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Context: As blood flow restriction gains popularity across different populations (eg, young and older adults) and settings (eg, clinical and sports rehabilitation), the accuracy of blood flow restricted percentage becomes crucial. We aimed to compare manually measured arterial occlusion pressure (AOP) among young adults to understand whether lower limb composition affects the pressure required to achieve AOP. The results will shed light on the adequacy of published calculations used to estimate AOP in practical and research settings. Design: An observational cross-sectional study design was implemented to examine the relationship between lower limb composition, lower limb circumference, and measured AOP. Methods: Twenty-two participants (12 males, 26 [4] y, 1.74 [0.07] m, 73.2 [12.5] kg) underwent a whole-body Dual-energy X-ray Absorptiometry scan before AOP (in millimeters of mercury) and lower limb circumference (in centimeters) were determined. In a supine position, a 10-cm wide cuff was manually inflated on the dominant leg to the point where a pulse could no longer be detected by a Doppler ultrasound of the posterior tibial artery to determine AOP. Lower limb composition (fat, muscle, and bone mass [in grams]) was obtained from the Dual-energy X-ray Absorptiometry scan. Results: Lower limb muscle mass had a moderate negative relationship with AOP (r2 =.433, β = −0.004) and a moderate positive relationship with lower limb circumference (r2 =.497, β = 0.001). Lower limb circumference had the weakest relationship with AOP (r2 =.316, β = 0.050) of all measures. Conclusions: The reported relationships between lower limb muscle mass, lower limb circumference, and AOP suggest that as muscle mass increases, lower limb circumference also increases, yet AOP decreases. This implies that limb circumference should not be used as the primary measure for calculating AOP within the sampled population. We recommend individually measuring AOP when implementing blood flow restriction in all exercise modalities. [ABSTRACT FROM AUTHOR]

Ischemic stroke (IS) is the leading cause of disability and the second most common cause of death in adults globally. Unfortunately, the recombinant tissue plasminogen activator (rt-PA), the only thrombolytic drug approved by the Food and Drug Administration (FDA), has numerous side effects such as hemorrhage risk and narrow therapeutic windows, which limits its clinical application. Butylphthalide (NBP) from celery seeds was approved against IS, and its derivative 6-amino-3-n-butylphthalide has been demonstrated to offer better neuroprotective effects against IS-induced injury. In this study, a series of 6-amino-3-n-butylphthalide (ABP) derivatives were designed and synthesized in order to obtain novel powerful compounds against IS. Permanent middle cerebral artery occlusion (pMCAO)-operated mice and oxygen and glucose deprivation (OGD)-treated primary cortical neurons and HT22 cell lines were used to evaluate the activity of these derivatives in protecting against ischemic injury. The results showed that the effect of compound ABP18 (ABP connecting with memantine) on alleviating OGD-induced cell death was better than that of NBP both in primary cortical neurons and HT22 cells, and the safety of ABP18 is comparable to that of NBP. In addition, ABP18 significantly reduced the brain infarct volume and improved neurological function in mice at 24 h after pMCAO. The acute toxicity test showed that ABP18 had high safety. Therefore, the present study identified that ABP18 is a potential candidate for the treatment of IS. [ABSTRACT FROM AUTHOR]

Background and Aims Glycoprotein VI (GPVI) is a platelet collagen/fibrin(ogen) receptor and an emerging pharmacological target for the treatment of thrombotic and thrombo-inflammatory diseases, notably ischaemic stroke. A first anti-human GPVI (hGPVI) antibody Fab-fragment (ACT017/glenzocimab, K D: 4.1 nM) recently passed a clinical phase 1b/2a study in patients with acute ischaemic stroke and was found to be well tolerated, safe, and potentially beneficial. In this study, a novel humanized anti-GPVI antibody Fab-fragment (EMA601; K D: 0.195 nM) was developed that inhibits hGPVI function with very high potency in vitro and in vivo. Methods Fab-fragments of the mouse anti-hGPVI IgG Emf6.1 were tested for functional GPVI inhibition in human platelets and in hGPVI expressing (hGP6tg/tg) mouse platelets. The in vivo effect of Emf6.1Fab was assessed in a tail bleeding assay, an arterial thrombosis model and the transient middle cerebral artery occlusion (tMCAO) model of ischaemic stroke. Using complementary-determining region grafting, a humanized version of Emf6.1Fab (EMA601) was generated. Emf6.1Fab/EMA601 interaction with hGPVI was mapped in array format and kinetics and quantified by bio-layer interferometry. Results Emf6.1Fab (K D: 0.427 nM) blocked GPVI function in human and hGP6tg/tg mouse platelets in multiple assays in vitro at concentrations ≥5 µg/mL. Emf6.1Fab (4 mg/kg)-treated hGP6tg/tg mice showed potent hGPVI inhibition ex vivo and were profoundly protected from arterial thrombosis as well as from cerebral infarct growth after tMCAO, whereas tail-bleeding times remained unaffected. Emf6.1Fab binds to a so far undescribed membrane proximal epitope in GPVI. The humanized variant EMA601 displayed further increased affinity for hGPVI (K D: 0.195 nM) and fully inhibited the receptor at 0.5 µg/mL, corresponding to a >50-fold potency compared with ACT017. Conclusions EMA601 is a conceptually novel and promising anti-platelet agent to efficiently prevent or treat arterial thrombosis and thrombo-inflammatory pathologies in humans at risk. [ABSTRACT FROM AUTHOR]

Background/Objectives: The Naples prognostic score (NPS), reflecting inflammation and nutritional status, has prognostic value, especially in cancer. This study evaluated its ability to predict in-hospital mortality in acute ischemic stroke (AIS) patients undergoing endovascular treatment (EVT). Methods: We retrospectively studied 244 patients with AIS who were admitted between April 2020 and December 2023. Patients were included if they presented within 6 h of symptom onset with evidence of intracranial proximal arterial occlusion. The EVT was performed using aspiration catheters, stent retrievers, or both. The NPS was calculated based on the neutrophil–lymphocyte ratio, lymphocyte–monocyte ratio, and albumin and total cholesterol levels. Results: We found a significant association between higher NPS scores and in-hospital mortality. Patients with a high NPS (3 or 4) had a mortality rate of 41.6% compared to 21.0% in the low-NPS group (0, 1, or 2). The full model incorporating NPS showed superior predictive ability for in-hospital mortality compared with the baseline model (areas under the curve 0.881 vs. 0.808). A receiver-operating characteristic analysis at a cutoff of >2.5 for the NPS showed a sensitivity of 86.6% and specificity of 41.9%. This study demonstrated that incorporating the NPS into the predictive model improved the accuracy and calibration for predicting in-hospital mortality. A decision curve analysis showed the net benefit of using the full model incorporating NPS over the baseline model, emphasizing its potential clinical application in prognostication. Conclusions: NPS is a reliable predictor of in-hospital mortality in AIS patients undergoing EVT. Incorporating NPS into clinical practice could help to identify high-risk patients and improve outcomes through tailored interventions. [ABSTRACT FROM AUTHOR]

A 35‐year‐old woman with antiphospholipid syndrome, with 29‐week pregnancy, developed left hemiparesis. Diffusion‐weighted imaging showed a low Alberta Stroke Program Early Computed Tomography (ASPECT) score. The right internal carotid artery occlusion was recanalized by mechanical thrombectomy (MT) and a pathologically white thrombus was confirmed. Clot analysis‐guided anti‐coagulant/platelet therapy was continued, and the patient delivered at 38 weeks and was discharged with a modified Rankin Scale score of 1. We conclude that MT should be considered, even in pregnancy with antiphospholipid syndrome and low ASPECT scores. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a leading cause of disability and mortality worldwide. Recently, increasing evidence implicates microRNAs (miRs) in the pathophysiology of ischemic stroke. Studies have shown that miR-15a/16-1 is abnormally expressed in brains after ischemic stroke, and its upregulation may increase ischemic damage. Given that sex and age are significant modifiers of stroke outcomes, here we investigated whether inhibiting miR-15a/16-1 with antagomirs mitigates cerebral ischemia/reperfusion (I/R) injury in a sex- and age-dependent manner. Young (3 months) and aged (18 months) male and female C57/BL mice underwent 1-h middle cerebral artery occlusion and 3–7 days reperfusion (tMCAO). We administered miR-15a/16-1 antagomir (30 pmol/g) or control antagomir (NC, 30 pmol/g) via tail vein 2 h post-MCAO. Neurobehavioral testing and infarct volume assessment were performed on days 3 and 7. Compared to controls, antagomir treatment significantly improved neurobehavioral outcomes and reduced infarct volume in tMCAO mice at day 7, with the effects being more pronounced in young mice. Notably, young female mice exhibited superior survival and sensorimotor function compared to young male mice. These results were also replicated in a permanent MCAO (pMCAO) mice model. This suggests miR-15a/16-1 antagomir and estradiol may synergistically regulate genes involved in neurovascular cell death, inflammation, and oxidative stress, with sex and age-dependent expression of miR-15a/16-1 and its targets likely underlying the observed variations. Overall, our findings identify miR-15a/16-1 antagomir as a promising therapeutic for ischemic stroke and suggest that sex and age should be considered when developing miR-based therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Evidence from randomized controlled trials has shown a benefit for endovascular treatment in basilar artery occlusion. We aimed to show the effect of the recanalization result on outcome and determine the role of underlying basilar stenosis in a real-world setting. Methods: A retrospective, single-center study of patients who received endovascular treatment for basilar artery occlusion from March 2008 to June 2022 was conducted. Clinical and outcome characteristics were gathered. Multivariate logistic regression analysis was performed to predict poor outcomes (post-treatment mRS 5 or 6). MRS shift analysis was performed. Results: This study includes 210 patients (mean age, 71.4 years +/− 13.3 [standard deviation]; 124 men). The variables age (OR, 1.04; 95% CI: 1.01–1.08; p = 0.014), underlying basilar stenosis (OR: 4.86; 95% CI: 2.15–10.98; p < 0.001), admission NHISS (OR: 1.09; 95% CI: 1.04–1.13; p < 0.001), and TICI (OR: 1.89; 95% CI: 1.09–3.25; p = 0.022) independently predicted a poor outcome. Patients with occlusions due to underlying stenosis had significantly worse recanalization rates. Median post-treatment mRS in all patients with embolic occlusion was 4; IQR, 2–5 (only patients with embolic occlusion: mTICI 0-2a, median: 5 [IQR, 4–5.5]; mTICI 2b, median: 4 [IQR, 2.5–6]; mTICI 3, median: 3 [IQR, 1–5]; p = 0.037). Median post-treatment mRS in all patients with occlusions due to underlying stenosis was 5; IQR, 4–6 (only patients with embolic occlusions: mTICI 0-2a, median: 6 [IQR, 4.5–6]; mTICI 2b, median: 6 [IQR, 4.25–6]; mTICI 3, median: 5 [IQR, 3.5–5.25]; p = 0.059). Conclusions: Successful recanalization is essential for preventing poor outcomes in basilar artery occlusion. Underlying basilar stenosis diminishes the effect of successful recanalization on the overall outcome. [ABSTRACT FROM AUTHOR]

Ischaemic stroke is a common condition that can lead to cerebral ischaemia–reperfusion injury. Phillygenin (PHI), a natural bioactive compound derived from Forsythia suspensa, has been shown to play a crucial role in regulating inflammation across various diseases. However, its specific regulatory effects in ischaemic stroke progression remain unclear. In this study, we established a middle cerebral artery occlusion (MCAO) rat model. Treatment with PHI (50 or 100 mg/kg) significantly reduced cerebral infarction in MCAO rats. PHI treatment also mitigated the increased inflammatory response observed in these rats. Additionally, PHI suppressed microglial activation by reducing iNOS expression, a marker of M1‐type polarization of microglia, and attenuated increased brain tissue apoptosis in MCAO rats. Furthermore, PHI's anti‐inflammatory effects in MCAO rats were abrogated upon co‐administration with GW9662, a peroxisome proliferator‐activated receptor γ (PPARγ) inhibitor. In summary, PHI attenuated microglial activation and apoptosis in cerebral ischaemia–reperfusion injury through PPARγ activation, suggesting its potential as a therapeutic agent for mitigating cerebral ischaemia–reperfusion injury. [ABSTRACT FROM AUTHOR]

Background: Lower extremity artery disease is increasingly prevalent, and complex lesions such as calcified chronic total occlusions pose significant challenges during endovascular therapy. The needle rendezvous technique, which involves puncturing a needle toward the guidewire within the lesion or lumen and advancing the guidewire into the needle lumen to achieve guidewire externalization, offers a potential solution. If device passage remains challenging, the Rendezvous-PIERCE technique can be subsequently employed by advancing the needle over the externalized guidewire to modify the lesion directly. This study aimed to evaluate the procedural outcomes of needle rendezvous in infrainguinal arterial occlusive lesions. Methods: This single-center, retrospective, single-arm study included patients treated with needle rendezvous between August 2020 and March 2024. The primary outcome was technical success rate, defined as the device passage following guidewire externalization using needle rendezvous. Secondary outcomes included the rates of procedural success, complications, and 30-day clinical-driven target lesion revascularization (CDTLR). Results: Twenty-five patients (25 limbs) with 52% on hemodialysis and 80% having chronic limb-threatening ischemia in 52% and 80% were enrolled. All cases involved bilateral calcified occlusions, and 72% targeted the infrapopliteal artery segment. The average needle rendezvous time was 3.7 ± 2.0 min. Rendezvous-PIERCE was performed in 28% of cases. All cases achieved 100% technical and procedural success, with no procedure-related complications. The 30-day CDTLR rate was 8%, limited to below-the-knee lesions. Conclusions: Needle rendezvous is a safe and effective technique for treating complex infrainguinal arterial occlusions, providing a viable alternative when conventional methods fail. [ABSTRACT FROM AUTHOR]

A 51‐year‐old male underwent vitrectomy with retrobulbar anesthesia for retinal detachment. Post surgery, he experienced systemic hypotension which normalized after 3 h. The day after, he complained of a central scotoma in the operated eye. Intraocular pressure was normal, but fundus examination revealed hemorrhages and whitening along the papillomacular bundle and macula, with additional whitening in the upper midperipheral region. Multimodal imaging confirmed branch retinal vein, artery, and cilioretinal artery occlusion. Further examination revealed mild‐to‐moderate obstructive sleep apnea syndrome. Vascular occlusions are potential complications of vitreoretinal surgery, warranting thorough preoperative assessment for underlying risk factors, even if causative mechanism is still unknown. [ABSTRACT FROM AUTHOR]

Introduction: The sheathless transradial (TR) technique is a novel approach that may offer potential benefits over the conventional TR approach. We aim to comprehensively investigate the safety and efficacy of sheathless versus conventional TR percutaneous coronary interventions (PCIs). Methods: We conducted comprehensive searches across PubMed, CENTRAL, Web of Science (WOS), Scopus, and EMBASE until July 2023. Pooled data were reported using risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, along with a 95% confidence interval (CI). PROSPERO ID: CRD42023443834. Results: We included 11 studies with 15,392 patients. The radial artery spasm (RAS) (RR: 0.26, 95% CI: [0.09, 0.77], p = 0.02) and cross‐over to the femoral site (RR: 0.28, 95% CI: [0.10, 0.81], p = 0.02) were significantly lower in the sheathless group. However, radial artery occlusion (RAO) (RR: 2.84, 95% CI: [1.78, 4.54], p < 0.0001) and success rate (RR: 1.011, 95% CI: [1.004, 1.019], p = 0.002) were significantly higher in the sheathless group. Also, we did not find a significant difference between both groups in all‐cause mortality (RR: 0.41, 95% CI: [0.16, 1.04], p = 0.06). Conclusion: The sheathless TR approach showed lower rates of RAS and femoral conversion. Sheathless has a higher success rate; however, it also increased RAO. Thus, more trials are needed to confirm this technique's long‐term outcomes and complications. [ABSTRACT FROM AUTHOR]

Background: Endovascular recanalization is a feasible option for treating symptomatic non-acute middle cerebral artery occlusion (MCAO) patients. Hence, we aimed to establish a new angiographic scoring to grade the recanalization difficulty of MCAO to determine the suitable patients for endovascular treatment. Methods: We retrospectively analyzed a total of 113 consecutive recurrent symptomatic non-acute MCAO patients who underwent endovascular recanalization from July 2015 to August 2021 in four Chinese comprehensive stroke centers. All patients were reappraised using a new angiographic scoring based on the stump morphology, the MCA occlusion length, MCA bend, and the distal vascular bed of MCAO. We used the final results to establish the patients' outcomes. Results: The total successful recanalization and perioperative complication rates were 83.2% (94/113) and 15.9% (18/113), respectively. No deaths occurred within 30 days. Moreover, 96.9, 90, 87.5, 52.6, and 50% of the patients achieved recanalization with scores of 0, 1, 2, 3, and 4 (p < 0.001), respectively. However, the perioperative complication rate showed the opposite trend. (3.1% vs. 7.5% vs. 6.3% vs. 52.6% vs. 50%; p < 0.001). The median time of successful microwire crossing of the occlusion lesion (TMO) in the score 0 group was shorter than the other groups (2 min, 9 min, 8.5 min, 14 min, and 20 min; p < 0.001). When a score of 2 was used as the optimal cut-off point, the sensitivity and specificity were 86.2 and 63.2%, respectively. Conclusion: The new angiographic scoring can effectively predict the successful recanalization rate, perioperative complication rate, and TMO of endovascular recanalization for non-acute MCAO. It can also be used as an effective clinical evaluation tool to determine the suitable non-acute MCAO patients for recanalization, especially with a score = 2. [ABSTRACT FROM AUTHOR]

Background: Sympathetic nervous system hyperactivity and chronic intermittent nocturnal hypoxia in individuals with obstructive sleep apnea (OSA) predispose them to microvascular impairment, which may contribute to increased daytime muscle fatigue. This study aimed to assess microvascular reactivity of the skeletal muscle, examine fatigability, and determine the relationship between fatigability and microvascular reactivity in adults with OSA. Methods: Twenty-six participants were allocated into two groups—those with OSA and those without i.e. non-OSA. Each group comprised of 13 individuals who underwent an arterial occlusion test on their non-dominant leg. The percentage change of maximal hyperemic response (MHR) and the time to achieve MHR (tM) of both the total myoglobin/hemoglobin (∆[Hbtot]) and the oxygenated myoglobin/hemoglobin (∆[HbO2]) signals from near-infrared spectroscopy were calculated to examine microvascular reactivity. In addition, a 10-min walk test was performed to assess performance and perceived fatigability. Results: The OSA group demonstrated a reduced in ∆[Hbtot]MHR (150.9 ± 16.2% vs. 235.8 ± 72.7%, p = 0.006), ∆[HbO2]MHR (131.4 ± 8% vs. 161.7 ± 10.6%, p = 0.001) and increased ∆[Hbtot]tM (80.5 ± 13.1 s vs. 47.7 ± 9.9 s, p < 0.001), ∆[HbO2]tM (85.2 ± 22.4 s vs. 52.1 ± 5.9 s, p = 0.001) compared to the non-OSA group. In addition, participants in the OSA group experienced greater perceived (6 ± 1 vs. 2.8 ± 0.1, p = 0.001) and performance fatigability (1.1 ± 0.1 vs. 0.9 ± 0.1, p = 0.001) compared to adults in the non-OSA group. Moreover, both performance and perceived fatigability were significantly associated with microvascular reactivity parameters (all p < 0.05). Conclusion: Microvascular dysfunction, as determined by an attenuated post-occlusive reactive hyperemia, is observed in individuals with OSA that may contribute to increased fatigability in these individuals. [ABSTRACT FROM AUTHOR]

Introduction: Given the high risk of peri-operative morbidity and mortality associated with open repair, endovascular repair for thoraco-abdominal aneurysms is increasingly performed. This study aims to describe mid to long-term results for patients who were treated with COOK Custom-Made Endograft Device at a single Southeast Asian tertiary centre. Methods: Mid to long-term results of patients treated from 2012 to 2022 were retrospectively reviewed. Indications for treatment were aortic diameter > 5.5 cm, enlargement > 5 mm in 6 months or high-risk morphology. Clinical, operative, early to late complications and reintervention details were captured. The endpoints were technical success, primary patency and primary assisted patency. Results: Electronic medical records of 29 consecutive patients (64.4 ± 1.6 years old; 26/29 males 89.6%) were reviewed. 24/29 (83%) were hypertensive, and 20/29 (69%) were smokers. The mean diameter was 5.5 cm, and the majority were treated for Crawford type IV (19/29, 65.5%). Endograft deployment was 100%. Catheterisation of fenestration was successful in 109/116 (94%). 30-day mortality and morbidity were observed in 12/29 (41%), for which access site complications were most common. No significant haemorrhage or graft explant was recorded. The mean follow-up period was 32.4 months (range 1–108 months). Primary patency was 92.9% (95% CI: 83.8–100.0) at 6 months and decreased to 77.7% (95% CI: 63.4–95.2) at 24 months. Sac shrinkage or stability was noted in 17/29 (58.6%). Re-intervention was performed in 9/29 (31%) for limb occlusion (2/9, 22.2%), renal artery stent occlusion (1/9, 11.1%) and endoleaks (6/9, 66.6%). Assisted patency was maintained at 100% for 12 months before decreasing to 66.7% (95% CI: 37.9–100.0) at 24 months. Conclusions: The study reports the first mid-long-term result in this region, though limited by the sample size. Re-intervention at 30% suggests that disease and procedures remain challenging, emphasising the need to assimilate lessons and experience at high-volume centres. [ABSTRACT FROM AUTHOR]

Background: With the launch of mechanical thrombectomy (MT), the prognosis of patients with cerebral infarction associated with large-vessel occlusion has improved. However, good outcomes are still not achieved in a few patients because of technical difficulties. Case presentation: A 79-year-old Japanese woman was admitted with sudden-onset left hemiplegia. Tissue plasminogen activator was administered and MT was performed for internal carotid artery occlusion distal to a large paraclinoid aneurysm. Some technical difficulties were unique, including contrast agent retention, difficulty in guiding the system, and avoidance of rupture of the aneurysm. Here, we discuss the technical issues and solutions of the MT procedure employed in this case. Conclusions: The procedure used in flow-diverter devices should be referenced and a stent-retrieving into an aspiration catheter with proximal balloon technique may be the most appropriate method. [ABSTRACT FROM AUTHOR]

Background: One key focus of partial nephrectomy is preserving renal function. Segmental renal artery occlusion with microdissection at the renal hilum confines ischemia, effectively reducing warm ischemic injury. Ultrasound-Guided Renal Artery Balloon Catheter Occluded Hybrid Partial Nephrectomy (UBo-HPN) can achieve branch occlusion without the need for dissecting the renal hilum. Objective: To investigate the feasibility and safety of UBo-HPN of branch renal artery occlusion in the treatment of localized renal tumors. Subject and methods: A prospective single-arm analysis involving 20 patients with renal localized tumors underwent robot assisted UBo-HPN with branch renal artery occlusion from August 2021 to July 2023, with an average follow-up of 12 months. Results: All patient was successfully operated on without conversion to conventional arterial clamping or radical nephrectomy. One case (5%) of minor complication occurred in the whole cohort, which was bruising around the puncture site. The mean total operative time was 95.8 min, with a mean operative time of 21.25 min for vascular intervention. The mean warm ischemia time was 20.35 min, and the median estimated blood loss was 50 ml. The median eGFR preservation percentage at postoperative 48 h, 30 days, and the latest follow-up were 87.52%, 91.47%, and 92.2%, respectively. After a median follow-up of 10.2 (2.3–19.2) months, no patients had radiological tumor recurrence or died from tumor-related causes. Conclusions: UBo-HPN with renal artery branch occlusion emerges as an efficient alternative to partial nephrectomy (PN), which achieved branch artery occlusion without dissecting the renal hilum. Long-term follow-up is expected for functional outcomes. [ABSTRACT FROM AUTHOR]

Background: Psilocybin is a psychedelic 5HT2A receptor agonist found in "magic mushrooms". Recent studies have indicated that 5HT2A agonists, such as dimethyltryptamine, given before middle cerebral artery occlusion (MCAo), improve staircase behavior, increased BDNF expression, and reduce brain infarction in stroke rats. The objective of this study is to determine the protective effect of psilocybin in cellular and animal models of stroke. Methods: Adult male and timed-pregnant Sprague-Dawley rats were used for this study. The neural protective effects of psilocybin were determined in primary rat cortical neurons and adult rats. Rats were subjected to a 60-min middle cerebral artery occlusion. Brain tissues were collected for histological and qRTPCR analysis. Results: Psilocybin reduced glutamate-mediated neuronal loss in rat primary cortical neuronal cultures. Psilocybin-mediated protection in culture was antagonized by the BDNF inhibitor ANA12. Pretreatment with psilocybin reduced brain infarction and neurological deficits in stroke rats. Early post-treatment with psilocybin improved locomotor behavior, upregulated the expression of MAP2 and synaptophysin, and down-regulated the expression of IBA1 in the stroke brain. ANA12 significantly attenuated psilocybin-mediated reduction in brain infarction and improvements in locomotor behavior. Conclusions: Psilocybin reduced brain infarction and improved locomotor behavior in stroke rats; the protective mechanisms involve regulating BDNF expression. Our data support a novel therapeutic approach of psilocybin in stroke. Highlights: Psilocybin reduced glutamate-mediated neuronal loss in primary cortical neuronal cultures. ANA12 reduced psilocybin-mediated protection in culture. Psilocybin reduced brain infarction, reduced neurological deficits, and increased locomotor behavior in stroke rats. Psilocybin enhanced the expression of MAP2 and synaptophysin, and down-regulated IBA1 in the stroke rat brain. [ABSTRACT FROM AUTHOR]

Out-of-hospital cardiac arrest (OHCA) is a global health problem affecting approximately 4.4 million individuals yearly. OHCA has a poor survival rate, specifically when unwitnessed (accounting for up to 75% of cases). Rapid recognition can significantly improve OHCA survival, and consumer wearables with continuous cardiopulmonary monitoring capabilities hold potential to "witness" cardiac arrest and activate emergency services. In this study, we used an arterial occlusion model to simulate cardiac arrest and investigated the ability of infrared photoplethysmogram (PPG) sensors, often utilized in consumer wearable devices, to differentiate normal cardiac pulsation, pulseless cardiac (i.e., resembling a cardiac arrest), and non-physiologic (i.e., off-body) states. Across the classification models trained and evaluated on three anatomical locations, higher classification performances were observed on the finger (macro average F1-score of 0.964 on the fingertip and 0.954 on the finger base) compared to the wrist (macro average F1-score of 0.837). The wrist-based classification model, which was trained and evaluated using all PPG measurements, including both high- and low-quality recordings, achieved a macro average precision and recall of 0.922 and 0.800, respectively. This wrist-based model, which represents the most common form factor in consumer wearables, could only capture about 43.8% of pulseless events. However, models trained and tested exclusively on high-quality recordings achieved higher classification outcomes (macro average F1-score of 0.975 on the fingertip, 0.973 on the finger base, and 0.934 on the wrist). The fingertip model had the highest performance to differentiate arterial occlusion pulselessness from normal cardiac pulsation and off-body measurements with macro average precision and recall of 0.978 and 0.972, respectively. This model was able to identify 93.7% of pulseless states (i.e., resembling a cardiac arrest event), with a 0.4% false positive rate. All classification models relied on a combination of time-, power spectral density (PSD)-, and frequency-domain features to differentiate normal cardiac pulsation, pulseless cardiac, and off-body PPG recordings. However, our best model represented an idealized detection condition, relying on ensuring high-quality PPG data for training and evaluation of machine learning algorithms. While 90.7% of our PPG recordings from the fingertip were considered of high quality, only 53.2% of the measurements from the wrist passed the quality criteria. Our findings have implications for adapting consumer wearables to provide OHCA detection, involving advancements in hardware and software to ensure high-quality measurements in real-world settings, as well as development of wearables with form factors that enable high-quality PPG data acquisition more consistently. Given these improvements, we demonstrate that OHCA detection can feasibly be made available to anyone using PPG-based consumer wearables. [ABSTRACT FROM AUTHOR]

Aims: Dopamine transporter (DAT) can regulate DA homeostasis and has been implicated in many nervous system diseases. Whether DAT is involved in the protection against ischemic stroke is unclear. Methods: In vivo microdialysis measurements of DA were recorded in the ischemic penumbral area of mice with middle cerebral artery occlusion (MCAO). DAT coding gene, Slc6a3 mutation, and DAT overexpression animals were performed MCAO. Madopar (compound formulation of levodopa) and nomifensine (DA reuptake inhibitor) were administered in MCAO animals. Brain slices were prepared in Slc6a3 mutation or wild‐type (WT) animals with MCAO to record miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs). The effects of DA and its dopamine‐1 receptor (D1R) antagonists (SCH‐23390) on mEPSCs, mIPSCs, and neurons protection were recorded. Results: MCAO caused a prominent increase in DA. Slc6a3 mutation significantly attenuated the ischemic injury, whereas DAT overexpression aggravated this injury. Both nomifensine and madopar protected against brain injury. Slc6a3 mutation and DA restored the disturbance of mEPSCs and mIPSC, and protected against neuron death, which was abolished by SCH‐23390. Conclusion: DAT inhibition might be explored as a strategy for ischemic stroke prevention. DA and D1R involve in the restoration of synaptic dysfunction and neuron protection. [ABSTRACT FROM AUTHOR]

Background: Aquaporin‐4 (AQP4), predominantly expressed in astrocytes, has been implicated in the development of brain edema following ischemic events. However, its role in post‐stroke neuroinflammation is not fully understood. Methods: Using a middle cerebral artery occlusion (MCAO) mouse model, we assessed AQP4's role in post‐stroke inflammation. Brain tissue slices from male C57BL/6 mice were subjected to immunohistochemistry and western blot post‐MCAO. Additionally, primary astrocytes were isolated for quantitative real‐time PCR and immunofluorescence assays to evaluate the expression of inflammatory markers glial fibrillary acidic protein (GFAP) and AQP4. AQP4 modulation was achieved using viral knockdown and overexpression methods. Neuronal damage was assessed using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) tests in co‐culture studies. Results: MCAO mice exhibited a significant upregulation in GFAP. This reactive astrogliosis corresponded with an elevation in inflammatory markers. AQP4 expression responded to this inflammatory trend, peaking at 6 h after OGD and returning to baseline levels at 24 and 48 h. Co‐culture experiments revealed that AQP4(+) astrocytes exacerbated injury in OGD‐treated neurons, as evidenced by increased TUNEL positivity and apoptotic events. Conversely, AQP4(−) astrocytes appeared to have a protective effect. Knockdown of AQP4 resulted in reduced post‐OGD inflammatory response, whereas AQP4 overexpression intensified the injury to neurons post‐OGD. In vivo experiments also confirmed that AQP4 inhibitor TGN‐020 reduced and overexpression of AQP4 increased behavioral abnormalities and brain infarcts. Conclusion: Our findings underscore AQP4's pivotal role in modulating post‐stroke neuroinflammation. Targeting AQP4 may present a novel therapeutic avenue for mitigating ischemia‐induced neuronal damage. [ABSTRACT FROM AUTHOR]

Background: Currently, there is still a lack of valuable neuroimaging markers to assess the clinical severity of stroke patients with small artery occlusion (SAO). Quantitative susceptibility mapping (QSM) is a quantitative processing method for neuroradiological diagnostics. Gray matter (GM) volume changes in stroke patients are also proved to be associated with neurological deficits. This study aims to explore the predictive value of QSM and GM volume in neurological deficits of patients with SAO. Methods: As neurological deficits, the National Institutes of Health Stroke Scale (NIHSS) was used. Sixty‐six SAO participants within 24 h of first onset were enrolled and divided into mild and moderate groups based on NIHSS. QSM values of infarct area and GM volume were calculated from magnetic resonance imaging (MRI) data. Two‐sample t‐tests were used to compare differences in QSM value and GM volume between the two groups, and the diagnostic efficacy of the combination of QSM value and GM volume was evaluated. Results: The results revealed both the QSM value and GM volume within the infarct area of the moderate group were lower compared to the mild group. Moderate group exhibited lower GM volume in some specific gyrus compared with mild group in the case of voxel‐wise GM volume on whole‐brain voxel level. The support vector machine (SVM) classifier's analysis showed a high power for the combination of QSM value, GM volume within the infarct area, and voxel‐wise GM volume. Conclusion: Our research first reported the combination of QSM value, GM volume within the infarct area, and voxel‐wise GM volume could be used to predict neurological impairment of patients with SAO, which provides new insights for further understanding the SAO stroke. [ABSTRACT FROM AUTHOR]

Postoperative care is essential to upper extremity replantation success and includes careful and frequent monitoring of the replanted part. During this period, pharmacologic agents such as antithrombotic and anticoagulants may prevent complications such as arterial thrombosis and venous congestion. Dressings and therapy can also impact short- and long-term outcomes following replantation. This article reviews the literature to provide guidance for postoperative protocols following upper extremity replantation. [ABSTRACT FROM AUTHOR]

Lipids and their bioactive metabolites, notably lysophosphatidylcholine (LPC), are increasingly important in ischemic stroke research. Reduced plasma LPC levels have been linked to stroke occurrence and poor outcomes, positioning LPC as a potential prognostic or diagnostic marker. Nonetheless, the connection between plasma LPC levels and stroke severity remains unclear. This study aimed to elucidate this relationship by examining plasma LPC levels in conjunction with brain LPC levels to provide a deeper understanding of the underlying mechanisms. Adult male Sprague–Dawley rats underwent transient middle cerebral artery occlusion and were randomly assigned to different groups (sham-operated, vehicle, LPC supplementation, or LPC inhibition). We measured multiple LPC species in the plasma and brain, alongside assessing sensorimotor dysfunction, cerebral perfusion, lesion volume, and markers of BBB damage, inflammation, apoptosis, and oxidative stress. Among five LPC species, plasma LPC(16:0) and LPC(18:1) showed strong correlations with sensorimotor dysfunction, lesion severity, and mechanistic biomarkers in the rat stroke model. Despite notable discrepancies between plasma and brain LPC levels, both were strongly linked to functional outcomes and mechanistic biomarkers, suggesting that LPC's prognostic value is retained extracranially. This study advances the understanding of LPC as a blood marker in ischemic stroke and highlights directions for future research to further elucidate its association with stroke severity, particularly through investigations in more clinically representative models. [ABSTRACT FROM AUTHOR]

Introduction : In this study, we aimed to evaluate and compare whether perioperative additional intravenous (IV) Iloprost therapy to percutaneous balloon angioplasty for peripheral arterial occlusive disease improves patency and reintervention. Methods : Between January 2018 and August 2020, 183 patients underwent Percutaneous transluminal angioplasty (PTA) with Drug-Eluting Balloons (DEB) for femoropopliteal lesions (TASC 2 A-C) due to claudication, and 161 patients (133 male, 28 female, mean age 63.65 ± 11.16 years, range 30-86 years) were included in this study. The patients were divided into two groups as DEB+ Intravenous Iloprost administration and DEB alone. Primary patency, reintervention, bailout stenting, and survival rates were analyzed in this retrospective study. Results : Primary patency rate at 12 months (79 vs 57 patients, 89.7 vs 78%, p = 0.041) and assisted primary patency rate (81 vs 59 patients, 92 vs 80.8%, p = 0.035) were found to be higher and Bailout stent deployment was lower in DEB + Iloprost group (3 vs 9 patients, 3.4 vs 12.3% p = 0.031). The reinterventions rate at 12 months was also lower among the DEB + Iloprost group (9 vs 16 patients, 10.2 vs 21.9%, p = 0.041). Conclusion : The present study demonstrated that primary patency at 12 months and assisted primary patency rates, freedom from reintervention was significantly higher and bailout stenting was found to be significantly lower. We believe that perioperative Intravenous Iloprost therapy is beneficial for PTA and improves outcomes. [ABSTRACT FROM AUTHOR]

The article highlights a significant advantage of endovascular thrombectomy for patients suffering from acute basilar artery occlusion, showing that the positive outcomes not only sustained at three months but also improved at one year. Topics discussed include the comparison of endovascular therapy to medical management, the differing results of various trials in assessing treatment effectiveness, and the implications of one-year outcomes for patients with basilar artery occlusions.

Purpose: To develop thrombus radiomics models based on dual-energy CT (DECT) for predicting etiologic cause of stroke. Methods: We retrospectively enrolled patients with occlusion of the middle cerebral artery who underwent computed tomography (NCCT) and DECT angiography (DECTA). 70 keV virtual monoenergetic images (simulate conventional 120kVp CTA images) and iodine overlay maps (IOM) were reconstructed for analysis. Five logistic regression radiomics models for predicting cardioembolism (CE) were built based on the features extracted from NCCT, CTA and IOM images. From these, the best one was selected to integrate with clinical information for further construction of the combined model. The performance of the different models was evaluated and compared using ROC curve analysis, clinical decision curves (DCA), calibration curves and Delong test. Results: Among all the radiomic models, model NCCT+IOM performed the best, with AUC = 0.95 significantly higher than model NCCT, model CTA, model IOM and model NCCT+CTA in the training set (AUC = 0.88, 0.78, 0.90,0.87, respectively, P < 0.05), and AUC = 0.92 in the testing set, significantly higher than model CTA (AUC = 0.71, P < 0.05). Smoking and NIHSS score were independent predictors of CE (P < 0.05). The combined model performed similarly to the model NCCT+IOM, with no statistically significant difference in AUC either in the training or test sets. (0.96 vs. 0.95; 0.94 vs. 0.92, both P > 0.05). Conclusion: Radiomics models constructed based on NCCT and IOM images can effectively determine the source of thrombus in stroke without relying on clinical information. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate whether the spatial coefficient of variation of arterial spin labeling (ASL-CoV) acquired in clinical settings can be used to estimate decreased cerebrovascular reactivity (CVR) measured with single-photon emission computed tomography (SPECT) and acetazolamide challenge in patients with atherosclerotic stenosis of intra- or extracranial arteries. Methods: We evaluated the data of 27 atherosclerotic stenosis patients who underwent pseudocontinuous ASL and SPECT. After spatial normalization, regional values were measured using the distributed middle cerebral artery territorial atlas of each patient. We performed comparisons, correlations, and receiver operating characteristic (ROC) curve analyses between ASL-cerebral blood blow (CBF), ASL-CoV, SPECT-CBF and SPECT-CVR. Results: Although the ASL-CBF values were positively correlated with SPECT-CBF values (r = 0.48, 95% confidence interval (CI) = 0.28–0.64), no significant difference in ASL-CBF values was detected between regions with and without decreased CVR. However, regions with decreased CVR had significantly greater ASL-CoV values than regions without decreased CVR. SPECT-CVR was negatively correlated with ASL-CoV (ρ = -0.29, 95% CI = -0.49 - -0.06). The area under the ROC curve of ASL-CoV in predicting decreased CVR (0.66, 95% CI = 0.51–0.81) was greater than that of ASL-CBF (0.51, 95% CI = 0.34–0.68). An ASL-CoV threshold value of 42% achieved a high specificity of 0.93 (sensitivity = 0.42, positive predictive value = 0.77, and negative predictive value = 0.75). Conclusion: ASL-CoV acquired by single postlabeling delay without an acetazolamide challenge may aid in the identification of patients with decreased CVR on SPECT. [ABSTRACT FROM AUTHOR]

Contemporary quality control methods are often insufficient in predicting clinical outcomes after revascularization in lower extremity arterial disease (LEAD) patients. This study evaluates the potential of near-infrared fluorescence imaging with indocyanine green to predict the clinical outcome following revascularization. Near-infrared fluorescence imaging was performed before and within 5 days following the revascularization procedure. Clinical improvement was defined as substantial improvement of pain free walking distance, reduction of rest- and/or nocturnal pain, or tendency toward wound healing. Time-intensity curves and 8 perfusion parameters were extracted from the dorsum of the treated foot. The quantified postinterventional perfusion improvement was compared within the clinical outcome groups. Successful near-infrared fluorescence imaging was performed in 72 patients (76 limbs, 52.6% claudication, 47.4% chronic limb-threatening ischemia) including 40 endovascular- and 36 surgical/hybrid revascularizations. Clinical improvement was observed in 61 patients. All perfusion parameters showed a significant postinterventional difference in the clinical improvement group (P -values <.001), while no significant differences were seen in the group without clinical improvement (P -values.168–.929). Four parameters demonstrated significant differences in percentage improvement comparing the outcome groups (P -values within.002–.006). Near-infrared fluorescence imaging has promising additional value besides clinical parameters for predicting the clinical outcome of revascularized LEAD patients. [ABSTRACT FROM AUTHOR]

Objectives This study reported a single-center clinical trial of endovascular treatment for symptomatic nonacute occlusion of the intracranial large artery (NA-ILAO). The aim of this study was to evaluate the safety, feasibility, and clinical effect of simple balloon dilatation and stent implantation. Methods The patients diagnosed with symptomatic NA-ILAO were enrolled. A total of 40 cases were included in this study. While recanalization failed in 4 patients, it was successful in 36 patients, who were then divided into two groups for further analysis: balloon dilatation group (n = 24) and stent implantation group (n = 12). The perioperative complications, clinical outcome, and follow-up results were analyzed. Results Perioperative complications in the stent implantation group were significantly higher than those in the simple balloon dilatation group (p < 0.05). There were 21 and 10 cases of 90-day good clinical outcome (modified Rankin scale [mRS] ≤ 2) in the balloon and stent groups, respectively (p = 0.518). All patients with successful recanalization underwent digital subtraction angiography (DSA) or CT angiography (CTA) during an average follow-up of 14 months. There were two cases of restenosis in the balloon dilatation group and one in the stent implantation group (p = 1.000). There were two cases of re-occlusion in the stent group and none in the balloon dilatation group (p < 0.001). Stroke recurred in two cases in the stent group and in one case in the simple balloon dilatation group (p = 0.013). Conclusion Endovascular recanalization is safe and feasible for patients with symptomatic NA-ILAO. Compared with stent implantation, simple balloon dilation may be a better recanalization method, but larger randomized controlled trials are needed to confirm it. [ABSTRACT FROM AUTHOR]

Background Collateral blood supply of distal vessels has been linked to clinical outcome, infarct volume and recanalization rates in patients with large vessel occlusion. Our study aimed to explore the effects of catheterization during mechanical thrombectomy in collaterals. Methods We quantified the flow diversion effect secondary to arterial occlusions in an in vitro model which was connected in a flow-loop setup with a saline reservoir and a pump supplying pulsatile flow. Clot analogs were embolized to the middle cerebral artery (MCA) M1 or M2 segments. We used the same model with a clamped anterior communicating artery (AComA) to simulate its absence. An ultrasound flow sensor was placed at the vessel of interest. Flow rates and pressures were evaluated according to the following catheter locations: baseline (1) before and (2) after the occlusion; (3) 8F guiding catheter at the internal carotid artery (ICA) bulb; (4) at the cavernous segment; (5) at the cavernous segment a 0.071" distal access catheter at proximal M1; (6) 8F balloon guide catheter inflated. Results Collateral blood flow measured at distal anterior cerebral artery (ACA) (M1-MCA occlusion) and M2-MCA (M2-MCA occlusion) was progressively reduced as catheters were advanced through the ICA and MCA. In the lacking AComA model, the flow was further diminished as compared with the model with a patent AComA. Conclusion Our in vitro study showed a progressive reduction of collateral blood flow due to the advance of catheters during mechanical thrombectomy. [ABSTRACT FROM AUTHOR]

Backgrounds Recent trials have shown improved outcomes after mechanical thrombectomy (MT) for vertebrobasilar occlusion (VBO) stroke. However, there is a paucity of data regarding safety and outcomes of rescue intracranial stenting (RS) after failed MT (FRRS+) for posterior circulation stroke. We sought to compare RS to failed reperfusion without RS (FRRS-). Methods This is a retrospective analysis of the Stenting and Angioplasty in NeuroThrombectomy (SAINT) study, a multicenter collaboration involving prospectively collected databases. Patients were included if they had posterior circulation stroke and failed MT. The cohort was divided into two groups: FRRS+ and FRRS- (defined as modified Thrombolysis In Cerebral Infarction (mTICI) score 0-2a). The primary outcome was a shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included mRS 0-2 and mRS 0-3 at 90 days. Safety measures included rates of symptomatic intracranial hemorrhage (sICH), procedural complications, and 90-day mortality. Sensitivity and subgroup analyses were performed to identify outcomes in a matched cohort and in those with VBO, respectively. Results A total of 152 failed thrombectomies were included in the analysis. FRRS+ (n=84) was associated with increased likelihood of lower disability (acOR 2.24, 95% CI 1.04 to 4.95, P=0.04), higher rates of mRS 0-2 (26.8% vs 12.5%, aOR 4.43, 95% CI 1.22 to 16.05, P=0.02) and mRS 0-3 (35.4% vs 18.8%, aOR 3.13, 95% CI 1.08 to 9.10, P=0.036), and lower mortality (42.7% vs 59.4%, aOR 0.40, 95% CI 0.17 to 0.97, P=0.04) at 90 days compared with FRRS- (n=68). The rates of sICH and procedural complications were comparable between the groups. Sensitivity and subgroup analyses showed similar results. Conclusion In patients with posterior circulation stroke who had failed MT, RS resulted in better functional outcomes with comparable safety profile to procedure termination. [ABSTRACT FROM AUTHOR]

Background Acute basilar artery occlusion is a disabling and life-threatening condition. The purpose of this study was to evaluate the impact of occluded vessel location on the prognostic outcomes of patients who underwent endovascular treatment for acute basilar artery occlusion. Methods Patient data for this study were obtained from the ATTENTION registry. Baseline data of the patients were described and compared across different occlusion locations. Univariable and multivariable regression analyses were performed to assess the effect of occluded vessel location on associated prognostic outcomes. Results A total of 1672 patients were included in the analysis, with 583 having distal occlusion, 540 having middle occlusion, and 549 having proximal occlusion. Unlike distal occlusion, both proximal and middle occlusions were significantly and negatively associated with favorable clinical outcomes (for modified Rankin Scale score 0-3: adjusted odds ratio (aOR) 0.634, 95% confidence interval (95% CI) 0.493 to 0.816, P<0.001 in middle occlusion, and aOR 0.620, 95% CI 0.479 to 0.802, P<0.001 in proximal occlusion). Mortality was higher in patients with proximal and middle occlusions (aOR 1.461, 95% CI 1.123 to 1.902, P=0.005 in middle occlusion, and aOR 1.648, 95% CI 1.265 to 2.147, P<0.001 in proximal occlusion). The occluded vessel location was not associated with symptomatic intracranial hemorrhage. Conclusions Proximal and middle basilar artery occlusions were predominantly associated with poor clinical outcomes and increased risk of death following endovascular treatment. [ABSTRACT FROM AUTHOR]

Lower limb arterial occlusive disease is treated with intraluminal devices, such as paclitaxel (PTX)-coated balloons (PCBs); however, post-procedural restenosis remains a significant challenge. NLRP3 activation is known to play a significant role in atherosclerosis, but its involvement in restenosis following PCB intervention remains to be investigated. We identified that NLRP3 was differentially expressed in lower-limb arterial tissues sourced from healthy controls and patients with arterial occlusive disease. Through cell experiments, we confirmed that PTX is involved in the activation of NLRP3. Subsequently, we demonstrated that NLRP3 activation promotes the proliferation and migration of vascular smooth muscle cell (VSMC), thereby reducing their sensitivity to PTX. NLRP3 activation also stimulates the secretion of the inflammatory cytokine interleukin IL-1β. RNA sequencing of IL-1β-treated VSMC revealed the upregulation of BRD4 and LIN9. Further mechanistic investigations confirmed that IL-1β facilitates BRD4 recruitment, leading to enhanced LIN9 expression. The transcription factor LIN9 binds to the promoter region of the cell-cycle regulator AURKA, thereby promoting its transcription and subsequently upregulating the expression of the cell proliferation-associated molecule FOXM1. These processes ultimately mediate the proliferation, migration, and PTX resistance of VSMC. Additionally, we discovered that JQ1 inhibited the overexpression of the above molecules, and exhibited a synergistic effect with PTX. Our conclusions were validated through in vivo experiments in Sprague-Dawley rats. Collectively, our findings provide insights into the molecular mechanisms underlying restenosis following PCB therapy, and suggest that the combined use of JQ1 and PTX devices may represent a promising therapeutic strategy. [ABSTRACT FROM AUTHOR]

Stroke related to large vessel occlusion is a leading cause of disability and death worldwide. Advances in endovascular therapy to reopen occluded arteries have been shown to reduce patient disability and mortality. Expanded indications to treat patients with large vessel occlusion in the late window (>6 h from symptom onset), with basilar artery occlusion, and with large ischaemic core at presentation have enabled treatment of more patients with simplified imaging methods. Ongoing knowledge gaps include an understanding of which patients with large ischaemic infarct are more likely to benefit from endovascular therapy, the role of endovascular therapy in patients who present with low National Institutes of Health Stroke Scale scores or medium or distal vessel occlusion, and optimal management of patients with underlying intracranial atherosclerotic disease. As reperfusion can now be facilitated by intravenous thrombolysis, mechanical thrombectomy, or both, the development of cytoprotective or adjunctive drugs to slow infarct growth, enhance reperfusion, or decrease haemorrhagic risk has gained renewed interest with the hope to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction Aims Methods Results Conclusion Limb dominancy has been suggested, by some, to influence arterial occlusion pressure (AOP). However, we hypothesized that the differences in AOP between the dominant and nondominant legs were more likely explained by differences in cuff position.To determine the impact of limb dominance, composition, and cuff position on AOP in the context of error associated with measuring AOP twice on the same leg.Fifty‐eight adults (30 males) volunteered to have AOP measured on their dominant legs with the cuff bladder covering their inner thighs and on their nondominant legs with the bladder covering their inner and outer thighs (in random order). Thigh circumference and muscle and fat thicknesses were also measured on each leg.We found evidence for differences in AOP between legs [median δ of −0.222, 95% credible interval: (−0.429, −0.016)] when the cuff position was matched. The mean difference was −2.8 mmHg, and the 95% limit of agreement in a Bland–Altman plot was −24.8 to 19.0 mmHg. When plotting this alongside an error range (i.e., 95% limits of agreement) of taking the same measurement twice from our previous study (Spitz et al., 2020), 52 out of 58 measurements were within the error range. This difference was not due to the cuff position. Additionally, there was no evidence that thigh circumference or composition (muscle/fat thickness) moderated any difference between limbs.The difference in AOP between limbs is small and is mostly indistinguishable from the difference observed from taking the measurement twice on the same limb. [ABSTRACT FROM AUTHOR]

Ischemic Preconditioning (IPC) has emerged as a promising approach to mitigate the impact of hypoxia on physiological functions. However, the heterogeneity of occlusion pressures for inducing arterial occlusion has led to inconsistent hemodynamic outcomes across studies. This study aims to evaluate the peripheral hemodynamic responses to partial and total blood-flow occlusions on the left arm at rest, using absolute or individualized pressures, on two occasions. Thirty-five young males volunteered to participate in this study. IPC procedure (3 × 7-min) was performed on the left upper arm with cuff pressures at 50 mmHg (G1), 50 mmHg over the systolic blood pressure (SBP + 50 mmHg) (G2) or 250 mmHg (G3). NIRS-derived parameters were assessed for each occlusion and reperfusion phase in the brachioradialis. Results showed a significantly lower magnitude of deoxygenation (TSIAUC) for G1 compared to G2 (-1959.2 ± 1417.4 vs. -10908.1 ± 1607.5, P < 0.001) and G3 -1959.2 ± 1417.4 vs. -11079.3 ± 1828.1, P < 0.001), without differences between G2 and G3. However, G3 showed a significantly faster reoxygenation only for tissue saturation index (TSIslope) compared to G2 (1.3 ± 0.1 vs. 1.0 ± 0.2, P = 0.010), but without differences in the speed of recovery of deoxyhemoglobin [(HHb) slope], or in the magnitude of post-occlusive hyperemia (PORH). Besides TSI reoxygenation speed, G2 and G3 elicit comparable resting hemodynamic responses measured by NIRS. Thus, this study highlights the practicality and effectiveness of using relative occlusion pressures based on systolic blood pressure (SBP) rather than relying on excessively high absolute pressures. [ABSTRACT FROM AUTHOR]

The treatment time window for acute cerebral infarction in global guidelines is within 24 h. We report a patient who was admitted to the hospital and underwent endovascular treatment reaching 40 h. During vascular examination, the thrombus moved to distant segment, and then the surgeon quickly performed endovascular treatment. The patient ultimately achieved a good outcome. This case indicates that thrombus is moveable at any time, we expected to provide advice to clinical doctors that vascular examination should also be arranged as soon as possible to clarify the etiology in stroke patients especially with low NIHSS scores. [ABSTRACT FROM AUTHOR]

Background: Stroke, a leading cause of death and disability, lacks effective treatments. Post-stroke secondary damage worsens the brain microenvironment, further exacerbating brain injury. Microglia's role in responding to stroke-induced damage in peri-infarct regions is crucial. In this study, we explored Weisheng-tang's potential to enhance ischemic outcomes by targeting microglia. Methods: We induced middle cerebral artery occlusion and reperfusion in mice, followed by behavioral assessments and infarct volume analyses after 48 h, and examined the changes in microglial morphology through skeleton analysis. Results: Weisheng-tang (300 mg/kg) significantly reduced infarction volume and alleviated neurological and motor deficits. The number of activated microglia was markedly increased within the peri-infarct territory, which was significantly reversed by Weisheng-tang. Microglial morphology analysis revealed that microglial processes were retracted owing to ischemic damage but were restored in Weisheng-tang-treated mice. This restoration was accompanied by the expression of the purinergic P2Y12 receptor (P2Y12R), a key regulator of microglial process extension. Weisheng-tang increased neuronal Kv2.1 clusters while suppressing juxtaneuronal microglial activation. The P2Y12R inhibitor--ticagrelor--eliminated the tissue and functional recovery that had been observed with Weisheng-tang after ischemic damage. Discussion: Weisheng-tang improved experimental stroke outcomes by modulating microglial morphology through P2Y12R, shedding light on its neuroprotective potential in ischemic stroke. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this paper are to evaluate the incidence of early graft occlusion during hospital stays following coronary bypass surgery (CABG) and to assess the factors influencing the odds of in-hospital early graft occlusion. Methods: Reports evaluating the early in-hospital occlusion of coronary bypass grafts were identified through PubMed, Embase, and Cochrane databases. The primary endpoint was to determine the incidence of early graft occlusion following CABG before discharge and to identify and quantify the impact of demographic, clinical, and procedural risk factors on the occurrence of early graft occlusion. The meta-analysis was conducted using a random-effects inverse-variance model with the DerSimonian–Laird estimator, assessing incidence rates, risk factors, and study heterogeneity, with statistical analysis performed using Stata. Results: A total of 22 studies with 35,798 patients were included in the analysis. The overall incidence of in-hospital early graft occlusion was 5% (95% CI: 3% to 7%). In studies using symptom-driven patency assessment, the incidence of occlusion was 2%, whereas in those employing systematic graft patency assessment, it was 6%. Only the presence of a vein graft OR 2.13 (95% CI: 1.19–3.82) was significantly associated with in-hospital graft occlusion. Conclusions: The incidence of in-hospital early graft occlusion seems substantially underestimated if imaging is restricted only to symptomatic patients. Moreover, female gender, increased PI, and the presence of a composite graft could also be potential risk factors for this complication. [ABSTRACT FROM AUTHOR]

Background: Transfemoral access (TFA) is a valuable alternative to upper extremity access (UEA) for branched endovascular aortic repair (bEVAR). However, TFA requires large introducer sheaths, which can reduce blood flow to lower limbs and the pelvis. This study aimed to evaluate the efficacy of sheath downsizing to maintain lower limb perfusion during TFA–bEVAR. Methods: A single-center retrospective review was conducted including patients managed with TFA-performed bEVAR between December 2020 and May 2021. Intra-operative lower limb perfusion was assessed using non-invasive ankle blood pressure measurements and great toe pulse oximetry, with measurements being taken prior to puncture (baseline), one minute after 10F-sheath insertion, three minutes after the main body delivery system insertion, and three minutes after downsizing to a 14F sheath. Outcomes included the incidence of limb perfusion reduction (LPR), defined as a drop in the ankle–brachial index (ABI) < 0.5 or peripheral oxygen saturation (SpO2) < 90%. Results: Out of 47 patients, 24 met the inclusion criteria. LPR occurred in 4.2% of cases after 10F-sheath placement, and 87.5% after main body delivery system placement, and decreased to 12.6% after downsizing to a 14F sheath. No periprocedural major bleeding occurred. Two patients required revision for inadequate hemostasis post-operatively. SCI occurred in 16% of patients, all recovered by discharge. Pre-operative hypogastric artery occlusion was related to persistent LPR after downsizing (100% vs. 16%, p = 0.009). Conclusions: Downsizing the introducer sheath during bEVAR is feasible and safe to restore lower limb and pelvic perfusion. Further research is needed to clarify the access downsizing value during bEVAR. [ABSTRACT FROM AUTHOR]

Background and Purpose: Thrombo‐inflammation is a key feature of stroke pathophysiology and provides multiple candidate drug targets. Thrombin exerts coagulation‐independent actions via protease‐activated receptors (PAR), of which PAR1 has been implicated in stroke‐associated neuroinflammation. The role of PAR4 in this context is less clear. This study examined if the selective PAR4 antagonist ML354 provides neuroprotection in experimental stroke and explored the underlying mechanisms. Experimental Approach: Mouse primary cortical neurons were exposed to oxygen–glucose deprivation (OGD) and simulated reperfusion ± ML354. For comparison, functional Ca2+‐imaging was performed upon acute stimulation with a PAR4 activating peptide or glutamate. Male mice underwent sham operation or transient middle cerebral artery occlusion (tMCAO), with ML354 or vehicle treatment beginning at recanalization. A subset of mice received a platelet‐depleting antibody. Stroke size and functional outcomes were assessed. Abundance of target genes, proteins, and cell markers was determined in cultured cells and tissues by qPCR, immunoblotting, and immunofluorescence. Key Results: Stroke up‐regulated PAR4 expression in cortical neurons in vitro and in vivo. OGD augments spontaneous and PAR4‐mediated neuronal activity; ML354 suppresses OGD‐induced neuronal excitotoxicity and apoptosis. ML354 applied in vivo after tMCAO reduced infarct size, apoptotic markers, macrophage accumulation, and interleukin‐1β expression. Platelet depletion did not affect infarct size in mice with tMCAO ± ML354. Conclusions and Implications: Selective PAR4 inhibition during reperfusion improves infarct size and neurological function after experimental stroke by blunting neuronal excitability, apoptosis, and local inflammation. PAR4 antagonists may provide additional neuroprotective benefits in patients with acute stroke beyond their canonical antiplatelet action. [ABSTRACT FROM AUTHOR]

Background: Endovascular therapy (EVT) for distal medium vessel occlusions requires prioritizing effectiveness and safety. We developed a technique combining the deployment of only the distal basket segment of the EMBOTRAP III and an aspiration catheter (AC) for M2 occlusions, called the "ONE-SEG technique," and evaluated its clinical and technical impacts. Methods: This was a retrospective review of 30 consecutive patients with M2 segment middle cerebral artery occlusion treated using the ONE-SEG technique. This method involves deploying the EMBOTRAP III through a microcatheter in only one segment and guiding the AC to the M2 origin or distal M1. The rates of final-pass expanded thrombolysis in cerebral infarction (eTICI) scores of 2c/3 or 2b/2c/3, safety (symptomatic intracranial hemorrhage [sICH]), and clinical outcomes (modified Rankin Scale [mRS] score 0-2, 0-3 at 90 days, and mortality at 90 days) were evaluated. Results: Of the 30 cases, 36.7% were female, and the mean age was 75.6 ± 11.0 years. The ONE-SEG technique was used for 17 cases (56.7%, median NIHSS 10 [5-15.5]) with primary M2 occlusion and 13 cases (43.3%, median NIHSS 20 [14-22.5]) with secondary M2 occlusion after proximal thrombus removal. The successful final reperfusion rate (eTICI 2b/2c/3) was 90% overall (27/30 cases). One case (3.3%) developed sICH with secondary M2 occlusion. At 3 months, mRS scores 0-2 were seen in 64.7% of patients with primary M2 occlusion (11/17 cases) and in 23.1% (3/13 cases) with secondary M2 occlusion. Conclusion: EVT using the ONE-SEG technique appears to be safe and effective for M2 occlusion. [ABSTRACT FROM AUTHOR]

Moyamoya disease, characterized by basal cerebral artery obstruction, was studied for differential protein expression to elucidate its pathogenesis. Proteomic analysis of cerebrospinal fluid from 10 patients, categorized by postoperative angiography into good and poor prognosis groups, revealed 46 differentially expressed proteins. Notably, cadherin 18 (CDH18) was the most significantly upregulated in the good prognosis group. In addition, the expression of cadherin 18 (CDH18) and phenotypic transformation-related proteins were measured by qRT-PCR and western blot. The effects of CDH18 in vascular smooth muscle cells were detected by CCK-8, EdU, transwell and wound healing assays. The overexpression of CDH18 in vascular smooth muscle cells (VSMCs) was found to inhibit proliferation, migration, and phenotypic transformation. These findings suggest CDH18 as a potential therapeutic target in moyamoya disease. [ABSTRACT FROM AUTHOR]

Brain edema robustly increases mortality and hinders functional recovery after acute ischemic stroke. However, there are currently no effective therapies available for treating or preventing it. The unchecked opening of the transient receptor potential M4 (TRPM4) channel results in an excessive influx of Na+ and water, which contributes significantly to the formation of brain edema after ischemic stroke. 9‐phenanthrol (9‐Phe), a potent TRPM4 inhibitor, has limited clinical applicability due to its potential cytotoxicity and poor solubility. A brain‐targeting T7 (HAIYPRH)‐modified lipid nanoparticle (LNP) encapsulated 9‐Phe (9‐Phe@T7‐LNP) is designed and synthesized to improve the physicochemical properties and pharmacokinetic properties of 9‐Phe for treating brain edema in vivo. These results demonstrated that 9‐Phe@T7‐LNP can penetrate the intact blood‐brain barrier (BBB) in normal mice and target the brain parenchyma. Moreover, 9‐Phe@T7‐LNP effectively reduced infarct volume and brain edema, prevented neuronal loss and BBB disruption, improved survival, and facilitated neurological function recovery after transient middle cerebral artery occlusion in mice. Additionally, 9‐Phe@T7‐LNP scavenged oxygen‐free radicals and prevented neuronal apoptosis in cultured neurons subjected to oxygen and glucose deprivation/reperfusion. In summary, these findings showed that 9‐Phe@T7‐LNP holds strong potential as a promising targeted therapy for brain edema after stroke, providing superior pharmacological neuroprotection against brain edema. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a common cause of mortality and severe disability in human and currently lacks effective treatment. Neuronal activation and neuroinflammation are the major two causes of neuronal damage. However, little is known about the connection of these two phenomena. This study uses middle cerebral artery occlusion mouse model and chemogenetic techniques to study the underlying mechanisms of neuronal excitotoxicity and severe neuroinflammation after ischemic stroke. Chemogenetic inhibition of neuronal activity in ipsilesional M1 alleviates infarct area and neuroinflammation, and improves motor recovery in ischemia mice. This study identifies that ischemic challenge triggers neuron to produce unique small extracellular vesicles (EVs) to aberrantly activate adjacent neurons which enlarge the neuron damage range. Importantly, these EVs also drive microglia activation to exacerbate neuroinflammation. Mechanistically, EVs from ischemia-evoked neuronal activity induce neuronal apoptosis and innate immune responses by transferring higher miR-100-5p to adjacent neuron and microglia. MiR-100-5p can bind to and activate TLR7 through U18U19G20-motif, thereby activating NF-κB pathway. Furthermore, knock-down of miR-100-5p expression improves poststroke outcomes in mice. Taken together, this study suggests that the combination of inhibiting aberrant neuronal activity and the secretion of specific EVs-miRNAs may serve as novel methods for stroke treatment. [ABSTRACT FROM AUTHOR]

The Wound Healing Society guidelines for the treatment of arterial insufficiency ulcers were originally published in 2006, with the last update in 2014. These guidelines provided recommendations, along with their respective levels of evidence, on seven categories: diagnosis, surgery, infection control, wound bed preparation, dressings, adjuvant therapy and long‐term maintenance. Over the last 9 years, additional literature regarding these aspects of arterial ulcer management has been published. An advisory panel comprised of academicians, clinicians and researchers was chosen to update the 2014 guidelines. Members included vascular surgeons, internists, plastic surgeons, anaesthesiologists, emergency medicine physicians and dermatologists, all with expertise in wound healing. The goal of this article is to evaluate relevant new findings upon which an updated version of the guidelines will be based. [ABSTRACT FROM AUTHOR]

Acute mesenteric ischaemia (AMI) is a serious disease with mortality between 50 and 80 %. Oxidative stress plays a major role in the pathophysiology of AMI. AMI should be considered for any acute abdominal pain that requires analgesia with morphine and for which no other obvious aetiology is found. CT is the main diagnostic procedure to confirm the diagnosis of AMI. There is no specific diagnostic biomarker for AMI that can be used in routine practice. AMI is an urgent diagnostic and therapeutic situation. Treatment of AMI includes a protocol combining digestive rest, curative anticoagulant, antiplatelet, antibiotic therapy, arterial revascularisation to salvage viable bowel and resection of necrotic digestive segments. The strategy of revascularisation depends on the mechanism of arterial occlusion, the morphological appearance of the lesions and the indications for exploratory laparotomy. Endovascular and open surgical techniques can be combined and complemented. Open surgical revascularisation is indicated in case of failure or impossibility of endovascular revascularisation and in case of need for laparotomy. Early diagnosis and timely surgical intervention are the cornerstones of modern treatment to reduce the high mortality of AMI. The emergence of endovascular approaches and modern imaging techniques is developing and providing new treatment options. A multidisciplinary approach based on early diagnosis and treatment is necessary. [ABSTRACT FROM AUTHOR]

We have previously demonstrated a rapid secretion of matrix metalloproteinase‐2 (MMP‐2) in the ischemic brain. Since Scube2 can interact with Sonic hedgehog (Shh) to maintain blood–brain barrier (BBB) integrity via regulating the interaction between brain capillary endothelial cells (ECs) and perivascular astrocytes, and it is also a substrate of MMP‐2, we hypothesized that the secreted MMP‐2 could degrade Scube2 and contribute to ischemic BBB disruption. Using an in vitro ischemic model of 90‐min oxygen–glucose deprivation/3‐h reoxygenation (OGD/R) and an in vivo mouse stroke model of 90‐min middle cerebral artery occlusion (MCAO) with 3‐h reperfusion, we established an important role of MMP‐2‐mediated Scube2 degradation in early ischemic BBB disruption. Exposure of C8‐D1A cells and bEnd.3 cells to OGD/R increased MMP secretion in both cells, and C8‐D1A cells appeared to secrete more MMPs than bEnd.3 cells. Co‐IP and double‐immunostaining revealed that Scube2 co‐localized well with MMP‐2 in C8‐D1A cells and could be pulled down by MMP‐2 antibodies. In MCAO mice, Scube2 protein showed a drastic reduction in ischemic brain tissue, which was accompanied by suppressed expression of Shh and its downstream molecules. Of note, specific knockdown of astrocytic Scube2 with AAV‐shScube2 augmented MCAO‐induced Shh suppression and exacerbated BBB leakage and inflammatory reactions in the ischemic brain. Last, incubation of bEnd.3 cells with conditioned medium derived from OGD‐treated C8‐D1A cells led to a significant inhibition of the Shh pathway in bEnd.3 cells and degradation of VE‐cadherin and ZO‐1. Inhibition of MMP‐2 with SB‐3CT or over‐expression of Scube2 with plasmids in C8‐D1A cells alleviated the above effect of C8‐D1A cells‐derived conditioned medium. Taken together, our data indicate that ischemia‐induced secretion of MMP‐2 may contribute to early BBB disruption in ischemic stroke via interrupting the shared Scube2‐Shh pathway between brain capillary ECs and perivascular astrocytes. [ABSTRACT FROM AUTHOR]

Background: The neurovascular unit (NVU) and neurovascular trophic coupling (NVTC) play a key regulatory role in brain injury caused by ischemic stroke. Salvianolic acids (SAL) and Panax notoginseng saponins (PNS) are widely used in China to manage ischemic stroke. Neuroprotective effects of SAL and PNS, either taken alone or in combination, were examined in this research. Methods: Wistar rats were randomly divided into the following groups: Sham group (Sham), cerebral ischemia/reperfusion group (I/R), I/R with SAL group (SAL), I/R with PNS group (PNS), I/R with SAL combined with PNS (SAL + PNS), and I/R with edaravone group (EDA). Treatment was administered once daily for two days after modeling of middle cerebral artery occlusion/reperfusion (MCAO/R). Results: Compared with the I/R group, SAL, PNS, or SAL + PNS treatment reduced infarct size, improved neurological deficit score, reduced Evans blue extravasation, increased expression of CD31 and tight junction proteins (TJs), including zonula occludens‐1 (ZO‐1), zonula occludens‐2 (ZO‐2), and junctional adhesion molecule‐1 (JAM‐1). Furthermore, SAL, PNS, or SAL + PNS suppressed the activations of microglia and astrocyte and led to the amelioration of neuron and pericyte injury. Treatment also inhibited NVU dissociation of GFAP/PDGFRβ and Collagen IV/GFAP while upregulated the expression level of BDNF/TrkB and BDNF/NeuN. Conclusions: SAL and PNS have significantly remedied structural and functional disorders of NVU and NVTC in I/R injury. These effects were more pronounced when SAL and PNS were combined than when used separately. [ABSTRACT FROM AUTHOR]

Rapid identification of the type and origin of a stroke is crucial for prompt and appropriate treatment, which can significantly influences patient outcomes. We report a multidisciplinary management case involving a 76-year-old man who presented with left-sided weakness and mild dysarthria. Imaging revealed a completely occluded right internal carotid artery. Despite multiple endovascular recanalization attempts, adequate flow could not be achieved, leading to the decision to perform an open thrombo-endarterectomy. The patient underwent carotid endarterectomy with microsurgical techniques under general anesthesia. The atheroma plaque and central thrombus were removed, which reestablished flow. Continuous intraoperative neuromonitoring was utilized to ensure patient safety. The patient woke up without new deficits and was discharged for rehabilitation. Follow-up imaging confirmed arterial patency, and the patient eventually made an excellent recovery, including being independent over one and a half years. Emergent recanalization with carotid endarterectomy following a failed endovascular recanalization is both safe and feasible, emphasizing the need for collaboration between different treatment providers to ensure optimal patient outcomes. Our report highlights the importance of a multidisciplinary approach and the advantages of a hybrid operating room in the treatment of acute complete carotid artery occlusion. [ABSTRACT FROM AUTHOR]