tbuckley/cabot-search huggingface dataset:
Baroreflex Activation Therapy for the Treatment of Heart Failure With a Reduced Ejection Fraction
Authors: William T. Abraham, Michael R. Zile, Fred A. Weaver, Christian Butter, Anique Ducharme, Marcel Halbach, Didier Klug, Eric G. Lovett, Jochen Müller-Ehmsen, Jill E. Schafer, Michele Senni, Vijay Swarup, Rolf Wachter, William C. Little
Journal: JACC Heart Failure (2015)

The objective of this clinical trial was to assess the safety and efficacy of carotid BAT in advanced HF.Increased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Baroreflex activation therapy (BAT) results in centrally mediated reduction of sympathetic outflow and increased parasympathetic activity.Patients with New York Heart Association (NYHA) functional class III HF and ejection fractions ≤35% on chronic stable guideline-directed medical therapy (GDMT) were enrolled at 45 centers in the United States, Canada, and Europe. They were randomly assigned to receive ongoing GDMT alone (control group) or ongoing GDMT plus BAT (treatment group) for 6 months. The primary safety end point was system- and procedure-related major adverse neurological and cardiovascular events. The primary efficacy end points were changes in NYHA functional class, quality-of-life score, and 6-minute hall walk distance.One hundred forty-six patients were randomized, 70 to control and 76 to treatment. The major adverse neurological and cardiovascular event-free rate was 97.2% (lower 95% confidence bound 91.4%). Patients assigned to BAT, compared with control group patients, experienced improvements in the distance walked in 6 min (59.6 ± 14 m vs. 1.5 ± 13.2 m; p = 0.004), quality-of-life score (-17.4 ± 2.8 points vs. 2.1 ± 3.1 points; p < 0.001), and NYHA functional class ranking (p = 0.002 for change in distribution). BAT significantly reduced N-terminal pro-brain natriuretic peptide (p = 0.02) and was associated with a trend toward fewer days hospitalized for HF (p = 0.08).BAT is safe and improves functional status, quality of life, exercise capacity, N-terminal pro-brain natriuretic peptide, and possibly the burden of heart failure hospitalizations in patients with GDMT-treated NYHA functional class III HF. (Barostim Neo System in the Treatment of Heart Failure; NCT01471860; Barostim HOPE4HF [Hope for Heart Failure] Study; NCT01720160).
Understanding the natural history of <scp>G</scp>aucher disease
Authors: Pramod K. Mistry, Nadia Belmatoug, Stephan vom Dahl, Roberto Giugliani
Journal: American Journal of Hematology (2015)

Gaucher disease is a rare and extraordinarily heterogeneous inborn error of metabolism that exhibits diverse manifestations, a broad range of age of onset of symptoms, and a wide clinical spectrum of disease severity, from lethal disease during infancy to first age of onset of symptoms in octogenarians. Before the advent of the International Collaborative Gaucher Group (ICGG) Gaucher Registry, the understanding of the natural history and phenotypic range of Gaucher disease was based on isolated case reports and small case series. Limited data hindered understanding of the full spectrum of the disease leading to some early misconceptions about Gaucher disease, notably, that nonneuronopathic (type 1) disease was a disease of adults only. The global scope of the ICGG Gaucher Registry, with its vast body of longitudinal data, has enabled a real appreciation of both the phenotypic spectrum of Gaucher disease and its natural history. This body of evidence represents the foundation for accurate assessment of the response to specific therapies for Gaucher disease and to the development of standard‐of‐care to monitor disease activity. Here, we outline the key developments in delineating the natural history of this highly complex disease and role of the ICGG Gaucher Registry in this effort. Am. J. Hematol. 90:S6–S11, 2015. © 2015 Wiley Periodicals, Inc.
Abstract P303: Economic Crisis in Western Europe and Ischemic Heart Disease Mortality
Authors: Usama Bilal, Claudia Nau, Manuel Franco, Thomas A Glass
Journal: Circulation (2014)

Introduction: The effects of economic crisis, like the current recession affecting Europe since 2008, on health have been widely debated. Our objective was to evaluate the effects of economic changes on mortality trends from ischemic heart disease (IHD) in Europe for the period 1980-2010. Hypothesis: We hypothesize that economic recession is associated with either increases in IHD mortality rates or halting of previous declining trends. Methods: We gathered economic (World Bank) and vital statistics data (WHO Mortality Database) for all Western European countries with more than 5 million inhabitants that had complete mortality data for the period 1980-2010. We defined a period of economic recession as an annual GDP (Gross Domestic Product) growth below 0%. We also computed the cumulative years lived through a given recession period (set to 0 if GDP growth rises above 0% in a given year). We computed age-adjusted (2013 European Standard Population) mortality rates for IHD (ICD9 Codes: 410-414, ICD10 Codes: I20-I25) for the study period and computed yearly changes. We modelled the association between recession and IHD mortality using Generalized Estimating Equations accounting for the correlation among data within country and time using first order autoregressive within-group correlation structures. Changes in ICD coding were introduced as a covariate to account for the shift from ICD-9 to ICD-10. We tested for associations using 0 to 10 year lags. Sensitivity analyses were conducted using unemployment as an alternative indicator of economic recession. Results: Twelve Western European countries were included (Austria, Finland, France, Germany, Greece, Ireland, Netherlands, Norway, Spain, Sweden, Switzerland and the United Kingdom). Economic recession was associated with a 2-year lagged 1.49% increase in IHD mortality in men (p=0.016) and 1.74% increase in women (p=0.019). Each additional year of recession was associated with a 2-year lagged 1.21% increase in IHD mortality in men (p=0.003) and 1.17% increase in women (p=0.016). Sensitivity analyses using unemployment as a second measure of economic recession showed analogous results with strongest associations seen in 0-year lags. GDP and Unemployment were highly correlated with two-year lags between GDP and Unemployment changes, confirming the robustness of these associations. Conclusions: This study showed a deleterious effect of economic recession on ischemic heart disease mortality rates in Europe for the period 1980-2010. Further studies should look into the specific mechanisms of this association and into the possible interaction with policy responses to economic crisis. 1
Association Between Intermittent Hypoxemia or Bradycardia and Late Death or Disability in Extremely Preterm Infants
Authors: Christian F. Poets, Robin S. Roberts, Barbara Schmidt, Robin K. Whyte, Elizabeth V. Asztalos, David Bader, Aida Bairam, Diane Moddemann, Abraham Peliowski, Yacov Rabi, Alfonso Solimano, Harvey Nelson
Journal: JAMA (2015)

IMPORTANCEExtremely preterm infants may experience intermittent hypoxemia or bradycardia for many weeks after birth.The prognosis of these events is uncertain.OBJECTIVE To determine the association between intermittent hypoxemia or bradycardia and late death or disability.DESIGN, SETTING, AND PARTICIPANTS Post hoc analysis of data from the inception cohort assembled for the Canadian Oxygen Trial in 25 hospitals in Canada, the United States, Argentina, Finland, Germany, and Israel, including 1019 infants with gestational ages of 23 weeks 0 days through 27 weeks 6 days who were born between December 2006 and August 2010 and survived to a postmenstrual age of 36 weeks.Follow-up assessments occurred between October 2008 and August 2012.EXPOSURES Episodes of hypoxemia (pulse oximeter oxygen saturation <80%) or bradycardia (pulse rate <80/min) for 10 seconds or longer.Values were sampled every 10 seconds within 24 hours after birth until at least 36 weeks' postmenstrual age. MAIN OUTCOMES AND MEASURESThe primary outcome was a composite of death after 36 weeks' postmenstrual age, motor impairment, cognitive or language delay, severe hearing loss, or bilateral blindness at 18 months' corrected age.Secondary outcomes were motor impairment, cognitive or language delay, and severe retinopathy of prematurity.RESULTS Downloaded saturation and pulse rate data were available for a median of 68.3 days (interquartile range, 56.8-86.0days).Mean percentages of recorded time with hypoxemia for the least and most affected 10% of infants were 0.4% and 13.5%, respectively.Corresponding values for bradycardia were 0.1% and 0.3%.The primary outcome was ascertained for 972 infants and present in 414 (42.6%).Hypoxemic episodes were associated with an estimated increased risk of late death or disability at 18 months of 56.5% in the highest decile of hypoxemic exposure vs 36.9% in the lowest decile (modeled relative risk, 1.53; 95% CI, 1.21-1.94).This association was significant only for prolonged hypoxemic episodes lasting at least 1 minute (relative risk, 1.66; 95% CI, 1.35-2.05vs for shorter episodes, relative risk, 1.01; 95% CI, 0.77-1.32).Relative risks for all secondary outcomes were similarly increased after prolonged hypoxemia.Bradycardia did not alter the prognostic value of hypoxemia.CONCLUSIONS AND RELEVANCE Among extremely preterm infants who survived to 36 weeks' postmenstrual age, prolonged hypoxemic episodes during the first 2 to 3 months after birth were associated with adverse 18-month outcomes.If confirmed in future studies, further research on the prevention of such episodes is needed.
Radiotherapy-Induced Malfunction in Contemporary Cardiovascular Implantable Electronic Devices
Authors: Jonathan D. Grant, Garrett L. Jensen, Chad Tang, Julianne M. Pollard, Stephen F. Kry, Sunil Krishnan, Anne H. Dougherty, Daniel R. Gomez, Marc A. Rozner
Journal: JAMA Oncology (2015)

Risk stratification and management paradigms for patients with cardiovascular implantable electronic devices (CIEDs) requiring radiotherapy (RT) vary widely and are based on limited clinical data.To identify the incidence and predictors of CIED malfunction and describe associated clinical consequences in a large cohort of patients treated with photon- and electron-based RT.Retrospective analysis of all patients with a functioning CIED who underwent RT between August 2005 and January 2014 with CIED interrogation data following RT at an academic cancer center. We identified 249 courses of photon- and electron-based RT in 215 patients (123 pacemakers [57%]; 92 implantable cardioverter-defibrillators [43%]). Substantial neutron production was generated in 71 courses (29%).Implantation of CIED with subsequent therapeutic radiation treatment (neutron producing with 15- or 18-MV photons and non-neutron producing with electrons, GammaKnife, or 6-MV photons).Malfunction of CIED, characterized as single-event upset (data loss, parameter resets, unrecoverable resets), and delayed effects including signal interference, pacing threshold changes, and premature battery depletion.Malfunction of CIED attributable to RT occurred during 18 courses (7%), with 15 CIEDs experiencing single-event upsets, and 3, transient signal interference. All single-event upsets occurred during neutron-producing RT, at a rate of 21%, 10%, and 34% per neutron-producing course for CIEDs, pacemakers, and implantable cardioverter-defibrillators, respectively. No single-event upsets were found among 178 courses of non-neutron-producing RT. Incident CIED dose did not correlate with device malfunction. Patients treated to the abdomen and pelvis region were more likely to undergo a single-event upset (hazard ratio, 5.2 [95% CI, 1.2-22.6]; P = .03). Six patients with a CIED parameter reset developed clinical symptoms: 3 experienced hypotension and/or bradycardia, 2 experienced abnormal chest ticking consistent with pacemaker syndrome, and 1 developed congestive heart failure. The 3 episodes of signal interference did not result in clinical effects. No delayed malfunctions were directly attributed to RT.In a cohort of contemporary CIEDs, all cases of single-event upset malfunction occurred in the setting of notable neutron production, at a rate of 21% for neutron-producing RT and 0% for non-neutron-producing RT. Where clinically feasible, the use of non-neutron-producing RT is recommended. Given the lack of correlation between CIED malfunction and incident dose observed up to 5.4 Gy, invasive CIED relocation procedures in these settings can be minimized.
Apoptosis and Cancer: Basic Mechanisms and Therapeutic Opportunities in the Postgenomic Era
Authors: Frank Stenner-Liewen, John C. Reed
Journal: Cancer Research (2003)

Apoptosis researchers gathered on the Island of Hawaii for an AACR Special Conference devoted to apoptosis and cancer. The meeting was organized by John C. Reed of the Burnham Institute and Scott Lowe of the CSHL [3][1] and was designed to explore the latest developments in understanding of
Contributions of TRPV4 to altered pulmonary vasoreactivity in mice with pulmonary hypertension
Authors: Yang Xia, Zhenzhen Fu, Omkar Paudel, James Sham
Journal: European Respiratory Journal (2013)

Chronic hypoxia pulmonary hypertension (CHPH) is a complex progressive disease and the underlying mechanism is still not fully understood. The hallmarks of CHPH include enhanced vasomotor tone, altered vasoreactivity to agonists and profound vascular remodeling. We have previously shown that the transient receptor potential vanilloid 4 (TRPV4) is upregulated in CH rat pulmonary arterial smooth muscle cells (PASMCs), contributing to the enhanced vasomotor tone and vascular remodeling. TRPV4 plays pivotal roles in modulating endothelium (EC) dependent and independent vasodilatation in systemic arteries. However, little is known about its contribution to the altered pulmonary vascular reactivity in CHPH. Here, we found that deletion of TRPV4 gene in mice (trpv4-/-) significantly attenuated CH induced-increase in right ventricle systolic pressure, mean pulmonary arterial pressure and pulmonary vascular resistance. Serotonin (5-HT) at 10-8 to 10-6 M caused concentration-dependent contraction of endothelium intact (EC+) and denuded (EC-) PAs of wildtype (WT) mice, and the maximal 5-HT induced contraction was significantly enhanced by CH. Similar enhancement in 5-HT induced response was observed in EC- PA of CH trpv4-/- mice, but it was significantly attenuated when endothelium was intact. In contrast, maximal contraction and EC50 of phenylephrine-induced contraction was minimally affected by CH in EC- PAs of WT mice. But, the EC50 was significantly increased in EC- PAs of CH trpv4-/- mice. These results suggest that TRPV4 contributes to CH-altered pulmonary vasoreactivity in both EC dependent and independent manner, depending on the specific vasoactive agonists.
A Bibliography of Infantile Paralysis 1789-1949, with Selected Abstracts and Annotations
Authors: Morris Fishbein, Ellan. Salmonsen, Luding Hektoen
Journal: JAMA (1952)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 3471: Ablation Of Phospholamban And Sarcolipin Has A Deleterious Effect On SERCA Pump Activity And Cardiac Contractility
Authors: Mayilvahanan Shanmugam, Shumin Gao, Evangelia Kranias, Muthu Periasamy, Gopal J Babu
Journal: Circulation (2008)

Recent studies have been directed towards the potential therapeutic value of improving the sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA) function in the failing myocardium. Overexpression of SERCA pump or inhibiting the function of phospholamban (PLB) has been shown to improve the cardiac function in failing myocardium. Towards this goal, we enhanced the SERCA pump activity in both atria and ventricle by ablating its key regulators, PLB and sarcolipin (SLN). The homozygous double knockout (dKO) pups were delivered in Mendelian ratio and reached adulthood without any visible abnormalities. However, these mice develop cardiac hypertrophy. The heart weight to body weight ratio significantly increased in 3– 4 months old dKO mice (WT-3.08±0.11 vs. dKO-4.14±0.14) and is associated with enlargement of myocytes (WT-117±8 μm2 vs. dKO-166±10 μm2). Ablation of PLB and SLN did not affect the expression of major Ca2+ handling proteins including SERCA2a, calsequestrin, L-type Ca2+ channel and ryanodine receptor in both atria and ventricles. Echocardiographic measurements showed increased diastolic (WT-0.90±0.02 mm vs. dKO-1.26±0.07 mm) and systolic (WT-1.33±0.03 mm vs. dKO-1.68±0.08 mm) septal wall thicknesses and diastolic (WT-0.91±0.02 mm vs. dKO-1.15±0.07 mm) and systolic (WT-1.15±0.03 mm vs. dKO-1.35±0.07 mm) post wall thickness in 3– 4 months old dKO mice hearts. However, left ventricular end-diastolic dimension (LVEDD), LV end-systolic dimension and ejection fraction (EF, %: WT-0.73±0.12 vs. dKO-0.69±0.03) are not very different from wildtype indicating preserved contractile function in the dKO mice. Our studies therefore suggest that the enhanced Ca2+ sensitivity of cardiac SERCA pump can progressively lead to cardiac hypertrophy and may have a deleterious effect on cardiac function during pathological conditions.
Abstract P283: Disparities in Long-term Risk of Cardiovascular Disease by Sexual Orientation and Race/Ethnicity: the National Longitudinal Study of Adolescent Health
Authors: Cari J Clark, Iris W Borowsky, Alvaro Alonso, Rachael A Spencer, Susan A Everson-Rose
Journal: Circulation (2014)

Background: Risk of cardiovascular disease (CVD) may be higher in sexual minorities, but epidemiologic evidence is sparse. We used a nationally representative sample of young adults to examine sex-specific disparities in global CVD risk by sexual orientation and race/ethnicity. Methods: Data were from National Longitudinal Study of Adolescent Health subjects who participated in wave 4 (2008-09) and who had valid weights and non-missing data (7087 women; 6340 men). Age, race/ethnicity, sexual orientation, education, financial stress, and CVD risk factors (body mass index, smoking, diabetes, systolic blood pressure, and use of antihypertensive medication) were collected via an in-home interview. We calculated the 30-Year risk for total CVD using a Framingham-based prediction model. Sex-specific differences in 30-year risk of CVD by sexual orientation were calculated with weighted linear models adjusted for age, race/ethnicity, education, and financial distress. Sex-specific interactions between race/ethnicity and sexual orientation were tested. Results: Mean age was 28.9 ± .2 years; 93% (n=5912) of male participants were heterosexual, 4% (n=258) were bisexual, and 2% (n=170) were gay. 80% (n=5713) of female participants were heterosexual, 18% (n=1243) were bisexual, and 2% (n=131) were lesbian. Average 30-year risk of CVD was 17.2 ± .5% in men and 9.0 ± .3% in women. Differences in CVD risk by sexual orientation were not detectable for men (p=.59). Compared to heterosexual women, bisexual and lesbian women had a .9% (95% CI: .3, 1.4) and 2.0% (95% CI: .7, 3.2) higher risk of CVD, respectively. In race/ethnicity stratified models (interaction p-value=.01), an increased risk among sexual minorities, especially lesbians, was detectable except among Hispanic women (Figure). Conclusion: Disparities in global CVD risk were observed by sexual orientation for women and persisted across most racial/ethnic groups. Sexual orientation may be a marker of increased risk of CVD but more research on contributing factors is needed.
Decrease in smoking is related to a decrease in respiratory symptoms but not asthma
Authors: Helena Backman, Linnea Hedman, Sigrid Sundberg, Bo Lundbäck, Eva Rönmark
Journal: European Respiratory Journal (2011)

Background:  In 2005, smoking was banned in public places in Sweden.   Aim:  To compare the prevalence of respiratory symptoms and asthma among adults in 1996 and 2006 by smoking habits.   Methods:  In 1996, 7104 randomly selected subjects (response rate 85%) in Northern Sweden aged 20-69 answered a postal questionnaire including questions about respiratory diseases, symptoms and smoking habits. Correspondingly, in 2006 a new sample of 6165 subjects (77% responded) of same age answered the same questionnaire.   Results:  All respiratory symptoms were strongly related to smoking. The prevalence of most respiratory symptoms decreased significantly from 1996 to 2006 parallel to a decrease in smoking, which decreased from 27 to19%. The prevalence of sputum production decreased from 19.1 to 15.0%, longstanding cough 12.4-10.8%, chronic bronchitis 7.4-6.3%, and recurrent wheeze 13.4-12.1%. The prevalence of these symptoms was similar among smokers, and decreased among non-smokers. Physician-diagnosed asthma increased among both smokers and non-smokers, totally from 9.3 to 11.5%. However, the proportion of medicine users and symptomatics among the asthmatics were lower in 2006. In multivariate analysis adjusted for confounders, a significant increase of asthma by study year was found (OR 1.4). Corresponding analysis for chronic bronchitis yielded a significant decreased effect by study year (OR 0.8).   Conclusions:  The decreased prevalence of respiratory symptoms was parallel to a decrease in smoking. The decrease in bronchitis symptoms among non-smokers may be related to a reduction of environmental tobacco smoke and occupational airborne exposures. Increased diagnostic activity can explain the increase in asthma.