bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from SALVO: Single-Arm Trial of Ipilimumab and Nivolumab as Adjuvant Therapy for Resected Mucosal Melanoma
Authors: Kottschade Lisa A. , Pond Gregory Russell , Olszanski Anthony J. , Zakharia Yousef , Domingo-Musibay Evidio , Hauke Ralph J. , Curti Brendan D. , Schober Sarah , Milhem Mohammed M. , Block Matthew Stephen , Hieken Tina , McWilliams Robert R.
Published: April 2023

AbstractPurpose:
Mucosal melanoma is a rare, aggressive form of melanoma with extremely high recurrence rates despite definitive surgical resection with curative intent. Currently there is no consensus on adjuvant therapy. Data on checkpoint inhibitors for adjuvant therapy are lacking.
Patients and Methods:
We performed a single-arm, multicenter clinical trial using “flip dose” ipilimumab (1 mg/kg q3w × 4 cycles), and nivolumab (3 mg/kg q3w × 4 cycles), then nivolumab 480 mg q4w × 11 cycles to complete a year of adjuvant therapy. Participants must have had R0/R1 resection ≤90 days before registration, no prior systemic therapy (adjuvant radiotherapy allowed), ECOG 0/1, and no uncontrolled autoimmune disease or other invasive cancer. Patients were recruited through the Midwest Melanoma Partnership/Hoosier Oncology Network.
Results:
From September 2017 to August 2021, 35 patients were enrolled. Of these, 29 (83%) had R0 resections, and 7 (20%) received adjuvant radiotherapy. Median age was 67 years, 21 (60.0%) female. Recurrence-free survival (RFS) rates at 1 and 2 years were 50% [95% confidence interval (CI), 31%–66%] and 37% (95% CI, 19%–55%), respectively. Overall survival rates at 1 and 2 years were 87% (95% CI, 68%–95%) and 68% (95% CI, 46%–83%), respectively. Median RFS was 10.3 months (95% CI, 5.7–25.8). Most common grade 3 toxicities were diarrhea (14%), hypertension (14%), and hyponatremia (11%), with no grade 4/5 toxicities.
Conclusions:
Flip-dose ipilimumab and nivolumab after resection of mucosal melanoma is associated with outcomes improved over that of surgical resection alone. Long-term follow-up, subgroup analyses and correlative studies are ongoing.
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 Jérôme , Varga Matthew Gordon , Schweitzer Brock L. , Cremolini Chiara
Published: April 2023

AbstractPurpose:
AtezoTRIBE phase II randomized study demonstrated that adding atezolizumab to first-line FOLFOXIRI (5-fluorouracil, oxaliplatin, irinotecan) plus bevacizumab prolongs progression-free survival (PFS) of patients with metastatic colorectal cancer (mCRC), 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.
Experimental Design:
Patients with mCRC unselected for MMR status were randomly assigned (1:2) to FOLFOXIRI plus bevacizumab (control arm) or the same regimen with atezolizumab (atezolizumab arm). qRT-PCR by DetermaIO was performed on RNA purified from pretreatment tumors of 132 (61%) of 218 enrolled patients. A binary result (IOpos vs. IOneg) adopting the preestablished DetermaIO cut-off point (0.09) was obtained, and an exploratory optimized cut-off point (IOOPT) was computed in the overall population and in pMMR subgroup (IOOPTpos vs. IOOPTneg).
Results:
DetermaIO was successfully determined in 122 (92%) cases, and 23 (27%) tumors were IOpos. IOpos tumors achieved higher PFS benefit from atezolizumab arm than IOneg (HR: 0.39 vs. 0.83; Pinteraction = 0.066). In pMMR tumors (N = 110), a similar trend was observed (HR: 0.47 vs. 0.93; Pinteraction = 0.139). In the overall population, with the computed IOOPT cut-off point (0.277), 16 (13%) tumors were IOOPTpos and they derived higher PFS benefit from atezolizumab than IOOPTneg (HR: 0.10 vs. 0.85, Pinteraction = 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-off point should be validated in independent mCRC cohorts.
ctDNA Monitoring for Small Cell Lung Cancer: Ready for Prime Time?
Authors: Pellini Bruna , Chaudhuri Aadel A.
Published: April 2023

Small cell lung cancer (SCLC) is the deadliest form of lung cancer and has few precision medicine approaches available. A recent study analyzed circulating tumor DNA (ctDNA) in 33 patients with extensive-stage SCLC and showed that ctDNA levels and response patterns correlate strongly with clinical response and survival outcomes.

See related article by Sivapalan et al., p. 2310
Dynamic Intestinal Stem Cell Plasticity and Lineage Remodeling by a Nutritional Environment Relevant to Human Risk for Tumorigenesis
Authors: Choi Jiahn , Zhang Xusheng , Li Wenge , Houston Michele , Peregrina Karina , Dubin Robert , Ye Kenny , Augenlicht Leonard
Published: April 2023

New Western-style diet 1 (NWD1), a purified diet establishing mouse exposure to key nutrients recapitulating levels that increase human risk for intestinal cancer, reproducibly causes mouse sporadic intestinal and colonic tumors reflecting human etiology, incidence, frequency, and lag with developmental age. Complex NWD1 stem cell and lineage reprogramming was deconvolved by bulk and single-cell RNA sequencing, single-cell Assay for Transposase-Accessible Chromatin using sequencing, functional genomics, and imaging. NWD1 extensively, rapidly, and reversibly, reprogrammed Lgr5hi stem cells, epigenetically downregulating Ppargc1a expression, altering mitochondrial structure and function. This suppressed Lgr5hi stem cell functions and developmental maturation of Lgr5hi cell progeny as cells progressed through progenitor cell compartments, recapitulated by Ppargc1a genetic inactivation in Lgr5hi cells in vivo. Mobilized Bmi1+, Ascl2hi cells adapted lineages to the nutritional environment and elevated antigen processing and presentation pathways, especially in mature enterocytes, causing chronic, protumorigenic low-level inflammation. There were multiple parallels between NWD1 remodeling of stem cells and lineages with pathogenic mechanisms in human inflammatory bowel disease, also protumorigenic. Moreover, the shift to alternate stem cells reflects that the balance between Lgr5-positive and -negative stem cells in supporting human colon tumors is determined by environmental influences. Stem cell and lineage plasticity in response to nutrients supports historic concepts of homeostasis as a continual adaptation to environment, with the human mucosa likely in constant flux in response to changing nutrient exposures.

Implications:

Although oncogenic mutations provide a competitive advantage to intestinal epithelial cells in clonal expansion, the competition is on a playing field dynamically sculpted by the nutritional environment, influencing which cells dominate in mucosal maintenance and tumorigenesis.
Supplemental Figure S8 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

TR-APC induction in solid tumor models attenuates tumor growth kinetics and prolongs survival
Supplemental Figure S5 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

In vivo TR-APC induction drives oligoclonal T cell expansion
Supplemental Figure S3 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

In vivo TR-APC induction results in expansion of activated and memory T cells, and decreased frequency of Tregs
Supplemental Figure S2 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

In vivo TR-APC induction results in no observable off-target toxicity
Data from Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer
Authors: Pradat Yoann , Viot Julien , Yurchenko Andrey A. , Gunbin Konstantin , Cerbone Luigi , Deloger Marc , Grisay Guillaume , Verlingue Loic , Scott Véronique , Padioleau Ismael , Panunzi Leonardo , Michiels Stefan , Hollebecque Antoine , Jules-Clément Gérôme , Mezquita Laura , Lainé Antoine , Loriot Yohann , Besse Benjamin , Friboulet Luc , André Fabrice , Cournède Paul-Henry , Gautheret Daniel , Nikolaev Sergey I.
Published: April 2023

Abstract
Metastatic relapse after treatment is the leading cause of cancer mortality, and known resistance mechanisms are missing for most treatments administered to patients. To bridge this gap, we analyze a pan-cancer cohort (META-PRISM) of 1,031 refractory metastatic tumors profiled via whole-exome and transcriptome sequencing. META-PRISM tumors, particularly prostate, bladder, and pancreatic types, displayed the most transformed genomes compared with primary untreated tumors. Standard-of-care resistance biomarkers were identified only in lung and colon cancers—9.6% of META-PRISM tumors, indicating that too few resistance mechanisms have received clinical validation. In contrast, we verified the enrichment of multiple investigational and hypothetical resistance mechanisms in treated compared with nontreated patients, thereby confirming their putative role in treatment resistance. Additionally, we demonstrated that molecular markers improve 6-month survival prediction, particularly in patients with advanced breast cancer. Our analysis establishes the utility of the META-PRISM cohort for investigating resistance mechanisms and performing predictive analyses in cancer.
Significance:
This study highlights the paucity of standard-of-care markers that explain treatment resistance and the promise of investigational and hypothetical markers awaiting further validation. It also demonstrates the utility of molecular profiling in advanced-stage cancers, particularly breast cancer, to improve the survival prediction and assess eligibility to phase I clinical trials.
Data 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

Abstract
Therapeutic cancer vaccination seeks to elicit activation of tumor-reactive T cells capable of recognizing tumor-associated antigens (TAA) 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-APC). 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.
Significance:
Despite recent advances, the clinical benefit provided by cancer vaccination remains limited. We present a cancer vaccination approach leveraging myeloid-lineage reprogramming of cancer cells into APCs, which subsequently activate anticancer immunity through presentation of self-derived cancer antigens. Both hematologic and solid malignancies derive significant therapeutic benefit from reprogramming-based immunotherapy.
Supplementary Table S2 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

Enriched markers in mutant and non-mutant colonies from our high throughput surface antigen screen.
Supplementary Figure S6 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

Correlation between estimated mutation frequency from Sanger sequencing and percent CD142-positive cells in heterogeneous desmoid tumor samples
Supplementary Figure S4 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

Podoplanin-based flow cytometry of mutant and non-mutant colonies.
Supplementary Figure S12 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

Representative gating strategy
Supplementary Figure S1 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

Decreasing mutational frequency with increasing passages in a desmoid tumor primary culture.
Early Detection of Pancreatic Cancer
Authors: Schwingel Jérôme , Decker Miriam , Schneider Lisa , Stürmer Carsten Johannes , Lutz Manfred P.
Published: April 2023

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy that is increasingly common. Screening for pancreatic cancer is not well established but might increase the chance of detection in early stages. Summary: We conducted a literature search to summarize current recommendations and to give an overview of patient groups that may benefit from screening. In the general population, screening is not recommended because the low prevalence of PDAC renders any diagnostic tests non-predictive and because there is no direct evidence that links early diagnosis to improved survival. To date, novel approaches like liquid biopsies and molecular markers are not yet able to improve screening in unselected individuals but offer promising potential. Screening efficiency increases considerably with increasing pretest probability. Therefore, the best way to improve early diagnosis is identifying high-risk individuals. Key Messages: There are well-defined populations with distinct genetic alterations with an increased risk for pancreatic cancer. Those may be screened with common diagnostic methods. In addition, new-onset diabetes is increasingly recognized as an early symptom, especially in elderly patients with weight loss.
The Glasgow Prognostic Score Predicts Survival in Patients with Advanced Non-Small Cell Lung Cancer Harboring Sensitive Epidermal Growth Factor Receptor Mutations Who Are Treated with Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors
Authors: Akazawa Yuki , Igawa Satoshi , Yamada Kaori , Yamamoto Hiroki , Yagami Yuri , Kaizuka Nobuki , Manaka Hiroya , Kasajima Masashi , Nakahara Yoshiro , Sato Takashi , Mitsufuji Hisashi , Yokoba Masanori , Kubota Masaru , Sasaki Jiichiro , Naoki Katsuhiko
Published: April 2023

Introduction: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) with sensitive EGFR mutations. The Glasgow prognostic score (GPS) is an inflammation-assessing score based on C-reactive protein and albumin concentrations. Information regarding the association between the GPS and EGFR-TKI treatment effectiveness is limited; hence, we investigated whether the GPS can predict the response of NSCLC to EGFR-TKIs. Methods: We evaluated 340 patients with NSCLC harboring sensitive EGFR mutations who received EGFR-TKI monotherapy between March 2009 and July 2021. The Kaplan-Meier method and Cox proportional hazards models were used to assess progression-free survival (PFS) and overall survival (OS). Results: After a median follow-up of 26.6 months, patients with a GPS of 0, 1, and 2 had PFS of 15.7, 10.0, and 6.3 months, respectively, and OS of 40.1, 25.8, and 14.4 months, respectively; patients with a GPS of 0 had significantly better PFS and OS than those with a GPS of 1 (p = 0.03, p = 0.001, respectively) or 2 (p < 0.001, p < 0.001, respectively). Multivariate analysis identified poor performance status, stage 4 at diagnosis, type of EGFR-TKI (gefitinib/erlotinib vs. afatinib), and GPS = 2 as predictors of a short PFS. Meanwhile, poor performance status, gefitinib/erlotinib administration, and GPS = 2 were predictors of a short OS. Conclusion: The GPS predicted the survival of NSCLC patients harboring sensitive EGFR mutations who were undergoing EGFR-TKI treatment. The GPS might be ideal for routine use in clinical practice, given that it is an easily calculated parameter.
Abstract Number ‐ 2: Intravenous Thrombolysis for Pediatric Ischemic Stroke: Twenty Years of Population‐Level Data in the United States
Authors: Dicpinigaitis Alis J , Shapiro Steven D , Nuoman Rolla , Kamal Haris , Overby Philip , Kaur Gurmeen , Chong Ji Y , Fifi Johanna T , Dangayach Neha , Miller Eliza C , Yaghi Shadi , Al‐Mufti Fawaz
Published: April 2023

Introduction

Although intravenous thrombolysis (IVT) represents standard‐of‐care treatment for acute ischemic stroke (AIS) in eligible adult patients, definitive evidence‐based guidelines and randomized clinical trial data evaluating its safety and efficacy in the pediatric population remain absent from the literature. We aim to evaluate the utilization and outcomes of IVT for the treatment of pediatric AIS using a large national registry.

Methods

Weighted hospitalizations for pediatric (<18 years of age) AIS patients were identified in the National Inpatient Sample during the period of 2001 to 2019. Complex samples statistical methods were performed to assess unadjusted and adjusted outcomes in patients treated with IVT or other medical management.

Results

Among 13,901 pediatric AIS patients, 270 (1.9%) were treated with IVT monotherapy (median age 12.8 years). IVT‐treated patients developed any intracranial hemorrhage (ICH) at a rate of 5.6% (n = 15), and 71.9% (n = 194) experienced favorable functional outcomes at discharge (to home or to acute rehabilitation). Following propensity‐score adjustment for age, acute stroke severity, infarct location, and etiological/comorbid conditions, IVT was not associated with an increased risk of any ICH [5.6% vs. 5.4%, p = 0.931; adjusted odds ratio (aOR) 1.01, 95% confidence interval (CI) 0.48, 2.14, p = 0.971], nor with favorable functional outcome (71.9% vs. 74.5%, p = 0.489; aOR 0.88, 95% CI 0.60, 1.29, p = 0.511) in comparison with other medical therapy.

Conclusions

Twenty years of population‐level data in the United States demonstrate that pediatric AIS patients treated with IVT experienced high rates of favorable outcomes without an increased risk of hemorrhagic transformation.
Abstract Number ‐ 6: Basilar Artery Occlusion Thrombectomy Technique: An International Survey of Practice Patterns
Authors: Klein Piers , Herning Ana , Drumm Brian , Raymond Jean , Abdalkader Mohamad , Sahoo Anurag , Siegler James E , Chen Yimin , Huo Xiaochuan , Schonewille Wouter J , Liu Xinfeng , Hu Wei , Ji Xunming , Lapergue Bertrand , Li Chuanhui , Alemseged Fana , Strbian Daniel , Fischer Urs , Kaesmacher Johannes , Yamagami Hiroshi , Puetz Volker , Sacco Simona , Kristoffersen Espen Saxhaug , Demeestere Jelle , Lobotesis Kyriakos , Aydin Kubilay , Diana Francesco , Masoud Hesham E , Ma Alice , Novakovic‐White Roberta , Al‐Mufti Fawaz , Ton Mai Duy , Gentric Jean Christophe , Caroff Jildaz , Psychogios Marios‐Nikos , Meyer Lukas , Fiehler Jens , English Joey , Gupta Rishi , Yan Bernard , Campbell Bruce , Jadhav Ashutosh P , Lee Jin Soo , Thomalla Götz , Nagel Simon , Zaidat Osama O , Qiu Zhongming , Miao Zhongrong , Banerjee Soma , Nguyen Thanh N
Published: April 2023

Introduction

Two recent trials demonstrated a benefit for endovascular thrombectomy (EVT) in the treatment of basilar artery occlusion (BAO). Considering the expected increase in the utilization of EVT for BAO, we sought to understand the technique preferences of neurointerventionalists currently performing EVT for BAO.

Methods

We conducted an international online survey of physician opinions on the use of EVT in BAO between January to March 2022. The survey was distributed through stroke and neurointerventional organizations. Survey questions examined selection of patients for the procedure and the techniques currently used for EVT in BAO.

Results

More than 3,000 participants were invited yielding 1,245 respondents, of which 543 were classified as neurointerventionalists across 52 countries and included in this analysis. Most neurointerventionalists would proceed to EVT for occlusions of the V4 segment, the basilar artery, or the PCA, without regard for prior IVT. For BAO of embolic etiology, aspiration only thrombectomy was the preferred method with 50.3% of neurointerventionalists. For BAO of intracranial atherosclerotic disease (ICAD) etiology, combined stent retriever and aspiration thrombectomy was the preferred method with 40.5% of neurointerventionalists (Figure 1). The majority of neurointerventionalists (88.0%) would proceed to stenting after three or fewer failed passes for patients with BAO of ICAD etiology. In patients undergoing stenting, aspirin and clopidogrel was the most common antiplatelet regime (52.4%).

Conclusions

Amongst the surveyed neurointerventionalists, the most common techniques for EVT of patients with BAO were contact aspiration or combined stent retriever with aspiration thrombectomy. For patients with BAO due to ICAD, the majority of neurointerventionalists were willing to stent and do so most often after three or fewer failed passes and with the use of dual antiplatelet medications. Further study is needed to determine the optimal technique for EVT of BAO with or without ICAD.
Abstract Number ‐ 10: Stroke Patients with Carotid Artery Web Have High RoPE Scores and Low Frequency of PFO
Authors: Alshaer Qasem N , Karunamuni Nilushi , Osehobo Ehizele M , Koneru Sitara , Landzberg David R , Al‐Bayati Alhamza R , Nahab Fadi , Nogueira Raul G , Haussen Diogo C
Published: April 2023

Introduction

PFO‐associated stroke is more common in young patients (<60 years) with less vascular risk factors, and with an infarct pattern consistent with embolic phenomena. These features are included in the Risk of Paradoxical Embolization (RoPE) score in which a high score (≥ 7) indicates a high likelihood of a symptomatic PFO. However, carotid artery webs (CaW) have been reported in patients with the same profile in which a PFO might be detected. In this study, we calculated RoPE score for patients with symptomatic CaW related strokes to identify how many of these patients would have been potentially misclassified as having a PFO‐associated stroke.

Methods

Patients presenting with ESUS and ipsilateral symptomatic CaW were included. Stroke work up was completed including cervicocranial vascular imaging that was reviewed by a neuroradiologist and an interventional neurologist. Shunt study was done with a TTE, TEE, and/or TCD, all with a bubble study. RoPE score of ≥ 7 was considered high.

Results

A total of 75 patients fulfilled the inclusion criteria of having an ipsilateral symptomatic CaW as the etiology of ESUS with no competing etiologies aside from PFO. The baseline characteristics are described in the table. The rates of vascular risk factors were generally low which is reflected by a high median RoPE score of 7 [IQR 5‐8], with 52% (n = 39) of patients having a score of ≥ 7. Ten patients (13%) had a PFO, of which 3 had high‐risk features. There was no significant difference in median RoPE score between patients with and without PFO (8 [6‐8] vs 6 [5‐8], p = 0.238), nor in the rate of patients with high RoPE score (78% vs 44%, p = 0.06). Recurrence happened in 16% (n = 12) of the patients and was always ipsilateral to the symptomatic CaW. No significant difference was detected in the rates of recurrence between high vs low RoPE scores (20.5% vs 11.1%, p = 0.351). Patients with a PFO had higher rates of recurrence compared to those without a PFO (40%, n = 4 vs 12.3%, n = 8, p = 0.048); however, none of the PFO patients with a recurrent stroke had a high‐risk PFO. A superimposed thrombus was seen on the CaW in 12.2% (n = 9) and was more commonly seen in patients who had recurrence (36%, n = 4 vs 8%, n = 5, p = 0.024).

Conclusions

Patients with ESUS from a presumably symptomatic CaW‐related stroke have high RoPE scores. The recurrence rates were high in this population and were always ipsilateral to the side of the CaW including in the PFO population. The PFO is likely incidental in this population despite having a high RoPE score. Neurologists should carefully evaluate the cervical vasculature before concluding that a PFO is stroke‐related and committing patients to PFO treatment.
Abstract Number ‐ 16: Thrombectomy alone versus Bridging intravenous alteplase in the US population: a pseudo‐randomized controlled trial
Authors: Salazar‐Marioni Sergio A , Abdelkhaleq Rania , Niktabe Arash , Tariq Bilal , Martinez‐Gutierrez Juan C , Sheth Sunil A , Kim Youngran
Published: April 2023

Introduction

Recent randomized controlled trials (RCT) failed to demonstrate non‐inferiority of skipping IV tPA in patients with planned endovascular therapy (EVT). None of these studies included patients from the US due to regulatory challenges. Given practice patterns vary relative to Asia and Europe, we sought to address this topic using a validated alternative to RCTs, fuzzy regression discontinuity design (RDD).

Methods

From our prospectively maintained multi‐center registry we identified patients with LVO AIS treated with EVT with and without IV tPA treatment from 1/2018 ‐ 9/2021. We used the time cutoff for IV tPA as our discontinuity and assumed subjects on either side of the cutoff have markedly different probabilities of receiving the treatment but are similar in other relevant characteristics. The primary outcome was good functional outcome defined as 90‐day mRS 0–2 and it was compared between these two populations immediately adjacent to the cutoff using local linear regressions.

Results

Among 694 patients with LVO AIS who received EVT, median age was 69 [IQR 59‐79], 50%, were female, 44% White, 24% Black, and 14% Hispanic. 51% received IV tPA, with median onset to treatment time of 109 min [IQR 79‐160]. We observed a sharp drop (47%) in the probability of tPA around the cutoff time of 4 hours (allowing 30 minutes for in‐hospital evaluation), while there were no significant differences in other relevant features at the cutoff, validating the underlying RDD assumptions (Figure A). Overall, 33% of patients achieved good functional outcomes and there were no significant differences around the cutoff time (Figure B). In fuzzy RDD, there was no evidence of an association of receiving tPA with good functional outcome with regression discontinuity of only 1.0% (p = 0.98)There were no significant differences in rates of hemorrhage in patients treated with or without IV tPA (22% vs 21%, p = 0.68).

Conclusions

Our study provides the highest quality US‐based evidence supporting the findings of the outside US trials, demonstrating no benefit of skipping IV tPA in patients with planned EVT.
Abstract Number ‐ 23: In vitro evaluation of thrombectomy techniques: What is the most efficient combined technique?
Authors: Kaneko Naoki , Imahori Taichiro , Takayanagi Ariel , Liebeskind David , Tateshima Satoshi
Published: April 2023

Introduction

A combined technique with contact aspiration and stent retriever is widely used for the treatment of patients with acute ischemic stroke due to the potential synergistic effect of the two technologies. However, there are no large studies that conclude the combined technique is more efficient compared to stent retriever only or contact aspiration. One of the issues in combined techniques may be the complexity, and multiple variations of combined techniques exist. We performed an in vitro study using three‐dimensional (3D) flow models and performed clot retrieval in order to explore effective and safe techniques for mechanical thrombectomy.

Methods

In a 3D silicone flow model with moderate tortuosity, we compared several techniques: 1. a pinching combination method (pull out stent retriever and aspiration catheter as a unit) with several variations of aspiration catheter locations; 2. an ingestion combination method (stent retriever removal through aspiration catheter); 3. stent retriever only; and 4. contact aspiration. We evaluated the success retrieval rates of a thrombus in the M2 branch. In addition, we measured pulling force during each technique to determine the amount of force exerted on the distal MCA vessel.

Results

The highest clot retrieval rate was achieved with a pinching combination technique with close contact with an aspiration catheter. The pulling force on the distal MCA vessel was high with the techniques that had high clot retrieval rates and low with the techniques that had low success rates. The pulling force was higher when the stent retriever was fully deployed compared with a pinching technique with a stent partially covered with an aspiration catheter.

Conclusions

In our in vitro model, the pinching combination method showed the highest clot retrieval rate when the aspiration catheter was advanced to the clot and the stent retriever. The pulling force experiments suggested the shorter stent retriever may decrease the rate of subarachnoid hemorrhage due to low pulling force.
Abstract Number ‐ 41: A Comparison of the Safety and Efficacy of Endovascular Techniques in Treating Basilar Tip Aneurysms
Authors: Ghochani Yasmin , Khurana Sukhdeep S , Kang Paul , Ducruet Andrew F
Published: April 2023

Introduction

Basilar‐tip aneurysm (BTA) is the most common aneurysm found in the posterior fossa circulation, representing 5–8% of the total intracranial aneurysms. Endovascular techniques are first‐line for treatment of the vast majority of posterior circulation artery aneurysms because of their deep location and the high mortality and morbidity associated with open surgical clipping. Coil embolization (CE) is considered safer and more efficacious in the treatment of BTAs compared to open surgery but has increased rate of recanalization. Twoadjunctivemodifications of CE ‐balloon remodeling techniques(BRT) and stent‐assisted coiling (SAC) ‐ are availableto address the occlusion needs of BTAs of variable anatomies/morphologies, sizes, and rupture status.We aimed to compare the clinical utility, safety and efficacy of these adjuvant therapies for treating BTAs.

Methods

We conducted a retrospective review of the Barrow Neurological Institute (BNI) endovascular database from January 1996 through January 2019. Primary outcomes were obliteration as assessed by the modified Raymond Score (MRS), perioperative complications, recurrence, retreatment, and time to 1stretreatment. Secondary outcomes were stratification of the results based on rupture and wide‐neck status and the type of stent.

Results

121 patients with an average follow‐up of 43.4 months were included. Ruptured aneurysms were more likely to be treated by CE vs. either adjuvant therapy (p< 0.001), and SAC was the preferred treatment for larger aneurysms (p = 0.004). SAC had significantly worse obliteration (MRS of 2.09±0.94) vs. BRT (MRS of 1.82±0.91; p = 0.038) but was less likely to be retreated as compared to BRT (35.3%; p = 0.047). However, SAC had a shorter time to first retreatment 13.4±13.8 months as compared to the BRT (25.3±26.7 months) and CE (50.3±68.5 months; p = 0.04 and 0.006, respectively). Lastly, SAC had significantly lower recurrence of 31.8% and near‐significantly lower retreatment rate of 27.3% (p = 0.045, 0.058, respectively) as compared to CE (recurrence of 46.2% and retreatment of 34.6%). There was no significant difference in peri‐operative complications among the three groups.

Conclusions

CE and its adjuvant therapies have similar safety profile but pose variable efficacy in terms of obliteration, recurrence, retreatment, and durability over time. This study represents one of the largest data sets on endovascular adjuvant therapy of BTAs and has the potential to inform clinical decision making when considering CE with BRT vs. SAC for BTA of specific size and morphology.As future directions, outcomes specifically in the old vs. new stent groups and according to further stratification of the largest dimension of the BTA will need to be analyzed, and we will further interrogate any association between the co‐morbidities, such as smoking status and hypertension, with aneurysm rupture, largest dimension, and wide‐neck status.
Abstract Number ‐ 45: Curative Embolization for Pediatric Low‐Grade Brain Arteriovenous Malformations
Authors: Galecio‐Castillo Milagros , Rodriguez‐Calienes Aaron , Vivanco‐Suarez Juan , Saal‐Zapata Giancarlo , Malaga Marco , Zevallos Cynthia , Ortega‐Gutierrez Santiago
Published: April 2023

Introduction

Improvements in the safety and efficacy of curative embolization for brain arteriovenous malformations (bAVMs) have allowed to achieve comparable results to microsurgical resection and radiosurgery, especially for low‐grade bAVMs (Spetzler Martin [SM] grade I and II). However, whether this treatment modality is beneficial in the pediatric population remains unknown. Hence, we assessed the safety and efficacy of curative embolization for low‐grade bAVMs in children. In addition, we determined predictors of intraprocedural complications and predictors of complete occlusion in one embolization session.

Methods

Between 2010 and 2022, a retrospective analysis of all pediatric (≤18 years) patients who underwent curative embolization for low‐grade bAVMs was conducted at two institutions. Demographic data, clinical presentation, SM grade, and procedural characteristics were retrieved. The safety (intraprocedural complications and mortality) and efficacy (complete angiographic obliteration after the last embolization session) were evaluated. Multivariable logistic regression analysis was performed to identify potential predictive factors of intraprocedural complications and complete occlusion in one session. For selected variables, odds ratios (OR) with 95% confidence intervals (CI) and p value of the likelihood‐ratio test were presented.

Results

Sixty‐eight patients (41 females; mean age 12.9 ± 3.6 years) underwent a total of 102 embolization sessions. Fifty‐one bAVMs (75%) presented ruptured, and headache was the most common clinical presentation (50%). There were 24 (35%) SM grade I lesions and 44 (65%) grade II. Onyx was the most used embolic agent (33%) and the transarterial approach was the most common (93%). The mean volume of embolic agents in each patient was 2.4 ml (range 0.2 to 7.5 ml). Fourteen intraprocedural complications (14% of procedures) were observed and no deaths were reported. The most common complication was microcatheter‐related vessel perforation (6%). Single venous drainage decreased the risk of intraprocedural complications (OR = 0.19; 95% CI 0.04 – 0.78). Complete angiographic obliteration was achieved in 44 patients (65%). In 35 patients (52%) the bAVM was occluded with a single session. A small bAVM size was predictor of complete occlusion in one session (OR = 0.42; 95% CI 0.21 – 0.73).

Conclusions

Curative embolization in pediatric low‐grade bAVMs can be performed with an acceptable complete occlusion rate but with a high rate of intraprocedural complications. The risk of intraprocedural complications was low in bAVMs with a single venous drainage. The odds of complete occlusion in one session are high in small bAVMs. Curative embolization should be selected on an individual basis in order to achieve optimal results.
Abstract Number ‐ 48: Cerebral Sinus Venous Thrombosis Secondary to Chronic Inflammatory Disorders in Children
Authors: Ravishankar Nidhi , Ahmed Anam , Karakas Cemal , Pehlivan Davut
Published: April 2023

Introduction

Cerebral Sinus Venous Thrombosis (CSVT) is a rare form of venous thromboembolism that can lead to significant morbidity and mortality predominantly in young people. While previous literature has identified prothrombotic and infectious pathologies as significant risk factors for CSVT, chronic systemic conditions such as connective tissue diseases (CTD) are less studied. The purpose of the current study is to describe the clinical features, neuroimaging characteristics, treatment, and long‐term neurological outcomes in children with CSVT secondary to CTD.

Methods

We reviewed electronic medical records of patients under 18 years of age diagnosed with CSVT secondary to CTD between 2002–2018 in a single center. We analyzed data regarding demographics, comorbidities, neuroimaging and neurological examination findings during the initial encounter. Subsequent long‐term follow‐up neurological examinations, lab and imaging workup, and medical management was also analyzed.

Results

Eight patients (Male:Female: 6:2) met the criteria and were included in the analysis. The patient’s age ranged from 6 weeks to 17 years. CTDs include Behcet’s (n = 2), Kawasaki (n = 1), systemic lupus erythematosus (n = 1), Wegener granulomatosis (n = 1), sarcoidosis (n = 1), and inflammatory bowel disease (n = 1). Five patients had a normal neurological examination on initial presentation, two had papilledema, and one had hypotonia and poor suck reflex. On initial neuroimaging, the most common thrombosis locations were transverse sinuses (n = 7). All patients received anti‐thrombolytic therapy (heparin, warfarin, or Lovenox) between 2.5 to 6 months. Three patients had complete resolution and one had partial resolution of thrombosis on follow‐up neuroimaging (average = 4.3 months, range 3–8 months). On long‐term clinical follow‐up (average: 41.3 months, SD: 62.1), all patients had normal neurological examinations.

Conclusions

Our case series demonstrated that 50% of patients with CSVT secondary to CTD showed full/partial resolution of thrombosis on follow‐up neuroimaging. In addition, they also had good clinical outcomes on long‐term clinical follow‐up with anticoagulation or antithrombotic treatment. This study uncovers the favorable outcomes of CSVT associated with CTD in children, but more cohort studies are required in order to make accurate conclusions.
Abstract Number ‐ 49: Risk of HT with Early DOACs after Acute Ischemic Stroke: A Pooled Analysis
Authors: Alrohimi Anas , Rose David Z , Burgin Scott , Renati Swetha , Corbin Hilker , Deng Wei , Oliveira Guilherme H , Beckie Theresa M , Labovitz Arthur J , Fradley Michael G , Tran Nhi , Gioia Laura C , Kate Mahesh , Ng Kelvin , Dowlatshahi Dar , Field Thalia S , Coutts Shelagh B , Siddiqui Muzzafar , Hill Michael D , Miller Jodi , Jickling Glen , Shuaib Ashfaq , Buck Brian , Sharma Mike , Butcher Ken S
Published: April 2023

Introduction

The risk of hemorrhagic transformation (HT) in the early phase of acute ischemic stroke (AIS) remains unknown, leading to potential unnecessary delays in initiation of anticoagulation for secondary stroke prevention. We sought to assess the rate of HT associated withdirect oral anticoagulant (DOAC) initiation within and beyond 48 hours after AIS, using a pooled analysis of available published data.

Methods

A pooled analysis of 6 studies (4 prospective observational blinded outcome studies and2 randomized trials) of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted. The primary endpoint was incident radiographic HT on follow‐up imaging. Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, mortality within the study period, and follow‐up modified Rankin Scale score.The results were reported as odds ratio (OR) andhazard ratio (HR)with 95% confidence interval (CI).

Results

We evaluated 509 patients; median infarct volume was1.5 (0.1‐7.8) ml, andmedian National Institutes of Health Stroke Scale was2 (0‐3).Incident radiographic HT was seen on follow‐up scan in 34 (6.8%) patients.DOAC initiation within 48 hours from index event was not associated with incident HT (adjusted OR 0.67, [0.30 – 1.50]P = 0.32).No patients developed symptomatic HT.Conversely, 31 (6.1%) patients developedrecurrent ischemic events, 64% of which occurred within 14 days.Initiating a DOAC within 48 hours of onset was associated with a trend towards lower rates of recurrent ischemic events, but this was not statistically significant (HR 0.42, [0.17 – 1.008]P = 0.052). In contrast to HT,recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84 – 16.24], p< 0.001).

Conclusions

Initiation of DOAC within 48 hours after stroke was not associated with decreased risk of recurrent ischemic events, or increasedincident risk of HT. Both recurrent ischemic events and incident HT occurred at similar rates.Unlike HT, however, recurrent ischemic events were associated with poor outcomes.
Abstract Number ‐ 58: Effects of Neck Geometry on Reccurence in CFD Analysis for Aneurysms after Low VER Coiling
Authors: Uchikawa Hayato , Takao Hiroyuki , Fujimura Soichiro , Kasai Tomoki , Sunami Shota , Yuzawa Kazuya , Ishibashi Toshihiro , Fukudome Koji , Yamamoto Makoto , Murayama Yuichi
Published: April 2023

Introduction

Although low volume embolization ratio is known as risk factor of aneurysmal recanalization, stable occlusion can be achieved in limited cases. Evaluation of hemodynamic parameters at the neck surface has usually been performed with a flat surface rather than a curved surface following the actual coil shape. In this study, we investigated the effect of the geometry of the neck surface on hemodynamics related to aneurysm recanalization after coil embolization in low volume embolization ratio.

Methods

We focused on aneurysms of 5–10 mm in size that were conducted coil embolization with 15–20% volume embolization ratio (low‐VER). Aneurysms that were recanalized after coil embolization and conducted additional coil deployment were defined as the recanalized case. We identified 25 aneurysms (7 recanalized and 18 stable). We randomly selected 3 recanalized cases and 6 stable cases. For each case, the three‐dimensional vascular geometry including aneurysm was reconstructed by preoperative angiographic images. To divide the aneurysm from the parent artery, two types of neck surfaces (flat neck surface and curved neck surface) were generated for each case. The embolized coil was modeled in the enclosed area with the neck plane and aneurysmal wall by our original virtual coiling simulation. CFD analyses were conducted with the flat neck surface and the curved neck surface. We estimated 6 morphological parameters and 35 hemodynamic parameters, and the mean values of hemodynamic parameters were compared between the flat neck surface and the curved neck surface. The change rate of each parameter in the curved neck was calculated based on that in the flat neck.

Results

Since the velocity and pressure were involved in recanalization factors by the previous studies, as illustrative hemodynamic parameters, the mean values and change rate of the spatially averaged velocity normal to the neck surface into the cerebral aneurysm (NVneck) and the pressure difference between the average pressure on the surface of control volume and the maximum pressure at the neck surface (PDneck) were summarized in Table 1. These parameters were higher with the curved neck surface geometry case than with the flat neck surface geometry case. Furthermore, the change rates were higher in the recanalized cases compared to those in the stable cases.

Conclusions

In the CFD analysis with the curved surface, the averaged inflow velocity and pressure difference at the neck surface were higher than those with the flat surface. In addition, the change rates of hemodynamic parameters in recanalized cases were higher than those of stable cases. Therefore, the hemodynamic parameters are changed depending on the geometry of the neck surface, which may affect the prediction accuracy for recanalization using CFD.