Cerebrovascular Complications Research Articles

Vascular Alterations following COVID-19 Infection: A Comprehensive Literature Review

SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic, has revealed a broader impact beyond the respiratory system, predominantly affecting the vascular system with various adverse manifestations. The infection induces endothelial dysfunction and immune system dysregulation, creating an inflammatory and hypercoagulable state. It affects both microvasculature and macrovasculature, leading to thromboembolic events, cardiovascular manifestations, impaired arterial stiffness, cerebrovascular complications, and nephropathy, as well as retinopathy—frequently observed in cases of severe illness. Evidence suggests that SARS-CoV-2 infection may result in persistent effects on the vascular system, identified as long-term COVID-19. This is characterized by prolonged inflammation, endotheliopathy, and an increased risk of vascular complications. Various imaging modalities, histopathological studies, and diagnostic tools such as video capillaroscopy and magnetic resonance imaging have been employed to visualize vascular alterations. This review aims to comprehensively summarize the evidence concerning short and long-term vascular alterations following COVID-19 infection, investigating their impact on patients’ prognosis, and providing an overview of preventive strategies to mitigate associated vascular complications.

Effects of different treatment modalities on cardiovascular disease in ARR-positive hypertensive patients.

Data on the prognosis of clinically undiagnosed hypertensive patients who are aldosterone-to-renin ratio (ARR) positive are still scarce. Therefore, we investigated the clinical characteristics of clinically undiagnosed hypertensive patients who were ARR-positive and the influence of their different treatments on the occurrence and development of complications. A total of 285 hypertensive patients data with ARR ≥ 3.8 in the Second People's Hospital of Huai'an from January 2019 to December 2021 were collected, and 135 undiagnosed hypertensive patients were ultimately included in the analysis. According to their treatment strategy in various clinical departments, 135 patients were divided into the operation, spironolactone and control groups. Then, the clinical characteristics and the occurrence and development of complications in the three groups were compared. The results suggested that: (1) Only 34 (11.9%) of 285 hypertensive patients with ARR ≥ 3.8 were clearly diagnosed with Primary aldosteronism (PA) through functional tests, and the blood pressure (BP) compliance rate was only 50.30% during follow-up. (2) Based on exclusion criteria, 135 undiagnosed hypertensive patients were eventually included in the analysis. Patients in the surgery group had lower blood potassium levels and higher aldosterone levels than those in the other two groups, and their risk of new cerebrovascular complications was lower than that of the patients in the spironolactone group. (3) The risk of new cerebrovascular complications in the spironolactone group was 9.520 times higher than that of the control group, and this risk mainly occurred in patients with ARR values of 3.8-5.7. On the whole, surgery remains a good option for hypertensive patients with severe hyperaldosteronism and hypokalemia and those unable to undergo confirmatory tests; however, spironolactone therapy in patients with clinically undiagnosed hypertension, especially those with 3.8 ≤ ARR < 5.7, confered a higher risk of new cerebrovascular complications.

Group B Streptococcus Meningitis in an Adult Woman with Type 2 Diabetes and Ethmoid Roof Defect. Impact on "frontal" Cognitive Functions.

Community-acquired bacterial meningitis in adults represents one of the most severe infectious diseases worldwide with potentially life-threatening medical complications. Several infectious agents can cause acute meningitis. Although group B Streptococcus is more prevalent in newborns, infection can also lead to meningitis in older adults, particularly those with underlying health issues. A 53-year-old woman with a body mass index of 28.7 kg/m2, type 2 diabetes mellitus, and dyslipidaemia presented to the emergency department of Santa Maria della Stella Hospital (Orvieto, Italy) with confusion, low-grade fever, echolalia, and hyperglycaemia. Computed tomography scans of the brain revealed a hypodensity in the left anterior frontal lobe and an osteodural defect of the rhinobase. Meningitis was suspected and empiric broad-spectrum antibiotic therapy with corticosteroids and insulin were administered while the results of the cerebrospinal fluid analysis confirmed the diagnosis of group B Streptococcus meningitis. Repeat imaging at 48 hours revealed enlargement of the hypodense lesion. The frontal assessment battery indicated deficits in executive functions. Prompt treatment led to rapid clinical improvement. Following the restoration of euglycemic status and hemodynamic stabilization, a follow-up magnetic resonance imaging confirmed the ischaemic lesion and showed cerebrospinal fluid in the sella turcica. The patient was then transferred to neurorehabilitation. The complex interactions among multiple risk factors resulted in an atypical clinical case of group B Streptococcus meningitis, which was promptly treated with empiric antibiotic therapy to mitigate neurocognitive deficits. Group B Streptococcus can cause meningitis in adults with poorly controlled type 2 diabetes mellitus and should be promptly treated with empiric broad-spectrum antibiotics.An osteodural defect of the ethmoid roof together with idiopathic intracranial hypertension may result in empty sella turcica and CSF rhinorrhoea, promoting the dissemination of the pathogen.Meningitis patients with pre-existing diabetic cerebral vasculopathy may develop cerebrovascular complications and cognitive impairments.

Sex Differences on Cerebrovascular Complications in Hospitalized COVID-19 Patients: A Meta-analysis (P11-5.030)

Sex Differences on Cerebrovascular Complications in Hospitalized COVID-19 Patients: A Meta-analysis (P11-5.030)

Should Chronological Age be a Consideration in Patients Undergoing Elective Primary Total Knee Arthroplasty?

The optimal time for total knee arthroplasty (TKA) requires a balance between patient disability and health state in order to minimize complications. While chronological age has not been shown to be predictive of complications in elective surgical patients, there is a point beyond which even optimized elderly patients would be at increased risk for complications. The purpose of this study was to examine the impact of chronological age on complications following primary TKA. Using an administrative database, the records of 2,129,191 patients undergoing elective unilateral TKA between 2006 and 2021 were reviewed. The primary outcomes of interest were cardiac and pulmonary complications, and their relationship to the Charlson-Deyo Comorbidity Index (CDI) and chronological age. Secondary outcomes included risk of renal, neurologic, infection, and intensive care utilization postoperatively. The results were analyzed using a graphical method. The impact of chronological age as a modifier of overall risk for complications was modeled as a continuous variable. An age cutoff threshold of 80 years was also assigned for clinical convenience. The risk of complications correlated more closely to the Charlson-Deyo index (OR [odds ratio] 1.37 to 2.1) than chronological age (OR 1.0 to 1.1) across the various complications [Table-1. However, beyond age 80 years, the risks of cardiac, pulmonary, renal, and cerebrovascular complications were significantly increased for all CDI categories (OR 1.73 to 3.40) compared to patients below age 80 years [Table-2] [Figures 1A and 1B]. Chronologic age can impact the risk of complications even in well-optimized elderly patients undergoing primary TKA. As arthroplasty continues to transition to outpatient settings and inpatient denials increase, these results can help patients, physicians, and payors mitigate risk while optimizing the allocation of resources.

Impact of extracorporeal membrane oxygenation-related complications on in-hospital mortality.

Although extracorporeal membrane oxygenation (ECMO) is a well-established treatment for supporting severe cardiopulmonary failure, the morbidity and mortality of patients requiring ECMO support remain high. Evaluating and correcting potential risk factors associated with any ECMO-related complications may improve care and decrease mortality. This study aimed to assess the predictors of ECMO-related vascular and cerebrovascular complications among adult patients and to test the hypothesis that ECMO-related complications are associated with higher in-hospital mortality rates. This single-center, retrospective study included 856 ECMO runs administered via cannulation of the femoral vessels of 769 patients: venoarterial (VA) ECMO (n = 709, 82.8%) and venovenous (VV) ECMO (n = 147, 17.2%). The study outcomes included the occurrence of ECMO-related vascular and cerebrovascular complications and in-hospital death. The association of ECMO-related complications with the risk of in-hospital death was analyzed. The incidences of ECMO-related vascular and cerebrovascular complications were 20.2% and 13.6%, respectively. The overall in-hospital mortality rate was 48.7%: 52.8% among VA ECMO runs and 29.3% among VV ECMO runs. Multivariable analysis indicated that age (P < 0.01), cardiopulmonary cerebral resuscitation (P < 0.01), continuous renal replacement therapy (P < 0.01), and initial platelet count [<50×103/μL (P = 0.02) and 50-100(×103)/μL (P < 0.01)] were associated with an increased risk of in-hospital death. ECMO-related vascular and cerebrovascular complications were not independently associated with higher in-hospital mortality rates for VA or VV ECMO runs. ECMO-related vascular and cerebrovascular complications were not associated with an increased risk of in-hospital death among adult patients.

Cerebrovascular Complications in Spinal Fusion Surgery: A Nationwide 8-year Follow-up Study in South Korea.

This retrospective study investigated the long-term incidence and risk of postoperative complications following spinal fusion. This study included 640,366 participants from a National Health Examination cohort in the Republic of Korea. Among them, 11,699 individuals underwent spinal fusion, and 56,667 individuals who underwent non-fusion spinal procedures served as controls. Propensity score matching was used to account for patient characteristics including demographic factors, comorbidities, and other relevant variables. The participants were followed for 8 years to assess the occurrence of cerebrovascular disease (CVD), hemorrhagic infarction (HA), ischemic infarction (II), occlusion and stenosis, and ischemic heart disease (IHD). The incidence rates of CVD and IHD were found to be 27.58 and 31.45 per 1,000 person-years in the spinal fusion group compared to 18.68 and 25.73 per 1,000 person-years in the control group (p < .001), respectively. Patients who underwent spinal fusion had a higher risk of CVD, HA, and IHD than those in the control group (all p < .001). In the subgroup analysis, thoracolumbar and noncervical spinal fusion were associated with a higher risk of CVD, II, and IHD (all p < .005). Patients undergoing thoracolumbar fusion may have an increased association with CVD, II in cerebral arteries, and IHD. This suggests a need for careful consideration of vascular risks in such patient populations.

The Internal mechanism of correlation between angiotensin II gene and serum adiponectin level in patients with cerebrovascular complications of H-type hypertension

Abstract: It was to explore the correlation between angiotensin II (Ang II) gene and serum adiponectin expression in patients with cerebrovascular complications of H-type hypertension (HH) and its mechanism. A total of 50 cases of outpatient patients in Tianjin Fourth Central Hospital were recruited from January 2022 to June 2023 and rolled into three groups according to their blood pressure and basic information, namely HH cerebrovascular complications group, the non-H-type hypertension (NHH) group, and the healthy control (HC)group. Peripheral blood samples were taken, one sample was utilized to test for the Ang II gene and the methylation of Ang II, and the other sample was utilized to measure serum adiponectin levels, so as to analyze the relationship between serum adiponectin level and Ang II in patients with cerebrovascular complications of HH. The ratio of male to female was 8:7 in the group of cerebrovascular complications of HH, and mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 167.34mmHg and 112.56mmHg, respectively. In NHH group, the mean SBP was 165.89mmHg and the mean DBP was 113.47mmHg. The blood pressure of HC group was in the normal range. The Ang II content was the highest in the group with cerebrovascular complications of HH, followed by the group with NHH, and the lowest in HC group. Pyrosequencing chart of patients with cerebrovascular complications of HH showed that the content of deoxyphosphate ribose G was the highest, while the content of A was the highest in NHH patients. Moreover, the serum adiponectin level of patients with HH and NHH was superior to that of HC group, and adiponectin level between the former two groups and HC groupdiffered considerably. Ang II levels were high in patients with cerebrovascular complications of HH and were positively correlated with adiponectin levels. The incidence of cerebrovascular complications of HH may be related to Ang II level in patients.

Safety of Perioperative Maintenance of Antiplatelet Agents in Elderly Patients Undergoing Lung Cancer Surgery.

The maintenance of antiplatelet therapy increases the risk of bleeding during lung cancer surgery. Conversely, the perioperative interruption of antiplatelet therapy may result in serious thrombotic complications. This study aimed to investigate the safety of continuing antiplatelet therapy in the context of lung cancer surgery. We retrospectively reviewed a cohort of 498 elderly patients who underwent surgery for lung cancer. These patients were categorized into 2 groups: group N, which did not receive antiplatelet therapy, and group A, which did. Group A was subsequently subdivided into group Am, where antiplatelet therapy was maintained, and group Ai, where antiplatelet therapy was interrupted. We compared the incidence of bleeding-related and thrombotic complications across the 3 groups. There were 387 patients in group N and 101 patients in group A (Ai: 70, Am: 31). No significant differences were found in intraoperative blood loss, thoracotomy conversion rates, transfusion requirements, volume of chest tube drainage, or reoperation rates for bleeding control between groups N and A or between groups Am and Ai. The duration of hospital stay was longer for group A compared to group N (7 days vs. 6 days, p=0.005), but there was no significant difference between groups Ai and Am. The incidence of cardiovascular or cerebrovascular complications did not differ significantly between groups Ai and Am. However, group Ai included a severe case of in-hospital ST-elevation myocardial infarction. The maintenance of antiplatelet therapy was found to be safe in terms of perioperative bleeding and thrombotic complications in elderly lung cancer surgery patients.

Paxlovid use is associated with lower risk of cardiovascular diseases in COVID-19 patients with autoimmune rheumatic diseases: a retrospective cohort study

BackgroundPaxlovid has been shown to be effective in reducing mortality and hospitalization rates in patients with coronavirus disease 2019 (COVID-19). It is not known whether Paxlovid can reduce the risk of cardiovascular diseases (CVD) in COVID-19-surviving patients with autoimmune rheumatic diseases (AIRDs).MethodsTriNetX data from the US Collaborative Network were used in this study. A total of 5,671,395 patients with AIRDs were enrolled between January 1, 2010, and December 31, 2021. People diagnosed with COVID-19 were included in the cohort (n = 238,142) from January 1, 2022, to December 31, 2022. The Study population was divided into two groups based on Paxlovid use. Propensity score matching was used to generate groups with matched baseline characteristics. The hazard ratios (HRs) and 95% confidence intervals of cardiovascular outcomes, admission rate, mortality rate, and intensive care unit (ICU) admission rate were calculated between Paxlovid and non-Paxlovid groups. Subgroup analyses on sex, age, race, autoimmune diseases group, and sensitivity analyses for Paxlovid use within the first day or within 2–5 days of COVID-19 diagnosis were performed.ResultsPaxlovid use was associated with lower risks of cerebrovascular complications (HR = 0.65 [0.47–0.88]), arrhythmia outcomes (HR = 0.81 [0.68–0.94]), ischemic heart disease, other cardiac disorders (HR = 0.51 [0.35–0.74]) naming heart failure (HR = 0.41 [0.26–0.63]) and deep vein thrombosis (HR = 0.46 [0.24–0.87]) belonging to thrombotic disorders in AIRD patients with COVID-19. Compared with the Non-Paxlovid group, risks of major adverse cardiac events (HR = 0.56 [0.44–0.70]) and any cardiovascular outcome mentioned above (HR = 0.76 [0.66–0.86]) were lower in the Paxlovid group. Moreover, the mortality (HR = 0.21 [0.11–0.40]), admission (HR = 0.68 [0.60–0.76]), and ICU admission rates (HR = 0.52 [0.33–0.80]) were significantly lower in the Paxlovid group than in the non-Paxlovid group. Paxlovid appears to be more effective in male, older, and Black patients with AIRD. The risks of cardiovascular outcomes and severe conditions were reduced significantly with Paxlovid prescribed within the first day of COVID-19 diagnosis.ConclusionsPaxlovid use is associated with a lower risk of CVDs and severe conditions in COVID-19-surviving patients with AIRD.

Bacterial load in cerebrospinal fluid predicts unfavourable outcome in pneumococcal meningitis: a prospective nationwide cohort study

ObjectivesThe objective of this study was to determine the role of cerebrospinal fluid (CSF) bacterial load in adults with pneumococcal meningitis. MethodsWe quantified bacterial load in CSF samples from the diagnostic lumbar puncture of adults with community-acquired pneumococcal meningitis. We also measured CSF concentrations of complement component 5a (C5a), and determined associations between bacterial load, clinical characteristics, C5a and unfavourable outcome (Glasgow Outcome Scale score <5). ResultsBacterial load was quantified in 152 CSF samples. Median age of these patients was 61 years (interquartile range [IQR] 51–68), and 69 of 152 (45%) were female. Median CSF bacterial load was 1.6 × 104 DNA copies/mL (IQR 3.4 × 103–1.2 × 105), and did not correlate with CSF white cell count nor with CSF protein concentrations. Median CSF C5a concentration was 35.8 mg/L (IQR 15.9–105.6), and was moderately correlated with CSF bacterial loads (Spearman's rho = 0.42; p < 0001). High bacterial loads were associated with development of complications, such as circulatory shock (OR per logarithmic increase: 2.4, 95% CI: 2.0–2.9; p < 0.001) and cerebrovascular complications [OR: 1.9, 95% CI: 1.6–2.3; p < 0.001]). High bacterial loads were also associated with unfavourable outcome (OR: 2.8, 95% CI: 2.4–3.3; p < 0.001) and death (OR: 3.1, 95% CI: 2.6–3.8; p < 0.001). In a multivariable regression model including age, immunocompromised state, extrameningeal infection focus, admission Glasgow Coma Scale score and CSF C5a concentration, CSF bacterial load remained an independent predictor of unfavourable outcome (adjusted OR: 2.5, 95% CI: 1.6–3.9; p < 0.001). DiscussionHigh CSF bacterial load predicts the development of complications and unfavourable outcome in adults with pneumococcal meningitis.

Astragali Radix: comprehensive review of its botany, phytochemistry, pharmacology and clinical application.

Astragali Radix (A. Radix) is the dried root of Astragalus membranaceus var. mongholicus (Bge) Hsiao or Astragalus membranaceus (Fisch.) Bge., belonging to the family Leguminosae, which is mainly distributed in China. A. Radix has been consumed as a tonic in China for more than 2000years because of its medicinal effects of invigorating the spleen and replenishing qi. Currently, more than 400 natural compounds have been isolated and identified from A. Radix, mainly including saponins, flavonoids, phenylpropanoids, alkaloids, and others. Modern pharmacological studies have shown that A. Radix has anti-tumor, anti-inflammatory, immunomodulatory, anti-atherosclerotic, cardioprotective, anti-hypertensive, and anti-aging effects. It has been clinically used in the treatment of tumors, cardiovascular diseases, and cerebrovascular complications associated with diabetes with few side effects and high safety. This paper reviewed the progress of research on its chemical constituents, pharmacological effects, clinical applications, developing applications, and toxicology, which provides a basis for the better development and utilization of A. Radix.

Challenges with medical tourism.

With the return of international travels to almost prepandemic levels, the number of patients who travel abroad to seek healthcare services is once again growing rapidly. Nevertheless, the expected benefits of medical tourism may be challenged by serious infectious complications. This review summarizes the evolving published evidence on infectious complications related with medical tourism of the last eighteen months. There has been an increase of reported infectious complications in patients who had received healthcare abroad. Such complications were frequently associated with serious and prolonged morbidity, repeated treatments and hospitalizations, high healthcare costs, and occasionally fatalities. A devastating outbreak of fungal meningitis occurred among US residents who underwent epidural anesthesia for cosmetic surgery in two clinics in Mexico. Overall, as of July 5, 2023 there were 31 cases with severe cerebrovascular complications and eight deaths. Infections caused by nontuberculum mycobacteria and Candida sp have been also reported the last years. Considering the expected expansion of medical tourism in the forthcoming years, public health authorities and scientific societies should raise awareness of such infections among physicians and other healthcare professionals and issue recommendations for their management. A system to report complications in patients receiving healthcare abroad is needed.

Higher perfusion pressure and pump flow during cardiopulmonary bypass are beneficial for kidney function-a single-centre prospective study.

Background: Kidneys play an essential role in the circulatory system, regulating blood pressure and intravascular volume. They are also set on maintaining an adequate filtration pressure in the glomerulus. During the CPB, a decrease in systemic blood pressure and hemoglobin concentration may lead to renal ischemia and subsequent acute kidney injury. Methods: One hundred nine adult patients were prospectively enrolled in this study. The intervention in this study was increasing the flow of the CPB pump to reach the target MAP of > 90mmHg during the procedure. The control group had a standard pump flow of 2.4L/min/m2. Results: Standard pump flow of 2.4L/min/m2 resulted in mean MAP < 90mmHg during the CPB in most patients in the control group. Maintaining a higher MAP during CPB in this study population did not affect CSA-AKI incidence. However, it increased the intraoperative and postoperative diuresis and decreased renin release associated with CPB. Higher MAP during the CPB did not increase the incidence of cerebrovascular complications after the operation; patients in the highest MAP group had the lowest incidence of postoperative delirium, but the result did not obtain statistical significance. Conclusion: Maintaining MAP > 90mmHg during the CPB positively impacts intraoperative and postoperative kidney function. It significantly reduces renal hypoperfusion during the procedure compared to MAP < 70mmHg. MAP > 90mmHg is safe for the central nervous system, and preliminary results suggest that it may have a beneficial impact on the incidence of postoperative delirium.

Risk of Early Postoperative Cardiovascular and Cerebrovascular Complication in Patients with Preoperative COVID-19 Undergoing Cancer Surgery.

As the COVID-19 pandemic shifts to an endemic phase, an increasing proportion of cancer patients with a preoperative history of COVID-19 will require surgery. This study aimed to assess the influence of preoperative COVID-19 on postoperative risk for major adverse cardiovascular and cerebrovascular events (MACE) among those undergoing surgical cancer resection. Secondary objectives included determining optimal time-to-surgery guidelines based on COVID-19 severity and discerning the influence of vaccination status on MACE risk. National COVID Cohort Collaborative (N3C) Data Enclave, a large multi-institutional dataset, was used to identify patients that underwent surgical cancer resection between January 2020 and February 2023. Multivariate regression analysis adjusting for demographics, comorbidities, and risk of surgery was performed to evaluate risk for 30-day postoperative MACE. Of 204,371 included patients, 21,313 (10.4%) patients had a history of preoperative COVID-19. History of COVID-19 was associated with an increased risk for postoperative composite MACE as well as 30-day mortality. Among patients with mild disease who did not require hospitalization, MACE risk was elevated for up to 4-weeks following infection. Postoperative MACE risk remained elevated 8+ weeks following infection in those with moderate disease. Vaccination did not reduce risk for postoperative MACE. Together, these data highlight that assessment of the severity of preoperative COVID-19 infection should be a routine component of both preoperative patient screening as well as surgical risk stratification. In addition, strategies beyond vaccination that increase patients' cardiovascular fitness and prevent COVID-19 infection are needed.

Abstract WP324: MCA/FeCl 3 Thromboembolic Model, an Easily Reproducible Model for COVID-19-Induced Embolic Cerebrovascular Complications

COVID-19 neurological complications such as strokes and cognitive impairment have been reported. Yet the molecular mechanisms are under investigation. A mild and reproducible thromboembolic model will be a helpful tool for investigating COVID-thromboembolic complications. The aim of this study is to investigate the middle cerebral artery/ferric chloride (MCA/FeCl 3 ) thromboembolic model as an easily and reproducible model for COVID-19-induced cerebrovascular embolic complications. Methods: SARS-CoV-2 spike-protein of the alpha variant were injected intravenously (4 ug/animal) in K18 (transgenic knock-in humanized ACE2 in epithelial cells). Seven days later, MCA/FeCl 3 thromboembolic model was induced in K18 mice by exposing the MCA and placing filter paper wet with FeCl 3 . Laser speckle imaging was used for the assessment of blood flow and recanalization after 1,2,6, and 24 hrs. TTC was used to assess the infarct volume. Cognitive function was assessed using a novel object recognition test. Cerebral vascular density and blood-brain barrier (BBB) were assessed by immunohistochemistry staining using Iso-B4 lectin and Occludin-5 antibody. Results: SARS-CoV-2 spike-protein caused a significant increase in the time required for vascular recanalization as detected by laser speckle imaging compared to control K18 mice. (P&lt;0.05). In parallel, spike protein caused a significant increase in infarct size compared to control K18 mice (P&lt;0.05). Our immunohistochemistry showed that spike protein decreased vascular density and increased vascular rarefaction compared to control K18 mice (P&lt;0.05). A novel object recognition test showed that spike protein increased cognitive dysfunction compared to control (P&lt;0.05). Western blot analysis showed that spike protein increased inflammatory markers and decreased BBB tight junction protein compared to control K18 mice (P&lt;0.05). In conclusion , the MCA/FeCl 3 thromboembolic model is an easily reproducible mouse model to examine COVID-19-induced stroke and cerebrovascular complications.

Abstract 17: SARS-CoV-2 Spike Protein Exacerbates Thromboembolic Cerebrovascular Complications in Humanized ACE2 Mouse Model

COVID-19 doubles the risk for acute ischemic stroke in patients with cardiovascular disorders, yet, the molecular mechanisms are unclear and remain unresolved medical challenges. We hypothesize that SARS-CoV-2 spike protein exacerbates stroke and neurovascular complications via increasing coagulation and decreasing fibrinolysis by disrupting the renin-angiotensin-aldosterone system (RAAS) balance. Methods: MCA/FeCl 3 thromboembolic model was induced in humanized ACE2 knock-in mice. hACE2 mice were treated with Losartan, an angiotensin receptor blocker, after one day of SARS-CoV-2 spike protein injection. Cerebral blood flow was measured using a Laser speckle imager. Infarct size was compared using TTC stain. Vascular-induced cognitive function and dementia (VCID) were assessed using a Novel object recognition test. D-dimmer, Tissue factor -3 (TF-3), and Plasminogen activator inhibitor-1 (PAI-1) were measured using ELISA and Western blot to assess coagulation and fibrinolysis. Human brain microvascular endothelial cells (HBMEC) were exposed to hypoxia with/without SARS-Co-V2 spike protein and were assessed for coagulation factors, inflammation, and RAAS balance. Results: SARS-CoV-2 spike protein increased neuronal death and decreased cognitive function after MCA/FeCl 3 thromboembolic occlusion. hACE2 mice subjected to SARS-CoV-2 spike protein showed diminished cerebral blood flow compared to control groups. SARS-CoV-2 spike protein increased coagulation factors (increased TF-3, P&lt;0.05) and decreased fibrinolysis (increased PAI-1, P&lt;0.05) in hACE2 and HBMVEC. Losartan reduced spike protein-induced infarction and improved cognitive function in hACE2 mice. SARS-CoV-2 spike protein caused RAAS system imbalances in hACE2 mice by increasing AT 1 R and downstream inflammatory signal. Moreover, spike protein decreased the protective RAAS arm by decreasing AT 2 R and Mas receptors in hACE2 mice and HBMVEC. Conclusion: SARS-CoV-2 spike protein exacerbates hypercoagulation and inflammation leading to increased cerebrovascular damage and cognitive dysfunction. However, the AT 1 R blocker, Losartan, restored the RAAS balance and reduced COVID-19-induced thromboembolic cerebrovascular complications.

Recent progress in unraveling cardiovascular complications associated with primary aldosteronism: a succinct review.

This comprehensive review offers a thorough exploration of recent advancements in our understanding of the intricate cardiovascular complications associated with Primary Aldosteronism (PA). PA encompasses a spectrum of conditions characterized by hypertension and excessive production of aldosterone operating independently of the renin-angiotensin system. Given its association with an elevated risk of cardiovascular and cerebrovascular complications, as well as a higher incidence of metabolic syndrome in comparison to individuals with essential hypertension (EH), an accurate diagnosis of PA is of paramount importance. This review delves into the intricate interplay between PA and cardiovascular health and focuses on the key pathophysiological mechanisms contributing to adverse cardiac outcomes. The impact of different treatment modalities on cardiovascular health is also examined, offering insights into potential therapeutic approaches. By highlighting the significance of recognizing PA as a significant contributor to cardiovascular morbidity, this review emphasizes the need for improved screening, early diagnosis, and tailored management strategies to both enhance patient care and mitigate the burden of cardiovascular diseases. The findings presented herein underscore the growing importance of PA in the context of cardiovascular medicine and emphasize the potential for translating these insights into targeted interventions to improve patient outcomes.

Therapeutic Opportunities of Apixaban in Patients With Atrial Fibrillation and Reducing the Risk of Cerebrovascular Complications in Chronic Kidney Disease

The review article is devoted to the possibilities of using the oral anticoagulant apixaban in patients with atrial fibrillation (AF) and to reduce the risk of cerebral complications in chronic kidney disease (CKD). The generality of risk factors and mechanisms of the occurrence of AF in patients with CKD are considered. The therapeutic possibilities have been demonstrated for the use of oral anticoagulants, in particular apixaban, in AF in the CKD association. The main mechanisms of kidney damage during therapy with vitamin K antagonists are shown. Apixaban is shown to be more effective than warfarin to prevent stroke regardless of the severity of renal dysfunction, and in patients with creatinine clearance less than 50 ml/min, the benefits of apixaban in reducing the frequency of major bleeding are most pronounced degrees. In AF patients with CKD C1-C4 gradations, dose adjustment of apixaban is not required. The safety of the use of apixaban in a full dose (5 mg 2 times a day) in patients with terminal CKD has been approved, subject to regular hemodialysis.

The S1 subunits of SARS-CoV-2 variants differentially trigger the IL-6 signaling pathway in human brain endothelial cells and downstream impact on microglia activation.

Cerebrovascular complications are prevalent in COVID-19 infection and post-COVID conditions; therefore, interactions of SARS-CoV-2 with cerebral microvascular cells became an emerging concern. We examined the inflammatory responses of human brain microvascular endothelial cells (HBMEC), the main structural element of the blood-brain barrier (BBB), following exposure to the S1 subunit of the spike protein of different SARS-CoV-2 variants. Specifically, we used the S1 subunit derived from the D614 variant of SARS-CoV-2, which started widely circulating in March of 2020, and from the Delta variant, which started widely circulating in early 2021. We then further examined the impact of the HBMEC secretome, produced in response to the S1 exposure, on microglial proinflammatory responses. Treatment with S1 derived from the D614 variant and from the Delta variant resulted in differential alterations of the IL-6 signaling pathway. Moreover, the HBMEC secretome obtained after exposure to the S1 subunit of the D614 variant activated STAT3 in microglial cells, indicating that proinflammatory signals from endothelial cells can propagate to other cells of the neurovascular unit. Overall, these results indicate the potential for different SARS-CoV-2 variants to induce unique cellular signatures and warrant individualized treatment strategies. The findings from this study also bring further awareness to proinflammatory responses involving brain microvasculature in COVID-19 and demonstrate how the surrounding microglia react to each unique variant derived response.