was analyzed. Results:z-DWI enabled DL-CAD to exhibit better diagnostic performance [area under the curve (AUC), 0.857 vs. 0.841; P=0.02], with a higher mean PI-RADS score for PCa lesions (4.26 vs. 3.92; P<0.001), and improved scores for 66 PCa lesions compared to f-DWI. When radiologists used DL-CAD, z-DWI also enabled radiologists to exhibit a higher mean PI-RADS score for PCa lesions (4.31 vs. 4.02; P<0.001) and improved scores for 56 PCa lesions compared to f-DWI, however, no statistically significant difference was found in diagnostic performance (AUC, 0.887 vs. 0.881; P=0.16). In multivariable logistic regression analyses, upgraded PI-RADS scores by z-DWI were significantly associated with csPCa risk. Conclusions:z-DWI, in comparison to f-DWI, enhances the diagnostic performance of DL-CAD for PCa, assigning higher PI-RADS scores to malignant lesions. Despite offering limited improvement for radiologists using DL-CAD, z-DWI shows promise in enhancing the detection of csPCa.

BACKGROUND:We aim to assess the efficacy of rapid local ischemic postconditioning (RL-IPostC) following successful reperfusion in patients with acute ischemic stroke with anterior circulation large vessel occlusion who underwent endovascular thrombectomy. METHODS:We conducted an ambidirectional cohort study with 78 prospectively enrolled patients with RL-IPostC and endovascular thrombectomy and 129 retrospectively enrolled patients with endovascular thrombectomy. The RL-IPostC procedure involved 5 cycles of 15-s balloon inflation and deflation in the ipsilateral internal carotid artery. The primary outcome was functional independence, defined as a modified Rankin Scale score of 0 to 2. Secondary outcomes included excellent outcomes (modified Rankin Scale score, 0-1) and early therapeutic response. Imaging outcomes involved infarct volume changes and cerebral edema measurements. Outcomes were compared with postpropensity score matching (1:1) and assessed using univariable and multivariable regression models. RESULTS:In the matched cohort of 136 patients (mean age, 71±14 years; 70 men [51%]), RL-IPostC was associated with a higher rate of functional independence (adjusted odds ratio, 2.47 [95% CI, 1.10-5.68]; P=0.030). The RL-IPostC group exhibited significantly reduced infarct volumes at 24 hours (difference, -12.2 [95% CI, -23.9 to -0.53]; P=0.041) and less infarct growth (difference, -12.2 [95% CI, -23.9 to -0.45]; P=0.042). Furthermore, RL-IPostC correlated with lower increases in net water uptake (difference, -0.04 [95% CI, -0.07 to -0.01]; P=0.018), lower decrease cerebrospinal fluid volume (difference, -7.75 [95% CI, -11.7 to -3.84]; P<0.001), and reduced midline shift at 24 hours (difference, -1.39 [95% CI, -2.48 to -0.30]; P=0.013). CONCLUSIONS:RL-IPostC tends to promote functional independence and reduces infarct growth and cerebral edema in patients with acute ischemic stroke post-reperfusion.

Background:Carotid blowout syndrome (CBS) frequently occurs at the distal internal carotid artery (distal-ICA) in patients with nasopharyngeal carcinoma (NPC), and remedial treatments run a high risk for neurologic complications. A case-control study was conducted to evaluate the safety and efficacy of protective stent insertion at the distal-ICA to prevent CBS in NPC patients, with a comparison to endovascular coil occlusion.Methods:A total of 28 consecutive NPC patients at high risk of CBS from June 2019 to December 2021 in Shanghai Sixth People's Hospital (a tertiary institution) were retrospectively included and divided into a stent protection group and occlusion group. Technique feasibility, treatment outcomes and neurological deficiency were compared between the two groups by two-sample test. Kaplan-Meier analysis compared patients' survival rates at mid-term follow-up.Results:Stent insertion was performed in 15 patients and ICA occlusion in 13 patients. The technical success rate was 100% in both groups. Procedure-related ischemic stroke was identified in 2 patients (15.4%) in the occlusion group, compared with none in the stent protection group. Bleeding was encountered in one patient in the stent protection group and one patient in the occlusion group, each. During a median follow-up of 10.5 (range, 2-31) months, 3 patients (20%) showed asymptomatic in-stent occlusion in the stent protection group. Notably, the median survival time was significantly longer in the stent protection group than in the occlusion group (23.3 vs. 15.8 months, P=0.04).Conclusions:Protective stenting the distal-ICA was similarly effective in preventing CBS in NPC patients but was safer than endovascular occlusion of ICA.

STUDY DESIGN:Retrospective. OBJECTIVE:To explore the value of time-resolved CE-MRA in evaluating and locating the SVM before digital subtraction angiography (DSA). SUMMARY OF BACKGROUND DATA:Spinal vascular malformations (SVM) can be detected with time-resolved contrast-enhanced MRA (CE-MRA). MATERIALS AND METHODS:One hundred seventy-eight patients with suspected SVM who underwent time-resolved CE-MRA examination and DSA were included in this study. DSA served as the reference standard. The type of SVM, feeding arteries, fistula/nidus, and proximal segment of draining veins were evaluated on time-resolved CE-MRA. The diagnostic performance and classification performance of time-resolved CE-MRA in the diagnosis of SVM is summarized in terms of overall accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The difference in catheterized vessels during spinal vascular DSA between the actual and estimated number was also analyzed. RESULTS:One hundred forty-seven patients were diagnosed with SVM (20 cervical, 118 thoracolumbar, and 9 deep lumbosacral), and 31 patients were diagnosed with non-SVM, according to DSA findings. The diagnostic sensitivity, specificity, PPV, NPV, and accuracy of time-resolved CE-MRA for a subtype of SVM were 0.961, 0.961, 0.993, 0.806, and 0.961, respectively. The overall accuracy of time-resolved CE-MRA for the diagnosis of SVM was 0.821 and 0.783, 0.793, and 0.778 for cervical, thoracolumbar, and deep lumbosacral SVM, respectively. The actual number of catheterized vessels during spinal vascular DSA with time-resolved CE-MRA as the reference was lower than the estimated number of catheterized vessels in both SVM and non-SVM patients ( P <0.001). CONCLUSIONS:Time-resolved CE-MRA could accurately evaluate SVM and reduce the number of catheterized vessels during spinal vascular DSA.

Esophageal cancer (EC) is a disease characterized by progressive malignant obstruction. Stent implantation restores lumen patency, but tumor progression is likely to cause re-occlusion shortly. An esophageal stent loaded with Ce6-SiO2@MnO2 nanoparticles was designed, for which a dense delta-MnO2 coating was synthesized using a novel one-step REDOX reaction. This stent reverses the hypoxic tumor microenvironment (TME) via explosive oxygen generation, thereby increasing the efficacy of photodynamic therapy (PDT). Furthermore, Mn2+ reprograms the polarity of tumor associated macrophages (TAMs) in the immunosuppressed TME to effectively activate innate anti-tumor immunity in combination with PDT. Mn2+ downregulates the high mobility group box 1 protein (HMGB1), upregulates the signal transducer and activator of transcription 1 (STAT1) mRNA, and ultimately expresses the tumor inhibition effect of TAMs. Additionally, Ce6-SiO2@MnO2 effectively suppresses the apoptosis of TAMs to enhance their anti-tumor effect. The proposed strategy highlights the multifaceted role of Ce6-SiO2@MnO2 in the treatment of advanced esophageal cancer. Manganese-based nanoparticles achieve macrophage reprogramming combined with enhanced photodynamic therapy for malignant esophageal obstruction via the STAT/HMGB1 pathway.

Background: Color Doppler ultrasonography (CDUS) is feasible to detect arteriovenous fistula (AVF) dysfunction in hemodialysis patients but is not sufficient to map the structure of fistula required for interventions. This study is designed to evaluate the diagnostic accuracy of three-dimensional time-of-flight magnetic resonance angiography (TOF-MRA) at 3.0T versus CDUS for AVF dysfunction, by using digital Methods: This prospective study enrolled 68 consecutive patients with dysfunctional AVF who underwent both CDUS and TOF-MRA at Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine. The analysis of the dysfunctional AVFs was divided into three regions: the feeding artery, fistula and draining veins. In the whole- and per-regional-based analyses, two observers who were blinded to the clinical and DSA results independently analyzed all CDUS and TOF-MRA datasets. The image quality and stenosis severity of the lesions on TOF-MRA were evaluated. A receiver operating characteristic curve was applied to analyze the detection of AVF dysfunction with TOF-MRA. Results: A total of 204 vessel regions were evaluated. The whole-region-based image quality of TOF-MRA was poorer in patients with a total occlusion (1.8 +/- 0.8) than in those with stenosis (2.7 +/- 0.6, P<0.001). In the P<0.001] and similar specificity [93.1% (85.0-97.1%) vs. 94.3% (86.5-97.9%), P=0.755] than CDUS. The per-region-based analyses showed that TOF-MRA yielded higher sensitivity [fistula region, 98.1% (88.4- 2.5%); P=0.003] and similar specificity [fistula region, 88.2% (62.3-97.8%) vs. 88.2% (62.3-97.9%); P>0.99; draining vein region, 100.0% (59.8-100.0%) vs. 87.5% (46.7-99.3%); P>0.99] than CDUS. Sensitivity and specificity of TOF-MRA were comparable to those of CDUS in feeding artery region. Conclusions: TOF-MRA is a feasible and accurate method to display AVF dysfunction in hemodialysis patients, and this method might fulfill the endovascular treatment planning requirements.

Introduction: As a marker of chronic cerebral small vessel disease, leukoaraiosis (LA) was reported to impact the recruitment of collaterals in acute ischemic stroke (AIS). We intended to explore the impact of LA on the infarct growth rate (IGR) and clinical outcome by impaired collateral development in AIS patients with large vessel occlusion (LVO) who underwent endovascular thrombectomy (EVT).Patients and methods: Two hundred thirty-six AIS patients who underwent EVT were retrospectively reviewed. The severity of LA was graded using the Fazekas scale with non-contrast CT. IGR was calculated by the acute core volume on CT perfusion divided by the time from stroke onset to imaging. The collateral status after LVO was assessed using the ASITN/SIR collateral scale. The clinical outcomes after EVT were evaluated using a modified Rankin Scale (mRS). The Alberta stroke program early CT score (ASPECTS), the National Institutes of Health Stroke Scale (NIHSS) score at admission, and the modified treatment in cerebral infarction (mTICI) score after EVT were also included. Correlations between those factors were analyzed.Results: Patients with severe LA had significantly larger core volume on CTP (p = 0.022) and lower collateral grade (p < 0.001). Faster IGR was significantly associated with higher LA severity (adjusted odds ratio [aOR]: 1.53; 95% CI: 1.02-2.33; p = 0.046), higher NIHSS (aOR: 1.04; 95% CI: 1.00-1.09; p = 0.032) and impaired collaterals (aOR: 2.26; 95% CI: 1.27-4.03; p = 0.005). In mediation analysis, collaterals explained 33% of the effect of LA on fast IGR. There was correlation between the severity of LA and mRS (p = 0.007).Discussion and Conclusion: The increasing severity of LA is associated with impaired collateral status and fast infarct growth. These findings suggest that LA may become a predictive imaging biomarker for the likelihood of progression of tissue injury and clinical outcome after EVT in acute large vessel occlusion stroke.

Brain iron homeostasis is maintained through the normal function of blood-brain barrier and iron regulation at the systemic and cellular levels, which is fundamental to normal brain function. Excess iron can catalyze the generation of free radicals through Fenton reactions due to its dual redox state, thus causing oxidative stress. Numerous evidence has indicated brain diseases, especially stroke and neurodegenerative diseases, are closely related to the mechanism of iron homeostasis imbalance in the brain. For one thing, brain diseases promote brain iron accumulation. For another, iron accumulation amplifies damage to the nervous system and exacerbates patients' outcomes. In addition, iron accumulation triggers ferroptosis, a newly discovered iron-dependent type of programmed cell death, which is closely related to neurodegeneration and has received wide attention in recent years. In this context, we outline the mechanism of a normal brain iron metabolism and focus on the current mechanism of the iron homeostasis imbalance in stroke, Alzheimer's disease, and Parkinson's disease. Meanwhile, we also discuss the mechanism of ferroptosis and simultaneously enumerate the newly discovered drugs for iron chelators and ferroptosis inhibitors.

Background We hypothesized that left ventricular systolic dysfunction (LVSD) would lead to an ischemic core overestimation in patients with acute ischemic stroke (AIS), and impaired collateral status might partly mediate this effect. Objective A pixel-based analysis of CT perfusion (CTP) and follow-up CT was undertaken to investigate the optimum CTP thresholds for the ischemic core if overestimation was found. Methods A total of 208 consecutive patients with AIS with large vessel occlusion in the anterior circulation, who received initial CTP evaluation and successful reperfusion, were retrospectively analyzed and divided into an LVSD (left ventricular ejection fraction (LVEF) ratio <50%; n=40) and a normal cardiac function (LVEF≥50%; n=168) group. Ischemic core overestimation was considered when the CTP-derived core was larger than the final infarct volume. We investigated the relationship between cardiac function, probability for core overestimation, and collateral scores using mediation analysis. A pixel-based analysis was undertaken to define the optimum CTP thresholds for ischemic core. Results LVSD was independently associated with impaired collaterals (aOR=4.28, 95% CI 2.01 to 9.80, P<0.001) and core overestimation (aOR=2.52, 95% CI 1.07 to 5.72, P=0.030). In mediation analysis, the total effect on core overestimation is composed of the direct effect of LVSD (+17%, P=0.034) and the mediated indirect effect of collateral status (+6%, P=0.020). Collaterals explained 26% of the effect of LVSD on core overestimation. Compared with relative cerebral blood flow (rCBF) thresholds of <35%, <30%, and <20%, a rCBF <25% cut-off point had the highest correlation (r=0.91) and best agreement (mean difference 3.2±7.3 mL) with the final infarct volume to determine the CTP-derived ischemic core in patients with LVSD. Conclusions LVSD increased the possibility of ischemic core overestimation on baseline CTP, partly due to impaired collateral status, and a stricter rCBF threshold should be considered.

Dear Editor, Endovascular recanalization was considered as a first-line treatment for diabetic patients with severe peripheral artery stenosis. The current treatment strategies, which include employing drug-eluting balloons and drug-eluting stents, have been shown to successfully achieve revascularization and relieve symptoms. However, long-term patency is often a challenge due to high rate of early restenosis (up to 33%), especially in infrapopliteal arteries. The pathogenesis might be attributed to inflammatory activation and endothelial dysfunction leading to neointimal hyperplasia and restenosis. Endothelial progenitor cell (EPC) transplantation was as a promising strategy for endothelial repair in peripheral artery diseases. EPCs are bone marrow-derived late-stage stem cells found circulating in the blood and possess the ability to proliferate and differentiate into endothelial cells, thereby contributing to vascular repair and angiogenesis.1 Recently, accumulating evidences suggested that microRNAs (miRNAs) could regulate the proliferation, migration, and angiogenesis of EPCs. miR-126-3p modulates the expression of proangiogenic cytokines, thereby regulating angiogenesis and the homing and retention of EPCs in injured vascular walls.2 Deficiency of miR-126 in diabetic EPCs was also associated with EPC functional disorders. Therefore, we investigated whether miR-126-3p overexpression could restore EPC biology and improve vascular repair in type 1 diabetes mellitus (T1DM). EPCs originated from the bone marrow of T1DM rats and healthy controls were isolated by density gradient centrifugation and grown in endothelial growth medium 2 (EGM-2) media. The attached EPCs elongated and became spindle-shaped after media changes on the 4th and 7th days of culture. Cellular immunostaining studies showed the binding of adherent cells to uptake FITC-Ulex Europaeus Agglutinin I (FITC-UEA-I) and Dil-acetylated low-density lipoprotein (Dil-ac-LDL) (Figure 1A). Meanwhile, early EPCs expressed endothelial markers (CD34 and CD133) at a comparable level (Figure S1). EPCs were transfected with the recombinant lentiviral expression vector using reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis to confirm a significant relative upregulation of miR-126-3p (Figure S2). Successfully isolated and transfected EPCs were allocated into an EPC/T1DM group (EPC from T1DM rats), an EPC/CON group (EPC from healthy controls), an EPC/CON-Blank group (EPC from healthy controls transfected with a blank vector), an EPC/T1DM-126 group, or an EPC/CON-126 group (EPCs from T1DM rats or healthy controls transfected with miR-126-3p). The proliferation of EPCs was assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assays. There was a significant decrease in cell proliferation in the EPCs isolated from T1DM rats compared with healthy controls (p = 0.023, Figure 1B). Nevertheless, the proliferation improved after transfection with miR-126-3p (p = 0.012). Similarly, the adhesive activity of T1DM EPCs showed a significant decrease (8.2 ± 1.5) when compared with EPCs from healthy controls (14.9 ± 1.4, p = 0.003, Figure 1C). The decrease was reversed in EPC-126 (17.8 ± 1.8), which showed a significant increase in adhesive activity compared with healthy controls (14.9 ± 1.4, p = 0.021). The migratory capacity of EPCs was evaluated using modified Boyden chamber assays. The results indicated that EPC migration was significantly impaired in T1DM rats (9.8 ± 2.3) compared with healthy controls (13.5 ± 2.3, p = 0.002, Figure 1D). miR-126-3p significantly increased EPC migration (17 ± 1.8) when compared with controls (13.5 ± 2.3, p = 0.001). These results showed that the proliferation, adhesion, and migration capacities of EPCs were significantly decreased in T1DM rats and were enhanced after transfection with miR-126. At 7 and 14 days after injury, reendothelialization was evaluated by staining of the Evans blue dye and was presented as percentage of reendothelialization area (defined as area not stained with Evans blue/total injured surface area). As expected, reendothelialization was significantly greater in the EPC-126-infected group than in the EPC-treated group (50.3 ± 4.7% vs. 33.6 ± 5.8% at day 7, p < 0.001; 84.9 ± 5.1% vs. 79.6 ± 5.7% at day 14, p = 0.003, Figure 1E). For intimal hyperplasia analysis, sections were stained with hematoxylin and eosin. A marked reduction in intima/media ratio was found in the EPC-126-treated group (0.278 ± 0.071 at day 7 and 0.683 ± 0.122 at day 14), whereas the intima/media ratios in the EPC group were 0.396 ± 0.107 at day 7 and 0.975 ± 0.167 at day 14 (p < 0.05 vs. EPC-126, Figure 1F). These results suggested that modulation of EPCs with overexpression of miR-126 could reduce neointimal hyperplasia and accelerate reendothelialization. EPCs are precursor cells derived from bone marrow and can proliferate and differentiate into vascular endothelial cells. There is growing evidence that EPCs are involved in the maintenance of normal endothelial function and angiogenesis. Previous studies have shown that the transfusion of exogenous EPCs can contribute to improved reendothelialization, neovascularization, and endothelial repair following balloon injury. However, reduced circulating EPC numbers and EPC dysfunction were found in diabetic patients. The EPC recruitment at reendothelialization sites following arterial injury was also impaired in T1DM, likely contributing to diabetic vasculopathy. Initially, we found that the EPCs in T1DM rats showed a significant decrease in number and impaired function when compared with normal controls in in vitro cell function assays. The EPCs mobilized into peripheral circulation participated in the process of vascular repair, while the poor functional state of EPC obliterates its potentiality to repair carotid injury. Furthermore, miR-126 was abundantly expressed in endothelial cells and crucial for maintaining vascular homeostasis. EPCs derived from DM patients reportedly had lower expression of miR-126, leading to their functional impairment. Overexpression of miR-126 increased migration and promoted homing and stemness maintenance in EPCs. Hence, modulation of EPC function is a potential therapeutic target in exogenous EPC transplantation. To prove it, we successfully transfected EPCs with miR-126 using lentiviral expression vectors and the expression status was confirmed by RT-qPCR analysis. The miR-126-overexpressing EPCs showed improved proliferative, adhesive, and migratory functions. Because miR-126 is specifically expressed in endothelial cells, the overexpression of miR-126 could positively activate the vascular endothelial growth factor (VEGF)-dependent signaling pathways and directly affect Spred-1, Syndecan-1, vascular cell adhesion molecule-1 (VCAM1), and phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2).3, 4 Inhibiting the expression of Spred-1 and PIK3R2 would enhance VEGF and fibroblast growth factor (FGF)-induced angiogenesis. We further produced a carotid artery injury model in T1DM rats, which were transplanted with EPCs overexpressing miR-126-3p, and evaluated for improvement in reendothelialization. As expected, the EPC-126 was incorporated into injured intima and improved reendothelialization after carotid artery injury. The reestablishment of an intact endothelium after injury is an important step in the prevention of neointimal hyperplasia and stent thrombosis. A previous study postulated that miR-126 promotes EPC function by modulating the expression of stromal cell-derived factor 1 (SDF-1) via repression of the regulator of G protein signaling 16 (RGS16).5 RGS16 silencing enabled chemokine receptor 4 (CXCR4) to mediate autoregulation and increase the expression of SDF-1. Pei et al.2 showed that miR-126 could also directly increased the production of CXCR4 and enhanced the function of EPCs in diabetic rats. Hence, miR-126 functioned in a complexed regulatory signaling network of EPCs that subsequently facilitated reendothelialization in endothelial injury. In conclusion, our study demonstrates that miR-126-3p could restore the biology of EPCs from diabetic rats. The transplantation of miR-126-3p-overexpressing EPCs promoted reendothelialization in carotid artery injury models by upregulation of the endothelial cell function. G.H. and L.W. conceived and drafted the manuscript. G.H. drew the figures. L.W. and Y.L. discussed the concepts of the manuscript. H.L. and Y.Z. provided valuable discussion and revised the manuscript. All authors contributed to the article and approved the submitted version. This work was supported by the National Natural Science Foundation of China (No. 81901845) and Shanghai Key Discipline of Medical Imaging (No. 2017ZZ02005). All the authors declare no conflicts of interest. This project was permitted and approved by the Committee of the Sixth People's Hospital at the Shanghai Jiao Tong University (License: SCXK2018-0006). All data are available from the corresponding author upon request. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.