tbuckley/cabot-search huggingface dataset:
Drug Survival of Biologics in Patients With Hidradenitis Suppurativa
Authors: Hans Christian Ring, Julia-Tatjana Maul, Yiqiu Yao, Jashin J. Wu, Jacob P. Thyssen, Simon F. Thomsen, Alexander Egeberg
Journal: JAMA Dermatology (2021)

Biologics are important in treating patients with hidradenitis suppurativa (HS). However, to our knowledge, data on their real-life performance and treatment patterns in HS are limited.To examine the drug survival of biologic therapies for HS in a real-world setting.This cohort study included all patients with HS between January 1, 2005, and December 31, 2018, who were treated with biologics at the 5 academic hospital clinics where all biologic treatment for HS is conducted in Denmark. Biologics included adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, secukinumab, and ustekinumab. Data were analyzed between June 1, 2021, and June 20, 2021.Drug survival was depicted through Kaplan-Meier curves, and Cox regression models were used to calculate adjusted (age, sex, previous number of biologic treatment series) hazard ratios (aHRs) with 95% CIs for the risk of treatment discontinuation. Switching patterns were visualized through a Sankey diagram.The study comprised 241 patients (176 women [61.8%]; total of 386 treatment series) with a mean (SD) age of 41.8 (12.6) years at initiation of first biologic therapy. There were a total of 256 (189 [73.8%] biologic naive), 66 (32 [48.5%] biologic naive), 23 (9 [39.1%] biologic naive), and 22 (9 [40.9%] biologic naive) treatment series with adalimumab, infliximab, etanercept, and ustekinumab, respectively. The median time to discontinuation was 36.0 (IQR, 21.9-63.0), 28.7 (IQR, 15.1-62.9), 26.0 (IQR, 16.9-155.9), and 17.9 weeks (IQR, 12.9-41.0) for adalimumab, infliximab, ustekinumab and etanercept, respectively. The risk of drug discontinuation was significantly higher for etanercept compared with adalimumab (aHR, 1.81; 95% CI, 1.16-2.82), infliximab (aHR, 1.77; 95% CI, 1.03-3.05), and ustekinumab (aHR, 2.49; 95% CI, 1.12-5.52), whereas no difference was observed when comparing these 3 therapies with each other. We found no significant differences in drug survival for biologic-naive vs nonnaive treatment series. Increasing C-reactive protein levels (aHR, 1.01; 95% CI, 1.00-1.03) and concomitant antibiotic treatment (aHR, 2.82; 95% CI, 1.36-5.86) were associated with the risk of discontinuing infliximab therapy. Men (aHR, 0.69; 95% CI, 0.51-0.91) had a reduced risk of discontinuing use of adalimumab.In this cohort study, drug survival was comparable between adalimumab, infliximab, and ustekinumab but significantly lower for etanercept. There were no differences in drug survival among biologic-naive and nonnaive patients.
Genomic Data Improves Prognostic Stratification in Adult T-Cell Acute Lymphoblastic Leukemia Patients Enrolled in Measurable Residual Disease-Oriented Trials
Authors: Celia González-Gil, Mireia Morgades, Francisco Fuster-Tormo, Jesus García-Chica, Pau Montesinos, Anna Torrent, Marina Diaz-Beyá, Rosa Coll, Jordi Ribera, Ran Zhao, Maria Lourdes Hermosin, Santiago Mercadal, José González-Campos, M Teresa Artola, Ferran Vall-Llovera, Mar Tormo, Cristina Gil, Pere Barba, Andrés Novo, Teresa Bernal del Castillo, Maria Queipo De Llano, Pilar Martínez, Teresa González, Antonia Cladera, Alfons Serrano, Rosa Fernández-Martín, Maria C. Ardaiz, Maria Jesus Vidal, Ángela Baena, Nuria Lopez-Bigas, Anna Bigas, Jaroslaw P. Maciejewski, Alberto Orfao, Josep-Maria Ribera, Eulàlia Genescà
Journal: Blood (2021)
Abstract 8879: Circulating Levels of MicroRNA-122 and Hepatic Fat Changes in Response to Lifestyle Intervention: Central Magnetic Resonance Imaging Randomized Controlled Trial
Authors: Qiaochu Xue, Mengying Wang, Xiang Li, Knut Krohn, Stefanie Ziesche, Uta Ceglarek, Matthias Bluher, Maria Keller, Anat Y Yaskolka Meir, Yoriko Heianza, Peter Kovacs, Iris Shai, Lu Qi
Journal: Circulation (2021)

Introduction: Compelling evidence has linked liver-specific microRNA-122 (miR-122) expression with hepatic fat distribution; however, little is known about the relations between changes in circulating miR-122 and liver fat in response to weight-loss interventions. We aimed to prospectively investigate the association between serum miR-122 and changes of hepatic fat content during 18-month diet and physical activity interventions. Methods: The CENTRAL trial is an 18-month randomized controlled trial among adults with abdominal obesity or dyslipidemia. Subjects were randomly assigned to a low-fat (LF) diet or a Mediterranean/low-carbohydrate (MED/LC) diet. After six months of dietary intervention, each diet group was further randomized into added physical activity groups (LFPA+, MED/LCPA+) or no added physical activity groups (LFPA-, MED/LCPA-) for the following 12 months of intervention. The current study included 220 participants with repeated measurements on serum miR-122 and hepatic fat content (percentage) over 18 months. Results: In the study participants, serum concentration of miR-122 significantly increased from baseline to 18 months, while no difference was observed across the four intervention groups. We found a significant association between miR-122 and hepatic fat percentage at baseline, as per unit increment in log-transformed miR-122 was associated with 3.79 higher hepatic fat content ( P trend&lt;0.001). In addition, we found that a higher elevation in log-transformed miR-122 was associated with a greater reduction in hepatic fat percentage during 18-month interventions, independent of weight loss (β=1.56, P trend=0.002). We also found a significant interaction between changes in miR-122 and baseline fasting plasma glucose with hepatic fat content changes in 18 months ( P interaction=0.02). The association between changes in miR-122 and hepatic fat content changes appeared to be stronger among participants with higher baseline fasting glucose levels than those with lower levels. Conclusion: Our data indicate that participants with higher serum miR-122 levels may benefit more in reduction of hepatic fat content in response to Mediterranean/low-carbohydrate diet and physical activity interventions.
Abstract 13606: Is Pulmonary Hypertension a Poor Prognostic Sign in Patients Hospitalized for Transcatheter Aortic Valve Replacement
Authors: Mohsin S Mughal, Ali Ghani, Sundeep Kumar, Ammar Nasir, Hamza Hafeez, Jagpreet Grewal, Talha Ahmad, Sara Aslam, Hafsa Akbar, Muhammad Khakwani, Mahboob Alam, najam wasty, Sergio Waxman
Journal: Circulation (2021)

Introduction: Pulmonary hypertension (PH) is common in patients with severe aortic stenosis (AS). The prevalence of PH in transcatheter aortic valve replacement (TAVR) patients is reported upto 78% and causes significant morbidity and mortality. We queried the National Inpatient Sample (NIS) database to explore the different outcomes of patients hospitalized for TAVR with and without the history of PH. Hypothesis: PH may increase mortality in hospitalized patients undergoing TAVR. Methods: This is a retrospective cohort study utilizing the 2016-2017 National Inpatient Sample. We identified patients hospitalized for TAVR with and without the history of PH using ICD10 codes. The primary outcome was inpatient mortality. The secondary outcomes were cost of hospitalization, and length of stay (LOS). Multivariate regression was used to adjust for potential confounders including age, gender, race, pulmonary embolism, acute coronary syndrome, heart block, left bundle branch block (LBBB), diabetes, heart failure, and chronic kidney disease. STATA 15.0 was utilized for data analysis. Results: A total of 18221 patients underwent TAVR in 2016-2017. Of these, 18.3% had PH. There were more women in the PH group (51% vs 46%, P&lt;0.001). Patients were relatively younger in the PH group (79 yrs vs 80 yrs; p&lt;0.001). The mean cost of hospitalization was 23022 USD in the PH group versus 209867 USD in the group without PH (p&lt; 0.001). The patients in the PH group had higher inpatient mortality compared to patients without PH (2.28 % versus 1.49 %; Odds Ratio 1.54; p&lt; 0.001; CI 1.1-2.0). The mean LOS was 6.0 days in the PH group versus 4.3 days in those without the PH group ( p:&lt; 0.001). The mortality didn’t differ by gender, location of the hospital, and teaching status of the hospital. Conclusions: Our study showed higher inpatient mortality, length of stay, and cost of hospitalization in patients undergoing TAVR with PH as compared to those without PH.
Abstract 11749: Rates of Adverse Cardiovascular Outcomes in Patients With Peripheral Arterial Disease Did Not Vary by Neighborhood Deprivation Estimates
Authors: Mohamed Farhan Nasser, Ahmad Jabri, Daryl Thornton, Yasir Tarabichi, Sanjay Gandhi
Journal: Circulation (2021)

Introduction: Socioeconomic factors including neighborhoods with limited resources have a negative impact on cardiovascular outcomes in peripheral arterial disease (PAD) patients. An area deprivation index (ADI) quantifies a region’s socioeconomic conditions, which have been linked to health outcomes. Hypothesis: The patients with PAD living in disadvantaged neighborhoods as identified with higher ADI, will have higher co-morbidities and lower access to treatment, resulting in higher incidence of ST-elevation myocardial infarction (STEMI). Methods: Using electronic medical records, we identified patients with PAD (n=6331), using ICD 10 code of I 70 and I 73, with encounter from January 1, 2019 to June 2, 2021. Patients were stratified into four different groups by ADI. Baseline characteristics, comorbidities and medications were recorded for all patients. Using Wilcoxon Rank Sum Test and Pearson Chi Square tests, descriptive statistics are presented for baseline characteristics and comorbidities in table 1. Results: Patients with PAD with the highest ADI (n=1582), were younger (64 ±12), more likely to be African American (59.5%) and current smokers (41.4%) (p&lt;0.001). There were significant differences in co-morbidities across the four groups of different ADIs (p&lt;0.001), with hypertension (83.9% vs 69.6%), CHF (25.3% vs. 17.7%) and diabetes mellitus (15.1% vs.10.4%) being more common in the group with the highest ADI, compared to the group with the lowest ADI. These patients with the highest ADI, were also more likely to be prescribed aspirin, any antiplatelet, a statin or an ACE inhibitor (p&lt; 0.001), suggesting appropriate access to medical therapy. However, the incidence of STEMI was not statistically significant between the groups (p=0.377). Conclusions: PAD patients living in neighborhoods with higher ADI have higher co-morbidities as compared to those in areas with lower ADI. The incidence of STEMI is low in all groups independent of ADI
Abstract 11386: Self-Service Analysis of Best Practice Alert Acknowledgement Comments as a Method for Evaluation Reveals Opportunities for Optimization of Clinical Decision Support for Patients with Prolonged QT Syndrome
Authors: Ray Qian, Paul Johnsen, Johan M Bos, Michael J Ackerman, Pedro Caraballo
Journal: Circulation (2021)

Introduction: The main goal of Clinical Decision Support (CDS) is to provide timely and useful information for providers to deliver high-quality and safe care. Issues, like alert fatigue and provider burnout are commonly cited as unintended consequences of the CDS systems. Herein, we describe leveraging electronic health record (EHR) self-service reporting tools to gain insights on a CDS rule designed to avoid providers from ordering QT-prolonging medication in patients with history of QT-prolongation. Methods: Our EHR (Epic) SlicerDicer reporting tool was used to identify the frequency of QT-prolongation Best Practice Advisory (BPA) triggerings from 1/1/2020 to 12/31/2020 across Mayo Clinic sites. Additionally, associated patient encounter and BPA-specific data were queried. Text from acknowledgement comments to the BPA were reviewed and central themes and comments were categorized. Epic Clarity Data Warehouse was queried to identify the BPA-triggering medications and frequencies. Comparisons of percent action taken on the BPA were compared internally to Mayo Clinic’s BPA benchmark, and with national benchmarks using Epic BestPractice Pulse dashboard. Results: A total of 17,538 BPAs of interest were triggered across the Mayo Clinic sites in 2020, of which 3,696 (20.1%) were acted upon through either monitoring or medication discontinuation. This is below Mayo Clinic’s median of 29.2% for inpatient BPAs and 45.6% BPAs for outpatient, but above the national median of 10% (IQR 6.1-13.1%) for inpatient and 10% (IQR 4.3-19.5%) for outpatient BPAs actioned upon. A total of 30 different medications triggered the BPA, with the most common being ondansetron (41.5%), amiodarone (11.3%), and haloperidol (10.1%). User comments were left on 2,382 orders (13.5%) that acknowledged the BPA, but provided argument to prescribe drug. Three most common themes identified from comments on overridden BPAs: patient previously tolerated medication (19.0%), QT interval not prolonged on recent ECG (14.2%), and patient on hospice care (5.2%). Conclusion: Analysis of free text comments of CDS can be and should be performed to reveal opportunities for further improvement of CDS. Providers should be encouraged to provide comments when encountering CDS interventions.
Abstract 12496: Plasma Growth Factors and Hormones Drive Constitutive Translation of a Broad-Spectrum Proteome in Circulating Platelets via Stimulation of Translation Initiation Signal Pathways, Necessary for Rapid Hemostasis
Authors: Lawrence Goldfinger, Jeremy G Wurtzel, Sophia Lazar
Journal: Circulation (2021)

Introduction: The ability of anucleate platelets to translate nascent protein from their inherited mRNAs was first demonstrated in 1967. Later studies supported these findings, but translation quickly ceased in washed ex vivo platelets, leading to a general presumption that platelet translation is not robust, and thus of limited biological significance. Agonist stimulation promotes platelet protein translation, and recent profiling studies confirmed &gt;6000 inherited mRNAs in polysomes, associated with inducible translation of cognate protein products in thrombin-stimulated human platelets. However, relevance of post-activation translation - a slow, rate-limiting step in cell response - to rapid hemostasis is not clear. Platelets express the requisite components and show broad ribosome occupancy of mRNAs under resting conditions. Hypothesis: Plasma-borne growth factors/hormones (GFH) drive constitutive translation in circulating platelets to modulate reactivity. Methods: We employed metabolic labeling of newly synthesized proteins by bio-orthogonal non-canonical amino acid tagging in plasma-starved human platelets fed back with autologous plasma or isolated GFH (VEGF, IGF-1, insulin, EGF, HMGB1), coupled with translation initiation signaling and functional tests. Results: We found that platelets undergo constitutive translation of a broad-spectrum translatome dependent on plasma or GFH exposure. Platelets freshly isolated from platelet-rich plasma showed homeostatic activation of translation initiation signaling, evidenced by phosphorylation of p38/ERK upstream kinases, essential intermediate MNK1/2, and downstream effectors eIF4E/4E-BP1. Plasma starvation led to a steady loss of phosphorylation of this pathway, which was fully restored within 5 min stimulation by either plasma or most GFH. Inhibition of translation with puromycin or cycloheximide suppressed thrombin-induced integrin GPIIb/IIIa activation, P-selectin exposure, and platelet aggregation in vitro , and delayed platelet clot retraction. Transfusion of puromycin or MNK inhibitor eFT-508 resulted in delayed hemostasis in a tail bleed assay in mice. Conclusions: Constitutive plasma GFH-driven translation supports hemostatic platelet function.
Abstract 11601: Single-Volume Quantitative CT Myocardial Perfusion Measurement - Validation in a Swine Model
Authors: Logan C Hubbard, Sabee Molloi
Journal: Circulation (2021)

Introduction: Dynamic CT myocardial perfusion imaging enables accurate assessment of coronary artery disease (CAD). However, it is limited by the high radiation dose of serial acquisition of 10 or more volume scans per exam. Hypothesis: A single-volume quantitative CT myocardial perfusion technique can accurately measure perfusion in mL/min/g at a low radiation dose, as compared to microsphere perfusion measurement. Methods: The single-volume quantitative CT perfusion technique was validated in 6 swine (37 ± 8 kg). In each swine, several intermediate severity stenoses were induced in the left anterior descending (LAD) coronary artery using a balloon under intracoronary adenosine stress. Contrast-enhanced imaging was performed at 100 kVp and 200 mA with a 320-slice CT scanner, where 20 consecutive volume scans were acquired to capture the entire aortic enhancement curve. The image data were then used retrospectively to simulate prospective 2-mm-slice dynamic bolus tracking with aortic triggering at 150 HU followed by “acquisition” of a single volume scan at approximately the peak of the aortic enhancement: identical to a coronary CT angiogram. The dynamic bolus tracking, trigger, and single volume scan data were then used as analytical inputs into a novel first-pass analysis model to derive perfusion in mL/min/g. The accuracy versus microsphere perfusion was assessed via regression analysis. Results: Single-volume quantitative CT perfusion measurements (P CT ) were related to microsphere perfusion measurements (P MICRO ) by P CT = 1.00 P MICRO - 0.05 (Pearson’s r = 0.96; RMSE = 0.48 mL/min/g). The average CT dose index of the technique was only 5.4 mGy. Conclusions: The single-volume quantitative CT perfusion technique provides accurate, low-dose, myocardial perfusion measurement in mL/min/g using only bolus tracking images and a single volume scan. The technique can also provide simultaneous CT angiography when acquired at an appropriate radiation dose.
Allogeneic-Hematopoietic Stem Cell Transplantation Is Effective and Safe for Relapsed/ Refractory B-ALL Patients Who Cannot Get Remission or MRD Negative after CART Treatment
Authors: Yanzhi Song, Zhihui Li, Yongqiang Zhao, Fan Yang, Erhui Yuan, Qi Wang, Tong Wu
Journal: Blood (2021)
Characterization of Peri-Infarct Zone by Cardiac Magnetic Resonance: Validation Compared to Ex-vivo Imaging and Post-Mortem Histology
Authors: O.R. Coelho, R.N. Mitchell, L.S. Lee, S.A. Mokash, R.J. van der Geest, J.D. Schmitto, F.Y. Chen, M. Jerosch-Herold, R.Y. Kwong
Journal: Circulation (2010)
Cysteine 253 of UCP1 regulates energy expenditure and sex-dependent adipose tissue inflammation
Authors: Evanna L. Mills, Cathal Harmon, Mark P. Jedrychowski, Haopeng Xiao, Anja V. Gruszczyk, Gary A. Bradshaw, Nhien Tran, Ryan Garrity, Dina Laznik-Bogoslavski, John Szpyt, Hannah Prendeville, Lydia Lynch, Michael P. Murphy, Steven P. Gygi, Bruce M. Spiegelman, Edward T. Chouchani
Journal: Cell Metabolism (2021)
Therapy-Induced Senescence As an Anti-Cancer and Immune-Stimulatory Strategy
Authors: Diego Gilioli, Simona Fusco, Kety Giannetti, Valentina Gambacorta, Teresa Tavella, Carmine Liberatore, Stefano Beretta, Martin Schönlein, Ivan Merelli, Fabio Ciceri, Luca Vago, Clemens A. Schmitt, Raffaella Di Micco
Journal: Blood (2021)
Abstract 11593: Survival from Sudden Cardiac Arrest Depends on Type of Diabetes
Authors: Faye L Norby, Sumeet S Chugh, Audrey Uy-Evanado, Jonathan Jui, Kyndaron Reinier
Journal: Circulation (2021)

Introduction: A diagnosis of diabetes prior to sudden cardiac arrest (SCA) is associated with decreased survival following resuscitation. Patients with Type 1 diabetes mellitus (T1D) vs Type 2 diabetes mellitus (T2D) can be quite different and potential differences in survival outcomes have not been evaluated. Our aim was to compare the SCA resuscitation profile between individuals with T1D, T2D, and no diabetes. Methods: Using data collected from 2002-19, we performed a case-case study of 2771 SCA (age ≥18 years) from the Oregon Sudden Unexpected Death Study. We used medical records to determine diabetes status and the resuscitation profile was based on EMS reports, time of 911 call, and medical records. We used logistic regression to evaluate the independent association between diabetes and resuscitation profile. Results: SCA cases had a mean age of 65 ± 16 years, were 33% female and 24% non-White race. In total, 37% (n=1016) of cases had diabetes, of which 6% (n=66) were T1D. Those with T1D were 2 times more likely (p=0.008) to have an unwitnessed SCA compared to those without diabetes, and 1.7 times more likely (p=0.04) compared to those with T2D. (Figure, panel A). T1D were half as likely (p=0.04) to have resuscitation attempted compared to both T2D and no diabetes. There were no significant differences in initial rhythm. Individuals with T1D or T2D had a higher risk of death (vs. survival to hospital discharge) compared to those without diabetes, and in diabetics, those with T1D had 1.9 times higher odds of death compared to T2D (p=0.19). Descriptively, those with T1D tended to have SCA between the hours of 6am-10am compared to those with T2D and no diabetes (Figure, Panel B). Conclusions: Diabetes reduces the chances of survival from SCA, and individuals with T1D have worse outcomes than T2D. Given the global epidemic of diabetes, these findings have important implications for sudden death prevention and should be investigated further.
Abstract 12036: Title: Improving RBC K-O2 Binding by Amiloride HCl Dihydrate in CHD: A Novel Treatment for Reversion of Angina and ST-T Alterations
Authors: Carlos Luis Delgado, Antonio Javier Delgado-Leon, Antonio Delgado-Almeida
Journal: Circulation (2015)

Introduction: Following our discovery of K-O2 binding by oxyhemoglobin we tested the hypothesis that increasing erythrocyte K (K i ) by Amiloride HCl Dihydrate (AHD) improves K-O2 binding in CHD. Aim: to evaluate the novel AHD in patients with angina and ST-T alterations. Methods: 195 patients (63% males, 59±7 years, central aortic BP 166 ±12/95±9 mmHg) with CHD (angina 73%, MI 49%, 3-vessel disease 66% and HF 48%) were randomized to double-blind trial of AHD (5 mg)+Optimal Medical Therapy (n=104 vs 91 OMT, 1 st year), followed by open-label trial of AHD+OMT vs OMT (2 nd year). Both phases were intention-to-treat. Methods: All cases had serial ECG, Ion Transport Laboratory (RBC, plasma and 12-hours overnight urinary electrolytes) and noninvasive central aortic BP and hemodynamic (DynaPulse 200M). SAS statistic analysis, p &lt;0.05 was significant. Results: 1 st Month, compared to OMT, 87% of subjects on AHD had increased K i (92.1±6 vs 85±5 mmol/lc, p&lt;0.001), reduction in angina class (1.6±0.7 vs 3.1±0.8, p &lt;0.0001), improved ST-T alterations (54%) and HF symptoms (35%) vs less angina (21%), and unchanged ST-T and HF in placebo. At 2-M, in severe HT (n=35) AHD+OMT decreases central aortic BP in 20 patients (158 ± 12/97 ±11 vs 190±14/112±9 mmHg, p &lt;0.0001), but was unchanged in 15 patients on OMT (179 ±11/107 ±9 mmHg, p NS). At 6-M , subjects on AHD had low recurrence of angina (17 vs 46% OMT), while the ST-T was normal in 34%, improved in 43%, and unchanged in 14%, but not improved ST-T was recorded in patients receiving OMT. At 1 st year, no cardiovascular events were reported during treatment with AHD and 25 cases (24%) showed R-voltages in areas of previous infarcts, suggesting improved LV function or electrical regeneration of LV. In OMT group significant recurrence of angina (28%) and CV events (12%) were reported. At 2 nd year, the trial was halted (Declaration of Helsinki, WMA 2000, Part C) and all subjects received AHD+OMT: Angina was reversed in 87% of 195 subjects, ST-T alteration improved (54%), reversed (31%) or were unchanged (15%). No CV event was reported in the 195 patients enrolled. Conclusions: This study confirms that AHD improves RBC K-O2 binding by oxyhemoglobin, and rapidly reverses angina, ST-T alterations and induces electrical regeneration of the LV in older infarcts.