bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathological Complete Response of Metastatic Clear Cell Renal Carcinoma with Pembrolizumab and Axitinib: A Case Report and Review of Literature
Authors: Beirat Amir F. , Menakuru Sasmith R , Khan Ibrahim , Siddiqui Salahuddin
Published: February 2023

The role of cytoreductive nephrectomy has become unclear since the introduction of immunotherapy which is now the backbone of the treatment for metastatic renal cell carcinoma. Different combinations are used based on the prognosis. Achieving a complete response would be ideal and includes radiographic disappearance of lesions. However, there have been a few reported cases of pathological complete response with persistent radiographic evidence of cancer. The authors report a case of pathological complete response despite persistent radiographic evidence of residual disease in a patient with metastatic renal cell carcinoma treated with pembrolizumab and axitinib. The patient subsequently underwent cytoreductive nephrectomy after the 13th dose of pembrolizumab. The resected mass consisted of scar tissue with no viable tumor cells seen on pathology but only scar tissue. This case reveals that persistent radiographic evidence of the tumor may be explained by scar tissue, challenging the role of cytoreductive nephrectomy in the era of immunotherapy.
Macular Choroidal Thickness and Choriocapillaris Vessel Density Alterations in Type 2 Diabetics with High Myopia
Authors: Su Ruifeng , Qi Zhiwei , Tan Xiaobo
Published: February 2023

Introduction: The purpose of this study was to investigate the change in macular choroidal thickness and choriocapillaris vessel density in type 2 diabetic (T2D) with high myopia. Methods: This cross-sectional study recruited a total of 182 patients (182 eyes) in the Affiliated Hospital of Chengde Medical University between January 2018 and December 2021, including myopia + diabetes patients (40 eyes), T2D patients without myopia patients (47 eyes), myopia patients (45 eyes), and healthy volunteers (50 eyes). The choroidal thickness and choriocapillaris vessel density of macular were measured in all subjects by optical coherence tomography and optical coherence tomography angiography. Results: The choroidal thicknesses in myopic, diabetes, myopia + diabetes groups were statistically significantly lower than those in control group (p < 0.001). Further pairwise comparisons showed that the choroidal thicknesses in myopia + diabetes group were statistically significantly lower than those in diabetes group (p < 0.001). The choriocapillaris vessel densities in diabetes, myopia + diabetes groups were statistically significantly lower than those in control group (p < 0.001). Interestingly, there were no significant differences in choriocapillaris vessel density between myopia group and control group (p > 0.05). Further pairwise comparisons showed that the choriocapillaris thicknesses in myopia + diabetes group were statistically significantly lower than those in myopia group (p < 0.001), while no statistically significant differences were found between diabetes group and myopia + diabetes group (p > 0.05). Conclusion: The choroidal thickness of the patients with high myopia and diabetes (without diabetic retinopathy [DR]) was significantly lower than that of normal people and diabetic patients, but the choriocapillaris vessel density was not significantly different from that of normal people, which may be one of the protective mechanisms of high myopia against DR.
Atypical Category of the Johns Hopkins Template Has Higher Risk of Malignancy than the Paris System but the Paris System Is More Applicable for Suspicious Category
Authors: Celik Betul , Kavas Gamze
Published: February 2023

Introduction: The aim of this study was to compare performance of individual categories between the Johns Hopkins template and the Paris system for reporting urinary cytology. Methods: Medical records of patients with bladder biopsy and relevant cytology slides were obtained from archived material. Slides were reclassified according to Johns Hopkins template and the Paris system. Results were compared to histological diagnoses. Results: BD SurePath preparations from 205 cases with biopsy follow-up (118 benign, 5 dysplasia, 23 low, and 59 malignant urothelial carcinoma [UC]) were reviewed. There were 2 inadequate specimens in each system. According to the Johns Hopkins template, there were 96 (46.8%) no urothelial atypia or malignancy, 37 (18%) atypical urothelial cells of uncertain significance (AUC-US), 21 (10.2%) atypical urothelial cells, cannot exclude high-grade urothelial carcinoma (HGUC), 38 (18.5%) HGUC, and 11 (5.4%) low-grade urothelial carcinoma (LGUC). The Paris system categorized 111 (54.1%) negative for high-grade urothelial carcinoma, 29 (14.1%) atypical urothelial cells (AUCs), 25 (12.2%) suspicious for HGUC (SHGUC), 36 (17.6%) HGUC, and 2 (1%) LGUC. The Johns Hopkins template had a sensitivity of 95.6%, specificity of 73.6%, positive predictive value of 61.5%, negative predictive value of 96.3, with an overall diagnostic accuracy of 79.8%. The Paris System had a sensitivity of 93.6%, specificity of 77.9%, positive predictive value of 65.6%, negative predictive value of 96.5, with an overall diagnostic accuracy of 82.8%. The risk of malignancy (ROM) for atypical category (AUC-US/AUC) in the Johns Hopkins template was 43.2%, while it has been 24.1% for the Paris System. The ROM for suspicious category was 47.6% and 68.0%, respectively. There were statistically significant differences between negative and atypical, suspicious, and HGUC categories in each system (p < 0.0001). Conclusions: Discrete negative or benign urine cytology had the same sensitivity and specificity between two systems. Although atypical category was associated with a higher ROM with the Hopkins template, the ROM for the suspicious category yielded better result with the Paris system.
Comparative Associations of Nonalcoholic Fatty Liver Disease and Metabolic Dysfunction–Associated Fatty Liver Disease With Coronary Artery Calcification: A Cross-Sectional and Longitudinal Cohort Study
Authors: Sung Ki-Chul , Yoo Tae Kyung , Lee Mi Yeon , Byrne Christopher D. , Zheng Ming-Hua , Targher Giovanni
Published: February 2023

Background:

In cross-sectional and retrospective cohort studies, we examined comparative associations between nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction–associated fatty liver disease (MAFLD) and risk of having or developing coronary artery calcification (CAC).

Methods:

Participants who had health examinations between 2010 and 2019 were analyzed. Liver ultrasonography and coronary artery computed tomography were used to diagnose fatty liver and CAC. Participants were divided into a MAFLD and no-MAFLD group and then NAFLD and no-NAFLD groups. Participants were further divided into no fatty liver disease (reference), NAFLD-only, MAFLD-only, and both NAFLD and MAFLD groups. Logistic regression modeling was performed. Cox proportional hazard model was used to examine the risk of incident CAC in participants without CAC at baseline and who had at least two CAC measurements.

Results:

In cross-sectional analyses, 162 180 participants were included. Compared with either the no-NAFLD or no-MAFLD groups, the NAFLD and MAFLD groups were associated with a higher risk of prevalent CAC (NAFLD: adjusted odds ratio [OR], 1.34 [95% CI, 1.29–1.39]; MAFLD: adjusted OR, 1.44 [95% CI, 1.39–1.48]). Among the 4 groups, the MAFLD-only group had the strongest association with risk of prevalent CAC (adjusted OR, 1.60 [95% CI, 1.52–1.69]). Conversely, the NAFLD-only group was associated with a lower risk of prevalent CAC (adjusted OR, 0.76 [95% CI, 0.66–0.87]). In longitudinal analyses, 34 233 participants were included. Compared with either the no-NAFLD or no-MAFLD groups, the NAFLD and MAFLD groups were associated with a higher risk of incident CAC (NAFLD: adjusted hazard ratio, 1.68 [95% CI, 1.43–1.99]; MAFLD: adjusted hazard ratio, 1.82 [95% CI, 1.56–2.13]). Among these 4 groups, the MAFLD-only group had the strongest associations with risk of incident CAC (adjusted hazard ratio, 2.03,[95% CI, 1.62–2.55]). The NAFLD-only group was not independently associated with risk of incident CAC (adjusted hazard ratio, 0.88 [95% CI, 0.44–1.78])

Conclusions:

Both NAFLD and MAFLD are significantly associated with an increased prevalence and incidence of CAC. These associations tended to be stronger for MAFLD.
Association of Brain Arterial Elongation With Risk of Stroke and Death in Stroke-Free Individuals: Results From NOMAS
Authors: Del Brutto Victor J. , Khasiyev Farid , Salehi Omran Setareh , Purohit Meghan , Liu Minghua , Wright Clinton B. , Rundek Tatjana , Elkind Mitchell S.V. , Sacco Ralph L. , Gutierrez Jose
Published: February 2023

Background:

Brain arterial dilation and elongation characterize dolichoectasia, an arteriopathy associated with risk of stroke and death. We aim to determine whether brain arterial elongation increases the risk of stroke and death independent of brain arterial diameters.

Methods:

We analyzed 1210 stroke-free participants (mean age 71±9 years, 41% men, 65% Hispanic) with available time-of-flight magnetic resonance angiogram from the Northern Manhattan Study, a population-based cohort study across a multiethnic urban community. We obtained baseline middle cerebral artery M1-segment (MCA-M1) and basilar artery (BA) mean lengths and diameters using a semi-automated software. Cox proportional hazards models adjusted for brain arterial diameters and potential confounders yielded adjusted hazards ratios with 95% CIs for the primary outcomes of incident stroke and all-cause mortality, as well as secondary outcomes including noncardioembolic stroke, vascular death, and any vascular event.

Results:

Neither MCA-M1 nor BA lengths correlated with incident stroke or all-cause mortality. Both MCA-M1 and BA larger diameters correlated with all-cause mortality (MCA-M1 aHR, 1.52 [95% CI, 1.03–2.23], BA aHR, 1.28 [95% CI, 1.02–1.61]), as well as larger MCA-M1 diameters with vascular death (aHR, 1.84 [95% CI, 1.02–3.31]). Larger MCA-M1 and BA diameters did not correlate with incident stroke. However, larger BA diameters were associated with posterior circulation noncardioembolic stroke (aHR, 2.93 [95% CI, 1.07–8.04]). There were no statistical interactions between brain arterial lengths and diameters in relation to study outcomes.

Conclusions:

In a multiethnic cohort of stroke-free adults, brain arterial elongation did not correlate with risk of stroke or death, nor influenced the significant association between brain arterial dilation and vascular risk.
Abstract 110: Why Diabetics Are More Vulnerable To Cerebrovascular Complications Of SARS-CoV-2? An In-vivo Animal Study
Authors: Burnett Faith , Bolduc Deanna , Coucha Maha , Abdelsaid Mohammed A
Published: February 2023

Diabetics are more vulnerable to SARS-CoV-2 cerebrovascular complications, including brain fog, cognitive impairment, and strokes. This study aims to identify the molecular mechanisms of SARS-CoV-2-induced cerebrovascular dysfunction in diabetes. We hypothesize that SARS-CoV-2 exacerbates diabetes-induced cerebral oxidative stress and inflammation via activation of the destructive arm of the renin-angiotensin system (RAAS) and Toll-Like receptor (TLR) signaling.

Methods:
SARS-CoV-2 spike-protein binds to human angiotensin-converting enzyme-2 (ACE2) receptors but not murine Ace2. Therefore, type-2 diabetes was induced in humanized ACE2 (hACE2) knock-in transgenic mice using low-dose streptozotocin followed by eight weeks of a high-fat diet. Recombinant SARS-CoV-2 spike-protein was injected intravenously in control and diabetic mice. Cognitive functions were tested using Y-maze and Barnes maze. RAAS system and TLR signaling were assessed using RT-PCR and western blot analysis. The cerebrovascular architecture was measured using immunohistochemistry.

Results:
Diabetes increased cerebrovascular oxidative stress markers NOX1 and NOX5 and inflammatory markers Il-6, Il-1β, and TNF-α gene expression (P<0.05). Diabetes upregulated angiotensin II and angiotensin 1 receptor (AT1R) expression, these effects were amplified by spike-protein (P<0.05). Moreover, spike-protein injection decreased RAAS protective arm, ACE2, and AT2R expression (P<0.05). In parallel, spike-protein exacerbated TLR signaling in diabetes. Spike-protein increased the TLR-8 receptors and its ligands HMGB1 and S100 and downstream adaptor proteins MyD88, TRAF6, and NF-κB expression (P<0.05). Spike-protein significantly increased cerebrovascular rarefaction and cognitive dysfunction in diabetes (P<0.05).

Conclusion:
SAR-CoV-2 spike-protein intensified RAAS and TLR signaling in diabetes leading to additional cerebrovascular damage and cognitive dysfunction. Targeting RAAS and TLR singling are possible therapeutic strategies to protect against SAR-CoV-2-induced cerebrovascular dysfunction in diabetes.
Abstract 129: Cerebral Oxygen Extraction Fraction Predicts White Matter Lesion Progression In Patients With A Monogenic Cerebral Small Vessel Disease
Authors: Kang Peter , Fellah Slim , Binkley Michael M , Chen Yasheng , Liszewski M. K , Lee Jin-Moo , Miner Jonathan , Atkinson John P , An Hongyu , Ford Andria L
Published: February 2023

Background:
A rare, monogenic cerebral small vessel disease (cSVD), retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S), is associated with progressive cerebral ischemia and accelerated vascular cognitive impairment, resulting in premature death. We hypothesized that low cerebral blood flow (CBF) and elevated oxygen extraction fraction (OEF), as metrics of microvascular ischemia, would predict growth of white matter lesions (WML) and other neuroimaging manifestations of cSVD.

Methods:
We prospectively performed sequential brain MRI in a cohort of RVCL-S participants. Pseudocontinuous arterial spin labeling and asymmetric spin echo quantified CBF and OEF in normal appearing white matter (NAWM), respectively. WMLs were manually delineated on FLAIR. WM volumes were segmented and quantified. Diffusion tensor imaging (DTI) was used to measure NAWM mean diffusivity (MD).

Results:
Each of 14 RVCL-S participants underwent a median of 4.5 scans (IQR 3 - 6.75) with a median of 6.5 months (IQR 5.8 - 8.6) between scans performed over 2.9 years (IQR 2.0 - 4.2). Elevated NAWM OEF from the previous MRI, but not CBF, was associated with WML growth (ρ = 0.672, p < 0.0001), WM atrophy (ρ = 0.654, p < 0.0001), and increased MD (ρ = 0.714, p < 0.0001, Figure). After adjusting for age, sex, previous WML volume, and participant, previous OEF remained an independent predictor of WML growth (β = 7.04 (1.08, 13.01), p = 0.021). NAWM OEF was not retained in the mixed models predicting WM atrophy and MD.

Conclusion:
We found evidence that hypoxic-ischemic physiology, as measured by elevated OEF in NAWM, independently predicted WML growth. Previous OEF was associated with WM atrophy and decrease in microstructural integrity on follow-up. This work suggests that ischemia in normal brain regions may be a harbinger of disease progression in patients with RVCL-S, an inherited cSVD. Additionally, OEF may serve as a potential predictive biomarker in sporadic cSVD.
Abstract 138: Hypoperfusion Delay Volume Predicts Early Stroke Recurrence Risk In Symptomatic Anterior Circulation Intracranial Atherosclerotic Disease
Authors: Chang Allison , Shu Liqi , Kala Narendra , Goldstein Eric D , Jayaraman Mahesh , Torabi Radmehr , Moldovan Krisztina , Perelstein Elizabeth , Furie Karen , Burton Tina M , Stretz Christoph , Gebregziabher Mulugeta , Liebeskind David S , Khatri Pooja , Prabhakaran Shyam , Yaghi Shadi
Published: February 2023

Introduction:
Data on predictors of early stroke recurrence in patients with symptomatic intracranial atherosclerotic disease (sICAD) is limited. We hypothesized that hypoperfusion delay predicts stroke recurrence within 90-days.

Methods:
We retrospectively collected all patients hospitalized with anterior circulation sICAD over 3 years (April 2019-April 2022) at a comprehensive stroke center. We collected demographics, clinical risk factors, radiological variables, and treatment strategies. Patients with an indication for anticoagulation such as atrial fibrillation and those with intracranial stenting or angioplasty were excluded. The outcome (verified by two independent reviewers) was recurrent stroke within 90 days in the affected artery. We assessed factors associated with stroke recurrence. We measured the effect of hypoperfusion delay volume on stroke recurrence using Cox-regression models.

Results:
Out of 131 sICAD hospitalizations during the study period, 66 involved the middle cerebral artery (MCA) M1 segment or intracranial internal carotid artery (ICA) and 44 patients met the inclusion criteria. The mean age was 71 years and 41% were women; 75% were treated with best medical management (dual antiplatelet therapy/high intensity statin therapy); and 75% had baseline perfusion imaging performed. Over 90 days, 11/44 (25%) patients had recurrent stroke. Factors associated with recurrence stroke were no best medical management (15.2% vs. 54.5%, p = 0.02), hypoperfusion Tmax>4 sec mismatch volume (p = 0.003), and hypoperfusion delay Tmax>6 sec mismatch volume (p=0.01). Using Youden’s cutoff for Tmax>4 sec mismatch (13 mL) and for Tmax>6 sec mismatch (5 mL), the risk of recurrent stroke at 90 days in separate models was higher in patients with Tmax>4 sec delay mismatch volume > 13 mL (HR 11.98 95% CI 1.48-96.96 p=0.02) and Tmax>6 sec mismatch volume > 5 mL (HR 4.37 95% CI 1.02-18.82, p=0.048). Effect size of the associations did not meaningfully change after adjusting for best medical management.

Conclusion:
Hypoperfusion delay is associated with an increased recurrent stroke risk within 90 days in patients with sICAD, despite best medical management. Validation by large prospective studies is warranted.
Abstract 43: Is Dual Antiplatelet Therapy Underutilized Following TIA And Minor Stroke?
Authors: Solomonow Jonathan , Marks Jamie R , Yarbrough Karen L , Mehndiratta Prachi , Chaturvedi Seemant
Published: February 2023

Background:
Initiation of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel plays a significant role in the secondary prevention of recurrent acute ischemic events following high risk transient ischemic attack (TIA) and minor acute ischemic stroke (AIS). However, some patients do not receive the same targeted therapy on discharge and are only maintained on single antiplatelet therapy. Our aim was to identify the variations in single vs dual antiplatelet prescribing practices at the time of discharge within a Stroke Clinical Network consisting of nine stroke centers located in rural, suburban, and urban geographical regions.

Methods:
The GWTG registry was queried for all patients >18 years old with a TIA or a minor AIS (admission NIHSS ≤5), who were admitted to a single hospital network between January 2018 and December 2021. Demographics collected including age, race, gender, and BMI. Patients on concurrent anticoagulation were excluded. We evaluated antiplatelet discharge practices at the tertiary stroke center vs the entire network, among men vs. women, African Americans (AA) vs whites, age 18-70 vs >70 years, and across BMI. Chi squared and generalized linear models were used to test significant relationships between subgroups.

Results:
Among 2953 patients with a TIA or minor AIS, the mean age was 67.3 (SD +/- 13.8 years), with 42% >70 years of age. 47.8% were women; 37% were AA and 60% were white. DAPT was prescribed at the time of discharge to 40% of patients overall. Gender was a significant factor with men (43%) more likely to get prescribed DAPT than females (37%) (p=.002). While BMI did not have a lone effect on number of antiplatelets (AP) prescribed, when it was included as a covariate, there was a significant effect on the number of AP prescribed; with the higher the BMI, the less likely patients were to receive DAPT. Differences according to age, race, and effect of whether the patient was discharged from a tertiary center were not significant.

Conclusion:
We identified underutilization of DAPT following TIA and minor stroke across a health system, especially in women. Targeted intervention to increase DAPT use could lead to reduced rate of short-term stroke recurrence.
Abstract TMP36: Determining The Association Between Characteristics Of Congestive Heart Failure And Cognition
Authors: Kong Sandra T , Gootee Emma , Williams Nicole , Gottesman Rebecca F , Johansen Michelle C
Published: February 2023

Introduction:
It is not well known if specific measures of congestive heart failure (CHF) severity are associated with cognitive performance. We therefore aim to determine if there is an association between CHF characteristics and cognitive test scores, controlling for risk factors.

Methods:
230 CHF outpatients presenting to an outpatient CHF clinic with no dementia, preceding transthoracic echocardiogram (TTE) within 1 year, and ability to provide consent were included. A trained psychometrist administered the Mini Mental State Exam (MMSE), Rey Complex Figure (RCF) Copy and Immediate Recall test, and Letter Number Sequencing (LNS) test. The New York Heart Association (NYHA) heart failure classification and heart failure type (HFpEF vs HFrEF) were collected at time of consent and verified with medical records. Two measures of diastolic function (deceleration time (DT), E/A ratio) were collected from TTEs. Multivariable linear regression models were used to estimate the association between each cardiac function measure and cognitive test (Z scores), adjusted for confounders, in distinct models.

Results:
Patients were mean age 67 years (SD 13.6), 34% Black, and 49% female. Median time from TTE to cognitive test was 97 days (IQR 31.5 - 198). NYHA class 3-4 patients had on average a worse LNS score when compared to NYHA class 1-2 patients, which remained significant after adjusting for covariates (β: -0.52; 95%CI: -0.87, -0.17). A worse NYHA class was associated with a worse RCF copy score, but only in univariate analysis (Table 1) and not with RCF immediate recall. HFpEF was associated with a worse immediate recall but not after adjustment. Diastolic dysfunction measures had no association with any cognitive test, nor any CHF measure with MMSE.

Conclusion:
In a cohort of CHF patients, we found an association between a worse stage of heart failure and worse performance on some, but not all cognitive tests. These data suggest that brain health is a critical outcome in CHF care.
Abstract TMP52: Racial And Ethnic Disparities In Hospitalization Cost After Accounting For The Influence Of Hospital Length Of Stay
Authors: de Havenon Adam , Bangad Aaron , Aldridge Chad , Southerland Andrew M , Sheth Kevin N
Published: February 2023

Background:
Hospitalization length of stay (LOS) and cost are used as quality metrics, but there are known racial and ethnic disparities. For individuals with ischemic stroke, the relationship between LOS, cost, and race/ethnicity has not been fully examined.

Methods:
We included adult discharges from the National Inpatient Sample 2016-2019 with a baseline NIHSS, primary discharge diagnosis of ischemic stroke (I63*), and LOS ≤14 days to limit outlier LOS admissions. The primary outcome was hospitalization cost, which the NIS defines as a cost-to-charge ratio times charges. The exposure was race/ethnicity, which was abstracted from the medical record. We fit linear regression models and compared models with and without LOS to determine if it changed the point estimates of our outcome.

Results:
The cohort contained 128,399 discharges (mean age 69.5±14.0, 49.0% Female, median NIHSS 4 (1-8), and median LOS of 3 (2-5) days). In the model without LOS, White individuals had the lowest cost. After LOS adjustment, Black individuals had significantly lower cost than other race/ethnicities (Figure 1). As shown in Table 1, after adjusting for LOS, Black stroke hospitalizations cost $256.8 less than White, while hospitalizations for other race/ethnicities cost anywhere from $300-867 more than White. A separate analysis of the same dataset yielded that a greater proportion of Black patients (16.4%) have Medicaid at discharge versus White patients (5.6%).

Conclusions:
Hospitalization cost for Black patients is confounded by their length of stay. More research into the factors influencing this mediation is necessary; considering for example, the influence of waiting time for public insurance.
Abstract TMP85: Initial CT Perfusion Imaging Is Not A Significant Predictor Of Functional Outcome In Patients Undergoing Thrombectomy
Authors: Laursen Rachel K , Amin Sonesh D , Miller Parker , Clark Wayne M
Published: February 2023

Background:
In patients with acute ischemic stroke involving the anterior circulation who undergo mechanical thrombectomy (MT), it is not known which, if any, measure of ischemic core volume (ASPECTS, CBF <30% volume, or Tmax >10 seconds volume) is best at predicting functional outcome as defined by 90-day mRS. This retrospective study investigated the relationship between measures of ischemic core volumes and functional outcomes and compared these to known outcome predictors including baseline NIHSS and thrombectomy reperfusion success (TICI) scores.

Methods:
We included 100 consecutive patients with ischemic stroke due to internal carotid artery or middle cerebral artery occlusion who underwent CT perfusion and were treated with MT. CBF <30% volumes and Tmax >10 s volumes were automatically estimated using RAPID software. ASPECTS were automatically scored using e-ASPECTS software. TICI scores were graded by the case interventionalist and neurologist. Pearson correlation coefficients (r) were calculated to evaluate relationships between each predictor variable (initial NIHSS, TICI score, ASPECTS, CBF <30% volume, and Tmax >10 s volume) and the dependent variable (90-day mRS).

Results:
As expected, there was a significant relationship between both baseline NIHSS and TICI score and 90-day mRS (NIHSS-mRS r=0.25, R
2
=0.063, p=0.01; TICI-mRS r=-0.28, R
2
=0.077, p=0.005). In contrast, all measures of ischemic core volume had very low, non-significant correlations with 90-day mRS (ASPECTS-mRS r=-0.057, R
2
=0.0032, p=0.6; CBF <30% volume-mRS r=0.0042, R
2
=0, p=0.9; Tmax >10 s volume-mRS r=-0.020, R
2
= 0.0004, p=0.9).

Conclusions:
Initial stroke severity and MT success remain the best predictors of functional outcomes in patients undergoing MT. None of the assessed markers of ischemic core volume predicted functional outcomes. These results only apply to thrombectomy patients and not to cases excluded by larger cores.
Abstract TP121: Association Between Neutrophil-lymphocyte Ratio And 30-day Infection And Thrombotic Outcomes After Intracerebral Hemorrhage: A CLEAR III Analysis
Authors: Kaleem Safa , Gusdon Aaron , Oh Stephanie , Merkler Alexander E , Avadhani Radhika , Awad Issam A , Hanley Daniel F , Kamel Hooman , Ziai Wendy C , Murthy Santosh
Published: February 2023

Introduction:
Serum neutrophil-lymphocyte ratio (NLR) is a surrogate marker for the inflammatory response after intracerebral hemorrhage (ICH), and is associated with perihematomal edema and long-term functional outcomes. Whether NLR is associated with short-term ICH complications is poorly understood.

Hypothesis:
NLR is associated with 30-day infection and thrombotic events after ICH.

Methods:
We performed a post hoc exploratory analysis of the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR) III trial. The study exposure was the serum NLR obtained at baseline, and on days 3 and 5. The co-primary outcomes, ascertained at 30 days, were any infection and a thrombotic event, defined as composite of cerebral infarction, myocardial infarction, or venous thromboembolism; both infection and thrombotic event were determined via adjudicated adverse event reporting. Binary logistic regression was used to study the relationship between NLR and outcomes, after adjustment for demographics, ICH severity and location, and treatment randomization.

Results:
Among the 500 patients enrolled in CLEAR III, we included 228 (45.6%) with no missing data on daily NLR in the first week. There were no differences in demographics, comorbidities, or ICH severity between patients with and without data on NLR. In adjusted logistic regression models, NLR at day 3 was associated with infection (OR, 1.2; 95% CI, 1.01-1.26), but not with thrombotic events (OR, 0.96; 95% CI, 0.85-1.10). Conversely, NLR at day 5 was associated with thrombotic events (OR, 1.2, 95% CI, 1.01-1.26), but not with infections (OR, 1.03; 95% CI, 0.94-1.14). NLR at baseline was not associated with either outcome.

Conclusions:
Serum NLR ascertained between days 3 and 5 was associated with 30-day infection and thrombotic events after ICH, suggesting that NLR could be a potential early biomarker for ICH-related complications.
Abstract TP142: Intravenous Thrombolysis In Combination With Mechanical Thrombectomy: An Updated Meta-Analysis Of Clinical Trials
Authors: Elfil Mohamed , Ghaith Hazem , Aladawi Mohammad , Morsi Rami , Al-Mufti Fawaz
Published: February 2023

Introduction:
Mechanical thrombectomy (MT) is the gold standard for large vessel occlusion (LVO) strokes. The current guidelines state that LVO patients who are eligible for intravenous thrombolysis (IVT) and MT should receive both treatments. However, a few trials investigated the benefits and safety of combining MT with IVT. We conducted this meta-analysis to provide collective evidence on the efficacy and safety of IVT+MT, and to estimate the risk of complications of this approach as compared to MT alone.

Methods:
We performed a comprehensive literature search of 4 databases (PubMed, Scopus, Web of Science, Cochrane CENTRAL). For outcomes with continuous data, the mean difference (MD) between both groups from the baseline to the endpoint, with its standard deviation (SD), were pooled in the DerSimonian-Laird (DL) random-effect model. For studies reporting data in multiple time points, we considered the last endpoint for the primary analysis. For outcomes with dichotomous data, the frequency of events and the total number of patients in each group were pooled as relative risk (RR) between both groups in the DL random-effect model. All statistical analyses were done by RevMan.

Results:
7 clinical trials were included in the meta-analysis with a total of 2,317 patients. There were no significant differences between both groups in terms of functional independence (90-day mRS score 0-2: RR 1.03, 95% CI [0.90 to 1.19], P=0.65), successful recanalization (TICI score ≥2b: RR 1.04, 95% CI [0.92 to 1.17], P=0.53), complete recanalization (TICI score 3: RR 1.06, 95% CI [0.86 to 1.30], P=0.60), or mortality (RR 0.94, 95% CI [0.76 to 1.18], P=0.61). Regarding complications, there were no significant differences between both groups in terms of symptomatic intracranial hemorrhage (RR 0.94, 95% CI [0.74 to 1.20], P=0.64), or any intracranial hemorrhage (RR 1.12, 95% CI [0.94 to 1.34], P=0.57).

Conclusion:
Our results did not favor either IVT+MT or MT alone in terms of clinical outcomes and complications. However, more trials are needed to further compare both approaches and to evaluate the impact of certain factors on this comparison such as MT technique (Stent Retriever versus Aspiration), LVO location, and the used thrombolytic agent (Alteplase versus Tenecteplase).
Abstract TP46: Eye Telestroke Exam Device For Improved Triage In Stroke Pilot Study
Authors: Jumaa Mouhammad A , Castonguay Alicia C , Salahuddin Hisham , Lateef Sohaib , Alhajala Hisham , Storad Zachary , Parlette Stacy L , Burgess Richard , Zaidi Syed F
Published: February 2023

Background:
Telemedicine has enabled hospitals without stroke specialists to efficiently triage acute ischemic stroke patients; however, ~10-15% of patients with posterior circulation stroke present with visual loss, visual field deficit, or visual obscuration that can only be detected by thorough bedside examination. We have developed a novel, provisionally patented, device which allows for remote visual field assessment in patients with suspected stroke. The Eye Telestroke Exam Device consists of 3D goggles and custom software that tracks a patient’s eye movements when they respond to visual stimuli within the goggle’s screens and verbal commands given by the remote Neurology specialist. The device system is designed to pair (via Bluetooth technology) with any telemedicine system and will allow the remote examiner to perform a detailed visual field examination remotely.

Objective:
In this pilot study, we aim to evaluate the sensitivity and specificity of the Telestroke Eye Exam device to evaluate visual fields in healthy individuals and in patients who already have suffered a posterior circulation stroke and have permanent visual field deficits.

Methods and Design:
The Eye Telestroke Exam Device for Improved Triage in Stroke (EYE-TEST) Pilot study is a 2-arm, prospective study of patients with either a history of posterior circulation stroke with visual disturbances (stroke group) or patients with no visual disturbances (control). A roll in phase of 5 patients in each group will be performed, prior to enrollment of 20 patients into each arm. Investigators performing the device exam will be blinded to patient history. Device performance (sensitivity and specificity) will be compared to conventional bedside visual field assessment in each group. The device exam will be repeated twice for each patient.

Results:
The roll-in phase of the EYE-STUDY showed 100% sensitivity and specificity for detecting visual field disturbances in the stroke group. No abnormalities were detected in the control group.

Conclusion:
Enrollment into the study is ongoing and estimated study completion will occur October 2022. Final results of the EYE-TEST study will be presented at ISC 2023. Results of this study will inform future design iterations and studies.
Abstract TP72: Advance Care Planning Engagement May Increase Among Stroke Survivors: Results From The Prepare For Your Care Trial
Authors: Skolarus Lesli E , Brown Devin , Reynolds Evan , Shi Ying , Volow Aiesha , Burke James F , Sudore Rebecca
Published: February 2023

Introduction:
Despite their high risk of mortality, recurrent stroke, and dementia, stroke survivors underutilize ACP. In a non-prespecified subgroup analysis of a randomized trial to increase ACP, we compared the efficacy of the PREPARE for Your Care (PREPARE) plus an easy-to-read advance directive (AD) to an AD alone among stroke survivors.

Methods:
PREPARE is an interactive digital program with easy-to-read, state-specific ADs, and video stories. Stroke survivors in the PREPARE trial were identified using the
International Classification of Diseases
codes. The primary outcome was new ACP documentation in the electronic medical record after 12 months; secondary outcome was self-reported ACP completion of: (1) signing official papers naming a surrogate decision maker; (2) discussion of patients’ wishes with surrogates; (3) discussion of patients’ wishes with medical providers; and (4) an AD, scored 0-4. We calculated the change from baseline to 12-month follow-up. Mixed-effects regression models were used, adjusted for health literacy (adequate or limited), baseline ACP documentation, and clustering by physician.

Results:
Of 986 PREPARE trial participants, 91 (9.2%) were stroke survivors and 72 had complete data. The mean age was 64 years (SD, 6.8 years), 47% were women, 74% identified as a minority race/ethnicity, 40% were Spanish-speaking, 49% had limited health literacy, and 41% had ACP before enrollment. There was a trend toward greater ACP documentation in the PREPARE-arm (table). The PREPARE-arm had significantly greater increase in completed ACP elements than the AD-only arm.

Discussion:
The PREPARE program shows promise to engage ethnically diverse stroke survivors in ACP and should be studied further. Addition of stroke-specific content and engagement of acute stroke survivors in adaptations may increase the impact of the program.
Abstract WMP18: Stroke Nurse Navigator Team Utilization Towards Reduction Of Unplanned 30-day Readmissions Following Stroke
Authors: Grigoriciuc Eliza , Gulati Akanksha , Henninger Nils , Silver Brian , Donahue Kelsey , Kobayashi Kimiyoshi , Moonis Majaz , Jun-Oconnell Adalia
Published: February 2023

Background:
Unplanned 30-day hospital readmissions following a stroke is recognized as a serious quality and safety issue in the United States. The transition period from the hospital discharge is recognized as a vulnerable period in which medication errors and loss of ambulatory follow-ups can potentially occur. There, we sought to determine if 30-day stroke readmission can be prevented with utilization of a stroke nurse navigator team. Our secondary outcome of interest was 90-day outcome events.

Methods:
We first retrospectively analyzed 1657 consecutive patients presenting with ischemic or hemorrhagic strokes, included in an institutional stroke registry between January 2018 and August 2020, the time before the utilization of stroke nurse navigator teams. The stroke nurse navigator interventions included medication reviews, hospitalization course review, stroke education, and establishment of outpatient follow-ups within 3 days following the discharge. Following the stroke nurse navigator team phone checks ins in September 2020, we then retrospectively analyzed 851 consecutive patients presenting with stroke, included in the registry between September 2020 and December 2021.

Results:
Baseline 30-day stroke readmission rate was 11.7% (194/1657) before nurse navigator team. The Readmission rate reduced to 8.2% (71/870), which was statistically significant (p<0.05) following the period that utilized stroke nurse navigator team. Baseline 90-day death and cardiovascular events before the stroke nurse intervention was 5.4% (89/1657) and 8.1% (134/1657), respectively. Following the intervention, there was also no statistical difference in the 90-day outcome events of death and cardiovascular event 6.2% (27/433) and 7.3% (32/433), p>0.05.

Conclusion:
Utilization of the Stroke nurse navigator team can reduce unplanned 30-day stroke readmissions, but it did not have an impact on 90-day clinical outcome. Further studies are warranted to study the relationship between resource utilization during transition period from discharge and quality outcome in stroke.
Abstract WMP93: Additional Endovascular Thrombectomy Passes After An Initial TICI2b Reperfusion To Improve Final Reperfusion Grade Does Not Improve Functional Outcomes
Authors: Tariq Muhammad Bilal , Jeevarajan Jerome , Nahhas Michael I , Salazar-Marioni Sergio , Abdelkhaleq Rania , Niktabe Arash , Sheth Sunil
Published: February 2023

Background:
First pass complete or near complete reperfusion defined as a modified Thrombolysis in Cerebral Infarction (mTICI) 2c/3 is the target for endovascular thrombectomy (EVT). Here, we examine whether additional passes in patients who achieve a first pass mTICI 2b, in order to attain mTICI 2c/3, improve clinical outcomes.

Methods:
From our prospectively maintained institutional registry at 4 comprehensive stroke centers, we identified patients treated with EVT (11/2017-12/2021). Per-pass mTICI grades were recorded at the time of the procedure. The primary outcome was functional independence rates at 90 days (mRS 0-2) in first pass mTICI 2b patients compared with multiple passes mTICI 2c/3 patients.

Results:
A total of 857 EVT patients were identified in the study period. The median age was 68 [58-79], 49.7% were female, median NIHSS was 16 [11-21], median ASPECTS was 9 [7-10], and 64% had MCA occlusions. First pass mTICI 2c/3 (FP-mTICI 2c/3) was achieved in 342 (39.9%) cases and first pass mTICI 2b (FP-mTICI 2b) was achieved in 123 (14.4%) patients. Of the FP-mTICI 2b group, 27 (21.9%) patients received additional passes to reach complete reperfusion. Good functional outcome was observed in 159 patients (46.5%) of the FP-mTICI 2c/3 reperfusion group as compared to 27 patients (28.1%) in the FP-mTICI 2b group (p=0.002). The rate of good functional outcome was not significantly different for patients who achieved mTICI 2c/3 following additional passes after a first pass mTICI 2b (28.1 vs. 29.6%, first pass mTICI 2b vs. first pass mTICI 2b with final mTICI 2c/3, p=0.954). Adjusted for age, sex and NIHSS at presentation, patients with FP-mTICI 2c/3 had a better chance of good outcomes than patients with FP-mTICI 2b (OR 2.23, 95% CI [1.38-3.62]). In multivariable analysis adjusting for age, sex, and NIHSS at presentation, patients with FP-mTICI 2b reperfusion followed by improved reperfusion to mTICI 2c/3 did not have better outcomes than patients with FP-mTICI 2b reperfusion (OR 1.14, 95% CI [0.41-3.12]).

Conclusions:
Additional EVT passes to achieve mTICI 2c/3 following a first pass mTICI 2b does not lead to significant improvement in functional outcomes. This study suggests that EVT can be terminated if FP-mTICI 2b-3 is achieved.
Abstract WP1: Tenecteplase Vs Alteplase For Large Vessel Occlusion Stroke: A Systematic Review And Meta-analysis
Authors: Cierny Marek , Herath Chehan , Moore Caitlin , Attar Hatim , Binder Jeffrey R , Licenik Radim , Uchino Ken
Published: February 2023

Introduction:
Patients with large vessel occlusion stroke (LVO) benefit from thrombolysis before thrombectomy. Previous meta-analysis suggested superiority of tenecteplase over alteplase in achieving good clinical outcome at 3 months.

Aim:
We aimed to compare clinical outcomes after tenecteplase 0.25 mg/kg versus alteplase in patients with LVO.

Methods:
An experienced librarian searched PubMed and Scopus databases through July 13, 2022 for randomized controlled trials comparing tenecteplase with alteplase in patients with LVO. We included trials using 0.25 mg/kg tenecteplase dose, reporting blindly assessed pre-specified clinical outcomes at 3-4 months among patients with LVO. Two authors independently reviewed eligibility and extracted the data. We used RevMan 5.4 and random effect models with inverse variance weights to calculate odds ratios (OR) and 95% confidence intervals (CI). This systematic review is registered (CRD42022349414).

Results:
From 585 retrieved abstracts, 3 trials and 1 pooled secondary analysis involving 704 unique patients met the inclusion criteria. Among patients with LVO, tenecteplase 0.25mg/kg is not superior to alteplase in achieving good clinical outcome (defined as modified Rankin Scale [mRS] 0-2, OR 1.82 (95% CI 0.91-3.65, panel A); nor all-cause mortality, OR 0.75 (95% CI 0.49-1.13, panel B); while tenecteplase increases the odds of excellent outcome (mRS 0-1), OR 1.52 (95% CI 1.11-2.09, panel C), and odds of functional improvement (defined as a shift on the ordinal mRS), OR 1.54 (95% CI 1.07-2.20, panel D). High heterogeneity was present (I2 =70%) for the good clinical outcome.

Conclusion:
Tenecteplase is not superior over alteplase in achieving good clinical outcome. Tenecteplase, as compared to alteplase, increases the odds of functional improvement and excellent outcome. These findings support bridging tenecteplase in patients with LVO.
Abstract WP242: Transcriptomic Changes In Peripheral Blood Leukocytes Associated With The Cerebral Amyloid Angiopathy Small Vessel Disease Score
Authors: Munsterman Danielle , Falcione Sarina , Long Rebecca , Joy Twinkle , Clarke Mike , Beaudin Andrew E , Camicioli Richard , Smith Eric E , Jickling Glen
Published: February 2023

Introduction:
Cerebral amyloid angiopathy (CAA) is a cerebrovascular disease characterized by beta-amyloid deposition within cerebral vessels. Clinical markers of CAA severity include recurrent ICH, cognitive decline, and imaging features of CAA including microhemorrhage, dilated perivascular spaces, cortical superficial siderosis, and white matter hyperintensities. CAA is an important cause of cognitive decline and intracerebral hemorrhage in the elderly, leading to the need for CAA treatments. The contribution of the immune system to CAA severity is not well understood. This study sought to evaluate changes in peripheral leukocyte gene expression associated with CAA severity.

Methods:
In 22 patients with CAA peripheral blood was collected into PAXgene tubes. RNA was isolated, and sequencing performed. Differentially expressed genes based on CAA small vessel disease (CAA-SVD) score as a marker of CAA severity were identified using ANOVA and functional pathway analysis. The relationship between leukocyte gene expression and CAA severity were assessed.

Results:
ANOVA was used to identify genes that were associated with CAA-SVD score (p≤0.05, partial correlation coefficient ≥;|0.5|).
HDAC11, IL23A, TRAIL, TRAILR1
,
TRAILR2
, and
ICAM-1
were associated with CAA severity (CAA-SVD score). Canonical pathway analysis identified included induction of T lymphocytes, binding of antigen presentation cells, IL-12 signaling in macrophages/monocytes, activation of phagocytes, tight junction signaling, and activation of antigen presenting cells to be associated with CAA severity (p≤0.05).

Conclusion:
An association between the peripheral immune system and CAA severity was identified. Changes in neutrophil, monocyte, and Th17 cell gene expression in peripheral blood was associated with CAA severity. Further evaluation of immune system changes associated with CAA severity is needed to understand contribution to cerebral small vessel disease, cognitive decline, and potential roles as treatment targets or risk stratification markers in CAA.
Abstract WP30: Positive Covid-19 Cases Requiring Neurology Consultation: Review Of Death Status
Authors: Bush Kelly
Published: February 2023

Background and Purpose:
Identify characteristics contributing to death in patients with Covid-19 and neurology consultation

Hypothesis:
We suspected many characteristics contributed to death in those with Covid-19 requiring neurologic consultation based on our clinical experience and prior descriptive study.

Methods:
A retrospective review of the characteristics of 200 patients with Covid-19 requiring neurology consultation from April 2020 to February 2021 were analyzed. Continuous variables were summarized by mean ± standard deviation and compared using the Student’s T-test of Wilcoxon rank-sum test. Categorical variables were summarized by frequency and percent and compared using Chi-squared or Fisher’s exact tests. Analyses were preformed with the use of SAS software (version 9.4). P-value < 0.01 was considered statistically significant.

Results:
The patients who were deceased tended to be older compared to the patients who were alive (73.1 ± 12.4 vs. 64.7 ± 17.6, P-value = 0.001). Patients who were deceased had lower RBC (3.9 ± 1.0 vs 4.5 ± 1.7, P-value=0.006) and higher creatinine (2.3 ± 2.5 vs 1.4 ± 1.3, P-value = 0.003). Patients who were deceased were more likely to have impaired consciousness, coma, acute stroke, and encephalopathy compared to patients who were alive (83.1% vs 41.3%, 56.9% vs 16.9%, 48.3% vs 22.7%, and 86.2% vs. 62.3%). Among 58 with acute stroke, there was no statistically significant difference in type of stroke (38.5% vs 53.6%, P-value = 0.265) or intervention on stroke (15.4% vs 20.7%, P-value = 0.732) by death status. The patients with stroke who were deceased had lower platelets (180.4 ± 98.5 vs 276.6 ± 145.5, P-value = 0.004). Stroke patients who were deceased were more likely to have impaired consciousness and coma (78.6% vs 43.4%, and 53.6% vs 17.2%, respectively).

Conclusion:
Patients requiring neurologic consultation with Covid-19 have a higher likelihood of death in the setting of acute stroke, coma, encephalopathy, low RBC count, and elevated creatinine; and those with stroke had higher mortality with low platelet count. Further studies with early intervention to improve these factors may play a role in reducing morality.