bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of advancing age on clinical presentation, treatment efficacy and safety, and long-term outcome of pre-excitation syndromes: a retrospective cohort study of 961 patients included over a 25-year period
Authors: Brembilla-Perrot Béatrice , Olivier Arnaud , Sellal Jean-Marc , Manenti Vladimir , Brembilla Alice , Villemin Thibaut , Admant Philippe , Beurrier Daniel , Bozec Erwan , Girerd Nicolas 
Published: May 2016

ObjectivesThere are very little data on pre-excitation syndrome (PS) in the elderly. We investigated the influence of advancing age on clinical presentation, treatment and long-term outcome of PS.SettingSingle-centre retrospective study of patient files.ParticipantsIn all, 961 patients (72 patients ≥60 years (mean 68.5±6), 889 patients <60 years (mean 30.5±14)) referred for overt pre-excitation and indication for electrophysiological study (EPS) were followed for 5.3±5 years. Usual care included 24 h Holter monitoring, echocardiography and EPS. Patients underwent accessory pathway (AP) ablation if necessary.Primary and secondary outcome measuresOccurrence of atrial fibrillation (AF) or procedure-induced adverse event.ResultsElectrophysiological data and recourse to AP ablation (43% vs 48.5%, p=0.375) did not significantly differ between the groups. Older patients more often had symptomatic forms (81% vs 63%, p=0.003), history of spontaneous AF (8% vs 3%, p=0.01) or adverse presentation (poorly tolerated arrhythmias: 18% vs 7%, p=0.0009). In multivariable analysis, patients ≥60 years had a significantly higher risk of history of AF (OR=4.2, 2.1 to 8.3, p=0.001) and poorly tolerated arrhythmias (OR=3.8, 1.8 to 8.1, p=0.001). Age ≥60 years was associated with an increased major AP ablation complication risk (10% vs 1.9%, p=0.006). During follow-up, occurrence of AF (13.9% vs 3.6%, p<0.001) and incidence of poorly tolerated tachycardia (4.2% vs 0.6%, p=0.001) were more frequent in patients ≥60 years, although frequency of ablation failure or recurrence was similar (20% vs 15.5%, p=0.52). In multivariable analysis, patients ≥60 years had a significantly higher risk of AF (OR=2.9, 1.2 to 6.8, p≤0.01).ConclusionsIn this retrospective monocentre study, patients ≥60 years referred for PS work up appeared at higher risk of AF and adverse presentation, both prior and after the work up. These results suggest that, in elderly patients, the decision for EPS and AP ablation should be discussed in light of their suspected higher risk of events and ablation complications. However, these findings should be further validated in future prospective multicentre studies.
Prevalence and trends of sensitisation to aeroallergens in patients with allergic rhinitis in Guangzhou, China: a 10-year retrospective study
Authors: Wang Weihao , Huang Xuekun , Chen Zhuanggui , Zheng Rui , Chen Yulian , Zhang Gehua , Yang Qintai 
Published: May 2016

ObjectiveTo investigate the prevalence and trends of sensitisation to common aeroallergens among outpatients with allergic rhinitis (AR) in Guangzhou, China, over the past decade.DesignA retrospective study; linear-by-linear association and simple linear regression were used to determine the trends in the prevalence of aeroallergen sensitisation.SettingOne grade-A hospital in Guangzhou, the largest city in southern China.ParticipantsA total of 5486 patients (2297 males and 2489 females) who visited the ear, nose and throat outpatient clinic, from January 2005 to December 2014, were enrolled. All patients who presented with nasal hyper-reactive symptoms and who completed serological allergy testing, measuring specific IgE (sIgE) in the serum, were included. Among them, 4085 participants (2269 males and 1816 females) were diagnosed as being patients with AR.Outcome measuresPrevalence and trends of sensitisation to various types of aeroallergens were assessed.ResultsThe overall prevalence of sIgE-mediated sensitisation to aeroallergens in these patients with AR were as follows: 84.4% for house dust mites (HDMs), 23.4% for pet allergens, 21.1% for cockroaches, 9.1% for mould allergens, 7.7% for tree pollen and 6.0% for weed pollen. When all patients with nasal hyper-reactivity were stratified by decade of age, increasing age was associated with a decrease in sIgE positivity by ∼5.13% (95% CI −7.28% to −2.98%, p<0.01). Within the past decade, the prevalence of sensitisation to pet allergens in patients with AR increased at an annual rate of 1.3% (95% CI 0.85% to 1.67%, p<0.01).ConclusionsThis study demonstrated that HDMs comprised the most common aeroallergen in Guangzhou. The prevalence of sensitisation to aeroallergens decreased with increasing age. During the past decade, the prevalence of sensitisation to pet allergens showed an upward trend, suggesting an urgent need for its prevention and treatment.
Mechanical thrombectomy with the ERIC retrieval device: initial experience
Authors: Raoult Hélène , Redjem Hocine , Bourcier Romain , Gaultier-Lintia Alina , Daumas-Duport Benjamin , Ferré Jean-Christophe , Eugène François , Fahed Robert , Bartolini Bruno , Piotin Michel , Desal Hubert , Gauvrit Jean-Yves , Blanc Raphaël 
Published: May 2016

ObjectiveTo report our experience with the Embolus Retriever with Interlinked Cage (ERIC) stentriever for use in mechanical endovascular thrombectomy (MET).MethodsThirty-four consecutive patients with acute stroke (21 men and 13 women; median age 66 years) determined appropriate for MET were treated with ERIC and prospectively included over a 6-month period at three different centers. The ERIC device differs from typical stentrievers in that it is designed with a series of interlinked adjustable nitinol cages that allow for fast thrombus capture, integration, and withdrawal. The evaluated endpoints were successful revascularization (Thrombolysis in Cerebral Infarction (TICI) 2b–3) and good clinical outcomes at 3 months (modified Rankin Scale (mRS) 0–2).ResultsLocations of the occlusions included the middle cerebral artery (13 patients), terminal carotid artery (11 patients), basilar artery (1 patient), and tandem occlusions (9 patients). IV thrombolysis was performed in 20/34 (58.8%) patients. Median times from symptom onset to recanalization and from puncture to recanalization were 325.5 min (180–557) and 78.5 min (14–183), respectively. Used as the first-line device, ERIC achieved a successful recanalization in 20/24 (83.3%) patients. Successful recanalization was associated with lower National Institutes of Health Stroke Scale scores at 24 h (8±6.5 vs 21.5±2.1; p=0.008) and lower mRS at 3 months (2.7±2.1 vs 5.3±1.1; p=0.04). Three procedural complications and four asymptomatic hemorrhages were recorded. Good clinical outcomes at 3 months were seen in 15/31 (48.4%) patients.ConclusionsThe ERIC device is an innovative stentriever allowing fast, effective, and safe MET.
Leucocyte subset-specific type 1 interferon signatures in SLE and other immune-mediated diseases
Authors: Flint Shaun M , Jovanovic Vojislav , Teo Boon Wee , Mak Anselm , Thumboo Julian , McKinney Eoin F , Lee James C , MacAry Paul , Kemeny David M , Jayne David RW , Fong Kok Yong , Lyons Paul A , Smith Kenneth GC 
Published: May 2016

ObjectivesType 1 interferons (IFN-1) are implicated in the pathogenesis of systemic lupus erythematosus (SLE), but most studies have only reported the effect of IFN-1 on mixed cell populations. We aimed to define modules of IFN-1-associated genes in purified leucocyte populations and use these as a basis for a detailed comparative analysis.MethodsCD4+ and CD8+ T cells, monocytes and neutrophils were purified from patients with SLE, other immune-mediated diseases and healthy volunteers and gene expression then determined by microarray. Modules of IFN-1-associated genes were defined using weighted gene coexpression network analysis. The composition and expression of these modules was analysed.Results1150 of 1288 IFN-1-associated genes were specific to myeloid subsets, compared with 11 genes unique to T cells. IFN-1 genes were more highly expressed in myeloid subsets compared with T cells. A subset of neutrophil samples from healthy volunteers (HV) and conditions not classically associated with IFN-1 signatures displayed increased IFN-1 gene expression, whereas upregulation of IFN-1-associated genes in T cells was restricted to SLE.ConclusionsGiven the broad upregulation of IFN-1 genes in neutrophils including in some HV, investigators reporting IFN-1 signatures on the basis of whole blood samples should be cautious about interpreting this as evidence ofbona fideIFN-1-mediated pathology. Instead, specific upregulation of IFN-1-associated genes in T cells may be a useful biomarker and a further mechanism by which elevated IFN-1 contributes to autoimmunity in SLE.
Practice what you preach? An exploratory multilevel study on rheumatoid arthritis guideline adherence by rheumatologists
Authors: Lesuis N , den Broeder A A , Hulscher M E J L , van Vollenhoven R F 
Published: May 2016

ObjectivesTo assess variation in and determinants of rheumatologist guideline adherence in patients with rheumatoid arthritis (RA), in daily practice.MethodsIn this retrospective observational study, guideline adherence in the first year of treatment was assessed for 7 predefined parameters on diagnostics, treatment and follow-up in all adult patients with RA with a first outpatient clinic visit at the study centre, from September 2009 to March 2011. Variation in guideline adherence was assessed on parameter and rheumatologist level. Determinants for guideline adherence were assessed in patients (demographic characteristics, rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibody (aCCP) positivity, erythrocyte sedimentation rate, erosive disease, comorbidity and the number of available disease modifying anti-rheumatic drug (DMARD) treatment options) and rheumatologists (demographic and practice characteristics, guideline knowledge and agreement, outcome expectancy, cognitive bias, thinking style, numeracy and personality).ResultsA total of 994 visits in 137 patients with RA were reviewed. Variation in guideline adherence among parameters was present (adherence between 21% and 72%), with referral to the physician assistant as lowest scoring and referral to a specialised nurse as highest scoring parameter. Variation in guideline adherence among rheumatologists was also present (adherence between 22% and 100%). Patient sex, the number of DMARD options, presence of erosions, comorbidity, RF/aCCP positivity, type of patient and the rheumatologists' scientific education status were associated with adherence to 1 or more guideline parameters.ConclusionsGuideline adherence varied considerably among the guideline parameters and rheumatologists, showing that there is room for improvement. Guideline adherence in our sample was related to several patient and rheumatologist determinants.
Bakers' cyst and tibiofemoral abnormalities are more distinctive MRI features of symptomatic osteoarthritis than patellofemoral abnormalities
Authors: Visser A W , Mertens B , Reijnierse M , Bloem J L , de Mutsert R , le Cessie S , Rosendaal F R , Kloppenburg M 
Published: May 2016

ObjectiveTo investigate which structural MR abnormalities discriminate symptomatic knee osteoarthritis (OA), taking co-occurrence of abnormalities in all compartments into account.MethodsThe Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort aged 45–65 years. In 1285 participants (median age 56 years, 55% women, median body mass index (BMI) 30 kg/m2), MRI of the right knee were obtained. Structural abnormalities (osteophytes, cartilage loss, bone marrow lesions (BMLs), subchondral cysts, meniscal abnormalities, effusion, Baker's cyst) at 9 patellofemoral and tibiofemoral locations were scored following the knee OA scoring system. Symptomatic OA in the imaged knee was defined following the American College of Rheumatology criteria. Logistic ridge regression analyses were used to investigate which structural abnormalities discriminate best between individuals with and without symptomatic OA, crude and adjusted for age, sex and BMI.ResultsSymptomatic knee OA was present in 177 individuals. Structural MR abnormalities were highly frequent both in individuals with OA and in those without. Baker's cysts showed the highest adjusted regression coefficient (0.293) for presence of symptomatic OA, followed by osteophytes and BMLs in the medial tibiofemoral compartment (0.185–0.279), osteophytes in the medial trochlear facet (0.262) and effusion (0.197).ConclusionsBaker's cysts discriminate best between individuals with and without symptomatic knee OA. Structural MR abnormalities, especially in the medial side of the tibiofemoral joint and effusion, add further in discriminating symptomatic OA. Baker's cysts may present as a target for treatment.
Conjunctival flora of healthy and diseased eyes of grey seals (Halichoerus grypus): implications for treatment
Authors: Fleming M. , Bexton S. 
Published: May 2016

Ocular pathology is relatively common in stranded seals admitted to wildlife rehabilitation hospitals. Some have pre‐existing problems, while others develop eye problems in captivity, and in particular ulcerative keratitis, due to factors such as large prominent eyes, suboptimal water quality, trauma and infighting. Despite treatment, corneal ulcerations can rapidly progress to ‘melting’ ulcers with subsequent rupture of the globe. In this case series, 32 grey seals (Halichoerus grypus) had conjunctival swabs taken on admission to a UK wildlife hospital to identify ocular bacterial flora and nine had subsequent swabs taken after four weeks to see if this changed in captivity. Additionally, nine seals with ocular pathology were also swabbed. Although a wide range of bacteria were cultured on admission, the most common isolates were Gemella haemolysans, Escherichia coli and Clostridium perfringens. All ‘melting’ ulcers were associated with Pseudomonas aeruginosa, which suggests this bacterial species may be significant in the pathogenesis of progressive stromal ulceration in grey seals.
Rapalogs Efficacy Relies on the Modulation of Antitumor T-cell Immunity
Authors: Beziaud Laurent , Mansi Laura , Ravel Patrice , Marie-Joseph Elodie Lauret , Laheurte Caroline , Rangan Laurie , Bonnefoy Francis , Pallandre Jean-René , Boullerot Laura , Gamonet Clémentine , Vrecko Sindy , Queiroz Lise , Maurina Tristan , Mouillet Guillaume , Hon Thierry Nguyen Tan , Curtit Elsa , Royer Bernard , Gaugler Béatrice , Bayry Jagadeesh , Tartour Eric , Thiery-Vuillemin Antoine , Pivot Xavier , Borg Christophe , Godet Yann , Adotévi Olivier 
Published: May 2016

AbstractThe rapalogs everolimus and temsirolimus that inhibit mTOR signaling are used as antiproliferative drugs in several cancers. Here we investigated the influence of rapalogs-mediated immune modulation on their antitumor efficacy. Studies in metastatic renal cell carcinoma patients showed that everolimus promoted high expansion of FoxP3+Helios+Ki67+ regulatory CD4 T cells (Tregs). In these patients, rapalogs strongly enhanced the suppressive functions of Tregs, mainly in a contact-dependent manner. Paradoxically, a concurrent activation of spontaneous tumor-specific Th1 immunity also occurred. Furthermore, a high rate of Eomes+CD8+ T cells was detected in patients after a long-term mTOR inhibition. We found that early changes in the Tregs/antitumor Th1 balance can differentially shape the treatment efficacy. Patients presenting a shift toward decreased Tregs levels and high expansion of antitumor Th1 cells showed better clinical responses. Studies conducted in tumor-bearing mice confirmed the deleterious effect of rapalogs-induced Tregs via a mechanism involving the inhibition of antitumor T-cell immunity. Consequently, the combination of temsirolimus plus CCR4 antagonist, a receptor highly expressed on rapalogs-exposed Tregs, was more effective than monotherapy. Altogether, our results describe for the first time a dual impact of host adaptive antitumor T-cell immunity on the clinical effectiveness of rapalogs and prompt their association with immunotherapies. Cancer Res; 76(14); 4100–12. ©2016 AACR.
All Things in Moderation: Prevention of Intestinal Adenomas by DNA Hypomethylation
Authors: Lee Kwang-Ho , Laird Peter W. 
Published: May 2016

Abstract
DNA hypomethylation can prevent intestinal tumorigenesis, presumably by reducing epigenetic silencing of tumor-suppressor genes. A study in this issue by Sheaffer and colleagues challenges this notion by showing that severe DNA hypomethylation by tissue-specific Dnmt1 knockout can actually promote intestinal adenoma formation. Cancer Prev Res; 9(7); 509–11. ©2016 AACR.
See related article by Sheaffer, et al., p. 534
The Encounter of the Emblematic Tradition with Optics
Authors: Gómez López Susana 
Published: May 2016

In his excellent work Anamorphoses ou perspectives curieuses (1955), Baltrusaitis concluded the chapter on catoptric anamorphosis with an allusion to the small engraving by Hans Tröschel (1585–1628) after Simon Vouet’s drawing Eight satyrs observing an elephant reflected on a cylinder, the first known representation of a cylindrical anamorphosis made in Europe. This paper explores the Baroque intellectual and artistic context in which Vouet made his drawing, attempting to answer two central sets of questions. Firstly, why did Vouet make this image? For what purpose did he ideate such a curious image? Was it commissioned or did Vouet intend to offer it to someone? And if so, to whom? A reconstruction of this story leads me to conclude that the cylindrical anamorphosis was conceived as an emblem for Prince Maurice of Savoy. Secondly, how did what was originally the project for a sophisticated emblem give rise in Paris, after the return of Vouet from Italy in 1627, to the geometrical study of catoptrical anamorphosis? Through the study of this case, I hope to show that in early modern science the emblematic tradition was not only linked to natural history, but that insofar as it was a central feature of Baroque culture, it seeped into other branches of scientific inquiry, in this case the development of catoptrical anamorphosis. Vouet’s image is also a good example of how the visual and artistic poetics of the baroque were closely linked – to the point of being inseparable – with the scientific developments of the period.
Phase 3 Trials of Thermosensitive Ciprofloxacin Gel for Middle Ear Effusion in Children with Tubes
Authors: Park Albert H. , White David R. , Moss Jonathan R. , Bear Moraye , LeBel Carl 
Published: May 2016

ObjectiveTo investigate the efficacy, safety, and microbiology of a thermosensitive otic suspension of ciprofloxacin (OTO‐201) in children with bilateral middle ear effusion undergoing tympanostomy tube placement.Study DesignTwo randomized, double‐blind, sham‐controlled phase 3 trials. Patients were randomized to intratympanic OTO‐201 or sham.SettingChildren with bilateral middle ear effusion undergoing tympanostomy tube placement.Subjects/MethodsStudies evaluated 532 patients (6 months to 17 years old) in a combined analysis of efficacy (treatment failure: presence of otorrhea, otic or systemic antibiotic use, lost to follow‐up, missed visits), safety (audiometry, otoscopy, tympanometry), and microbiology.ResultsThere was a lower cumulative proportion of treatment failures in patients receiving OTO‐201 vs tympanostomy tubes alone (1) on days 4, 8, 15, and 29; (2) on day 15, primary end point (23.0% vs 45.1%; age‐adjusted odds ratio, 0.341; P <. 001; reduction in relative risk, 49%); and (3) on day 15, blinded‐assessor otorrhea treatment failure (7.0% vs 19.4%; age‐adjusted odds ratio, 0.303; P <. 001; reduction in relative risk, 64%). Per‐protocol and subgroup analyses (baseline demographics, pathogen type, culture status, effusion type, microbiologic response) supported these findings. There were no drug‐related serious adverse events; the most frequent treatment‐emergent adverse events in both groups were pyrexia, postoperative pain, nasopharyngitis, cough, and upper respiratory tract infection. OTO‐201 administration had no evidence of increased tube occlusion and no negative effect on audiometry, tympanometry, or otoscopy.ConclusionsCombined analysis of 2 phase 3 trials demonstrated a lower cumulative proportion of treatment failures through day 15 compared with TT alone when OTO‐201 was administered intratympanically for otitis media with bilateral middle ear effusion at time of tympanostomy tube placement.
Dystonia‐Causing Mutations as a Contribution to the Etiology of Spasmodic Dysphonia
Authors: de Gusmão Claudio M. , Fuchs Tania , Moses Andrew , Multhaupt‐Buell Trisha , Song Phillip C. , Ozelius Laurie J. , Franco Ramon A. , Sharma Nutan 
Published: May 2016

ObjectiveSpasmodic dysphonia is a focal dystonia of the larynx with heterogeneous manifestations and association with familial risk factors. There are scarce data to allow precise understanding of etiology and pathophysiology. Screening for dystonia‐causing genetic mutations has the potential to allow accurate diagnosis, inform about genotype‐phenotype correlations, and allow a better understanding of mechanisms of disease.Study DesignCross‐sectional study.SettingTertiary academic medical center.Subjects and MethodsWe enrolled patients presenting with spasmodic dysphonia to the voice clinic of our academic medical center. Data included demographics, clinical features, family history, and treatments administered. The following genes with disease‐causing mutations previously associated with spasmodic dysphonia were screened: TOR1A (DYT1), TUBB4 (DYT4), and THAP1 (DYT6).ResultsEighty‐six patients were recruited, comprising 77% females and 23% males. A definite family history of neurologic disorder was present in 15% (13 of 86). Average age (± standard deviation) of symptom onset was 42.1 ± 15.7 years. Most (99%; 85 of 86) were treated with botulinum toxin, and 12% (11 of 86) received oral medications. Genetic screening was negative in all patients for the GAG deletion in TOR1A (DYT1) and in the 5 exons currently associated with disease‐causing mutations in TUBB4 (DYT4). Two patients tested positive for novel/rare variants in THAP1 (DYT6).ConclusionGenetic screening targeted at currently known disease‐causing mutations in TOR1A, THAP1, and TUBB4 appears to have low diagnostic yield in sporadic spasmodic dysphonia. In our cohort, only 2 patients tested positive for novel/rare variants in THAP1. Clinicians should make use of genetic testing judiciously and in cost‐effective ways.