Search Results (179)

Ischemic stroke is a primary cause of cerebrovascular diseases and continues to be one of the leading causes of death and disability among patients worldwide. Pathological processes caused by vascular damage due to stroke occur in a time-dependent manner and are classified into three categories: acute, subacute, and chronic. Current treatments for ischemic stroke are limited to effectiveness in the early stages. In this study, we investigated the therapeutic effect of an oriental medicine, Gosha-jinki-gan (TJ107), on improving chronic ischemic stroke using the mouse model with middle cerebral artery occlusion (MCAO). The changes in the intracerebral inflammatory response (macrophages (F4/80), TLR2•4, IL-23, IL-17, TNF-α, and IL-1β) were examined using real-time RT-PCR. The MCAO mice showed the increased expression of glial fibrillary acidic protein (GFAP) and of F4/80, TLR2, TLR4, IL-1β, TNF-α, and IL-17 in the brain tissue from the MCAO region. This suggests that they contribute to the expansion of the ischemic stroke infarct area and to the worsening of the neurological symptoms of the MCAO mice in the chronic phase. On the other hand, the administration of TJ107 was proven to reduce the infarct area, with decreased GFAP expression, suppressed macrophage infiltration in the brain, and reduced TNF-α, IL-1β, and IL-17 production compared with the MCAO mice. This study first demonstrated Gosha-jinki-gan’s therapeutic effects on the chronic ischemic stroke. Full article

Background and Objectives: Ischemic stroke (IS) is a critical health issue, affecting individuals of all ages, sexes, and backgrounds. Mounting evidence suggests that sex indeed could play some distinct role in shaping the incidence, outcomes, and treatment of IS. In the context of the COVID-19 pandemic, contradictory findings from previous studies that also addressed sex differences in cerebrovascular diseases demonstrate the need for further focused research. This study aimed to evaluate the sex discrepancies in the clinical presentation of IS and its outcomes in patients admitted to Kaunas Hospital of the Lithuanian University of Health Sciences (LUHS), Lithuania. Materials and Methods: This is a retrospective record-based single-center study. All the study patients—727 men and 1082 women—enrolled between 1 January 2020, and 27 February 2022; suffered from acute IS; and had absolute contraindications against interventional IS treatment. These patients received a conservative non-interventional IS treatment at the neurological department of the LUHS’s Kaunas Hospital. The sociodemographic data; laboratory findings; comorbidities, including COVID-19; in-hospital complications; and outcome factors were obtained from the patients’ medical records and evaluated by deploying appropriate statistical tests. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by the Cox proportional hazards regression for in-hospital lethality. Results: The mean age of IS patients was significantly higher in women compared to men (p < 0.001), as was the proportion of in-hospital deaths (19.10% and 15.36%, respectively; p < 0.05). The mean total number of in-hospital complications was again significantly higher in the group of women compared to men (p < 0.05). The prevalence of COVID-19 was higher in men compared to women (p < 0.05). COVID-19 diagnosis (HR = 1.53; p = 0.02) and acute in-hospital pulmonary complications (HR = 1.91; p = 0.008) significantly increased the risk of in-hospital lethality in men. The risk of in-hospital lethality was significantly higher in women with comorbid diabetes mellitus type 2 (DM) compared to those with comorbid isolated arterial hypertension (AH) (HR = 2.25, p = 0.007). Increased C-reactive protein elevated the risk of in-hospital lethality by more than twice in both men and women (HR = 2.46; p < 0.001 and HR = 2.28; p < 0.001, respectively). Conclusions: The following differences between men and women with IS were determined: Acute in-hospital pulmonary complications, including COVID-19, significantly increased the risk of in-hospital lethality in the male group, but not in women. However, women suffering from DM had a significantly increased risk of in-hospital lethality compared with those women IS patients with AH or chronic ischemic heart disease (IHD). Increased C-reactive protein was associated with an elevated risk of in-hospital lethality both in male and female groups. Full article

Objectives: Previous studies have suggested differences in vasculitic and eosinophilic phenotypes based on anti-neutrophil cytoplasmic antibody (ANCA) positivity in eosinophilic granulomatosis with polyangiitis (EGPA). However, their relevance under the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria remains unclear. We aimed to evaluate the clinical features and outcomes of EGPA according to myeloperoxidase (MPO)-ANCA status in a Korean cohort. Methods: We conducted a retrospective cohort study that included 57 patients with EGPA without proteinase 3-ANCA positivity who fulfilled the 2022 ACR/EULAR classification criteria. Patients were classified into MPO-ANCA-positive (n = 25) and MPO-ANCA-negative (n = 32) groups. Clinical manifestations, laboratory findings, and outcomes, including all-cause mortality, relapse, end-stage kidney disease (ESKD), cerebrovascular accident (CVA), and acute coronary syndrome (ACS), were compared between the two groups. Results: MPO-ANCA-positive patients exhibited higher Five-Factor Scores (1.0 [0.0–1.0] vs. 0.0 [0.0–1.0], p = 0.038), lower Short Form 36 Physical Component Summary scores (35.0 [19.7–56.3] vs. 52.5 [43.5–69.7], p = 0.048), and elevated systemic inflammation markers (higher erythrocyte sedimentation rate: 58.0 [16.0–97.5] mm/hr vs. 25.5 [7.0–63.8] mm/hr, p = 0.026). Constitutional symptoms were more frequent among MPO-ANCA-positive patients (n = 14 [56.0%] vs. n = 3 [9.4%], p < 0.001), whereas no significant differences were found in vasculitic or eosinophilic manifestations. Kaplan–Meier analysis revealed no differences in the overall (p = 0.36), relapse-free (p = 0.80), ESKD-free (p = 0.87), CVA-free (p = 0.26), or ACS-free (p = 0.94) survival rates between the two groups. Conclusions: In Korean patients with EGPA classified under the 2022 ACR/EULAR classification criteria, MPO-ANCA positivity, as compared to ANCA-negative status, was associated with a higher disease burden and poorer quality of life but not with distinct vasculitic or eosinophilic manifestations and adverse outcomes. Full article

Hypoxia leads to endothelial dysfunction and increased blood–brain barrier (BBB) permeability, promoting the incidence of diseases such as stroke and acute high-altitude illness. Brain microvascular endothelial cells (BMECs) are important structural and functional components of the BBB; however, the molecular changes that occur in BMECs during hypoxia remain unknown. We reported the molecular and functional changes in BMECs under hypoxia through whole-transcriptome sequencing, small RNA microarray, TMT quantitative proteomic, and untargeted metabolomic analyses. We found that hypoxia affected pathways such as ncRNA processing, the HIF-1 signaling pathway, the cell cycle, DNA replication, glucose metabolism, protein synthesis, and inflammation pathways. ncRNA processing was significantly downregulated. However, the levels of some miRNAs, tRNAs, tsRNAs, snoRNAs, lncRNAs, and circRNAs were significantly upregulated under hypoxia. These results suggest that ncRNAs may play an important role in oxidative stress and cellular adaptation to hypoxia, helping us understand the pathological process of BBB injury and providing potential targets for the treatment of BBB-related cerebrovascular diseases. Full article

Background: Atherothrombosis is a systemic disease that may affect one or more than one vascular bed. Data on the impact of polyvascular disease (PVD) on the long-term prognosis of patients with coronary artery disease (CAD) are still scarce. Aim: To assess the prevalence of symptomatic PVD in a cohort of patients with a new episode of acute coronary syndrome (ACS) and to investigate the impact of multiple vascular beds involvement on long-term outcomes. Methods: We analysed a nationwide, comprehensive administrative database of consecutive patients aged ≥ 40 years admitted for a new episode of ACS in Italy in 2017–2018. Patients with ACS were stratified according to the presence of peripheral artery disease (PAD) only; cerebrovascular disease (CeVD) only; PAD+CeVD; or neither (no PAD/noCeVD, i.e., ACS only). A multivariate Cox proportional hazards model was used to assess the impact of PAD only; CeVD only and PAD+CeVD on 5-year MACCE. Results: A total of 342,052 patients hospitalised with ACS were identified. Among them, 24,727 (7.2%) were patients with PAD only, 16,887 (4.9%) with CeVD only, and 5810 (1.7%) with PAD+CeVD. After adjusting for age, sex, and comorbidities, the hazard ratio (HR) for 5-year MACCE was 1.37 (95% CI: 1.35–1.40), 1.36 (95% CI: 1.33–1.39), and 1.45 (95% CI: 1.40–1.50) in patients with PAD only, CeVD only, and PAD+CeVD, respectively, compared with patients with ACS only. Conclusions: In patients with ACS, the involvement of a second vascular bed increases the risk of long-term outcomes; the simultaneous involvement of three vascular beds further increases the risk of long-term outcomes. Full article

Background and Objectives: This study investigated the frequency and clinical significance of subclinical but substantial peripheral arterial disease (PAD), identified using PAD evaluation, including pulse volume recording/ankle–brachial index (PVR/ABI), transcutaneous oxygen pressure (TcpO2), and skin perfusion pressure (SPP) tests in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 54 patients with PAD evaluation results at or after AAV diagnosis. PVR/ABI and/or TcpO2 and/or SPP were performed on the same day. Abnormal PVR/ABI, TcpO2, and SPP were defined as PVR/ABI < 0.97, TcpO2 < 40 mmHg, and SPP < 50 mmHg, respectively. Poor outcomes included all-cause mortality, end-stage kidney disease (ESKD), cerebrovascular accidents, and acute coronary syndrome after PAD evaluation. Results: The median age of the 54 patients was 67 years, and 48.1% were male. In total, 3 of 54 patients (5.6%), 6 of 16 (37.5%), and 6 of 23 (26.1%) had abnormal PVR/ABI, TcpO2, and SPP, respectively. The concordance rate between abnormal PVR/ABI and abnormal TcpO2 or SPP was very low. Among the 54 patients, 5 (9.3%) died, and 2 (3.7%) progressed to ESKD. Abnormal SPP was significantly associated with cutaneous and renal manifestations at the time of PAD evaluation and had the potential to predict progression to ESKD during follow-up in patients with AAV. Conclusions: This study is the first to reveal the clinical usefulness of PAD evaluation: abnormal SPP may have the potential to identify subclinical but substantial PAD and can predict simultaneous kidney involvement as well as future progression to ESKD in patients with AAV. Full article

The prevalence of Alzheimer’s Disease (AD) is increasing worldwide, with more emergency providers and neurologists expecting to encounter these patients. The paradigm of management of AD is expected to change given the recent approval of anti-amyloid therapies (AATs). The most concerning complication of these therapies is amyloid-related imaging abnormalities (ARIA), which can lead to an increased risk of cerebrovascular complications. Given a growing population of patients with AD and growing use of AATs, providers must be prepared to manage patients at risk of cerebrovascular disease and those presenting with neurologic deficits. This subpopulation warrants a unique approach given the risk of ischemic stroke and the associated risk of hemorrhage present in the use of AATs. In this narrative review, we present and propose management considerations in the acute stroke setting and patients at risk of cerebrovascular disease, including patients with indications for anticoagulation, to most appropriately manage this special population. Future cross-disciplinary collaboration and use of registry data will be essential to narrow management approaches and develop safety data. Full article

Background/Objectives: This study aimed to develop and validate comorbidity-based severity adjustment methods for acute cerebrovascular disease by recalibrating the Charlson Comorbidity Index (CCI) and constructing a CCS-based comorbidity index to improve mortality risk prediction. Methods: Using the Korea Disease Control Agency’s Discharge Injury In-depth Survey Dataset (2013–2022), we applied Cox proportional hazards regression and machine learning techniques, including LASSO, CART, Random Forests, GBM, and ANN, to recalibrate the CCI and develop a CCS-based comorbidity index. Results: The recalibrated Charlson Comorbidity Index (m-CCI) and the newly developed CCS-based comorbidity index (m-CCS) demonstrated improved predictive performance for in-hospital mortality. Among the machine learning models, GBM (AUC = 0.835) and ANN (AUC = 0.830) demonstrated the highest predictive accuracy, with m-CCS consistently outperforming other indices. Conclusions: The recalibrated m-CCI and newly developed m-CCS comorbidity indices enhance mortality risk adjustment for acute cerebrovascular disease patients in Korea. The superior performance of machine learning models underscores their potential for enhancing severity adjustment in hospital benchmarking and quality assessment. Full article

Background: Ischemic stroke (IS), a major cerebrovascular disease, is associated with high disability and mortality rates. Acute kidney injury (AKI) often complicates IS and increases in-hospital mortality. While antiplatelet agents are commonly used for IS treatment, their effectiveness in IS patients with AKI is unclear. Methods: This study, using data from the MIMIC-IV database, divided patients into non-combination (clopidogrel or ticagrelor alone) and combination (with aspirin) groups. The primary outcome was 28-day mortality, with secondary outcomes including 90-day, 1-year, and in-hospital mortality. Multivariable Cox and logistic regression models were used to analyze the relationship between antiplatelet regimens and mortality. Subgroup analyses and interaction tests were conducted. Results: Results showed the combination group had lower 28-day, 90-day, 1-year, and in-hospital mortality risks than the non-combination group (all p < 0.001). Subgroup analysis revealed an interaction effect by AKI stage, with combination therapy not significantly reducing mortality in severe AKI (stages 2 and 3, p = 0.743, p = 0.244). Conclusions: This study demonstrates that combination antiplatelet therapy significantly reduces 28-day, 90-day, 1-year, and in-hospital mortality risks of IS patients with AKI, suggesting its potential benefits in improving both short- and long-term clinical outcomes. However, this does not apply to patients with severe AKI, indicating heterogeneous survival benefits of combination therapy across AKI severity. Clinical decision-making should incorporate AKI stage stratification to evaluate the applicability of combination antiplatelet therapy. Further research is needed to explore the impact of AKI staging on antiplatelet therapy in IS patients. Full article

Background: In patients with coronary artery disease, bare-metal stents (BMS) are considered a safer but less effective treatment than drug-eluting stents (DES). Oral colchicine therapy may compensate for this limitation of BMS. This randomized trial compared the cost-effectiveness of two different revascularization strategies during percutaneous coronary intervention (PCI). Methods: Between March 2020 and April 2022, 410 patients were randomly treated with PCI with BMS plus colchicine (BMS-CO: 205 patients) or DES (205 patients) The patients in the BMS-CO group received 0.5 mg oral doses of colchicine for 3 months. The primary endpoint was major adverse cardiac and cerebrovascular events (MACEs), defined as the composite of death, myocardial infarction, stroke, or target vessel revascularization (TVR), and the costs of each treatment strategy. The secondary endpoints included the individual components of MACEs. Results: No significant differences were observed in baseline characteristics, and 76% of the patients presented with acute coronary syndromes. The median follow-up period was 36.8 months. Five percent of the patients in the BMS-CO group discontinued study medication. The cumulative incidence of MACEs was not significantly different, with 12.7% in the BMS-CO group and 15.6% in the DES2G group (p = 0.39) as well individual components of the clinical endpoint. The cumulative costs were lower in the BMS-CO group than in the DES2G group (USD 4826.4 ± 2512 vs. USD 5708 ± 3637, p < 0.001). Conclusions: In the 3 years, the DES strategy failed to be cost-saving compared to BMS-CO. However, due to the small sample size, the equivalence in clinical outcomes with both strategies can occur by chance (NCT04382443). Full article

Background/Objectives: Current evidence suggests that levosimendan may have a beneficial effect in the treatment of acute heart failure (AHF) or cardiogenic shock following primary percutaneous coronary intervention (PCI). However, there is a paucity of data on the use of levosimendan prior to PCI. Therefore, our pilot study aimed to assess the short-term prognosis of a new therapeutic protocol involving preprocedural infusion of levosimendan in patients with reduced left ventricular ejection fraction undergoing high-risk PCI for acute coronary syndrome (ACS). Methods: The study is a retrospective observational study, and the population includes all subjects who received levosimendan infusion prior to high-risk PCI for ACS. Subjects requiring urgent revascularization (cardiogenic shock, cardiac arrest) or with mechanical complications of ACS were excluded. Results: The study cohort consisted of 90 subjects, predominantly men (91.1%) with significantly reduced left ventricular function (28.7% (12)) and advanced coronary artery disease, mean SYNTAX Score 25.8 (19.3–33). During in-hospital follow-up, we observed 2 primary outcomes—death. The major adverse cardiac and cerebrovascular events (MACCE) rate was 7.8%. Two clinical adverse events that did not lead to discontinuation were observed during the in-hospital period. Both were related to hypotension. Conclusions: In short-term observation, novel therapeutic approach in the management of high-risk PCI in ACS patients—pre-procedural levosimendan—was a relatively safe approach. No significant adverse events were reported. Full article

Background: Sepsis in patients with acute myeloid leukemia (AML) is one of the causes of acute kidney injury (AKI). There are no available data on the outcomes of AML-related AKI patients. Methods: We researched the 2016–2020 National Inpatient Sample (NIS) database to collect data on hospitalizations of patients ≥18 years old with sepsis and AML. These admissions were divided into two weighted groups, with and without AKI. A multivariable logistic regression was used with adjustment for possible confounders to generate the adjusted odds ratios for the outcomes of the study. A p-value of <0.05 was considered significant. The primary outcome was all-cause inpatient mortality. Secondary outcomes were septic shock, fluid and electrolyte disorders, length of stay (LOS), vasopressor support, and the requirement for mechanical ventilation. Results: Out of 288,435 hospital admissions of patients with sepsis and AML, 61,955 (21.4%) had AKI. Patients with AKI were older (mean age 66.1 vs. 60.4 years), males (63.1% vs. 52.8%), and more Black individuals were affected (12% vs. 9.2). They also had more comorbidities but had a significantly higher percentage of diabetes mellitus, congestive heart failure, cardiac arrhythmias, cerebrovascular disease, and chronic kidney disease. Tumor lysis syndrome was present in 11.1%. Compared to patients without AKI, patients with AKI had longer LOS days (15.4 ± 18 vs. 10.8 ± 13.1, p < 0.001. Multivariable analysis showed that the patients with AKI had higher odds of mortality (OR: 3.8, 95% CI: 3.6–4.1, p < 0.001). They also had a higher risk for fluid and electrolyte disorders (OR: 2.2, 95% CI: 2.1–2.4, p < 0.001), septic shock (OR: 6.3, 95% CI: 5.7–6.9, p < 0.001), vasopressor requirement (OR: 5.0, 95% CI: 4.3–5.8, p < 0.001), and mechanical ventilation (OR: 5.2, 95% CI: 4.7–5.7, p < 0.001). Conclusions: AKI in patients with sepsis and AML was associated with higher mortality compared to sepsis alone, as well as other complications. Further large studies are required to identify factors that could improve outcomes. Full article

Chronic graft-versus-host disease (cGVHD) is a prognostically negative event following hematopoietic stem cell transplant (HSCT). While cGVHD mainly affects the muscles, skin, oral mucosa, eyes, lungs, gastrointestinal tract, and liver, central nervous system (CNS) involvement remains possible and, moreover, is rare when it occurs isolated. CNS-cGVHD can manifest with a wide spectrum of CNS disorders, including cerebrovascular diseases, autoimmune demyelinating diseases, and immune-mediated encephalitis. We present a case of 65-year-old man previously treated with HSCT presenting with progressive cerebrovascular disorder and optic neuropathy without any clear alternative causal processes except for immune-mediated CNS microangiopathy in the context of possible CNS-cGVHD, along with suggestive imaging and instrumental and laboratory findings. Starting one year after HSCT for acute myeloid leukemia, when the first cerebral ischemic event occurred and was then associated with a reduction in visual acuity, an extensive diagnostic work-up had remained inconclusive over many years, leading us to the hypothesis of CNS-cGVHD and, therefore, to the start of immunosuppressive therapy. Our experience highlighted not ignoring the possibility of cGVHD as the underlying mechanism of CNS disorder, even in the absence of other systemic presentations, once more common etiologies of CNS pathological processes have been ruled out. Full article

Background/Objectives: Ischemic arterial stroke (AIS) is a cerebrovascular event that can occur acutely within the first hours or days of life, presenting as a neurological emergency. To date, clearly defined genetic risk factors for AIS have not been established, although certain genes involved in cerebrovascular regulation mechanisms are suspected to play a role. The Interferon Regulatory Factor 6 (IRF6) gene is a transcription factor involved in craniofacial and epidermal development. Recently, pathogenic variants of IRF6 have been implicated in the cytoprotective pathway of ischemic cerebrovascular disease. The aim of this manuscript is to further support the already-reported association between IRF6 and AIS. Materials and Methods: Genetic counseling and exome sequencing analysis were conducted for diagnostic purposes. Results: We report the case of a female newborn with palatoschisis, cleft palate, sensorineural deafness, facial dysmorphisms, and cutaneous defects who suffered an ischemic stroke in the territory of the left middle cerebral artery on day 1 of life. Family and pregnancy histories revealed no identifiable risk factors, and coagulation studies were normal. Exome sequencing identified a de novo c.1124T>C (p.Phe375Ser) variant in the IRF6 gene. The child developed right spastic hemiplegia and began motor rehabilitation therapy. Recently, a genome-wide association study (GWAS) using m6A-SNPs identified a statistical association between AIS and a single nucleotide polymorphism (SNP) that influences the expression of the IRF6 gene as an expression quantitative trait locus (eQTL). Conclusions: To our knowledge, this is the first report of neonatal ischemic stroke in a child carrying a de novo IRF6 pathogenic variant, further supporting its potential role as a genetic factor influencing cerebrovascular events. Further studies are needed to elucidate the precise relationship between IRF6 and AIS. Full article

Atherosclerosis is a chronic progressive disease which is known to cause acute cardiovascular events as well as cerebrovascular events with high mortality. Unlike many other diseases, atherosclerosis is often diagnosed only after an acute or fatal event. At present, the clinical problems of atherosclerosis mainly involve the difficulty in confirming the plaques or identifying the stability of the plaques in the early phase. In recent years, the development of nanotechnology has come with various advantages including non-invasive imaging enhancement, which can be studied for the imaging of atherosclerosis. For targeted imaging and atherosclerosis treatment, nanoliposomes provide enhanced stability, drug administration, extended circulation, and less toxicity. This review discusses the current advances in the development of tailored liposomal nano-radiopharmaceutical-based techniques and their applications to atherosclerotic plaque diagnosis. This review further highlights liposomal nano-radiopharmaceutical localisation and biodistribution—key processes in the pathophysiology of atherosclerosis. Finally, this review discusses the direction and future of liposomal nano-radiopharmaceuticals as a potential clinical tool for the assessment and diagnosis of atherosclerotic plaque. Full article