tbuckley/cabot-search huggingface dataset:
Utilisation of an electronic incident report to document injury-related demographics and medical triage in youth, high school and college athletes
Authors: Jay L Alberts, Susan M Linder, Andrew Russman, Rick Figler, Jason Cruickshank, Bob Grey, Maureen Lally, Tanujit Day
Journal: British Journal of Sports Medicine (2017)

Objective To develop and utilise a custom mobile application to provide a portable yet systematic method to characterise injury demographics, post-injury disposition, and immediate medical care of sport-related concussion in youth, high school and college settings. Design Retrospective observational study. Setting Academic medical centre. Participants Athletes under the care of Cleveland Clinic Concussion Centre clinicians from August 5, 2014-March 1, 2016. The sample included youth (n=110), high school (n=1175) and college (n=309) athletes; approximately 35% of the sample were female. Intervention Electronic incident reports were completed on all student-athletes with suspected concussion to triage injury severity, document injury-related demographics along with immediate medical management. Total time to complete the incident report was less than three minutes. Outcome measures Sport, mechanism of injury, red flags, immediate symptoms, and post-injury disposition were recorded for all participants. Main results Football and soccer represented the greatest frequency of injury across males and females respectively. Despite significantly fewer red flags in youth, they were sent to the emergency department four times more frequently (22%) than high school or college athletes (5%). Conclusions The systematic characterisation of injury profiles indicates athletes across the continuum of age share general characteristics in terms of incidence as a function of sport and setting (practice vs. competition). The disproportional disposition to emergency departments, despite the absence of red flags, indicates a more conservative approach to youth concussion triage compared to high school and college athletes. Competing interests None.
Feasibility and Safety of Uninterrupted Rivaroxaban for Periprocedural Anticoagulation in Patients Undergoing Radiofrequency Ablation for Atrial Fibrillation
Authors: Dhanunjaya Lakkireddy, Yeruva Madhu Reddy, Luigi Di Biase, Ajay Vallakati, Moussa C. Mansour, Pasquale Santangeli, Sandeep Gangireddy, Vijay Swarup, Fadi Chalhoub, Donita Atkins, Sudharani Bommana, Atul Verma, Javier E. Sanchez, J. David Burkhardt, Conor D. Barrett, Salwa Baheiry, Jeremy Ruskin, Vivek Reddy, Andrea Natale
Journal: Journal of the American College of Cardiology (2014)
"Hemophilia Vertical": Effects of Therapeutic Rock Climbing on Joint Health in Hemophilia Patients with Severe Arthropathies
Authors: Courtney Schroeder, Felix Kallenbach, Lena Volland, Richard FW Barnes, Colleen M Moran, Christine Geyer, Regina von Velsen, Annette von Drygalski, Michaela Andrea Stemberger
Journal: Blood (2016)
Developmentally‐faithful and effective human erythropoiesis in immunodeficient and <i>Kit</i> mutant mice
Authors: Claudia Fiorini, Nour J. Abdulhay, Sean K. McFarland, Mathias Munschauer, Jacob C. Ulirsch, Roberto Chiarle, Vijay G. Sankaran
Journal: American Journal of Hematology (2017)

Immunodeficient mouse models have been valuable for studies of human hematopoiesis, but high-fidelity recapitulation of erythropoiesis in most xenograft recipients remains elusive. Recently developed immunodeficient and Kit mutant mice, however, have provided a suitable background to achieve higher-level human erythropoiesis after long-term hematopoietic engraftment. While there has been some characterization of human erythropoiesis in these models, a comprehensive analysis from various human developmental stages has not yet been reported. Here, we have utilized cell surface phenotypes, morphologic analyses, and molecular studies to fully characterize human erythropoiesis from multiple developmental stages in immunodeficient and Kit mutant mouse models following long-term hematopoietic stem and progenitor cell engraftment. We show that human erythropoiesis in such models demonstrates complete maturation and enucleation, as well as developmentally appropriate globin gene expression. These results provide a framework for future studies to utilize this model system for interrogating disorders affecting human erythropoiesis and for developing improved therapeutic approaches.
Heart rhythm conundrum
Authors: Rhodri Huw Davies, Dewi Eurfyl Thomas
Journal: BMJ (2017)

A 40 year old man was referred to the cardiology team because of bradycardia. He was an inpatient undergoing treatment for an infection of unknown origin and he had developed acute-on-chronic kidney dysfunction. His medical history included type 1 diabetes, a previous renal transplant for diabetic nephropathy, and permanent atrial fibrillation.

The patient was asymptomatic, with a blood pressure of 122/74 mm Hg and a pulse oximetry reading of 97% on room air (normal value ≥94%) His electrocardiogram (ECG) at the time of referral is shown in figure 1⇓.



Fig 1  12 lead electrocardiogram (ECG) at the time of referral



1.  What is the underlying rhythm on the ECG?

2.  What are the potential causes of bradycardia in this patient?

3.  How should the patient be managed and what is the definitive treatment?

### 1. What is the underlying rhythm on the ECG?

#### Short answer

The atrial rhythm is atrial fibrillation. However, the ventricular rate is slow (36 beats/min) and regular with broad QRS complexes. The patient has developed atrial fibrillation with complete heart block.

#### Discussion

The ECG has no discernible p waves, but there are fibrillatory waves seen in some leads. The appearance of the atrial activity in lead V1 can sometimes be confused with atrial flutter or a focal atrial tachycardia. This phenomenon occurs because the right atrial appendage lies between the V1 electrode and the left atrium and effectively “filters” the waves so that they appear organised. However, there is no organised atrial activity in the other leads and closer inspection of the fibrillatory waves in lead V1 shows an irregular and rapid rate, …
FRI0309 Cardiovascular events in anca-associated vasculitis: a meta-analysis of observational studies
Authors: E Houben, EL Penne, AE Voskuyl, JW van der Heijden, M Boers, T Hoekstra
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Several chronic inflammatory diseases are associated with cardiovascular disease, but the cardiovascular risk in ANCA-associated vasculitis is poorly quantified. <h3>Objectives</h3> The aim of the present study is to review the evidence for the increased cardiovascular risk in patients with ANCA-associated vasculitis. <h3>Methods</h3> A comprehensive systematic review was conducted in accordance with guidelines of preferred reporting items for systematic reviews and meta-analyses (PRISMA). The databases PubMed, Embase.com and the Cochrane Library (Wiley) were searched for original observational studies reporting an estimate of the association between ANCA-associated vasculitis and cardiovascular events, including ischemic heart disease, cerebrovascular accidents and/or peripheral arterial disease. The quality of the included studies was assessed with the Newcastle–Ottawa Scale. Summary estimates were derived with a random-effects model and reported as relative risks. <h3>Results</h3> 1375 studies were identified and 7 studies were included comprising 14098 ANCA-associated vasculitis patients versus general population controls in 6 studies and chronic kidney disease patients in 1 study. ANCA-associated vasculitis carried a relative risk of 1.65 (95% confidence interval, 1.23–2.22) for all cardiovascular events, 1.60 (1.39–1.84) for ischemic heart disease and 1.20 (0.98–1.48) for cerebrovascular accidents. We did not find studies that addressed the risk for peripheral arterial disease separately. No heterogeneity was seen in the estimates. <h3>Conclusions</h3> This meta-analysis of observational studies supports an increase in cardiovascular risk of about 65% in patients with ANCA-associated vasculitis, similar to that found in other chronic inflammatory diseases. Hence, there is a clear need for active cardiovascular risk management in patients with ANCA-associated vasculitis. <h3>Disclosure of Interest</h3> None declared
Corrigendum to “LNA aptamer based multi-modal, Fe3O4-saturated lactoferrin (Fe3O4-bLf) nanocarriers for triple positive (EpCAM, CD133, CD44) colon tumour targeting and NIR, MRI and CT imaging” [Biomaterials 71C (2015) 84–99]
Authors: Kislay Roy, Rupinder K. Kanwar, Jagat R. Kanwar
Journal: Biomaterials (2017)
Erratum: A defective response to hedgehog signaling in disorders of cholesterol biosynthesis (Nature Genetics (2003) 33 (508-513))
Authors: M. K. Cooper, C. A. Wassif, P. A. Krakowiak, J. Taipale, R. Gong, R. I. Kelley, F. D. Porter, P. A. Beachy
Journal: Nature Genetics (2003)
Abstract 262: Depolarization Stimulates Neonatal Cardiomyocyte Proliferation In Vitro
Authors: Corin Williams, Michael Levin, Lauren D Black
Journal: Circulation Research (2012)

Cardiac tissue engineering is a promising approach for treating children with congenital heart defects. However, as cardiomyocytes (CMs) undergo a rapid transition from hyperplastic to hypertrophic growth after birth, a major challenge to the development of engineered cardiac tissue is the limited proliferation of CMs. Mature CMs and other terminally differentiated cell types tend to have a highly negative resting membrane potential (Vmem) while stem cells and less mature cells tend to have Vmem closer to zero. Vmem has been shown to play an important role in cell differentiation and proliferation. We hypothesized that depolarization of cardiac cells would stimulate CM proliferation in vitro . To test our hypothesis, we isolated neonatal rat cardiac cells and cultured them for 24 hr under standard conditions. Cells were then subjected to depolarization treatment for 72 hr using potassium gluconate or ouabain at various concentrations. Samples were fixed and stained for cardiac α-actin (Fig 1A, red) and phospho-histone H3 (Fig 1A, green) to assess CM mitosis. We found that potassium gluconate had no significant effect while ouabain significantly increased CM mitosis, suggesting Vmem regulation via Na/K-ATPase. CM-specific proliferation was significantly higher with 10nM (p= 0.015) and 100nM (p=0.008) ouabain treatment compared to controls (n=3) (Fig 1B). Cell density was significantly higher with 100μM ouabain versus controls (2656 ± 50 vs. 2026 ± 117 cells/mm 2 ), indicating increased cardiac cell proliferation (Fig 1C). Our findings suggest that depolarization promotes CM proliferation and may be a novel approach to encourage growth of engineered cardiac tissue in vitro .
La SMSO (Sphinctérotomie avec Macrodilatation du Sphincter d'Oddi) est-elle plus efficace et moins risquée que le traitement endoscopique conventionnel (SE ± LM) pour les gros calculs de la VBP? Etude prospective, multicentrique, randomisée sur 150 patients
Authors: D Karsenti, E Coron, G Vanbiervliet, J Privât, E Kull, P Bichard, B Perrot, V Quentin, A Duriez, F Cholet, C Subtil, JC Duchmann, F Fumex, H Hudziak, S Koch, P Grandval, S Lecleire, A Charachon, E Métivier-Cesbron, A De widerspach thor, Y Le baleur, M Barthet, L Poincloux
Journal: Endoscopy (2016)

Après sphinctérotomie endoscopique (SE), près de 10% des lithiases de la voie biliaire principale (LVBP) restent inextirpables. Le recours à la lithotritie mécanique (LM) est alors nécessaire mais cette technique est coûteuse, augmente la durée de procédure et est de succès inconstant.
Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort
Authors: Tracy A Williams, Jacques W M Lenders, Paolo Mulatero, Jacopo Burrello, Marietta Rottenkolber, Christian Adolf, Fumitoshi Satoh, Laurence Amar, Marcus Quinkler, Jaap Deinum, Felix Beuschlein, Kanako K Kitamoto, Uyen Pham, Ryo Morimoto, Hironobu Umakoshi, Aleksander Prejbisz, Tomaz Kocjan, Mitsuhide Naruse, Michael Stowasser, Tetsuo Nishikawa, William F Young, Celso E Gomez-Sanchez, John W Funder, Martin Reincke, Tracy Ann Williams, Celso E Gomez-Sanchez, John W Funder, Martin Reincke, Christian Adolf, Laurence Amar, Richard J Auchus, Detlef K Bartsch, Rene Baudrand, Felix Beuschlein, Peyman Björklund, Morris J Brown, Jacopo Burrello, Robert M Carey, Cristiana Catena, John M Connell, Jaap Deinum, Tanja Dekkers, Thomas J Fahey, Francesco Fallo, Carlos E. Fardella, Gilberta Giacchetti, Giuseppe Giraudo, Per Hellman, Andrzej Januszewicz, Kanako Kiriyama Kitamoto, Gregory A Kline, Tomaz Kocjan, Jacques W M Lenders, Franco Mantero, Barbra S Miller, Ryo Morimoto, Paolo Mulatero, Mitsuhide Naruse, Tetsuo Nishikawa, Uyen Pham, Pierre-François Plouin, Alexander Prejbisz, Marcus Quinkler, Marietta Rottenkolber, Christian L Rump, Fumitoshi Satoh, Leonardo A Sechi, Michael Stowasser, Hironobu Umakoshi, Franco Veglio, Jirí Widimský, Holger S Willenberg, William F Young
Journal: The Lancet Diabetes & Endocrinology (2017)
DIPG-02. RADIOSENSITIVITY OF DIPG CELLS IS ENHANCED BY TARGETING GLUCOSE METABOLISM IN VITRO AND IN VIVO
Authors: Han Shen, Cecilia Chang, Swapna Joshi, Jie Liu, Maria Tsoli, Eric Hau, David Ziegler
Journal: Neuro-Oncology (2017)

Diffuse Intrinsic Pontine Glioma (DIPG) is the most aggressive of all childhood cancers and the leading cause of brain tumour-related death in children. There is no effective treatment for DIPG, and all patients die from this disease. Hitherto, radiotherapy (RT) is the only form of treatment that offers a transient benefit in DIPG. Following completion of RT, almost all DIPGs recur locally within 12 months. Therefore, the identification of therapeutic targets that modulate the radioresistance of DIPG offers a pathway to the development of effective therapies. It is well established that derangements in glucose metabolism of cancer cells can lead to radioresistance. Dichloroacetate (DCA), currently being used to treat lactic acidosis, can modify tumour metabolism by activating mitochondrial activity to force glycolysis into oxidative phosphorylation. In vitro, our data have shown that DCA inhibits cell proliferation and has profound anti-tumour activity across a panel of DIPG neurospheres. We have also observed that the efficacy of RT is significantly improved when DCA is added. Strikingly, the anti-tumour effect of DCA is further enhanced by the addition of metformin, a widely used anti-diabetic biguanide with anti-cancer activity, through the induction of a higher level of oxidative stress and DNA damage. Metabolically, the metformin-induced lactate production is attenuated by DCA and the energy homeostasis of DIPG cells is perturbed by this combination through the dual-targeting of glucose metabolism. This ultimately leads to a more potent radiosensitising effect when triple combination is administered. In vivo, the combined treatments significantly extend the survival of an orthotopic model of DIPG compared to RT alone, with greatest effect seen with the triple combination therapy of DCA, metformin and RT. Our conclusion is that targeting glucose metabolism represents a novel radiosensitising approach for incurable DIPG that is readily translatable to clinical trial for this deadly paediatric brain tumour.
Angiotensin-Converting Enzyme Inhibition With Quinapril Improves Endothelial Vasomotor Dysfunction in Patients With Coronary Artery Disease
Authors: G.B. John Mancini, Gregory C. Henry, Carlos Macaya, Blair J. O'Neill, Anthony L. Pucillo, Ronald G. Carere, Thomas J. Wargovich, Harald Mudra, Thomas F. Lu¨scher, Michael I. Klibaner, Harry E. Haber, Andrew C.G. Uprichard, Carl J. Pepine, Bertram Pitt
Journal: Circulation (1996)

Background Angiotensin-converting enzyme (ACE) inhibitors may exert some of their benefits in the therapy of hypertension, congestive heart failure, and acute myocardial infarction by their improvement of endothelial dysfunction. TREND (Trial on Reversing ENdothelial Dysfunction) investigated whether quinapril might improve endothelial dysfunction in normotensive patients with coronary artery disease and no heart failure, cardiomyopathy, or major lipid abnormalities so that confounding variables that affect endothelial dysfunction could be minimized. Methods and Results Using a double-blind, randomized, placebo-controlled design, we measured the effects of quinapril (40 mg daily) on coronary artery diameter responses to acetylcholine using quantitative coronary angiography. The primary response variable was the net change in the acetylcholine-provoked constriction of target segments between the baseline (prerandomization) and 6-month follow-up angiograms. The constrictive responses to acetylcholine were comparable in the placebo (n=54) and quinapril (n=51) groups at baseline. After 6 months, only the quinapril group showed significant net improvement in response to incremental concentrations of acetylcholine (4.5±3.0% [mean±SEM] versus −0.1±2.8% at 10 − 6 mol/L and 12.1±3.0% versus −0.8±2.9% at 10 − 4 mol/L, quinapril versus placebo, respectively; overall P =.002). Conclusions TREND shows that ACE inhibition with quinapril improved endothelial dysfunction in patients who were normotensive and who did not have severe hyperlipidemia or evidence of heart failure. These benefits of ACE inhibition are likely due to attenuation of the contractile effects and superoxide-generating effects of angiotensin II and to enhancement of endothelial cell release of nitric oxide secondary to diminished breakdown of bradykinin.
Dietary intake of fibre and risk of knee osteoarthritis in two US prospective cohorts
Authors: Zhaoli Dai, Jingbo Niu, Yuqing Zhang, Paul Jacques, David T Felson
Journal: Annals of the Rheumatic Diseases (2017)

Dietary fibre reduces body weight and inflammation both of which are linked with knee osteoarthritis (OA). We examined the association between fibre intake and risk of knee OA.We used data from the Osteoarthritis Initiative (OAI) of 4796 participants and Framingham Offspring Osteoarthritis Study (Framingham) of 1268 persons. Dietary intake of fibre was estimated at baseline, and incident radiographic OA (ROA) and symptomatic OA (SxOA) were followed annually until 48 months in OAI and assessed 9 years later in Framingham. Knee pain worsening was also examined in OAI. Generalised estimating equations were applied in multivariable regression models.In OAI, we identified 869 knees with SxOA, 152 knees with ROA and 1964 knees with pain worsening among 4051 subjects with valid dietary intake (baseline mean age: 61.2 years; mean body mass index (BMI): 28.6). In Framingham, 143 knees with SxOA and 176 knees with ROA among 971 such subjects (baseline mean age: 53.9 years; mean BMI: 27.0) were identified. In both cohorts, dietary total fibre was inversely associated with risk of SxOA (p trend <0.03) with significantly lower risk at the highest versus lowest quartile (OR (95% CI): 0.70 (0.52, 0.94) for OAI and 0.39 (0.17, 0.88) for Framingham). Furthermore, dietary total and cereal fibre were significantly inversely associated with knee pain worsening in OAI (p trend <0.02). No apparent association was found with ROA.Findings from two longitudinal studies consistently showed that higher total fibre intake was related to a lower risk of SxOA, while the relation to ROA was unclear.
Sixty seconds on . . . GP numbers
Authors: Nigel Hawkes
Journal: BMJ (2017)

Yes and no.

Take a deep breath: this is a statistical minefield. The decline to which you refer is a fall of 46 (40 085 to 40 039 reported by NHS Digital in England’s GP headcount excluding locums) between the end of last December and the end of March this year. But if we look at full …
Analysis of BRAF alterations and molecular profiling in glioblastoma and astrocytoma.
Authors: Nadia Faiq, Juliann Chmielecki, Michael Goldberg, Phil Stephens, Razelle Kurzrock, Santosh Kesari, David Eric Piccioni
Journal: Journal of Clinical Oncology (2015)

2074 Background: Although well characterized in pilocytic astrocytoma and pleomorphic xanthroastrocytoma, the prevalence of BRAF alterations in glioblastoma (GBM) and astrocytoma is not well established. Characterization of BRAF mutations in glioblastoma and astrocytoma may identify a subgroup of patients with sensitivity to BRAF inhibitors. Methods: DNA was extracted from 95 diffuse gliomas (grade II-IV) at our institution and an independent set of 714 gliomas, and was subjected to hybrid capture for 315 or 265 cancer-related genes plus select intronic regions. Sequencing was performed to a mean coverage depth of > 500x and analyzed for the presence of base substitutions, insertions/deletions, copy number alterations, and rearrangements. Results: 7 of 95 gliomas (7.4%) analyzed harbored BRAF alterations; 6 (6.3%) were identified with either a V600E mutation (3 GBM + 1 gliosarcoma) or a D594G mutation (2 GBM). One glioma with a BRAF rearrangement was identified (astrocytoma grade II). There were no alterations found in oligodendrogliomas. Molecular profiles in all 6 tumors with BRAF point mutations were similar; all were wild type for IDH1/2 and exhibited CDKN2A/B loss. Conversely, the BRAF rearrangement was IDH1 mutated and CDKN2A/B intact. To confirm the frequency of BRAF alterations, an independent database of 714 gliomas was queried. Thirty-four (4.8%) tumors were found to have BRAF alterations, including 24 BRAF point mutations. Of those, 96% (n = 23) were IDH1/2 wild type and 83% (n = 21) harbored CDKN2A/B loss. Conversely, BRAF rearrangements and amplifications (n = 10) did not share this profile. 40% harbored IDH1/2 mutations and only 40% displayed CDKN2A/B loss. In our patients, 5 of the 6 with BRAF point mutations are alive. The median overall survival is 28.8 months (10.7-40.6). One patient with recurrent GBM and V600E mutation was treated with the BRAF inhibitor vemurafenib with a PFS > 12 months. Conclusions: BRAF alterations occur in GBM and astrocytoma. BRAF point mutations are associated with a specific molecular profile, specifically IDH1/2 wild-type and CDKN2A/B loss. This profile identifies a molecular subgroup of gliomas that may exhibit improved survival and are amenable to targeted therapy with BRAF inhibitors.