Cytokine Registry Database of Stroke Patients (CRISP)

Purpose/Background: The aim of the study is to identify molecular biomarkers involve in patients who present with stroke and to determine their clinical usefulness as potential biomarkers in stroke patients as compared to patients without stroke. Materials & Methods: All patients presenting with ischemic stroke and hemorrhagic stroke at University of New Mexico Hospital (UNMH) will be screened for potential participation in this study based on following inclusion and exclusion criteria: Inclusion criteria: male/female of ages ≥ 18 years, patients whose standard stroke admission order sets are obtained for clinical care. Exclusion criteria: Patients \u3c18 year, with the history of prior stroke or any neurodegenerative or neuroinflammatory disease except multiple sclerosis (MS), pregnant women and prisoners. Cytokines will be measured in serum at two different time points: on admission and after 24 hours of admission. The biomarkers which will measured in serum will include interleukin (IL)-1, 4, 6, 10, 17, 23, 33, 36, 37, PDGF, VEGFM, TNF-a, ANNULIN, MMP-9, 12, NFk-B, MPO and glial factors; GMF, SI000-B and GM-6001. These biomarkers will be evaluated using enzyme linked immunosorbent assay (ELISA). Twenty-five percent of the total stroke patient serum samples will be matched by controls without ischemic or hemorrhagic stroke. The study was approved by UNM institutional review board (IRB). All sample and data collection is being done after patient or legally authorized individual sign the informed consent form. All the data is being collected on secured RedCAP database. Results: A total of 105 patients will be enrolled during the study period. Two sets of samples; one at baseline and the other after 24 hours of admission, will collected from each enrolled patient. At present, two patients are enrolled and their samples have been collected and stored per study protocol. The study is currently under recruitment phase and it is anticipated that the enrollment will be completed within next 2 months. Biomarker analysis will be done sequentially as patients will be enrolled per study protocol. Discussion/Conclusion: The CRISP study will give us understanding about the role of various cytokines and/or other biomarkers in the pathogenesis of formation of stroke. These biomarkers can potentially serve as identifiers in the clinical surveillance for acute stroke patients. The data from this study can be beneficial in the acute management of stroke patients

Functional and Safety Outcomes of Carotid Artery Stenting and Mechanical Thrombectomy for Large Vessel Occlusion Ischemic Stroke With Tandem Lesions

Arteria carótida; Trombectomía mecánica; Accidente cerebrovascular isquémicoArtèria caròtida; Trombectomia mecànica; Accident cerebrovascular isquèmicCarotid artery; Mechanical thrombectomy; Ischemic strokeImportance Approximately 10% to 20% of large vessel occlusion (LVO) strokes involve tandem lesions (TLs), defined as concomitant intracranial LVO and stenosis or occlusion of the cervical internal carotid artery. Mechanical thrombectomy (MT) may benefit patients with TLs; however, optimal management and procedural strategy of the cervical lesion remain unclear. Objective To evaluate the association of carotid artery stenting (CAS) vs no stenting and medical management with functional and safety outcomes among patients with TL-LVOs. Design, Setting, and Participants This cross-sectional study included consecutive patients with acute anterior circulation TLs admitted across 17 stroke centers in the US and Spain between January 1, 2015, and December 31, 2020. Data analysis was performed from August 2021 to February 2022. Inclusion criteria were age of 18 years or older, endovascular therapy for intracranial occlusion, and presence of extracranial internal carotid artery stenosis (>50%) demonstrated on pre-MT computed tomography angiography, magnetic resonance angiography, or digital subtraction angiography. Exposures Patients with TLs were divided into CAS vs nonstenting groups. Main Outcomes and Measures Primary clinical and safety outcomes were 90-day functional independence measured by a modified Rankin Scale (mRS) score of 0 to 2 and symptomatic intracranial hemorrhage (sICH), respectively. Secondary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction score ≥2b), discharge mRS score, ordinal mRS score, and mortality at 90 days. Results Of 685 patients, 623 (mean [SD] age, 67 [12.2] years; 406 [65.2%] male) were included in the analysis, of whom 363 (58.4%) were in the CAS group and 260 (41.6%) were in the nonstenting group. The CAS group had a lower proportion of patients with atrial fibrillation (38 [10.6%] vs 49 [19.2%], P = .002), a higher proportion of preprocedural degree of cervical stenosis on digital subtraction angiography (90%-99%: 107 [32.2%] vs 42 [20.5%], P < .001) and atherosclerotic disease (296 [82.0%] vs 194 [74.6%], P = .003), a lower median (IQR) National Institutes of Health Stroke Scale score (15 [10-19] vs 17 [13-21], P < .001), and similar rates of intravenous thrombolysis and stroke time metrics when compared with the nonstenting group. After adjustment for confounders, the odds of favorable functional outcome (adjusted odds ratio [aOR], 1.67; 95% CI, 1.20-2.40; P = .007), favorable shift in mRS scores (aOR, 1.46; 95% CI, 1.02-2.10; P = .04), and successful reperfusion (aOR, 1.70; 95% CI, 1.02-3.60; P = .002) were significantly higher for the CAS group compared with the nonstenting group. Both groups had similar odds of sICH (aOR, 0.90; 95% CI, 0.46-2.40; P = .87) and 90-day mortality (aOR, 0.78; 95% CI, 0.50-1.20; P = .27). No heterogeneity was noted for 90-day functional outcome and sICH in prespecified subgroups. Conclusions and Relevance In this multicenter, international cross-sectional study, CAS of the cervical lesion during MT was associated with improvement in functional outcomes and reperfusion rates without an increased risk of sICH and mortality in patients with TLs

Thrombectomy for Large‐Vessel Occlusion With Pretreatment Intracranial Hemorrhage

Background Many patients treated with endovascular thrombectomy (EVT) in clinical practice would not have qualified for inclusion in the initial clinical trials demonstrating benefit for EVT, yet likely will benefit from reperfusion. One such subset for which data are sparse is patients with emergent large‐vessel occlusion and concomitant intracranial hemorrhage (ICH). The objective of this report is to document patients who underwent thrombectomy for large‐vessel occlusion in the presence of concomitant ICH and evaluate their clinical characteristics and outcomes. Methods We retrospectively reviewed prospectively collected patient records at 4 comprehensive stroke centers from 2012 to 2019. Patients were identified who had pre‐EVT ICH. Data collected included baseline patient demographics and laboratory values, stroke characteristics, ICH radiographic variables, antiplatelet/anticoagulant/thrombolytic medication use, and procedural factors. The primary safety outcome was any worsening of ICH on neuroimaging obtained 24 hours after EVT. Results Eight patients were identified who underwent thrombectomy with concomitant ICH. The mean age was 71.9 years (range, 37–90). Median National Institutes of Health Stroke Scale score was 25 (interquartile range, 16.5–28.8), and 5 (63%) received tissue plasminogen activator. All patients underwent EVT and had mTICI2B or greater reperfusion. In 7 patients (88%), the initial ICH remained stable on postprocedure imaging. In 1 patient who received intravenous antiplatelet agents during thrombectomy, the hemorrhagic transformation was radiographically increased but without clinical correlate or mass effect. Conclusions In a multi‐institution evaluation of 8 patients with ICH at the time of thrombectomy, 1 patient had radiographic worsening of hemorrhage, and no patient experienced clinical worsening related to hemorrhage progression. These findings suggest that thrombectomy may be safe in this population

Safety and efficacy of balloon-mounted stent in the treatment of symptomatic intracranial atherosclerotic disease: a multicenter experience

Background Randomized clinical trials have failed to prove that the safety and efficacy of endovascular treatment for symptomatic intracranial atherosclerotic disease (ICAD) is better than that of medical management. A recent study using a self-expandable stent showed acceptable lower rates of periprocedural complications. Objective To study the safety and efficacy of a balloon-mounted stent (BMS) in the treatment of symptomatic ICAD. Methods Prospectively maintained databases from 15 neuroendovascular centers between 2010 and 2020 were reviewed. Patients were included if they had severe symptomatic intracranial stenosis in the target artery, medical management had failed, and they underwent intracranial stenting with BMS after 24 hours of the qualifying event. The primary outcome was the occurrence of stroke and mortality within 72 hours after the procedure. Secondary outcomes were the occurrence of stroke, transient ischemic attacks (TIAs), and mortality on long-term follow-up. Results A total of 232 patients were eligible for the analysis (mean age 62.8 years, 34.1% female). The intracranial stenotic lesions were located in the anterior circulation in 135 (58.2%) cases. Recurrent stroke was the qualifying event in 165 (71.1%) while recurrent TIA was identified in 67 (28.9%) cases. The median (IQR) time from the qualifying event to stenting was 5 (2–20.75) days. Strokes were reported in 13 (5.6%) patients within 72 hours of the procedure; 9 (3.9%) ischemic and 4 (1.7%) hemorrhagic, and mortality in 2 (0.9%) cases. Among 189 patients with median follow-up time 6 (3–14.5) months, 12 (6.3%) had TIA and 7 (3.7%) had strokes. Three patients (1.6%) died from causes not related to stroke. Conclusion Our study has shown that BMS may be a safe and effective treatment for medically refractory symptomatic ICAD. Additional prospective randomized clinical trials are warranted

Repeated Mechanical Endovascular Thrombectomy for Recurrent Large Vessel Occlusion: A Multicenter Experience

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is now the standard of care for large vessel occlusion (LVO) stroke. However, little is known about the frequency and outcomes of repeat MT (rMT) for patients with recurrent LVO. METHODS: This is a retrospective multicenter cohort of patients who underwent rMT at 6 tertiary institutions in the United States between March 2016 and March 2020. Procedural, imaging, and outcome data were evaluated. Outcome at discharge was evaluated using the modified Rankin Scale. RESULTS: Of 3059 patients treated with MT during the study period, 56 (1.8%) underwent at least 1 rMT. Fifty-four (96%) patients were analyzed; median age was 64 years. The median time interval between index MT and rMT was 2 days; 35 of 54 patients (65%) experienced recurrent LVO during the index hospitalization. The mechanism of stroke was cardioembolism in 30 patients (56%), intracranial atherosclerosis in 4 patients (7%), extracranial atherosclerosis in 2 patients (4%), and other causes in 18 patients (33%). A final TICI recanalization score of 2b or 3 was achieved in all 54 patients during index MT (100%) and in 51 of 54 patients (94%) during rMT. Thirty-two of 54 patients (59%) experienced recurrent LVO of a previously treated artery, mostly the pretreated left MCA (23 patients, 73%). Fifty of the 54 patients (93%) had a documented discharge modified Rankin Scale after rMT: 15 (30%) had minimal or no disability (modified Rankin Scale score ≤2), 25 (50%) had moderate to severe disability (modified Rankin Scale score 3-5), and 10 (20%) died. CONCLUSIONS: Almost 2% of patients treated with MT experience recurrent LVO, usually of a previously treated artery during the same hospitalization. Repeat MT seems to be safe and effective for attaining vessel recanalization, and good outcome can be expected in 30% of patients

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry

© 2020 World Stroke Organization.[Background]: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. [Aim]: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. [Methods]: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020–16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). [Results]: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970–1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920–1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130–280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4–60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63–15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07–2.94, p ¼ 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34–0.98, p ¼ 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. [Conclusions]: COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

Latent class trajectories of biochemical parameters and their relationship with risk of mortality in ICU among acute organophosphorus poisoning patients

Acute poisoning is a global public health challenge. Several factors played role in high mortality among acute organophosphorus poisoning (OP) poisoning patients including clinical, vitals, and biochemical properties. The traditional analysis techniques use baseline measurements whereas latent profile analysis is a person-centered approach using repeated measurements. To determine varying biochemical parameters and their relationship with intensive care unit (ICU) mortality among acute organophosphorus poisoning patients through a latent class trajectory analysis. The study design was a retrospective cohort and we enrolled data of 299 patients admitted between Aug’10 to Sep’16 to ICU of Dr. Ruth K. M. Pfau, Civil Hospital, Karachi. The dependent variable was ICU-mortality among OP poisoning patients accounting for ICU stay, elapsed time since poison ingestion, age, gender, and biochemical parameters (including electrolytes (potassium, chloride, sodium), creatinine, urea, and random blood sugar). Longitudinal latent profile analysis is used to form the trajectories of parameters. In determining and comparing the risk of ICU-mortality we used Cox-Proportional-Hazards models, repeated measures and trajectories were used as independent variables. The patients’ mean age was 25.4 ± 9.7 years and ICU-mortality was (13.7%, n = 41). In trajectory analysis, patients with trajectories (normal-increasing and high-declining creatinine, high-remitting sodium, normal-increasing, and high-remitting urea) observed the highest ICU-mortality i.e. 75% (6/8), 67% (2/3), 80% (4/5), 75% (6/8), and 67% (2/3) respectively compared with other trajectories. On multivariable analysis, compared with patients who had normal consistent creatinine levels, patients in normal-increasing creatinine class were 15 times [HR:15.2, 95% CI 4.2–54.6], and the high-declining class was 16-times [HR 15.7, 95% CI 3.4–71.6], more likely to die. Patients in with high-remitting sodium, the trajectory was six-times [HR 5.6, 95% CI 2.0–15.8], normal-increasing urea trajectory was four times [HR 3.9, 95% CI 1.4–11.5], and in extremely high-remitting urea trajectory was 15-times [HR 15.4, 95% CI 3.4–69.7], more likely to die compared with those who were in normal-consistent trajectories of sodium and urea respectively. Among OP poisoning patients an increased risk of ICU-mortality were significantly associated with biochemical parameters (sodium, urea, creatinine levels) using latent profile technique

Abstract Number ‐ 142: Flow Diversion for Posterior Communicating Artery Aneurysms: Systematic Review and Meta‐Analysis

Introduction Posterior communicating artery (PComA) aneurysms are common and have a high risk of rupture. Flow diverters (FD) have demonstrated a safe and effective profile. However, the use of FD in PComA aneurysms has shown controversial results with high rates of recurrence and a high risk of potential ischemic complications. There, we aimed to evaluate the safety and efficacy of flow diversion for the treatment of PComA aneurysms with a meta‐analysis of the literature. Methods We performed a systematic search in Scopus, Embase, Medline, and Web of Science from inception until May 2022 for all the studies that reported the safety and effectiveness of FD for the treatment of intracranial aneurysms located in the posterior communicating artery. The primary effectiveness endpoint was a complete aneurysm occlusion rate at final follow‐up. The primary safety endpoint was a composite measure of cumulative events that occurred during and after the procedure. Events included death and ischemic/hemorrhagic complications. Random‐effects meta‐analysis was used to calculate proportions. Statistical heterogeneity across studies was assessed with I2 statistics. Results A total of 13 studies with 397 patients harboring 403 aneurysms were included in our analysis. Mean age was 48 years and mean aneurysm size was 5.3 mm. Complete aneurysm occlusion at final follow‐up was 74% (95% CI 66–81%; I2 = 54%). The primary safety composite outcome was 5% (95% CI 3–9%; I2 = 0%). The mortality rate was 1% (95% CI 0–2%; I2 = 0%). Subgroup analysis showed that patients with a non‐fetal PComA had a higher rate (76%; 95% CI 62%‐86%; I2 = 53%) of complete aneurysm occlusion compared to those with a fetal PComA (36%; 95% CI 21%‐54%; I2 = 0%). Conclusions Our findings show that flow diversion for the treatment of aneurysms located in the PComA is effective and safe. However, the same treatment for aneurysms located in a fetal‐type PComA did not show the same efficacy profile suggesting that these cases might require an alternative treatment to achieve permanent occlusion rates

Naproxen inhibits spontaneous lung adenocarcinoma formation in KrasG12V mice

Lung cancer is the leading cause of cancer related deaths worldwide. The present study investigated the effects of naproxen (NSAID) on lung adenocarcinoma in spontaneous lung cancer mouse model. Six-week-old transgenic KrasG12V mice (n = 20; male + female) were fed modified AIN-76A diets containing naproxen (0/400 ppm) for 30 wk and euthanized at 36 wk of age. Lungs were evaluated for tumor incidence, multiplicity, and histopathological stage (adenoma and adenocarcinoma). Lung tumors were noticeable as early as 12 wk of age exclusively in the KrasG12V mice. By 36 wk age, 100% of KrasG12V mice on control diet developed lung tumors, mostly adenocarcinomas. KrasG12V mice fed control diet developed 19.8 ± 0.96 (Mean ± SEM) lung tumors (2.5 ± 0.3 adenoma, 17.3 ± 0.7 adenocarcinoma). Administration of naproxen (400 ppm) inhibited lung tumor multiplicity by ∼52% (9.4 ± 0.85; P < 0001) and adenocarcinoma by ∼64% (6.1 ± 0.6; P < 0001), compared with control-diet-fed mice. However, no significant difference was observed in the number of adenomas in either diet, suggesting that naproxen was more effective in inhibiting tumor progression to adenocarcinoma. Biomarker analysis showed significantly reduced inflammation (COX-2, IL-10), reduced tumor cell proliferation (PCNA, cyclin D1), and increased apoptosis (p21, caspase-3) in the lung tumors exposed to naproxen. Decreased serum levels of PGE2 and CXCR4 were observed in naproxen diet fed KrasG12V mice. Gene expression analysis of tumors revealed a significant increase in cytokine modulated genes (H2-Aa, H2-Ab1, Clu), which known to further modulate the cytokine signaling pathways. Overall, the results suggest a chemopreventive role of naproxen in inhibiting spontaneous lung adenocarcinoma formation in KrasG12V mice