tbuckley/cabot-search huggingface dataset:
Abstract 16830: Functional Stenosis After Undersizing Mitral Annuloplasty is Governed by Pre-Operative Mitral Valve Opening Geometry
Authors: Dongyang Xu, Kristin Begley, Kirthana S Suresh, Muralidhar Padala
Journal: Circulation (2020)

Introduction: Surgical repair of functional mitral regurgitation (FMR) with undersizing mitral annuloplasty (UMA) is a common practice. Though excessive annular downsizing can improve coaptation, it raises the risk of functional mitral stenosis (FMS). Predicting if certain patients can develop FMS after UMA, can help with surgical planning and inform the safe levels of downsizing. In this study, we sought to investigate that the pre-operative diastolic geometry of the mitral valve can predict the risk of developing FMS with UMA. Methods: Pig mitral valves (n=8) were excised and mounted into a left heart simulator with steady diastolic flow only [ Fig1A ]. Three leaflet tethering patterns were mimicked in this model: annular dilation (AD), AD + asymmetric tethering (Asym) and AD + symmetric tethering (Sym) [ Fig1B ]. Under each condition, the annulus was downsized to different levels by an adjustable UMA [ Fig1C ]. Millar pressure catheter and Echocardiography were used to measure MV pressure gradient and diastolic configuration under various conditions. Results: Under each tethering geometry (AD, AD + Asym and AD + Sym respectively), pressure gradient gradually increases as the downsizing level increases. Also, at each specific level of downsizing, pressure gradient increases as the subannular tethering increases. Similarly, at each specific level of downsizing, EOA decreases as the subannular tethering increases. Under each tethering geometry, EOA also decreases as the downsizing level increases [ Fig1D ]. In addition, it is demonstrated that at different flow rates, both pressure gradient and EOA correlates with anterior diastolic angle, which is impacted mainly by preoperative subannular tethering [ Fig1E ]. Conclusions: In FMR, the hemodynamic outcome of MV after UMA depends on both the extent of annular downsizing and preoperative leaflet tethering geometry, both of which should be taken into account when deciding the optimal surgical intervention.
Abstract 14267: Evinacumab Lowers LDL-C in Patients With Homozygous Familial Hypercholesterolemia Irrespective of Background Lipid-lowering Medication
Authors: Frederick J Raal, Robert S Rosenson, Laurens F Reeskamp, G. Kees Hovingh, John J Kastelein, Paolo Rubba, Shazia Ali, Poulabi Banerjee, Kuo-Chen Chan, Nagwa Khilla, Jennifer McGinniss, Robert Pordy, Yi Zhang, Daniel Gaudet
Journal: Circulation (2020)

Background: Homozygous familial hypercholesterolemia (HoFH) is characterized by very premature atherosclerotic cardiovascular disease due to profoundly elevated levels of LDL-C. Attempts to lower LDL-C in patients with HoFH often require multiple lipid-lowering medications (LLMs). Evinacumab, an angiopoietin-like protein 3 inhibitor, has been shown to reduce LDL-C in patients with HoFH by approximately 50% when added to maximally tolerated background LLMs. Objective: In this post-hoc analysis we assessed efficacy of evinacumab in patients with HoFH according to background LLM type. Methods: This was a double-blind, placebo-controlled, 24-week phase 3 trial (NCT03399786) that randomized patients 2:1 to receive intravenous (IV) evinacumab 15 mg/kg (n=43) or IV placebo (n=22) every 4 weeks. The effect of background LLMs on the efficacy of evinacumab to lower LDL-C was assessed for the following subgroups: high intensity-statin, low-intensity statins, lomitapide, triple therapy (ezetimibe + PCSK9 inhibitor + statin), and quadruple therapy (triple therapy + lomitapide). Primary endpoint was % LDL-C reduction from baseline to week 24. Results: At baseline, 55.4% (evinacumab, 58.1%; placebo, 50.0%) of HoFH patients were on triple therapy. Overall, 93.8% were on statins (76.9% on high intensity statins). Across LLM subgroups, mean baseline LDL-C levels ranged from 166.8 mg/dL to 281.8 mg/dL (Table). From baseline to week 24, marked reductions in LDL-C occurred with evinacumab treatment, which were observed in all groups: quadruple therapy (66.8%), triple therapy (56.0%), lomitapide (49.6%), high-intensity statins (48.6%) and low-intensity statins (41.0%). Evinacumab was generally well-tolerated. Conclusions: Evinacumab substantially lowers LDL-C levels in patients with HoFH irrespective of background LLM.
Abstract 117: Critical Care Management, Hospital Case Volume, and Survival After Extracorporeal Cardiopulmonary Resuscitation
Authors: Joseph Tonna, Craig Selzman, Jason Bartos, Angela Presson, Yeonjung Jo, Lance B Becker, Scott T Youngquist, Ravi R Thiagarajan, Austin Johnson, Peter Rycus, Heather Keenan
Journal: Circulation (2020)

Introduction: For patients who receive extracorporeal cardiopulmonary resuscitation (ECPR), the relationship between post-resuscitation management and survival is unknown. Additionally, it is not known if management varies between centers, and if this variation and hospital case volume, are associated with survival. Hypothesis: There is center level variability in post-resuscitation management for ECPR patients. This variability, and hospital annual case volume, are associated with survival. Methods: We performed an observational study of 4,296 adults who received ECPR from the Extracorporeal Life Support Organization registry from 2014 until 2019. We examined clinical variables within the first 24 hours after arrest, and hospital annual ECPR volume. The primary outcome was case-mix adjusted survival at hospital discharge, adjusting for factors previously associated with survival after cardiac arrest or extracorporeal membrane oxygenation (ECMO). Mixed effects regression models were used to account for clustering of outcomes by center. Case volume was stratified into low (&lt;6 cases/year), medium (6-12 cases/year) and high (&gt;12 cases/year). Results: Patient-level clinical variables after cardiac arrest, varied widely across individual hospitals, including the use of percutaneous coronary intervention (PCI), mechanical venting of the left ventricle, and the use of inotropic medications. Increased ECMO circuit blood flow at 4 hours was associated with survival (OR 1.14 per liter per minute of flow [95% CI 1.04 to 1.24];p=0.004). After 24 hours of ECMO, increased arterial pulsatility (OR 1.44 [95% CI 1.32 to 1.58]; p&lt;0.001), the placement of a distal perfusion catheter (OR 1.79 [95% CI 1.19 to 2.67]; p=0.005), and the placement of a mechanical left ventricular vent (OR 1.37 [95% CI 1.07 to 1.76]; p=0.012) were all significantly associated with survival. There was a nonsignificant association of the use of PCI after ECMO cannulation with survival (OR 1.31 [95% CI 0.998 to 1.91]; p=0.051). High case volume was not associated with survival (OR 1.32 [95% CI 0.98 to 1.78];p=0.072). Conclusions: Clinical management of ECPR patients varies across hospitals. These clinical variables and therapies are associated with survival, however center volume is not.
Abstract 349: Target Temperature Management After Return of Spontaneous Circulation Did Not Ameliorate Mid-term (30 to 90-day) Neurological Improvement in Out-of-hospital Cardiac Arrest Patients
Authors: Hiromichi Naito, Takashi Yorifuji, Tetsuya Yumoto, Tsuyoshi Nojima, Noritomo Fujisaki, Hiromasa Yakushiji, Atsunori Nakao
Journal: Circulation (2020)

Introduction: Mid/long-term outcomes of out-of-hospital cardiac arrest (OHCA) survivors have not been extensively studied. Targeted temperature management (TTM) after return of spontaneous circulation is one known therapeutic approach to ameliorate short-term neurological improvement of OHCA patients; however, the prognostic significance of TTM in the mid/long-term clinical setting have not been defined. Hypothesis: TTM would confer additional improvement of OHCA patients’ mid-term neurological outcomes. Methods: Retrospective study using the Japanese Association for Acute Medicine OHCA Registry (Jun 2014 - Dec 2017): a nationwide multicenter registry. Patients who did not survive 30 days after OHCA, those with missing 30-day Cerebral Performance Category (CPC) scores, and those &lt; 18 years old were excluded. Primary endpoint was alteration of neurological function evaluated with 30-day and 90-day CPC. Association between application of TTM (33-36°C) and mid-term CPC alteration was evaluated. Multivariable logistic regression analysis was used for the primary outcome; results are expressed with odds ratio (OR) and 95% confidence interval (CI). Results: We included 2,905 in the analysis. Patient characteristics were: age: 67 [57 - 78] years old, male gender: 70.8%, witnessed collapse: 81.4%, dispatcher instruction for CPR: 51.6%, initial shockable rhythm: 67.0%, and estimated cardiac origin: 76.5%. TTM was applied to 1,352/2,905 (46.5%) patients. Thirty-day CPC values in surviving patients were: CPC 1: 1,155/2,905 (39.8%), CPC 2: 321/2,905 (11.1%), CPC 3: 497/2,905 (17.1%), and CPC 4: 932/2,905 (32.1%), respectively. Ninety-day CPC values were: CPC 1: 866/1,868 (46.4%), CPC 2: 154/1,868 (8.2%), CPC 3: 224/1,868 (12.0%), CPC 4: 392/1,868 (20.1%), and CPC 5: 232/1,868 (12.4%), respectively. Of 1,636 patients with 90-day survival, 28 (1.7%) demonstrated improved CPC at 90 days, whereas, 133 (8.1%) showed worsened CPC at 90 days compared with 30-day CPC, respectively. Multivariable logistic regression analysis revealed TTM did not result in favorable mid-term neurological changes (adjusted OR: 1.44, 95% CI: 0.48 - 4.31). Conclusions: TTM may not contribute to the beneficial effect on OHCA patients’ mid-term neurological changes.
Abstract 205: Effect of Prehospital Noninvasive Positive Pressure Ventilation for Rescue of Acute Respiratory Distress
Authors: Daniel Walter, Hei Kit Chan, Henry E Wang
Journal: Circulation (2020)

Background: Emergency medical services (EMS) patients in respiratory distress require prompt rescue treatment. Only limited data describe the outcomes of prehospital rescue treatment with non-invasive positive pressure ventilation (NIPPV), including continuous positive airway pressure (CPAP) or bilevel positive air pressure (BiPAP). We sought to characterize the outcomes of prehospital CPAP/BiPAP in a national EMS cohort. Methods: We analyzed 2018 cross-sectional data on 1289 EMS agencies from ESO Solutions, Inc. (Austin, Texas). We included adult (age ≥18 years) patients with respiratory distress (respiratory rate (RR) ≥30 breaths/min. We divided the patients between those receiving NIPPV and standard care (SC). The primary outcome was change in RR during EMS care. We censored the analysis at 40 minutes of treatment. We compared baseline characteristics between NIPPV and SC. Using mixed linear, fractional polynomial and multiple spline models, we determined the associations of prehospital NIPPV with changes in RR. Results: Of the 6,156,846 adult 911 cases, we included 87,219 with respiratory distress, including 11,271 (12.9%) NIPPV (11,206 CPAP and 65 BiPAP) and 75,948 (87.1%) SC. Median treatment duration were: NIPPV 20.0 minutes (IQR 13.5-29.2 minutes), SC 18.5 minutes (IQR 11.1-27.6 minutes). Common concurrent treatments for NIPPV and SC included: Albuterol (48.6%, 20.9%), Ipratropium (27.9%, 11.2%) and Methylprednisolone (23.7%, 7.8%). At 20 minutes, mean RR change was greater for SC than NIPPV; SC -7.8 breaths/min vs. NIPPV -6.0 breaths/min, difference 2.3 (95% CI 1.9-2.6), p&lt;0.001. At 40 minutes, mean RR change was greater for SC than NIPPV; SC -9.5 breaths/min vs. NIPPV -8.2 breaths/min, difference 1.6 (95% CI 0.8 - 2.5), p&lt;0.001. On linear mixed modeling adjusted for age, sex, incident location, race, ethnicity, agency type, initial RR, and medication use, SC was associated with a larger decrease in respiratory rate across time than NIPPV; [NIPPV X time] interaction p&lt;0.001. Conclusions: In this multicenter series of prehospital respiratory distress, SC was associated with greater reductions in RR than NIPPV.
Abstract #674: Small molecules that target the nuclear export signal of topoisomerase II alpha for the treatment of multiple myeloma
Authors: Joel Turner, Thomas Rowe, David Ostrov, Jana Dawson, Chris Cubitt, Daniel Sullivan
Journal: Cancer Research (2009)

Background We have previously demonstrated that topoisomerase II\#945; (topo II\#945;) is exported from the nucleus of human multiple myeloma (MM) cells by a CRM1-dependent mechanism (Engel et al, Exp. Cell Res. 295(2):421-31, 2004). We have also identified the nuclear export signals (NES) for topo II\#945; at amino acids 1017-28 and 1054-66 using mutated full-length FLAG-tagged topo II\#945; protein and immunofluorescence microscopy, (Turner et al, J. Cell Sci. 117:3061-71, 2004). Drug resistance to topo II poisons occurs when topo II is trafficked to the cytoplasm where it is not in contact with the DNA, and thus unable to induce cell death. In addition, we have recently shown that blocking nuclear export with a CRM1 inhibitor or by siRNA sensitizes MM cells to topo II poisons. Materials and Methods The structure of S. cerevisiae topo II was used to create a model of human topo II\#945; using the program PhyreA. The procedure for molecular docking involved selection of structural pockets at the NES in topo II\#945; suitable for interactions with drug-like small molecule inhibitors (SMI) and molecular docking simulations where 140,000 small molecules (mw   Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 674.
Isotope Microscopic Observation of Osteogenesis Process Forming Robust Bonding of Double Network Hydrogel to Bone
Authors: Takayuki Nonoyama, Lei Wang, Masumi Tsuda, Yuki Suzuki, Ryuji Kiyama, Kazunori Yasuda, Shinya Tanaka, Kousuke Nagata, Ryosuke Fujita, Naoya Sakamoto, Noriyuki Kawasaki, Hisayoshi Yurimoto, Jian Ping Gong
Journal: Advanced Healthcare Materials (2020)

Abstract Tough double network (DN) hydrogels are promising substitutes of soft supporting tissues such as cartilage and ligaments. For such applications, it is indispensable to robustly fix the hydrogels to bones with medically feasible methods. Recently, robustly bonding the DN hydrogels to defected bones of rabbits in vivo has been proved successful. The low crystalline hydroxyapatite (HAp) of calcium‐phosphate‐hydroxide salt coated on the surface layer of the DN hydrogels induced spontaneous osteogenesis penetrating into the semi‐permeable hydrogels to form a gel/bone composite layer. In this work, the 44 Ca isotope‐doped HAp/DN hydrogel is implanted in a defect of rabbit femoral bone and the dynamic osteogenesis process at the gel/bone interface is analyzed by tracing the calcium isotope ratio using isotope microscopy. The synthetic HAp hybridized on the surface layer of DN gel dissolves rapidly in the first two weeks by inflammation, and then the immature bone with a gradient structure starts to form in the gel region, reutilizing the dissolved Ca ions. These results reveal, for the first time, that synthetic HAp is reutilized for osteogenesis. These facts help to understand the lifetime of bone absorbable materials and to elucidate the mechanism of spontaneous, non‐toxic, but strong fixation of hydrogels to bones.
Abstract 14171: Association of Women Authors With Women Enrollment in the Clinical Trials of Atrial Fibrillation
Authors: Safi U Khan, Muhammad Z KHAN, Ahmad N Lone, Chraumathi Raghu Subramanian, Swapna Talluri, JANET K HAN, Nino Isakadze, Annabelle Volgman, Erin D Michos
Journal: Circulation (2020)

Introduction: Women with atrial fibrillation (AF) are more symptomatic, have poorer quality of life and carry a higher risk of stroke than men. Despite this woman have been underrepresented in randomized controlled trials (RCTs) of AF. Hypothesis: Women representation in the author panel might influence enrollment of women in RCTs of AF. Methods: We performed a systematic literature search from 1989 through December 2019 to identify RCTs of AF with a follow-up duration of ≥3 months. The multivariate linear regression model was constructed with the proportion of women enrollment in the RCTs as the dependent variable and the proportion of women in the author panel as a key independent variable. The model was adjusted for publication year, region, sponsor, and type of RCTs (invasive or medical treatment). Results: A total of 134 RCTs (n=149,162) were included. The median number of participants per trial was 205 (IQR, 74-676). The median number of women per trial was 71 (IQR, 27-218). The overall representation of women was 35.1% (95% CI, 32.6-37.6%), which did not improve between 1989 to 2019 (from 27.3% to 29.6%; P=0.10). RCTs of AF were authored by 1,568 authors. The median number of authors per trial publication was 10 (IQR, 7-10). The median number of women authors was 1 (IQR, 0-3). First (93%) and senior (92%) authors were predominantly men. Only 13.3% (n=18) of publications had women as first or senior authors, which did not improve over time (P=0.07). Multivariate model showed that each 1% increase in women in the author panel was associated with 19% increase in women enrollment in RCTs (P=0.02) (Table). Conclusions: Women remained underrepresented both as participants and as authors of RCTs of AF. Higher representation of women in the author panel was associated with higher enrollment of women in RCTs of AF. Efforts to recruitment and retain women AF investigators may be a critical mechanism to help lessen the disparities in both areas.
Abstract 14962: Empagliflozin’s Cardiovascular Impact in High-Risk Patients With Type 2 Diabetes and Obstructive Pulmonary Disease: An Inquiry From EMPA-REG OUTCOME
Authors: Stefan D Anker, David H Fitchett, Bernard Zinman, Anne Pernille Ofstad, Christoph Wanner, Ola Vedin, Birgit Schinzel, Henry K Yaggi, Jyothis T George, Leif Erik Sander, Silvio E Inzucchi, Subodh Verma
Journal: Circulation (2020)

Introduction: Type 2 diabetes (T2D) and chronic obstructive pulmonary disease (COPD) often co-exist yielding increased risk of cardiovascular (CV) complications, including heart failure (HF). In the EMPA-REG OUTCOME trial, empagliflozin (EMPA) reduced the risk of CV death and hospitalization for HF (HHF) in patients with T2D and CV disease (CVD). We hypothesized that patients with COPD had a higher risk of CV outcomes than those without COPD, but similar treatment benefits on CV outcomes from EMPA as the overall population. Methods: In total, 7020 patients were treated with EMPA 10mg, 25mg, or placebo (PBO) with median follow-up of 3.1 years. We defined COPD at baseline (BL) by investigator reported presence of COPD or emphysema, or the use of medications for obstructive airways disease. We explored the effect of pooled EMPA groups vs. PBO within the subgroups of patients with vs. without COPD on CV death, HHF, HHF or CV death (excluding fatal stroke), all-cause death and 3-point-MACE by Cox regression adjusted for baseline risk factors. Results: The 707 (10.1%) patients with COPD at BL were slightly older (65±8 vs. 63±9 yrs), had more often HF at BL (17 vs. 9%) and coronary artery disease (84 vs. 75%), used insulin (56 vs. 47%) and diuretics (57 vs. 42%,) more frequently, but had similar beta-blocker use (64 vs. 65%) as compared to those without COPD. During follow-up, those with COPD in the placebo group had increased risk of HHF (HR 2.15 [95%CI 1.32-3.49], p=0.002), HHF or CV death (HR 1.60 [1.10-2.33], p&lt;0.015), and all-cause death (HR 1.60 [1.09-2.35], p&lt;0.02). EMPA consistently reduced all CV outcomes irrespective of COPD status (Fig). Conclusions: In EMPA-REG OUTCOME, 10% of patients had concomitant COPD. COPD patients were at increased risk of HHF, HHF or CV death, as well as all-cause death. EMPA consistently reduced these outcomes vs PBO among patients with and without COPD. These data suggest that EMPA’s benefits in patients with T2D and CVD are not attenuated by presence of COPD.
Tobacco Product Use Among Adults — United States, 2019
Authors: Monica E. Cornelius, Teresa W. Wang, Ahmed Jamal, Caitlin G. Loretan, Linda J. Neff
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Cigarette smoking remains the leading cause of preventable disease and death in the United States (1). The prevalence of current cigarette smoking among U.S. adults has declined over the past several decades, with a prevalence of 13.7% in 2018 (2). However, a variety of combustible, noncombustible, and electronic tobacco products are available in the United States (1,3). To assess recent national estimates of tobacco product use among U.S. adults aged ≥18 years, CDC analyzed data from the 2019 National Health Interview Survey (NHIS). In 2019, an estimated 50.6 million U.S. adults (20.8%) reported currently using any tobacco product, including cigarettes (14.0%), e-cigarettes (4.5%), cigars (3.6%), smokeless tobacco (2.4%), and pipes* (1.0%).† Most current tobacco product users (80.5%) reported using combustible products (cigarettes, cigars, or pipes), and 18.6% reported using two or more tobacco products.§ The prevalence of any current tobacco product use was higher among males; adults aged ≤65 years; non-Hispanic American Indian/Alaska Native (AI/AN) adults; those whose highest level of educational attainment was a General Educational Development (GED) certificate; those with an annual household income <$35,000; lesbian, gay, or bisexual (LGB) adults; uninsured adults and those with Medicaid; those with a disability; or those with mild, moderate, or severe generalized anxiety disorder. E-cigarette use was highest among adults aged 18-24 years (9.3%), with over half (56.0%) of these young adults reporting that they had never smoked cigarettes. Implementing comprehensive, evidence-based, population level interventions (e.g., tobacco price increases, comprehensive smoke-free policies, high-impact antitobacco media campaigns, and barrier-free cessation coverage), in coordination with regulation of the manufacturing, marketing, and sale of all tobacco products, can reduce tobacco-related disease and death in the United States (1,4). As part of a comprehensive approach, targeted interventions are also warranted to reach subpopulations with the highest prevalence of use, which might vary by tobacco product type.
NICE backtracks on graded exercise therapy and CBT in draft revision to CFS guidance
Authors: Ingrid Torjesen
Journal: BMJ (2020)

Graded exercise therapy (GET) should no longer be offered for the treatment of chronic fatigue syndrome (CFS, also known as myalgic encephalomyelitis), the National Institute for Care and Health Excellence (NICE) says in draft guidance.1 Instead patients should be encouraged to remain within their “energy envelope” so as not to worsen their symptoms, it advises.

Likewise, cognitive behavioural therapy (CBT) should no longer be offered as a treatment, NICE adds, although it can be offered as a psychological therapy that aims to help patients to manage their symptoms.

The revisions have been based not only on published evidence but also on patient reports that the treatments did not benefit them, and that in some cases GET caused harm.

In July, NICE cautioned against the use of GET for patients recovering from …