tbuckley/cabot-search huggingface dataset:
Elucidating the molecular pathogenesis of glioma: integrated germline and somatic profiling of a familial glioma case series
Authors: Daniel I Jacobs, Kazutaka Fukumura, Matthew N Bainbridge, Georgina N Armstrong, Spiridon Tsavachidis, Xiangjun Gu, Harsha V Doddapaneni, Jianhong Hu, Joy C Jayaseelan, Donna M Muzny, Jason T Huse, Melissa L Bondy
Journal: Neuro-Oncology (2018)

The genomic characterization of sporadically arising gliomas has delineated molecularly and clinically distinct subclasses of disease. However, less is known about the molecular nature of gliomas that are familial in origin. We performed molecular subtyping of 163 tumor specimens from individuals with a family history of glioma and integrated germline and somatic genomic data to characterize the pathogenesis of 20 tumors in additional detail.Immunohistochemical analyses were performed on formalin-fixed, paraffin-embedded tumor sections to determine molecular subtypes of glioma. For 20 cases, tumor DNA was exome sequenced on an Illumina HiSeq 2000 platform and copy number profiling was performed on the Illumina HumanOmniExpress BeadChip. Genotypes at glioma risk polymorphisms were determined from germline DNA profiled on the Illumina Infinium OncoArray and deleterious germline mutations were identified from germline sequencing data.All 3 molecular subtypes of sporadic glioma were represented in the overall case series, including molecular glioblastoma (n = 102), oligodendroglioma (n = 21), and astrocytoma (n = 20). Detailed profiling of 20 of these cases showed characteristic subtype-specific alterations at frequencies comparable to sporadic glioma cases. All 20 cases had alterations in genes regulating telomere length. Frequencies of common glioma risk alleles were similar to those among sporadic cases, and correlations between risk alleles and same-gene somatic mutations were not observed.This study illustrates that the molecular characteristics of familial tumors profiled largely recapitulate what is known about sporadic glioma and that both germline and somatic molecular features target common core pathways involved in gliomagenesis.1. Familial and sporadic gliomas display highly comparable molecular landscapes. 2. Germline and somatic molecular events target common core pathways involved in gliomagenesis. 3. Carriage of germline glioma risk variants is not associated with somatic events in the same gene.
Don’t use our fees to pay Bawa-Garba’s court costs, doctors tell GMC
Authors: Clare Dyer
Journal: BMJ (2018)

Nearly 700 doctors have signed a petition asking the General Medical Council (GMC) to find alternative means of paying Hadiza Bawa-Garba’s legal costs rather than using doctors’ registration and licensing fees.

The GMC faces a large legal bill, still to be assessed, after losing the appeal brought by the trainee paediatrician against a High Court ruling striking her off the medical register.1

She was found guilty of gross negligence manslaughter in 2015 after 6 year old Jack Adcock, who was under her care, died from septic shock. But a medical practitioners tribunal, which considered evidence that she was working under …
Abstract 13095: Phenotype, Genotype and Natural History of Arrhythmogenic Dilated Cardiomyopathy
Authors: Anita Spezzacatene, Gianfranco Sinagra, Marco Merlo, Giulia Barbati, Dobromir Slavov, Andrea Dilenarda, Ernesto E Salcedo, Sharon Graw, Xiao Zhu, Matthew Taylor, Luisa Mestroni, Familial Cardiomyopathy Registry
Journal: Circulation (2013)

Background: Arrhythmogenic dilated cardiomyopathy (aDCM) is a form of dilated cardiomyopathy (DCM) frequently encountered in clinical practice and characterized by severe ventricular arrhythmias. The purpose of this study was to determine the prevalence, genotype-phenotype correlations and long-term outcome predictors of aDCM, to implement current criteria for risk-stratification. METHODS: From February 1979 to November 2012, we studied a 461 patients (364 families) with DCM enrolled in the Familial Cardiomyopathy Registry. Criteria for aDCM were DCM with VT, SD, AICD shock, syncope, cardiac arrest, PVC>1000/24h. A subgroup of patients was tested for DCM genes (MYH6, MYH7, MYBPC3, TNNT2, TTN, LMNA, LAP2, SCN5A, DES). For survival analysis, endpoints were: 1) death or heart transplant, 2) death, heart transplant or malignant ventricular arrhythmias (MVA), 3) MVA. RESULTS: Over a follow-up of 96±82 months (up to 20 years), we identified 211 patients (45.8%) with aDCM: among them 72 (15.6% of the total DCM p...
Imaging Coronary Anatomy and Reducing Myocardial Infarction
Authors: Udo Hoffmann, James E. Udelson
Journal: New England Journal of Medicine (2018)

In 1998, the Journal published one of the early studies evaluating the sensitivity and specificity of coronary computed tomographic angiography (CTA), as compared with invasive coronary angiography, for the detection of obstructive coronary artery disease.1 Subsequent studies have established that CTA has excellent sensitivity (95 to 99%) and high specificity (64 to 83%) for the detection of coronary stenoses of 50% or greater.2 An analysis from the Prospective Multicenter Imaging Study for the Evaluation of Chest Pain (PROMISE) showed that CTA predicted subsequent cardiovascular events at least as well as, and perhaps better than, functional testing (C-statistic, 0.72 vs. 0.64; . . .
Effect of the CXCR2 antagonist danirixin on symptoms and health status in COPD
Authors: Aili L. Lazaar, Bruce E. Miller, Maggie Tabberer, John Yonchuk, Nancy Leidy, Claire Ambery, Jackie Bloomer, Henrik Watz, Ruth Tal-Singer
Journal: European Respiratory Journal (2018)

Approximately one-third of patients with chronic obstructive pulmonary disease (COPD) have chronic mucus hypersecretion (CMH) [1], often referred to as chronic bronchitis. Despite treatment with inhaled medications and other therapies, such as expectorants or methylxanthines, patients with CMH may continue to experience exacerbations, substantial symptom burden and poor health status [1]. CXCR2 antagonists are effective in multiple preclinical and human models of airway inflammation [2–5]. Danirixin is a competitive, reversible, oral CXCR2 antagonist that has been well tolerated in healthy subjects and in patients with influenza [6, 7]. We report the results of a 52-week Phase 2 study conducted in Germany and the USA (GSK protocol 200163; ClinicalTrials.gov identifier [NCT02130193][1]) assessing the effects of danirixin when added to standard-of-care inhaled medications in participants with symptomatic COPD. Participants with a forced expiratory volume in 1 s (FEV1) ≥50% of predicted normal and a history of two exacerbations in the prior 12 months, or one exacerbation and elevated plasma fibrinogen ≥3 mg·mL−1, as well as a history of chronic cough and/or mucus hypersecretion on most days for at least the previous 3 months prior to screening, were eligible. Full inclusion and exclusion criteria are available online at clinicaltrials.gov. The study was approved by the Western Institutional Review Board (Puyallup, WA, USA) and the Ethikkommission I, Ärztekammer Schleswig-Holstein (Bad Segeberg, Germany). Written informed consent was obtained from all participants. Danirixin was associated with improved respiratory symptoms and health status in patients with mild-to-moderate COPD <http://ow.ly/5m6P30luwfh> [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02130193&atom=%2Ferj%2F52%2F4%2F1801020.atom
Abstract 18569: Deletion of AT2 Receptor Prevents SHP-1 Expression and Improves Blood Flow in Diabetic Ischemic Hindlimb
Authors: Judith Paquin-Veillette, Andréanne Guay, Pedro Geraldes
Journal: Circulation (2015)

Introduction: Ischemia due to narrowing of femoral artery and distal vessels is also a major cause of peripheral arterial disease and morbidity affecting patients with diabetes. We have previously reported that the inhibition of the angiogenic response to PDGF and VEGF in diabetic mice (DM) is associated with the increase expression of SHP-1, a protein that can be activated by the AT2 receptors. It has been shown that the deletion of AT2 receptor in mice promotes angiogenesis within the ischemic muscle, but its role in diabetic condition remains unknown. Hypothesis: Our hypothesis is that AT2 receptor induced SHP-1 which contributed to inhibition of pro-angiogenic factor actions in DM mice during ischemia. Methods: Non-DM and DM AT2 null mice underwent femoral artery ligation after two months of diabetes. Blood perfusion was measured every week up to 4 weeks post-surgery. Expression of AT1, AT2, angiotensin-converting enzymes (ACE1/2), SHP-1 and angiogenic factors was evaluated. Results: Blood flow in the ischemic muscle of DM-AT2KO mice recovered faster and up to 80% four weeks following the surgery, compared to a 51% recovery in DM mice. After four weeks, the expression of pro-angiogenic factors (HIF-1α and VEGF) was diminished in the DM and remained at a basal state in the DM-AT2KO suggesting a faster recovery process in these mice. Interestingly, two weeks after ligation, the expression of VEGF and HIF-1α are elevated in DM-AT2DM compared to DM mice and correlated with a reduction of SHP-1 expression in the ischemic muscles. Conclusion: Our results suggest that the deletion of AT2 receptor prevented SHP-1 expression induced by diabetes and restored pro-angiogenic factors causing blood flow reperfusion following ischemia.
Abstract 16135: Hyponatremia is Related to Higher 30-Day Rehospitalization and 1-Year Mortality Rates in Patients Admitted With an Acute Coronary Syndrome: TRACE-CORE
Authors: Brendan C Merchant, David D McManus, Darleen Lessard, Joel M Gore, Robert J Goldberg, Catarina I Kiefe
Journal: Circulation (2015)

Introduction: Although hospital survival rates are improving among patients admitted with an acute coronary syndrome (ACS), early readmission is common and 1-year survival remains less than optimal. Improved risk stratification during an index ACS admission could direct greater surveillance or transitional care interventions for vulnerable patient populations prior to discharge from the hospital. While hyponatremia is associated with adverse outcomes after acute decompensated heart failure, less is known about whether hyponatremia relates to key post-discharge outcomes in patients discharged from the hospital after an ACS. Hypothesis: Hyponatremia is associated with early readmission and 1-year mortality in hospital survivors of an ACS. Methods: Using data from TRACE-CORE (Transitions, Risks, and Actions in Coronary Events - Center for Outcomes Research and Education), a diverse cohort of 2,081 patients discharged after an ACS, we examined the associations of admission hyponatremia (serum sodium ≤ 134 mmol/L) with 30-day readmission and 1-year all-cause mortality. Results: Cohort mean age was 61 (SD 11.3) years, 34% were women and 19% non-white. Hyponatremia was present in 10.9% and patients with hyponatremia had more pre-existing hypertension (p=0.002) and diabetes mellitus (p=0.001). GRACE scores and maximum troponin values were significantly higher in hyponatremic patients (p= 0.001 and 0.05, respectively). There was no significant difference in prior heart failure or home diuretic use between the two groups. Overall 1-year mortality was 4.58% and 30-day all-cause readmission rate was 13.46%. For patients with hyponatremia on admission, unadjusted odds of 30-day readmission were 36% higher (Odds Ratio 1.36, 95% CI 1.00 to 1.85) and 1-year mortality odds were almost 3-fold higher (Odds Ratio 2.79, 95% CI 1.71 to 4.55). Conclusions: Hyponatremia was associated with higher early readmission and lower 1-year survival. Serum sodium levels may represent a cost-effective biomarker of adverse post-discharge outcomes. The potential incremental prognostic information of serum sodium when added to existing readmission and post-discharge mortality risk prediction instruments should be investigated.
Reducing the Rate of Minimally Invasive Hysterectomy for Fibroids in Favor of Abdominal Surgery—There Is Always Something Evil in Good Intentions
Authors: Stefano Uccella, Alex Federico, Giovanni Scambia
Journal: JAMA Surgery (2018)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Surgery journal
Antibiotics and Acid-Suppressing Medications in Early Life and Allergic Disorders
Authors: Jennifer L. P. Protudjer, Elissa M. Abrams
Journal: JAMA Pediatrics (2018)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients
Authors: Erin A. Bohula, Stephen D. Wiviott, Darren K. McGuire, Silvio E. Inzucchi, Julia Kuder, KyungAh Im, Christina L. Fanola, Arman Qamar, Conville Brown, Andrzej Budaj, Armando Garcia-Castillo, Milan Gupta, Lawrence A. Leiter, Neil J. Weissman, Harvey D. White, Tushar Patel, Bruce Francis, Wenfeng Miao, Carlos Perdomo, Shobha Dhadda, Marc P. Bonaca, Christian T. Ruff, Anthony C. Keech, Steven R. Smith, Marc S. Sabatine, Benjamin M. Scirica
Journal: New England Journal of Medicine (2018)

Lorcaserin, a selective serotonin 2C receptor agonist that modulates appetite, has proven efficacy for weight management in overweight or obese patients. The cardiovascular safety and efficacy of lorcaserin are undefined.We randomly assigned 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive either lorcaserin (10 mg twice daily) or placebo. The primary safety outcome of major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) was assessed at an interim analysis to exclude a noninferiority boundary of 1.4. If noninferiority was met, the primary cardiovascular efficacy outcome (a composite of major cardiovascular events, heart failure, hospitalization for unstable angina, or coronary revascularization [extended major cardiovascular events]) was assessed for superiority at the end of the trial.At 1 year, weight loss of at least 5% had occurred in 1986 of 5135 patients (38.7%) in the lorcaserin group and in 883 of 5083 (17.4%) in the placebo group (odds ratio, 3.01; 95% confidence interval [CI], 2.74 to 3.30; P<0.001). Patients in the lorcaserin group had slightly better values with respect to cardiac risk factors (including blood pressure, heart rate, glycemic control, and lipids) than those in the placebo group. During a median follow-up of 3.3 years, the rate of the primary safety outcome was 2.0% per year in the lorcaserin group and 2.1% per year in the placebo group (hazard ratio, 0.99; 95% CI, 0.85 to 1.14; P<0.001 for noninferiority); the rate of extended major cardiovascular events was 4.1% per year and 4.2% per year, respectively (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P=0.55). Adverse events of special interest were uncommon, and the rates were generally similar in the two groups, except for a higher number of patients with serious hypoglycemia in the lorcaserin group (13 vs. 4, P=0.04).In a high-risk population of overweight or obese patients, lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo. (Funded by Eisai; CAMELLIA-TIMI 61 ClinicalTrials.gov number, NCT02019264 .).
Abstract 17659: Leaflet Calcification and Matrix Damage Due to Transcatheter Heart Valve Crimping
Authors: Aditi Sinha, Arash Kheradvar
Journal: Circulation (2015)

Introduction: Previous studies suggest that crimping causes permanent structural damage to the leaflet tissues of transcatheter heart valves (THV). However, this damage is not yet known to facilitate calcification process. Hypothesis: Our hypothesis is to test whether crimp-induced damage promotes valvular calcification. Methods: Self-expandable THVs with Glutaraldehye-fixed bovine pericardial leaflets was used. The valves were divided into two groups; crimped and uncrimped, and each group was split into two to be exposed either to a calcifying solution or to a control -normal phosphate buffered saline- solution. For the crimped group, the valves were carefully crimped with a standard crimper at 14Fr and held crimped for 20 minutes. The calcifying solution contains ionic concentrations corresponding to normal human plasma. All groups were maintained at pH 7.5, 37°C, on an orbital shaker at 400 rpm for 7 weeks. At the end, each tissue sample was individually embedded, sectioned and stained for calcium stain (Von Kossa), Verhoff’s Van Geison (VVG) stain for elastin and collagen stain (trichrome III). Results: Fig 1A show the normal bovine pericardium with arranged collagen layers in blue whereas intermittent striations are seen across the collagen fibers in the crimped group (Fig 1B). VVG stains show similar results with continuous elastin fibers (black) in the uncrimped group (Fig 1C) versus fragmented elastin fibers in the crimped group (Fig 1D). Of most significance are the results from the von kossa stains where crimped samples in saline show minimal hydroxyapatite deposition (Fig 1E) while crimped samples in calcifying buffer show brown deposits of hydroxyapatite along the crimped regions (Fig 1F). No hydroxyapatite deposition was observed in uncrimped group exposed to calcifying solution. Conclusions: Our results indicate that severe structural changes due to crimping are associated with greater levels of calcium deposition along the crimped sites.
Association of Changes in Effusion‐Synovitis With Progression of Cartilage Damage Over Eighteen Months in Patients With Osteoarthritis and Meniscal Tear
Authors: Lindsey A. MacFarlane, Heidi Yang, Jamie E. Collins, Mohamed Jarraya, Ali Guermazi, Lisa A. Mandl, Scott D. Martin, John Wright, Elena Losina, Jeffrey N. Katz
Journal: Arthritis & Rheumatology (2018)

Objective Synovitis is a feature of knee osteoarthritis ( OA ) and meniscal tear and has been associated with articular cartilage damage. This study was undertaken to examine the associations of baseline effusion‐synovitis and changes in effusion‐synovitis with changes in cartilage damage in a cohort with OA and meniscal tear. Methods We analyzed data from the Meniscal Tear in Osteoarthritis Research (MeTe OR ) trial of surgery versus physical therapy for treatment of meniscal tear. We performed semiquantitative grading of effusion‐synovitis and cartilage damage on magnetic resonance imaging, and dichotomized effusion‐synovitis as none/small (minimal) and medium/large (extensive). We assessed the association of baseline effusion‐synovitis and changes in effusion‐synovitis with changes in cartilage damage size and depth over 18 months, using Poisson regression models. Analyses were adjusted for patient demographic characteristics, treatment, and baseline cartilage damage. Results We analyzed 221 participants. Over 18 months, effusion‐synovitis was persistently minimal in 45.3% and persistently extensive in 21.3% of the patients. The remaining 33.5% of the patients had minimal synovitis on one occasion and extensive synovitis on the other. In adjusted analyses, patients with extensive effusion‐synovitis at baseline had a relative risk ( RR ) of progression of cartilage damage depth of 1.7 (95% confidence interval [95% CI ] 1.0–2.7). Compared to those with persistently minimal effusion‐synovitis, those with persistently extensive effusion‐synovitis had a significantly increased risk of progression of cartilage damage depth ( RR 2.0 [95% CI 1.1–3.4]). Conclusion Our findings indicate that the presence of extensive effusion‐synovitis is associated with subsequent progression of cartilage damage over 18 months. The persistence of extensive effusion‐synovitis over time is associated with the greatest risk of concurrent cartilage damage progression.
Trends and Disparities in Cardiovascular Mortality Among U.S. Adults With and Without Self-Reported Diabetes, 1988–2015
Authors: Yiling J. Cheng, Giuseppina Imperatore, Linda S. Geiss, Sharon H. Saydah, Ann L. Albright, Mohammed K. Ali, Edward W. Gregg
Journal: Diabetes Care (2018)

OBJECTIVE Cardiovascular disease (CVD) mortality has declined substantially in the U.S. The aims of this study were to examine trends and demographic disparities in mortality due to CVD and CVD subtypes among adults with and without self-reported diabetes. RESEARCH DESIGN AND METHODS We used the National Health Interview Survey (NHIS) (1985–2014) with mortality follow-up data through the end of 2015 to estimate nationally representative trends and disparities in major CVD, ischemic heart disease (IHD), stroke, heart failure, and arrhythmia mortality among adults ≥20 years of age by diabetes status. RESULTS Over a mean follow-up period of 11.8 years from 1988 to 2015 of 677,051 adults, there were significant decreases in major CVD death (all P values &amp;lt;0.05) in adults with and without diabetes except adults 20–54 years of age. Among adults with diabetes, 10-year relative changes in mortality were significant for major CVD (−32.7% [95% CI −37.2, −27.9]), IHD (−40.3% [−44.7, −35.6]), and stroke (−29.2% [−40.0, −16.5]), but not heart failure (−0.5% [−20.7, 24.7]), and arrhythmia (−12.0% [−29.4, 77.5]); the absolute decrease of major CVD among adults with diabetes was higher than among adults without diabetes (P &amp;lt; 0.001). Men with diabetes had larger decreases in CVD death than women with diabetes (P &amp;lt; 0.001). CONCLUSIONS Major CVD mortality in adults with diabetes has declined, especially in men. Large reductions were observed for IHD and stroke mortality, although heart failure and arrhythmia deaths did not change. All race and education groups benefitted to a similar degree, but significant gaps remained across groups.