bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normative data for flow cytometry immunophenotyping of benign lymph nodes sampled by surgical biopsy
Authors: Scott Gregory David , Atwater Susan K , Gratzinger Dita A 
Published: September 2017

AimsTo create clinically relevant normative flow cytometry data for understudied benign lymph nodes and characterise outliers.MethodsClinical, histological and flow cytometry data were collected and distributions summarised for 380 benign lymph node excisional biopsies. Outliers for kappa:lambda light chain ratio, CD10:CD19 coexpression, CD5:CD19 coexpression, CD4:CD8 ratios and CD7 loss were summarised for histological pattern, concomitant diseases and follow-up course.ResultsWe generated the largest data set of benign lymph node immunophenotypes by an order of magnitude. B and T cell antigen outliers often had background immunosuppression or inflammatory disease but did not subsequently develop lymphoma.ConclusionsDiagnostic immunophenotyping data from benign lymph nodes provide normative ranges for clinical use. Outliers raising suspicion for B or T cell lymphoma are not infrequent (26% of benign lymph nodes). Caution is indicated when interpreting outliers in the absence of excisional biopsy or clinical history, particularly in patients with concomitant immunosuppression or inflammatory disease.
SERAC1 deficiency causes complicated HSP: evidence from a novel splice mutation in a large family
Authors: Roeben Benjamin , Schüle Rebecca , Ruf Susanne , Bender Benjamin , Alhaddad Bader , Benkert Tanja , Meitinger Thomas , Reich Selina , Böhringer Judith , Langhans Claus-Dieter , Vaz Frédéric M , Wortmann Saskia B , Marquardt Thorsten , Haack Tobias B , Krägeloh-Mann Ingeborg , Schöls Ludger , Synofzik Matthis 
Published: September 2017

ObjectiveTo demonstrate that mutations in the phosphatidylglycerol remodelling enzyme SERAC1 can cause juvenile-onset complicated hereditary spastic paraplegia (cHSP) clusters, thus adding SERAC1 to the increasing number of complex lipid cHSP genes.MethodsCombined genomic and functional validation studies (whole-exome sequencing, mRNA, cDNA and protein), biomarker investigations (3-methyl-glutaconic acid, filipin staining and phosphatidylglycerols PG34:1/PG36:1), and clinical and imaging phenotyping were performed in six affected subjects from two different branches of a large consanguineous family.Results5 of 6 affected subjects shared cHSP as a common disease phenotype. Three subjects presented with juvenile-onset oligosystemic cHSP, still able to walk several miles at age >10–20 years. This benign phenotypic cluster and disease progression is strikingly divergent to the severe infantile phenotype of all SERAC1 cases reported so far. Two family members showed a more multisystemic juvenile-onset cHSP, indicating an intermediate phenotype between the benign oligosystemic cHSP and the classic infantile SERAC1 cluster. The homozygous splice mutation led to loss of the full-length SERAC1 protein and impaired phosphatidylglycerol PG34:1/PG36:1 remodelling. These phosphatidylglycerol changes, however, were milder than in classic infantile-onset SERAC1 cases, which might partially explain the milder SERAC1 phenotype.ConclusionsOur findings add SERAC1 to the increasing list of complex lipid cHSP genes. At the same time they redefine the phenotypic spectrum of SERAC1 deficiency. It is associated not only with the severe infantile-onset ‘Methylglutaconic aciduria, Deafness, Encephalopathy, Leigh-like’ syndrome (MEGDEL syndrome), but also with oligosystemic juvenile-onset cHSP as part of the now unfolding SERAC1 deficiency spectrum.
A balance and proprioception intervention programme to enhance combat performance in military personnel
Authors: Funk Shany , Jacob T , Ben-Dov D , Yanovich E , Tirosh O , Steinberg N 
Published: September 2017

BackgroundOptimal functioning of the lower extremities under repeated movements on unstable surfaces is essential for military effectiveness. Intervention training to promote proprioceptive ability should be considered in order to limit the risk for musculoskeletal injuries. The aim of this study was to assess the effect of a proprioceptive intervention programme on static and dynamic postural balance among Israel Defense Forces combat soldiers.MethodsTwenty-seven male soldiers, aged 18–20 years, from a physical fitness instructor’s course, were randomly divided into two groups matched by age and army unit. The intervention group (INT) underwent 4 weeks of proprioceptive exercises for 10 min daily; the control group underwent 4 weeks of upper body stretching exercises for 10 min daily. All participants were tested pre and postintervention for both static and dynamic postural balance.ResultsSignificant interaction (condition*pre-post-test*group) was found for static postural balance, indicating that for the INT group, in condition 3 (on an unstable surface—BOSU), the post-test result was significantly better compared with the pretest result (p<0.05). Following intervention, the INT group showed significant correlations between static postural stability in condition 2 (eyes closed) and the dynamic postural stability (length of time walked on the beam following fatigue) (r ranged from 0.647 to 0.822; p<0.05).ConclusionsThe proprioceptive intervention programme for combat soldiers improved static postural balance on unstable surfaces, and improved the correlation between static postural balance in the eyes closed condition and dynamic postural balance following fatigue. Further longitudinal studies are needed to verify the relationship between proprioception programmes, additional weight bearing and the reduction of subsequent injuries in combat soldiers.
Safety, pharmacokinetics and pharmacodynamics of AMG 811, an anti-interferon-γ monoclonal antibody, in SLE subjects without or with lupus nephritis
Authors: Boedigheimer Michael J , Martin David A , Amoura Zahir , Sánchez-Guerrero Jorge , Romero-Diaz Juanita , Kivitz Alan , Aranow Cynthia , Chan Tak Mao , Chong Yip Boon , Chiu Kit , Wang Christine , Sohn Winnie , Arnold Gregory E , Damore Michael A , Welcher Andrew A , Sullivan Barbara A , Kotzin Brian L , Chung James B 
Published: September 2017

ObjectiveTo evaluate safety, pharmacokinetics and pharmacodynamics of anti-interferon (IFN)-γ monoclonal antibody AMG 811 in subjects with SLE without or with lupus nephritis (LN).MethodsIn this phase Ib, randomised, multiple-dose escalation study (NCT00818948), subjects without LN were randomised to subcutaneous AMG 811 (6, 20 or 60 mg) or placebo and subjects with LN were randomised to subcutaneous AMG 811 (20, 60 or 120 mg) or placebo every four weeks for three total doses. Outcomes included incidence of adverse events (AEs); pharmacokinetics; levels of serum proteins (CXCL-10, interleukin 18, monocyte chemotactic protein-1); changes in gene transcript profiles and clinical parameters (Safety of Estrogen in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores, proteinuria, anti-double-stranded DNA (anti-dsDNA) antibodies, C3 complement, C4 complement).ResultsFifty-six subjects enrolled (28 SLE without LN; 28 with LN). Baseline mean SELENA-SLEDAI scores were 2.2 and 12.0 for SLE subjects without and with LN, respectively. Most subjects reported an AE; no meaningful imbalances were observed between AMG 811 and placebo. Pharmacokinetic profiles were similar and mostly dose-proportional in subjects without or with LN. AMG 811 treatment reduced CXCL-10 protein levels and blood-based RNA IFN-γ Blockade Signature compared with placebo. Reductions were less pronounced and not sustained in subjects with LN, even at the highest dose tested, compared with subjects without LN. No effect on SELENA-SLEDAI scores, proteinuria, C3 or C4 complement levels, or anti-dsDNA antibodies was observed.ConclusionAMG 811 demonstrated favourable pharmacokinetics and acceptable safety profile but no evidence of clinical impact. IFN-γ-associated biomarkers decreased with AMG 811; effects were less pronounced and not sustained in LN subjects.Trial registration numberNCT00818948; results.
Impact of coil price knowledge by the operator on the cost of aneurysm coiling. A single center study
Authors: Finitsis Stephanos , Fahed Robert , Gaulin Ian , Roy Daniel , Weill Alain 
Published: September 2017

BackgroundEndovascular treatment of aneurysms with coils is among the most frequent treatments in interventional neuroradiology, and represents an important expense. Each manufacturer has created several types of coils, with prices varying among brands and coil types. The objective of this study was to assess the impact of cost awareness of the exact price of each coil by the operating physician on the total cost of aneurysm coiling.Materials and methodsThis was a comparative study conducted over 1 year in a single tertiary care center. The reference cohort and the experimental cohort consisted of all aneurysm embolization procedures performed during the first 6 months and the last 6 months, respectively. During the second period, physicians were given an information sheet with the prices of all available coils and were requested to look at the sheet during each procedure with the instruction to try to reduce the total cost of the coils used. Expenses related to the coiling procedures during each period were compared.Results77 aneurysms (39 ruptured) in the reference cohort and 73 aneurysms (36 ruptured) in the experimental cohort were treated, respectively. There was no statistically significant difference regarding aneurysm location and mean size. The overall cost of the coiling procedures, the mean number of coils used per procedure, and the median cost of each procedure did not differ significantly between the two cohorts.ConclusionAwareness of the precise price of coils by operators without any additional measure did not have a scientifically proven impact on the cost of aneurysm embolization.
Study of fall risk-increasing drugs in elderly patients before and after a bone fracture
Authors: Beunza-Sola Mónica , Hidalgo-Ovejero Ángel M , Martí-Ayerdi Jon , Sánchez-Hernández José Germán , Menéndez-García Miguel , García-Mata Serafín 
Published: September 2017

AbstractBackgroundAccidental falls have a significant economic and human impact. The use of certain drugs is one of the modifiable risk factors associated with these events.ObjectiveThe aim of this study was to determine the prevalence of use and to explore changes in treatment with fall-related drugs in patients over 65 years of age admitted as a result of a fall-related fracture.MethodsObservational and prospective study performed in a tertiary level hospital. A list of fall risk-increasing drugs (FRIDs) was drawn up. The main study variables were number and type of FRIDs prescribed at admission and 1 month after the fracture and number, type, treating physician and place where changes in FRIDs were implemented.ResultsIn total, 252 patients were included. At admission, 91.3% were receiving at least one FRID, mean daily use was 3.1 FRIDs and the most frequently prescribed FRIDs were diuretics (18%), renin–angiotensin system-acting agents (15.8%) and antidepressants (15%). One month later, mean daily use was 3.4 FRIDs (p=0.099) and a significant increase was detected in the use of hypnotics (p=0.003) and antidepressants (p=0.042). A total of 327 changes in treatment were recorded (1.3 changes/patient). Of the changes, 52.6% were new prescriptions, 72.2% occurred at discharge and 56.6% were ordered by a geriatrician.ConclusionsThe use of FRIDs among patients with a fall-related fracture is very high. This use rises 1 month after the fracture, significantly in the case of hypnotics and antidepressants.
Effect of celastrol on bone structure and mechanics in arthritic rats
Authors: Cascão Rita , Vidal Bruno , Jalmari Finnilä Mikko Arttu , Lopes Inês Pascoal , Teixeira Rui Lourenço , Saarakkala Simo , Moita Luis Ferreira , Fonseca João Eurico 
Published: September 2017

ObjectiveRheumatoid arthritis (RA) is characterised by chronic inflammation leading to articular bone and cartilage damage. Despite recent progress in RA management, adverse effects, lack of efficacy and economic barriers to treatment access still limit therapeutic success. Therefore, safer and less expensive treatments that control inflammation and bone resorption are needed. We have previously shown that celastrol is a candidate for RA treatment. We have observed that it inhibits both interleukin (IL)-1β and tumor necrosis factor (TNF) in vitro, and that it has anti-inflammatory properties and ability to decrease synovial CD68+ macrophages in vivo. Herein our goal was to evaluate the effect of celastrol in local and systemic bone loss.MethodsCelastrol was administrated intraperitoneally at a dose of 1 µg/g/day to female Wistar adjuvant-induced arthritic rats. Rats were sacrificed after 22 days of disease progression, and blood, femurs, tibiae and paw samples were collected for bone remodelling markers quantification, 3-point bending test, micro-CT analysis, nanoindentation and Fourier transform infrared spectroscopy measurements, and immunohistochemical evaluation.ResultsWe have observed that celastrol preserved articular structures and decreased the number of osteoclasts and osteoblasts present in arthritic joints. Moreover, celastrol reduced tartrate-resistant acid phosphatase 5b, procollagen type 1 amino-terminal propeptide and C terminal crosslinked telopeptide of type II collagen serum levels. Importantly, celastrol prevented bone loss and bone microarchitecture degradation. Celastrol also preserved bone nanoproperties and mineral content. Additionally, animals treated with celastrol had less fragile bones, as depicted by an increase in maximum load and yield displacement.ConclusionsThese results suggest that celastrol reduces both bone resorption and cartilage degradation, and preserves bone structural properties.
Patient burden of Sjögren’s: a comprehensive literature review revealing the range and heterogeneity of measures used in assessments of severity
Authors: Hammitt Katherine M , Naegeli April N , van den Broek Remon W M , Birt Julie A 
Published: September 2017

ContextThe severity of Sjögren’s syndrome has been evaluated using a wide variety of clinical measures and patient-reported outcomes (PROs). This may contribute to the lack of clarity concerning the burden of Sjögren’s from the patient perspective.ObjectiveTo perform a comprehensive peer-reviewed literature analysis of the patient aspects of Sjögren’s, focusing on PROs, to investigate the complexity underlying the evaluation of the syndrome and to elucidate the discordance between the different measures.MethodsWe searched Embase for articles published between January 2005 and September 2015. Research articles, clinical and diagnostic reviews, and validation studies with a focus on patient aspects of Sjögren’s were selected as the primary information source.Results157 articles met the eligibility criteria. A wide variety of assessment measures used to evaluate glandular, extraglandular and functional domains were observed. Many different, non-validated Visual Analogue Scales, with a wide range of anchor words, were used in the quantification of Sjögren’s disease burden, impeding comparisons between studies. Relatively few clinical trials of drug therapies used validated scales: European League Against Rheumatism Sjögren’s Syndrome Patient Reported Index was used most often for symptom assessment and 36 Item Short Form Survey for quality of life (QoL).ConclusionA wide range and diversity of measures are used to evaluate the patient burden of Sjögren’s; most are not validated for use in this disease. PRO endpoints, validated specifically in Sjögren’s, that demonstrate improvement are needed. These measures should focus on QoL aspects important to patients and will most likely involve gauging change in function rather than patient-reported symptoms.
Impact of tocilizumab monotherapy on patient-reported outcomes in patients with rheumatoid arthritis from two randomised controlled trials
Authors: Strand Vibeke , Michalska Margaret , Birchwood Christine , Pei Jinglan , Tuckwell Katie , Finch Rebecca , Gabay Cem , Kavanaugh Arthur , Jones Graeme 
Published: September 2017

ObjectiveTwo randomised controlled trials, AMBITION (NCT00109408) and ADACTA (NCT01119859), showed tocilizumab (TCZ) monotherapy superior to methotrexate (MTX) and adalimumab (ADA) monotherapy, respectively, for improving rheumatoid arthritis (RA) disease activity. This study compared the benefit of TCZ versus MTX or ADA monotherapy for improving patient-reported outcomes (PROs) in patients with RA.MethodsPROs included patient global assessment (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and Short Form-36 (SF-36) physical component summary (PCS) and mental component summary (MCS) and eight domain scores. Outcomes included proportions of patients reporting changes from baseline in PRO scores ≥minimum clinically important differences (MCID) and ≥age-matched and gender-matched normative values at 24 weeks.ResultsIn AMBITION, TCZ-treated patients reported significantly greater mean improvements in HAQ (−0.7 vs −0.5), FACIT-Fatigue (8.7 vs 5.7), SF-36 PCS (9.8 vs 7.8) and five SF-36 domains at week 24 than with MTX; 45.0%–84.0% of TCZ-treated patients reported improvements ≥MCID, and 24.3%–52.1% reported scores ≥normative values across all PROs versus 39.4%–81.8% and 14.5%–45.0%, respectively, with MTX. In ADACTA, TCZ-treated patients reported significantly greater improvements in PtGA (−42.3 vs −31.8), pain (−40.1 vs −28.7), SF-36 MCS (7.9 vs 5.0) and three SF-36 domains than with ADA; 57.7%–83.3% of TCZ-treated patients reported improvements ≥MCID, and 22.1%–49.3% reported scores ≥normative values across all PROs versus 13.6%–37.8%, respectively, with ADA.ConclusionsTCZ monotherapy resulted in more patients reporting clinically meaningful PRO improvements and PRO scores ≥normative values compared with MTX or ADA monotherapy.Trial registration numbersNCT00109408andNCT01119859; Post-results.
Delayed neutrophil apoptosis enhances NET formation in cystic fibrosis
Authors: Gray Robert D , Hardisty Gareth , Regan Kate H , Smith Maeve , Robb Calum T , Duffin Rodger , Mackellar Annie , Felton Jennifer M , Paemka Lily , McCullagh Brian N , Lucas Christopher D , Dorward David A , McKone Edward F , Cooke Gordon , Donnelly Seamas C , Singh Pradeep K , Stoltz David A , Haslett Christopher , McCray Paul B , Whyte Moira K B , Rossi Adriano G , Davidson Donald J 
Published: September 2017

BackgroundCystic fibrosis (CF) lung disease is defined by large numbers of neutrophils and associated damaging products in the airway. Delayed neutrophil apoptosis is described in CF although it is unclear whether this is a primary neutrophil defect or a response to chronic inflammation. Increased levels of neutrophil extracellular traps (NETs) have been measured in CF and we aimed to investigate the causal relationship between these phenomena and their potential to serve as a driver of inflammation. We hypothesised that the delay in apoptosis in CF is a primary defect and preferentially allows CF neutrophils to form NETs, contributing to inflammation.MethodsBlood neutrophils were isolated from patients with CF, CF pigs and appropriate controls. Neutrophils were also obtained from patients with CF before and after commencing ivacaftor. Apoptosis was assessed by morphology and flow cytometry. NET formation was determined by fluorescent microscopy and DNA release assays. NET interaction with macrophages was examined by measuring cytokine generation with ELISA and qRT-PCR.ResultsCF neutrophils live longer due to decreased apoptosis. This was observed in both cystic fibrosis transmembrane conductance regulator (CFTR) null piglets and patients with CF, and furthermore was reversed by ivacaftor (CFTR potentiator) in patients with gating (G551D) mutations. CF neutrophils formed more NETs and this was reversed by cyclin-dependent kinase inhibitor exposure. NETs provided a proinflammatory stimulus to macrophages, which was enhanced in CF.ConclusionsCF neutrophils have a prosurvival phenotype that is associated with an absence of CFTR function and allows increased NET production, which can in turn induce inflammation. Augmenting neutrophil apoptosis in CF may allow more appropriate neutrophil disposal, decreasing NET formation and thus inflammation.
CT scan incidental findings in trauma patients: does it impact hospital length of stay?
Authors: Andrawes Peter , Picon Antonio I , Shariff Masood A , Azab Basem , von Waagner Wolf , Demissie Seleshi , Fasanya Charles 
Published: September 2017

BackgroundCT scans are heavily relied on for assessment of solid organ injuries complementing clinical examination. These CT scans could also reveal pathologies not related to trauma called incidental findings. We aimed to evaluate the frequency of these findings and their outcome on hospital services.MethodsA retrospective chart review of prospectively collected data of the emergency department’s trauma database from January 2005 to December 2011 to evaluate incidental findings on CT scans on trauma admissions. These incidental findings were divided into three classes: class 1—minor degenerative, non-degenerative, normal variants or congenital finding that does not require further investigation or workup; class 2—findings not requiring urgent intervention with scheduled outpatient follow-up and class 3—all findings that require urgent evaluation/further investigation during the same hospital admission. One-year follow-up was done to review hospital length of stay, trauma clinic follow-up and post-trauma surgery.ResultsOf 1000 charts reviewed, 957 were selected after 43 patients were excluded due to incomplete documentation. Of the 957 patients, 385 (40%) were found to have incidental findings. A total of 560 incidental findings were found on the CT scan reports with one-third of patients having multiple findings (144 patients, 37.4%). The largest number of incidental findings were in class 2. The incidental group had significantly longer length of stay after adjusted multivariate analysis (8.7±0.48 vs 6.7±0.55, p=0.005).ConclusionThe incidental findings are commonly found during CT imaging in trauma centers and our rate was 40%. Appropriate documentation, communication and follow-up of those findings is necessary. A classification system for these findings practiced nationwide will aid in categorizing the urgency of continued follow-up. This also will help decrease the length of hospital stay and healthcare cost.Level of evidenceLevel 4