tbuckley/cabot-search huggingface dataset:
Abstract 10547: Communication of Potential Adverse Drug Reactions in Patients Undergoing Percutaneous Coronary Intervention
Authors: Trond Pettersen, Heather Allore, Bjorn Bendz, Britt Borregaard, Bengt Fridlund, Sara Ghaderi, Alf Inge Larsen, Jan Erik Nordrehaug, Trine B Rasmussen, Svein Rotevatn, Jan Schjøtt, Irene Valaker, Tone Merete Norekvål
Journal: Circulation (2021)

Background: Patients need information on all aspects of prescribed drug therapy to make informed decisions about their treatment for autonomy. Purpose: This study assessed whether patients received information about potential adverse drug reactions (ADRs) from prescribed drug therapy before or after discharge following percutaneous coronary intervention (PCI). Furthermore, we sought to estimate associations with socio-demographics and concerns related to prescribed drug therapy. Methods: CONCARD PCI is a prospective multicentre cohort study including 3424 patients undergoing PCI. The study was conducted between June 2017 and May 2020 at seven large referral PCI centres in two Scandinavian countries. Clinical data were collected from patients’ medical records. Socio-demographic characteristics were obtained by self-report during index hospitalization. Four questions from the Heart Continuity of Care Questionnaire were used to determine if information about potential ADRs was provided before or after discharge. The Specific-Concerns Scale of the Beliefs about Medicines Questionnaire was used to assess concerns related to prescribed drug therapy. Logistic regression estimated whether lack of information was associated with sociodemographic characteristics. Results: Most patients were men (78%), with a mean age of 66 years (SD11, range 20-96 years) and married or living with a partner (75%). Before discharge from hospital, 59% reported being informed of potential ADRs and 50% were informed what to do if ADRs occurred. After hospital discharge, 26% reported having reviewed potential ADRs with healthcare providers, and 24% had reviewed what to do if ADRs occurred. Those who were not informed had increased concerns about their prescribed drug therapy compared to those who were informed at both time points (p&lt;0.001). Women (51%) were less likely to receive information about potential ADRs than men (63%) (p&lt;0.001). However, there were no substantial associations with age, education, income, or marital status. Conclusion: Four in ten patients reported not receiving information on potential ADRs from prescribed drug therapy, and this applied especially for women. Efforts to improve communication on ADRs and gender equity should be a priority.
Abstract 11584: Prevalence of Isolated Nocturnal Hypertension in Adolescents with Use of Adult Hypertension Criteria
Authors: Shannon M Lyon, Jacob Hartz, Ming Hui Chen, Sarah D De Ferranti
Journal: Circulation (2021)

Introduction: The 2017 Blood Pressure Guidelines aligned clinic hypertensive thresholds for children ≥13 years of age with adult BP criteria, increasing the predictive value for adverse cardiovascular outcomes. However, thresholds for adolescents have not been updated for ambulatory blood pressure monitoring (ABPM), a confirmatory test in the diagnosis of hypertension. We examined the impact of using adult ABPM criteria in adolescents, including the contribution of daytime (DH) and isolated nocturnal hypertension (INH), and associations with left ventricular hypertrophy (LVH). Methods: This retrospective study included all ABPMs obtained in 13–16-year-olds at Boston Children’s Hospital (2015-2020). ABPMs were interpreted using both pediatric and adult thresholds. For studies newly classified as hypertensive using adult criteria, available echocardiograms were reviewed for LVH. Independent T-test and Chi-square were used to compare age, gender, BMI, left ventricular mass (LVM), indexed LVM &gt;95 th percentile, and LVM z-score &gt;2 in individuals with INH vs. DH. Results: 347 ABPMs were included in this study; 92 studies (87 unique patients) were reclassified as hypertensive using adult thresholds; 96.7% of these studies were obtained in males. Of the 92 studies, 31 (33.7%) studies had INH and 58 (63.0%) had DH (54/58 had day &amp; night hypertension). There was no difference in age or BMI between INH and DH groups; more studies in the INH group were from females (p=0.05). We reviewed 14 and 42 echocardiograms for the INH and DH groups, respectively. There were no differences in indexed LVM or LVM z-score between the 2 groups. Though a small sample size, we found that 3/14 (21.4%) and 12/42 (28.6%) in the INH and DH groups respectively had an indexed LVM &gt;95 th percentile; there was no significant difference between groups (p=0.601). An LV mass z-score &gt; 2 was not seen in the INH group and was in 4/42 (9.5%) of the DH group. Conclusions: With use of adult ABPM criteria, INH significantly contributed to ABPMs reclassified as hypertensive. Prevalence of LVH was similar in INH and DH groups. Further study is needed to investigate the appropriateness of using adult thresholds for nocturnal hypertension in adolescents, whose sleep patterns may differ from adult counterparts.
ITVT-07. Robotic alignment module Cirq for navigated brainstem tumor biopsies
Authors: Kirsten van Baarsen, Peter Woerdeman, Mariam Slot, Eelco Hoving
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND With the incorporation of the robotic alignment module Cirq (Brainlab, Germany) into our neurosurgical armamentarium, we aimed to know our baseline accuracy in stererotactic biopsies. We therefore retrospectively reviewed our data on biopsy accuracy for brain(stem) tumors using the non-robotic alignment instrument Varioguide (Brainlab, Germany). Because of unexpectedly large deviations from the intended target, we sought to improve our registration accuracy when we introduced Cirq. Intraoperative 3D CT with bone fiducials was added to the pre-operative 3D T1 MRI with skin fiducials. This made it possible to compare surgical devices as well as registration methods. AIMS To share our experience with the new robotic alignment module Cirq for navigated brain(stem) tumor biopsies and to evaluate its target accuracy with bone fiducial registration, as compared to the previously used Varioguide with skin fiducial registration. METHODS All patients (0–18 years old) that underwent a brain(stem) biopsy in our institution were included. Over 2018–2020, data were collected retrospectively (cohort Varioguide with 3D T1 MRI registration with skin fiducials). From 2021, data were collected prospectively (cohort Cirq with both 3D T1 MRI registration with skin fiducials and intraoperative CT registration with bone fiducials). For both cohorts, Euclidian distances were calculated between the intended target and the obtained target. For the prospective cohort, registration errors were calculated for bone versus skin fiducials. PRELIMINARY REUSLTS The deviation from the intended target was much smaller in the Cirq cohort versus the Varioguide cohort. Within the Cirq cohort, registration errors were submillimetric for bone fiducial registration as compared to several millimeters for skin fiducial registration. CONCLUSION: The Cirq robotic arm is convenient, safe and highly accurate, especially when combined with intraoperative 3D CT bone fiducial registration. Skin fiducial registration does not offer the level of precision that is mandatory in brainstem tumor biopsies.
STEM-27. A PERIVASCULAR STEM CELL UNDERLIES VERTEBRATE MENINGEAL TUMORIGENESIS
Authors: Abrar Choudhury, Martha Cady, Calixto Lucas, Brisa Palikuqi, Ophir Klein, Shawn Hervey-Jumper, Joanna Phillips, Peter Dickinson, Stephen Magill, Aparna Bhaduri, Elizabeth Crouch, David Raleigh
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Meningiomas are the most common primary intracranial tumors in humans and dogs, but biologic drivers and cell types underlying meningeal tumorigenesis are incompletely understood. Here we integrate meningioma single-cell RNA sequencing with stem cell approaches to define a perivascular stem cell underlying vertebrate meningeal tumorigenesis. METHODS Single-cell RNA sequencing was performed on 57,114 cells from 8 human meningiomas, 54,607 cells from 3 dog meningiomas, and human meningioma xenografts in mice. Results were validated using immunofluorescence (IF), immunohistochemistry (IHC), and deconvolution of bulk RNA sequencing of 200 human meningiomas. Mechanistic and functional studies were performed using clonogenic and limiting dilution assays, xenografts, and genetically engineered mouse models. RESULTS Copy number variant identification from human meningioma single cells distinguished tumor cells with loss of chr22q from non-tumor cells with intact chr22q. A single cluster distinguished by expression of Notch3 and other cancer stem cell genes had an intermediate level of loss of chr22q, suggesting this cluster may represent meningioma stem cells. In support of this hypothesis, pseudotime trajectory analysis demonstrated transcriptomic progression starting from Notch3+ cells and encompassing all other meningioma cell types. Notch3+ meningioma cells had transcriptomic concordance to mural pericytes, and IF/IHC of prenatal and adult human meninges, as well as lineage tracing using a Notch3-CreERT2 allele in mice, confirmed Notch3+ cells were restricted to the perivascular stem cell niche in mammalian meningeal development and homeostasis. Integrating human and dog meningioma single cells revealed Notch3+ cells in tumor and non-tumor clusters in dog meningiomas. Notch3 IF/IHC and cell-type deconvolution of bulk RNA sequencing showed Notch3+ cells were enriched in high-grade human meningiomas. Notch3 overexpression in human meningioma cells increased clonogenic growth in vitro, and increased tumorigenesis and tumor growth in vivo, decreasing overall survival. CONCLUSIONS Notch3+ stem cells in the perivascular niche underlie vertebrate meningeal tumorigenesis.
Abstract P324: Brd4 Degradation Enhances Cardiac Reprogramming And Regeneration By Inhibiting JAK/STAT Pathway
Authors: Liu Liu, Yijing Guo, Ienglam Lei, Shuo Tian, Wenbin Gao, Zhong Wang
Journal: Circulation Research (2021)

Reprogramming of fibroblasts into induced cardiomyocytes (iCMs) is a potentially promising strategy for regenerating a damaged heart. However, low conversion rate of fibroblasts to cardiomyocytes and poor in vivo application efficacy are major challenges in this reprogramming process. To address this issue, we attempted to identify small molecules related to histone acyl post-translational modifications that could enhance the reprogramming ability towards cardiac fate. Using α-muscle heavy chain-GFP-tagged mouse embryo fibroblasts as a starting cell type, we screened 46 inhibitors target histone acyl post-translational modifications and related epigenetic factors and identified an important role of Brd4 in modulating iCM reprogramming. In particular, we observed that a novel Brd4 degrader repressed many genes involved in immune responses especially JAK/STAT pathway. Mechanically, Brd4 degrader repressed JAK/STAT related gene expressions by affecting Brd4 binding to promoters of those genes. More importantly, Brd4 degrader treatment enhanced MGT induced cardiac regeneration in vivo and markedly improved myocardial performance after myocardial infarction. These findings shed new light on the molecular mechanisms underlying the cardiac conversion of fibroblasts and provide novel targets and small molecules to improve iCM reprogramming for clinical applications.
Genetic Perturbation of CD70/CD27 Co-Stimulation Promotes the Development of <i>Bcl6</i>-Driven Diffuse Large B-Cell Lymphoma
Authors: Elisa Mandato, Yanbo Sun, Vignesh Shanmugam, Il-Kyu Choi, Kyle T. Wright, Robert A. Redd, Lee N. Lawton, Donna S. Neuberg, Scott J. Rodig, Baochun Zhang, Margaret A. Shipp
Journal: Blood (2021)
IMMU-44. AN IMMUNOTHERAPEUTIC VACCINE COMPOSED OF IRRADIATED WHOLE TUMOR CELLS PULSED WITH MANNAN-BAM, TLR LIGANDS AND ANTI-CD40 ANTIBODY INDUCES POTENT IMMUNE RESPONSE IN PRECLINICAL GBM ANIMAL MODEL
Authors: Herui Wang, Rogelio Medina, Juan Ye, Pashayar Lookian, Ondrej Uher, Jan Zenka, Mark Gilbert, Karel Pacak, Zhengping Zhuang
Journal: Neuro-Oncology (2021)

Abstract Despite numerous therapeutic advances, the treatment of glioblastoma multiforme (GBM) remains a challenge, with current 5-year survival rates estimated at 4%. Multiple characteristic elements of GBM contribute to its treatment-resistance, including its low immunogenicity and its highly immunosuppressive microenvironment that can effectively disarm adaptive immune responses. Hence, therapeutic strategies that aim to boost T-lymphocyte mediated responses against GBM are of great therapeutic value. Herein, we present a therapeutic vaccination strategy that promotes the phagocytosis of tumor cells, enhances tumor antigen presentation, and induces a tumor-specific adaptive immune response. This strategy consists of vaccinations with irradiated whole tumor cells (rWTC) pulsed with phagocytic agonists (Mannan-BAM), TLR ligands [LTA, Poly (I:C), and R-848], and anti-CD40 antibody (collectively abbreviated as rWTC-MBTA). We evaluated the therapeutic efficacy of rWTC-MBTA strategy in a mouse syngeneic GL261 orthotopic GBM tumor model. rWTC-MBTA or vehicle control were administered subcutaneously over the right foreleg three days after intracranial injection of GL261 cells. Complete regression (CR) of intracranial tumors was achieved in 70% (7/10) of rWTC-MBTA treated animals while none survived in the control group. Immunophenotyping analyses of peripheral lymph nodes and brain tumors of rWTC-MBTA treated mice demonstrated: (1) increased mature dendritic cells and MHC II+ monocytes; (2) increased effector (CD62L-CD44+) CD4-T and CD8-T cells; (3) increased cytotoxic IFNγ-, TNFα-, and granzyme B-secreting CD4-T and CD8-T cells. Of note, the therapeutic efficacy of rWTC-MBTA disappeared in CD4-T and/or CD8-T lymphocyte depleted mice. Three mice that achieved CR were rechallenged with 50k GL261 cells intracranially 14 months after the last rWTC-MBTA treatment and all rechallenged animals resisted GL261 tumor development, confirming the establishment of long-term immunological memory against GL261 tumor cells. Collectively, our study demonstrated that rWTC-MBTA strategy can effectively activate antigen presenting cells and induce more favorable T-cell signatures in the GBM tumors.
Abstract 11371: Prevalence of Cardiometabolic, Mental, and Other Somatic Chronic Conditions in Patients Enrolled in Phase II Outpatient Cardiac Rehabilitation
Authors: Audry Chacin Suarez, Jose R Medina-inojosa, Karen Fischer, Alanna M Chamberlain, Amanda R Bonikowske, Thomas P Olson
Journal: Circulation (2021)

Introduction: Multimorbidity is associated with physical disability, increased health care utilization, reduced quality of life, and mortality. Whereas most literature has focused on the co-occurrence of somatic conditions, we aim to (i) establish the prevalence of combined somatic and mental health multimorbidity (SMM) in cardiac rehabilitation (CR) patients, and (ii) determine the most prevalent co-occurrence of cardio-metabolic conditions (CMC) with other somatic or mental health conditions in CR patients. Methods: Using the Rochester Epidemiology Project records-linkage system, we identified residents of Southern MN and Western WI who attended (≥1) CR sessions from 1995 to 2019. The prevalence of 18 chronic conditions defined by the US Department of Health and Human Services was electronically extracted. Heat maps were created to assess the pairwise prevalence of cardio-metabolic (CMC; n=6) with mental (n=5) and other somatic (n=7) chronic conditions (Table 1) . Results: We included 13,056 patients; 68.5% were male. Patients were 65.5±12.5 years old with 44.7% ≤65 years old. Median number of conditions was 7 (Range 0-18) with 52.6% of patients having ≥7 conditions. Hyperlipidemia (89.3%), hypertension (79.5%), and arrhythmias (72.4%) were the most prevalent CMC. The prevalence of combined SMM (≥2 conditions) was 44.9% and was higher in those &lt;65 years ( p &lt;.0001). Depression (26.8%) and anxiety (24.7%) were the most common mental conditions involved in SMM and frequently co-occurred with CMC. Among other prevalent somatic conditions, arthritis (51.7%), chronic obstructive pulmonary disease (33.5%), and cancer (29.3%) co-occurred with CMC (Figure 1). Conclusions: Half of patients in CR have ≥7 chronic conditions. Somatic and mental health multimorbidity (SMM) is highly prevalent and is more frequent in those younger than 65 years old. Our results highlight the critical need to better understand the clinical burden of SMM in patients undergoing CR.
Characteristics of Post-Infusion Chimeric Antigen Receptor (CAR) T Cells and Endogenous T Cells Associated with Early and Long-Term Response in Lisocabtagene Maraleucel (liso-cel)-Treated Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)
Authors: Jerill Thorpe, Yue Jiang, Julie A Rytlewski, Ana Kostic, Yeonhee Kim, Leanne Peiser
Journal: Blood (2021)
NL-201, a De Novo Agonist of IL-2 and IL-15 Receptors, Demonstrates Synergistic Antitumor Activity with Anti-PD-1 Checkpoint Inhibitor Therapy in a Preclinical Non-Hodgkin Lymphoma Model
Authors: Justin Huard, Laurie Tatalick, Carl Walkey, Ryan Swanson
Journal: Blood (2021)
Quadriplegic man is first person to be allowed to die by assisted suicide in Italy
Authors: Marta Paterlini
Journal: BMJ (2021)

A 43 year old man has become the first person in Italy to be granted permission to have a legal death by assisted suicide.

The ethics committee of the local healthcare system of the Marche region authorised the action for the man, referred to as “Mario,” who is quadriplegic and has been unable to move for 10 years following a car collision. He has been asking the local hospital for over a year to put an end to his suffering. The Luca Coscioni Association, a non-profit organisation dedicated to promoting end-of-life choice in Italy, has …
EXTH-35. INCREASING THERAPEUTIC INDUCED NEURAL STEM CELL PERSISTENCE IN THE GLIOBLASTOMA TUMOR RESECTION CAVITY
Authors: Hunter Bomba, Lauren Kass, Kevin Sheets, Abigail Carey-Ewend, Morgan Goetz, Juli Bago, Simon Khagi, Shawn Hingtgen, Ingrid Findlay
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Induced neural stem cells (iNSCs) have emerged as a promising therapeutic platform for glioblastoma (GBM). iNSCs have the innate ability to home to tumor foci, making them ideal carriers for anti-tumor payloads. However, iNSC persist for only two weeks in the murine GBM tumor resection cavity. We hypothesized that by encapsulating iNSCs in a scaffold matrix, we could increase both the persistence of the cells the therapeutic durability. METHODS iNSCs expressing TRAIL were encapsulated in a gelatin-thrombin matrix; fibrinogen was used to polymerize the matrix. SEM was used to explore interactions between iNSCs and the scaffold matrix. To evaluate persistence, iNSCs encapsulated in the matrix were implanted into mock resection cavities of athymic nude mice and followed via BLI. To study the impacts of encapsulation on iNSC efficacy, athymic nude mice were implanted with U87 or GBM8 tumors. Tumors were then resected, and iNSCs encapsulated in the matrix were implanted; tumor volume was monitored via BLI. RESULTS SEM images showed homogeneous distribution of iNSCs throughout the matrix; iNSCs were completed encased in the fibrin clot component of the matrix and did not adhere to gelatin. In vivo, encapsulated iNSCs persisted for nearly 100 days whereas iNSCs directly injected into the brain parenchyma persisted &amp;lt; 20 days. Using mice bearing GBM8 tumors, animals treated with a high dose of therapeutic encapsulated iNSCs survived ~60 days longer than animals treated with non-therapeutic cells. A similar trend was observed in animals inoculated with U87 tumors. While not statistically significant, 25% of mice treated with iNSCs encapsulated in the gelatin-thrombin matrix survived longer than those treated with iNSCs encapsulated in a fibrin-only matrix, suggesting additional benefit due to the gelatin component. FUTURE DIRECTIONS: Prospective experiments will explore the impact of the scaffold on iNSC phenotype, including proliferation, differentiation, and migration markers.
Pamiparib Monotherapy for Patients with Germline <i>BRCA1/2</i>-Mutated Ovarian Cancer Previously Treated with at Least Two Lines of Chemotherapy: A Multicenter, Open-Label, Phase II Study
Authors: Xiaohua Wu, Jianqing Zhu, Jing Wang, Zhongqiu Lin, Rutie Yin, Wei Sun, Qi Zhou, Songling Zhang, Danbo Wang, Hong Shi, Yunong Gao, Yi Huang, Guiling Li, Xiuli Wang, Ying Cheng, Ge Lou, Qinglei Gao, Li Wang, Xiuping Du, Mei Pan, Xiyan Mu, Li Li, Miao Li, Song Mu, Beihua Kong
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Phase I results of this phase I/II study showed that pamiparib 60 mg twice a day had antitumor activity and an acceptable safety profile in Chinese patients with advanced cancer, including epithelial ovarian cancer. Patients and Methods: This open-label phase II study was conducted in China and enrolled adult (≥18 years) patients with platinum-sensitive ovarian cancer (PSOC; disease progression occurring ≥6 months after last platinum treatment) or platinum-resistant ovarian cancer (PROC; disease progression occurring &amp;lt;6 months after last platinum treatment). Eligible patients had known or suspected deleterious germline BRCA mutation (gBRCAmut) and had previously received ≥2 lines of therapy. Pamiparib 60 mg orally twice a day was administered until disease progression, toxicity, or patient withdrawal. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per RECIST version 1.1. Results: In the total patient population (N = 113; PSOC, n = 90; PROC, n = 23), median age was 54 years (range, 34–79) and 25.6% of patients received ≥4 prior systemic chemotherapy lines. Median study follow-up was 12.2 months (range, 0.2–21.5). Eighty-two patients with PSOC and 19 patients with PROC were evaluable for efficacy. In patients with PSOC, 8 achieved a complete response (CR) and 45 achieved a partial response (PR); ORR was 64.6% [95% confidence interval (CI), 53.3–74.9]. In patients with PROC, 6 achieved a PR; ORR was 31.6% (95% CI, 12.6–56.6). Frequently reported grade ≥3 adverse events were hematologic toxicities, including anemia and decreased neutrophil count. Conclusions: Pamiparib 60 mg twice a day showed antitumor activity with durable responses in patients with PSOC or PROC with gBRCAmut, and had a manageable safety profile.
Primary nasal epithelial cells from patients with cystic fibrosis hold promise for guiding precision medicine and expanding treatment
Authors: Stephen R. Reeves
Journal: European Respiratory Journal (2021)

<b>Sette <i>et al.</i> should be commended for their excellent work appearing in the current issue of the <i>ERJ</i>. These studies provide a roadmap for expanding treatments and delivering personalised medicine for people with cystic fibrosis.</b>https://bit.ly/31qe9zZ
Fixed Duration Combination Therapy with Ibrutinib (ibr) and Venetoclax (ven) Leads to Deep Responses in Relapsed/Refractory (rel/ref) Chronic Lymphocytic Leukemia (CLL): Results of a Phase 2 Study
Authors: Tanya Siddiqi, Pamela Clay, Kate Murray, Navshina Shekh, Alexandra Muir, Steven T. Rosen, Steven Coutre
Journal: Blood (2021)