Ischemic Cerebrovascular Disease Research Articles

Imaging and blood flow characteristics of cerebrovascular fenestration malformation and its relationship with the occurrence of ischemic cerebrovascular disease.

To explore the imaging and transcranial Doppler cerebral blood flow characteristics of cerebrovascular fenestration malformation and its relationship with the occurrence of ischemic cerebrovascular disease. A retrospective analysis was conducted on the imaging data of 194 patients with cerebrovascular fenestration malformation who visited the Heyuan People's Hospital from July 2021 to July 2023. The location and morphology of the fenestration malformation blood vessels as well as the presence of other cerebrovascular diseases were analyzed. Transcranial Doppler cerebral blood flow detection data of patients with cerebral infarction and those with basilar artery fenestration malformation were also analyzed. A total of 194 patients with cerebral vascular fenestration malformation were found. Among the artery fenestration malformation, basilar artery fenestration was the most common, accounting for 46.08% (94/194). 61 patients (31.44%) had other vascular malformations, 97 patients (50%) had cerebral infarction, of which 30 were cerebral infarction in the fenestrated artery supply area. 28 patients with cerebral infarction in the fenestrated artery supply area received standardized antiplatelet, lipid-lowering and plaque-stabilizing medication treatment. During the follow-up period, these patients did not experience any symptoms of cerebral infarction or transient ischemic attack again. There were no differences in peak systolic flow velocity and end diastolic flow velocity, pulsatility index and resistance index between the ischemic stroke group and the no ischemic stroke group in patients with basal artery fenestration malformation (P > 0.05). Cerebrovascular fenestration malformation is most common in the basilar artery. Cerebrovascular fenestration malformation may also be associated with other cerebrovascular malformations. Standardized antiplatelet and statin lipid-lowering and plaque-stabilizing drugs are suitable for patients with cerebral infarction complicated with fenestration malformation. The relationship between cerebral blood flow changes in basilar artery fenestration malformation and the occurrence of ischemic stroke may not be significant.

The Epidemiological Burden of Neurovascular Pathology in Nigeria: A Systematic Review and Pooled Patient-Level Analysis

Vascular neurosurgery has developed significantly in Nigeria, but its burden and challenges remain unclear. This study systematically reviewed vascular neurosurgical literature from Nigeria. Four research databases and gray literature sources were searched from 1962-2021. ROBINS-I tool was used to assess risk of bias. Descriptive, narrative, and statistical analyses were conducted on all variables. Where appropriate, paired t-tests and Chi-squared independence tests were used (α= 0.05). 56 articles were included and 3203 patients pooled for analysis. Risk of bias was moderate-high. Most articles were published over the last 20 years with retrospective cohort studies and case reports being the most common study designs. The cohort had a relatively even gender split and an average age of 49 years (±22). Cerebrovascular accidents accounted for over 85% of diagnoses, with most etiologies being traumatic. Headache and motor deficit were the most prevalent clinical features. X-ray and carotid angiography were the most commonly reported imaging modalities, closely followed by computed tomography (CT) and CT angiography. The top two radiological diagnoses were ischemic cerebrovascular disease and intracerebral hematoma. Aneurysmal clipping and hematoma evacuation were the most commonly reported treatment modalities. Outcome at last follow-up was favorable in 48%. The mortality rate was 6%. Post-treatment complications included chest infection and rebleeding. This study illustrates the epidemiological burden of neurovascular pathology (based on the available data in published literature) in Nigeria, and raises awareness amongst service providers and researchers of the attendant challenges and epochal trends seen within vascular neurosurgery in Nigeria.

Cuproptosis and copper deficiency in ischemic vascular injury and repair.

Ischemic vascular diseases are on the rise globally, including ischemic heart diseases, ischemic cerebrovascular diseases, and ischemic peripheral arterial diseases, posing a significant threat to life. Copper is an essential element in various biological processes, copper deficiency can reduce blood vessel elasticity and increase platelet aggregation, thereby increasing the risk of ischemic vascular disease; however, excess copper ions can lead to cytotoxicity, trigger cell death, and ultimately result in vascular injury through several signaling pathways. Herein, we review the role of cuproptosis and copper deficiency implicated in ischemic injury and repair including myocardial, cerebral, and limb ischemia. We conclude with a perspective on the therapeutic opportunities and future challenges of copper biology in understanding the pathogenesis of ischemic vascular disease states.

Grouped mixtures of air pollutants and seasonal temperature anomalies and cardiovascular hospitalizations among U.S. Residents

BackgroundAir pollution is a recognized risk factor for cardiovascular disease (CVD). Temperature is also linked to CVD, with a primary focus on acute effects. Despite the close relationship between air pollution and temperature, their health effects are often examined separately, potentially overlooking their synergistic effects. Moreover, fewer studies have performed mixture analysis for multiple co-exposures, essential for adjusting confounding effects among them and assessing both cumulative and individual effects. MethodsWe obtained hospitalization records for residents of 14 U.S. states, spanning 2000–2016, from the Health Cost and Utilization Project State Inpatient Databases. We used a grouped weighted quantile sum regression, a novel approach for mixture analysis, to simultaneously evaluate cumulative and individual associations of annual exposures to four grouped mixtures: air pollutants (elemental carbon, ammonium, nitrate, organic carbon, sulfate, nitrogen dioxide, ozone), differences between summer and winter temperature means and their long-term averages during the entire study period (i.e., summer and winter temperature mean anomalies), differences between summer and winter temperature standard deviations (SD) and their long-term averages during the entire study period (i.e., summer and winter temperature SD anomalies), and interaction terms between air pollutants and summer and winter temperature mean anomalies. The outcomes are hospitalization rates for four prevalent CVD subtypes: ischemic heart disease, cerebrovascular disease, heart failure, and arrhythmia. ResultsChronic exposure to air pollutant mixtures was associated with increased hospitalization rates for all CVD subtypes, with heart failure being the most susceptible subtype. Sulfate, nitrate, nitrogen dioxide, and organic carbon posed the highest risks. Mixtures of the interaction terms between air pollutants and temperature mean anomalies were associated with increased hospitalization rates for all CVD subtypes. ConclusionsOur findings identified critical pollutants for targeted emission controls and suggested that abnormal temperature changes chronically affected cardiovascular health by interacting with air pollution, not directly.

Understanding Antithrombotic Agents for Rehabilitation Therapy: A Comprehensive Narrative Review.

In rehabilitation medicine, attention must be paid to the medication. Among them, antithrombotic drugs are used for the initial treatment and secondary prevention of stroke, so as a basic knowledge, the pharmacological actions, characteristics, indications, and precautions for the use of antithrombotic drugs should be known. Antithrombotic agents are divided into antiplatelet agents and anticoagulants, and the appropriate antithrombotic agent is selected according to the main disease or condition. Antiplatelet agents include aspirin, clopidogrel, ticlopidine, prasugrel, ticagrelor, and cilostazol. Each antiplatelet agent has a different mechanism of action, characteristics, and indications, and should be prescribed with due consideration. Anticoagulants include heparin, synthetic Xa inhibitors, direct oral anticoagulants (DOACs), synthetic antithrombin agents, and warfarin. Knowledge of the mechanism of action, characteristics, and indications of each anticoagulant is necessary, as well as monitoring and dose adjustment. With regard to ischemic cerebrovascular disease (ICD) and antithrombotic agents, the first step is to classify cerebral infarction and to determine whether antiplatelet agents or anticoagulants should be used. Bleeding and recurrence prevention are important considerations in the selection of appropriate antithrombotic agents for the pathophysiology of ICD.

Long-term outcomes after formation of a low-flow STA-MCA bypass for treatment of symptomatic occlusion of the internal carotid artery

Aim. To evaluate short‑ and long‑term effectiveness of low‑flow bypass between superficial temporal artery and M4 segment of middle cerebral artery (low‑flow STA‑MCA bypass) in patients with symptomatic occlusion of the internal carotid artery (ICA).Materials and methods. Between 2016 and 2019 at the Department of Neurosurgery of the N. V. Sklifosovsky Research Institute of Emergency Medicine, 54 patients who underwent low‑flow STA‑MCA bypass formation at the side of symptomatic ICA occlusion between 2013 and 2015 were examined. Symptomatic ICA occlusion was more common in men than in women (7:1 ratio). Patient age varied between 48 and 73 years (mean age was 62 years).During low‑flow STA‑MCA bypass formation surgery for symptomatic ICA occlusion, intraoperative flowmetry was used in 52 (96 %) patients, in 2 (4 %) patients this diagnostic method was impossible to perform due to technical difficulties. The main examination methods in the long term after cerebral revascularization were evaluation of neurological status dynamics per the National Institute of Health Stroke Scale (NIHSS); modified Rankin scale; Rivermead mobility index; computed tomography angiography of the extra‑intracranial arteries; ultrasound (US) examination of the STA‑MCA bypass for eval uation of linear and volumetric blood flow velocities; single‑photon emission computed tomography. The type and size of trephination were evaluated, and operative time was taken into account.The patients were divided into 3 groups: group 1 included patients with follow‑up period of 1–2 years after cerebral revascularization, group 2 – 3–4 years, group 3 – 5–6 years. All results were compared to preoperative, early, and longterm measurements.Results. In the long‑term postoperative period between 1 and 6 years after cerebral revascularization, 54 patients were examined. Computed tomography angiography and US showed functioning STA‑MCA bypass in 53 (98 %) patients. According to single‑photon emission computed tomography of the brain, regional cerebral blood flow in the longterm postoperative period varied between 28 and 40 mL / 100 g / min, median regional cerebral blood flow in the long‑term postoperative period was 38 mL / 100 g / min. Intraoperative flowmetry was performed in 52 (96 %) patients, median was 15.5 mL / min. US showed that linear blood flow velocity in the STA‑MCA bypass varied between 20 and 95 cm / s, median was 49 cm / s. Volumetric blood flow varied between 30 and 85 mL / min with median of 75 mL / min.Resection trephination was performed in 36 (67 %) patients, mean size of trephination hole was 3 cm3. In the study, operative time was measured: mean value was 212 min; no significant correlation between operative time and trephination size was observed.Improved neurological status was observed in all study groups. Per the NIHSS, in group 1 (1–2 years) improvement was observed in 59 % of patients, in group 2 (3–4 years) in 48 %, in group 3 (5–6 years) in 47 %. Per the modified Rankin scale, in group 1 improvement was observed in 36.4 % of patients, in group 2 – in 48 %, in group 3 – in 42.9 %. Per the Rivermead mobility index, in group 1 improvement was observed in 63.3 % patients, in group 2 – in 56 %; in group 3 – in 57.1 %. The best outcomes were observed in group 1 (63.3 %).Conclusion. Instrumental diagnostic methods and evaluation of neurological status showed positive dynamics both in the postoperative period and in long‑term period between 1 and 6 years after low‑flow STA‑MCA bypass formation. In the long term, repeat abnormalities of cerebral blood flow of ischemic type and repeat transient ischemic attacks were not observed. Correct selection of patients in the preoperative period and comprehensive treatment including drug therapy in the postoperative and long‑term periods allow to prevent repeat ischemic cerebrovascular disease and therefore improve patients’ quality of life.

Total Tau Protein Mediates the Association of Ischemic Cerebrovascular Disease with Cognitive Decline

Background: Patients with transient ischemic attack (TIA) or ischemic stroke demonstrate an increased risk of cognitive dysfunction. Accumulating evidence indicates that ischemic cerebrovascular disease (ICVD) may interact with the amyloid/tau/neurodegeneration (AT[N]) biomarkers to promote dementia. However, the precise pathological mechanisms remain to be fully characterized. Objective: To elucidate the interrelationships among ICVD, ATN biomarkers in cerebrospinal fluid (CSF), and cognition. Methods: A total of 2524 participants were recruited from the CABLE study. ICVD referred to TIA/ischemic stroke. Cognitive performance was assessed by China Modified Mini-Mental State Examination (CM-MMSE) and Montreal Cognitive Assessment-b (MoCA-b). Multivariate linear regression analyses were performed to evaluate the associations of ICVD with CSF ATN biomarkers and cognition. Causal mediation analyses were used to identify whether the association was mediated by ATN biomarkers. Results: ICVD was associated with higher total-tau (t-tau) (p = 2.828×10–2) and poorer cognition (CM-MMSE: p = 1.539×10–5, MoCA-b: p = 4.552×10–6). Additionally, no discernible correlation surfaced between ICVD and amyloid-β (Aβ) 42 (p = 6.910×10–1) or phosphorylated tau (p-tau) (p = 4.324×10–1). The influence of ICVD on cognitive function was partially mediated by CSF t-tau (CM-MMSE: proportion: 2.74%, MoCA-b: proportion: 2.51%). Subgroup analyses revealed the influences of t-tau were especially evident in male (CM-MMSE: proportion: 5.45%, MoCA-b: proportion: 5.38%) and mid-life group (CM-MMSE: proportion: 9.83%, MoCA-b: proportion: 5.31%). Conclusions: These results delineated t-tau as a potential mediator for the influence of ICVD on cognition. Targeting brain ischemia and alleviating neuronal injury induced by ischemia may be a promising approach for preventing cognitive decline.

Evaluating Total Atherosclerosis Burden of Baroreceptor-Resident Arteries after Ischemic Cerebrovascular Disease for Identifying Patients with Heavy Coronary Atherosclerosis Burden.

The carotid sinuses and aortic arch are baroreceptor-resident arteries (BRAs) and atherosclerosis-susceptible sites of brain-supplying arteries, which would impair baroreflex-mediated blood pressure (BP) regulation and prompt coronary atherosclerosis. We sought to determine the relationship between total atherosclerosis burden (TAB) of BRAs and coronary atherosclerosis burden (AB) in patients with ischemic cerebrovascular disease (ICVD) and explore the potential contribution of BP profiles to this relationship. In this cross-sectional analysis of patients with ICVD who simultaneously undertook computed tomography angiography and 24-hour ambulatory BP monitoring, TAB of BRAs was scored based on the atherosclerotic vessel circumference ratio of the carotid sinuses and aortic arch, while the ABs of the intracranial, cervical, aortic, and coronary arteries were scored based on stenosis severity and plaque complexity as routine. Among the 230 patients analyzed, coronary AB was significantly correlated with TAB of BRAs, independently of, and more tightly than the ABs of the intracranial, cervical, and aortic arteries, and the stenosis- and complexity-based AB of BRA-located arteries (bilateral common and extracranial internal carotid arteries and aortic arch). Both coronary AB and TAB of BRAs were negatively associated with the night-to-day BP dipping ratios, which was quite different from the relationship between intracranial AB and 24-hour BP characteristics. These findings were also true for patients with ICVD without a history of coronary artery disease. Evaluating TAB of BRAs might provide a new link between atherosclerosis of brain- and heart-supplying arteries, connected partially by BP circadian rhythm. It might facilitate identifying patients with ICVD with heavy coronary AB and comprehensively managing vascular risk.

Factors associated with clopidogrel resistance and clinical outcomes in ischemic cerebrovascular disease: A retrospective study

ObjectiveClopidogrel resistance may lead to the recurrence of cerebrovascular diseases. We aimed to identify potential factors associated with clopidogrel resistance and evaluate the clinical outcomes of the patients. Materials and methodsIn this retrospective study, patients with ischemic cerebrovascular disease treated with clopidogrel were included and classified into 2 groups according to the adenosine diphosphate (ADP)-induced platelet aggregation. Patients with the ADP inhibition rate of <30 % were included in clopidogrel resistance group, otherwise were included in clopidogrel sensitive group. CYP2C19 genotype and other clinical data were analyzed to identify factors and clinical features in the multivariate analysis. The outcomes were vascular events in 6 months. ResultsIn total, 139 patients were enrolled with 81 (58.27 %) in clopidogrel sensitive group and 58 (41.73 %) in clopidogrel resistance group. Female and CYP2C19 *2*3 carrying were risk factors for clopidogrel resistance, and female was an independent risk factor (OR 2.481, 95 % CI 1.066-5.771, P=0.035). The clopidogrel resistance group showed a higher use rate of argatroban (P=0.030) and a lower arachidonic acid-induced inhibition of platelet aggregation (P=0.036). Clopidogrel resistance was related to the progressing stroke (HR 3.521, 95 % CI 1.352-9.170, P=0.010), but had no influence on the bleeding events (P>0.05). ConclusionsThe risk of clopidogrel resistance increased significantly in female patients. Patients with clopidogrel resistance may have an increased incidence of stroke progression in the acute phase.

Has the first year of the COVID pandemic impacted the trends in obesity-related CVD mortality between 1999 and 2019 in the United States?

BackgroundDuring the covid-19 pandemic there was a marked rise in the number of cardiovascular deaths. Obesity is a well-known modifiable risk factor for cardiovascular disease and has been identified as a factor which leads to poorer covid-19 related outcomes. In this study we aimed to analyse the impact of covid-19 on obesity-related cardiovascular deaths compared to trends seen 20 years prior. We also analysed the influence different demographics had on mortality. MethodsMultiple Cause of Mortality database was accessed through CDC WONDER to obtain the obesity-related and general cardiovascular crude mortality and age adjusted mortality rates (AMMR) between 1999 and 2020 in the US. The obesity-related sample was stratified by demographics and cardiovascular mortality was subdivided into ischemic heart disease, heart failure, hypertension and cerebrovascular disease. Joinpoint Regression Program (Version 4.9.1.0) was used to calculate the average annual percent change (AAPC) in AAMR, and hence projected AAMR. Excess mortality was calculated by comparing actual AAMR in 2020 to projected values. Results and discussionThere were an estimated 3058 excess deaths during the early stages of the pandemic impacting all cohorts. The greatest excess mortalities were seen in men, rural populations and in Asian/Pacific Islander and Native Americans. Interestingly the greatest overall mortality was seen in the Black American population. Our study highlights important, both pre and during the pandemic, in obesity related cardiovascular disease mortality which has important implications for ongoing public health measures.

Species Distribution, Typical Clinical Features and Risk Factors for Poor Prognosis of Super-Elderly Patients with Bloodstream Infection in China.

Bloodstream infection (BSI) is characterized by high mortality, especially among these increasing super-elderly patients (≥85 years), and this study was conducted to understand the species distribution, typical clinical features and risk factors for poor prognosis of super-elderly patients with BSI. Based on previous work, this retrospective study was performed by reviewing an ongoing prospective medical database in a comprehensive tertiary center in China, and all super-elderly patients with BSI in the past 6 years were enrolled in this study. Out of 5944 adult-patients with BSI, there were totally 431 super-elderly patients (≥85 years old) enrolled in this study and age ≥90 years accounted for 31.1% (134/431). Among these 431 super-elderly patients with BSI, 40 patients (9.3%) were diagnosed with BSI and the remained 401 super-elderly patients (90.7%) were defined as hospital-acquired BSI. The typical feature of these super-elderly patients with BSI was the high proportion of patients with various comorbidities, such as cardiovascular disease (83.8%), ischemic cerebrovascular disease (63.3%) and pulmonary infection (61.0%). The other typical feature was that most (60.1%) of these patients had been hospitalized for long time (≥28 days) prior to the onset of BSI, and most patients had received various invasive treatments, such as indwelling central venous catheter (53.1%) and indwelling urinary catheter (47.1%). Unfortunately, due to these adverse features above, both the 7-day short-term mortality (13.2%, 57/431) and the 30-day long-term mortality (24.8%, 107/431) were high. The multivariate analysis showed that both chronic liver failure (OR 7.9, 95% CI 2.3-27.8, P=0.001) and indwelling urinary catheter (OR 2.3, 95% CI 1.1-4.7, P=0.023) were independent risk factors for 7-day short-term mortality, but not for 30-day long-term mortality. In addition, the microbiology results showed that the most common species were associated with nosocomial infection or self-opportunistic infection, such as Staphylococcus hominis (18.3%), Staphylococcus epidermidis (11.8%), Escherichia coli (9.7%), Klebsiella pneumoniae (9.3%) and Candida albicans (8.6%, fungi). Super-elderly patients with BSI had typical features, regardless of the pathogenic species distribution and their drug resistance, or clinical features and their risk factors for poor prognosis. These typical features deserved attention and could be used for the prevention and treatment of BSI among super-elderly patients.

Statin administration ameliorates ischemia-induced overactive bladder with improvement of blood flow and anti-inflammatory effects in rats.

Statins are widely used to treat dyslipidemia and have been shown to reduce the risk of ischemic heart disease and cerebrovascular disease. The effects of statins on ischemia-induced overactive bladder (OAB) and the associated mechanisms were investigated in a rat model of chronic pelvic ischemia. A pelvic ischemia model was created by iliac arterial injury (AI) and a high-fat diet using male Sprague-Dawley rats. Rats were assigned to 3 groups: control group, AI group, and AI + statin group. The control group underwent sham operation and was fed a normal diet. The AI group underwent AI surgery and was fed a high-cholesterol diet. The AI + statin group was administered a statin for 4 weeks. Cystometry was performed for 8 weeks after surgery. Blood flow was evaluated by laser meter. Thickness of the iliac arteries was measured, and microvascular density in the lamina propria was evaluated by immunostaining for CD31. Expressions of inflammatory cytokines in the bladder were measured by real-time PCR. Cystometry showed a significantly shorter voiding interval and lower bladder capacity in the AI group than in the control group. The AI + statin group showed improvement of these findings. The AI group showed decreased bladder blood flow, increased iliac arterial wall thickening, and decreased microvascular density compared to the control group. Statin administration improved blood flow. Iliac arterial wall thickening was suppressed, and microvascular density was increased by statin administration, though not significantly. Real-time PCR showed significantly higher expressions of inflammatory cytokines (IL-6, IL-8, and TNF-α) in the AI group than in the control group, and IL-6 and IL-8 expressions were lower in the AI + statin group than in the AI group. The present results suggest that statins are effective in OAB caused by arteriosclerosis and ischemia. The mechanism of their effects involves improved bladder blood flow and decreased bladder inflammation.

Medium-intensity statin with ezetimibe versus high-intensity statin in acute ischemic cerebrovascular disease (MESIA): A randomized clinical trial

BackgroundHigh-risk stroke patients are recommended to receive high-intensity statin therapy to reduce the risk of stroke recurrence. However, doubling the dosage of statin drugs did not increase the achievement rate of LDL-C target or provide additional clinical benefits, but significantly increased the risk of adverse reactions. Statins and ezetimibe work through different mechanisms and the combined use of statins and ezetimibe significantly improves outcomes with comparable safety profiles. We tested the hypothesis that moderate-intensity statin with ezetimibe may offer advantages over the conventional high-intensity statin regimen in terms of efficacy and safety. MethodsWe conducted a randomized controlled trial. Eligible participants were aged 18 years or older with acute ischemic cerebrovascular disease. We randomly assigned (1:1) participants within the acute phase of ischemic stroke, i.e., within 1 week after the onset of mild ischemic stroke (NIHSS score ≤ 5), within 1 month for severe cases (NIHSS score ≥ 16), and within 2 weeks for the rest, as well as patients with TIA within 1 week of symptom onset, to receive either moderate-intensity statin with ezetimibe (either 10–20 mg atorvastatin calcium tablets plus a 10 mg ezetimibe tablet, or 5–10 mg rosuvastatin calcium tablets once per day plus a 10 mg ezetimibe tablet once per day) or high-intensity statin (40 mg atorvastatin calcium tablets or 20 mg rosuvastatin calcium tablets once per day) for 3 months. Randomization was performed using a random number table method. The primary efficacy outcome was the level and achievement rate of LDL-C after 3 months of treatment, specifically LDL-C ≤ 1.8 mmol/L or a reduction in LDL-C ≥ 50 %. The secondary outcome was the incidence of new stroke or transient ischemic attack (TIA) within 3 months. The safety outcome was liver and renal function tests, and the occurrence of statin-related muscle events within 3 months. FindingsThis trial took place between March 15, 2022, and March 7, 2023. Among 382 patients screened, 150 patients were randomly assigned to receive either medium-intensity statins with ezetimibe (n = 75) or high-intensity statins (n = 75). Median age was 60.0 years (IQR 52.75-70.25); 49 (36.6 %) were women and 85 (63.4 %) were men. The target achievement of LDL-C at 3 months occurred in 62 (89.86 %) of 69 patients in the medium-intensity statin with ezetimibe group and 46 (70.77 %) of 65 patients in the high-intensity statin group (P=0.005, OR=0.273, 95 % CI: 0.106, 0.705). The reduction magnitude of LDL-C in moderate-intensity statin with ezetimibe group was significantly higher (-56.540 % vs -47.995 %, P=0.001). Moderate-intensity statin with ezetimibe group showing a trend of a greater reduction in LDL-C absolute value than high-intensity statin group but without statistical significance (-1.77±0.90 vs -1.50±0.89, P=0.077). New AIS or TIA within 3 months, liver and renal function tests, and the occurrence of statin-related muscle events within 3 months were also statistically insignificant. Multivariate logistic regression analysis showed that both gender and lipid-lowering regimen as independent risk factors influencing the rate of LDL-C achievement in individuals diagnosed with acute ischemic cerebrovascular disease, but only lipid-lowering regimen had predictive value. InterpretationCompared to guideline-recommended high-intensity statin therapy, moderate-intensity statin with ezetimibe further improved the achievement rate of LDL-C in patients with acute ischemic cerebrovascular disease, with a higher reduction magnitude in LDL-C. In terms of safety, there was no significant difference between the two regimens, suggesting that moderate-intensity statin with ezetimibe can also be considered as an initial treatment option for patients with acute ischemic cerebrovascular disease.

Inhibition of Endoplasmic Reticulum Stress Improves Chronic Ischemic Hippocampal Damage Associated with Suppression of IRE1α/TRAF2/ASK1/JNK-Dependent Apoptosis.

Chronic cerebral ischemia is a complex form of stress, of which the most common hemodynamic characteristic is chronic cerebral hypoperfusion (CCH). Lasting endoplasmic reticulum (ER) stress can drive neurological disorders. Targeting ER stress shows potential neuroprotective effects against stroke. However, the role of ER stress in CCH pathological processes and the effects of targeting ER stress on brain ischemia are unclear. Here, a CCH rat model was established by bilateral common carotid artery occlusion. Rats were treated with 4-PBA, URB597, or both for 4weeks. Neuronal morphological damage was detected using hematoxylin-eosin staining. The expression levels of the ER stress-ASK1 cascade-related proteins GRP78, IRE1α, TRAF2, CHOP, Caspase-12, ASK1, p-ASK1, JNK, and p-JNK were assessed by Western blot. The mRNA levels of TNF-α, IL-1β, and iNOS were assessed by RT-PCR. For oxygen-glucose deprivation experiments, mouse hippocampal HT22 neurons were used. Apoptosis of the hippocampus and HT22 cells was detected by TUNEL staining and Annexin V-FITC analysis, respectively. CCH evoked ER stress with increased expression of GRP78, IRE1α, TRAF2, CHOP, and Caspase-12. Co-immunoprecipitation experiments confirmed the interaction between TRAF2 and ASK1. ASK1/JNK signaling, inflammatory cytokines, and neuronal apoptosis were enhanced, accompanied by persistent ER stress; these were reversed by 4-PBA and URB597. Furthermore, the ASK1 inhibitor GS4997 and 4-PBA displayed synergistic anti-apoptotic effects in cells with oxygen-glucose deprivation. In summary, ER stress-induced apoptosis in CCH is associated with the IRE1α/TRAF2/ASK1/JNK signaling pathway. Targeting the ER stress-ASK1 cascade could be a novel therapeutic approach for ischemic cerebrovascular diseases.

Clinical Features and Treatment of Patients Infected With SARS-CoV-2 Omicron Variant While Hospitalized Due to Stroke: A Single Center Study in Japan.

In December 2019, COVID-19 spread rapidly across the globe. Throughout the pandemic, SARS-CoV-2 repeatedly mutated, transitioning from the alpha variant to the omicron variant. The severity and mortality of COVID-19 have been linked to age, sex, and the presence of underlying diseases (respiratory, cerebrovascular, cardiovascular, metabolic, and immune diseases, as well as cancer). The clinical features of patients infected with COVID-19 following a stroke, however, are fully unknown. Therefore, it is significant to explore the appropriate treatment for these patients based on their clinical features. Of the 6175 patients who visited Asahi Hospital (Tokyo, Japan) between November 2022 and February 2023, 206 were admitted. Of these 206 patients, the 44 that contracted COVID-19 while hospitalized for strokes were retrospectively analyzed. Six (13.6%) of these patients died; four expired due to coagulopathy associated with ischemic heart failure and recurrent ischemic cerebrovascular disease. The mean D-dimer level increased to 3.53 in the deceased patients, while it was 1.64 in all patients. The platelet count was low in three of the deceased patients, while it was high in two patients. The severity of COVID-19 was significantly correlated with a high modified Rankin Scale (mRS) score and a high National Institute of Health Stroke Scale (NIHSS) score. The timing of vaccination is inversely correlated with COVID-19 severity. Patients with COVID-19 after a stroke have high mortality rates due to coagulopathy. Stroke patients with high mRS scores and high NIHSS scores are more likely to develop severe COVID-19. Anticoagulant therapy should be administered to COVID-19 patients with high mRS scores following a stroke.

Factors affecting seizure recurrence in the emergency department

BackgroundInformation on Emergency Department (ED) follow-up of patients presenting with epileptic seizures is limited. ObjectivesIt was planned to investigate the factors affecting the recurrence of epileptic seizures in the follow-up of patients presenting to the ED with the complaint of epileptic seizures. Materials and methodsThis prospective, observational, single-center study was carried out in an adult population presenting to the ED. The study included patients older than 18 years of age presenting to the ED with the complaint of epileptic seizures. ResultsOf the 205 patients included in the study, 68 (33.2%) had seizure recurrence during the 6 h. In the univariable analysis, advanced age, prolonged post-ictal duration, increased seizure duration, generalized tonic clonic seizure, alcohol consumption within past 24 h, hypertension, coronary artery disease, Alzheimer's disease, prior ischemic cerebrovascular disease, low Glascow Coma Scale (GCS), high glucose, high C-Reactive Protein, high phosphorus, low potassium, high blood urea nitrogen, high lactate, increased anion gap, high osmolarity were statistically significant in predicting recurrent seizure recurrence within 6 h. According to the logistic regression, postictal duration, GCS score, and age were independent predictors in our model. The cut-off value of postictal duration in predicting seizure recurrence at the highest sensitivity (66.2%) and specificity (89.8%) was 22.5 min. ConclusionA prolonged postictal state, low GCS score, advanced age may be an indication of seizure recurrence. Therefore, patients with a long postictal duration, low GCS score, advanced age should be followed up more carefully in terms of recurrent seizures in the ED.

Exposure-response associations between chronic exposure to fine particulate matter and risks of hospital admission for major cardiovascular diseases: population based cohort study

ObjectiveTo estimate exposure-response associations between chronic exposure to fine particulate matter (PM2.5) and risks of the first hospital admission for major cardiovascular disease (CVD) subtypes.DesignPopulation based cohort study.SettingContiguous US.Participants59 761...

Fusobacterium nucleatum bacteremia complicated with intracranial Porphyromonas gingivalis and HSV-1 infection: a case report and literature review

BackgroundFusobacterium nucleatum (F. nucleatum) belongs to the genus Fusobacterium, which is a gram-negative obligate anaerobic bacterium. Bacteremia associated with F. nucleatum is a serious complication, which is not common in clinic, especially when it is combined with other intracranial pathogenic microorganism infection. We reported for the first time a case of F. nucleatum bacteremia combined with intracranial Porphyromonas gingivalis (P. gingivalis) and herpes simplex virus type 1(HSV-1) infection.Case presentationA 60-year-old woman was admitted to our hospital with a headache for a week that worsened for 2 days. Combined with history, physical signs and examination, it was characterized as ischemic cerebrovascular disease (ICVD). F. nucleatum was detected in blood by matrix-assisted laser desorption/ionization time-offight mass spectrometry (MALDI-TOF-MS). Meanwhile, P. gingivalis and HSV-1 in cerebrospinal fluid (CSF) were identified by metagenome next generation sequencing (mNGS). After a quick diagnosis and a combination of antibiotics and antiviral treatment, the patient recovered and was discharged.ConclusionTo our knowledge, this is the first report of intracranial P. gingivalis and HSV-1 infection combined with F. nucleatum bacteremia.

Statins-Their Role in Bone Tissue Metabolism and Local Applications with Different Carriers.

Statins, widely prescribed for lipid disorders, primarily target 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase competitively and reversibly, resulting in reduced low-density lipoprotein cholesterol (LDL-C). This mechanism proves effective in lowering the risk of lipid-related diseases such as ischemic cerebrovascular and coronary artery diseases. Beyond their established use, statins are under scrutiny for potential applications in treating bone diseases. The focus of research centers mainly on simvastatin, a lipophilic statin demonstrating efficacy in preventing osteoporosis and aiding in fracture and bone defect healing. Notably, these effects manifest at elevated doses (20 mg/kg/day) of statins, posing challenges for systematic administration due to their limited bone affinity. Current investigations explore intraosseous statin delivery facilitated by specialized carriers. This paper outlines various carrier types, characterizing their structures and underscoring various statins' potential as local treatments for bone diseases.

Chronic diseases spectrum and multimorbidity in elderly inpatients based on a 12-year epidemiological survey in China

BackgroundThe number and proportion of the elderly population have been continuously increasing in China, leading to the elevated prevalence of chronic diseases and multimorbidity, which ultimately brings heavy burden to society and families. Meanwhile, the status of multimorbidity tends to be more complex in elderly inpatients than community population. In view of the above concerns, this study was designed to investigate the health status of elderly inpatients by analyzing clinical data in Chinese People's Liberation Army (PLA) General Hospital from 2008 to 2019, including the constitution of common diseases, comorbidities, the status of multimorbidity, in-hospital death and polypharmacy among elderly inpatients, so as to better understand the diseases spectrum and multimorbidity of elderly inpatients and also to provide supporting evidence for targeted management of chronic diseases in the elderly.MethodsA clinical inpatients database was set up by collecting medical records of elderly inpatients from 2008 to 2019 in Chinese PLA General Hospital, focusing on diseases spectrum and characteristics of elderly inpatients. In this study, we collected data of inpatients aged ≥ 65 years old, and further analyzed the constitution of diseases, multimorbidity rates and mortality causes in the past decade. In addition, the prescriptions were also analyzed to investigate the status of polypharmacy in elderly inpatients.ResultsA total of 210,169 elderly patients were hospitalized from January 1st, 2008 to December 31st, 2019. The corresponding number of hospitalizations was 290,833. The average age of the study population was 72.67 years old. Of the total population, 73,493 elderly patients were re-admitted within one year, with the re-hospitalization rate of 25.27%. Malignant tumor, hypertension, ischemic heart disease, diabetes mellitus and cerebrovascular disease were the top 5 diseases. Among the study population, the number of patients with two or more long-term health conditions was 267,259, accounting for 91.89%, with an average of 4.68 diseases. In addition, the average number of medications taken by the study population was 5.4, among which, the proportion of patients taking more than 5 types of medications accounted for 55.42%.ConclusionsBy analyzing the constitution of diseases and multimorbidity, we found that multimorbidity has turned out to be a prominent problem in elderly inpatients, greatly affecting the process of healthy aging and increasing the burden on families and society. Therefore, multidisciplinary treatment should be strengthened to make reasonable preventive and therapeutic strategies to improve the life quality of the elderly. Meanwhile, more attention should be paid to reasonable medications for elderly patients with multimorbidity to avoid preventable side effects caused by irrational medication therapy.