Predictors and Impact of Sulcal SAH after Mechanical Thrombectomy in Patients with Isolated M2 Occlusion.

BACKGROUND AND PURPOSE: Data on SAH after M2 mechanical thrombectomy are limited. We aimed to determine the prevalence of sulcal SAH after mechanical thrombectomy for M2 occlusion, its associated predictors, and the resulting clinical outcome. MATERIALS AND METHODS: The study retrospectively reviewed the data of patients with acute ischemic stroke who underwent mechanical thrombectomy for isolated M2 occlusion. The patients were divided into 2 groups according to the presence of sulcal SAH after M2 mechanical thrombectomy. Angiographic and clinical outcomes were compared. Multivariable analysis was performed to identify independent predictors of sulcal SAH and unfavorable outcome (90-day mRS, 3-6). RESULTS: Of the 209 enrolled patients, sulcal SAH was observed in 33 (15.8%) patients. The sulcal SAH group showed a higher rate of distal M2 occlusion (69.7% versus 22.7%), a higher of rate of superior division occlusion (63.6% versus 43.8%), and a higher M2 angulation (median, 128° versus 106°) than the non-sulcal SAH group. Of the 33 sulcal SAH cases, 23 (66.7%) were covert without visible intraprocedural contrast extravasation. Distal M2 occlusion (OR, 12.04; 95% CI, 4.56-35.67; P < .001), superior division (OR, 3.83; 95% CI, 1.43-11.26; P = .010), M2 angulation (OR, 1.02; 95% CI, 1.01-1.04; P < .001), and the number of passes (OR, 1.58; 95% CI, 1.22-2.09; P < .001) were independent predictors of sulcal SAH. However, covert sulcal SAH was not associated with an unfavorable outcome (P = .830). CONCLUSIONS: After mechanical thrombectomy for M2 occlusion, sulcal SAH was not uncommon and occurred more frequently with distal M2 occlusion, superior division, acute M2 angulation, and multiple thrombectomy passes (≥3). The impact of covert sulcal SAH was mostly benign and was not associated with an unfavorable outcome.

Local Intra-arterial Thrombolysis during Mechanical Thrombectomy for Refractory Large-Vessel Occlusion: Adjunctive Chemical Enhancer of Thrombectomy.

BACKGROUND AND PURPOSE: Data on adjunctive intra-arterial thrombolysis during mechanical thrombectomy for refractory thrombus are sparse. The aim of this study was to evaluate the efficacy and safety of local intra-arterial urokinase as an adjunct to mechanical thrombectomy for refractory large-vessel occlusion. MATERIALS AND METHODS: We retrospectively evaluated patients with acute ischemic stroke who underwent mechanical thrombectomy for anterior circulation large-vessel occlusion between January 2016 and December 2019. Patients were divided into 2 groups based on the use of intra-arterial urokinase as an adjunctive therapy during mechanical thrombectomy for refractory thrombus: the urokinase and nonurokinase groups. Herein, refractory thrombus was defined as the target occlusion with minimal reperfusion (TICI 0 or 1) despite >3 attempts with conventional mechanical thrombectomy. The baseline characteristics, procedural outcomes, and clinical outcome were compared between the 2 groups. RESULTS: One hundred fourteen cases of refractory thrombus were identified. A total of 45 and 69 patients were in the urokinase and the nonurokinase groups, respectively. The urokinase group compared with the nonurokinase group showed a higher rate of successful reperfusion (82.2% versus 63.8%, P = .034), with lower procedural times (54 versus 69 minutes, P = .137). The rates of good clinical outcome, distal embolism, and symptomatic intracranial hemorrhage were similar between the 2 groups. The use of intra-arterial urokinase (OR = 3.682; 95% CI, 1.156-11.730; P = .027) was an independent predictor of successful reperfusion. CONCLUSIONS: The use of local intra-arterial urokinase as an adjunct to mechanical thrombectomy may be an effective and safe method that provides better recanalization than the conventional mechanical thrombectomy for refractory thrombus in patients with embolic large-vessel occlusion.

Predictors of the Effects of Flow Diversion in Very Large and Giant Aneurysms.

BACKGROUND AND PURPOSE: The treatment paradigm for very large and giant aneurysms has recently changed to flow diversion, in light of the results of the Pipeline for Uncoilable or Failed Aneurysms trial. However, the effects of flow diversion were definitely unknown. We explored this topic and identified the predictors of such effects. MATERIALS AND METHODS: We retrospectively reviewed 51 patients with unruptured aneurysms admitted to our institution for flow diversion between February 2014 and August 2019. Patients were categorized into an effect group (no filling or remnant entry) and a no-effect group (subtotal or total filling). We evaluated the aneurysm size and shape, incorporation vessel, parent artery stenosis and curvature, stagnation of contrast medium within the aneurysm, use of balloon angioplasty, and intra-aneurysm thrombus as potential predictors of the effects of flow diversion. RESULTS: The effect group comprised 34 patients (66.7%, 34/51; no filling, 35.3%, 18/51; and remnant entry, 31.4%, 16/51). The no-effect group comprised 17 patients (33.3%, 17/51; subtotal filling, 29.4%, 15/51; and total filling, 3.9%, 2/51). An incorporation vessel and balloon angioplasty were independent risk factors for the no-effect group in multivariate logistic regression analyses (OR = 0.13 and 0.05; 95% confidence intervals, 0.02-0.62 and 0.00-0.32; P values, .021 and .004, respectively). CONCLUSIONS: Flow diversion is effective for very large and giant aneurysms, but the outcomes require further improvement. The results of this study show that an incorporated vessel and excessive balloon angioplasty might compromise flow diversion. This finding can help improve the outcomes of flow diversion.

Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

Causal analysis of self-sustaining processes in the logarithmic layer of wall-bounded turbulence.

Despite the large amount of information provided by direct numerical simulations of turbulent flows, their underlying dynamics remain elusive even in the most simple and canonical configurations. Most common approaches to investigate the turbulence phenomena do not provide a clear causal inference between events, which is essential to determine the dynamics of self-sustaining processes. In the present work, we examine the causal interactions between streaks, rolls and mean shear in the logarithmic layer of a minimal turbulent channel flow. Causality between structures is assessed in a non-intrusive manner by transfer entropy, i.e., how much the uncertainty of one structure is reduced by knowing the past states of the others. We choose to represent streaks by the first Fourier modes of the streamwise velocity, while rolls are defined by the wall-normal and spanwise velocity modes. The results show that the process is mainly unidirectional rather than cyclic, and that the log-layer motions are sustained by extracting energy from the mean shear which controls the dynamics and time-scales. The well-known lift-up effect is also identified, but shown to be of secondary importance in the causal network between shear, streaks and rolls.

Turbulence intensities in large-eddy simulation of wall-bounded flows.

A persistent problem in wall-bounded large-eddy simulations (LES) with Dirichlet no-slip boundary conditions is that the near-wall streamwise velocity fluctuations are overpredicted, while those in the wall-normal and spanwise directions are underpredicted. The problem may become particularly pronounced when the near-wall region is underresolved. The prediction of the fluctuations is known to improve for wall-modeled LES, where the no-slip boundary condition at the wall is typically replaced by Neumann and no-transpiration conditions for the wall-parallel and wall-normal velocities, respectively. However, the turbulence intensity peaks are sensitive to the grid resolution and the prediction may degrade when the grid is refined. In the present study, a physical explanation of this phenomena is offered in terms of the behavior of the near-wall streaks. We also show that further improvements are achieved by introducing a Robin (slip) boundary condition with transpiration instead of the Neumann condition. By using a slip condition, the inner energy production peak is damped, and the blocking effect of the wall is relaxed such that the splatting of eddies at the wall is mitigated. As a consequence, the slip boundary condition provides an accurate and consistent prediction of the turbulence intensities regardless of the near-wall resolution.

Feasibility of Permanent Stenting with Solitaire FR as a Rescue Treatment for the Reperfusion of Acute Intracranial Artery Occlusion.

BACKGROUND AND PURPOSE: The Solitaire FR can be used not only as a tool for mechanical thrombectomy but also as a detachable permanent stent. Our aim was to assess the feasibility and safety of permanent stent placement with the Solitaire FR compared with other self-expanding stents for intracranial artery recanalization for acute ischemic stroke. MATERIALS AND METHODS: From January 2011 through January 2016, we retrospectively selected 2979 patients with acute ischemic stroke. Among them, 27 patients who underwent permanent stent placement (13 patients with the Solitaire FR [Solitaire group] and 14 patients with other self-expanding stents [other stent group]) were enrolled. The postprocedural modified TICI grade and angiographic and clinical outcomes were assessed. The safety and efficacy of permanent stent placement of the Solitaire FR for acute large-artery occlusion were evaluated. RESULTS: Stent placement was successful in all cases. Modified TICI 2b-3 reperfusion was noted in 84.6% of the Solitaire group and in 78.6% of the other stent group. Procedural time was significantly shorter in the Solitaire group than in the other stent group (P = .022). Shorter procedural time was correlated with favorable outcome (ρ = 0.46, P = .035). No significant differences were found in the modified TICI grade, NIHSS score, mRS, and hemorrhagic transformation rate between the 2 groups. The acute in-stent thrombosis rate at discharge was significantly lower when a glycoprotein IIb/IIIa inhibitor was injected during the procedure (P = .013). CONCLUSIONS: Permanent stent placement with the Solitaire FR compared with other self-expanding stents appears to be feasible and safe as a rescue tool for refractory intra-arterial therapy.

Clinical Outcome of Simultaneous Native Nephrectomy and Kidney Transplantation in Patients With Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: End-stage renal disease patients with autosomal dominant polycystic kidney disease may require native nephrectomy for various indications. However, the appropriate timing for nephrectomy in kidney transplantation and its effect on allograft survival have not been fully investigated. METHODS: We retrospectively analyzed 41 kidney transplant recipients with autosomal dominant polycystic kidney disease in whom transplantation was done simultaneously, after, or without native nephrectomy at Seoul St. Mary's hospital between January 1987 and February 2014. We divided patients into 2 groups based on when native nephrectomy was performed: simultaneously (group A, n = 13) and after or without nephrectomy (group B, n = 28), and compared perioperative outcomes, posttransplantation complications, and allograft survival rates. RESULTS: The mean operative time was significantly longer in group A than in group B (6.48 ± 1.84 vs 5.27 ± 0.84 hours; P = .048). The mean numbers of units required for intraoperative blood transfusions were also significantly higher in group A than in group B (3.66 ± 3.43 vs 0.75 ± 0.26 units; P = .018). However, there were no differences between groups in the incidence of acute rejection and other complications such as postoperative bleeding and infectious complications (P > .05, for all). The allograft survival rate also did not differ between groups (P > .05). CONCLUSIONS: Our study showed that patients undergoing simultaneous nephrectomy and kidney transplantations had clinical outcomes, in terms of complications and allograft survival, that were comparable to those in patients undergoing kidney transplantations with or without previous nephrectomy.

Simultaneous determination of arbutin and its decomposed product hydroquinone in whitening creams using high-performance liquid chromatography with photodiode array detection: Effect of temperature and pH on decomposition.

OBJECTIVE: Arbutin is an effective agent for the treatment of melanin disorders. Arbutin may be converted to hydroquinone under conditions of high temperature, ultraviolet (UV) radiation and dilute acid. The aim of the current study was to develop an analytical method to determine the levels of arbutin and hydroquinone in whitening cosmetic products using high-performance liquid chromatography with photodiode array detection (HPLC-DAD). In addition, we investigated the effects of high temperature and pH on the decomposition of arbutin. METHODS: Samples extracted using two-step sonications were separated on a C18 column using a gradient mobile phase consisting of water and methanol. A 60-mm (40 µL) DAD cell was used to enhance the sensitivity of hydroquinone determination. Thermal decomposition of arbutin was evaluated at temperatures ranging from 60 to 120°C for 1-36 h. RESULTS: The method showed good linearity (R(2) ≥ 0.9997), precision (relative standard deviation, RSD < 5%) and acceptable extraction recovery (90-102.6%). The limits of quantitation for arbutin and hydroquinone were 0.0085 and 0.0119 µg mL(-1) , respectively. One sample of 21 cosmetic products tested contained arbutin at a concentration 1.61 g 100 g(-1) cream and 0.12 g 100 g(-1) cream of hydroquinone. Arbutin (327.18 ppm) decomposed after 6 h at 120°C and produced 10.73 ppm of hydroquinone. CONCLUSION: The developed method is simple to detect both arbutin and hydroquinone simultaneously in cosmetic products, at an adequate level of sensitivity. Notably, temperature and pH did not influence the decomposition of arbutin to hydroquinone in a 2% arbutin cream.

Potential for the use of the Solitaire stent for recanalization of middle cerebral artery occlusion without a susceptibility vessel sign.

BACKGROUND AND PURPOSE: Absence of the MCA susceptibility vessel sign (negative MCA susceptibility vessel sign) on gradient recalled-echo MR imaging in acute stroke is commonly associated with in situ stenosis and thrombotic occlusion. We evaluated the effectiveness and safety of the Solitaire stent as the first-line device for the recanalization of MCA occlusion with a negative MCA susceptibility vessel sign. MATERIALS AND METHODS: Thirty-eight consecutive patients presenting with acute ischemic stroke due to MCA occlusion were treated by using the Solitaire AB stent alone or combined with thrombolytic drugs. Among these patients, 11 (7 men and 4 women; median age, 70 years; range, 49-89 years) who underwent multimodal stroke MR imaging before the endovascular procedure and had no MCA susceptibility vessel sign on the initial gradient recalled-echo MR imaging were included in this study. The primary end point was the recanalization of the occluded artery evaluated by the arterial occlusive lesion score. Clinical outcome was assessed at discharge and 90 days, as was the degree of residual MCA stenosis or reocclusion. RESULTS: Successful recanalization (arterial occlusive lesion score ≥ II) without balloon angioplasty was obtained in 9 patients (81.8%). Six patients (54.5%) had an mRS score of ≤2 at 90 days. After a median of 147 days, no patient showed reocclusion on follow-up imaging. There were no symptomatic intracerebral hemorrhages. CONCLUSIONS: The Solitaire stent is a feasible tool as the first-line device for multimodal endovascular recanalization therapy in acute ischemic stroke with a negative MCA susceptibility vessel sign. It has a good rate of successful and complete recanalization and is a fast yet safe procedure.

MicroRNA-29c functions as a tumor suppressor by direct targeting oncogenic SIRT1 in hepatocellular carcinoma.

Mammalian sirtuin 1 (SIRT1) has connected to an ever widening circle of activities that encompass cellular stress resistance, energy metabolism and tumorigenesis. However, underlying mechanisms leading to oncogenic SIRT1 overexpression are less understood. In this study, we identified SIRT1 regulatory microRNA (miRNA) and its function in hepatocellular carcinoma (HCC). Aberrant SIRT1 overexpression was demonstrated in a subset of human HCCs. SIRT1 knockdown suppressed HCC cell growth by transcriptional deregulation of cell cycle proteins. This led to hypophosphorylation of pRb, which inactivated E2F/DP1 target gene transcription, and thereby caused significant increase of HCC cells to remain in the G1/S phase. A comprehensive miRNA profiling analysis indentified five putative endogenous miRNAs that are significantly downregulated in HCC. Ectopic expression of miRNA mimics evidenced miR-29c to suppress SIRT1 in HCC cells. Notably, ectopic miR-29c expression repressed cancer cell growth and proliferation, and it recapitulated SIRT1 knockdown effects in HCC cells. In addition, miR-29c expression was downregulated in a large cohort of HCC patients, and low expression of miR-29c was significantly associated with poor prognosis of HCC patients. Taken together, we demonstrated that miR-29c suppresses oncogenic SIRT1 by way of binding to 3'-untranslated region of SIRT1 mRNA causing translational inhibition in liver cancer cells. The loss or suppression of miR-29c may cause aberrant SIRT1 overexpression and promotes liver tumorigenesis. Overall, we suggest that miR-29c functions as a tumor suppressor by regulating abnormal SIRT1 activity in liver.

Effects of celecoxib on hematoma and edema volumes in primary intracerebral hemorrhage: a multicenter randomized controlled trial.

BACKGROUND AND PURPOSE: We investigated the effect of celecoxib, a selective inhibitor of cyclo-oxygenase 2, in patients with intracerebral hemorrhage (ICH). METHODS: We conducted a multicenter, randomized, controlled, and open with blinded end-point trial of 44 Korean patients 18 years or older with ICH within 24 h of onset. The intervention group (n = 20) received celecoxib (400 mg twice a day) for 14 days. The control group (n = 24) received the standard medical treatment for ICH. The primary end-point was the number of patients with a change in the volume of perihematomal edema (PHE) from the 1st to the 7th ± 1 day (cut-off value, 20%). RESULTS: The time from onset to computed tomography scan slightly differed between groups (177 ± 160 min for control vs. 297 ± 305 min for the celecoxib group; P = 0.10). In the primary end-point analysis using cut-off values, there was a significant shift to reduced expansion of PHE in the celecoxib group (P = 0.005). With respect to the secondary end-points, there was also a significant shift to reduced expansion of ICH in the celecoxib group (P = 0.046). In addition, the expansion rate of PHE at follow-up tended to be higher in the control group than in the celecoxib group (90.6 ± 91.7% vs. 44.4 ± 64.9%; P = 0.058). CONCLUSIONS: In our small, pilot trial, administration of celecoxib in the acute stage of ICH was associated with a smaller expansion of PHE than that observed in controls.

Vertebrobasilar dolichoectasia as a risk factor for cerebral microbleeds.

BACKGROUND: Both vertebrobasilar dolichoectasia (VBD) and cerebral microbleeds (CMBs) are related with the risk of intracerebral hemorrhage. We aimed to examine the relationship between the VBD and CMB in ischaemic stroke patients. METHODS: A consecutive series of 182 patients hospitalized because of ischaemic stroke or transient ischaemic attack (TIA), and who underwent gradient echo brain magnetic resonance imaging were retrospectively recruited from a prospective stroke registry. CMB locations were categorized into anterior and posterior circulation. Ectasia was defined as basilar artery (BA) diameter > 4.5 mm, and dolichosis, as either BA bifurcation above the suprasellar cistern or lateral to the margin of the clivus or dorsum sellae. Whether VBD is associated with CMB anywhere in the brain or in anterior or posterior circulation territories was analysed using binary and multinomial logistic regression models. RESULTS: Twenty-four subjects (13.2%) had VBD and 48 (26.4%) had CMBs. CMBs were more frequently observed in patients with VBD than without (66.7% vs. 20.3%, P < 0.001). VBD was significantly associated with CMBs in any location (crude odds ratio, 7.88; 95% confidence interval, 3.10-20.02), in the posterior circulation territory only (9.63; 2.60-34.94), and in both territories (9.25; 3.40-26.29), but not in the anterior circulation only (1.14; 0.009-11.20). These associations remained unchanged after adjusting for age, gender, hypertension, leukoaraiosis and stroke subtype. CONCLUSIONS: VBD in patients with ischaemic stroke or TIA is independently associated with CMBs, especially in the posterior circulation territory.