tbuckley/cabot-search huggingface dataset:
CTIM-03. AUTOLOGOUS ADOPTIVE IMMUNE-CELL THERAPY ELICITED A DURABLE RESPONSE WITH ENHANCED IMMUNE REACTION SIGNATURES IN PATIENTS WITH RECURRENT GLIOBLASTOMA: AN OPEN LABEL, PHASE I/IIA TRIAL
Authors: Jaejoon Lim, Young Joon Park, Ju Won Ahn, Jeong Min Sim, Suwan Kim, Sojung Hwang, Kyungsu Sung, Kyunggi Cho
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma multiforme (GBM) is an aggressive malignancy classified by the World Health Organization as a grade IV glioma. Despite the availability of aggressive standard therapies, most patients experience recurrence, for which there are currently no effective treatments. We aimed to conduct a phase I/IIa clinical trial to investigate the safety and efficacy of adoptive, ex-vivo-expanded, and activated natural killer cells and T lymphocytes from peripheral blood mononuclear cells of patients with recurrent GBM. This study was a single-arm, open-label, investigator-initiated trial on 14 patients recruited between 2013 and 2017. The immune cells were administered via intravenous injection 24 times at 2-week intervals after surgical resection or biopsy. The safety and clinical efficacy of this therapy was examined by assessing adverse events and comparing 2-year overall survival (OS). Transcriptomic analysis of tumor tissues was performed using NanoString to identify the mechanism of therapeutic efficacy. No grade 4 or 5 severe adverse events were observed. The most common treatment-related adverse events were grade 1 or 2 in severity. The most severe adverse event was grade 3 fever. Median OS was 22.5 months, and the median progression-free survival was 10 months. Five patients were alive for over 2 years and showed durable response with enhanced immune reaction transcriptomic signatures without clinical decline until the last follow-up after completion of the therapy. In conclusion, autologous adoptive immune-cell therapy was safe and showed durable response in patients with enhanced immune reaction signatures. This therapy may be effective for recurrent GBM patients with high immune response in their tumor microenvironments. Trial registration: The Korea Clinical Research Information Service database: KCT0003815, Registered 18 April 2019, retrospectively registered.
Abstract P318: Dna Tension Probes Show That Cardiomyocyte Maturation Is Sensitive To The Pico-Newton Traction Forces Transmitted By Integrins
Authors: Sk A Rashid
Journal: Circulation Research (2021)

Cardiac muscle cells (CMCs) are the unit cells that comprise the heart. CMCs go through different stages of differentiation and maturation pathways to fully mature into beating cells. These cells can sense and respond to mechanical cues through receptors such as integrins which influence maturation pathways. For example, cell traction forces are important for the differentiation and development of functional CMCs, as CMCs cultured on varying substrate stiffness function differently. Most work in this area has focused on understanding the role of bulk ECM (extracellular matrix) stiffness in mediating the functional fate of CMC. Given that stiffness sensing mechanisms are mediated by individual integrin receptors, an important question in this area pertains to the specific magnitude of integrin piconewton (pN) forces that can trigger CMC functional maturation. To address this knowledge gap, we used DNA adhesion tethers that rupture at specific thresholds of force (~12, ~56, and ~160 pN) to test whether capping peak integrin tension to specific magnitudes affects CMC function. The work shows that adhesion tethers with greater force tolerance lead to functionally mature CMCs as determined by morphology, twitching frequency, transient calcium flux measurements and protein expression (F-actin, vinculin, α-actinin, YAP and SERCA2). Additionally, sacromeric actinin alignment and multinucleation were significantly enhanced as the mechanical tolerance of integrin tethers was increased. Taken together, the results show that CMCs harness defined pN integrin forces to influence early stage development. This study represents an important step toward biophysical characterization of the contribution of pN forces in early stage cardiac differentiation.
Abstract 11341: Diabetes and Chronic Kidney Disease: Prevalence, Associated Factors and Influence on Optimal Medical Therapy in Patients with Coronary Artery Disease
Authors: Eduardo M Moreira, Henrique Trombini Pinesi, Paula Bolta, Eduardo Martins, Fabiana H Rached, Fabio G Pitta, Desiderio Favarato, Eduardo G Lima, Cibele L Garzillo, Carlos A Segre, Carlos V Serrano
Journal: Circulation (2021)

Introduction: Diabetes mellitus (DM) and chronic kidney disease (CKD) are comorbidities of great therapeutic and prognostic importance in patients with coronary artery disease (CAD). Knowledge about their prevalence, associated factors and influence on optimal medical therapy are needed to best manage this population. Methods: This is a unicentric cross-sectional analysis of 869 patients enrolled in a CAD registry in Brazil. To be included, patients needed to have a previous coronary artery revascularization procedure (either percutaneous or surgical), documented previous acute coronary syndrome, or known coronary stenosis greater than 50%. CKD was defined as creatinine clearance &lt; 60 mL/min. DM was defined as prescription of glucose-lowering drugs or a HbA1c &gt; 6.5%. Results: Overall, mean age was 64.7 years, 261 (30%) were women, 528 (61%) had previous myocardial infarction, and 547 (63.4%) had a previous revascularization procedure. DM was prevalent in 449 (51.7%) patients and CKD in 280 (32.2%). Both comorbidities were concomitant in 151 (17.4%) patients. On multivariate analysis, CKD was correlated to female sex (OR 2.94; 95%CI 1.88-4.67), age (OR 1.20; 95%CI 1.16-1.23), BMI (OR 0.80, 95%CI 0.76-0.84), and HDL-cholesterol (OR 0.97; 95%CI 0.96-0.99). DM was associated with age (OR 1.02, 95%CI 1.00-1.04), BMI (OR 1.05, 95%CI 1.01-1.08), high blood pressure (OR 2.1, 95%CI 1.39-3.21), and heart rate (OR 1.02, 95%CI 1.00-1.03). Concomitant presence of CKD and DM was associated with age (OR 1.09, 95%CI 1.06-1.13) and left ventricular ejection fraction (OR 0.97, 95%CI 0.95-0.98). Patients with DM were more likely to receive ACE inhibitors or ARBs (79.3% x 67.1%, p&lt; 0.001) and calcium channel blockers (41.9% x 31.2%, p=0.001). Patients with DM and CKD had higher use of nitrates (38.4% x 25.6%, p=0.002). There was no difference in the prescription of antithrombotic drugs, beta-blockers or statins between groups. Conclusion: DM and CKD are both very prevalent comorbidities in patients with CAD. They are associated with age and risk markers such as high blood pressure and lower left ventricular ejection fraction. Although typically these populations are undertreated in others registries, this fact was not observed in our study.
Abstract 11159: Prevalence and Prognostic Relevance of Heart Failure Stages Among Black Americans in the Community: The Jackson Heart Study
Authors: Katja Vu, Rani Zierath, Brian Claggett, Michael E Hall, Donald Clark, Kenneth R Butler, Adolfo Correa, Amil M Shah
Journal: Circulation (2021)

Introduction: Black Americans experience a heightened risk of heart failure (HF) and develop HF at earlier ages than other racial/ethnic groups. Limited data exist regarding the prevalence and prognostic relevance of ACC/AHA HF stages among Black Americans. We aimed to quantify the distribution and prognostic relevance of ACC/AHA HF stages among Black Americans in mid- and late-life. Methods: We classified 4,763 Black participants in the community-based Jackson Heart Study who underwent echocardiography at study Exam 1 (2000-2004) by HF stage as follows: Stage A: presence of clinical HF risk factors (prevalent cardiovascular disease, hypertension, diabetes, obesity, metabolic syndrome, or chronic kidney disease) in the absence of structural heart disease; Stage B: structural heart disease (LVEF &lt;50%, LV hypertrophy or enlargement, moderate to severe valvular disease); and Stage C: prevalent HF. Multivariable Cox proportional hazard regression models adjusted for age and gender were used to assess the associations of the HF stage at Exam 1 with incident HF hospitalization and all-cause mortality post-Exam 1. Results: Mean age was 55.3 ± 12.7 years and 64% were women. No clinical risk factors or cardiac structural or functional abnormalities (Stage 0) were present in 13% of participants. Stage A was present in 59%, Stage B was present in 26%, and prevalent HF (Stage C) was present in 3%. Over a median of 12.8 [IQR 11.8-13.5] years follow up, 332 participants developed HF and 1,060 participants died. Compared to those free of risk factors or structural remodeling (Stage 0), a more advanced HF stage was associated with greater risk of incident HF, and the composite of HF or death (Figure). Conclusions: In this large community-based cohort of Black Americans, HF risk factors (Stage A) and/or asymptomatic structural heart disease (Stage B) was present in 85% of participants. Stage A and Stage B were each associated with heightened risk of HF hospitalization.
NCMP-20. PRE-INFUSION NEUROFILAMENT LIGHT CHAIN (NFL) LEVELS PREDICT THE DEVELOPMENT OF IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME (ICANS) – A MULTICENTER RETROSPECTIVE STUDY
Authors: Omar Butt, Alice Zhou, Kenneth Lee, Gregory Wu, Paolo Caimi, Marcos de Loma, Jian Campian, John DiPersio, Armin Ghobadi, Beau Ances
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Neurological side effects after chimeric antigen receptor-modified (CAR) T cell therapy, termed immune effector cell-associated neurotoxicity syndrome (ICANS), are common and potentially devastating. We previously demonstrated that pre-infusion plasma neurofilament light chain (NfL), a well-established marker of neurodegeneration, may predict subsequent development of ICANS in a small, single-center cohort. This larger, retrospective multicenter study compares pre-infusion NfL to known post-infusion risk factors for developing ICANs including white blood cell (WBC) count, platelet count, C-reactive protein (CRP), fibrinogen, and ferritin levels. METHODS Inclusion criteria included available pre-infusion (up to 4 weeks prior to lymphodepletion) plasma from patients treated with a CAR T cell therapy (n = 30, 36% with ICANS, ASTCT consensus ICANS grade range 1-4). Exclusion criteria included confounding diagnoses known to elevate NfL levels (dementia, multiple sclerosis, recent stroke). Plasma NfL was assayed using a Simoa HD-1/HD-X kit (QuanterixTM). Post-infusion Day 3 or Day 5 WBC, Platelet, CRP, fibrinogen, and ferritin were obtained from the medical record. Group comparisons were done using log-rank tests with a Bonferroni-derived significance threshold, followed by receiver operating characteristic (ROC) curve classification. RESULTS Prior to infusion, individuals who ultimately developed ICANS had elevations in NfL ([87.6 v 29.4 pg/ml], p = 0.00004) with excellent classification (AUC 0.96), sensitivity (0.91) and specificity (0.95). Among known post-infusion risk factors, only post-infusion Day 3 ferritin (p = 0.004) and Day 5 ferritin (p = 0.003) differed between groups. Classification was inferior for both time points (Day 3 AUC = 0.87, specificity 0.71; Day 5 AUC 0.87, specificity 0.86). CONCLUSION Pre-infusion plasma NfL levels are a robust early marker for the development of ICANS that exceeds known post-infusion markers. Our findings suggest the risk of developing ICANS reflects pre-existing host-factors. Foreknowledge of ICANS development of may permit early, aggressive (preemptive or prophylaxis) ICANS-directed therapies, improving patient outcomes.
Chronic Obstructive Pulmonary Disease
Authors: Sharon Parmet, Cassio Lynm, Richard M. Glass
Journal: JAMA (2003)

Chronic Obstructive Pulmonary DiseaseC hronic obstructive pulmonary disease (COPD) is a term used to describe 2 related lung diseases: chronic bronchitis and emphysema.Chronic bronchitis is inflammation and eventual scarring of the bronchi (airway tubes).Emphysema is enlargement and destruction of the alveoli (air sacs) within the lungs.Many persons with COPD have both of these conditions.Persons with COPD have difficulty breathing because they develop smaller air passageways and have partially destroyed alveoli.The air passageways also become clogged with mucus, a slimy substance.Smoking cigarettes is the most important risk factor and cause of COPD.About 80% to 90% of COPD cases are caused by smoking, and a smoker is 10 times more likely than a nonsmoker to die of COPD.The November 5, 2003, issue of JAMA includes an article about treatments for COPD.
Safety and Efficacy of Combination Maintenance Therapy with Ixazomib and Lenalidomide in Post-Transplant Myeloma Patients
Authors: Krina K. Patel, Jatin J. Shah, Lei Feng, Hans C. Lee, Elisabet E. Manasanch, Jasper B. Olsem, Ashley N. Morphey, Xiao Jiao Huo, Qaiser Bashir, Sheeba K Thomas, Muzaffar H. Qazilbash, Donna M. Weber, Robert Z. Orlowski
Journal: Blood (2021)
Abstract 9872: Cardiac Enhancer Variants at the Mtss1 Locus Are Associated with Smaller, More Contractile Hearts
Authors: Megan F Burke, Michael P Morley, Yifan Yang, Theodore G Drivas, dongwook choe, Sharlene Day, Kiran Musunuru, Mingyao Li, Marylyn Ritchie, Thomas P Cappola
Journal: Circulation (2021)

Introduction: Variants at the MTSS1 locus influence cardiac structure, function, and failure in multiple genome wide association studies (GWAS), yet the genetic mechanisms remain unclear. We previo...
The Plasma Level of IL-1β As a Biomarker of Angiopathy in Systemic Chronic Active EBV Infection
Authors: Ayaka Ohashi, Yu Uemura, Mayumi Yoshimori, Naomi Wada, Ken-Ichi Imadome, Kazuo Yudo, Takatoshi Koyama, Miwako Nishio, Ayako Arai
Journal: Blood (2021)
Abstract 10290: The Relationship Between Brain Derived Neurotrophic Factor (BDNF) and Symptoms Following Catheter Ablation for Paroxysmal Atrial Fibrillation (AF)- NEURO-AF Study
Authors: Nicolas Berbenetz, Jennifer Reed, David H Birnie, Tasuku Terada, Matheus Mistura, Pablo B Nery, Calum J Redpath, Mouhannad M Sadek, Li Chen, George A Wells, Frans M Leenen, Heather Tulloch, Girish M Nair
Journal: Circulation (2021)

Introduction: Reduced BDNF concentrations have been observed in patients with depression and heart failure, with treatment and improvement in symptoms associated with increased concentrations. AF is associated with symptoms of depression and poor Quality of Life (QoL). Hypothesis: We hypothesized that patients without AF recurrence following catheter ablation would have higher BDNF concentrations, less depression severity, and improved QoL scores. Methods: A prospective observational study was conducted. BDNF (biosensis® Rapid ™ ELISA) concentrations were performed and the Beck Depression Inventory-II (BDI-II), Short Form-36 Health Survey (SF-36) and AF Severity Scale (AFSS) were administered before and 12 weeks after catheter ablation. The primary outcome was change in BDNF blood concentrations following catheter ablation and its relationship with depression severity and AF related QoL. Results: One hundred patients with paroxysmal AF were recruited of which 98 completed the study. Eighty-nine patients were free of recurrent AF/atrial arrhythmias (AA) following catheter ablation. The baseline demographics and results are summarized in the accompanying table. Statistically significant changes were observed in BDNF concentrations, BDI scores and AFSS (perceived AF burden and symptoms) in patients without AF recurrence, after adjustments for CHADS2 score, age, and sex. The number of patients with AF recurrence were too few to make meaningful interpretation of results. Conclusions: BDNF concentrations significantly improved in subjects without AF recurrence after catheter ablation and were associated with a concomitant reduction in depression severity, perceived AF burden and symptoms of paroxysmal AF. Further research is required to determine the mechanism(s) that explain this novel association between BDNF and AF related symptoms.
Abstract 9940: Role Of Cardiology Clinical Pharmacist In The Management Of Peripartum Cardiomyopathy; Vulnerable Condition With Critical Interventions
Authors: Israa Fadhil Yaseen, Hasan Ali Farhan
Journal: Circulation (2021)

Introduction: Peripartum cardiomyopathy (PPCM) is a rare disease, however, mortality rate is reaching 24% as reported in the 2018 ESC guidelines for the management of cardiovascular disease during pregnancy. Awareness about optimal management and avoiding drug therapy complications is one of the essential keys to improve the outcomes of PPCM patients and could be achieved by expert multidisciplinary team work. Methods: To identify the role of cardiology clinical pharmacist among heart team in the management of PPCM patients, data about cardiology clinical pharmacist’s interventions in the management of 66 patients with PPCM was retrospectively collected and categorized into 6 categories. Study conducted at the cardio-maternal clinic where all the enrolled patients were prospectively diagnosed and followed up during and after pregnancy between 2015 - 2021 by heart team. Patients' follow-up was done either by clinic visit or by using telemedicine. All the pharmacist's interventions were agreed by the senior consultant cardiologist. Results: The cardiology clinical pharmacist performed 37 interventions and categorized into six categories as shown in figure 1. It was found that 8% of interventions were to stop duplication or triplication of the drug doses, as some patients were using two or three brands from the same drug believing that they are different therapies. Also 8% of interventions were correcting the use of wrong dose or drug, a problem which was happened due to an error by dispensing the dose or the drug to the patients from the private pharmacies. Conclusions: Cardiology clinical pharmacist has a vital role among heart team in the management of PPCM patients to reduce the serious drug therapy errors; which could be harmful for both mother and fetus, optimization of drug therapy, and reduce drug related complications.
EPID-04. THE NATURAL HISTORY OF NEUROFIBROMATOSIS-1, THE MONTEFIORE EXPERIENCE
Authors: Tiffany Lin, Nagma Dalvi
Journal: Neuro-Oncology (2021)

Abstract Neurofibromatosis type 1 (NF1) is a genetic disorder with varying phenotypes that can affect many organ systems. Notably, it has significant clinical variability involving different systems in each individual. Manifestations may also develop and evolve with age. Although current literature has looked into the prevalence of the manifestations of NF1, few have compared the prevalence in populations of diversity. The objective of our study is to describe the clinical manifestations of NF1 seen in an urban neurocutaneous clinic that serves a diverse ethnic and socioeconomic population. We intend to see how the clinical manifestations of our patients compare to what is reported and to better understand the clinical impact and prognoses of NF1 in this population. We performed a retrospective study of patients in our neurocutaneous clinic from May 2014 to December 2020. Of the 89 that fit study criteria, we had a majority of Hispanic and Black patients. We compared our data to two recent NF1 natural history studies, Boulanger et al. and Cnossen et al., using chi-square or Fisher exact test. Results showed that we had a lower incidence of cutaneous neurofibromas (23.6% vs the reported 40%) and lisch nodules (32.6% vs the reported 50%), but a higher incidence of symptomatic plexiform neurofibromas (48.3% vs the reported 25%) and CNS tumors requiring intervention (4.5% vs estimated 2% in compared studies). This may indicate that our population is at higher risk for more serious complications. We speculate that socioeconomic and ethnic diversity may be the driver behind these differences. Our center has also initiated treatment using MEK inhibitors in indicated patients. Due to the differences in clinical manifestations and more severe complications, we recommend closer surveillance in diverse populations. We also advocate for further research in the application of MEK inhibitors beyond second-line therapy.
Abstract 13796: Diffuse Regional Strain Abnormalities Despite Normal Ejection Fraction Suggestive of Occult Myocardial Dysfunction in Multisystem Inflammatory Syndrome in Children
Authors: Simon Lee, Lydia Wright, Cristin Blaney, Amy Cooper, Samantha Low, Catherine Dimes, Guliz Erdem, Marc Lee, Kan N Hor
Journal: Circulation (2021)

Background: Multisystem Inflammatory Syndrome in Children (MIS-C) patients frequently present with significant hypotension and ventricular dysfunction. While they appear to recover quickly after treatment of MIS-C, long-term sequelae of the myocardium are unknown. We aimed to evaluate ventricular function longitudinally using TTE and CMR. Methods: Retrospective review was performed of all patients with MIS-C who underwent CMR from September 2020 to May 2021. Measures of ventricular size and function during admission, 2-week, and 6-week follow up by TTE as well as global and regional longitudinal strain, as measured by Strain ENCoded imaging (SENC) by CMR were analyzed. The magnitude of strain is expressed as an absolute value, with &gt;17% considered normal. Results: Nineteen patients (13.9±1.9 years, 63% males) with MIS-C underwent CMR. Troponin leak was seen in 16/19 (84%), 15/19 (79%) had ventricular dysfunction, 3/19 (16%) had coronary abnormality, and 1/19 (5%) required ECMO. All patients had normalized function at 2- and 6-week visits (mean LVEF 62±6.3% on TTE at 6-weeks). Group 1 (n=2) had CMR during hospital admission (5, 11 days), Group 2 (n=13) during early outpatient follow-up (median 34 days, range 15-59 days), and Group 3 (n=5) during later outpatient follow-up (median 98 days, range 72-231 days). All patients had normal LVEF on CMR. LVGLS by SENC was significantly impaired throughout follow up. The mean LVGLS of Group 1, Group 2, and Group 3 were 15±0.8%, 15.4±2.4%, and 16.6±1.6%, respectively. The mean number LV segments (from the AHA modified 16 segment model) with abnormal LS in each group were 10±2, 9.2±3.2, and 8.6±2, respectively. Conclusions: There were significant global and regional strain abnormalities despite normalized LVEF on TTE and CMR. This represents occult myocardial dysfunction after MIS-C. It is unclear if these findings will persist. Longitudinal studies are needed to monitor for progression or resolution of these findings.
Isolation of pancreatic microbiota from cystic precursors of pancreatic cancer with intracellular growth and DNA damaging properties
Authors: Asif Halimi, Giorgio Gabarrini, Michał Jacek Sobkowiak, Zeeshan Ateeb, Haleh Davanian, Rogier Aäron Gaiser, Urban Arnelo, Roberto Valente, Alicia Y.W. Wong, Carlos Fernández Moro, Marco Del Chiaro, Volkan Özenci, Margaret Sällberg Chen
Journal: Gut Microbes (2021)

Emerging research suggests gut microbiome may play a role in pancreatic cancer initiation and progression, but cultivation of the cancer microbiome remains challenging. This pilot study aims to investigate the possibility to cultivate pancreatic microbiome from pancreatic cystic lesions associated with invasive cancer. Intra-operatively acquired pancreatic cyst fluid samples showed culture-positivity mainly in the intraductal papillary mucinous neoplasm (IPMN) group of lesions. MALDI-TOF MS profiling analysis shows Gammaproteobacteria and Bacilli dominate among individual bacteria isolates. Among cultivated bacteria, Gammaproteobacteria, particularly Klebsiella pneumoniae, but also Granulicatella adiacens and Enterococcus faecalis, demonstrate consistent pathogenic properties in pancreatic cell lines tested in ex vivo co-culture models. Pathogenic properties include intracellular survival capability, cell death induction, or causing DNA double-strand breaks in the surviving cells resembling genotoxic effects. This study provides new insights into the role of the pancreatic microbiota in the intriguing link between pancreatic cystic lesions and cancer.