tbuckley/cabot-search huggingface dataset:
Lipid nutrition: “In silico” studies and undeveloped experiments
Authors: Bill Lands
Journal: Progress in Lipid Research (2021)

This review examines lipids and lipid-binding sites on proteins in relation to cardiovascular disease. Lipid nutrition involves food energy from ingested fatty acids plus fatty acids formed from excess ingested carbohydrate and protein. Non-esterified fatty acids (NEFA) and lipoproteins have many detailed attributes not evident in their names. Recognizing attributes of lipid-protein interactions decreases unexpected outcomes. Details of double bond position and configuration interacting with protein binding sites have unexpected consequences in acyltransferase and cell replication events. Highly unsaturated fatty acids (HUFA) have n-3 and n-6 motifs with documented differences in intensity of destabilizing positive feedback loops amplifying pathophysiology. However, actions of NEFA have been neglected relative to cholesterol, which is co-produced from excess food. Native low-density lipoproteins (LDL) bind to a high-affinity cell surface receptor which poorly recognizes biologically modified LDLs. NEFA increase negative charge of LDL and decrease its processing by "normal" receptors while increasing processing by "scavenger" receptors. A positive feedback loop in the recruitment of monocytes and macrophages amplifies chronic inflammatory pathophysiology. Computer tools combine multiple components in lipid nutrition and predict balance of energy and n-3:n-6 HUFA. The tools help design and execute precise clinical nutrition monitoring that either supports or disproves expectations.
Abstract 13331: Case Report Of Transient Right Bundle Branch Block With S1q3t3 Pattern In Acute Pulmonary Embolism
Authors: sabu john, MARY MALLAPPALLIL, Kamal P Singh, Adam Budzikowski
Journal: Circulation (2021)

69 year old woman with hypertension, sleep apnea and who had a recent knee replacement, was brought in to the emergency room (ER) for syncope. She had her physiotherapy session earlier in the day and became symptomatic with dizziness and shortness of breath and passed out. In the ER she had a systolic blood pressure (SBP) of 90mmHg and an oxygen saturation (O2 sat) of 80% on room air. She was given fluid bolus with improvement of SBP to 110mmHg. O2 sat improved to 99% with 10L of oxygen. Treatment was started with full dose of Enoxaparin subcutaneously. A 12-lead electrocardiogram (EKG) showed sinus tachycardia (ST) at 117 beats per minute (BPM), right bundle branch block (RBBB) and S1Q3T3 pattern. A bedside echocardiogram showed right ventricular (RV) distension. A CT-angiogram showed bilateral main stem pulmonary emboli (PE) with signs of RV strain. Patient was admitted and remained hemodynamically stable. A repeat EKG done the following day showed ST at 110 BPM with resolution of RBBB. An echocardiogram done now showed normal RV size and function. Patent was eventually discharged home on full dose apixaban. Q3S1T3 Figure 1 - ST, RBBB, S1Q3T3 pattern Figure 2 - ST Discussion: The patient presented with new RBBB (Figure 1) due to RV strain from acute PE as shown by the CT-angiogram and bedside echocardiogram. The EKG also showed S1Q3T3 pattern. With the resolution of the RV strain the following day, as noted on the subsequent echocardiogram, the 12 lead EKG showed the resolution of the RBBB and the QRS complex became narrow (Figure 2). RBBB is thought to be caused by acute RV overload and dilatation, accompanied by subendocardial ischemia in the right bundle. The S1Q3T3 pattern is historically considered as a “classic” EKG pattern associated with acute PE, even though it is neither sensitive nor specific for acute PE. Conclusion: The RBBB along with the S1Q3T3 pattern and its resolution with improvement of RV hemodynamics, is the first reported case in the literature.
Assessment of the Promoting Resilience in Stress Management Intervention for Adolescent and Young Adult Survivors of Cancer at 2 Years
Authors: Abby R. Rosenberg, Chuan Zhou, Miranda C. Bradford, John M. Salsman, Katie Sexton, Alison O’Daffer, Joyce P. Yi-Frazier
Journal: JAMA Network Open (2021)

Adolescents and young adults (AYAs) with cancer have a high risk of poor psychosocial outcomes. The Promoting Resilience in Stress Management (PRISM) intervention is one of few psychosocial interventions targeting younger people with cancer that has demonstrated efficacy in a randomized clinical trial.To explore 2-year trajectories of patient-reported well-being among AYA cancer survivors. The hypothesis was that AYAs who initially responded to PRISM would report sustained positive changes.This secondary analysis of data from a single-center, parallel, phase 2 randomized clinical trial was conducted from January 2015 to October 2016. Eligible participants were English-speaking AYAs between ages 13 and 25 years with cancer treated at a single, quaternary children's hospital in the US. Participants were randomly assigned (1:1) to PRISM or usual care. Data were analyzed between March 2021 and June 2021.PRISM is a brief, skills-based coaching program targeting 4 resilience resources (stress management, goal setting, cognitive reframing, and meaning making).Patient-reported cancer-related quality of life (QoL) (PedsQL scale), hope (Hope scale), resilience (Connor-Davidson Resilience scale), and psychological distress (Kessler-6 scale) were collected at baseline, 6, 12, and 24 months. Data from AYAs who remained alive at 24 months were analyzed. Improvement was defined as a positive change in instrument scores between baseline and 6 months (ie, the end of the PRISM program) and used linear mixed effects regression to assess changes over time.A total of 57 AYAs were included in analysis at 24 months (62% of 92 randomized). Twenty-six participants (46%) were female; 36 (63%) were between ages 13 and 17 years; and 20 (35%) identified as part of a racial or ethnic minority group (4 [7%] Asian, 11 [19%] Hispanic or Latino, 16 [28%] mixed race or other). PRISM was associated with improved QoL, hope, resilience, and distress between baseline and 6 months, and these associations were sustained for QoL over 12 months (β = 7.4; 95% CI, 0.8 to 14; P = .03) and hope throughout the study period (12 months: β = 6.2; 95% CI, 2.7 to 9.6; P < .001; 24 months: β = 4.6; 95% CI, 1 to 8.3; P = .01). Of those whose scores improved between baseline and 6 months, PRISM participants more commonly reported sustained improvements in QoL (16 of 21 participants [76%] vs 8 of 17 [47%]), hope (14 of 24 participants [58%] vs 6 of 14 [43%]), resilience (9 of 18 participants [50%] vs 4 of 14 [29%]), and distress (14 of 19 participants [74%] vs 6 of 19 [32%]) at 24 months compared with usual care.These results suggest that PRISM was associated with sustained improvements in psychosocial outcomes as reported by adolescents and young adults. Those who responded to PRISM in the first 6 months reported continued well-being 2 years later.ClinicalTrials.gov Identifier: NCT02340884.
Updates in the Management of CLL/SLL: Management of Relapsed/Refractory Disease and the Role of Minimal Residual Disease
Authors: Jennifer R. Brown
Journal: Journal of the National Comprehensive Cancer Network (2021)

In relapsed chronic lymphocytic leukemia (CLL), the choice of therapy depends on the risk profile, prior therapy, and patient comorbidities. The first novel agent for patients who had previously received chemoimmunotherapy is typically a BTK inhibitor or combination venetoclax + rituximab. For patients with problematic comorbidities, however, a PI3K inhibitor can be used, but generally this is reserved for later lines of therapy. For those who stop ibrutinib due to adverse events, there are broad options but data are still limited. For those whose disease progresses on a BTK inhibitor, the only prospective data are for use of venetoclax . For patients who have been treated with venetoclax + rituximab and experience relapse, retreatment is a possibility if they have had a durable remission. Finally, undetectable minimal residual disease is strongly predictive of durability of response for time-limited regimens but not for continuous BTK inhibition, and is generally not indicated for monitoring patients.
Independent Prognostic Value of Flow Cytometry (FCM) in Myelodysplastic Syndromes (MDS) - Composition of a Prognostic FCM-Score for Overall Survival
Authors: Uta Oelschlaegel, Aida Santaolalla, Jessica A. Timms, Susann Winter, Katja Sockel, Martin Bornhäuser, Farzin Farzaneh, Claire N. Harrison, Theresia M. Westers, Arjan van de Loosdrecht, Mieke Van Hemelrijck, Uwe Platzbecker, Shahram Kordasti
Journal: Blood (2021)
Anti-CD37 Alpha-Amanitin Conjugated Antibodies As Therapeutic Weapons for Richter's Syndrome
Authors: Tiziana Vaisitti, Nicoletta Vitale, Andrea Iannello, Lorenzo Brandimarte, Matilde Micillo, Mauro Giulio Papotti, Arianna Di Napoli, Christian Orlik, Michael Kulke, Andreas Pahl, Silvia Deaglio
Journal: Blood (2021)
TAMI-34. TARGETING CSF1R AND PD1 IN EXPERIMENTAL GLIOMA
Authors: Hannes Becker, Justyna M Przystal, Denis Canjuga, Foteini Tsiami, Nicole Anderle, Anna-Lena Keller, Anja Pohl, Carola H Ries, Martina Schmittnaegel, Nataliya Korinetska, Marilin Koch, Jens Schittenhelm, Marcos Tatagiba, Christian Schmees, Susanne C Beck, Ghazaleh Tabatabai
Journal: Neuro-Oncology (2021)

Abstract The treatment of glioblastoma remains a challenge. Novel therapeutic strategies are urgently needed. Targeting the immunosuppressive glioblastoma-associated microenvironment is an interesting approach in this regard. Tumor-associated macrophages represent a distinct population of tumor-infiltrating immune cells with tumor-promoting features. The colony stimulating factor-1/ colony stimulating factor-1 receptor (CSF-1/CSF1R) axis plays an important role for macrophage differentiation and survival inside the tumor microenvironment. We thus aimed at investigating the antiglioma activity of CSF1R inhibition alone or in combination with blockade of programmed death (PD) 1. We detected CSF1R expression in paired tissue samples of primary and corresponding progressive glioblastoma. We investigated anti-CSF1R treatment alone or in combination with anti-PD1 antibodies in the orthotopic syngeneic VM/Dk SMA560 glioma mouse model, evaluated post-treatment effects and assessed treatment-induced cytotoxicity in a coculture model of patient-derived microtumors (PDM) and autologous tumor-infiltrating lymphocytes (TILs) ex vivo. Anti-CSF1R monotherapy increased the latency until the onset of neurological symptoms. Combinations of anti-CSF1R and anti-PD1 antibodies prolonged the latency until the onset of neurological symptoms and led to long-term survivors in vivo. Immunohistochemical analysis of post-treatment SMA-560 glioma revealed a modulation of the microenvironment, including increased T cell infiltration and reduced numbers of tumor-associated macrophages. Furthermore, we observed treatment-induced cytotoxicity of combined anti-CSF1R and anti-PD1 treatment in the PDM/TILs cocultures ex vivo. Taken together, our data indicates that CSF1R is a promising therapeutic target for glioblastoma, potentially in combination with PD1 inhibition.
Abstract 11850: Targeted Next-Generation Sequencing of 36 Lipid-Related Genes in Patients With Clinically Diagnosed Familial Hypercholesterolemia
Authors: Takeshi Okada, Masahiro Koseki, Makoto Nishida, Takashi Omatsu, Katsunao Tanaka, Hiroyasu Inui, Jiuyang Chang, Kotaro Kanno, Ayami Saga, Tohru Ohama, Mitsuaki Ishihara, Takeshi Kujiraoka, Hiroaki Hattori, Daisaku Masuda, Shizuya Yamashita, Yasushi Sakata
Journal: Circulation (2021)

Background: Familial hypercholesterolemia (FH) is characterized by elevated serum low-density lipoprotein cholesterol (LDL-C) levels and premature coronary artery disease. This condition is considered to be caused by mutations of conventional FH genes such as LDL receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9). However, it is not fully elucidated whether other lipid-related gene variants may be overlapped in addition to these FH genes. Methods and Results: One hundred twenty-five heterozygous FH (HeFH) patients in Osaka University Hospital and Rinku General Medical Center, who met the clinical FH criteria of Japan Atherosclerosis Society were enrolled. Genomic DNA for each patient was extracted from peripheral blood cells. Targeted exon sequencing was performed to investigate 36 lipid-related genes including conventional FH genes. Among variants with a minor allele frequency of &lt;5% in 1000 Genomes Project of East-Asian population, we have defined pathogenic variants if they fulfilled i) protein truncating variants, ii) damaging missense variants, and iii) ClinVar-registered pathogenic or likely pathogenic variants. Among 125 HeFH patients, we have identified LDLR pathogenic variants in 89 patients (71.2%), PCSK9 variants in 6 patients (4.8%), and APOB variants in 1 patient (0.8%). Among these 96 patients, 37 patients (38.5%) additionally have pathogenic variants of other lipid-related genes, which include apolipoprotein E2 (APOE2) in 3 patients, apolipoprotein E4 (APOE4) in 19 patients, variants of ATP-binding cassette subfamily G member 5 (ABCG5) in 3 patients, apolipoprotein C3 (APOC3) in 1 patient, and CD36 in 11 patients. As for remaining 29 patients without conventional FH gene variants, 17 patients (58.6%) have pathogenic variants of other lipid-related genes, which include APOE4 in 13 patients, apolipoprotein E5 (APOE5) in 1 patient, variants of ABCG5 in 1 patient, and CD36 in 2 patients. Conclusion: Approximately 40% clinically diagnosed HeFH patients have pathogenic variants of other lipid-related genes in addition to those of conventional FH genes. These overlapping variants may affect the atherogenicity of patients and selection of medication.
Abstract 11875: Cardiac Tumor: Multiparametric Myo-Mapping Study by Cardiac Magnetic Resonance in Cardiac Tumors
Authors: Pengfei Yue, Ziqian Xu, Yuanwei Xu, Yucheng Chen
Journal: Circulation (2021)

Introduction: The characteristics and diagnostic value of T1, T2 mapping in cardiac tumors and myocardium are currently unknown. Hypothesis: We aim to explore tissue characteristics and diagnostic values of native T1, T2, and ECV values of left ventricular (LV) myocardium and cardiac tumors. Methods: In this prospective study, patients with suspected cardiac mass who underwent cardiac MRI between Nov 2011 and Mar 2021 were evaluated. Inclusion criteria were patients diagnosed with primary cardiac tumors and cardiac metastases based on surgical resection, biopsy, and comprehensive evaluations of medical history, imaging, and long-term follow-up. Patients were separated into primary benign, malignant cardiac tumors and cardiac metastases. Statistical analyses were performed using independent-samples t-test, Mann-Whitney U test, and receiver operating characteristic (ROC) analysis. Reproducibility was assessed by Bland-Altman analysis and coefficient of variation (CoV). Results: A total of 87 patients diagnosed as primary benign (n = 54), malignant cardiac tumors (n = 24), and cardiac metastases (n = 9), and 50 age and sex-matched healthy volunteers were included. Patients with primary malignant cardiac tumors (1362.5 ms ± 63.2) showed significantly higher myocardial T1 mapping values compared with patients with benign tumors (1259.7 ms ± 46.0), cardiac metastases (1287.6 ms ± 52.1), and with normal controls (1206.4 ms ± 44.0, all p value &lt; 0.05). No significant difference in T2 mapping values were observed. Myocardial native T1 showed the highest diagnostic value between primary malignant and benign tumors (AUC: 0.917, cutoff value: 1300.2 ms) compared with myocardial T2 and ECV. Conclusions: This study indicated that while it is difficult to distinguish benign and malignant tumors based on mapping of cardiac tumors due to the high heterogeneity, myocardial T1 mapping value showed good diagnostic value between primary malignant and benign tumors.
A Phase 1 Study of CFT7455, a Novel Degrader of IKZF1/3, in Multiple Myeloma and Non-Hodgkin Lymphoma
Authors: Jesus Berdeja, Sikander Ailawadhi, Steven M. Horwitz, Jeffrey V. Matous, Neha Mehta-Shah, Thomas Martin, Eli Muchtar, Paul G. Richardson, Shambavi Richard, Manisha Bhutani, Andrew J. Yee, Michael R. Palmer, Cathleen Gorman, Oliver Schoenborn-Kellenberger, Sanela Bilic, Adam Crystal, Michelle Mahler, Sagar Lonial
Journal: Blood (2021)
International Consensus Statement on the diagnosis, multidisciplinary management and lifelong care of individuals with achondroplasia
Authors: Ravi Savarirayan, Penny Ireland, Melita Irving, Dominic Thompson, Inês Alves, Wagner A. R. Baratela, James Betts, Michael B. Bober, Silvio Boero, Jenna Briddell, Jeffrey Campbell, Philippe M. Campeau, Patricia Carl-Innig, Moira S. Cheung, Martyn Cobourne, Valérie Cormier-Daire, Muriel Deladure-Molla, Mariana del Pino, Heather Elphick, Virginia Fano, Brigitte Fauroux, Jonathan Gibbins, Mari L. Groves, Lars Hagenäs, Therese Hannon, Julie Hoover-Fong, Morrys Kaisermann, Antonio Leiva-Gea, Juan Llerena, William Mackenzie, Kenneth Martin, Fabio Mazzoleni, Sharon McDonnell, Maria Costanza Meazzini, Josef Milerad, Klaus Mohnike, Geert R. Mortier, Amaka Offiah, Keiichi Ozono, John A. Phillips, Steven Powell, Yosha Prasad, Cathleen Raggio, Pablo Rosselli, Judith Rossiter, Angelo Selicorni, Marco Sessa, Mary Theroux, Matthew Thomas, Laura Trespedi, David Tunkel, Colin Wallis, Michael Wright, Natsuo Yasui, Svein Otto Fredwall
Journal: Nature Reviews Endocrinology (2021)
Abstract 13847: Sex-Differences by Body Mass Index After ST-Elevation Myocardial Infarction
Authors: Georgia Mattingly, Mehmet Yildiz, Rebekah Lantz, Brynn Okeson, Frank V Aguirre, Mark Tannenbaum, Santiago Garcia, Timothy D Henry, Odayme Quesada
Journal: Circulation (2021)

Introduction: There are significant differences in body composition by sex; however, differences by sex on the association of BMI with cardiovascular outcomes after STEMI remains poorly understood. Methods: The Midwest STEMI Consortium consists of 15,039 consecutive STEMI activations. 4,682 patients with 1-year follow-up were included to examine sex-differences in characteristics, treatment, in-hospital and 1-year MACE and mortality risk by BMI groups: normal (18.5-24.9 kg/m 2 ), overweight (25.0-29.9 kg/m 2 ), and obese (≥30.0 kg/m 2 ). Results: Among 4,682 patients, 30% were women and 70% were men. Among women, 28% had normal BMI, 30% were overweight, and 42% obese. In normal BMI patients women were significantly older, had higher rates of HTN, lower rates of smokers, lower peak troponin, and longer door-to-balloon times compared to men. Women had lower risk of 30-day MACE (1.1% vs. 3%, p=0.045) but there were no sex-differences in 1-year MACE or mortality. Among overweight patients, women were significantly older, had higher rates of HTN and diabetes, and lower rates of smokers. Bleeding complication was more common in women (38% vs. 32%, p=0.03) as was cardiogenic shock pre-PCI (13% vs. 8.8%, p=0.02) but no sex-differences were seen in 1-year MACE or mortality. Among obese patients, women were significantly older and had higher rates of HTN, diabetes and stroke. Women had lower rates of out of hospital cardiac arrest (8.8% vs. 13%, p=0.005) and more bleeding complication (39% vs. 33%, p=0.025). Women had higher risk of 30-day death (2% vs. 0.8%, p=0.02), 1-year stroke (2.4% vs. 0.7%, p=0.004), and 1-year MACE and mortality (Figure). Discussion: Among STEMI patients, we found that obese women were at increased risk of MACE and mortality. Interestingly, there were no differences in MACE or mortality between men and women of normal and overweight BMI ranges, suggesting the importance of BMI when risk stratifying patients, particularly women, that warrants further research.
Abstract 10866: Effect of Preoperative Atrial Fibrillation on Outcomes After Left Ventricular Assist Device Implantation
Authors: Siddharth Shah, Kuldeep Shah, Mohit K Turagam, Rahul Bhardwaj, Tahmeed Contractor, Ravi Mandapati, Andrea Natale, Dhanunjaya Lakkireddy, Jalaj Garg
Journal: Circulation (2021)

Introduction: Although preoperative atrial fibrillation (AF) is common in patients undergoing left ventricular assist device (LVAD) implantation, how AF affects clinical outcomes remains unclear. Objectives: We aimed to assess the safety and efficacy of LVAD implantation in AF patients Methods: Statistical analysis was performed using meta-package for R version 4.0 and Rstudio version 1.2. Mantel Haenszel Odds ratio (OR) random effects model (DerSimonian and Laird method) was used to summarize data. Outcomes studied were - (1) all-cause mortality; (2) systemic thromboembolism; (3) stroke (ischemic and hemorrhagic); (4) pump thrombosis; (5) gastrointestinal (GI) bleed. Results: Nine retrospective studies with a total of 6,782 patients (AF=2,170 and non-AF =4,612) were included in analysis. When compared with non-AF group, AF group patients were older (57.9±2.9 vs 52.2±5.8 years, p&lt;0.001) and had less proportion of patients with INTERMACS profile 1, 2 (50.2% vs 54.3%, p&lt;0.001). Preoperative AF was not associated with increased risk of all-cause mortality at 6 months (OR 1.20,95% 0.91-1.57, p=0.19), 12 months (OR 1.35, 95% CI 0.74-2.47, p=0.33) and 24 months (OR 1.23, 95% CI 0.95-1.60, p=0.12). Preoperative AF did not increase the risk of thromboembolism (OR 1.04, 95% CI 0.75-1.43, p=0.81), stroke (OR 0.89, 95% CI 0.74-1.08, p=0.24), and pump thrombosis (OR 1.28, 95% CI 0.97-1.70, p=0.08) after LVAD implantation. However, AF was associated with increased risk of GI bleeding (OR 1.28, 95% CI 1.12-1.47, p&lt;0.001) [median follow up 11.5 months (9.6, 24)]. Conclusion: Our study demonstrates a significantly increased risk of GI bleeding in LVADs recipients with concomitant AF, with no significant effect on all-cause mortality, stroke, or thromboembolic events (likely driven less sick patient population in AF group).