tbuckley/cabot-search huggingface dataset:
CTNI-29. SAFETY AND FEASIBILITY OF RHENIUM-186 NANOLIPOSOME (186RNL) IN RECURRENT GLIOMA: THE RESPECT™ PHASE 1 TRIAL
Authors: Andrew Brenner, Ande Bao, William Phillips, Vibhudutta Awasthi, Toral Patel, Jeffrey Weinberg, John Floyd
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Liposomal rhenium-186 (186RNL) is a potent source of beta particles with short path length, variable dose rate, high radiation density and gamma emission. Preclinically, 186RNL delivered via convection enhanced delivery (CED) achieves very high doses of targeted radiation with a wide therapeutic index. We report the results of ReSPECT, the first in man, dose escalation phase 1 trial of 186RNL in recurrent glioma. METHODS Following computer assisted treatment planning and placement of intracranial catheter(s), we performed a single administration of 186RNL by CED. We obtained whole body planar and SPECT/CT imaging on days 1-8 following treatment for dosimetry and distribution and followed patients for safety, progression and survival. RESULTS Twenty-one patients across 7 cohorts received 1.0-22.3mCi in a volume of 0.6-8.80mL. Mean tumor volume was 8.3mL (0.9-22.8mL). Patients had a mean of 1.7 recurrences, 5 received prior bevacizumab. Overall, 19/21 patients and all after cohort 4 had grade 4 glioma (glioblastoma). We used a CED rate of 5-20µl/min per catheter, with 1-4 catheters used per patient. Mean absorbed radiation dose to the tumor was 255Gy (8.9-740Gy) while exposure outside the brain was negligible. The mean percentage tumor in the treated volume (Tu/Tv) was 60.3% (19.8%-100%). Thus far, we have observed no dose limiting toxicities, one grade 3 treatment related adverse event (AEs), and the majority of AEs were mild in intensity. The incidence and severity of AEs did not correlate with increasing dose. Mean Tu/Tv in patients not receiving prior bevacizumab was 75% vs. 48% in those that had. Thus far, overall survival (OS) in 16 bevacizumab naïve patients is 49 weeks with 7 (44%) patients still alive and a positive correlation of OS to Tu/Tv. CONCLUSIONS 186RNL achieves high absorbed doses without significant toxicity with favorable overall survival.
Autosomal Recessive Congenital Dyserythropoietic Anemia Type III Is Caused By Mutations in the Centralspindlin RACGAP1 Component
Authors: Lídia Romero-Cortadellas, Gonzalo Hernández, Xènia Ferrer-Cortès, Veronica Venturi, Mireia Olivella, Concepción Pérez de Soto, Rosario M. Morales-Camacho, Ana Villegas, F. Ataulfo Gonzalez-Fernandez, Marta Morado, Santiago Pérez-Montero, Cristian Tornador, Mayka Sánchez
Journal: Blood (2021)
Accuracy of commercially available smartphone applications for the detection of melanoma
Authors: M.D. Sun, J. Kentley, P. Mehta, S. Dusza, A.C. Halpern, V. Rotemberg
Journal: British Journal of Dermatology (2021)

Artificial intelligence (AI) has shown promise in the analysis of images for detection of melanoma.1 The number of available dermatology smartphone applications (apps) is rapidly growing and there is increasing interest in apps that provide diagnosis or triage of skin lesions.2, 3 A 2020 systematic review found that nine studies evaluating six apps had poor study design and high risk of bias.3 To date, no studies have evaluated the accuracy of apps using an independent test set of clinical images comparable to those submitted through smartphones .
Abstract 6907: Implementing Quality Improvement With Fellow-in-Training Super Users: Preventing Preventable Strokes Initiative
Authors: Kun Xiang, Jose Morales, Kyeesha Becoats, Sebastian Mikulic, Andres Martinez, Jose Rivas, Judella Haddad-Lacle, Christina Catalano, Sue Ash, Patrick Fry, Anne Marie Smith, Mary Martin Lowe, Almaz Araia, Hammad Sadiq, Alok Kapoor, John N Catanzaro
Journal: Circulation (2021)

Introduction: Quality improvement (QI) is an integral requirement of post graduate training. To reduce stroke by addressing lack of anticoagulation (AC) for patients with atrial fibrillation (AF), the Heart Rhythm Society (HRS) led QI initiatives at metropolitan area “safety-net” hospitals, health systems that deliver a significant level of service to medically and socially vulnerable populations. We incorporated a fellow-in-training “Superuser” team in the design of a QI initiative at University of Florida Health Jacksonville. Hypothesis: Our hypothesis was that the use of a team of fellows in training to conduct academic detailing can enhance the impact of QI intervention Methods: This initiative was designed to integrate guideline-based treatment algorithms and alerts into the Electronic Health Record (EHR) and to disseminate education for the provider and patient, with emphasis on shared-decision making. An interdisciplinary team was organized among divisions of cardiology, internal medicine, family medicine, information technology and pharmacy. The first stage was to collect benchmark data to identify gaps in guideline-directed AC. EHR records from July through December 2020 were reviewed. To assist with PDSA (Plan, Do, Study, Act) interventions, a Superuser team was formed by fellows-in-training in cardiology and electrophysiology, as well as residents in internal medicine. The information technology department generated bi-weekly data reports to monitor progress. Bi-weekly Superuser meetings were held to analyze data, identify improvement strategies, and form a plan of action. A total of five PDSA cycles were planned and conducted over a 6-month period. Results: At benchmark, 43.67% of AF patients with a CHA 2 DS 2 -VASc score of 2 or more were untreated with AC. This percentage was reduced to 42.16% after five PDSA cycles. There were 1.5% more patients treated with AC after six months, compared to the benchmark data. This improvement in AC percentage could have resulted in the prevention of 1.5 strokes. Conclusion: Appropriate and sustained interventions can improve quality measurement in guideline-based AF management. Fellows-in-training can be mobilized to support these efforts. The QI initiative achieved some success and built a foundation for future outcomes-based improvement, as well as an enthusiasm for QI by fellows-in-training.
NIMG-11. VOLUMETRIC ENDPOINTS IN DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG): COMPARISON TO CROSS-SECTIONAL MEASURES AND CORRELATION WITH OUTCOMES
Authors: Margot Lazow, Martijn Nievelstein, Adam Lane, Pratiti Bandopadhayay, Mariko DeWire-Schottmiller, Maryam Fouladi, John Glod, Robert Greiner, Lindsey Hoffman, Trent Hummel, Lindsay Kilburn, Sarah Leary, Jane Minturn, Roger Packer, David S Ziegler, Brooklyn Chaney, Katie Black, Peter de Blank, James Leach
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Cross-sectional tumor measures are used as endpoints in clinical trials of DIPG, but may not capture meaningful changes in disease burden. Volumetric measures may provide a more accurate assessment of tumor growth. We measured the correlation between cross-sectional and volumetric measures and compared their prognostic impact to better understand response evaluation in DIPG. METHODS Patients from the International DIPG Registry with diagnostic and post-radiation MRIs were included. Utilizing mint LesionTM software, tumors were manually contoured by an experienced pediatric neuro-radiologist to extrapolate cross-sectional product (CP) and volume measures. Correlation between CP and volume was assessed by linear regression. Landmark analyses were performed to determine differences in overall survival (OS) (via log-rank) between patients classified as progressive disease (PD) versus non-PD according to CP and volumetric measurements at one-, three-, and five-months post-radiation. Imaging consistent with pseudoprogression was designated non-PD. Hazard ratios (HR) for survival after these timepoints were calculated by Cox regression. RESULTS A total of 317 MRIs from 46 patients were analyzed. When comparing change from smallest previous tumor size, CP increase of 25% (PD by RAPNO) correlated with volume increase of 28% (R2=0.685). There was no difference in OS between patients classified as PD versus non-PD by CP at one-month, three-months, or five-months post-radiation (p &amp;gt;0.05). However, significant differences in OS were observed between patients classified as PD versus non-PD by volume (28% increase) at one-month (2.7 vs. 12.8 months, p=0.005), three-months (1.9 vs. 10.7 months, p=0.036), and five-months post-radiation (3.7 vs. 9.1 months, p=0.023). PD by volume, but not by CP, was predictive of survival at all timepoints (HR: 5.0, 2.4, 2.4). CONCLUSIONS Volumetric assessments of PD correlated better with survival than CP at all post-radiation timepoints. Tumor volume likely represents a more accurate, prognostically-relevant measure of disease burden that deserves investigation in future DIPG trials.
TAMI-62. METHIONINE METABOLISM CLOSELY RELATED WITH SELF-RENEW, PLURIPOTENCY AND CELL DEATH IN GICS THROUGH MODIFICATION OF CHOLESTEROL BIOSYNTHESIS, RIBOSOMAL RNA AND AUTOPHAGY
Authors: Kiyotaka Yokogami, Hideo Takeshima
Journal: Neuro-Oncology (2021)

Abstract Glioma initiating cells (GICs) are the source of glioma cells that have the ability to self-renew and pluripotency, which are treatment-resistant, starting point for relapse and eventual death despite multimodality therapy. Since high accumulation is observed in 11cMet-PET at the time of recurrence, it is important to understand the mechanism of tumor cell activation caused by the reorganization of methionine metabolism. We cultured cells in methionine-deprived culture medium and performed a comprehensive analysis, and found that methionine depletion markedly decreased proliferation and increasing cell death of GICs. Decreased SAM, which is synthesized intracellularly catalyzed by methionine adenosyltransferase (MAT) using methionine, triggered the following: (i) global DNA demethylation, (ii) hyper-methylation of signaling pathways regulating pluripotentcy of stem cells, (iii) decreased expression of the core-genes and pluripotent marker of stem cells, (iv) decreased cholesterol synthesis and increased excretion mainly through decreased SREBF2 and FOXM1, (v) down-regulation of the large subunit of ribosomal protein configured 28S and ACA43, snoRNA guiding the pseudouridylation of 28S ribosomal RNA, which has crucial role for translation and (vi) possible connection between methionine metabolism and pluripotency, protein synthesis through cholesterol metabolism: SREBF2-FOXM1 and ACA43 axis, respectively. (vii) Disruption of autophagy by insufficient formation of macroautophagosomes. In conclusion, methionine metabolism closely related with self-renew, pluripotency and cell death in GICs through modification of cholesterol biosynthesis, ribosomal RNA and autophagy.
Abstract 10888: Lipid Profile Predicts Number and Length of Coronary Artery Stents
Authors: Christine P Shen, Samantha R Bagsic, Ashley Jaravata, Richard A Schatz, Matthew J Price, Curtiss Stinis, Paul Teirstein, Amitabh C Pandey
Journal: Circulation (2021)

Introduction: Higher levels of low-density lipoprotein (LDL) are associated with an increased incidence of cardiovascular events. Little is known about the impact of lipid profile on the severity and extent of disease. This study aims to characterize the lipid profile’s ability to predict the number of and total length of coronary artery stents. Hypothesis: In patients undergoing percutaneous coronary intervention, the lipid panel is predictive of the total length and number of coronary stents deployed. Methods: We retrospectively identified unique, consecutive patients undergoing percutaneous coronary intervention at a single center from April 2018 to March 2021. Inclusion criteria included the availability of a lipid panel in the electronic medical record. Associations between lipid levels with stent number or stent length were tested by univariable linear regression. Results: For a single coronary angiogram procedure, 1547 unique patients had a lipid panel in the EMR within 2 weeks of the procedure with a median of 2 stents deployed with median total stent length of 38 mm. High-density lipoprotein (HDL), LDL, but not total cholesterol, triglycerides (TG), were predictive of stent length (HDL inversely, p =0.004; LDL p =0.01) and number of stents (HDL inversely, p =0.008; LDL p =0.04). Conclusions: These results indicate that the lipid panel has implications for the severity and extent of coronary artery disease found during coronary angiography, reflected in the number of and total length of coronary artery stents.
Updates in the Management of Newly Diagnosed Acute Myeloid Leukemia
Authors: Alice S. Mims
Journal: Journal of the National Comprehensive Cancer Network (2021)

For patients with newly diagnosed acute myeloid leukemia (AML) who are candidates for intensive induction regimens, all therapies include anthracycline- and cytarabine-based backbones. Core-binding factor AML is typically treated with gemtuzumab ozogamicin and 7 + 3 chemotherapy. Patients with FLT3 -mutated (ITD or TKD) disease should have midostaurin + 7 + 3 and consolidation, and those with secondary or therapy-related AML should be considered for CPX-351. For patients ineligible for intensive induction regimens, venetoclax has changed the game and should be used in combination with hypomethylating agents or cytarabine. Glasdegib is also approved in combination with low-dose cytarabine. Patients with IDH1/2 -mutated disease can be treated with ivosidenib and enasidenib, respectively. Although enasidenib has yet to secure its spot in the up-front setting, data support its use in newly diagnosed AML. An ongoing question in the field concerns how to treat patients with TP53 -mutated AML, because most patients do not respond well to currently available therapies and continue to have poor overall outcomes.
Abstract 10637: A Pooled Multi-National Validation Study of a Machine Learning, High-Sensitivity Troponin-Based Multi-Proteomic Model to Predict the Presence of Obstructive Coronary Artery Disease as Compared to High Sensitivity Troponin Alone in a Subset of Patients with Diabetes
Authors: Raghav Gattani, Emmanuel Ekanem, Araba Ofosu-Somuah, Johannes T Neumann, Cian McCarthy, Palak Shah, Craig Magaret, Rhonda F Rhyne, Grady Barnes, Celine Peters, Dirk Westermann, Christopher Defilippi, James L Januzzi
Journal: Circulation (2021)

Introduction: Diabetes Mellitus (DM) is a major risk factor for coronary artery disease (CAD) associated with a two-fold increase in mortality. We aimed to validate the performance of a machine learning based multi-biomarker diagnostic panel to predict obstructive coronary artery disease (oCAD) compared to high-sensitivity cardiac troponin-I (hs-cTnI) alone in a subset of patients with DM. Methods: A previously developed multiple biomarker scoring model was utilized. The pooled cohort included 132 patients at Inova Fairfax Hospital, 69 patients at Massachusetts General Hospital and 46 patients at the University Hospital Hamburg-Eppendorf with a mixture of acute and lesser acute presentations. Three clinical factors (sex, age, and previous coronary percutaneous intervention) and three biomarkers (hs-cTnI, Adiponectin, and Kidney Injury Molecule-1) were combined. oCAD was defined as &gt;50% coronary obstruction in at least one coronary artery (for the University Hospital Hamburg-Eppendorf cohort) or &gt;70% coronary obstruction in at least one coronary artery (for the other two cohorts). The multiple biomarker diagnostic panel’s performance to predict oCAD was also compared to hs-cTnI alone. Results: The multiple protein panel had an area under the receiver-operating characteristic curve of 0.77 (95% CI, 0.70, 0.84, p &lt;0.001) for the presence of oCAD (Figure 1). At optimal cutoff, the score had 79% sensitivity, 57% specificity, and a positive predictive value of 81% for oCAD. The multiple biomarker panel had a diagnostic odds ratio of 4.82 (95% CI 2.68, 8.67, p&lt;0.01). In comparison, in patients without an acute MI, hs-cTnI alone had an area under the receiver-operating characteristic curve of 0.53 (95% CI, 0.49, 0.57, p = 0.253) for oCAD (Figure 1). Conclusions: In this multinational pooled cohort, a previously described novel machine learning, multiple protein biomarker panel provided high accuracy to diagnose patients for oCAD in a subset of patients with DM.
Abstract 11580: Platelet Activity and Cardiovascular Events in Patients with Diabetes and Peripheral Artery Disease: Findings from the American Heart Association Cardiometabolic Health Strategically Focused Research Network
Authors: Manila Jindal, Lucas Cofer, Yuhe Xia, Elliot Luttrell-Williams, Khrystyna Myndzar, Chiara Giannarelli, Edward A A Fisher, Jonathan D Newman, Ira J Goldberg, Jeffrey S Berger
Journal: Circulation (2021)

Introduction: Peripheral artery disease (PAD) and diabetes mellitus (DM) are significant risk factors for atherothrombosis. Platelets mediate atherothrombosis and are therapeutic targets in PAD and DM. We investigated the relationships between PAD, DM, platelet activity, and cardiovascular risk. Methods: The Platelet Activity and Cardiovascular Events (PACE) study enrolled 289 PAD patients undergoing lower extremity revascularization (LER). Prior to LER, platelet activity was measured via light transmission aggregometry in response to submaximal ADP, collagen (coll), serotonin (ser), epinephrine (epi), and arachidonic acid (AA). Patients were followed for a median of 18 months for the composite of major adverse cardiac or limb events (MACLE; MI, stroke, death, major amputation, and limb revascularization). Results: There were 93 (32%) patients with insulin-dependent DM (IDDM), 60 (21%) with non-insulin dependent DM (NIDDM), and 136 (47%) without-DM. Patients with IDDM were more likely than those without DM to be female, non-white, and Hispanic, and to have history of coronary artery disease, heart failure, and critical limb ischemia (P&lt;0.05 for all). Use of antiplatelet therapy was similar across groups. Maximum platelet aggregation was highest in the IDDM group in response to multiple agonists ( Figure) . MACLE occurred in 51%, 57%, and 69% of the without-DM, NIDDM, and IDDM groups, respectively (P=0.02). Compared to subjects without DM, only those with IDDM were at increased risk of MACLE after multivariable adjustment (aHR 1.6 [95% CI 1.02-2.4]; P=0.04) ( Figure ). After further adjustment for platelet aggregation, the association between IDDM and MACLE was no longer statistically significant (1.4 [0.9-2.3]; P=0.17); platelet aggregation mediated 24% of the excess MACLE risk in individuals with IDDM. Conclusions: In patients with PAD, IDDM is associated with increased platelet activity that mediates, in part, the risk for incident cardiac and limb events.
Abstract 13253: Prevalence of Preclinical Cardiomyopathy in Patients With Type 2 Diabetes With No Apparent Cardiovascular Involvement
Authors: Rajesh Rajput, JC Mohan, JPS Sawhney, Jamshed Dalal, Mullasari Sankardas, Hardik Vasnawala, Amit Kumar
Journal: Circulation (2021)

Background: Hyperglycemia is associated with changes in cardiac structure and function, increased atherosclerosis and diabetic cardiomyopathy (1,2). Currently there is scarcity of robust large scale studies evaluating prevalence of asymptomatic left ventricular dysfunction and/or pre-clinical Heart Failure (HF) in patients with T2DM, particularly in India. Therefore, this study was conducted to determine prevalence of pre-clinical cardiomyopathy in Indian patients with T2DM. Methodology: Cross sectional, multi-center study was conducted in India. Institutional ethics committee had approved study protocol. Patients aged ≥ 18 years, T2DM with duration of ≥1 year and willing to provide informed consent were included. Patients with coronary artery or valvular disease, previously diagnosed with HF stage III/IV, chronic kidney disease, peripheral artery disease, arrhythmias, diabetes other than T2DM or currently under treatment with digoxin or loop diuretics were excluded. Two-dimensional echocardiography and natriuretic peptide estimation were conducted. Results: This is an interim analysis of 569 patients. Mean HbA1c was 8.3%. Total subjects with LVD were 52% (95% CI 0.48,0.56). Diastolic dysfunction was 20% (95% CI 0.17,0.24) and systolic dysfunction was 42% (95% CI 0.38,0.46) (Table 1). Prevalence of HF according to BNP levels &gt;105 pg/ml was 9% (95% CI 0.07,0.11). Correlation analysis between HbA1c and prevalence of LVD was statistically significant for systolic LVD, while it was not statistically significant for diastolic LVD. Patients in the age group of 51 to 60 were more vulnerable to LVD at 35% (95% CI 0.30,0.41). Conclusion: Using suitable echocardiographic indexes and laboratory investigations LVD is detectable in almost half of the T2DM patients and has a direct correlation with older age and HbA1c. Thus, we conclude that HF goes undetected and early intervention to diagnose and treat LVD can improve outcome.
Jersey is set to allow assisted dying
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Jersey is poised to become the first jurisdiction in the British Isles and the Channel Islands to permit assisted dying after its parliament backed a proposition on the issue by 36 votes to 10 on 25 November.

The channel island’s States Assembly was asked to agree in principle that assisted dying should be allowed in Jersey in limited circumstances. This came after a citizens’ jury was asked to examine the arguments for and against …
On Cave Paintings and Shallow Waters—The Case for Advancing Spinal Cord Imaging in Multiple Sclerosis
Authors: Stephen Krieger
Journal: JAMA Neurology (2021)

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Low-Density Granulocytes Are Decreased in Acute Myeloid Leukemia and in Myelodysplastic Syndromes with Negative Prognostic Factors
Authors: Valentina Giudice, Marisa Gorrese, Idalucia Ferrara, Rita Pepe, Angela Bertolini, Rosa Vitolo, Rossella Marcucci, Paola Manzo, Matteo D'Addona, Maria Carmen Martorelli, Maria Teresa Buonanno, Maddalena Langella, Bianca Serio, Carmine Selleri
Journal: Blood (2021)