Study of type 1 vascular adhesion molecules in patients with acute myocardial infarction with ST segment elevation at different body weights

Objective: to study the level of adhesion molecules in patients with STEMI with different BMI at the hospital stage and 12 months after the index event.Materials and methods: the study included 126 people with STEMI who had undergone PCI and 27 people in the control group. The analysis of the level of svcam‑1 in peripheral blood at the beginning of the disease and after 12 months was carried out, BMI and waist volume were measured. An assessment of the nature and frequency of complications after STEMI was performed.Results: the levels of biomarkers of the vascular endothelial adhesion molecule type 1 increase during the acute period of stemi, statistically signifi tly decrease, but remain increased by 3.5 times 12 months after the index event compared with the initial values. There was no association of VCAM‑1 with visceral obesity in the groups of our patients. Vascular endothelial adhesion molecules of type 1 increase in patients with a fatal outcome, as well as with an increase in the severity of OSN and CHF. Thus, VCAM 1 can be a predictor of an unfavorable outcome of AMI.Conclusions: the article presents the study of a marker of systemic inflammation VCAM‑11 in patients with STEMI with various types of obesity or BMI at the stage of hospitalization and outpatient follow‑up during the year. The determination of the VCAM‑1 level can be used to assess the intensity of the inflammatory process and the risk of adverse outcomes.

One-Year Risk of Stroke After Transient Ischemic Attack or Minor Stroke in Hunter New England, Australia (INSIST Study)

Background: One-year risk of stroke in transient ischemic attack and minor stroke (TIAMS) managed in secondary care settings has been reported as 5–8%. However, evidence for the outcomes of TIAMS in community care settings is limited.Methods: The INternational comparison of Systems of care and patient outcomes In minor Stroke and TIA (INSIST) study was a prospective inception cohort community-based study of patients of 16 general practices in the Hunter–Manning region (New South Wales, Australia). Possible-TIAMS patients were recruited from 2012 to 2016 and followed-up for 12 months post-index event. Adjudication as TIAMS or TIAMS-mimics was by an expert panel. We established 7-days, 90-days, and 1-year risk of stroke, TIA, myocardial infarction (MI), coronary or carotid revascularization procedure and death; and medications use at 24 h post-index event.Results: Of 613 participants (mean age; 70 ± 12 years), 298 (49%) were adjudicated as TIAMS. TIAMS-group participants had ischemic strokes at 7-days, 90-days, and 1-year, at Kaplan-Meier (KM) rates of 1% (95% confidence interval; 0.3, 3.1), 2.1% (0.9, 4.6), and 3.2% (1.7, 6.1), respectively, compared to 0.3, 0.3, and 0.6% of TIAMS-mimic-group participants. At one year, TIAMS-group-participants had twenty-five TIA events (KM rate: 8.8%), two MI events (0.6%), four coronary revascularizations (1.5%), eleven carotid revascularizations (3.9%), and three deaths (1.1%), compared to 1.6, 0.6, 1.0, 0.3, and 0.6% of TIAMS-mimic-group participants. Of 167 TIAMS-group participants who commenced or received enhanced therapies, 95 (57%) were treated within 24 h post-index event. For TIAMS-group participants who commenced or received enhanced therapies, time from symptom onset to treatment was median 9.5 h [IQR 1.8–89.9].Conclusion: One-year risk of stroke in TIAMS participants was lower than reported in previous studies. Early implementation of antiplatelet/anticoagulant therapies may have contributed to the low stroke recurrence.

Rationale, Design and Methods of the Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA (PRODAST) Study

Background The optimal timing of anticoagulation following acute ischaemic stroke or TIA in patients with atrial fibrillation (AF) is a frequent challenge. Early initiation of anticoagulation can reduce the risk for recurrent ischaemic events, but may lead to an increased risk for intracerebral haemorrhage. Aim The Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA (PRODAST) study was initiated to investigate outcome events under antithrombotic therapy after ischaemic stroke or TIA in patients with AF. The main objective is to compare the three-month rates of major haemorrhagic events between early (≤ 7 days) versus late (> 7 days) administration of dabigatran or treatment with vitamin-K antagonists started at any time. Occurrences of ischaemic and major haemorrhagic events will be evaluated to determine the optimal time point for initiation or resumption of anticoagulation. Design and Methods PRODAST is a prospective, multicenter, observational, non-interventional post-authorization safety study. 10,000 patients with recent (≤ 1 week from index event) ischaemic stroke or TIA and non-valvular AF were recruited at 86 German sites starting in July 2015. The observational plan includes a baseline visit, documentation of data during hospitalization and a telephone-based, central follow-up at three months after the index event. The primary endpoint is the major bleeding rate within three months. Secondary endpoints include rates of recurrent ischaemic or haemorrhagic stroke, TIA, systemic embolism, myocardial infarction and death. Summary PRODAST will provide important real-world data on safety and efficacy of antithrombotic therapy after acute stroke and TIA in patients with AF.

Changes in Hemoglobin Measures Observed in PNH Patients Treated with Both C5 Inhibitors Ravulizumab and Eculizumab: Real-World Evidence from a US-Based EMR Network

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired blood disease characterized by hemolytic anemia, bone marrow failure, and thrombosis. Prior to the FDA approval of the C3 inhibitor pegcetacoplan, PNH treatment only included the C5 inhibitors (C5i) ravulizumab (RAV) and eculizumab (ECU) to decrease intravascular hemolysis and improve anemia. A Phase III trial of RAV in a treatment-naïve PNH population reported hemoglobin (Hb) stabilization (avoidance a >2 g/dL decrease in baseline Hb) occurred in 68% of RAV and 64% of ECU patients after 6 months. (Lee et al, 2019). However, real world (RW) evidence of the efficacy of these agents on Hb measures in clinical practice are lacking. The objectives of this study were to describe the demographic, healthcare resource utilization (HCRU), and clinical characteristics of PNH patients prior to C5i therapy, and to examine changes in Hb levels from baseline to 6 months after treatment initiation in a PNH patient population using a RW electronic medical record (EMR) network. Methods: This was a retrospective study of PNH patients aged ≥ 12 years seen between 2010-2021 within the TriNetX Dataworks USA Network, a federated EMR network of 68+ million de-identified patients. Included patients had a diagnosis of PNH on or before the index event of C5i therapy initiation. Patients were excluded if there was no visit recorded ≥6 months before the index event or if they had a diagnosis of atypical hemolytic uremic syndrome, myasthenia gravis, or neuromyelitis optica spectrum disorder. Demographic, HCRU, and clinical characteristics were captured for the year prior to therapy initiation. Hb results closest to the first treatment date and to the 6-month follow-up dates were used for Hb values. Mean and median Hb and distribution of Hb were calculated, as well as Hb stabilization (avoidance of a >2 g/dL decrease in baseline Hb) and response (Hb≥1 g/dL improvement) rates. Results: Fifty-eight PNH patients treated with RAV and 124 patients treated with ECU met inclusion criteria. Among the RAV and ECU cohorts respectively, patients were on average 50 and 43 years old and 59% and 56% female. Both cohorts experienced an average of ~3 inpatient visits in the year prior to C5i initiation. Aplastic anemia (36% vs 43%) and myelodysplastic syndromes (3% vs 6%) were less common among the RAV vs ECU cohort. Previous ECU treatment occurred in 34 of 58 (59%) RAV patients. All ECU patients were treatment-naïve at baseline. Hb results were available at baseline and 6 mo. in 50 and 32 RAV patients and in 110 and 81 ECU patients. The mean (SD) baseline and 6 mo. Hb values were 10.6 (2.0) and 10.7 (2.2) g/dL for the RAV cohort and 9.8 (2.2) and 10.4 (2.2) g/dL for the ECU cohort. Analysis of baseline and 6 mo. Hb values showed trends toward Hb increase for both cohorts driven by the larger proportion of patients achieving Hb≥12 g/dL (Figure). While the proportion of patients with Hb<10 g/dL decreased in the treatment-naïve ECU cohort (47 to 36% at 6 mo.), it remained unchanged from baseline to 6 mo. (34%) in the RAV cohort. Hb stabilization and response at 6 mo. were observed in 94% and 34% of RAV and 93% and 51% of ECU patients. However, these do not take transfusion requirements into account, which may lower these results. Conclusions: This analysis shows that patients treated with ECU had modest improvements in Hb measures after 6 mo., likely reflecting the effects of C5i in a treatment-naïve population. However, RAV treatment did not markedly alter Hb measures, perhaps due to this being mainly a cohort switching between two therapies with identical mechanisms of action. These RW Hb results suggest that despite C5i treatment, anemia was still largely persistent in this PNH cohort, possibly due to incomplete control of ongoing hemolysis, including extravascular hemolysis, which is not treated by these therapies. Our current analysis has limitations that we plan to address: Subgroup analysis by prior treatment is planned to further characterize RAV efficacy. Transfusion requirements have not yet been incorporated into this analysis; however, their inclusion is likely to attenuate the observed Hb efficacy. Other labs, such as absolute reticulocyte count and LDH, will be incorporated to gain a more holistic picture of therapeutic response. Finally, HCRU encounters reflecting adverse events, such as breakthrough hemolysis, need to be analyzed to understand the real-world safety profile of these therapies. Figure 1 Figure 1. Disclosures Yeh: Apellis Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Kuranz: TriNetX: Current Employment; Apellis Pharmaceuticals, Inc.: Other: Payments from Apellis Pharmaceuticals to my institution TriNetX. Brzozowski: Apellis Pharmaceuticals, Inc.: Other: Payments from Apellis Pharmaceuticals to my institution TriNetX; TriNetX: Current Employment. Hoffman: Apellis Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Fishman: Apellis Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Chen: TriNetX: Current Employment; Apellis Pharmaceuticals, Inc.: Other: Payments from Apellis Pharmaceuticals to my institution TriNetX.

Index event of cerebral amyloid angiopathy (CAA) determines long-term prognosis and recurrent events (retrospective analysis and clinical follow-up)

Background The modified Boston criteria (mBC) define the probability for the diagnosis of cerebral amyloid angiopathy (CAA). Its initial clinical presentation differs from asymptomatic cerebral microbleedings (cMBs), acute ischemic stroke (AIS), cortical hemosiderosis (cSS), to lobar ICH (lICH). Methods Retrospective analyses and clinical follow-ups of individuals with at least mBC “possible” CAA from 2005 to 2018. Results 149 patients were classified in subgroups due to the index event: lICH (n = 91), AIS (n = 32), > 3 cMBs only (n = 16) and cSS (n = 10). Patients in the lICH subgroup had a significantly higher percentage of single new lICHs compared to other groups, whereas patients in the AIS-group had a significantly higher percentage of multiple new AIS. cMBs as index event predisposed for AIS during follow up (p < 0.0016). Patients of the cMBs- or cSS-group showed significantly more TFNEs (transient focal-neurological episodes) and lower numbers of asymptomatic patients (for epilepsy and TFNEs) at the index event than patients with lICH or AIS (p < 0.0013). At long-term follow-up, the cMBs- and cSS-group were characterized by more TFNEs and fewer asymptomatic patients. Conclusions A new classification system of CAA should add subgroups according to the initial clinical presentation to the mBCs allowing individual prognosis, acute treatment and secondary prophylaxis.

664 Factors and Outcomes Associated with Delays in Carotid Endarterectomy in Symptomatic Patients

Introduction Carotid artery disease (CAD) contributes to 20% of ischaemic stroke. Carotid endarterectomy (CEA) reduces stroke risk significantly if performed within 14 days of the index event in symptomatic patients. Studies report delayed CEA is common in practice, however underlying reasons are poorly understood. The aim is to assess factors associated with delayed CEA, and to compare outcomes between timely and delayed CEA. Method This retrospective cohort study included 24 symptomatic CAD patients planned for CEA between October 2018 and December 2019 in a tertiary vascular unit. Time from index event to CEA was measured in “timely” (≤14 days) and “delayed” (&gt;14 days) cohorts and causes for delay were explored. Univariate logistic regression was performed to assess factors associated with delay. Surgical outcomes at 30-days and 1-year were compared between cohorts. Results Overall, 58.3% (n = 14/24) patients underwent delayed CEA. Median time from index event to CEA was 10.5 (IQR 7.5-12) and 22 (IQR 16-32) days in timely and delayed cohorts respectively (P &lt; 0.0001). The main cause of delay was deterioration in patient condition (50%, n = 7/14). In 35.7% (n = 5/14) reasons were unclear. No statistically significant factors were associated with a delay. All surgical outcomes, including 30-day mortality (0%, n = 0/10 vs 7.1%, n = 1/14;P&gt;0.9999) and all-stroke (0%, n = 0/10 vs 14.3%, n = 2/14;P=0.4928), were not statistically significant between timely and delayed cohorts respectively. Conclusions A substantial proportion of patients undergo delayed CEA, with inconclusive associated factors. Those undergoing a delayed CEA did not comparatively have an adverse outcome, but numbers in our study were limited. A larger scale study with increased power is required.

Predictors for one-year outcomes of cardiorespiratory fitness and cardiovascular risk factor control after cardiac rehabilitation in elderly patients: The EU-CaRE study

Introduction Studies on effectiveness of cardiac rehabilitation (CR) in elderly cardiovascular disease patients are rare, and it is unknown, which patients benefit most. We aimed to identify predictors for 1-year outcomes of cardiorespiratory fitness and CV risk factor (CVRF) control in patients after completing CR programs offered across seven European countries. Methods Cardiovascular disease patients with minimal age 65 years who participated in comprehensive CR were included in this observational study. Peak oxygen uptake (VO2), body mass index (BMI), resting systolic blood pressure (BPsys), and low-density lipoprotein-cholesterol (LDL-C) were assessed before CR (T0), at termination of CR (T1), and 12 months after start of CR (T2). Predictors for changes were identified by multivariate regression models. Results Data was available from 1241 out of 1633 EU-CaRE patients. The strongest predictor for improvement in peak VO2 was open chest surgery, with a nearly four-fold increase in surgery compared to non-surgery patients. In patients after surgery, age, female sex, physical inactivity and time from index event to T0 were negative predictors for improvement in peak VO2. In patients without surgery, previous acute coronary syndrome and higher exercise capacity at T0 were the only negative predictors. Neither number of attended training sessions nor duration of CR were significantly associated with change in peak VO2. Non-surgery patients were more likely to achieve risk factor targets (BPsys, LDL-C, BMI) than surgery patients. Conclusions In a previously understudied population of elderly CR patients, time between index event and start of CR in surgery and disease severity in non-surgery patients were the most important predictors for long-term improvement of peak VO2. Non-surgery patients had better CVRF control.

Unprovoked or provoked venous thromboembolism: not the prevalent criterion to decide on anticoagulation extension in clinical practice of various countries—the prospective, international, observational WHITE study

The decision on treatment after a first venous thromboembolism (VTE) to prevent recurrences may be influenced by many factors. The prospective, observational, WHITE study aimed to analyze how this issue was tackled in every-day clinical practice in various countries, which have sensibly different socio-economic conditions and healthcare systems. Doctors active in 79 Internal or Vascular clinical centers in 7 countries (China, Czechia, Poland, Portugal, Russia, Slovakia, and Tunisia) enrolled VTE patients after the maintenance treatment phase. The present report analyzed information, collected in the central database, regarding the baseline characteristics, index events, type and duration of anticoagulant therapy and decision on post-maintenance treatment. From April 2018 to December 2020, 1240 patients were enrolled, 58% with an unprovoked index event. Direct oral anticoagulants (DOACs) were used in > 85% of all cases in China, Poland, Portugal, Russia and Czechia, in 52% in Slovakia and in no patient in Tunisia. The maintenance anticoagulation lasted in average approximately 6 months. Altogether, anticoagulation was stopped in 20%, extended in about 50%, regardless of whether the event was unprovoked or provoked and shifted to antithrombotics (mainly sulodexide or aspirin) in the remaining patients. In conclusion, some differences in VTE patient management were found between countries. The provoked/unprovoked nature of the index event, instead, was not the prevalent criterion to drive the decision on extension of anticoagulation, without large variations between countries. DOACs were the most widely used anticoagulant drugs, whereas > 25% of patients received antithrombotic drugs instead of anticoagulants as extended treatment.

Multicenter Prospective Analysis of Hypertrophic Olivary Degeneration Following Infratentorial Stroke (HOD-IS): Evaluation of Disease Epidemiology, Clinical Presentation, and MR-Imaging Aspects

Introduction: Ischemic and hemorrhagic strokes in the brainstem and cerebellum with injury to the functional loop of the Guillain-Mollaret triangle (GMT) can trigger a series of events that result in secondary trans-synaptic neurodegeneration of the inferior olivary nucleus. In an unknown percentage of patients, this leads to a condition called hypertrophic olivary degeneration (HOD). Characteristic clinical symptoms of HOD progress slowly over months and consist of a rhythmic palatal tremor, vertical pendular nystagmus, and Holmes tremor of the upper limbs. Diffusion Tensor Imaging (DTI) with tractography is a promising method to identify functional pathway lesions along the cerebello-thalamo-cortical connectivity and to generate a deeper understanding of the HOD pathophysiology. The incidence of HOD development following stroke and the timeline of clinical symptoms have not yet been determined in prospective studies—a prerequisite for the surveillance of patients at risk.Methods and Analysis: Patients with ischemic and hemorrhagic strokes in the brainstem and cerebellum with a topo-anatomical relation to the GMT are recruited within certified stroke units of the Interdisciplinary Neurovascular Network of the Rhine-Main. Matching lesions are identified using a predefined MRI template. Eligible patients are prospectively followed up and present at 4 and 8 months after the index event. During study visits, a clinical neurological examination and brain MRI, including high-resolution T2-, proton-density-weighted imaging, and DTI tractography, are performed. Fiberoptic endoscopic evaluation of swallowing is optional if palatal tremor is encountered.Study Outcomes: The primary endpoint of this prospective clinical multicenter study is to determine the frequency of radiological HOD development in patients with a posterior fossa stroke affecting the GMT at 8 months after the index event. Secondary endpoints are identification of (1) the timeline and relevance of clinical symptoms, (2) lesion localizations more prone to HOD occurrence, and (3) the best MR-imaging regimen for HOD identification. Additionally, (4) DTI tractography data are used to analyze individual pathway lesions. The aim is to contribute to the epidemiological and pathophysiological understanding of HOD and hereby facilitate future research on therapeutic and prophylactic measures.Clinical Trial Registration: HOD-IS is a registered trial at https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&amp;TRIAL_ID=DRKS00020549.

Impact of cancer type on the incidence of cutaneous toxicities after immune checkpoint inhibitor therapy: A population-level analysis.

e14553 Background: Cutaneous immune-related adverse events (cirAEs) from immune checkpoint inhibitor (ICI) therapy are increasing as these drugs are more widely used. Population-level studies are lacking. In this retrospective cohort study, we analyzed the primary tumor’s effect on cirAE incidence and downstream utilization of systemic immunosuppression in a national healthcare database (TriNetX). Methods: Index event was defined as day of ICI initiation; outcomes were restricted to 2 years from index. cirAEs were defined as 42 dermatoses identified in a comprehensive review of the cirAE literature (Sibaud 2018) and expert opinion. Systemic immunosuppression was classified as steroidal or non-steroidal. Primary outcomes included aggregate and cancer-specific incidence of cirAEs across the four most common cancer indications for ICI therapy (melanoma, lung, urinary, and gastrointestinal). Secondary outcomes included utilization of new steroidal or non-steroidal systemic immunosuppression. For each analysis, we excluded patients with an outcome prior to the index event. Risk ratios (RR) were calculated after 1-to-1 propensity score matching, adjusting for age at index, sex, race, ethnicity, and ICI target, with the lung cancer group as reference. Results: We identified 27,481 eligible subjects. Aggregate incidence of cirAEs across all cancer types was 23.41%, with non-specific rashes, pruritus, and drug eruptions as the most common diagnoses. Among all patients, new steroidal and non-steroidal immunosuppression use following ICI initiation was 16.1% and 4.1%, respectively. After adjusting for covariates, melanoma (RR 1.60, 95% CI 1.43-1.79, p < 0.001) was associated with a higher risk of cirAE, while urinary and gastrointestinal tract cancers were not significantly different from the reference. Melanoma (RR 0.64, 95% CI 0.55-0.74), urinary tract (RR 0.71, 95% CI 0.62-0.81) and gastrointestinal tract (RR 0.46, 95% CI 0.39-0.53) cancers were all less likely to require steroidal immunosuppression (all p < 0.001). However, patients with urinary tract cancer (RR 4.03, 95% CI 3.04-5.35) and melanoma (RR 2.44, 95% CI 1.75-3.40) were more likely to receive non-steroidal systemic immunosuppression (both p < 0.001). Conclusions: Our results reinforce that ICI recipients commonly develop skin toxicities and provide robust evidence that melanoma is independently associated with their incidence. Furthermore, we found that patients with lung cancers received steroidal systemic immunosuppression most frequently, an intervention associated with poorer overall survival (Riudavets 2020). In contrast, patients with melanoma were more likely to receive non-steroidal immunosuppression. This study is the first population-based analysis of an irAE across tumor types and is proof-of-concept for future investigations into clinical risk factors in a large dataset.