bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Thermodiffusion and Chemical Reaction on Magnetohydrodynamic-Radiated Unsteady Flow Past an Exponentially Accelerated Inclined Permeable Plate Embedded in a Porous Medium
Authors: Prabhakar Reddy B. , Simba M. H. , Hugo Alfred
Published: April 2023

A finite difference computational study is conducted to assess the influence of thermodiffusion and chemical reaction on unsteady free convective radiated magnetohydrodynamic flow past an exponentially accelerated inclined permeable plate embedded in a saturated porous medium of uniform permeability with variable temperature and concentration. The governing nondimensional set of coupled nonlinear partial differential equations with related initial and boundary conditions are solved numerically by using the accurate and efficient DuFort–Frankel’s explicit finite difference method. The physical features of fluid flow, heat, and mass transfer under the influence of the magnetic field, angle of inclination, plate acceleration, radiation, heat source/sink, thermodiffusion, chemical reaction, and time are scrutinized by plotting graphs and then discussed in detail. It was found that the effective magnetic field and angle of inclination tend to decline the fluid motion, whereas the reverse result is detected by increasing the porosity parameter and plate acceleration. The velocity and temperature of the fluid lessen with increasing the radiation parameter. The effect of thermodiffusion raises the fluid velocity and concentration, whereas a chemical reaction has the opposite impact. The Nusselt number increases with increasing the radiation parameter and time. Increasing chemical reaction and time causes to improve the Sherwood number. This kind of problem finds momentous industrial applications such as food processing, polymer production, inclined surfaces in a seepage flow, and design of fins.
Superior Optimization for a Hybrid PEMFC Power System Employing Model Predictions
Authors: Wang Fu-Cheng , Wang Jian-Zhi
Published: April 2023

This research investigated the impacts of model prediction on the optimization of hybrid energy systems using a system consisting of solar panels, batteries, a proton exchange membrane fuel cell (PEMFC), and a chemical hydrogen generation system. A PEMFC has several advantages, such as low operating temperatures, fast response times, high power density, and environmental friendliness, and it can convert hydrogen into electricity. However, because hydrogen costs are an important consideration, the PEMFC is usually integrated with hybrid energy systems to guarantee system sustainability. Therefore, in this study, a whole-year household load and solar radiation data were applied to optimize the system components and power management, thereby reducing the system cost by 42.43% and improving system sustainability by 7.05%. The system responses showed that some hydrogen consumption might be saved if the solar and load profiles could be foreseen. Two prediction models were developed that could accurately forecast the radiation and load profiles. Next, a second-year dataset was employed to verify the effectiveness of the model prediction. The results showed that the system cost was reduced by 40.20% without model prediction and by 44.06% with model prediction compared to the original system settings. Finally, experiments to illustrate the feasibility of the hybrid energy system were conducted using prediction models. Based on the results, the model prediction was deemed effective in improving the performance of hybrid energy systems.
Supplementary Figure 2 from Co-Clinical Study of [fam-] Trastuzumab Deruxtecan (DS8201a) in Patient-Derived Xenograft Models of Uterine Carcinosarcoma and Its Association with Clinical Efficacy
Authors: Yagishita Shigehiro , Nishikawa Tadaaki , Yoshida Hiroshi , Shintani Daisuke , Sato Sho , Miwa Maiko , Suzuki Mikiko , Yasuda Masanori , Ogitani Yusuke , Jikoh Takahiro , Yonemori Kan , Hasegawa Kosei , Hamada Akinobu
Published: April 2023

ER and p53 immunohistochemistry of original and patient-derived xenograft (PDX) tumors
Supplementary Table S4 from Osimertinib and Selpercatinib Efficacy, Safety, and Resistance in a Multicenter, Prospectively Treated Cohort of EGFR-Mutant and RET Fusion-Positive Lung Cancers
Authors: Rotow Julia , Patel Jyoti D. , Hanley Matthew P. , Yu Helena , Awad Mark , Goldman Jonathan W. , Nechushtan Hovav , Scheffler Matthias , Kuo Chih-Hsi S. , Rajappa Senthil , Harada Guilherme , Clifford Sarah , Santucci Alison , Silva Laura , Tupper Rebecca , Oxnard Geoffrey R. , Kherani Jennifer , Drilon Alexander
Published: April 2023

Adverse events observed with combination therapy
Data from An immune-related gene expression signature predicts benefit from adding atezolizumab to FOLFOXIRI plus bevacizumab in metastatic colorectal cancer
Authors: Antoniotti Carlotta , Boccaccino Alessandra , Seitz Robert , Giordano Mirella , Catteau Aurélie , Rossini Daniele , Pietrantonio Filippo , Salvatore Lisa , McGregor Kimberly , Bergamo Francesca , Conca Veronica , Leonetti Simone , Morano Federica , Papiani Giorgio , Tamburini Emiliano , Bensi Maria , Murgioni Sabina , Ross Douglas Teller. , Passardi Alessandro , Boquet Isabelle , Nielsen Tyler J. , Galon Jerome , Varga Matthew Gordon. , Schweitzer Brock L. , Cremolini Chiara
Published: April 2023

Abstract
Background: AtezoTRIBE phase II randomized study demonstrated that adding atezolizumab to first-line FOLFOXIRI (5fluoruracil, oxaliplatin, irinotecan) plus bevacizumab prolongs progression-free survival (PFS) of metastatic colorectal cancer (mCRC) patients, with a modest benefit among proficient mismatch repair (pMMR). DetermaIO is an immune-related 27-gene expression signature able to predict benefit from immune-checkpoint inhibition in triple-negative breast cancer. In this analysis of AtezoTRIBE, we investigated the predictive impact of DetermaIO in mCRC. Methods: mCRC patients unselected for MMR status were randomized(1:2) to FOLFOXIRI plus bevacizumab (control arm) or the same regimen with atezolizumab (atezolizumab arm). RT-qPCR by DetermaIO was performed on RNA purified from pre-treatment tumours of 132(61%) out of 218 enrolled patients. A binary result (IOpos versus IOneg) adopting the pre-established DetermaIO cut-point (0.09) was obtained, and an exploratory optimized cut-point (IOOPT) was computed in the overall population and in pMMR subgroup (IOOPTpos versus IOOPTneg). Results: DetermaIO was successfully determined in 122 (92%) cases, and 23 (27%) tumours were IOpos. IOpos tumours achieved higher PFS benefit from atezolizumab arm than IOneg (HR:0.39 versus 0.83, P interaction=0.066). In pMMR tumours (N=110), a similar trend was observed (HR:0.47 versus 0.93, P interaction=0.139). In the overall population, with the computed IOOPT cut-point (0.277), 16 (13%) tumours were IOOPTpos and they derived higher PFS benefit from atezolizumab than IOOPTneg(HR:0.10 versus 0.85, P interaction=0.004). Similar results were found in the pMMR subgroup. Conclusions :DetermaIO may be useful to predict benefit of adding atezolizumab to first-line FOLFOXIRI plus bevacizumab in mCRC. The exploratory IOOPT cut-point should be validated in independent mCRC cohorts.
Data from Co-clinical study of [fam-] trastuzumab deruxtecan (DS8201a) in patient-derived xenograft models of uterine carcinosarcoma and its association with clinical efficacy
Authors: Yagishita Shigehiro , Nishikawa Tadaaki , Yoshida Hiroshi , Shintani Daisuke , Sato Sho , Miwa Maiko , Suzuki Mikiko , Yasuda Masanori , Ogitani Yusuke , Jikoh Takahiro , Yonemori Kan , Hasegawa Kosei , Hamada Akinobu
Published: April 2023

Abstract
Background: Uterine carcinosarcoma (UCS), a subtype of endometrial carcinoma, is a rare and aggressive cancer with a poor prognosis. High clinical efficacy of trastuzumab deruxtecan (T-DXd) in HER2-expressing UCS was recently reported in phase 2 trial (STATICE trial). We performed a co-clinical study of T-DXd using patient-derived xenograft (PDX) models of participants in the STATICE trial. Patients and methods: Tumor specimens were resected during primary surgery or biopsied at recurrence from patients with UCS and transplanted into immunodeficient mice. Seven UCS-PDXs from six patients were established and HER2, estrogen receptor (ER), and p53 expression in PDX and the original tumor was assessed. Drug efficacy tests were performed using six of the seven PDXs. Of the six UCS-PDXs tested, two were derived from patients enrolled in the STATICE trial. Results: The histopathological characteristics of the six PDXs were well-conserved from the original tumors. HER2 expression was 1+ in all PDXs, and ER and p53 expression was almost similar to that in the original tumors. Remarkable tumor shrinkage after T-DXd administration was observed in four out of the six PDXs (67%), comparable to the response rate (70%) of HER2 1+ patients in the STATICE trial. Two patients enrolled in the STATICE trial showed partial response as the best response, and the clinical effect was well-replicated with marked tumor shrinkage. Conclusion: We successfully performed a co-clinical study of T-DXd in HER2-expressing UCS, along with the STATICE trial. Our PDX models can predict clinical efficacy and serve as an effective preclinical evaluation platform.
Supplemental Table 1 from Reprogramming Cancer into Antigen-Presenting Cells as a Novel Immunotherapy
Authors: Linde Miles H. , Fan Amy C. , Köhnke Thomas , Trotman-Grant Aaron C. , Gurev Sarah F. , Phan Paul , Zhao Feifei , Haddock Naomi L. , Nuno Kevin A. , Gars Eric J. , Stafford Melissa , Marshall Payton L. , Dove Christopher G. , Linde Ian L. , Landberg Niklas , Miller Lindsay P. , Majzner Robbie G. , Zhang Tian Yi , Majeti Ravindra
Published: April 2023

Summary of clinical features of primary B-ALL specimens
Data from Reprogramming Cancer into Antigen Presenting Cells as a Novel Immunotherapy
Authors: Linde Miles H. , Fan Amy C. , Kohnke Thomas , Trotman-Grant Aaron C. , Gurev Sarah F. , Phan Paul , Zhao Feifei , Haddock Naomi L. , Nuno Kevin A. , Gars Eric J. , Stafford Melissa , Marshall Payton L. , Dove Christopher G. , Linde Ian L. , Landberg Niklas , Miller Lindsay P. , Majzner Robbie G. , Zhang Tian Yi. , Majeti Ravindra
Published: April 2023

Abstract
Therapeutic cancer vaccination seeks to elicit activation of tumor-reactive T cells capable of recognizing tumor-associated antigens (TAAs) and eradicating malignant cells. Here, we present a cancer vaccination approach utilizing myeloid lineage reprogramming to directly convert cancer cells into tumor reprogrammed-antigen presenting cells (TR-APCs). Using syngeneic murine leukemia models, we demonstrate that TR-APCs acquire both myeloid phenotype and function, process and present endogenous TAAs, and potently stimulate TAA-specific CD4+ and CD8+ T cells. In vivo TR-APC induction elicits clonal expansion of cancer-specific T cells, establishes cancer-specific immune memory, and ultimately promotes leukemia eradication. We further show that both hematologic cancers and solid tumors, including sarcomas and carcinomas, are amenable to myeloid-lineage reprogramming into TR-APCs. Finally, we demonstrate the clinical applicability of this approach by generating TR-APCs from primary clinical specimens and stimulating autologous patient-derived T cells. Thus, TR-APCs represent a cancer vaccination therapeutic strategy with broad implications for clinical immuno-oncology.
Supplementary Figure S9 from CD142 Identifies Neoplastic Desmoid Tumor Cells, Uncovering Interactions Between Neoplastic and Stromal Cells That Drive Proliferation
Authors: Al-Jazrawe Mushriq , Xu Steven , Poon Raymond , Wei Qingxia , Przybyl Joanna , Varma Sushama , van de Rijn Matt , Alman Benjamin A.
Published: April 2023

Cytokine antibody array to identify differentially secreted factors from isolated mutant and non-mutant cells.
Supplementary Figure S8 from CD142 Identifies Neoplastic Desmoid Tumor Cells, Uncovering Interactions Between Neoplastic and Stromal Cells That Drive Proliferation
Authors: Al-Jazrawe Mushriq , Xu Steven , Poon Raymond , Wei Qingxia , Przybyl Joanna , Varma Sushama , van de Rijn Matt , Alman Benjamin A.
Published: April 2023

Co-culturing of mutant desmoid tumor cells with non-mutant fibroblasts increases their proliferation rate
Odds of Medical Comorbidities in Essential Tremor: Retrospective Analysis of a Large Claims Database in the United States
Authors: Kapinos Kandice A. , Louis Elan D.
Published: April 2023

Introduction: Essential tremor (ET) is the most common tremor disorder, estimated to affect 7 million individuals in the USA. There is little empirical evidence on comorbidities among this population beyond higher prevalence of brain-related and stress-related disorders. This study aims to examine differences in the prevalence of the 31 Elixhauser comorbidities among ET patients compared to statistically similar control patients. Methods: An extract from Optum’s de-identified Clinformatics® Data Mart Database (CDM) from 2018 to 2019 of adults aged 40–80 years with at least one claim with an ET diagnosis was propensity score matched to controls. Logistic regression was used to generate doubly robust adjusted odds ratios for each of the 31 Elixhauser comorbidities. Results: In these analyses, ET patients had significantly greater adjusted odds of depression, alcohol abuse, and other neurological disorders, as well as chronic pulmonary disease, renal failure, hyperthyroidism, and cardiac arrhythmias relative to controls. They also had lower odds of uncomplicated diabetes, congestive heart failure, metastatic cancer, paralysis, peripheral vascular disease, and fluid and electrolyte disorders. Conclusion: A number of recent studies, including our own, suggest that psychiatric, neurologic, and stress-related disorders may be more prevalent among ET patients than controls. Additional differences in the prevalence of a range of medical comorbidities have also been variably reported across studies, suggesting that some combination of these might be more prevalent. Further studies would be of value in sorting through these associations.
Relationship between Serial Serum Neutrophil-Lymphocyte Ratio, Cardiovascular Mortality, and All-Cause Mortality in Chinese Peritoneal Dialysis Patients
Authors: Lau Lik Fung Sam , Ng Jack K.C. , Fung Winston W.S. , Chan Gordon C.K. , Cheng Phyllis Mei-Shan , Chow Kai Ming , Leung Chi Bon , Li Philip Kam-To , Szeto Cheuk Chun
Published: April 2023

Introduction: It is believed that the excessive cardiovascular (CV) burden of patients on peritoneal dialysis (PD) is closely associated with chronic inflammation. Neutrophil-lymphocyte ratio (NLR) is an inflammatory marker that was shown to correlate with CV outcomes. However, little is known about the significance of serial monitoring of serum NLR. We aimed to determine the prognostic value of serial NLR on all-cause mortality and CV mortality in PD patients. Methods: Serial measurement of NLR was obtained from 225 incident PD patients in a single center, with each measurement 1 year apart. Patients were divided into two groups (“high” vs. “low”) by the median value of NLR. The primary and secondary outcome measure was all-cause and CV mortality, respectively. Results: After a median of follow-up for 43.9 months, patients with lower baseline NLR demonstrated a higher survival rate (p = 0.01). Patients with persistently high NLR values on serial measurement had the lowest survival rate (p = 0.03). Multivariate Cox regression showed that this group of patients had significantly higher all-cause mortality (HR: 1.74, 95% CI: 1.09–2.79, p = 0.02). However, the NLR failed to demonstrate a statistically significant relationship with CV mortality. Conclusions: While baseline NLR was an independent predictor of all-cause mortality in PD patients, persistent elevation in NLR appeared to further amplify the risk. Regular monitoring of serial serum NLR may enable early identification of patients who are at risk of adverse outcome.
Brain Structural Correlates of Obstacle Negotiation in Mild Cognitive Impairment: Results from the Gait and Brain Study
Authors: Pieruccini-Faria Frederico , Hassan Haddad Seyyed Mohammad , Bray Nickolas W , Sarquis-Adamson Yanina , Bartha Robert , Montero-Odasso Manuel
Published: April 2023

Introduction: Mild cognitive impairment (MCI) affects obstacle negotiation capabilities, potentially increasing the risk of falls in older adults. However, it is unclear whether smaller brain volumes typically observed in older individuals with MCI are related to the observed hazardous obstacle negotiation in this population. Methods: A total of 93 participants (71.9 ± 5.36 years of age; MCI = 53/control = 40) from the Gait and Brain Study were analyzed. Gray matter (GM) volumes from the frontal, temporal, and parietal lobes were entered in the analysis. Gait performance was recorded using a 6-m electronic walkway during two cognitive load conditions while approaching and stepping over an obstacle: (1) single-task and (2) while counting backwards by 1s from 100 (dual-task). Anticipatory adjustments in gait performance to cross an “ad hoc” obstacle were electronically measured during pre-crossing phases: early (3 steps before the late phase) and late (3 steps before obstacle). Association between the percentage of change in average gait speed and step length from early to late (i.e., anticipatory adjustments) and GM volumes was investigated using multivariate models adjusted for potential confounders. Results: Anticipatory adjustments in gait speed (Wilks’ lambda: 0.35; Eta2: 0.64; p = 0.01) and step length (Wilks’ lambda: 0.33; Eta2: 0.66; p = 0.01) during dual-task conditions were globally associated with GM volumes in MCI. Individuals with MCI with smaller GM volumes in the left inferior frontal gyrus, left hippocampus, right hippocampus, and right entorhinal cortex made significantly fewer anticipatory gait adjustments prior to crossing the obstacle. Conclusion: Frontotemporal atrophy may affect obstacle negotiation capabilities potentially increasing the risk of falls in MCI.
Comparative Study of Cerebral Venous Thrombosis-Risk Factors, Clinical Course, and Outcome in Subjects with and without COVID-19 Infection
Authors: Hameed Sajid , Hamza Anwar , Taimuri Bushra , Khan Maria , Mehndiratta Man Mohan , Wasay Mohammad
Published: April 2023

Background/Objective: Cerebral venous thrombosis (CVT) has been increasingly reported in patients with COVID-19. Most published literature is descriptive and focuses only on CVT in COVID-19 patients. The objective of our study was to compare CVT patients’ characteristics with and without an associated COVID-19 infection. Materials and Methods: This is a retrospective cross-sectional study. All adult patients with a confirmed diagnosis of CVT admitted to our hospital over a period of 30 months, from January 2019 to June 2021, were included. They were further divided into two groups, with and without COVID-19 infection. Results: A total of 115 CVT patients were included, 93 in non-COVID-CVT and 22 in COVID-CVT group. COVID-CVT patients were male predominant and of older age, with longer hospital stay, and higher inpatient mortality. COVID-CVT patients presented with a higher frequency of headache (82% vs. 63%), seizures (64% vs. 37%, p = 0.03), hemiparesis (41% vs. 24%), and visual changes (36% vs. 19%) as compared to non-COVID-CVT patients. Venogram showed a higher frequency of superior sagittal sinus (64% vs. 42%) and internal jugular vein (23% vs. 12%) involvement in the COVID-CVT cohort. More than 90% of patients in both groups received therapeutic anticoagulation. Mortality rates were higher in COVID-CVT group (18% vs. 11%). Conclusion: COVID-CVT patients were male predominant and of older age, with higher hospital stay, and higher inpatient mortality as compared to non-COVID-CVT patients.
Abstract 10180: Systolic Blood Pressure Time in Target Range and Cognitive Outcomes: Insights From the SPRINT Trial
Authors: Li Sitong , Jiang Chao , Wang Yufeng , Lai Yiwei , HE liu , Tang Ribo , Jiang Chen-Xi , Sang Caihua , Long Deyong , Du Xin , Dong jz , Ma Changsheng
Published: April 2023

Introduction:
Systolic blood pressure (SBP) time in target range (TTR) was proven to be a new parameter to predict cardiovascular outcomes. However, the prognostic value for cognitive function is unclear.

Hypothesis:
Higher TTR was associated with lower incidence of cognitive outcomes.

Methods:
We performed a post hoc analysis from the Systolic Blood Pressure Intervention Trial (SPRINT), a randomized controlled trial comparing intensive (<120 mm Hg) and standard (<140 mm Hg) SBP interventions in 9361 individuals with hypertension. SBP target range was defined as 110 to 130 mm Hg for the intensive group and 120 to 140 mm Hg for the standard group. Participants who had less than 3 SBP measurements during this period or no cognitive assessment in the follow-up were excluded. TTR was calculated by linear interpolation using SBP from baseline to the first 3 months of follow-up. Cognitive outcomes were probable dementia, mild cognitive impairment (MCI), and a composite of probable dementia or MCI. Cox regression models were used to evaluate the relationship between TTR and cognitive outcomes.

Results:
A total of 8415 patients were included in this study. In univariate Cox regression analysis, higher time in target range was associated with lower risk of probable dementia. After adjustment for age, sex and race, a 1-SD increase in TTR was independently associated with a 16% lower risk of probable dementia (hazard ratio [HR] =0.84, 95% CI 0.75-0.93, P =0.002) (Figure). When we further added demographics, medical history and mean SBP to the multivariate Cox regression model, TTR remained significantly associated with a decreased risk of probable dementia (HR =0.84, 95% CI 0.74-0.96, P =0.012). No significant relationship was found between TTR and MCI or a composite of probable dementia or MCI.

Conclusions:
In this post hoc analysis of the SPRINT trial, SBP time in target range was an independent predictor of probable dementia beyond mean SBP levels.
Serum and Pulmonary Expression Profiles of the Activin Signaling System in Pulmonary Arterial Hypertension
Authors: Guignabert Christophe , Savale Laurent , Boucly Athénaïs , Thuillet Raphaël , Tu Ly , Ottaviani Mina , Rhodes Christopher J. , De Groote Pascal , Prévot Grégoire , Bergot Emmanuel , Bourdin Arnaud , Howard Luke S. , Fadel Elie , Beurnier Antoine , Roche Anne , Jevnikar Mitja , Jaïs Xavier , Montani David , Wilkins Martin R. , Sitbon Olivier , Humbert Marc
Published: April 2023

Background:

Activins are novel therapeutic targets in pulmonary arterial hypertension (PAH). We therefore studied whether key members of the activin pathway could be used as PAH biomarkers.

Methods:

Serum levels of activin A, activin B, α-subunit of inhibin A and B proteins, and the antagonists follistatin and follistatin-like 3 (FSTL3) were measured in controls and in patients with newly diagnosed idiopathic, heritable, or anorexigen-associated PAH (n=80) at baseline and 3 to 4 months after treatment initiation. The primary outcome was death or lung transplantation. Expression patterns of the inhibin subunits, follistatin, FSTL3, Bambi, Cripto, and the activin receptors type I (ALK), type II (ACTRII), and betaglycan were analyzed in PAH and control lung tissues.

Results:

Death or lung transplantation occurred in 26 of 80 patients (32.5%) over a median follow-up of 69 (interquartile range, 50–81) months. Both baseline (hazard ratio, 1.001 [95% CI, 1.000–1.001];
P
=0.037 and 1.263 [95% CI, 1.049–1.520];
P
=0.014, respectively) and follow-up (hazard ratio, 1.003 [95% CI, 1.001–1.005];
P
=0.001 and 1.365 [95% CI, 1.185–1.573];
P
<0.001, respectively) serum levels of activin A and FSTL3 were associated with transplant-free survival in a model adjusted for age and sex. Thresholds determined by receiver operating characteristic analyses were 393 pg/mL for activin A and 16.6 ng/mL for FSTL3. When adjusted with New York Heart Association functional class, 6-minute walk distance, and N-terminal pro-B-type natriuretic peptide, the hazard ratios for transplant-free survival for baseline activin A <393 pg/mL and FSTL3 <16.6 ng/mL were, respectively, 0.14 (95% CI, 0.03–0.61;
P
=0.009) and 0.17 (95% CI, 0.06–0.45;
P
<0.001), and for follow-up measures, 0.23 (95% CI, 0.07–0.78;
P
=0.019) and 0.27 (95% CI, 0.09–0.78,
P
=0.015), respectively. Prognostic values of activin A and FSTL3 were confirmed in an independent external validation cohort. Histological analyses showed a nuclear accumulation of the phosphorylated form of Smad2/3, higher immunoreactivities for ACTRIIB, ALK2, ALK4, ALK5, ALK7, Cripto, and FSTL3 in vascular endothelial and smooth muscle layers, and lower immunostaining for inhibin-α and follistatin.

Conclusions:

These findings offer new insights into the activin signaling system in PAH and show that activin A and FSTL3 are prognostic biomarkers for PAH.
Abstract Number ‐ 5: Interim Results of PRE‐SEAL IT Saccular Endovascular Aneurysm Lattice System First in Human Interventional Trial
Authors: Pabon Boris , Torres Victor , Patiño Manuel , Peláez Felipe , Mútis Jorge , Cardozo Margarita , Pereira Edgard , Badruddin Aamir , Woodward Keith , Wolfe Thomas , Zaidat Osama
Published: April 2023

Introduction

Preliminary in vivo animal intracranial aneurysm (IA) studies have demonstrated promising immediate and follow‐up aneurysm occlusion rates using the novel Saccular Endovascular Aneurysm Lattice (SEAL) system. The PRE‐SEALTM IT trial was designed to assess the feasibility, safety, and effectiveness of the SEAL system in patients with previously untreated ruptured and unruptured wide‐neck IA.

Methods

PRE‐SEAL IT is an on‐going, prospective, interventional, core‐lab adjudicated, single‐arm study performed in Medellin, Columbia. Key inclusion criteria included: 1. Age 20–80 years, 2. Saccular shape, bifurcation, or terminus IA, 3. Wide neck aneurysm with neck size ≥4 mm or dome‐to‐neck ratio <2, and 4. IA diameter 2mm to 25mm. Consented and enrolled patients were treated with the SEALTM device. A follow‐up DSA was performed at 24‐hours, 6 months, and 12 months and a MRA at 3 months. Final clinical follow‐up was at 24‐months. Primary efficacy outcome was achieving complete occlusion (WOS grade A or B) at 6 months angiographic follow up. Primary safety outcome was any stroke with an increase in NIHSS of 4 up to discharge.

Results

From December 2021 through June 2022, 15 patients have been enrolled into the PRE‐SEAL IT trial. Ten women and 5 men were treated with the SEAL device, with a mean age of 56.8±9.5 years. Of the 15 IA, 12 were anterior circulation (ICA‐T (1), MCA (7), AcomA (3), A2‐A3 (1)) and 3 posterior circulations (Basilar, VBJ‐fenestration, SCA), and 14 were unruptured (93.3%). Mean aneurysm width was 6.1±2.5mm. Immediate post‐procedure complete occlusion (Grade A, B) was achieved in 9 patients (60%) and adequate occlusion (Grade A, B, C) in 13 (86.6%). At 24‐hours follow‐up, 12 patients (80%) had complete occlusion and 15 (100%) achieved adequate occlusion. Six‐month complete occlusion rate (Grade A and B) was 100% (8/8). Interim results were site adjudicated. No cases of intraoperative rupture, or bleeding or re‐bleeding, or clinical stroke were observed.

Conclusions

The interim results of the PRE SEAL‐IT trial demonstrated promising complete occlusion rates at 24‐hour and 6 month follow‐up with no safety concerns. Trial enrollment will be completed in October, and final 24‐hour results will be presented at the 2022 SVIN Annual Meeting.
Abstract Number ‐ 18: Potential impact in low and middle‐income countries stroke networks of a deep learning triage tool
Authors: Lagos‐Servellon Javier , Bonifacio‐Delgadillo Dulce , Ribo Marc , Santamaria Cristina Granés , Punsoda Victor Salvia , Urtasun Agustina , Díaz Facundo Nahuel , Pou Cristian Martí
Published: April 2023

Introduction

Early and accurate identification of large vessel occlusion (LVO) and intracranial hemorrhage (ICH) on initial neuroimaging is essential in a stroke network. A machine learning algorithm (MLA) able to predict LVO or ICH on non‐contrast computed tomography (NCCT) may accelerate workflows.We performed a validation analysis to measure the MLA accuracy among suspected stroke patients transferred to a Comprehensive Stroke Centre (CSC) in Mexico and the possible impact on the workflow in low and middle income countries (LMIC) .

Methods

From February 2021 to March 2022 consecutive patients with suspected acute stroke who underwent NCCT and computed tomography angiography (CTA) were included. MLA prediction of LVO and ICH was tested against expert physicians readings and clinical follow‐up. We calculated sensitivity, specificity, positive predictive value and negative predictive value. Receiver operating curves were generated for MLA‐LVO, MLA‐ICH and; areas under the curve were calculated. Potential time savings and impact on workflow times were calculated for a scenario in which MLA could analyse initial NCCT at PSC avoiding imaging repetition at CSC.

Results

140 consecutive patients admitted from march 2021 to February 2022 were included in the study, final physicians diagnostics were: 22 ICH (15.7%) and 53 LVO (37.8%) MLA detected 22 ICH (15.7%) and 58 LVO (41.4%).The area under the curve for the identification of ICH with MLA was 0.97 (sensitivity: 94%, specificity: 91%, positive predictive value: 83.3%[MR1][JL2], negative predictive value: 100%). The area under the curve for the identification of LVO with MLA was 0.91 (sensitivity: 100%, specificity: 95.8%, positive predictive value: 85.7%, negative predictive value: 96.4%). Implementation of MLA‐LVO in the network could save CTA acquisition times of 40 (IQR 26) minutes by taking patients directly to the angiosuite for endovascular treatment.

Conclusions

In patients with suspected acute stroke, a MLA can quickly and reliably predict ICH and LVO. Such a tool could accelerate the diagnosis, mitigate the contrast imaging dependency and improve the workflow efficiency in stroke networks in LMIC where access to contrast imaging is often limited.
Abstract Number ‐ 22: Hemorrhagic Outcomes in Patients Demonstrating Early Venous Filling After Mechanical Thrombectomy For Acute Ischemic Stroke
Authors: Al‐Shaibi Faisal , Pujara Deep , Hassan Ameer , Abraham Michael , Sitton Clark , Shaker Faris , Duncan Kelsey , Chugh Arunit , Haussen Diogo , Ortega‐Gutierrez Santiago , Sundararajan Sophia , Hu Yin , Ray Abhishek , Sila Cathy , Bambakidis Nicholas , Sarraj Amrou
Published: April 2023

Introduction

Endovascular thrombectomy (EVT) for acute ischemic infarcts with large vessel occlusion have been shown to improve functional outcomes. However, there is still the risk of hemorrhagic transformation (HT). Early identification of patients at risk of HT is paramount to enhance EVT outcomes. EVF can be an indicator of the hyperemia that occurs following an infarct. We evaluated if early venous filling (EVF) defined as contrast filling of any cerebral vein within the arterial phase on angiogram can predict individuals at a higher risk of HT after EVT.

Methods

From the SELECT cohort,EVT patients with evaluable digital subtraction angiography were included in the study. Baseline clinical and imaging characteristics as well as clinical and hemorrhagic outcomes were compared between patients demonstrating EVF and no EVF. Association between EVF with symptomatic ICH and parenchymal hemorrhage was examined using multivariable logistic regression models.

Results

46/254 (18%) patients had EVF at the end of the procedure. Age and NIHSS were similar between the patients with and without EVF, although patients with EVF presented earlier (1.39 (0.88‐2.75) hours vs 2.62 (1.10‐4.28) hours, p = 0.024), and demonstrated lower CT ASPECTS (7 (6‐9) vs 8 (7‐9), p = 0.022). The presence of EVF was associated with significantly higher odds of sICH (EVF: 8.7% vs no EVF: 5.6%, aOR: 4.72, 95% CI: 1.05‐21.28, p = 0.043) and demonstrated a trend towards higher odds of parenchymal hemorrhage type 1 or 2 (EVF: 10.9% vs no EVF: 6.3%, aOR: 3.64, 95% CI: 0.96‐13.73, p = 0.057) and mortality (EVF: 17% vs no EVF: 12%, aOR: 3.22, 95% CI: 0.93‐11.13, p = 0.064). Functional outcomes did not differ at 90 days between the two groups

Conclusions

Early identification of EVF may help to identify patients with increased risk of hemorrhagic transformation after EVT. This finding was independent from time last known well. While EVF is suggestive of hyperemia it is also a biomarker of infarct volume and may help to implement early therapeutic measurements to reduce hemorrhagic transformation risk such as strict blood pressure control. Further studies to evaluate EVF as a potential marker for hemorrhagic transformation are required.
Abstract Number ‐ 24: Endovascular thrombectomy with or without bridging thrombolysis in patients with ischemic stroke: A cost‐utility analysis
Authors: Morsi Rami Z. , Zhang Yuan , Zhu Meng , Xie Shitong , Carrión‐Penagos Julián , Desai Harsh , Tannous Elie , Kothari Sachin , Khamis Assem , Tarabichi Ammar , Bastin Reena , Hneiny Layal , Thind Sonam , Coleman Elisheva , Brorson James R , Mendelson Scott J , Mansour Ali , Prabhakaran Shyam , Kass‐Hout Tareq
Published: April 2023

Introduction

There is clinical equipoise behind bridging intravenous thrombolysis (BT) with endovascular thrombectomy (EVT). We performed a cost‐effectiveness analysis comparing EVT and BT versus EVT alone.

Methods

We conducted a model‐based cost‐utility analysis comparing the cost‐effectiveness of EVT alone vs. EVT and BT for patients with acute ischemic stroke. We used a decision tree to examine the short‐term costs and outcomes at 90 days after the index stroke. Subsequently, we developed a Markov state transition model to assess the costs and outcomes over 1‐year, 5‐year, and 20‐year time horizons. Treatment costs were based on administrative data. Clinical outcome inputs were derived from literature included in our systematic review. We considered the impact of disability and recurrent stroke on mortality risk, health‐related quality of life, and costs. We estimated total and incremental cost, quality‐adjusted life years (QALYs), and incremental cost‐effectiveness ratio (ICER), expressed as an incremental cost per QALY gained of EVT and BT compared with EVT alone.Probabilistic analysis was used to calculate the reference case estimates.

Results

The average costs per patient were estimated to be $55,503, $57,814, $68,183, and $84,946 for EVT only strategy, and $47,311, $49,556, $59,625, and $75,898 for EVT and BT over 90‐day, 1‐year, 5‐year, and 20‐year, respectively. The cost saving of EVT only strategy was driven by the avoided medication costs of IVT (ranging from $8,193 to $9,048). The additional thrombolytics led to slight decrease in QALY estimate during the 90‐day time horizon (loss of 0.0016 QALY), but a small gain over 1‐year, 5‐year, and 20‐year time horizons (0.0108, 0.0638, and 0.1481 QALY). With similar outcomes and less cost, the EVT only strategy was cost‐effective compared with EVT and BT. Analyses with longer time horizon show lower probabilities of EVT only strategy being cost‐effective. At a fixed willingness to pay threshold of $50,000, the probabilities of EVT only to be cost‐effective were 100%, 100%, 99.0%, and 65.9% over 90‐day, 1‐year, 5‐year, and 20‐year time horizons. At the willingness to pay thresholds of $100,000 per QALY, the probabilities of EVT only strategy being cost‐effective was 22.8% over the 20‐year time horizon.

Conclusions

Our cost‐effectiveness model suggested that bridging with thrombolytics may not be cost‐effective for patients with acute ischemic stroke secondary to large vessel occlusion.
Abstract Number ‐ 25: Acute Ischemic Stroke Intervention With Penumbra RED Reperfusion Catheters: Updated Subset Analysis From INSIGHT Registry
Authors: Teleb Mohamed S , Kellner Christopher P , Dabney Alan R , Baltan Selva , Sohrabji Farida , Pennypacker Keith R , Woodward Keith B , Nanda Ashish , Rivet Dennis J , Fraser Justin F
Published: April 2023

Introduction

The prospective INSIGHT Registry is a multicenter ‘multi‐omic’ analysis of thrombi associated with acute hemorrhagic or ischemic stroke. This updated interim analysis evaluated the performance of Penumbra RED catheters used during aspiration thrombectomy for acute ischemic stroke (AIS).

Methods

All AIS cases in which Penumbra RED aspiration catheters (RED 62, 68, or 72) were utilized as a frontline treatment were included in the analysis. Retrieved clot fragments were classified based on their gross appearance. Key time metrics and procedural data were also collected, including first‐pass / post‐procedure modified Treatment in Cerebral Ischemia (mTICI) score.

Results

Of 400 patients enrolled across 25 US centers, 161 underwent thrombectomy with Penumbra RED catheters over ten months (Jul 2021 through Apr 2022). The mean patient age was 70.7 years, and 50.9% were female. The middle cerebral artery first segment (M1) was the most common primary occlusion site (60.4%; 96/159). IV t‐PA was administered before the procedure in 13.7% (22/161) of patients. The median time from stroke onset / last known well to mTICI≥ 2b was 5.0 hrs. [IQR 3‐11], and the median time from a puncture to mTICI≥ 2b was 23.0 mins [IQR 15‐31]. Firm‐red clots represented 45.3% (67/148), while soft‐red clots were found in 37.8% (56/148) of retrieved clots. In turn, firm‐white and soft‐white clots were seen in 11.5% (17/148) and 5.4% (8/148) of cases, respectively. Rates of the first pass and final mTICI≥ 2b scores by clot type are shown in Table 1.

Conclusions

Aspiration thrombectomy with Penumbra RED catheters resulted in good revascularization rates for all clot types.
Abstract Number ‐ 46: Automated Magnetic Resonance Perfusion Imaging in the Management of Delayed Cerebral Ischemia: A Pilot Study
Authors: Khatibi Kasra , Vespa Paul , Blanco Manuel Buitrago
Published: April 2023

Introduction

Inadequate perfusion secondary to changes in vascular narrowing and breakdown of cerebral autoregulation is thought to be a major contributor to delayed cerebral ischemia (DCI). Subjective evaluation of narrowing of large and medium intracranial vessels on angiography detects vasospasm in up to 70% of patients, though only 30% become clinically symptomatic. There are no available tools for the quantification of tissue level perfusion to detect critical levels of ischemia in this setting. We aimed to evaluate focal perfusion changes using MR‐perfusion weighted imaging with automated thresholding of flow and timing parameters in the setting of DCI.

Methods

This is a prospective observational pilot study that includes seven patients with SAH. All patients underwent multimodality MRI including diffusion and perfusion imaging when there was concern for DCI. RAPID software was used to process diffusion and perfusion images and obtain threshold maps for diffusion restriction, Tmax prolongation and drops in cerebral blood volume (CBV), and cerebral blood flow (CBF). Correspondence of neuroanatomic location of focal perfusion alteration and pattern of perfusion alteration was evaluated.

Results

Neuroanatomical location of perfusion alteration corresponded to neurological symptoms in 86% (6/7) of patients. The prominent patterns were: prolongation of Tmax greater than four seconds (7/7), greater than 20% drop in CBF (3/7), and greater than 20% drop in CBV (3/7). Significant radiographic vasospasm on concurrently catheter angiogram and/or MR angiogram which corresponded to the supplying vessels to the neuroanatomic area with altered perfusion was seen in 71% (5/7) of the patients.

Conclusions

MRI‐perfusion imaging using RAPID software can help detect and quantify the presence of inadequate focal perfusion for DCI in real‐time. This tool could guide the timing and extent of endovascular vasodilatory and medical hyperdynamic treatment and larger studies of MRI‐perfusion imaging for DCI are warranted.
Abstract Number ‐ 69: Intrathecal Nicardipine for Severe Intractable Reversible Cerebral Vasoconstriction Syndrome (RCVS): A Novel Case Report
Authors: Wakefield Colin , Ngo Brendon , Naydin Stanislav , Rahme Rudy , Binning Mandy
Published: April 2023

Introduction

Reversible Cerebral Vasoconstriction Syndrome (RCVS) is a poorly understood but increasingly recognized entity, likely multifactorial in nature and characterized by diffuse cerebral vasospasm that present as sudden, intense, fluctuating headaches. A subset of RCVS patients can present with concomitant TIAs, cerebral infarctions, leukoencephalopathy, subarachnoid hemorrhages (SAH), and seizures. Due to insufficient evidence, there is currently no consensus on RCVS treatment guidelines. Calcium channel blockers such as nimodipine and verapamil have reportedly been employed with varying degrees of efficacy. Nicardipine, an L‐type calcium channel blocker, may prove effective in RCVS treatment because of its ability to penetrate the blood‐brain barrier. However, to date, only 5 case reports have discussed the use of intrathecal (IT) nicardipine for the treatment of severe RCVS, and there has been very limited exploration of continuous intraarterial (IA) administration. This case report examines the use of IT and continuous IA nicardipine in an RCVS patient refractory to traditional management.

Methods

We present the case of a 58‐year‐old female who was noted to have a non‐traumatic non‐aneurysmal SAH secondary to RCVS. The patient’s only risk factor for RCVS was alcoholic use. Initially managed with oral verapamil, she later developed refractory symptomatic vasoconstriction requiring multiple angiograms for spasmolysis via balloon angioplasty and IA nicardipine. Due to the refractory nature of her spasm despite the IA therapy, we decided to attempt intrathecal nicardipine, starting at 4 mg q12hours via an external ventricular drain (EVD). This dose was escalated to 4mg q6hours. The patient stabilized for 24 hours but again decompensated, requiring continuous IA spasmolysis via a microcatheter that was placed in the L MCA and left for continuous IA nicardipine infusion (5mg/hr). The patient showed slow incremental improvement clinically and a decrease in vasospasms on imaging, ultimately suffering minimal stroke burden.

Results

The patient subsequently showed improvement over time in neurological function and a decrease in vasospasms on CTA, MRA, and angiogram imaging, ultimately suffering minimal stroke burden (Fig. 1B).

Conclusions

Nicardipine, administered intrathecally utilizing an EVD or even intraarterial through a microcatheter, could potentially be beneficial in select patients with refractory RCVS to minimize repeat angiography/angioplasty. We suggest further studies to determine SAH incidence following RCVS and the efficacy of continuous intrathecal administration of the blood‐brain barrier penetrating calcium channel blocker, nicardipine, in RCVS patients.
Abstract Number ‐ 85: Distal Anterior Choroidal Artery Fusiform Aneurysm Successfully Treated with Flow Diversion
Authors: Mahmoud Noor A , Ernst Griffin , Grossen Audrey A , Bauer Andrew
Published: April 2023

Introduction

Anterior choroidal artery (AChA) aneurysms account for 3–5% of intracranial aneurysms, and are often saccular, arising at or near the origin of the AChA, with distal lesions being exceedingly rare. Contrary to saccular aneurysms, fusiform aneurysms are associated with a higher risk of rebleeding and mortality due to their formidable anatomy requiring advanced techniques including bypass, stent‐assisted coiling, and, more recently, flow diversion. While flow diverters are becoming more popular, they are currently only approved forinternal carotid artery segment aneurysms. However, many institutions areexpanding their use to more distal and smaller caliber vessels. Herein we present a novel pathology of a dissecting distal AChA fusiform pseudoaneurysm with a small vessel caliber treated successfully with flow diversion.

Methods

Case presentation and surgical technique.

Results

We describe a 40‐year‐old woman with monoclonal gammopathy of unknown significance (MGUS), lichen sclerosis, and an unspecified connective tissue disease presenting with diffuse subarachnoid hemorrhage (SAH) (World Federation of Neurosurgical Societies 1; Hunt & Hess scale 2; Modified Fisher Scale 3). A digital subtraction cerebral angiogram revealed a dissecting (5×3 mm) left AChA pseudoaneurysm, 4mm distal to the origin (Figure 1). Flow Redirection Endoluminal Device (FRED Jr, Microvention, CA) (2.5mm 8/13 working/total length) was deployed within the vessel proximal to the aneurysm, preceded by an infusion of 5mg of verapamil to facilitate stent placement (Figure 2). Post procedure, she remained neurologically intact and was discharged on dual antiplatelet therapy (aspirin/ticagrelor). Repeat cerebral angiogram at six months showed patent flow diversion device and no pseudoaneurysm remnant (Figure 3) with a nonfocal physical examination.

Conclusions

Flow diversion may be a successful, and safe, therapeutic intervention for challenging distal intracranial aneurysms with smaller caliber vessels.
Abstract Number ‐ 88: Stroke Secondary to Free Floating Thrombus in a Post‐COVID Patient
Authors: Nagendra Shashank
Published: April 2023

Introduction

In non COVID ‐19 patients, carotid intraluminal floating thrombi are rare, with a prevalence of 1.6% among patients with acute stroke/TIA In the COVID era, considerable number of cases with thrombus have been reported.

Methods

Here we report a case of a 47 year old female patient who presented with sudden onset left hemiparesis, dysarthria and facial deviation since 12 hours. She had h/o covid 1 month ago MRI Brain – DWI showed multiple embolic infarcts in right MCA territory MRI Angio – moderate to high grade stenosis at the origin of ICA

Results

Patient was taken up for DSA. Thromboaspiration done and Xact stent deployed across carotid bifurcation into right ICA Post op patient did well and her weakness had almost completely resolved

Conclusions

Highlighting points in this patient: lack of or only mild underlying atherosclerosis, no cardioembolic source. The highly prothrombotic state of some COVID 19 patients explains the presence of thrombus in medium and large vessels with or without mild atherosclerotic disease.
Abstract Number ‐ 117: Sandwich technique as rescue therapy. (Stent retriever)
Authors: Pabon Boris , Torres Victor , Patiño Manuel , Pelaez Juan , Mutis Jorge , Cardozo Margarita
Published: April 2023

Introduction

system to extract foreign bodies in the cerebral circulation with 2 stent retrievers (solitare)

Methods

We present 2 cases in which we have had to withdraw devices. (Flow diverter due to poor opening and coil due to distal migration.)

Results

2 cases are presented, in which we used the technique developed by angioteam. In the first case we rescued a flow diverter stent that was exchanged for another stent. In the second case, we the rescued the coils that migrated from the internal carotid artery to the medium cerebral artery.

Conclusions

It is a rescue technique in which a distal stent retriever and a second proximal device are pulled between them to catch the device that is going to be removed Both cases were successfull in removing the flow diverter stent and coil.