tbuckley/cabot-search huggingface dataset:
Abstract 16330: Evaluation of Cardiac Function in Children Undergoing Liver Transplantation
Authors: Neha Bansal, Nadia Ovchinsky, Jacqueline M Lamour, Debora Kogan-Liberman, Trang Nguyen, Nadine Choueiter
Journal: Circulation (2020)

Introduction: Cirrhotic cardiomyopathy is a hemodynamic complication of cirrhosis resulting in cardiac dysfunction. It remains poorly characterized in children. Our aim was to assess cardiac function using speckle tracking echocardiography (STE), a marker of subclinical cardiac dysfunction, in patients undergoing liver transplant (LT) and correlate it with their post-operative (op) clinical course. Methods: This is a retrospective study of pre-LT echocardiograms performed on pediatric patients (pts) with cirrhosis at a single tertiary care center who received a LT. Demographic clinical and echocardiographic data was collected and STE was performed by a single observer using TomTec system. Descriptive data was expressed as mean (SD) and number (%). The relationship between clinical data and echocardiographic variables was assessed using Pearson correlation coefficient. Significance was set at P value &lt; 0.05. Results: Twenty-three pts underwent LT between 03/2013-12/2019 with median age 7.5 (IQR 0.1, 17) years and 31 % with biliary atresia. Five patients were listed as status 1A/1B. Their mean natural pediatric/model end-stage lived disease (PELD/MELD) score was 15. Their pre-LT echocardiogram showed normal left ventricular (LV) ejection fraction and normal right ventricular (RV) fractional area change. Tricuspid annular plane systolic excursion (TAPSE) was abnormal in 50% of pts. While LV global longitudinal strain (GLS) (23 ± 3%) and LV circumferential strain (27 ± 4%) were normal, RV GLS was abnormal in 65% of pts (22 ± 3%). There was no correlation between echocardiographic parameters and post-operative LT course (length of stay, duration of mechanical ventilation, surgical complications). Conclusions: Children undergoing liver transplant have RV dysfunction as evidenced by abnormal TAPSE and RV GLS on speckle tracking echocardiography. Echocardiographic parameters do not correlate with the immediate post-LT clinical status.
Abstract 210: Flavin Containing Monooxygenase 2 Confers Cardiac Protection via Unfolded Protein Response Signaling Modulated by Disulfide Bond Catalysis
Authors: Qingnian Liu, Yue Tao, Hao Ding, Changchen Xiao, Yu Zhou, Cheng Ni, Changle Ke, Jingyi Wang, Rongrong Wu, Lin Fan, Xianpeng Wu, Jing Zhao, Yan Wu, Xin Yang Hu, Jian'an Wang
Journal: Circulation (2020)

Introduction: Myocardial infarction (MI) is characterized by cardiac dysfunction and increased cardiomyocyte death, induced mainly by apoptosis. Using an unbiased transcriptome analysis, we identified flavin containing monooxygenase 2 (FMO2) as one of the top-ranked genes involved in the process of MI. In this study, we investigate the roles of FMO2 in ischemic injury and its potential mechanisms. Hypothesis: FMO2 exhibits the cardiac protection from MI injury. Methods: Male SD rats receiving either adeno-associated virus serotype 9 containing FMO2 shRNA particles (AAV-shFMO2) or FMO2 (AAV-FMO2), and FMO2 knockout rats were subjected to myocardial infarction surgery. Cardiac function, fibrosis, and apoptosis were examined in these rats and related cellular and molecular mechanisms were investigated. Results: Cardiac ischemia injury was associated with significant increases of FMO2 levels both in ex vivo and in vivo models. Loss of FMO2 significantly enhanced cardiomyocyte apoptosis and deteriorated cardiac function accompanied by augmented infarct size in infarcted rat hearts, while elevated expression of FMO2 exhibited the opposite results. Mechanically, located on the ER membrane, FMO2 inhibited activation of ER stress-initiated apoptotic proteins including caspase 12 and C/EBP homologous protein (CHOP), via down-regulating upstream unfolded protein response (UPR) pathway. Furthermore, we found that FMO2, as a novel chaperone in ER, directly catalyzed disulfide-bond synthesis to facilitate proteins folding. Finally, structure analysis of FMO2 revealed the active site GVSG for disulfide-bond catalysis, which was confirmed by the molecular docking experiment of GSH with FMO2. However, FMO2 with GVSG mutation failed to catalyze disulfide-bond formation and lost protection from ER stress or apoptosis in cardiomyocytes. Conclusion: FMO2 confers cardiac protection from ischemic damage due to improved cardiomyocyte apoptosis through UPR pathway, which is mediated by disulfide-bond catalysis at GVSG active site. Our findings uncover a novel FMO2-involved regulatory mechanism which could serves as a potential therapeutic target for ischemic cardiovascular diseases.
TV: On The Edge
Authors: P. Byrne
Journal: BMJ (2001)

Black Dog , BBC1, Tuesday 9 January at 10 35 pm Secret Life of Happiness , BBC1, Wednesday 10 January at 9 10 pm All The Rage , BBC1, Wednesdays at 10 35 pm, 10 to 24 January

The BBC has begun the year with a series of television and radio programmes, accompanied by internet information and booklets, that focuses on mental health issues. The ambiguously titled “On The Edge” season is a major initiative to inform the public about mental illness from a variety of perspectives. The principal theme of these programmes, everyday emotional wellbeing, is considered through a broad based approach spearheaded by the three core programmes listed above. All three are shown on the BBC's main television channel but differ in form and audience appeal.



Why is life sweet for some and not others?



Before …
Is mitral regurgitation a viable treatment target in heart failure?: The plot just thickened**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Mandeep R. Mehra, Bartley P. Griffith
Journal: Journal of the American College of Cardiology (2005)
Improvement of Health Status Following Initiation of Sacubitril/Valsartan in Heart Failure and Reduced Ejection Fraction
Authors: Ileana L. Piña, Alexander Camacho, Nasrien E. Ibrahim, G. Michael Felker, Javed Butler, Alan S. Maisel, Margaret F. Prescott, Kristin M. Williamson, Brian L. Claggett, Akshay S. Desai, Scott D. Solomon, James L. Januzzi
Journal: JACC Heart Failure (2020)

Treatment of heart failure with reduced ejection fraction (EF) may improve patient-reported health outcomes.The purpose of this study was to determine timing and magnitude of change in Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 scores following initiation of sacubitril/valsartan and interaction with change in amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations.From a single-arm, open-label study of patients initiated on sacubitril/valsartan, KCCQ-23 scores and NT-proBNP were obtained at baseline and follow-up through 12 months. Cross-sectional and longitudinal analyses evaluated magnitude and rate of change in KCCQ-23 scores and associations with NT-proBNP. Patient-level data from the randomized EVALUATE-HF study were used as historic controls.The analysis cohort (n = 678, age 64.7 years, 71.5% men, EF 28.9%) had a baseline KCCQ-23 overall score (OS) of 65.6. Following sacubitril/valsartan initiation, the majority (n = 412; 60.8%) of participants experienced a rise in KCCQ-23 OS ≥10 points; 26.0% increased by ≥20 points. Comparable improvement in KCCQ-23 scores was seen in various subgroups. Change in KCCQ-23 OS was inversely associated with change in circulating NT-proBNP concentrations. Among a control group of patients in EVALUATE-HF, linear rate of change in KCCQ-12 OS/14-day interval in the enalapril arm was 0.37 points (p = 0.06), whereas in the sacubitril/valsartan arm, scores increased at a rate of 1.19 points (p < 0.001), nearly identical to this dataset (1.08 points; p < 0.001).Treatment of heart failure with reduced EF with sacubitril/valsartan is associated with rapid and significant improvement in KCCQ-23 scores which was significantly related to change in NT-proBNP. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).
Noninvasive Oxygenation Strategies for Acute Hypoxemic Respiratory Failure—Reply
Authors: Bruno L. Ferreyro, Federico Angriman, Damon C. Scales
Journal: JAMA (2020)

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GDF-15 Neutralization Alleviates Platinum-Based Chemotherapy-Induced Emesis, Anorexia, and Weight Loss in Mice and Nonhuman Primates
Authors: Danna M. Breen, Hanna Kim, Donald Bennett, Roberto A. Calle, Susie Collins, Ryan M. Esquejo, Tao He, Stephanie Joaquim, Alison Joyce, Matthew Lambert, Laura Lin, Betty Pettersen, Shuxi Qiao, Michelle Rossulek, Gregory Weber, Zhidan Wu, Bei B. Zhang, Morris J. Birnbaum
Journal: Cell Metabolism (2020)
Abstract 15684: Discordance Between Severity of Heart Failure as Determined by Patient Report versus Cardiopulmonary Exercise Testing
Authors: Katherine C Michelis, Justin L Grodin, Lin Zhong, Ambarish Pandey, Kathleen Toto, Jennifer T Thibodeau, Mark H Drazner
Journal: Circulation (2020)

Introduction: Although patient-reported outcomes are increasingly emphasized, symptoms may be discordant to objective parameters of heart failure severity. The frequency of such discordance, associated characteristics, and its influence on clinical outcomes is unknown. Methods: This is a post-hoc analysis of the HF-ACTION trial (N=2062). Participants were divided by median baseline values for Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ, subjective measure) and V E /VCO 2 slope (objective measure) into 4 groups: “concordant-lower severity” (high KCCQ, low V E /VCO 2 slope), “concordant-higher severity” (low KCCQ, high V E /VCO 2 slope), “symptom magnifier” (low KCCQ, V E /VCO 2 slope), and “symptom minimizer” (high KCCQ, V E /VCO 2 slope). Baseline characteristics were compared, and the relationship between group and clinical outcomes over a median follow-up of 442 days was assessed in adjusted Cox models. Results: Discordance of patient-reported and objective illness severity was common (46%). Depression was more prevalent among symptom magnifiers (N=480) versus concordant-lower severity (N=566) and symptom minimizer (N=465) groups (30%, 18%, 14%, respectively; P&lt;0.001). Compared to concordant-lower severity participants, those who were symptom magnifiers, symptom minimizers, or concordant-higher severity were at increased risk of hospitalization (Table). Concordant-higher severity participants and symptom minimizers, but not symptom magnifiers, were at an increased risk of death versus concordant-lower severity participants. Conclusion: A high rate of discordance was observed between patient-reported and objective heart failure severity. Depression was associated with symptom magnification. Hospitalization was influenced by patient-reported severity but mortality tracked more closely with objective data, highlighting potential limitations of static patient-reported outcomes for risk stratification.
Abstract 363: Just Another Post-Arrest?: Predicting Outcomes in Traumatic Arrest and Hemorrhagic Shock
Authors: David T Poliner, Daniel N Holena, Mark Seamon, Benjamin Abella
Journal: Circulation (2020)

Introduction: Traumatic cardiac arrest is a challenging presentation at trauma centers globally, with a high mortality and subsequent morbidity among survivors. For those who do obtain return of spontaneous circulation (ROSC), there is even less clarity with respect to how best to prognosticate outcomes. The previously derived and validated Pittsburgh Cardiac Arrest Categories (PCAC) have demonstrated value in predicting functional outcome and survival to hospital discharge in non-traumatic arrest. It is a 1 to 4 categorical score wherein a higher category is correlative to a worse clinical outcome. We hypothesized that the PCAC would be able to accurately predict outcomes in a trauma cohort. Methods: Utilizing the Pennsylvania Trauma Outcome System registry, 30 patients from 2018-2020 presented to a single, urban, tertiary trauma center with traumatic arrest. Demographics, vital statistics, injury patterns, and hospital course were abstracted and matched with subsequent PCAC scoring in accordance with previously published methods. Results: Population was predominantly male 16 (80%), black (75%) with a mean age 33 y (SD 13) . Penetrating trauma comprised 76% with average injury severity score of 38 (SD 22). Six (30%) were discharged alive with 5 requiring inpatient rehabilitation. Average length of hospital stay was 16 days (SD 18) with approximately 11 ventilator free days (SD 9). Average GFR at time of discharge was 44mg/dl (SD 31). The majority, 12 (57%), were PCAC 4 on arrival owing to predominant evidence of coma, 61%. By post-arrest day 1, there was a more even distribution between PCAC categories with category 2 (28%) and 3 (28%) each having 3 survivors and PCAC 4 (28%) having 2. By day 3, PCAC scores were less normally distributed with PCAC 1 having 6 survivors (42%) and PCAC 4 having 5 (35%). Day 1 and 3 categories continued to be driven principally be median Coma scores 0 (IQR: 0-8) but with regression of median SOFA cardiopulmonary scores 4 (IQR:0-6). SOFA Renal scores in survivors predictably increased from no injury to moderate dysfunction across this same period (IQR:1-4). Conclusion: PCAC scores in traumatic cardiac arrest patients who achieve ROSC do not predict multisystem organ failure but do predict neurologic outcome.
Global measles mortality, 2000-2008.
Authors: A. Dabbagh, M. Gacic-Dobo, E. Simons, D. Featherstone, P. Strebel, J. M. Okwo-Bele, E. Hoekstra, M. Chopra, A. Uzicanin, S. Cochi
Journal: MMWR Morbidity and Mortality Weekly Report (2009)
Abstract 15745: Health Outcomes in Pulmonary Arterial Hypertension Patients With COVID-19: A Real-world Analysis
Authors: jeremy feldman, melisa wilson, Alexander Kantorovich, Alexander DeRuiter, Kevin Schreur, Peter Classi, Andrew Nelsen
Journal: Circulation (2020)

Introduction: Patients with underlying chronic conditions, including PAH, are predicted to have worse outcomes with COVID-19. This analysis aimed to assess the impact of COVID-19 on outcomes in PAH patients. Methods: Over a 5-month period starting 1/1/2020, PAH patients with COVID-19 were compared to PAH patients without COVID-19. In addition, COVID-19 patients with and without PAH were analyzed. Differences in all-cause mortality, all-cause hospitalization, and need for mechanical ventilation (MV) at any time after COVID-19 diagnosis were evaluated. Similar analyses were performed between subgroups of hospitalized patients. PAH and COVID-19 patients were identified by ICD and CPT codes along with PAH-specific medications from the TriNetX Dataworks Network of 35 international healthcare organizations. Cohorts were compared using unmatched and propensity-matched data (PMH, demographics, labs, and non-PAH medications) with categorical variables evaluated using χ 2 /Fisher’s Exact tests. Results: A total cohort of 566 patients were identified with a diagnosis of PAH; 510 without COVID-19 and 56 with COVID-19. In PAH patients with COVID-19, there were significantly higher rates of all-cause mortality, all-cause hospitalization, and need for MV (p&lt;0.00001) compared to PAH patients without COVID-19. Mortality in the PAH with COVID-19 cohort was 16% compared to 2% in the PAH group without COVID-19. After matching, significance was maintained in all-cause hospitalization (P=0.0013) and need for MV (P=0.0009). Adjusting for disease severity examining only matched all-cause hospitalized patients, death and need for MV was significantly higher in the PAH patients with COVID-19. When comparing PAH patients with COVID-19 versus a matched COVID-19 cohort without PAH, there were no differences in any evaluated outcomes. Conclusions: This real-world analysis demonstrates that PAH patients with COVID-19 have worse outcomes, including a higher rate of all-cause mortality at 5 months, compared to PAH patients without COVID-19. Additionally, no differences were observed between COVID-19 patients with or without PAH. In a subset of patients with more severe disease that were hospitalized, the results were consistent to those from the overall cohort.
Abstract 10349: Preventive Effect of Empagliflozin on Neointimal Hyperplasia After Drug Eluting Stent Implantation in Patients With Type2 Diabetes
Authors: Takehiro Hashikata, Mikio Kishi, Masayasu Ikutomi, Takahiro Jimba, Masashirou Matsushita, Akito Shindo, Susumu Katsushika, Takahiro Sato, Satoshi Ohnishi, Masao Yamasaki, Nobutaka Kakuda
Journal: Circulation (2019)

Introduction: The effects of sodium-glucose co-transporter 2 inhibitor (SGLT2i) after drug eluting stent (DES) implantation remains unknown. Here, we evaluated whether empagliflozin, a SGLT2i, affe...
THU0196 Efficacy of and predisposing factors for response to leflunomide (lef) in patients with rheumatoid arthritis (ra)
Authors: M Dougados, C Antoine, S Brin, P Emery, EM Lemmel, A Rodriguez de la Serna, CA Zerbini, P Van Riel
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> LEF is a new DMARD for the treatment of active RA in adults. Large phase III clinical trials have shown that LEF significantly improves the signs and symptoms of RA compared to placebo. LEF also significantly improved patient functional ability and individual health-related quality of life compared with placebo and methotrexate, and slowed radiographically assessed disease progression. In addition, LEF has an early onset of action, with a clinical response being seen by 4 weeks and a sustained response observed at up to 2 years. <h3>Objectives</h3> To evaluate the efficacy of, and predisposing factors for response to LEF in a large multinational, multicenter, open-label cohort study at 24 weeks. <h3>Methods</h3> Patients with active RA classified by a disease activity score (DAS &gt;3.2) were enrolled and treated with LEF (100 mg loading dose x 3 days with 20 mg QD thereafter). The efficacy variables analysed at week 24 were the DAS 28 responder rate, the response rate according to ACR 20%, ACR 50% and ACR 70%, and change from baseline for both scores. All subjects who received at least one dose of study medication were included in the intent-to-treat with last observation carried forward analysis. At week 24, baseline data (including RA duration and ARA functional class) from patients who were classified as responders compared with non-responders at week 24 were analysed to determine predictive factors of response. <h3>Results</h3> Of the 966 patients treated with LEF for 24 weeks, 720 (75%) were female with a mean age of 55 years (range 19?75). The mean duration of previous RA was 7.5 years with 62% patients first being diagnosed &gt;2 years. The mean duration of morning stiffness was 2.1 h and 83% of patients tested positive for rheumatoid factor at baseline. For those patients who had previously had DMARD treatment (72%), the mean number of previous treatments was 2.6. At week 24, 78% of patients were responders according to the DAS 28 responder rate. The percentage of patient responders at week 24 for ACR 20%, ACR 50% and ACR 70% were 67, 36, and 10% respectively. At week 24, 13% patients fulfilled the disease remission criteria (DAS 28 &lt; = 3.2). Of the patients, 35% and 50% were responders at week 4 and 8, respectively, and maintained efficacy until week 24. One hundred and ninety patients were withdrawn from the study (11% due to an adverse event, 3% for a lack of efficacy). ARA functional class 1 and RA duration &gt;2 years were identified as predisposing factors for treatment response. <h3>Conclusion</h3> This study confirms the efficacy of LEF in patients with RA. Further evaluation may suggest the clinical relevance of identified predisposing factors for treatment response.
Abstract 229: Cardiopulmonary Resuscitation Compliance of Clinical Nurses Using Feedback Technology from the Zoll R Series Defibrillator
Authors: Martha A Boudreau
Journal: Circulation (2020)

Use of technology driven devices aimed at providing audio-visual feedback during CPR have been developed, however research is limited to their usefulness effecting chest compression quality of clinical nurses who are often first to respond and begin chest compression on patients experiencing cardiac arrest. This study aimed to examine CPR chest compression compliance of nurses with and without feedback from the Zoll R Series® defibrillator on a manikin. Hypothesis: Audio-visual feedback technology use from the Zoll R Series defibrillator improves the percentage of appropriate chest compression depth and rate of nurses during a CPR manikin demonstration exercise. Methods: Thirty-four nurses participated using an AHA approved manikin. Each nurse performed two minutes of uninterrupted chest compressions without feedback, followed by a rest period and two minutes of uninterrupted chest compressions using feedback technology from the defibrillator. Compression data for rate and depth and total compressions in target within AHA 2015 ECC Guidelines were recorded by the defibrillator and entered into Zoll RescueNet® software. Demographics obtained for years of BLS and ACLS certification. Results: Of the 34 nurses, mean years of ACLS certification was 3.4 years and 11.7 certified years of BLS. Compressions performed with feedback showed a higher percentage of compressions in target (M = 87.37, SD= 15.95) including rate (M= 86.33, SD =15.13) and depth (M= 97.12, SD = 5.63) of compressions compared to percent compressions in target without feedback (M= 64.42, SD = 30.54) including rate (M= 65.73, SD = 32.44) and depth (M=93.34, SD = 19.99) of compressions. Twenty nine or 85% of the 34 nurses improved chest compression performance using feedback. No significant correlation found between years of BLS and ACLS certification and pre and post feedback compliance. Conclusions: Defibrillators offering verbal encouragement and a visual display allow for adjustments in rate and depth of compressions to maintain chest compressions compliance within ECC Guidelines. Further studies should investigate whether the incorporation of feedback technology use in mock code and CPR training sessions could improve CPR performance of healthcare providers including nurses.
IGLV3-21R110 identifies an aggressive biological subtype of chronic lymphocytic leukemia with intermediate epigenetics
Authors: Ferran Nadeu, Romina Royo, Guillem Clot, Martí Duran-Ferrer, Alba Navarro, Silvia Martín, Junyan Lu, Thorsten Zenz, Tycho Baumann, Pedro Jares, Xose S. Puente, José I. Martín-Subero, Julio Delgado, Elías Campo
Journal: Blood (2020)