Cerebrovascular Research Articles

Evaluation of the causal effects of immune cells on ischemic stroke: a Mendelian randomization study

BackgroundIschemic stroke (IS) is a cerebrovascular disease caused by various factors, and its etiology remains inadequately understood. The role of immune system dysfunction in IS has been increasingly recognized. Our objective was to evaluate whether circulating immune cells causally impact IS risk.MethodsWe conducted two-sample Mendelian randomization analyses to evaluate the causal effects of 731 immune cell traits on IS, utilizing publicly available genome-wide association studies (GWAS) summary statistics for 731 immune cell traits as exposure data, and two GWAS statistics for IS as outcome data. A set of sensitivity analyses, including Cochran’s Q test, I2 statistics, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out sensitivity analyses, were performed to assess the robustness of the results. Additionally, meta-analyses were conducted to combine the results from the two different IS datasets. Finally, we extracted instrumental variables of immune cell traits with causal effects on IS in both IS datasets for SNP annotation.ResultsA total of 41 and 35 immune cell traits were identified to have significant causal effects on IS based on two different IS datasets, respectively. Among them, the immune cell trait CD62L- plasmacytoid Dendritic Cell AC and CD4+ CD8dim T cell%leukocyte respectively served as risk factor and protective element in both IS datasets. The robustness of the causal effects was confirmed through the sensitivity analyses. The results of the meta-analyses further support the causal effects of CD62L- plasmacytoid Dendritic Cell AC (pooled OR=1.030, 95%CI: 1.011–1.049, P=0.002) and CD4+ CD8dim T cell%leukocyte (pooled OR=0.959, 95%CI: 0.935–0.984, P=0.001). Based on these two immune cell traits, 33 genes that may be related to the causal effects were mapped.ConclusionsOur study demonstrated the potential causal effects of circulating immune cells on IS, providing valuable insights for future studies aimed at preventing IS.

Clinical Features and Analysis in Pituitary Stalk Interruption Syndrome

Objective. Pituitary stalk interruption syndrome (PSIS) is characterized by the absence of pituitary stalk, pituitary hypoplasia, and ectopic posterior pituitary. Because the etiology and clinical cognition of PSIS remain elusive, we analyzed the clinical features of PSIS in Chinese patients. Methods. A retrospective analysis was conducted on the clinical presentation, laboratory data, imaging examination, and management of 24 PSIS inpatients from our center over 10 years. Results. Among the 24 PSIS patients, there were 22 males (91.7%) and 2 females (8.3%). Growth hormone deficiency was present in all 24 cases (100%), hypogonadism in 24 cases (100%), secondary adrenal insufficiency in 22 cases (91.2%), and hypothyroidism in 21 cases (87.5%). 20 cases (83.3%) of PSIS patients exhibited deficiencies in four anterior pituitary hormones, 3 cases (12.5%) exhibited deficiencies in three anterior pituitary hormones, and 1 case (4.2%) exhibited deficiencies in two anterior pituitary hormones, with none exhibiting deficiencies in posterior pituitary hormones. Among the 24 PSIS patients, 12 had a history of growth hormone therapy before admission, and 12 had no such history. Additionally, 19 cases (79.2%) with PSIS were complicated by dyslipidemia, 15 cases (62.5%) were complicated by nonalcoholic fatty liver disease, and 9 cases (37.5%) were complicated by hyperuricemia. Conclusions. PSIS often presents with growth retardation and hypogonadotropic hypogonadism, but in some cases, short stature is not exhibited. PSIS is prone to complications such as dyslipidemia, nonalcoholic fatty liver disease, and hyperuricemia, increasing the risk of cardiovascular and cerebrovascular diseases. In clinical practice, the diagnostic ability of PSIS should be improved, and pituitary function and complications should be evaluated in a timely manner to avoid delayed treatment.

Spontaneous dissection of the carotid artery in a young patient with the development of ischemic stroke

Carotid artery dissection is a cerebrovascular disease, the cause of which is assumed to be connective tissue dysplasia. The provoking factors may be injury, infections, high-intensity sports. This disease can occur both asymptomatically and manifest itself with various neurological symptoms (headache, Gorner syndrome). In our clinical case, the young patient showed no signs of connective tissue dysplasia, nor provoking factors. Timely diagnosis contributed to the rapid determination of arterial dissection, and early treatment provided stabilization of the patient’s condition and regression of neurological deficit. The literature data on the diagnosis and treatment of the disease are presented.

Leading causes of death in Vietnamese Americans: An ecological study based on national death records from 2005-2020.

Disaggregated data is a cornerstone of precision health. Vietnamese Americans (VietAms) are the fourth-largest Asian subgroup in the United States (US), and demonstrate a unique burden of disease and mortality. However, most prior studies have aggregated VietAms under the broader Asian American category for analytic purposes. This study examined the leading causes of death among VietAms compared to aggregated Asian Americans and non-Hispanic Whites (NHWs) during the period 2005-2020. Decedent data, including underlying cause of death, were obtained from the National Center for Health Statistics national mortality file from 2005 to 2020. Population denominator estimates were obtained from the American Community Survey one-year population estimates. Outcome measures included proportional mortality, age-adjusted mortality rates per 100,000 (AMR), and annual percent change (APC) in mortality over time. Data were stratified by sex and nativity status. Due to large differences in age structure, we report native- and foreign-born VietAms separately. We identified 74,524 VietAm decedents over the study period (71,305 foreign-born, 3,219 native-born). Among foreign-born VietAms, the three leading causes of death were cancer (26.6%), heart disease (18.0%), and cerebrovascular disease (9.0%). Among native-born VietAms the three leading causes were accidents (19.0%), self-harm (12.0%), and cancer (10.4%). For every leading cause of death, VietAms exhibited lower mortality compared to both aggregated Asians and NHWs. Over the course of the study period, VietAms witnessed an increase in mortality in every leading cause. This effect was mostly driven by foreign-born, male VietAms. While VietAms have lower overall mortality from leading causes of death compared to aggregated Asians and NHWs, these advantages have eroded markedly between 2005 and 2020. These data emphasize the importance of racial disaggregation in the reporting of public health measures.

Cardiac and Neurological Complications Post COVID-19 Vaccination: A Systematic Review of Case Reports and Case Series

Following mass vaccinations for the control of the COVID-19 epidemic, a spectrum of cardiac and neurological disorders was reported among vaccinated individuals. This study examined the range of complications documented and factors related to their occurrence. Three electronic databases were searched for case reports and case series with descriptions of cardiac and/or neurological complications in COVID-19 vaccine recipients. A total of 698 vaccinees were included in this review, of which 259 (37.1%) had cardiac and 439 (62.9%) had neurological complications. Inflammatory conditions were the commonest among the cardiac complications; while polyneuropathy, demyelinating diseases and cerebrovascular disorders were the more common neurological complications. The mean age of those with cardiac complications (33.8 years) was much younger than those with neurological complications (49.7 years). There was no notable difference in the gender distribution between these two groups of vaccine recipients. mRNA vaccines (all brands) were associated with almost 90.0% of the cardiac complications, whereas viral vector vaccines were associated with slightly over half (52.6%) of the neurological complications. With regard to the dose, cardiac complications were more common after the second (69.1%), whereas neurological complications were more common after the first dose (63.6%). The majority of the cases had an uncomplicated clinical course. Nevertheless, 5.9% of cases with neurological complications and 2.5% of those with cardiac complications were fatal, underscoring the significance of the consistent surveillance and vigilant monitoring of vaccinated individuals to mitigate these occurrences.

Impact of homocysteine on acute ischemic stroke severity: possible role of aminothiols redox status

BackgroundAcute ischemic stroke (AIS) is one of the most common cerebrovascular diseases which accompanied by a disruption of aminothiols homeostasis. To explore the relationship of aminothiols with neurologic impairment severity, we investigated four aminothiols, homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CG) and glutathione (GSH) in plasma and its influence on ischemic stroke severity in AIS patients.MethodsA total of 150 clinical samples from AIS patients were selected for our study. The concentrations of free reduced Hcy (Hcy), own oxidized Hcy (HHcy), free reduced Cys (Cys), own oxidized Cys (cysteine, Cyss), free reduced CG (CG) and free reduced GSH (GSH) were measured by our previously developed hollow fiber centrifugal ultrafiltration (HFCF-UF) method coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The concentration ratio of Hcy to HHcy (Hcy/HHcy), Cys to Cyss (Cys/Cyss) were also calculated. The neurologic impairment severity of AIS was evaluated using National Institutes of Health Stroke Scale (NIHSS). The Spearman correlation coefficient and logistic regression analysis was used to estimate and perform the correlation between Hcy, HHcy, Cys, Cyss, CG, GSH, Hcy/HHcy, Cys/Cyss and total Hcy with NIHSS score.ResultsThe reduced Hcy and Hcy/HHcy was both negatively correlated with NIHSS score in AIS patients with P = 0.008, r=-0.215 and P = 0.002, r=-0.249, respectively. There was no significant correlation of Cys, CG, GSH, HHcy, Cyss, Cys/Cyss and total Hcy with NIHSS score in AIS patients with P value > 0.05.ConclusionsThe reduced Hcy and Hcy/HHcy, not total Hcy concentration should be used to evaluate neurologic impairment severity of AIS patient.

Estimating Flow Direction of Circle of Willis Using Dynamic Arterial Spin Labeling Magnetic Resonance Angiography.

The Circle of Willis (COW) is a crucial mechanism for cerebral collateral circulation. This proof-ofconcept study aims to develop and assess an analysis method to characterize the hemodynamics of the arterial segments in COW using arterial spin labeling (ASL) based non-contrast enhanced dynamic magnetic resonance angiography (dMRA). The developed analysis method uses a graph model, bootstrap strategy, and ensemble learning methodologies to determine the time-curve shift from ASL dMRA to estimate the flow direction within the COW. The performance of the method was assessed on 52 subjects, using the flow direction, either antegrade or retrograde, derived from 3D phase contrast (PC) MRI as the reference. A total of 340 arterial segments in COW were evaluated, among which 30 (8.8%) had retrograde flow according to 3D PC. The ASL dMRA-based flow direction estimation has an accuracy, sensitivity, and specificity of 95.47%, 80%, and 96.34%, respectively. Using ASL dMRA and the developed image analysis method to estimate the flow direction in COW is feasible. This study provides a new method to assess the hemodynamics of the COW, which could be useful for the diagnosis and study of cerebrovascular diseases. COW = Circle of Willis; ASL = arterial spin labeling; dMRA =dynamic magnetic resonance angiography; PC = phase contrast.

B.3 Neuroimaging markers of cerebrovascular disease and cognition in adults with moderate-great complexity congenital heart disease

Background: Adults with congenital heart disease (ACHD) are at risk for stroke and dementia. We report baseline and Year 1 results from an ongoing study assessing brain health in people with moderate- and great-complexity ACHD. Methods: Participants aged ≥18 undergo baseline and Year-3 brain MRI/MRA and annual cognitive assessment (MoCA, NIH Toolbox-Cognitive Battery (NIH-TB)). Results: Of 93 participants to date, 79 (85%) have completed Year 1 follow-up. At baseline, the great-complexity group had lower MoCA (26.32 vs. 27.38; p=0.04) and NIH-TB scores (total composite 45.63 vs. 52.80; p=0.002) than the moderate-complexity group. Year-1 testing showed numerical improvements across cognitive batteries in both groups. More participants with great-complexity ACHD had white matter hyperintensities (WMH; 72% vs. 55%; p=0.21) and cerebral microbleeds (CMBs; 72% vs. 54%; p=0.17) on baseline neuroimaging, but differences were not significant. Conclusions: Baseline neuroimaging shows a greater-than-expected burden for age of CMB and WMH in the context of previous cardiac surgery. Baseline cognitive performance was worse with great-complexity ACHD. Improved cognitive battery performance across both subgroups at Year-1 suggests a practice effect. Repeat neuroimaging will be performed in Year-3 and cognitive performance is reassessed annually.

#2183 Does thrombotic microangiopathy drive the occurrence and pattern of cerebrovascular disease in malignant hypertension?

Abstract Background and Aims Malignant hypertension (MHT) is characterized by diffuse microvascular damage caused by severe hypertension, often presenting with multiple organ involvement. Cerebrovascular injury, occurring in both acute and chronic forms, stands as a hallmark of the disease, being identified in up to half of patients. Thrombotic microangiopathy (TMA), defined as the association of mechanical hemolytic anemia with thrombocytopenia, also emerges as a frequent complication in MHT patients. However, the potential contribution of TMA to cerebrovascular disease remains unexplored. The secondary objective of this study was to provide a comprehensive description of the patterns of cerebrovascular injury occurring in MHT, with a focus on acute ischemic strokes (AIS). Method We retrospectively assessed the brain MRI of patients admitted to the kidney intensive care unit at Tenon hospital for malignant hypertension during the 2017-2023 period. Brain MRIs were performed on a systematic basis regardless of neurological symptoms and were independently reviewed by two trained specialists in a blinded fashion. Patterns of acute cerebrovascular disease, defined as AIS, intracerebral hematoma (ICH) or posterior reversible encephalopathy syndrome (PRES), were systematically assessed. Number of AIS lesions, their size and localization were recorded. Underlying chronic cerebral small vessel disease (CSVD) was defined as presence of lacunes, white matter hyperintensities, cerebral microbleeds or perivascular spaces. Severity of the chronic cerebrovascular disease was measured using a validated CSVD score. Results A total of 60 patients were admitted for malignant hypertension, with a mean age of 42.9 years. 40 patients (66.7%) presented with severe acute kidney injury. Cerebrovascular disease, either acute or chronic, was found in 42 patients (70.0%). Underlying chronic CSVD was present in 33 patients (55.0%). Acute patterns of injury occurred in 27 patients (45.0%). AIS was the most frequent (33.3%), followed by PRES (21.7%). Only one patient presented with ICH. Among patients with AIS, 14 (70%) presented with multiple simultaneous lesions. Of note, most patients with AIS exhibited diffuse encephalopathy syndrome (60.0%) rather than focal deficit (40.0%). Systemic TMA was present at admission in 34 patients (56.7%). In an exploratory data analysis, presence of AIS on brain MRI was associated with the presence of underlying CVSD (p = 0.013), but not with the presence of TMA at admission (p = 0.79). No association was found between TMA and PRES (p = 0.22). Conclusion Our study confirmed the high incidence of cerebrovascular disease during MHT. Most notably, 1 in 3 patients presented with AIS. TMA did not appear to increase the incidence nor to influence the pattern of brain injury.

Photobiomodulation Inhibits Ischemia-Induced Brain Endothelial Senescence via Endothelial Nitric Oxide Synthase

Recent research suggests that photobiomodulation therapy (PBMT) positively impacts the vascular function associated with various cerebrovascular diseases. Nevertheless, the specific mechanisms by which PBMT improves vascular function remain ambiguous. Since endothelial nitric oxide synthase (eNOS) is crucial in regulating vascular function following cerebral ischemia, we investigated whether eNOS is a key element controlling cerebrovascular function and the senescence of vascular endothelial cells following PBMT treatment. Both rat photothrombotic (PT) stroke and in vitro oxygen–glucose deprivation (OGD)-induced vascular endothelial injury models were utilized. We demonstrated that treatment with PBMT (808 nm, 350 mW/cm2, 2 min/day) for 7 days significantly reduced PT-stroke-induced vascular permeability. Additionally, PBMT inhibited the levels of endothelial senescence markers (senescence green and p21) and antiangiogenic factor (endostatin), while increasing the phospho-eNOS (Ser1177) in the peri-infarct region following PT stroke. In vitro study further indicated that OGD increased p21, endostatin, and DNA damage (γH2AX) levels in the brain endothelial cell line, but they were reversed by PBMT. Intriguingly, the beneficial effects of PBMT were attenuated by a NOS inhibitor. In summary, these findings provide novel insights into the role of eNOS in PBMT-mediated protection against cerebrovascular senescence and endothelial dysfunction following ischemia. The use of PBMT as a therapeutic is a promising strategy to improve endothelial function in cerebrovascular disease.

#488 Differences in characteristics and outcomes between Patients suffering AKI in medical vs surgical ICU units

Abstract Background and Aims AKI is a public health problem, affecting one in every five hospitalized adults. It's incidence in the ICU fluctuates between 16-36%, with a mortality rate between 28%-50%. The need for HD in the ICU varies from 3-7%, and these patients have twice the risk of death. But few studies have compared patients in medical (MD-ICU) and surgical (Qx-ICU) critical care units. Method We conducted a single center, retrospective study of individuals admitted to ICU units that underwent nephrology consultation. We examined a 5-y period, in the pre-COVID era, we excluded the pandemic period, because COVID patients were admitted to MD- and Qx-ICU indistinctly. We compared epidemiological and clinical characteristics and hard outcomes between patients in both groups. Results We included 433 patients, 42% in the MD-ICU. We found no statistical differences between sex, HTN, DM, Charlson's-Index, and previous CKD. Qx-ICU patients were older, suffered less Coronary Artery (CAD), and Cerebrovascular Disease (CVD), and their AKI etiology was more frequently obstructive. MD-ICU individuals showed less hospital acquired AKI, and were more frequently classified in KDIGO Stage 3, (Fig. A, Features). We found no differences in time to nephrology consultation, length of hospital-stay and in-hospital mortality. Qx-ICU patients had shorter ICU stay, needed less frequently acute HD, and were less HD dependent at discharge (Fig. B, Results). In-hospital mortality for patients that needed HD in MD-ICU OR 2.2 (1.2-4.1, P = 0.12), Qx-ICU OR 4.4 (2.2-8.6, P < 0.001). Conclusion Individuals don't differ remarkably in their baseline clinical characteristics (Charlson`s, DM, CKD). Nevertheless, Qx-ICU patients are older, suffer less CAD, and CVD, and show significantly more hospital acquired AKI. We found that medical ICU patients suffered worst AKI stage, longer ICU stay, required acute HD and were HD dependent more frequently, but had a lower risk of death when needing acute HD. We found no differences in general mortality rate, and general hospital stay, and time to nephrology consultation between groups. We need multicentric and well-powered studies to explore these differences more profoundly, find clusters of patients and phenotypes of AKI and discover protective factors and new preventive measures against hospital acquired AKI, and need for acute HD.

#308 The impact of multimorbidity on the effects of empagliflozin in chronic kidney disease (CKD): exploratory analyses from the EMPA-KIDNEY trial

Abstract Background and Aims Sodium-glucose co-transporter-2 (SGLT2) inhibitors slow kidney disease progression and reduce cardiovascular risk in patients with CKD. Multimorbidity is common in CKD and associated with poor prognosis. Multimorbidity may identify patients with most to gain from, or at increased risk of adverse effects of, such treatment, so uncertainty exists around the risk-benefit profile. We assessed the effects of empagliflozin according to baseline multimorbidity, polypharmacy and health-related quality of life in EMPA-KIDNEY trial participants. Method EMPA-KIDNEY was a double-blind, placebo-controlled randomised trial which compared empagliflozin 10 mg once daily versus placebo among 6609 patients with CKD (Clinicaltrials.gov: NCT03594110). Eligible patients had an eGFR of 20 to <45; or 45 to <90 ml/min/1.73 m2 with a urinary albumin-to-creatinine ratio (uACR) ≥200 mg/g. Multimorbidity was defined by the presence or absence of eight self-reported conditions at randomisation (diabetes, heart failure, ischaemic heart disease [any history of myocardial infarction or angina], cerebrovascular disease [any history of stroke or transient ischaemic attack], peripheral arterial disease, atrial fibrillation, peripheral neuropathy and gout), in addition to CKD. Polypharmacy was derived from the number of concomitant medications recorded at randomisation. Health-related quality of life at randomisation was assessed using the EuroQoL EQ-5D-5L tool. To enable subgroup analyses, participants were categorised into approximate thirds of each variable's distribution. The relative effects of allocation to empagliflozin versus placebo on the trial's pre-specified efficacy and safety outcomes were assessed using Cox regression models adjusted for age, sex, region, eGFR, uACR and diabetes status. Tests for heterogeneity across subgroups were used to assess for any evidence that multimorbidity modifies relative treatment effects, and used to inform approaches to estimate absolute benefits. Results The median (Q1-Q3) number of comorbid conditions (other than CKD) recorded at randomisation was 1 (0-2); range 0-7. At randomisation, the median (Q1-Q3) number of concomitant medications recorded was 7 (5-10), range 0-36, and polypharmacy (≥5 medications) was prevalent in 5044/6609 (76%) of participants. There was considerable overlap between multimorbidity, polypharmacy and deficits in health-related quality of life (Fig. 1). Empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death by 28% (hazard ratio 0.72, 95% CI 0.64-0.82). There was no evidence of heterogeneity relative effects by categories reflecting multimorbidity, nor by level of polypharmacy or self-reported quality of life at randomisation (P value for heterogeneity all >0.05; Fig. 2). Absolute benefits for the primary outcome were at least as large in the highest categories of multimorbidity or polypharmacy versus the lowest (and for those with poorer versus greater health-related quality of life). Safety outcomes were infrequent with no evidence of a difference in effect by baseline levels of multimorbidity, polypharmacy or quality of life, including no excess of symptomatic dehydration or fractures. Conclusion In EMPA-KIDNEY, the estimated absolute benefits of empagliflozin on kidney disease progression or cardiovascular death substantially outweigh potential for harm, irrespective of multimorbidity, polypharmacy or quality of life. The analyses encourage safe widespread use of SGLT2 inhibitors in CKD.

Local Application of Tanshinone IIA protects mesenchymal stem cells from apoptosis and promotes fracture healing in ovariectomized mice

BackgroundElderly patients suffering from osteoporotic fractures are more susceptible to delayed union or nonunion, and their bodies then are in a state of low-grade chronic inflammation with decreased antioxidant capacity. Tanshinone IIA is widely used in treating cardiovascular and cerebrovascular diseases in China and has anti-inflammatory and antioxidant effects. We aimed to observe the antioxidant effects of Tanshinone IIA on mesenchymal stem cells (MSCs), which play important roles in bone repair, and the effects of local application of Tanshinone IIA using an injectable biodegradable hydrogel on osteoporotic fracture healing.MethodsMSCs were pretreated with or without different concentrations of Tanshinone IIA followed by H2O2 treatment. Ovariectomized (OVX) C57BL/6 mice received a mid-shaft transverse osteotomy fracture on the left tibia, and Tanshinone IIA was applied to the fracture site using an injectable hydrogel.ResultsTanshinone IIA pretreatment promoted the expression of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes, and inhibited H2O2-induced reactive oxygen species accumulation in MSCs. Furthermore, Tanshinone IIA reversed H2O2-induced apoptosis and decrease in osteogenic differentiation in MSCs. After 4 weeks of treatment with Tanshinone IIA in OVX mice, the bone mineral density of the callus was significantly increased and the biomechanical properties of the healed tibias were improved. Cell apoptosis was decreased and Nrf2 expression was increased in the early stage of callus formation.ConclusionsTaken together, these results indicate that Tanshinone IIA can activate antioxidant enzymes to protect MSCs from H2O2-induced cell apoptosis and osteogenic differentiation inhibition. Local application of Tanshinone IIA accelerates fracture healing in ovariectomized mice.

#842 Validation of the excessive salt intake screening questionnaire in CKD patients

Abstract Background and Aims Excessive salt intake is implicated in the progression of hypertension, chronic kidney disease (CKD), diabetic nephropathy, cardiovascular diseases, cerebrovascular diseases, and increased mortality. In Japan, average salt consumption surpasses the levels recommended by national guidelines and the WHO. However, individuals seldom have the chance to gauge their salt intake accurately. This study aimed to validate a screening tool initially developed by Sasaki et al. to identify individuals with excessive salt intake using health check-up data from Asahi City, Chiba Prefecture, Japan. Method This study was conducted as a part of the Cities Changing Diabetes (CCD). CCD is Novo Nordisk's commitment to drive action against type 2 diabetes and obesity in cities globally. It is a partnership program to accelerate the prevention of diabetes and obesity by addressing the systemic change in urban environments. Participants of this study were drawn from specific health examinations in Asahi City. Consent was obtained, and dialysis patients were excluded. Spot urine samples were analyzed for sodium and creatinine to estimate daily salt intake via Tanaka's formula. The screening tool incorporated risk factors such as age, gender, Body Mass Index (obesity), hypertension (use of antihypertensive drugs), frequency of soup intake, saltiness of home-cooked meals compared to restaurants, efforts to reduce salt intake, and frequency of dining out. The primary outcome was excessive salt intake, defined as an intake exceeding one standard deviation above the mean. Discrimination was assessed using the Area Under the Curve (AUC), while calibration was evaluated with a calibration plot and the Hosmer-Lemeshow test. Results Of the 1532 CKD participants, the mean age was 76.3 years, with males comprising 46%. The average daily salt intake was 9.3 g (SD: 2.39), and the estimated Glomerular Filtration Rate (GFR) was 50.6 ml/min/1.73 m² (SD: 14.5). The distribution of CKD stages included 1198 stage 3a, 285 stage 3b, 43 stage 4, and 5 stage 5 patients. The AUC of screening tool was 0.65 (95% CI: 0.61 to 0.69), and its calibration slope (with an intercept) was 0.98 (95% CI: 0.72 to 1.25). The Hosmer-Lemeshow test yielded a p-value of 0.626. Conclusion The predictive capability of the existing model for excessive salt intake was limited in the CKD population, which may suggest a need for a screening method distinct from that used in the general population. Factors such as changes in sodium excretion due to reduced renal function and the effects of diuretics should also be considered when interpreting these results. Integrating this questionnaire into routine health check-ups could enhance dietary monitoring and intervention, potentially attenuating the progression of CKD and its associated complications. There remains scope for further refinement of the tool's accuracy by incorporating additional predictors.

#2022 Clinical outcomes in US patients initiating finerenone – a report from the FOUNTAIN platform

Abstract Background and Aims Evidence from clinical trials demonstrates that finerenone reduces the risk of cardiovascular and renal complications among patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). What is lacking is the evidence on finerenone use in real-world clinical practice. Method The present analysis is based on a longitudinal single-arm cohort study of patients initiating finerenone between July 2021 and August of 2023 and with prior diagnoses of CKD and T2D. Data were obtained from US electronic health records and insurance claims (OM1 Real-World Data CloudTM). CKD was defined as either having 1 diagnostic code for CKD stage 2-4 or unspecified stage, two estimated glomerular filtration rate (eGFR) measurements between 15 and 60 ml/min/1.73 m2, or two urine albumin to creatinine ratio (UACR) measurements over 30 mg/g; T2D was defined as having a diagnostic code for T2D. We described patient demographics, comorbidities, and comedications at baseline (365 days prior and including index date), and incidence rates of cardiovascular and renal outcomes, including eGFR and UACR changes over time. The presented analysis (NCT05703880) is part of the multi-national, multi-database observational research platform FOUNTAIN. Results We identified 28,056 new users of finerenone with prior CKD and T2D. The users had a mean (SD) age of 68.8 (10.8) years and 44.8% were female. Comorbidities of interest at baseline were hypertension (89.8%), cardiovascular disease (21.2%), neuropathy (13.4%), retinopathy (8.1%), heart failure (7.9%), and cerebrovascular disease (4.2%). Assessment of comedication use at baseline indicates that patients who initiate finerenone had exposure to renin–angiotensin system inhibitors (52.5%), sodium-glucose cotransporter-2 inhibitors (39.2%), or glucagon-like peptide-1 receptor agonists (27.4%) within 180 days prior to initiating finerenone. Overall, 82.5% of patients initiated finerenone at 10 mg/d, while 17.5% of patients started with 20 mg/d. Complete results including incidence rates of cardiovascular and renal outcomes, hyperkalemia events, and changes in kidney function measures (eGFR, UACR) during follow-up will be presented as part of the conference presentation. Conclusion Data from patients receiving finerenone as part of clinical practice in the USA suggest that finerenone is used concurrently with other renal and cardiovascular protective medication-classes recommended for patients with CKD and T2D.

#2141 Lipoprotein a levels and atherosclerotic cardiovascular disease in hemodialysis patients

Abstract Background and Aims Lipoprotein a (Lp(a)) is an LDL cholesterol-like particle to which two apolipoprotein(a) molecules are attached. Epidemiological and genetic studies strongly support a causal and continuous association between Lp(a) concentration and atherosclerotic cardiovascular (CV) disease, including aortic valve stenosis, even with low levels of low-density lipoprotein cholesterol. On the other hand, it is well known that patients on hemodialysis (HD) have high comorbidity due to cardiovascular pathology. Method We conducted a cross-sectional, observational, retrospective study in a cohort of patients on HD, with the aim of evaluating whether there was any correlation between Lp(a) concentration and atherosclerotic cardiovascular disease (ASCVD). For this purpose, in December 2023 we measured Lp(a) levels (in nmol/L) in all prevalent HD patients in the province of Cáceres (Spain) and collected their major adverse coronary events (MACE): acute myocardial infarction (AMI) and angina, as well as major adverse non-coronary cardiovascular events (MANCE): cerebrovascular disease and peripheral artery disease. Aortic valve stenosis/calcification was also assessed by echocardiography. SPSS version 21 software was used for statistical analysis. Results A total of 214 patients were included, 68.7% male, with a mean age of 70.5 years. The mean Lp(a) value was 76.9 nmol/L, without differences in both sexes. A total of 66.4% had Lp(a) < 75 nmol/L and 23.8% had levels ≥ 125 nmol/L. The main cardiovascular event was peripheral artery disease (14.9%), followed by AMI (14.1%), aortic valve stenosis (10.7%), stroke (8.4%), angina (2.8%) and transient ischemic attack (1.4%). Some 23.4% (50 patients) had a CV event and, among them, almost half (42%) had Lp(a) levels >75 nmol/L. A statistically significant linear correlation was found between Lp(a) concentration and AMI (p 0.03) and aortic valve stenosis (p 0.001). No correlation was observed between Lp(a) and the other CV events analyzed (peripheral artery disease, stroke, angina, transient ischemic attack), nor between Lp(a) and sex. Conclusion There is a linear and positive correlation between Lp(a) levels and coronary pathology, and with aortic valve stenosis in HD patients in the cohort studied. Studies are needed to assess whether reducing their levels reduces cardiovascular disease in these patients.

#2598 Risk of vascular access complications in haemodialysis patients initiating dialysis with arteriovenous fistula or arteriovenous graft

Abstract Background and Aims Patients (pts) with end-stage kidney disease (ESKD) rely on successful vascular access (VA) for continual hemodialysis (HD) treatments. Possible VA complications are numerous and complex, which makes them difficult to study. We developed a comprehensive VA complication metric to evaluate VA complications holistically. The goal of this analysis was to describe the risk of having high VA complications in in-center hemodialysis (ICHD) pts whose initial VA included arteriovenous fistula (AVF) or arteriovenous graft (AVG), and who have been successfully receiving regular dialysis care for at least 2 years. Method Adult ICHD pts, with Charlson Comorbidity Index <8, who initiated treatment at one of the clinics of a large dialysis organization between Jan 2016 and Dec 2021, received continuous treatment for ≥2 years, remained on ICHD until censored, and whose initial VA included an AVF or an AVG were investigated. Pts could be censored by death, transplant, discharge from FKC, or study end. Initial VA was determined by use of either AVF or AVG during ICHD treatments in the 90-120 days after initiation of ICHD. Individual-level vascular access complication rates (VACR) were defined as the sum of a patient's VA complication events divided by their duration of follow-up until censor date. VA complication events include: hospitalization due to VA problems or VA infection, VA infections not requiring hospitalization, VA removal due to infection, symptoms of VA infection, symptoms of thrombosis/stenosis, documented stenosis, documented thrombosis, cannulation issues, bacteremia, sepsis. The threshold for high VACR was the highest quintile values. Logistic regression was used to determine the risk of having a high VACR by demographic and comorbid conditions. Results Analyses included 94,208 pts who met our inclusion criteria. The mean VACR for the population was 2.7 VA complications per patient per year (PPY). Pts whose VACR was in the highest quintile, ≥4.34 PPY, were categorized as having high VACR. Table 1 shows the risk of having high VACR by demographic characteristics and comorbid conditions present at ICHD initiation. In general, we observed lower or neutral risk of having high VACR in the demographic characteristics we examined. However, older patients as well as patients with higher BMI had an increase in risk of having high VACR. We observed significant increased risk of having high VACR in diabetic pts (20%), pts with cerebrovascular disease (35%), pts with COPD (10%), pts with Congestive Heart Failure (21%), patients with dementia (22%), and patients with history of myocardial infarction (26%). Conclusion We observed that being older, having increased BMI, or having several comorbid conditions are associated with increased risk of having high VACR in successful ICHD patients who initiated dialysis with an AVF or AVG. Multivariate analyses to further explore these associations are warranted.

#3031 Cell free DNA methylation analysis reveals cerebral cell death during hemodialysis

Abstract Background and Aims Patients treated with hemodialysis demonstrate a significant cognitive decline, likely explained by cerebrovascular disease and hypoperfusion. Despite the significant morbidity and mortality associated, no method exists to detect subclinical cerebral injury. This prevents early diagnosis and precludes mitigation strategies. Following cell death, cell free DNA (cfDNA) is released into the peripheral blood. Since DNA methylation is cell-type specific, cfDNA methylation analysis can reveal the cellular origin of cfDNA and cell-type specific changes in cell death. Here, we evaluate if subclinical cerebral ischemia during hemodialysis is detectable through cfDNA methylome analyses. Method Chronic hemodialysis patients with a high cardiovascular risk profile were studied during a single hemodialysis session. Brain tissue oxygenation was measured continuously by near-infrared spectroscopy using two sensors on the forehead. Plasma samples were taken immediately before and after hemodialysis. cfDNA was extracted from the blood plasma and converted into whole genome bisulfite sequencing libraries using tailored protocols. Next, in-solution target enrichment was applied to analyze 4,989 genomic loci, selected for showing specific methylation in one of 15 tissues or cell types. After sequencing, reads were aligned to the hg38 reference genome using BisMark, and deconvoluted using EMeth-Laplace to disclose the relative contribution of the 15 selected tissues or cell types. Results 41 hemodialysis patients participated in the study, with a mean age of 75 ± 8 years (46% male). The median ultrafiltration volume was 2.3 L (IQR 1.6-3.0 L). After targeted bisulfite sequencing and QC-based filtering, 35 patients remained for cfDNA methylation analysis. In 30 patients, cfDNA concentrations were increased following dialysis. Deconvolution analysis revealed a relative increase in granulocyte-derived cfDNA from 36.7% to 55% before versus after dialysis. Consequently, for most other tissues and cell types we observed a relative decrease in their cfDNA contribution. Interestingly, a subset of patients (n = 13) showed an increase in neuron-derived cfDNA from 0% to 0.26%, while no neuron-derived cfDNA was detectable in the remaining 22 patients. Near-infrared spectroscopy showed a significantly reduced cerebral oxygenation in these 13 patients (P < 0.0001) at 2 separate time windows during hemodialysis treatment (at 20-60 and 207-251 minutes into the session) (Fig.). Conclusion In patients with a high cardiovascular risk profile, cfDNA in peripheral blood increased after hemodialysis. cfDNA methylome analyses suggested this to be due to an increased contribution of granulocytes, indicating elevated levels of NETosis. In addition, we observed more neuron-derived cfDNA after dialysis in about 1 in 3 patients. This was most apparent in patients with a reduced brain tissue oxygenation during hemodialysis. Together, these findings suggest that hypoperfusion during hemodialysis can evoke neuronal cell death, detectable through methylome analyses of cfDNA isolated from a minimally invasively obtainable bodily fluid. Follow-up studies are ongoing to assess if this translates to progressive cognitive impairment.

#445 Octogenarians in hemodialysis: not everyone ages the same

Abstract Background and Aims The average life expectancy in Western Europe in 2022 was 79 years for males and 84 years for females. Over the past years, the number of ageing patients in hemodialysis (HD) has increased significantly in all countries. There are several considerations for dialysis maintenance in older patients with an increased burden of age-related problems. It is important to identify the specific characteristics of this elderly population to develop appropriate care strategies and to estimate future needs for renal support services. The aim was to describe the clinical characteristics of our prevalent dialysis population by age, with particular reference to octogenarians. Method In this retrospective observational study between 2008 and 2022, the medical charts of 253 prevalent HD patients in a referral university hospital were analyzed. Patients were divided into four groups according to their age (four age groups: ≤60, 61–70, 71–80, 80> years old). Patient demographics and comorbidities were compared between age groups. Percentage and type of AVF (arteriovenous fistula), primary failures, and AVF reparations were recorded at onset of HD and at follow-up. Interdialytic weigh gain (average for pre-dialysis measurement of three hemodialysis sessions per week for two weeks) was also informed. Results 57 patients older than 81 years underwent dialysis (mean age 85.2±3.3 years), 31 (54%) older than 84 years (11 women, 20 men). 48% of patients over the age of 80 had to start HD urgently. In octogenarian, length on time in hemodialysis was 4.3 ± 6.46 years, they were no differences based on age; vintage HD in women and men older than 84 years was 5.2 ± 3.4 years and 5.3 ± 3.7 years, respectively. Females accounted for 40.4%, higher than other age groups, but not statistically significant. None of the over-80s self-reported active smoking, with differences between groups (p=0,000). Diabetes was less common in the youngest and oldest patients (23.9%vs 49.1%vs 56.8% vs 43.9% for patients ≤60, 61-70, 71-80 and 80>age, respectively, p=0.001). Similar trends were observed for ischemic heart disease and peripheral vascular disease (3%vs23,6%vs25,7% vs15,7% and 9%vs27,3%vs24,3vs15,8%; p=0,000 and p=0,035, respectively). Among octogenarians, 36.8% had experienced heart failure, the highest proportion of any age group (14,9%vs23,6%vs25,7% vs36,8% for patients ≤60, 61-70, 71-80 and 80>age, p=0.046), but interdialytic gains were not greater in this group than in others (70%vs53,7%vs45,9%vs47,4% for patients ≤60, 61-70, 71-80 and 80>age, p=0.019). Chronic lung disease occurred significantly less often in octogenarians compared to younger patients (17,9%vs30,9%vs36,5%vs15,2% in the ≤60, 61-70, 71-80 and 80> age groups respectively (p=0.026). Cerebrovascular disease and active neoplasm did not differ based on age. Underlying chronic kidney disease was unknown in 28.1% of patients over 80 years of age. Diabetic nephropathy was the main known condition of nephropathy (16,4%vs27,3%vs23%vs15,8% for patients ≤60, 61-70, 71-80 and 80>age, p=0.052). (see Table 1). In all age groups, AVF was the most common VA in incident and in prevalent HD patients (52,2%vs61,8%vs62,2%vs 77,2% and 82,1%vs80%vs86,5%vs 78,9 % in the ≤60, 61-70, 71-80 and 80> age groups respectively (p=0,086, p=0,640)). Radio-cephalic made up the largest proportion of AVFs in the total population. VA primary failure is more common in octogenarians (1,5%vs16,4%vs10,8%vs19,3% for patients ≤60, 61-70, 71-80 and 80> age, p=0.010). There were no differences in the need for AVF repair between groups (see Table 2). Conclusion Our octogenarian HD population is a selected population with a lower-than-expected comorbidity burden compared to younger age groups. Very elderly patients are more compliant and survive more than five years after HD initiation. Although vascular access may be more difficult to achieve initially, the outcome is comparable to that of younger patients in our study. Strategies to best manage this vulnerable hemodialysis population remain to be explored.

Cerebral venous thrombosis and deep medullary vein thrombosis: Padua experience over the last two decades.

Cerebral venous thrombosis (CVT) is a cerebrovascular disorder that accounts for 20% of perinatal strokes. CVT incidence ranges from 0.67 to 1.12 per 100,000 newborns, while the incidence of "deep medullary vein thrombosis" (DMVT), a subtype of CVT, cannot be accurately estimated. This study aims to analyze the case history of CVT in the neonatal period, with a specific focus on DMVT. Newborns diagnosed with CVT, with or without DMVT, between January 2002 and April 2023, were collected using the Italian Registry of Infantile Thrombosis (RITI). Cerebral MRIs were reviewed by an expert neuroradiologist following a standardized protocol. Forty-two newborns with CVT were identified, of which 27/42 (64%) had CVT, and the remaining 15/42 (36%) had DMVT (isolated DMVT in 9/15). Symptom onset occurred in the first week of life (median 8days, IQR 4-14) with a male prevalence of 59%. The most common risk factors for CVT were complicated delivery (38%), prematurity (40%), congenital heart diseases (48%), and infections (40%). Seizures were the predominant presenting symptom in 52% of all cases. Hemorrhagic infarction was higher in cases with isolated DMVT (77%) compared to patients with CVT without DMVT (p = 0.013). Antithrombotic treatment was initiated in 36% of patients. Neurological impairment was observed in 48% of cases at discharge, while 18 out of 31 infants (58%) presented one or more neurological deficits at long term follow up. Conclusion:DMVT occurs in over a third of neonates with CVT. Multicentric studies are essential to establish standardized protocols for therapy, neuroimaging, and follow-up in these patients.