Ischemic Events Research Articles

Vascular Abnormalities and Neurofibromatosis Type 1: A Paediatric Case Series.

Neurofibromatosis type 1 (NF1) is a multisystemic neurocutaneous disease caused by a heterozygous mutation of the NF1 gene that encodes neurofibromin. Complications include vascular and neurologic abnormalities such as moyamoya syndrome, a cerebrovascular disorder with progressive occlusion of the large intracranial arteries, leading to ischemic events and the formation of abnormal vascular networks. Stenosis of the renal artery is another frequent complication of neurofibromatosis type 1, and it represents the most common cause of secondary hypertension in these patients. The purpose of the article is to describe the clinical manifestations of neurofibromatosis type 1 vasculopathy in 4 patients presenting with a wide range of neurologic and reno-vascular manifestations, as well as to examine current diagnostic management and follow-up, current therapeutic options, and to discuss further perspectives in terms of screening, diagnosis, and treatment.

Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury

Blood transfusions are commonly administered to patients with acute brain injury. The optimal hemoglobin transfusion threshold is uncertain in this patient population. To assess the impact on neurological outcome of 2 different hemoglobin thresholds to guide red blood cell transfusions in patients with acute brain injury. Multicenter, phase 3, parallel-group, investigator-initiated, pragmatic, open-label randomized clinical trial conducted in 72 intensive care units across 22 countries. Eligible patients had traumatic brain injury, aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage; hemoglobin values below 9 g/dL within the first 10 days after injury; and an expected intensive care unit stay of at least 72 hours. Enrollment occurred between September 1, 2017, and December 31, 2022. The last day of follow-up was June 30, 2023. Eight hundred fifty patients were randomly assigned to undergo a liberal (transfusion triggered by hemoglobin <9 g/dL; n = 408) or a restrictive (transfusion triggered by hemoglobin <7 g/dL; n = 442) transfusion strategy over a 28-day period. The primary outcome was occurrence of an unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score between 1 and 5, at 180 days following randomization. There were 14 prespecified serious adverse events, including occurrence of cerebral ischemia after randomization. Among 820 patients who completed the trial (mean age, 51 years; 376 [45.9%] women), 806 had available data on the primary outcome, 393 in the liberal strategy group and 413 in the restrictive strategy group. The liberal strategy group received a median of 2 (IQR, 1-3) units of blood, and the restrictive strategy group received a median of 0 (IQR, 0-1) units of blood, with an absolute mean difference of 1.0 unit (95% CI, 0.87-1.12 units). At 180 days after randomization, 246 patients (62.6%) in the liberal strategy group had an unfavorable neurological outcome compared with 300 patients (72.6%) in the restrictive strategy group (absolute difference, -10.0% [95% CI, -16.5% to -3.6%]; adjusted relative risk, 0.86 [95% CI, 0.79-0.94]; P = .002). The effect of the transfusion thresholds on neurological outcome at 180 days was consistent across prespecified subgroups. In the liberal strategy group, 35 (8.8%) of 397 patients had at least 1 cerebral ischemic event compared with 57 (13.5%) of 423 in the restrictive strategy group (relative risk, 0.65 [95% CI, 0.44-0.97]). Patients with acute brain injury and anemia randomized to a liberal transfusion strategy were less likely to have an unfavorable neurological outcome than those randomized to a restrictive strategy. ClinicalTrials.gov Identifier: NCT02968654.

Lower-Ischemic-Risk Profile of Coated Flow Redirection Endoluminal Device X Compared With Uncoated Flow Redirection Endoluminal Device Flow Diverter in the Treatment of Unruptured Intracranial Aneurysms.

Flow Redirection Endoluminal Device (FRED) X is a new generation flow diverter with an antithrombotic surface coating. This study compares the procedural safety and short-term efficacy of FRED X with its uncoated predecessor, the FRED. Patients treated with FRED and FRED X devices for unruptured aneurysms between 2013 and 2023 at 3 neurovascular centers were retrospectively reviewed. The procedural ischemic event rate was the safety end point, and the complete aneurysm occlusion rate at 1 year was the efficacy end point. Multivariable regression adjustment and 1:1 propensity score matching were performed to control for potential confounding. The FRED X group (137 patients) had a higher prevalence of recurrent and bifurcation aneurysms and fewer aneurysms with branch involvement than the FRED X group (156 patients). The ischemic event rate was lower in FRED X (1/156 [0.6%]) than in FRED (7/137 [5.1%]), which was significant after multivariable adjustment (odds ratio: 8.8, 95% CI: 1.1-72.7, P = .04), and tended to be significant in the propensity score analysis (P = .07). Morbidity was comparable between FRED (2.2%) and FRED X (0%, P = .10). The complete occlusion rates of FRED vs FRED X were 73/117 (62.4%) vs 39/54 (72.2%) aneurysms at 6 months (P = .21) and 52/74 (70.3%) vs 27/37 (73.0%) at 12 months (P = .77). Hemorrhagic complications, in-stent stenosis, and clinical events during follow-up and retreatments were not significantly different between groups. This study indicates an improved ischemic risk profile of FRED X while maintaining a favorable efficacy profile, warranting further study and translation into clinical use.

Cerebrovascular implications of takayasu arteritis: a review.

Takayasu arteritis (TA) is a rare, chronic, inflammatory large-vessel vasculitis that affects the aorta and its main branches, including the cerebrovascular system. This review analyzes current knowledge and patient outcomes concerning the cerebrovascular implications of TA. A literature search, with publications from 1994 to 2024, identified pertinent studies through PubMed. An illustrative case report details a 19-year-old female with Type 1 TA, illustrating the complex decision required in the absence of surgical or endovascular options. Our results offer a demographic analysis of 1,698 TA patients, highlighting a female predominance of 89.99% and a mean symptom onset at 33 years. The clinical spectrum of cerebrovascular involvement presented varied symptoms, most notably dizziness, with significant incidences of ischemic events and bilateral stenosis primarily affecting the carotid and subclavian arteries. The most common type of TA was Type V, affecting 40% of patients studied. Endovascular treatment had a 95% initial success rate, with a 67% restenosis rate. Surgical treatment was successful in 84% of cases, but 21% had notable post-operative complications. Similar to the endovascular population, those treated with stand-alone conservative therapy saw a 93% initial remission rate with 52% having relapsed. Assessing the disease activity of TA is crucial when planning vascular intervention due to its significant impact on treatment outcomes. Despite its greater initial invasiveness, surgical interventions showed lower restenosis rates compared to either endovascular interventions or standalone conservative management. We emphasize advancements in TA management and the pressing need for continued research into diagnostic and treatment protocols for improved patient outcomes.

Cost analysis of CYP2C19 genetic testing in percutaneous coronary intervention patients.

CYP2C19 loss of function (LOF) carriers undergoing percutaneous coronary intervention (PCI) have an increased risk of ischemic events when treated with clopidogrel. PCI patients in TAILOR-PCI were randomized to clopidogrel or genotype-guided (GG) therapy in which LOF carriers received ticagrelor and non-carriers clopidogrel. Direct medical costs associated with a GG approach have not been described before. TAILOR-PCI participants for whom direct medical costswere available for the duration from the date of PCI to one-year post PCI were included. Primary cost estimates were obtained from the Mayo Clinic Cost Data Warehouse. There were no differences in direct medical costs between the GG and clopidogrel groups (mean $20,682 versus $19,747, p = 0.11) however total costs were greater in the GG group (mean $21,245 versus $19,891, p = 0.02) which was primarily driven by ticagrelor costs. In conclusion the increased expense of a GG strategy post PCI as compared to clopidogrel for allis primarily driven by the cost of ticagrelor.

Duration of Benefit and Risk of Dual Antiplatelet Therapy up to 72 Hours After Mild Ischemic Stroke and Transient Ischemic Attack.

Clopidogrel-aspirin initiated within 72 hours of symptom onset is effective in patients with mild ischemic stroke or transient ischemic attack (TIA) in the Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial. Uncertainties remain about the duration of the treatment effect. This study aimed to assess duration of benefit and risk of clopidogrel-aspirin in these patients. The INSPIRES trial was a 2*2 factorial placebo-controlled randomized trial conducted in 222 hospitals in China. The 2 treatments did not interact and were evaluated separately. In this study, we performed secondary analyses based on antiplatelet treatment. All patients with mild stroke or TIA of presumed atherosclerotic cause within 72 hours of symptom onset enrolled in the trial were included. Patients were randomly assigned to receive clopidogrel-aspirin on days 1-21 followed by clopidogrel on days 22-90 or aspirin alone for 90 days. The primary efficacy outcome was major ischemic event which included the composite of ischemic stroke and nonhemorrhagic death. The primary safety outcome was moderate-to-severe bleeding. We estimated the risk difference between the 2 treatments for each stratified week. All 6,100 patients in the trial were included (3,050 in each group). The mean age was 65 years, and 3,915 patients (64.2%) were men. Compared with aspirin alone, the reduction of major ischemic events by clopidogrel-aspirin mainly occurred in the first week (absolute risk reduction [ARR] 1.42%, 95% CI 0.53%-2.32%) and remained in the second week (ARR 0.49%, 95% CI 0.09%-0.90%) and the third week (ARR 0.29%, 95% CI -0.05% to 0.62%). Numerical higher risk of moderate-to-severe bleedings in the clopidogrel-aspirin group was observed in the first 3 weeks (absolute risk increase 0.05% [95% CI -0.10% to 0.20%], 0.10% [95% CI -0.09% to 0.29%], and 0.18% [95% CI -0.03% to 0.40%] in the first, second, and third weeks, respectively). Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low, but ongoing hemorrhagic risk. ClinicalTrials.gov Identifier: NCT03635749. This study provides Class II evidence that among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low but ongoing hemorrhagic risk.

8291 Graves’ Disease and Moyamoya Syndrome: A Complex Case of Thyroid Dysfunction and Neurovascular Abnormalities

Abstract Disclosure: A. Jamil: None. Q.V. Luong: None. A. Llorens Bonilla: None. A. Siddiqui: None. Background: Moyamoya disease is a cerebrovascular disease characterized by progressive stenosis and occlusion of cerebral arteries, particularly the internal carotid arteries, proximal anterior and middle cerebral arteries associated with a net-like collateral vessel formation. Moyamoya disease in association with certain systemic conditions (e.g. Graves’ disease, sickle cell anemia, neurofibromatosis type 1, and Down Syndrome) has been referred to as moyamoya syndrome. Graves’ disease is an autoimmune disease in which the development of thyroid-stimulating hormone (TSH) receptor autoantibodies leads to overproduction of thyroid hormones. Although the pathophysiology is unclear, Graves’ disease can adversely impact the clinical course of moyamoya syndrome.Clinical Case: A 26-year-old woman diagnosed with Graves’ disease at the age of 20 years who was in remission presented to the ED with right upper extremity weakness and headache. A stroke work-up was performed, and an initial CT head without contrast showed an acute infarct in the left temporal area. Extensive workup for hypercoagulability and cardiac causes were negative. MRI brain showed multiple infarcts of the left cerebral hemisphere with ivy sign, which are prominent linear or punctate high intensity areas in the subarachnoid space reflecting the development of collaterals that occurs in moyamoya disease. TSH at the time was noted to be &amp;lt;0.01 uIU/mL (range: 0.30-4.20 uIU/mL), indicating a thyrotoxic state. She was discharged on methimazole and antiplatelet therapies. However, the patient continued to have hypertension and headaches which did not resolve with the return to euthyroidism. At age 29, she again developed acute right upper and lower extremity weakness, and consequently presented to the ED. Imaging studies showed multiple punctate infarcts in her bilateral frontal lobes and bilateral ICA stenosis consistent with moyamoya disease. However, her biochemical studies showed euthyroidism. Ultimately, she underwent right frontotemporal craniotomy and direct parietal superficial temporal artery to middle cerebral artery bypass by neurosurgery to decrease her future stroke risk for her moyamoya syndrome, and her Graves’ disease remains in remission.Conclusions: The coexistence of Graves’ disease in moyamoya syndrome may suggest a pathophysiologic connection. It has been suggested that hemodynamic changes in cerebrovascular flow due to thyrotoxicosis might contribute to ischemic neurologic deficits. Surgical intervention for revascularization procedures should be attempted after optimal control of thyrotoxicosis, as this may help to prevent further ischemic events in the future and improve patient outcomes. Presentation: 6/1/2024

8281 Continuous Low-Dose Etomidate Infusion For The Management Of Severe Hypercortisolism In Metastatic Adrenocortical Carcinoma

Abstract Disclosure: A. Jamil: None. N. Mohammad: None. S. Narayana: None. Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy of the adrenal glands with a poor prognosis that often presents with excess hormone secretion. Approximately, 45% of cases present with hypercortisolism.1 A key component of management is achieving control of hypercortisolism. Though there are multiple enteral therapies that can inhibit cortisol production, few treatment options are available for use in critically ill patients who are not surgical candidates and cannot take oral medications. Though primarily known as a short-acting intravenous anesthetic agent used for sedation, etomidate also inhibits 11-β-hydroxylase, a key enzyme involved in corticosteroid biosynthesis.2 Clinical Case: A 28-year-old woman with metastatic adrenocortical carcinoma with associated hypercortisolism was initially admitted for anemia and thrombocytopenia, with an initial cortisol on admission of 29.3 μg/dl (normal range: 2.3-19.4 ug/dl). Due to her large tumor burden with metastasis to the liver and invasion into the inferior vena cava, she was deemed a poor surgical candidate with a poor overall prognosis. Her hospital course was complicated by acute hypoxemic respiratory failure requiring intubation, and thus her enteral steroidogenesis inhibitors (mitotane, ketoconazole, and metyrapone) were discontinued as none were administrable via nasogastric tube. Consequently, her hypercortisolism worsened rapidly with a cortisol level of 351.3 μg/dl , prompting initiation of continuous low-dose etomidate infusion, which resulted in significant improvements in her cortisol levels. After eight days of etomidate treatment, her cortisol levels reached a goal value of 25.0 μg/dl. However, she then suffered an ischemic cerebrovascular event and multiorgan failure, and was subsequently transitioned to hospice care. Conclusion: Low-dose etomidate infusion is an effective therapeutic agent for hypercortisolism in patients with ACC that are unable to take oral medications.

Long-term clinical outcomes of drug-coated balloon angioplasty for de novo coronary lesions in patients with diabetes mellitus.

We investigated whether drug-coated balloon (DCB) treatment is effective for all de novo cases of coronary artery disease (CAD) in patients with diabetes mellitus. Furthermore, we also investigated the relationship between the degree of diabetes mellitus and clinical outcomes after DCB treatment. In this study, we included 516 consecutive patients with de novo CAD who were treated with DCB. The patients were divided into the diabetic and non-diabetic groups. Patients with diabetes mellitus were further classified into non-insulin-treated diabetes mellitus (NITDM) and insulin-treated diabetes mellitus (ITDM). The primary endpoints were major adverse cardiovascular ischemic events (MACE) and clinically driven target lesion revascularization (CD-TLR). Within a mean clinical follow-up period of 2.5years, the incidence of MACE among patients with diabetes mellitus (22.1%) was almost twice that of non-diabetic patients (11.9%) with a relative risk of 1.86 (95% CI 1.24-2.79, p = 0.002). The 3-year CD-TLR occurred in 28 patients with diabetes mellitus (10.6%) and 13 non-diabetic patients (5.1%, p = 0.02). ITDM patients had a significantly higher rate of MACE compared with non-diabetic patients with a relative risk of 2.86 (95% CI 1.76-4.63, p = 0.0002). ITDM remained an independent predictor of 3-year MACE with an odd ratio of 1.96 (95% CI 1.00-3.83, p = 0.05). In patients undergoing DCB, the presence of DM was associated with a higher risk of MACE and CD-TLR. Particularly in DCB, treatment was still inadequately effective for ITDM patients.

Paraoxonase-1 as a Cardiovascular Biomarker in Caribbean Hispanic Patients Treated with Clopidogrel: Abundance and Functionality.

Clopidogrel, a prescription drug to reduce ischemic events in cardiovascular patients, has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders and disease severity in this population. Thirty-six patients on clopidogrel (cases divided into poor and normal responders) were enrolled, along with 11 cardiovascular patients with no clopidogrel indications (positive control) and 13 healthy volunteers (negative control). Residual on-treatment platelet reactivity unit (PRU), PON1 abundance by Western blotting, and PON1 activity by enzymatic assays were measured. PON1 genotyping and computational haplotype phasing were performed on 512 DNA specimens for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups (p > 0.05). However, a significantly lower enzymatic activity was found in poor responders (10.57 ± 6.79 µU/mL) when compared to controls (22.66 ± 8.30 µU/mL and 22.21 ± 9.66 µU/mL; p = 0.004). PON1 activity among carriers of the most prevalent PON1 haplotype (AA|AA) was significantly lower than in wild types (7.90 µU/mL vs. 22.03 µU/mL; p = 0.005). Our findings suggested that PON1 is a potential biomarker of cardiovascular disease severity in Caribbean Hispanics.

Successful Percutaneous Rescue Treatment of Acute Carotid Stent Thrombosis Utilizing a Modified Embolic Protection Device.

Acute Carotid Stent Thrombosis (ACST) is a rare complication of Carotid Artery Stenting (CAS) with a potentially fatal outcome. We report a case of ACST occurring five minutes after the end of a successful CAS procedure that was promptly treated by carotid stent-in-stent implantation using a new percutaneous strategy based on the creation of a modified embolic protection device. Following the procedure, we did not observe brain lesions suggestive of acute cerebral ischemic events at the CT scan performed at 48 hours, as well as no neurological deficits in the following days.

Physiological provocation compared to acetazolamide in the assessment of cerebral hemodynamics: a case report

BackgroundSevere large vessel disease may lead to cerebral hemodynamic failure that critically impairs cerebral blood flow (CBF) regulation elevating the risk of ischemic events. Assessment of the condition is often based on changes in CBF during vasodilatation; however, pharmacologically induced vasodilation does not reflect the physiological condition during an ischemic event caused by hemodynamic failure. We compared a [15O]H2O PET brain scan during vasodilation to a [99mTc]HMPAO SPECT brain scan during an ongoing transient ischemic attack (TIA).Case presentationA single patient presenting with limb-shaking TIA underwent CT, Digital Subtraction Angiography, and two different modalities of cerebral perfusion scans: [15O]H2O PET and [99mTc]HMPAO SPECT. Acetazolamide was used in the PET scan to induce vasodilatation, and during the SPECT scan physiological stress, standing up rapidly, was used to induce limb-shaking TIA. CT-angiography and Digital Subtraction Angiography revealed an occlusion in the distal part of the right A2 segment of the anterior cerebral artery, with a corresponding infarction in the watershed area. Collaterals supplied the main vascular territory of the anterior cerebral artery. During rest, neither perfusion modalities demonstrated reduced perfusion outside of the ischemic core. However, we found a pronounced difference between the PET utilizing acetazolamide and the SPECT during the TIA. The PET scan demonstrated relative hypoperfusion in vascular territory supplied by collaterals, while the area around the ischemic core was not affected. Contrary, the SPECT had only minor relative hypoperfusion in the collateral-supplied area, whereas the watershed area proximal to the infarct core had pronounced relative hypoperfusion.ConclusionsThe observed discrepancy in compromised areas during physiological provocation compared to pharmacological induced vasodilation questions the use of an unphysiological stressor for assessment of cerebrovascular hemodynamics. A physiological provocation test may achieve more clinically relevant evaluation.

Association Between Moyamoya Revascularization Surgery and Neurologic Events During Pregnancy: Systematic Review.

The management of moyamoya disease during pregnancy and recommendations for the mode of delivery remain controversial. We investigated factors associated with neurologic events during pregnancy in women with moyamoya disease and its association with prepregnancy surgical revascularization. We performed a literature search from January 1, 1970, through September 30, 2021, using Embase, Web of Science, Medline, and Cochrane to identify cases of moyamoya disease with pregnancy. Primary outcome was neurologic events during pregnancy and were subcategorized into antepartum, intrapartum (within 24 hours of delivery), and postpartum events. Univariate and multivariate regression analyses using pooled results were performed to assess risk factors associated with neurologic events. Fifty-two relevant studies with 182 individuals diagnosed with moyamoya before pregnancy, and 229 pregnancies were included in the study. 59% underwent surgical revascularization before pregnancy. Of the 229 pregnancies, 22 (9.6%) patients had ischemic events and 3 (1.3%) had hemorrhagic events. In addition, there were 7 (3%) seizures and 4 (1.7%) other neurologic events not associated with ischemia or hemorrhage. There were fewer neurologic events during pregnancy in patients treated with surgery than those without surgery (11% surgical vs 24% medical, P = .009). Multivariable regression analysis demonstrated prior surgical revascularization as the only factor associated with lower number of neurologic events during pregnancy (odds ratio 0.42 [95% CI 0.19-0.96]). Mode of delivery (vaginal vs cesarean section) was not associated with a difference in overall intrapartum and postpartum neurologic events. We found that prior revascularization surgery was the only factor associated with fewer neurologic events during pregnancy in women with moyamoya disease. Mode of delivery was not associated with increased neurologic events during or after delivery.

Direct Oral Anticoagulants for RheumaticHeart Disease-Associated Atrial Fibrillation Post-Bioprosthetic Mitral Valve Replacement.

The efficacy of direct oral anticoagulants (DOACs) in preventing ischemic and thromboembolic events may be suboptimal in atrial fibrillation (AF) patients with rheumatic mitral stenosis. However, their safety and effectiveness after mitral valve replacement (MVR) using bioprosthetic valves is unclear. This study sought to evaluate the safety and effectiveness of DOACs vs warfarin among patients with rheumatic heart disease (RHD)-associated AF after bioprosthetic MVR. We performed an observational analysis identifying patients with RHD and AF who underwent bioprosthetic MVR. Primary effectiveness and safety outcomes were ischemic events and major bleeding, respectively. Secondary outcomes included all-cause mortality, cardiac thrombosis, myocardial infarction, and all-cause hospitalization. Propensity score matching was performed to account for the differences in baseline characteristics and comorbidities. A total of 3,950 patients were identified; 76% were on warfarin and 24% on DOAC post-MVR. The DOAC group had a higher burden of baseline comorbidities and prior cardiovascular procedures compared with the warfarin group. The propensity score matching balanced baseline characteristics in 1,832 patients (916 in each group), with a mean age of 69 years. At the 5-year follow-up, DOACs were associated with a lower incidence of major bleeding compared with warfarin (HR: 0.76; 95%CI: 0.62-0.94), with no significant difference in ischemic events, mortality, cardiac thrombosis, myocardial infarction, or hospitalization. Among patients with RHD-associated AF patients post-bioprosthetic MVR, DOACs are associated with lower major bleeding and comparable effectiveness, indicating a potential alternative to warfarin. Further randomized controlled trials are warranted to validate these findings in this population.

Neuroprotective Role of AQP4 Knockdown in Astrocytes After Oxygen-Glucose Deprivation.

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. 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. 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. 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.

Long-Term Clinical Outcomes After Cerebral Revascularization in Moyamoya Disease With Extracranial Internal Carotid Artery Occlusion

ObjectiveThe aim of this study is to evaluate the efficacy of cerebral revascularization for Moyamoya disease (MMD) with extra-cranial internal carotid artery occlusion (ICAO). MethodsThis study retrospectively analyzed 37 patients diagnosed with MMD with extra-cranial ICAO who underwent cerebral revascularization surgery. We conducted propensity score matching for MMD patients without extra-cranial ICAO from database of 932 MMD patients. Outcome data, recurrent strokes and modified Rankin Scale (mRS) were collected during follow-up. ResultsA total of 37 MMD patients with extra-cranial ICAO were included in the study. The average follow-up time of MMD patients with extra-cranial ICAO included in the study was 74 months. During the follow-up period, there were 15 hemispheres recurred stroke events. All hemispheres underwent surgery, and the follow-up mRS score was significantly reduced (P <0.001). Kaplan-Meier analysis showed no significant statistical difference in stroke events between the indirect bypass (IB), direct bypass (DB), and combined bypass (CB) groups (P = 0.131). After propensity matching, 48 hemispheres of MMD patients without extra-cranial ICAO were identified from a review of 932 MMD patients. There was no significant statistical difference in stroke events between the MMD patients with extra-cranial ICAO group and the MMD group (P = 0.271). ConclusionsCerebral revascularization can prevent recurrent ischemic and hemorrhagic stroke events for MMD patients with extra-cranial ICAO. There was no difference on long-term clinical outcomes after CB, DB, and IB surgery. The cerebral revascularization has similar effect on the MMD patients with extra-cranial ICAO and MMD patients without.

Meta-Analysis Comparing Oral Anticoagulant Monotherapy Versus Dual Antithrombotic Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease.

Oral anticoagulants (OACs) are routinely used for the management of atrial fibrillation (AF) while antiplatelet agents are used in coronary artery disease (CAD). However, data regarding the comparative clinical outcomes of OAC monotherapy versus dual antithrombotic therapy (anticoagulant plus antiplatelet agent) in patients with AF and stable CAD are limited. A comprehensive search of major databases including PubMed/MEDLINE, Cochrane Library, and Embase was performed from inception to September 1, 2024 to identify randomized control trials (RCTs) that compared OAC monotherapy with dual antithrombotic therapy in patients with AF and stable CAD. The risk ratios (RRs) were estimated with corresponding 95% confidence intervals (CIs) for all outcomes. A total of three RCTs reported data for 3945 patients with AF and stable CAD. The mean age of patients was 73.8 (±11.85) years and the mean follow-up was 22 months. OAC monotherapy was associated with a significantly reduced relative risk of major bleeding (RR: 0.55, 95% CI: 0.32-0.95) compared to dual therapy. The risk of all-cause death (RR: 0.85, 95% CI: 0.49-1.48), cardiovascular death (RR: 0.84, 95% CI: 0.50-1.41), any stroke event (RR: 0.74, 95% CI: 0.46-1.18), and myocardial infarction (RR: 1.57, 95% CI: 0.79-3.12) remained comparable across the two groups. OAC monotherapy led to a significant relative risk reduction for major bleeding with similar rates of ischemic events and mortality compared to dual antithrombotic therapy in patients with AF and stable CAD.

Transcarotid arterial revascularization for symptomatic carotid web

ObjectivesSymptomatic carotid web is an increasingly recognized cause of acute ischemic stroke with a high risk of recurrent ischemic events despite aggressive medical interventions. Surgical interventions including transfemoral carotid artery stenting (TFCAS) and carotid endarterectomy have been described to reduce this risk, but transcarotid arterial revascularization (TCAR) has not been evaluated for this purpose. Materials and MethodsPatients with cerebral ischemia from carotid web underwent TCAR with flow reversal. Patients were monitored for periprocedural complications and assessed at follow-up for clinical evidence of recurrent ischemia. ResultsSix cases over the course of 21 months were identified, 2 males and 4 females with a median age of 59.5 (interquartile range of 39). All underwent technically successful TCAR without periprocedural complications no post-procedural cerebral ischemia over a median follow-up time of 21 months. ConclusionsIn this small series of patients, TCAR provided a safe and effective treatment of carotid webs that had previously caused cerebral ischemia.

The association between triglyceride-glucose atherogenic predictor index and central retinal artery occlusion

Purpose: Central retinal artery occlusion (CRAO) is an acute ischemic event causing severe visual loss and is a precursor to further cerebrovascular and cardiovascular events. The triglyceride-glucose index (TyG) indicates insulin resistance in healthy individuals. Numerous research links the TyG index to metabolic syndrome, hypertension, and new-onset diabetes. Recent research also suggests its role as a sign of atherosclerosis in cardiovascular diseases, with potential clinical significance in assessing vascular damage. In this study, the relationship between CRAO and TyG index was evaluated. Materials and Methods: This case-control study involved 116 adults (50 CRAO patients and 66 control subjects without chronic eye diseases) at our hospital from January 2018 to March 2023. The TyG index was formulated as ln[fasting TG (mg/dL) × fasting plasma glucose (mg/dL)/2]. Results: The CRAO group had a mean age of 65.0±14.7 years, with 27 (55.1 % 54) females. The control group had a mean age of 61.2±12.1 years, with 32 (48.5) females. The mean TyG index was 9.05±0.7 in the CRAO group and 8.7±0.7 in controls, a statistically significant difference. Univariate regression analysis showed an association between the TyG index and CRAO (OR=2.04; CI: 1.11-3.73). This association remained significant in multivariate logistic regression analysis (OR=1.88; CI: 1.01-3.50). Conclusion: This study found a significantly higher mean TyG index, an atherogenic indicator, in CRAO patients compared to controls.

Body temperature, systemic inflammation and risk of adverse events in patients with acute coronary syndromes.

Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low-cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS. From 2012 until 2017, a total of 1044 ACS patients, 517 with STEMI and 527 with NSTE-ACS, were prospectively recruited at the University Hospital Zurich. BT was measured by digital tympanic thermometer along with high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin-T (hs-cTnT) levels prior to coronary angiography. Patients were stratified according to initial BT and uni- and multivariable regression models were fit to assess associations of BT with future MACE risk. Among patients with STEMI, BT was not predictive of 1-year MACE, but a U-shaped relationship between BT and MACE risk was noted in those with NSTE-ACS (p = .029), translating into a 2.4-fold (HR, 2.44, 95% CI, 1.16-5.16) increased 1-year MACE risk in those with BT >36.8°C (reference: 36.6-36.8°C). Results remained robust in multivariable-adjusted analyses accounting for sex, age, diabetes, renal function and hs-cTnT. However, when introducing hs-CRP, the BT-MACE association did not prevail. In prospectively recruited patients with ACS, initial BT shows a U-shaped relationship with 1-year MACE risk among those with NSTE-ACS, but not in those with STEMI. BT is a broadly available low-cost marker to identify ACS patients with high inflammatory burden, at high risk for recurrent ischaemic events, and thus potentially suitable for an anti-inflammatory intervention. ClinicalTrials.gov Identifier: NCT01000701.