tbuckley/cabot-search huggingface dataset:
Postoperative Management of Resected Brain Metastases: When Can Radiotherapy Be Deferred?
Authors: Minesh P. Mehta, Rupesh Kotecha
Journal: Journal of Clinical Oncology (2018)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 67-year-old woman was diagnosed 17 months ago with stage IIIB non-small-cell lung cancer (NSCLC; adenocarcinoma), without a targetable mutation, for which she received chemotherapy and thoracic radiotherapy. She developed new-onset gait ataxia, nausea, morning emesis, and headaches. A brain magnetic resonance imaging (MRI) scan demonstrated a 3.2-cm left cerebellar enhancing metastatic lesion, with surrounding vasogenic edema and mass effect, and three additional enhancing cortical, parenchymal lesions, each < 1.2 cm in maximum diameter, and none with significant mass effect ( Fig 1A ). A restaging positron emission tomography scan revealed no new sites of metastatic disease and no obvious intrathoracic progression. She underwent craniotomy, with piecemeal resection of the cerebellar metastatic lesion that proved to be recurrent lung cancer ( Fig 1B ). Her medical history was significant for mild hypertension and diet-controlled type II diabetes. She had smoked one pack a day for 32 years and had quit 3 years earlier. Postoperatively, her neurologic symptoms resolved, and physical and neurologic examinations were unrevealing; she had an Eastern Cooperative Oncology Group performance status (PS) of 0 and a Mini-Mental State Examination (MMSE) score of 29 of 30. A 3-week postoperative MRI scan confirmed the presence of 1-cm right frontal, 1.2-cm right parietal, and 1.2-cm left temporal enhancing lesions with minimal enhancement and no evidence of mass effect or edema. In addition, there was an ill-defined residual tumor bed, estimated to be approximately 3.7 cm in maximum diameter ( Fig 1C ). The patient was no longer receiving any steroids and was not receiving any anticonvulsants. Because of the residual three brain metastatic lesions, as well as the consideration of a high risk of surgical failure, she was referred for radiotherapy.
Abstract 20360: Modeling Coronary Artery Calcium and the Competing Long-Term Risk of Cardiovascular Versus Non-cardiovascular Mortality: The Cac Consortium
Authors: Seamus Whelton, Khurram Nasir, Roger Blumenthal, Zeina Dardari, Michael iedema, John Rumberger, Leslee Shaw, Dan Berman, Matt Budoff, Michael Blaha
Journal: Circulation (2016)

Background: Coronary artery calcium (CAC) is one of the strongest predictors of cardiovascular disease (CVD), but it is also associated with chronic non-CVD such as cancer. There is limited data on the relative associations between CAC and CVD versus non-CVD mortality. Methods: Four participating institutions contributed 66,636 individuals with CAC scans results and risk factor data to the CAC Consortium. All CAC scans were performed for clinical CVD risk assessment in patients without known coronary heart disease (CHD). CAC was categorized as 0, 1-99, 100-399, and ≥400. Mortality was assessed through linkage to the Social Security Death Index and death certificates were subsequently obtained from the National Death Index. The risk of cause-specific mortality was calculated using Cox models and competing risks models were calculated using the Fine and Gray method. Results: The mean age was 54 ± 11 years, 67% of patients were male, 45% of patients had CAC=0, and half had a 10-year ASCVD risk of <5%. There ...
THU0144 Performance of the ers-ra cardiovascular risk prediction tool: external validation in a large swedish cohort with ra
Authors: L. Ljung, P. Ueda, K.P. Liao, J.D. Greenberg, C.J. Etzel, D.H. Solomon, J. Askling
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Risk prediction tools developed for the general population tend to underestimate the risk of cardiovascular (CV) disease in patients with RA<sup>1</sup>. An accurate and RA-specific CV risk prediction tool would ideally be integrated as a routine part of clinical practice in rheumatology, to identify patients with increased CV risks. For example, 10 year CV risks above 7.5%, or 10%, could warrant specific preventive measures<sup>2,3</sup>. The ERS-RA was derived and internally validated in the US Corrona RA registry<sup>4</sup>. ERS-RA estimates the 10 year CV risk using dichotomous clinical variables, and includes variables on RA disease severity and activity. <h3>Objectives</h3> To assess the external validity of the ERS-RA in Swedish cohorts of patients with RA, with focus on the risk intervals of main clinical interest. <h3>Methods</h3> We identified two cohorts of patients with RA: (i) an "incident 2006 cohort" with RA patients in the Swedish Rheumatology Register from Jan 1, 2006 – Dec 31, 2011 who were also in the EIRA case-control study (n=2047, mean age 55±13 years, 72% women), and (ii) a "prevalent 2012 cohort" that included all RA patients in the Swedish Rheumatology Register between Jan 1, 2012 – Dec 31, 2015 (n=14485, mean age 61±14 years, 74% women). The 10 year CV risk was estimated using ERS-RA. Patients with a history of myocardial infarction or stroke were excluded. All patients were followed for the first of any of the following: a CV event (myocardial infarction, stroke, cardiovascular death), death, 10 years of follow-up, or Dec 31, 2015. Ten-year CV rates were expressed using the Kaplan-Meier method. <sup>In the prevalent 2012</sup> cohort, the 10 year event rates were extrapolated from the observed (maximally four-year) rates.<sup>5</sup> The C-statistic was estimated to assess discrimination. A measure of model calibration, the observed event rates were compared with the mean predicted 10 year risks. <h3>Results</h3> The C-statistic was 0.75 for both cohorts. Most patients had an estimated CV risk &lt;5% or of &gt;10% (See table 1). An accurate risk prediction was observed for estimated risks in the intervals&lt;5%, and 5.0 to &lt;7.5%. ERS-RA underestimated risk in the interval 7.5 to &lt;10% (see table 1 and figure 1). <h3>Conclusions</h3> In a Swedish population with RA, ERS-RA performed well in identifying patients with a very low and very high CV 10 year CV risk. In clinical routine practice, ERS-RA could be used to identify low and high risk individuals, who might be considered for additional CV risk factor evaluation and subsequent intervention. <h3>References</h3> [1] Crowson CS, et al. Ann Rheum Dis. 2018. [2] Stone NJ, et al. Circulation. 2014. [3] https://www.nice.org.uk [4] Solomon DH, et al. Arthritis Rheum. 2015. [5] Cook NR, Ridker PM. JAMA Intern Med. 2014. <h3>Disclosure of Interest</h3> None declared
Use of a Metabolic Syndrome Severity <i>Z</i> Score to Track Risk During Treatment of Prediabetes: An Analysis of the Diabetes Prevention Program
Authors: Mark D. DeBoer, Stephanie L. Filipp, Matthew J. Gurka
Journal: Diabetes Care (2018)

We assessed whether changes in metabolic syndrome (MetS) severity during the treatment of prediabetes are associated with reduced risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD).
Abstract 19640: Factors Associated With Dialysis-Requiring Acute Kidney Injury in Patients With Heart Failure
Authors: Saman Setareh-Shenas, Di Pan, Sung Lee, Nader Ishak Gabra, Eyal Herzog
Journal: Circulation (2017)

Background: Acute kidney injury (AKI) poses significant burden on patients with Heart Failure (HF), particularly for those who potentially will require renal replacement therapy (RRT). The aim of t...
Locum GP struck off after sexually motivated behaviour
Authors: Clare Dyer
Journal: BMJ (2018)

A medical practitioners’ tribunal has ordered a locum GP to be struck off the UK medical register after finding that he had displayed sexually motivated behaviour towards one woman while under General Medical Council investigation for an “inappropriate sexualised conversation” with another.

Mohammad Qasim Ihsan, 36, who qualified at Manchester University in 2007, took a shower with the door open while a woman employed by his landlord was cleaning his serviced apartment. He emerged wearing only a towel, which soon fell off.

The woman, …
More Evidence Supporting Fluorodeoxyglucose Positron Emission Tomography for Diagnosing Prosthetic Valve Infective Endocarditis
Authors: Márcio Sommer Bittencourt, Ron Blankstein
Journal: Circulation (2018)

rosthetic valve endocarditis (PVE) may affect up to 5% of individuals after valve replacement, and appears more common than previously reported. 1 Its diagnosis is challenging because the Modified Duke Criteria 2 rely on transesophageal echocardiography and blood cultures. 3However, the diagnostic accuracy of echocardiography in individuals with prosthetic valves is lower than native valves, and blood cultures results may be delayed. 4Because delays in diagnosis are associated with exceedingly high complication rates and mortality, there is an unmet clinical need for new faster more accurate diagnostic strategies.Recent studies have proposed that 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) may have adequate diagnostic accuracy to be routinely used in the investigation of infective endocarditis, with a particularly good performance for PVE. 5 In this scenario, an incremental diagnostic accuracy when compared to usual care has been demonstrated. 6,7Consequently, the European Society of Cardiology Guidelines now include 18 F-FDG PET and cardiac CT findings as major criteria for diagnosing PVE when the level of suspicion is high, but the diagnosis is not confirmed. 8Nevertheless, at the present time neither 18
Abstract 17861: Injectable Shear-thinning Hydrogels to Deliver Endothelial Progenitor Cells, Reduce Ventricular Strain, and Dynamic Stiffness to Stabilize Cardiac Function Following Ischemic Injury
Authors: Ann C Gaffey, Minna H Chen, Alen Trubelja, Chantel M Venkataraman, Carol W Chen, Susan S, Chandra M Sehgal, Jason A Burdick, Pavan Atluri
Journal: Circulation (2015)

The ventricle undergoes adverse remodeling, post-infarction. We developed an injectable shear-thinning hyaluronic acid hydrogel(STG) and endothelial progenitor cell construct(STG-EPC) to enhance vasculogenesis(shown previously) and mechanically stabilize the infarcted myocardium. We hypothesize that this tissue-engineered therapy will minimize adverse remodeling and maintain myocardial tensile properties in a clinically translatable therapy. EPCs(DiLDL+ VEGFR2+ CD34+) were harvested from adult Wistar Rats and suspended in STG. STG-EPC constructs were circumferentially injected at the borderzone of ischemic rat myocardium, following LAD ligation. Engraftment and retention were assessed by near infrared cellular tag. Myocardial remodeling, tensile properties, and hemodynamic function were analyzed in 4 groups: control(PBS), EPC injection(EPC), STG injection(STG), and STG-EPC construct(STG-EPC). High-resolution ultrasound with speckle tracking (VSI Vevo 2100) allowed analysis of regional epicardial and endocardial strain. Uniaxial testing assessed tensile strength. STG-EPC injection significantly increased engraftment, migration, and retention of the EPCs one-week post implant compared to EPC (0.7 vs 0.4 RFU, p=0.02). Using strain echocardiography a significant increase in left ventricular function was noted in the STG-EPC cohort. Strain echocardiography examination revealed a significant retention of myocardial longitudinal displacement with subsequent stabilization of myocardial velocity with STG-EPC therapy. A reduction in dynamic stiffness was noted in the STG-EPC cohort.(Table) This novel injectable shear-thinning hyaluronic acid hydrogel seeded with EPCs demonstrates stabilization of borderzone myocardium with reduction in adverse myocardial remodeling and preservation of myocardial biomechanics. There is a markedly increased retention of delivered stem cells with this tissue engineered therapy.
Angiopoietin-2 exacerbates cardiac hypoxia and inflammation after myocardial infarction
Authors: Seung-Jun Lee, Choong-kun Lee, Seok Kang, Intae Park, Yoo Hyung Kim, Seo Ki Kim, Seon Pyo Hong, Hosung Bae, Yulong He, Yoshiaki Kubota, Gou Young Koh
Journal: Journal of Clinical Investigation (2018)

Emerging evidence indicates that angiopoietin-2 (Angpt2), a well-recognized vascular destabilizing factor, is a biomarker of poor outcome in ischemic heart disease. However, its precise role in postischemic cardiovascular remodeling is poorly understood. Here, we show that Angpt2 plays multifaceted roles in the exacerbation of cardiac hypoxia and inflammation after myocardial ischemia. Angpt2 was highly expressed in endothelial cells at the infarct border zone after myocardial infarction (MI) or ischemia/reperfusion injury in mice. In the acute phase of MI, endothelial-derived Angpt2 antagonized Angpt1/Tie2 signaling, which was greatly involved in pericyte detachment, vascular leakage, increased adhesion molecular expression, degradation of the glycocalyx and extracellular matrix, and enhanced neutrophil infiltration and hypoxia in the infarct border area. In the chronic remodeling phase after MI, endothelial- and macrophage-derived Angpt2 continuously promoted abnormal vascular remodeling and proinflammatory macrophage polarization through integrin α5β1 signaling, worsening cardiac hypoxia and inflammation. Accordingly, inhibition of Angpt2 either by gene deletion or using an anti-Angpt2 blocking antibody substantially alleviated these pathological findings and ameliorated postischemic cardiovascular remodeling. Blockade of Angpt2 thus has potential as a therapeutic option for ischemic heart failure.
Empagliflozin as Adjunctive to Insulin Therapy in Type 1 Diabetes: The EASE Trials
Authors: Julio Rosenstock, Jan Marquard, Lori M. Laffel, Dietmar Neubacher, Stefan Kaspers, David Z. Cherney, Bernard Zinman, Jay S. Skyler, Jyothis George, Nima Soleymanlou, Bruce A. Perkins
Journal: Diabetes Care (2018)

To evaluate the safety and efficacy of empagliflozin 10- and 25-mg doses plus a unique lower dose (2.5 mg) as adjunct to intensified insulin in patients with type 1 diabetes (T1D).The EASE (Empagliflozin as Adjunctive to inSulin thErapy) program (N = 1,707) included two double-blind, placebo-controlled phase 3 trials: EASE-2 with empagliflozin 10 mg (n = 243), 25 mg (n = 244), and placebo (n = 243), 52-week treatment; and EASE-3 with empagliflozin 2.5 mg (n = 241), 10 mg (n = 248), 25 mg (n = 245), and placebo (n = 241), 26-week treatment. Together they evaluated empagliflozin 10 mg and 25 mg, doses currently approved in treatment of type 2 diabetes, and additionally 2.5 mg on 26-week change in glycated hemoglobin (primary end point) and weight, glucose time-in-range (>70 to ≤180 mg/dL), insulin dose, blood pressure, and hypoglycemia.The observed largest mean placebo-subtracted glycated hemoglobin reductions were -0.28% (95% CI -0.42, -0.15) for 2.5 mg, -0.54% (-0.65, -0.42) for 10 mg, and -0.53% (-0.65, -0.42) for 25 mg (all P < 0.0001). Empagliflozin 2.5/10/25 mg doses, respectively, reduced mean weight by -1.8/-3.0/-3.4 kg (all P < 0.0001); increased glucose time-in-range by +1.0/+2.9/+3.1 h/day (P < 0.0001 for 10 and 25 mg); lowered total daily insulin dose by -6.4/-13.3/-12.7% (all P < 0.0001); and decreased systolic blood pressure by -2.1/-3.9/-3.7 mmHg (all P < 0.05). Genital infections occurred more frequently on empagliflozin. Adjudicated diabetic ketoacidosis occurred more with empagliflozin 10 mg (4.3%) and 25 mg (3.3%) but was comparable between empagliflozin 2.5 mg (0.8%) and placebo (1.2%). Severe hypoglycemia was rare and frequency was similar between empagliflozin and placebo.Empagliflozin improved glycemic control and weight in T1D without increasing hypoglycemia. Ketoacidosis rate was comparable between empagliflozin 2.5 mg and placebo but increased with 10 mg and 25 mg. Ketone monitoring for early ketoacidosis detection and intervention and lower empagliflozin doses may help to reduce this risk.
GSK will resume paying doctors to promote its drugs after policy U turn
Authors: Jacqui Wise
Journal: BMJ (2018)

The pharmaceutical giant GlaxoSmithKline (GSK) has announced that it will once again pay doctors to speak on its behalf about its drugs and associated diseases.

The UK based company announced at the end of 2013 that it would stop paying key opinion leaders and instead would rely more on its own clinical experts.1 That move came amid a major bribery investigation in China, which resulted in a record fine, and was an attempt to improve the company’s reputation.23 …
HOW SHOULD WE SUPPORT PATIENTS WITH PRIMARY BRAIN TUMOURS WHO ELECT TO TAKE CANNABINOIDS?
Authors: Jessica La, Victoria Hurwitz, Laura Mullens, Lucy Brazil, Richard Gullan, Ranj Bhangoo, Francesco Vergani, Ronald Beaney, Keyoumars Ashkan, Bali Rooprai, Angela Swampillai
Journal: Neuro-Oncology (2018)

Primary brain tumours account for 3% of new cancer cases (2015) but account disproportionately in terms of mortality and morbidity. With radical treatment prognosis is variable; ranging from 80% survival for 5 years or more for benign meningiomas to a dismal 5% for Glioblastoma multiforme (GBM). Understandably, increasing numbers of cancer patients are seeking Complementary and Alternative Medicine (CAM) to improve prognosis and alleviate treatment related toxicities. There is legitimate CAM research in the UK. Yet it is challenging for vulnerable patients to disentangle legitimate researchers from dubious ones. These patients are open to manipulation and abuse via unsolicited sources offering a magical ‘cure’. It is also challenging to support patients through treatment when they may be self-medicating without their treating team being aware of the details, and possible interactions. We propose to investigate whether there is a need for specialist support for this patient population. Questionnaires were distributed across 3 Neuro oncology clinics over one week (N=51). These were completed anonymously to encourage honest responses. 30 patients were on active surveillance and 21 patients were on active treatment (either radiotherapy or chemotherapy). A significant number of patients were already taking some form of CAM such as turmeric, or were interested in speaking to a CAM Specialist regarding it. Of particular interest was the use of Cannabinoids (CBD) which are being explored in pre-clinical and clinical trials in brain tumours. We are seeing an increase in the use of CBD use amongst our patient groups who were surveyed. This survey has given us insight into our patient population and guides us on how we can best support them. We are continuing to collect questionnaires and full evaluation will be presented.
Abstract 101: Serum Pro Brain Natriuretic Peptide (pro BNP) Levels In Children With Kawasaki Disease
Authors: Amit Rawat, Mounika V Reddy, Deepti Suri, Anju Gupta, Surjit Singh
Journal: Circulation (2015)

Introduction: Brain natriuretic peptide (BNP) is a useful biomarker for diagnosing heart failure in adults and children. ProBNP, the precursor form of BNP has been shown to predict myocardial involvement in acute Kawasaki disease (KD) especially in cases of incomplete KD. As the phenotype of KD in North India is different from that in Japan and North America, this study was carried out to validate the utility of proBNP in North Indian children with KD. Objectives: To assay the levels of proBNP in North Indian children with KD. Methodology: Serum pro brain natriuretic peptide (pro BNP and NT-proBNP) levels were estimated in 25 children with Kawasaki disease, both during acute phase and later in convalescence. The levels were similarly assayed in an equal number of age and sex matched controls. The proBNP levels were estimated by an enzyme linked immunosorbent assay (ELISA) using the RayBio Human proBNP ELISA kit which detects both pro BNP and NT-pro BNP. Results: Pro BNP levels were significantly elevated in children during acute phase of KD (4259±8015 pg/ml) when compared to febrile controls (407±542pg/ml) or to children in convalescent phase of KD (509±1066 pg/ml). Pro BNP levels were also higher in children with coronary abnormalities in acute phase. Conclusions: In our experience, pro BNP is a useful biomarker for KD especially with regard to myocardial involvement. ProBNP level is markedly elevated during the acute phase in all children with KD. In children with persistent coronary artery abnormalities, the proBNP level remains elevated even during convalescence. Future impact: ProBNP may be useful marker for children with incomplete forms of KD
Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome: an exploratory analysis of the ELIXA randomised, placebo-controlled trial
Authors: Marcel H A Muskiet, Lennart Tonneijck, Yao Huang, Minzhi Liu, Aramesh Saremi, Hiddo J L Heerspink, Daniël H van Raalte
Journal: The Lancet Diabetes & Endocrinology (2018)
Response to: ‘Aortic ulceration in a tocilizumab-treated patient with Takayasu arteritis’ by Liebling <i>et al</i>
Authors: Yoshikazu Nakaoka
Journal: Annals of the Rheumatic Diseases (2018)

I thank Liebling and colleagues for their interest in our manuscript1 and for sharing their experience with a patient with refractory Takayasu arteritis who developed aortic ulceration while on tocilizumab therapy.2 Our first multicentre, randomised, double-blind, placebo-controlled study (the TAKT study) showed a favourable effect for tocilizumab over placebo in patients with refractory Takayasu arteritis. As shown in online supplementary figure S1 of our manuscript,1 the study included patients who did not respond to conventional or biologic disease-modifying antirheumatic drugs, similar to the patient reported by Liebling et al . The data from an open-label extension of this study, the largest …
Abstract 19798: Guiding the End-of-Life Discussion in Patients With Implantable Cardiac Defibrillators and Bi-Ventricular Implantable Cardiac Defibrillators
Authors: Walter P Paladino, Deborah Dillon
Journal: Circulation (2016)

Introduction: Patients with terminal diseases and their families fear multiple defibrillator shocks at the end-of-life. Despite conversations discussing deactivation of device tachy therapies, even...
Abstract 14403: Neuregulin Attenuates Right Ventricular and Pulmonary Endothelial Dysfunction in an Experimental Model of Pulmonary Hypertension
Authors: Pedro Mendes-Ferreira, Carolina Maia-Rocha, Rui M Adão, Rui J Cerqueira, Maria J Mendes, André P LourenÇo, Gilles W De Keulenaer, Adelino Leite-Moreira, Carmen Brás-Silva
Journal: Circulation (2012)

Neuregulin (NRG)-1 is implicated in the preservation of left ventricular function in pathophysiological conditions. However, the role of NRG-1 in right ventricular (RV) failure is still unknown. We analysed the effects of NRG-1 treatment in an animal model of pulmonary arterial hypertension (PAH) and RV heart failure (HF). Male Wistar rats (180-200g) randomly received monocrotaline (MCT, 60mg/Kg,sc) or vehicle. After 14 days, animals randomly received NRG-1 (40µg/Kg/day,ip) or vehicle, resulting in 4 groups: ctrl (n=10); ctrl+NRG (n=10); MCT (n=10); MCT+NRG (n=10). RV hemodynamics and sample collection for vascular, morphometric, histologic and molecular studies were performed 25-28 days after MCT administration. Only significant results (mean±SEM, p<0.05) are given. MCT group developed PAH, as shown by increased RV maximum pressure (MCT vs ctrl: 63±3 vs 34±3mmHg) and by decreased cardiac output (MCT vs ctrl: 34±4 vs 65±4mL/min) which were both attenuated in the MCT+NRG group (53±3mmHg and 52±2mL/min). An...