tbuckley/cabot-search huggingface dataset:
Abstract 12229: Left Ventricular Non-Compaction in Childhood: Echocardiographic Follow-Up and Prevalence in First-Degree Relatives
Authors: Thilde Olivia Kock, Marie F Boerresen, Anne-sophie Sillesen, Jakob B Norsk, Maria Munk M Paerregaard, Niels G Vejlstrup, Alex Christensen, Kasper Iversen, Henning Bundgaard, Anna Axelsson Raja
Journal: Circulation (2021)

Introduction: Left ventricular non-compaction (LVNC) is characterized by excessive trabeculations of the left ventricular wall and may be associated with reduced systolic function. It is debated whether LVNC is congenital or may develop later as part of other cardiomyopathies. The clinical importance and heredity of LVNC with normal systolic function is unclear. We aimed to describe the cardiac development in children with LVNC from birth to 2-4 years of age, compared to matched controls. Additionally, we aimed to describe the prevalence of LVNC in first-degree relatives. Methods: A follow-up transthoracic echocardiography was performed in children at 2-4 years of age diagnosed with LVNC at birth (&lt;30 days) in the Copenhagen Baby Heart Study. Cases were matched to controls on mothers age at delivery, parity, and age of child at follow-up. First-degree relatives (parents, siblings and half-siblings) were also included. LVNC was defined as a non-compact to compact ratio of myocardium of ≥2 in at least one left ventricular segment, measured in 24 segments in end-diastole perpendicular to the left ventricular cavity as previously suggested. Results: Of the 16 children diagnosed with LVNC at birth, 10 have been reevaluated (age 3.5 (interquartile range (IQR) 3, 4) years, 80% male) together with 20 matched controls (age 4 (IQR 3, 4) years, 70% male), 29 first-degree relatives in case group (age 29 (IQR 4, 35) years, 45% male) and 55 first-degree relatives in control group (age 32 (IQR 11, 36) years, 51% male). In probands, the extent of trabeculation (13% vs. 12%, p=0.97) and fractional shortening (FS) (29% vs. 31%, p=0.24) were unchanged from birth to follow-up. At follow-up, the median left ventricular FS was significantly lower in probands compared to matched controls (31% vs. 33%, p=0.03). Ten (35%) first-degree relatives to probands fulfilled criteria for LVNC compared to 0 (0%) of first-degree relatives to controls (p&lt;0.001). Conclusions: Children with LVNC diagnosed neonatally as part of a population study had no further progression of left ventricular dysfunction or extent of trabeculation at the age of 2-4 years, but systolic function was reduced compared to matched controls. One third of first-degree relatives to children with LVNC fulfilled criteria for LVNC.
NCOG-09. PREDICTIVE GERIATRIC FACTORS IN ELDERLY PATIENTS TREATED FOR IDH-MUTANT HIGH-GRADE GLIOMAS: A FRENCH POLA NETWORK STUDY
Authors: Coline Montégut, Jean-Sébastien Guillamo, François Ducray, Caroline Dehais, Cohen-Jonathan Moyal Elisabeth, Christine Desenclos, Antoine Petit, Romuald Seizeur, Lien Bekaert, Claude Gaultier, Marie Jeannette Motuo Fotso, Marie Blonsky, Jean Sébastien Frenel, Elodie Vauléon, Olivier Langlois, Georges Noël, Antoine Carpentier, Anna Luisa Di Stefano, Charlotte Bronnimann, Dominique Figarella-Branger, Olivier Chinot, Emeline Tabouret
Journal: Neuro-Oncology (2021)

Abstract We aimed to describe the characteristics, patterns of care and predictive geriatric factors of elderly patients with IDH-mutant (IDHm) high-grade gliomas (HGG) included in the French POLA network, dedicated to HGG (including 68% of IDHm HGG). For IDHm HGG patients over the age of 70 years, geriatric features were collected: G8 score items (appetite, weight loss, mobility, neuropsychological disorders, body mass index, medications, self-rated health, age), Activities and Instrumental Activities of Daily Living (ADL, IADL) scores, Charlson’s comorbidity Index (CCI) and biological markers. Out of the 1433 HGG patients included in the POLA Network, 119 (8.3%) occurred in patients ≥ 70 years. Among them, 39 presented with IDHm HGG. Of these 39 patients, estimated G8 score was ≤ 14/17 for 16 patients (64%), ADL score was &amp;lt; 6 for 33.3%, IADL score was &amp;lt; 4 for 47% and CCI was ≥ 5 for 72%. Regarding treatment feasibility, 6 of the 19 patients treated by temozolomide prematurely discontinued chemotherapy including 2 for toxicity and 4 for progression. Five of the 10 patients treated by PCV prematurely discontinued chemotherapy, all for toxicity. In multivariate analysis, loss of mobility (p=0.018; p=0.008), severe neuropsychological disorders (p=0.005; p=0.047), body mass index &amp;lt; 21 kg/m2 (p=0.002; p=0.006) and ADL score &amp;lt; 6 (p=0.002; p=0.01) were significantly predictive of poor PFS and OS. Then we generated a specific brain geriatric score including these four items with a sensibility, specificity and AUC for long term survivor (≥ 48 months) of 100%, 83% and 0.948 respectively. Using a cutoff of &amp;lt; 10/13, this score was significantly correlated to PFS and OS (p&amp;lt; 0.001 both). In conclusion, geriatric predictive factors may contribute to the elderly management improvement: the brain geriatric score must now be validated in a prospective independent cohort including IDHm and IDHwt elderly patients.
Abstract 11167: Prevalent Locations of Left Atrial Scar in Patients with Non-Paroxysmal Atrial Fibrillation: A Single-Center Experience
Authors: Sanghamitra Mohanty, CHINTAN G TRIVEDI, Domenico G Della Rocca, William Zagrodzky, Carola Gianni, Angel Mayedo, Bryan MacDonald, John Burkhardt, G Gallinghouse, Amin Al-ahmad, Rodney Horton, Luigi Di Biase, Andrea Natale
Journal: Circulation (2021)

Introduction: Left atrial (LA) scar, identified by bipolar voltage mapping, is a frequent finding in patients with non-paroxysmal atrial fibrillation (NPAF). We evaluated the most common sites of scar formation in the LA in a series of NPAF patients. Methods: Consecutive NPAF patients undergoing their first catheter ablation at our center were included in this analysis. Voltage mapping was performed in sinus rhythm (SR) using a 3D electro-anatomic mapping system and a 10-pole circular mapping catheter. The LA was divided into following regions: septum, posterior wall, lateral wall, anterior wall and roof. The threshold for low voltage was &lt;0.5 mV (with a color range setting 0.2-0.5 mV). Results: A total of 359 NPAF (224, 62.4% persistent AF) patients undergoing their first ablation procedure with voltage mapping performed in SR were included in this study. Mean number of points taken to map the scar was 281.2±96.3. Low voltage area was detected in 209/359 (58%) cases; 108 (48.62%) persistent AF, 101(74.8%) long-standing persistent AF, p&lt;0.001). The scarring was observed to be located in the anterior septum in 98 (46.9%) and posterior wall of the LA in 136 (65%) patients (FIGURE) Conclusion: In the NPAF population, LA scar was detected in significantly less number of persistent AF patients. Scars were mostly located in the posterior wall of left atrium followed by the antero-septum region. Characterization of the LA scars would be helpful in optimizing the ablation targets.
Engineering β Cell Replacement Therapies for Type 1 Diabetes: Biomaterial Advances and Considerations for Macroscale Constructs
Authors: Michelle J. Quizon, Andrés J. García
Journal: Annual Review of Pathology Mechanisms of Disease (2021)

While significant progress has been made in treatments for type 1 diabetes (T1D) based on exogenous insulin, transplantation of insulin-producing cells (islets or stem cell-derived β cells) remains a promising curative strategy. The current paradigm for T1D cell therapy is clinical islet transplantation (CIT)-the infusion of islets into the liver-although this therapeutic modality comes with its own limitations that deteriorate islet health. Biomaterials can be leveraged to actively address the limitations of CIT, including undesired host inflammatory and immune responses, lack of vascularization, hypoxia, and the absence of native islet extracellular matrix cues. Moreover, in efforts toward a clinically translatable T1D cell therapy, much research now focuses on developing biomaterial platforms at the macroscale, at which implanted platforms can be easily retrieved and monitored. In this review, we discuss how biomaterials have recently been harnessed for macroscale T1D β cell replacement therapies.
CSIG-03. GBP5 DRIVES MALIGNANCY OF GLIOBLASTOMA
Authors: Ming Li, Clark Chen
Journal: Neuro-Oncology (2021)

Abstract Guanylate binding proteins (GBPs), a family of interferon-inducible large GTPase, play a pivotal role in cell-autonomous immunity and tumor malignant transformation. Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor in adults. Here we show that GBP5 was highly expressed in GBM cell lines and in clinical samples, especially in the mesenchymal subtype. The expression levels of GBP5 were negatively correlated with the prognosis of GBM patients. Overexpression of GBP5 promoted the proliferation, migration, and invasion of GBM cells in vitro and in vivo. In contrast, silencing GBP5 by RNA interference exhibited the opposite effects. Consequently, targeting GBP5 in GBM cells resulted in impaired tumor growth and prolonged survival time of mice with GBM tumors. We further identified that the Src/ERK1/2/MMP3 axis was essential for GBP5-promoted GBM aggressiveness. These findings suggest that GBP5 may represent a novel target for GBM intervention.
Outcomes after First Rescue Treatment in Patients with Relapsed or Refractory Multiple Myeloma in Colombia
Authors: Humberto Martinez-Cordero, Virginia Abello, William Armando Mantilla Duran, Rigoberto Gomez, Jheremy Reyes, Henry Idrobo, Kenny Galvez, Claudia Patricia Casas, Maria Helena Solano, Daniel Espinosa, Ivan Alfredo Perdomo Amar, Monica Osuna Pérez, Alvaro Gomez Diaz, Domingo Saavedra, Guillermo Quintero, Lina Abenoza, Lina Gaviria, Alicia Henao-Uribe, Claudia Lucia Sossa, Carmen Rosales, Claudia Paredes, Jair Figueroa Emiliani, Isabel Munevar, Carlos Daniel Bermudez Silva, Yasmin Borjas, Alvaro Guerrero, Paola Guerrero, Juan Manuel Herrera
Journal: Blood (2021)
NIMG-01. INTEROBSERVER VARIABILITY OF THE REVISED IMAGING SCORECARD FOR LEPTOMENINGEAL METASTASIS: A JOINT EORTC BRAIN TUMOR GROUP AND RANO EFFORT
Authors: Emilie Le Rhun, Patrick Devos, Sebastian Winklhofer, Hafida Lmalem, Dieta Brandsma, Jaime Gállego Pérez-Larraya, Antonella Castellano, Annette Compter, Frederic Dhermain, Enrico Franceschi, Peter Forsyth, Julia Furtner, Norbert Galldiks, Jens Gempt, Michael Glantz, Elke Hattingen, Johann Martin Hempel, Kurt Jaeckle, Priya Kumthekar, Slavka Lukacova, Giuseppe Minniti, Barbara O'Brien, Tjeerd J Postma, Patrick Roth, Roberta Rudà, Niklas Schäfer, Nils Ole Schmidt, Marion Smits, Tom Snijders, Steffi Thust, Jörg-Christian Tonn, Martin van den Bent, Anouk van den Hoorn, Guillaume Vogin, Matthias Preusser, Patrick Wen, Martin Bendszus, Michael Weller
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Validation of the 2016 LANO MRI scorecard for leptomeningeal metastasis failed for multiple reasons. The objective of this joint EORTC Brain Tumor Group and RANO effort was to validate the feasibility of the revised MRI scorecard for assessing response in leptomeningeal metastasis. METHODS Coded paired cerebrospinal MRI of 20 patients with leptomeningeal metastases from solid cancers at baseline and follow-up after treatment and instructions for assessment were provided via the EORTC imaging platform. The kappa coefficient (K) was used to evaluate inter-observer pairwise agreement. Statistical analyses were performed using SAS V9.4 software (Cary, NC). The sponsor of the study was the University Hospital Zurich (2018-00192). RESULTS Thirty-five raters participated, including 9 neuroradiologists, 17 neurologists, 4 radiation oncologists, 3 neurosurgeons and 2 medical oncologists. Among leptomeningeal metastases-related items at baseline, the best median concordance was noted for hydrocephalus (K=0.63), and the worst median for spinal linear enhancing disease (K=0.46). The median concordance for overall response was moderate (K=0.44). Notably, the interobserver agreement for the presence of parenchymal brain metastases at baseline was minimal (K=0.29). Significant differences were observed when considering the specialty of the raters. Only 394 of 700 ratings (56%) were fully completed. Among 394 fully completed ratings, perfect concordance was noted in 293 ratings (74%) when comparing the overall response according to the guidelines provided in the scorecard and the overall response provided by the raters. The main discordances were noted for partial response according to the rater versus stable disease according to the guidelines (n=44), followed by progression according to the raters versus stable disease according to the guidelines (n=23). CONCLUSION Electronic case report forms with "blocking solutions" are probably required to enforce completeness and quality of scoring. These results confirm the necessity of central review and the need for training of MRI assessment in clinical trials.
Abstract 13560: Household Income Less Than 150% of Federal Poverty Level is Associated With Heart Failure Mortality
Authors: Olayinka J Agboola, Chidi Okoroafor, Valentine Yanchou Njike, Jeph Herrin, Erica S Spatz
Journal: Circulation (2021)

Introduction: The per capita cost of managing heart failure (HF) is rising and so is the patient’s financial responsibility. This study examined the association between household income expressed as percentage of federal poverty level (FPL) and HF mortality. Methods: The United States Census National Longitudinal Mortality Study (NLMS), consisting of surveys administered between March 1973 and March 2011, was designed to study the effect of socioeconomic factors on mortality rates in the US. Matching the NLMS database to the National Death Index, we identified and retrospectively analyzed data of all cases of heart failure deaths in the NLMS. For this analysis, we included only records that could be prospectively followed for 11 years from time of survey. Study sample was categorized into three groups by baseline household income expressed as a percentage of FPL: Group 1 ≤ 150%FPL (n=1260); 2 &gt;150% but ≤ 300% (n=1059) and 3 &gt; 300% (n=907). We assessed the association between the 3 groups and risk of mortality using unadjusted and adjusted Cox regression. Kaplan Meir plots were computed and survival between the three groups was compared using log-rank statistics. Result: Among the 1,835,072 records that could be followed for 11 years, there were 3,226 HF deaths. Median (IQR) survival (in years) were 5.6 (2.9 – 8.3), 6.2 (3.4 – 8.6) and 6.3 (3.4 – 8.8) for groups 1, 2, and 3 respectively [p=0.002]. Having income less than 150% FPL was associated with 14% increased risk of mortality (hazards ratio [HR]= 1.14 (1.07 – 1.23; P=0.0002) compared with income &gt;150%FPL. Adjusting for age, race, sex, and health insurance status, income less than 150% was independently associated with a 21% higher risk of mortality (HR=1.21 (1.11 – 1.32; p=&lt;.0001)) compared with income &gt;150%FPL. Conclusion: Low income is associated with increased risk of HF mortality. This finding may help guide planning for social interventions and resource allocation.
Abstract 14462: RBM20 Regulation In Healthy And Diseased Cardiomyocytes: A New Opportunity For Targeted Therapeutics
Authors: Francesca Briganti, Arjun Verma, Prashila L Amatya, Mark Mercola
Journal: Circulation (2021)

Introduction: Mutations in the splicing factor RBM20 cause a severe form of dilated cardiomyopathy (DCM) characterized by early onset, fast disease progression, and high risk of sudden death. We have previously shown that modulation of RBM20 expression is a promising strategy for patient with mutations in RBM20. However, our understanding of its endogenous regulation is limited. Hypothesis: DCM-causing mutations in RBM20 interfere with phosphorylation of RBM20 RS domain and with localization of the protein. We hypothesize that modulation of RBM20 phosphorylation could be used to normalize function in the presence of mutations that impair it. We sought to uncover the pathways responsible for such regulation and test their therapeutic potential. Methods: We developed a fluorescent in vitro reporter system that allows for the quantification of RBM20 expression and localization in human cardiomyocytes. We generated an induced Pluripotent Stem cells (iPSC) line in which the endogenous RBM20 is tagged at the C-term with an in-frame mCherry (RBM20-mCh). The tag leaves the regulatory regions at the 5’ end of the gene intact. RBM20-mCh hiPSC were differentiated into cardiomyocytes (iPSC-CMs) and matured for 4 weeks. We screened 2-month-old matured iPSC-CM on Matrigel-coated 384-well plates against a library of siRNA targeting all human kinases and phosphatases. We tested the hits in a contractility assay Results: We identified 35 kinases and 16 phosphatases that alter RBM20 expression and localization. Functional studies showed that the kinases that upregulated RBM20 expression increased cardiomyocyte contractility while downregulating kinases reduced contractility. Conclusions: In conclusion, understanding the kinase regulation of RBM20 provides insight into control of mRNA splicing of proteins such as Titin and may point to new targeted therapeutic strategies for RBM20 mutant DCM.
Abstract 10063: Implementation of Appropriate Use Criteria for Cardiac Computed Tomography and Magnetic Resonance Imaging in the Follow-Up Care of Patients with Conotruncal Congenital Heart Disease
Authors: Sarah S Pickard, Aimee K Armstrong, Sowmya Balasubramanian, Sujatha Buddhe, Kimberly Crum, Michael Kelleman, Grace Kong, Sean Lang, Marc Lee, Leo Lopez, Shobha S Natarajan, Mark D Norris, David Parra, Anitha Parthiban, Andrew J Powell, Bryant Priromprintr, Lindsay Rogers, Shagun Sachdeva, Sanket S Shah, Clayton A Smith, Kenan W Stern, Courtney Wagner, Luciana T Young, Ritu Sachdeva
Journal: Circulation (2021)

Introduction: To promote the rational use of cardiovascular imaging in the delivery of high-quality and cost-effective care to patients with congenital heart disease (CHD), the American College of Cardiology developed Appropriate Use Criteria (AUC). We aimed to evaluate the appropriateness of indications for cardiac CT and MRI in patients with conotruncal defects and to identify factors associated with Maybe or Rarely Appropriate (M/R) indications. Methods: Twelve US centers contributed a median of 147 studies performed prior to AUC publication (01/2020) on patients with conotruncal defects. Studies were excluded if the patient did not receive primary cardiac care at the center or were not seen &gt; 5 years prior to study date. To account for the nesting of physicians within center, a hierarchical generalized linear mixed model was used to account for center-level variation with physicians nested within center. Results: Of the 1,753 studies (20% CT, 80% MRI) from 12 centers, 16% (range 4-39%) were rated M/R and 2.4% were unclassifiable (Figure 1). Patients age &lt;1 year accounted for 8.4% of studies. In multivariable analyses, patient- and study-level factors associated with M/R rating included: age &lt;1 year (OR 1.9 [95% CI 1.1-3.4]), truncus arteriosus (vs. TOF, OR 2.2 [95% CI 1.2-4.0]), and CT (vs. MRI, OR 2.5 [95% CI 1.7-3.8]). Center-level factors included: part of an adult hospital (vs. stand-alone children’s, OR 0.8 [95% CI 0.2-0.7]) and annual MRI volume (for every 50 unit increase, OR 0.96 [95% CI 0.92-0.99]. Provider-level factors did not remain significant in the multivariable model. Conclusions: Most cardiac CTs and MRIs ordered for the follow-up care of patients with conotruncal defects were rated Appropriate and nearly all were able to be classified. However, there was significant center-level variation and higher annual MRI volume was independently associated with lower odds of M/R rating. These findings inform future quality improvement initiatives.
Methionine Restriction As a Novel Therapeutic Strategy for MLL (<i>KMT2A)</i>-Rearranged Acute Lymphoblastic Leukemia
Authors: Trisha Tee, Titine Ruiter, Ahmed Dahaoui, Dorette van Ingen Schenau, Rico Hagelaar, Laurens van der Meer, Frank van Leeuwen
Journal: Blood (2021)
Treatment of COVID-19 Patients: Insights into the Use of Bone Marrow-Derived Mesenchymal Stem Cells
Authors: Heitor Duarte Andrade, Andrea Tiemi Kondo, Lucila Kerbauy, Raquel de Melo Alves Paiva, Denise Cristine Oliveira, Larissa Leggieri Coa, Kelen Cristina Arcuri Alvarez, Mariana Lorenzi Savioli, Bruna Melo Coelho Loureiro, Oswaldo Keith Okamoto, Nelson Hamerschlak, Jose Mauro Kutner, Juliana Aparecida Preto Godoy
Journal: Blood (2021)
Abstract 11384: Discharge and De-Escalation After VAD Implant in Children with Dilated Cardiomyopathy: A Multi-Center Quality Improvement Initiative
Authors: Arene Butto, Chloe Connelly, David Bearl, Angela Lorts, Matthew J O'Connor, David N Rosenthal, Hari Tunuguntla, Jennifer Conway
Journal: Circulation (2021)

Introduction: Children with dilated cardiomyopathy (DCM) are increasingly bridged to heart transplant (Tx) with intracorporeal continuous flow ventricular assist devices (VADs), but there continues to be variability in hospital discharge. We sought to assess the impact of a quality improvement (QI) project promoting hospital discharge in pediatric VAD patients with DCM. Methods: Patients enrolled at sites participating in the Discharge and De-Escalation QI project of the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry were eligible. Patients with a HeartWare (HVAD) or HeartMate3 (HM3) VAD, implanted between April 2018 and February 2021, were included. Patient characteristics and outcomes were compared before and after the QI initiative, which targeted team and family expectations, was implemented in November 2019. Results: There were 85 patients (75%) with DCM and/or myocarditis who were included in this study (median age 14 years; median weight 57.1 kg; 67% male). Among 57 patients in the baseline group, 56% (n=32) were discharged with a mean post-implant hospital length of stay (LOS) of 36 days and 44% (n=25) underwent Tx during index VAD admission, with a mean of 52 days on device. There were 28 patients in the intervention group; 64% (n=18) were discharged with a mean LOS of 45 days, while 29% (n=8) patients underwent Tx during index VAD admission, with a mean of 44 hospital days on device. There was no significant difference in the frequency of hospital discharge or in hospital LOS between groups. Conclusions: Pediatric centers discharged just over half of DCM patients supported on an HVAD or HM3, with nearly one third of patients undergoing transplant during the index VAD admission. The QI intervention did not significantly alter the discharge rate. Further work is required to understand practice variation between centers with respect to Tx listing and organ acceptance for children on intracorporeal continuous flow VADs.