tbuckley/cabot-search huggingface dataset:
AB0156 The efficacy of alendronate in postmenopausical osteoporosis
Authors: J Fernández-Melón, M Bernad, A García-Aparicio, G Bonilla, ML Gonzalez, ME Martinez, E Martín-Mola
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> This is a prospective study of bone mineral density in postmenopausical women treated with alendronate. <h3>Objectives</h3> To evaluate the efficacy of alendronate in postmenopausical osteoporotic women for 1, 2 and 3 years. <h3>Methods</h3> In a prospective study, we included 98 women diagnosed of postmenopausical osteoporosis attended from 1997 to 2000. The mean age was 59.07 (SD: 6.68). Patients received alendronate 10 mg daily, they were allowed to take calcium and vitamine D supplementation. The subjects were assessed at baseline, 12, 24 and 36 months for bone mineral density (BMD) measurements and X-ray and every 6 months blood and urinary biochemistries and markers of bone turnover were done. <h3>Results</h3> Sixteen patients (16%) have dropped out because of adverse effects, the most common was gastrointestinal events. 34 (34.6%) patients had previous fractures (17 had spine fractures, 12 Colles´s fractures and one hip fracture). Three patients on treatment with alendronate had new fractures (1 spine, 1 scaphoid and one Colles´s fracture). 70, 24 and 7 subjects have completed one, two and three years of treatment, respectively. The results were analysed by Student´s t-test. Patients treated with alendronate for 1 year had significantly greater improvement in BMD at spine. The mean BMD at baseline was 0.373 vs 0.773 (p &lt; 0.005) and at hip 0.665 vs 0.643 at baseline (p &lt; 0.005). Patients who completed two years had similar values of BMD as the year before, the mean BMD was 0.745 at spine and 0.646 at hip. <h3>Conclusion</h3> Patients treated with alendronate for one year had significantly greater improvement in BMD at both the spine and hip.
Image Gallery: Merkel cell carcinoma under the rainbow
Authors: N. di Meo, S. Vernoni, M. Longone, G. Trevisan
Journal: British Journal of Dermatology (2017)

Funding sources: no external funding. Conflicts of interest: none to declare. Dear Editor, An 83‐year‐old man presented with a nodule located in the right fronto‐temporal area (a). Dermoscopic polarized examination showed rainbow‐patterned areas (yellow asterisks) surrounded by a reddish background; ectatic vessels were seen in the whole lesion (b,c). The histopathological examination, revealed a Merkel cell carcinoma (MCC) (chromogranin +, synaptophysin +, EMA+, S100–, TTF‐1–, CK7–CK20–) (d–f). Ectatic vascular structures were described in the whole lesion (d,e). The chaotic neoangiogenesis that characterizes MCC could explain the presence of the rainbow pattern in this kind of lesion. Its finding, usually recognizable in Kaposi sarcoma,1,2 could be useful to guide a diagnosis even in the case of MCC.
RV568, a narrow-spectrum kinase inhibitor with p38 MAPK-α and -γ selectivity, suppresses COPD inflammation
Authors: Catherine E. Charron, Paul Russell, Kazuhiro Ito, Simon Lea, Yasuo Kizawa, Charlie Brindley, Dave Singh
Journal: European Respiratory Journal (2017)

Novel anti-inflammatory approaches targeting chronically activated kinase pathways in chronic obstructive pulmonary disease (COPD) are needed. We evaluated RV568, a p38 mitogen-activated protein kinase-α and -γ and SRC family kinase inhibitor, in cellular and in vivo models relevant to COPD and examined its safety and efficacy in COPD patients. The anti-inflammatory activities of RV568 were tested in primary cultured monocytes, macrophages and bronchial epithelial cells and in vivo in lipopolysaccharide and cigarette smoke-exposed murine models. RV568 was evaluated in a 14-day trial in COPD patients. RV568 showed potent anti-inflammatory effects in monocytes and macrophages, which were often greater than those of corticosteroids or the p38 inhibitor Birb796. RV568 combined with corticosteroid had anti-inflammatory effects suggestive of a synergistic interaction in poly I:C-stimulated BEAS-2B cells and in the cigarette smoke model. In COPD patients, inhaled RV568 (50 µg and 100 µg) improved pre-bronchodilator forced expiratory volume in 1 s (69 mL and 48 mL respectively) and significantly reduced sputum malondialdehyde (p&lt;0.05) compared to placebo, although there were no changes in sputum cell counts. Adverse events during RV568 and placebo treatment were similar. RV568 shows potent anti-inflammatory effects on cell and animal models relevant to COPD. RV568 was well-tolerated and demonstrated a modest clinical benefit in a 14-day COPD clinical trial.
TCT-257 Influence of heart rate on the FFR measurement - experimental and clinical study
Authors: Przemyslaw Kwasiborski, Wojciech Czerwiński, Paweł Kowalczyk, Kamil Derbisz, Mateusz Kachel, Adam Janas, Piotr Buszman, Paweł Buszman, Krzysztof Milewski
Journal: Journal of the American College of Cardiology (2017)
Abstract 19774: Weight Confirmed as a Risk Factor for Atrial Fibrillation in 39,023 Subjects
Authors: Anthony J White, Philip Mottram
Journal: Circulation (2015)

Introduction: Several risk factors for atrial fibrillation (AF) are long established including age, hypertension and left atrial volume (LAV). A more recently appreciated risk factor for AF is obesity. Hypothesis: We hypothesize that increased weight associates independently with atrial fibrillation. Methods: The database of all trans-thoracic echocardiograms (TTE) performed in a single cardiology department was interrogated for the five year period January 1, 2010 - December 31, 2014. Cardiac rhythm, age, sex, LAV, height, weight, systolic and diastolic BP data were extracted. Duplicate studies were removed. Data were analysed according to cardiac rhythm (AF vs sinus rhythm (SR)) by univariate comparisons (t tests) and multivariate linear regression. Results: 39,023 studies were analysed [age 61±17 years, 52.8% male]. In 3,993 studies (10.2%) the cardiac rhythm was AF. The group with AF were older (74±11 vs 59±17 yrs, p&lt;10 -20 ), heavier (81.6±20.7 vs 78.6±20.0 kg, p&lt;10 -19 ), more likely male (58.9 vs 52.1%, p&lt;10 -15 ) and had larger LA volumes (71±33 vs 40±14 mL/m2, p&lt;10 -20 ) than those in SR. Height (166±11cm) was not different (p=0.69). A multivariate linear regression model was constructed incorporating age, LAV, weight, sex, diastolic and systolic BP (R 2 =0.28, p&lt;10 -20 ). In this model, weight was confirmed as an independent factor associated with AF (co-efficient 0.09, p&lt;10 -20 ). Conclusions: Patients with AF were 3.0 kg heavier than those in SR. Weight remained independently associated with AF in the multivariate model. These retrospective observational data lend support to recent compelling data from a prospective randomised clinical trial showing that weight loss improved control of AF.
TCT-198 Transcatheter Aortic Valve Replacement versus Conservative Management in Patients with Severe Aortic Stenosis and Advanced Kidney Disease
Authors: Guy Witberg, Tali Steinmetz, Avry Chagnac, Heftziba Green, Alexander Sagie, Benaya Rozen-Zvi, Ran Kornowski
Journal: Journal of the American College of Cardiology (2017)
Bruce Campbell Ogilvie
Authors: David Ogilvie
Journal: BMJ (2017)

Bruce Campbell Ogilvie was born in Edinburgh and educated at George Heriot’s School. After considering a variety of possible careers including forestry and meteorology, towards the end of his school years, he had the opportunity to spend time at his uncle’s clinics and subsequently decided to study medicine. He started at the University of Edinburgh in 1959, where he also played rugby for the medical school. After graduating, apart from a year in obstetrics and neonatology Bruce undertook his initial postgraduate training in general medicine in Galashiels, Edinburgh, and Kirkcaldy. He gained his membership of the Royal College of Physicians of Edinburgh with cardiology as his special subject, and as medical registrar in Kirkcaldy he helped establish one of the first coronary care units in a district general hospital in the UK.

The idea of the diagnostic detective poring over clues in a darkened room a …
TCT-519 TAVI versus SAVR in Patients with a History of Previous Cardiac Surgery: A National Inpatient Sample Database Analysis
Authors: Nikhil Nalluri, Varun Kumar, Shilpkumar Arora, Dixitha Anugula, Nileshkumar Patel, Deepak Asti, Sainath Gaddam, Anusha Chidharla, Bhavi Pandya, Emad Barsoum, Samer Saouma, Srinivas Duvvuri, Sushruth Edla, Gregory Maniatis, Roman Royzman, Frank Tamburrino, Ruben Kandov, James Lafferty, Mauricio Cohen, Chad Kliger
Journal: Journal of the American College of Cardiology (2017)
Association of Bone Mineral Density With the Risk of Intracranial Aneurysm
Authors: Yong-Won Shin, Kyung-Il Park, Jangsup Moon, Soon-Tae Lee, Kon Chu, Sang Kun Lee, Jae-Kyu Roh, Keun-Hwa Jung
Journal: JAMA Neurology (2017)

Disruption of extracellular matrix integrity is critically involved in both intracranial aneurysm and bone fragility. Furthermore, both intracranial aneurysm and osteoporosis have a female predominance, and sex hormones are considered to affect this discrepancy.To evaluate the association between bone mineral density and intracranial aneurysm.A cross-sectional study conducted with 14 328 patients who underwent brain magnetic resonance angiography and bone mineral densitometry as a part of a health examination at a specialized center for comprehensive health examination in Seoul, the largest metropolitan area in the Republic of Korea, between December 2004 and November 2015. After excluding patients with insufficient clinical information (n = 1102) and with ambiguous intracranial arterial lesion (n = 441), 12 785 were included in the analysis.Bone mineral density was measured at the lumbar vertebrae (L1 to L4), femur neck, and total hip using dual-energy x-ray absorptiometry.Multiple logistic regression or linear regression was used to examine the association between tertiles of bone mineral density and the presence, size, and multiplicity of intracranial aneurysms. In secondary analyses, we analyzed postmenopausal women and men 50 years and older (n = 8722) because they are particularly at risk of decreased bone mineral density.Among 12 785 patients in the study (7242 women [56.6%]; mean [SD] age, 54.8 [10.1] years) intracranial aneurysms were found in 472 patients (3.7%). Lower bone mineral density was associated with an increased risk of harboring intracranial aneurysm. In multivariable logistic regression analyses, odds ratios for the highest compared with the lowest bone mineral density tertile were 1.30 (95% CI, 1.03-1.64) in the lumbar spine, 1.30 (95% CI, 1.03-1.64) in the femoral neck, and 1.27 (95% CI, 1.01-1.60) in the total hip after adjusting for age, sex, and vascular risk factors. In a linear regression model adjusted for age, sex, and vascular risk factors, the lowest tertile of bone mineral density in the lumbar spine was associated with an increased log-transformed size of aneurysm (β, 0.196; SE, 0.047). In secondary analyses, these associations were more definite and a low T score (<-1 SD) was additionally associated with multiple aneurysms (OR, 1.84; 95% CI, 1.05-3.30) after adjusting for age, sex, and vascular risk factors.Bone mineral density may be associated with the presence, size, and multiplicity of intracranial aneurysm. The study findings provide evidence for shared pathophysiology between intracranial aneurysm and bone fragility.
Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate)
Authors: Dinesh Khanna, Christopher P Denton, Celia J F Lin, Jacob M van Laar, Tracy M Frech, Marina E Anderson, Murray Baron, Lorinda Chung, Gerhard Fierlbeck, Santhanam Lakshminarayanan, Yannick Allanore, Janet E Pope, Gabriela Riemekasten, Virginia Steen, Ulf Müller-Ladner, Helen Spotswood, Laura Burke, Jeffrey Siegel, Angelika Jahreis, Daniel E Furst
Journal: Annals of the Rheumatic Diseases (2017)

Objectives Assess the efficacy and safety of tocilizumab in patients with systemic sclerosis (SSc) in a phase II study. Methods Patients with SSc were treated for 48 weeks in an open-label extension phase of the faSScinate study with weekly 162 mg subcutaneous tocilizumab. Exploratory end points included modified Rodnan Skin Score (mRSS) and per cent predicted forced vital capacity (%pFVC) through week 96. Results Overall, 24/44 (55%) placebo-tocilizumab and 27/43 (63%) continuous-tocilizumab patients completed week 96. Observed mean (SD (95% CI)) change from baseline in mRSS was –3.1 (6.3 (–5.4 to –0.9)) for placebo and –5.6 (9.1 (–8.9 to–2.4)) for tocilizumab at week 48 and –9.4 (5.6 (–8.9 to –2.4)) for placebo-tocilizumab and –9.1 (8.7 (–12.5 to –5.6)) for continuous-tocilizumab at week 96. Of patients who completed week 96, any decline in %pFVC was observed for 10/24 (42% (95% CI 22% to 63%)) placebo-tocilizumab and 12/26 (46% (95% CI 27% to 67%)) continuous-tocilizumab patients in the open-label period; no patients had &gt;10% absolute decline in %pFVC. Serious infection rates/100 patient-years (95% CI) were 10.9 (3.0 to 27.9) with placebo and 34.8 (18.0 to 60.8) with tocilizumab during the double-blind period by week 48 and 19.6 (7.2 to 42.7) with placebo-tocilizumab and 0.0 (0.0 to 12.2) with continuous-tocilizumab during the open-label period. Conclusions Skin score improvement and FVC stabilisation in the double-blind period were observed in placebo-treated patients who transitioned to tocilizumab and were maintained in the open-label period. Safety data indicated increased serious infections in patients with SSc but no new safety signals with tocilizumab. Trial registration number NCT01532869; Results.
Correction to: Venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock post-cardiac arrest
Authors: Marc Pineton de Chambrun, Nicolas Bréchot, Guillaume Lebreton, Matthieu Schmidt, Guillaume Hekimian, Pierre Demondion, Jean-Louis Trouillet, Pascal Leprince, Jean Chastre, Alain Combes, Charles-Edouard Luyt
Journal: Intensive Care Medicine (2017)
“Culture of short termism” threatens health and care services, warn lords
Authors: Matthew Limb
Journal: BMJ (2017)

Leading members of the House of Lords have warned that the UK’s crisis in long term care will never be solved until social care funding is guaranteed to be sufficient for many years ahead.

Norman Warner, a former Labour health minister (2003-07), said that the failure to fund social care adequately over a long period had left the NHS facing its “biggest external threat.” He said that a 10% cut in social care funding in real terms since 2010 had put the NHS and social care in a “very bad place financially” for the future.

Warner is a member of the House of Lords committee looking at the long term sustainability of the NHS and adult …
Molecular staging of NSCLC using tumor specific autoantibodies
Authors: Kalpa Patel, Andres Jaramillo, John Coon, Michael Liptay, Anthony Kim, L. Faber, Philip Bonomi, Jeffrey Borgia
Journal: Cancer Research (2008)

4445    Introduction : The establishment of a blood test that can accurately assign disease stage based on a molecular phenotype for non-small cell lung cancer (NSCLC) would have substantial clinical value for the development of individualized patient care plans. Recently, serum autoantibody profiling has been actively explored as a means to provide novel biomarker candidates to aid in the early clinical diagnosis of NSCLC. Herein, we appraise our collection of NSCLC serum specimen for novel auto-antibodies that show promise for accurately discerning disease progression and prognosis.  Methods : Serum from NSCLC patients was divided into 2 groups based on the presence (n=36) or absence (n=38) of lymph node metastases. A control group consisting of age- and sex-matched patients with no lung disease (n=34) was used as a comparison. All serum specimens were collected preceding either tumor resection or chemotherapy and was compliant with institutional IRB policies. Screening for autoantibodies by one-dimensional immunoblotting consisted of resolving cellular lysates (150ug) from A549 cells via preparative SDS-PAGE, electroblotting on nitrocellulose, and blocking with 5% BSA. Membranes were then transferred to a Bio-Rad multi-screen apparatus and screened in duplicate with 20 distinct serum specimens (1:200 to 1: 800 dilutions) per membrane. After washing with PBST, the membranes were probed with HRP-conjugated goat anti-human IgG and developed using the ECL substrate. The banding pattern was documented via X-ray film and analyzed on a VersaDoc 4000 (BioRad).  Results : Although there were many commonalities to the banding profile of auto-antibodies detected amongst our patient groups, there were several points of distinction within 32 kDa to 98 kDa region. Most notable of these were two bands, one at 98 kDa and the other at 32 kDa, that were very prominent in the NSCLC lymph node positive group (15/36 and 21/36, respectively), but undetectable in our control group. Moreover, we revealed a doublet at 50 kDa in the lymph node positive group (26/36) that was not present in the control or the lymph node negative group. Although the protein masses at 32 kDa is consistent with mass of the previously reported NY-ESO-1 auto-antigen, from our surveys of the literature, the 50 kDa and 98 kDa auto-antigens appear to be novel targets. These will be verified by mass spectrometry in future studies.  Conclusions:  Herein we reveal several tumor-specific auto-antibodies that show promise for improving our ability to stage NSCLC patients. Interestingly, these auto-antibodies are primarily associated with disease with lymph node involvement, which is the prominent feature used to assign prognosis. Our current efforts are focused on identifying the auto-antigens via mass spectrometry and confirming the results of this analysis on additional cell lines.
Attenuation of Myeloid-Specific TGFβ Signaling Induces Inflammatory Cerebrovascular Disease and Stroke
Authors: M. Christine Hollander, Lawrence L. Latour, Dan Yang, Hiroki Ishii, Zhiguang Xiao, Yongfen Min, Abhik Ray-Choudhury, Jeeva Munasinghe, Anand S. Merchant, P. Charles Lin, John Hallenbeck, Manfred Boehm, Li Yang
Journal: Circulation Research (2017)

Cryptogenic strokes, those of unknown cause, have been estimated as high as 30% to 40% of strokes. Inflammation has been suggested as a critical etiologic factor. However, there is lack of experimental evidence.In this study, we investigated inflammation-associated stroke using a mouse model that developed spontaneous stroke because of myeloid deficiency of TGF-β (transforming growth factor-β) signaling.We report that mice with deletion of Tgfbr2 in myeloid cells (Tgfbr2Myeko) developed cerebrovascular inflammation in the absence of significant pathology in other tissues, culminating in stroke and severe neurological deficits with 100% penetrance. The stroke phenotype can be transferred to syngeneic wild-type mice via Tgfbr2Myeko bone marrow transplant and can be rescued in Tgfbr2Myeko mice with wild-type bone marrow. The underlying mechanisms involved an increased type 1 inflammation and cerebral endotheliopathy, characterized by elevated NF-κB (nuclear factor-κB) activation and TNF (tumor necrosis factor) production by myeloid cells. A high-fat diet accelerated stroke incidence. Anti-TNF treatment, as well as metformin and methotrexate, which are associated with decreased stroke risk in population studies, delayed stroke occurrence.Our studies show that TGF-β signaling in myeloid cells is required for maintenance of vascular health and provide insight into inflammation-mediated cerebrovascular disease and stroke.
Phase Ib Study of Immune Biomarker Modulation with Neoadjuvant Cetuximab and TLR8 Stimulation in Head and Neck Cancer to Overcome Suppressive Myeloid Signals
Authors: Gulidanna Shayan, Benjamin A. Kansy, Sandra P. Gibson, Raghvendra M. Srivastava, James Kyle Bryan, Julie E. Bauman, James Ohr, Seungwon Kim, Umamaheswar Duvvuri, David A. Clump, Dwight E. Heron, Jonas T. Johnson, Robert M. Hershberg, Robert L. Ferris
Journal: Clinical Cancer Research (2017)

Abstract Purpose: The response rate of patients with head and neck squamous cell carcinoma (HNSCC) to cetuximab therapy is only 15% to 20%, despite frequent EGFR overexpression. Because immunosuppression is common in HNSCC, we hypothesized that adding a proinflammatory TLR8 agonist to cetuximab therapy might result in enhanced T-lymphocyte stimulation and anti–EGFR-specific priming. Experimental Design: Fourteen patients with previously untreated HNSCC were enrolled in this neoadjuvant trial and treated preoperatively with 3 to 4 weekly doses of motolimod (2.5 mg/m2) and cetuximab. Correlative tumor and peripheral blood specimens were obtained at baseline and at the time of surgical resection and analyzed for immune biomarker changes. Preclinical in vitro studies were also performed to assess the effect of cetuximab plus motolimod on myeloid cells. Results: TLR8 stimulation skewed monocytes toward an M1 phenotype and reversed myeloid-derived suppressor cell (MDSC) suppression of T-cell proliferation in vitro. These data were validated in a prospective phase Ib neoadjuvant trial, in which fewer MDSC and increased M1 monocyte infiltration were found in tumor-infiltrating lymphocytes. Motolimod plus cetuximab also decreased induction of Treg and reduced markers of suppression, including CTLA-4, CD73, and membrane-bound TGFβ. Significantly increased circulating EGFR-specific T cells were observed, concomitant with enhanced CD8+ T-cell infiltration into tumors. These T cells manifested increased T-cell receptor (TCR) clonality, upregulation of the costimulatory receptor CD27, and downregulation of inhibitory receptor TIGIT. Conclusions: Enhanced inflammatory stimulation in the tumor microenvironment using a TLR agonist overcomes suppressive myeloid and regulatory cells, enhancing the cellular antitumor immune response by therapeutic mAb in HNSCC. Clin Cancer Res; 24(1); 62–72. ©2017 AACR.
University of Birmingham: an innovative Masters of Exercise and Sports Medicine in partnership with the Football Association (Continuing Professional Development series)
Authors: Adam G Culvenor
Journal: British Journal of Sports Medicine (2017)

School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.

Master of Science (MSc) in Exercise and Sports Medicine (Football).

Sports medicine within football in the UK and throughout the world remains a developing specialty. Although the medical team generally ranks poorly in the hierarchy of elite-level football teams, team success is highly influenced by injuries and player health.1 With a particular focus on football medicine, the MSc in Exercise and Sports Medicine at the University of Birmingham enables demonstration of advanced practice in football medicine and leadership within a multidisciplinary team providing clinical management in football, and enhancing employability in this, and the wider, sports medicine setting.2 

Setting itself apart from other Sports and Exercise Medicine postgraduate programmes, the MSc in Exercise and Sports Medicine (Football) is delivered in partnership with the Football Association, English football’s governing body. The MSc programme has been developed for UK and international physiotherapists and medical doctors working within, or interested in moving into, football medicine.

The MSc …
Reversal of Glaucoma Hemifield Test Results and Visual Field Features in Glaucoma
Authors: Mengyu Wang, Louis R. Pasquale, Lucy Q. Shen, Michael V. Boland, Sarah R. Wellik, Carlos Gustavo De Moraes, Jonathan S. Myers, Hui Wang, Neda Baniasadi, Dian Li, Rafaella Nascimento E. Silva, Peter J. Bex, Tobias Elze
Journal: Ophthalmology (2017)