Association of ultrasound-confirmed axillary artery vasculitis and clinical outcomes in giant cell arteritis.

OBJECTIVES: The aim of this observational study was to compare clinical outcomes including glucocorticoid treatment and relapses between giant cell arteritis (GCA) patients with (axGCA) and without axillary artery involvement (non-axGCA). METHODS: Axillary artery ultrasound was performed in 101 GCA patients at multiple time points. Patients with signs of vasculitis of the axillary arteries at baseline were compared to patients without signs of axillary artery involvement. Cumulative GC doses and relapse rates were calculated as well as survival curves to compare the time until GC discontinuation and occurrence of the first clinical relapse. A linear mixed model was used to assess the effect of a clinical relapse on the intima media thickness (IMT) in axGCA patients. RESULTS: Sixty-seven patients were classified as axGCA, 34 as non-axGCA patients. Compared with non-axGCA, axGCA patients yielded a higher (albeit not significant) median time until GC discontinuation (42 months (95% CI: 33-84) vs 30 months (95% CI: 21-42), p=0.060) and median cumulative GC dose (6801mg (range 1748-34169) vs 5633mg (range: 2553-19967), p=0.051). Time until the first relapse (axGCA: 12 months (95% CI: 8-42) vs non-axGCA: 13.5 months (95% CI: 6-27), p=0522) and relapse rates (2 (range: 0-16) vs 1 (range: 0-13), p=0.67) were similar in both groups. Relapses resulted in an increase of the IMT by 0.18mm (95% CI: 0.07-0.30, p=0.003). CONCLUSION: Patients with axGCA have a trend towards longer treatment duration and higher GC requirements as compared to non-axGCA patients. A relapse leads to an increase of the IMT by 0.18mm.

The accuracy of diagnostic Imaging techniques in patients with a suspected Fracture-related Infection (IFI) trial: study protocol for a prospective multicenter cohort study.

INTRODUCTION: The optimal diagnostic imaging strategy for fracture-related infection (FRI) remains to be established. In this prospective study, the three commonly used advanced imaging techniques for diagnosing FRI will be compared. Primary endpoints are (1) determining the overall diagnostic performances of white blood cell (WBC) scintigraphy, fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) in patients with suspected FRI and (2) establishing the most accurate imaging strategy for diagnosing FRI. METHODS AND ANALYSIS: This study is a non-randomised, partially blinded, prospective cohort study involving two level 1 trauma centres in The Netherlands. All adult patients who require advanced medical imaging for suspected FRI are eligible for inclusion. Patients will undergo all three investigational imaging procedures (WBC scintigraphy, FDG-PET and MRI) within a time frame of 14 days after inclusion. The reference standard will be the result of at least five intraoperative sampled microbiology cultures, or, in case of no surgery, the clinical presence or absence of infection at 1 year follow-up. Initially, the results of all three imaging modalities will be available to the treating team as per local protocol. At a later time point, all scans will be centrally reassessed by nuclear medicine physicians and radiologists who are blinded for the identity of the patients and their clinical outcome. The discriminative ability of the imaging modalities will be quantified by several measures of diagnostic accuracy. ETHICS AND DISSEMINATION: Approval of the study by the Institutional Review Board has been obtained prior to the start of this study. The results of this trial will be disseminated by publication of peer-reviewed manuscripts, presentation in abstract form at scientific meetings and data sharing with other investigators through academically established means. TRIAL REGISTRATION NUMBER: The IFI trial is registered in the Netherlands Trial Register (NTR7490).

Hallazgos capilaroscópicos en niños sanos / Capillary findings in healthy children

RESUMEN En el niño, la microcirculación cutánea (MCC) experimenta cambios desde sus primeros días de vida hasta la adolescencia. Mediante la video capilaroscopia (VC), se puede acceder a la visualización in vivo e incruenta de la MCC, en niños de cualquier edad. El sitio de elección es el pliegue peri ungular de los dedos de las manos. Se observan las asas capilares, dispuestas en corona sobre la matriz peri ungular y el plexo vascular superficial. Los recién nacidos presentan una red primitiva. Posteriormente, evolucionaalcanzando alrededor de los 10 años, los parámetros similares al adulto.El conocimiento de los parámetros de la MCC preservada en niños,será de gran importancia en la exploración diagnóstica de las patologías que afectan este territorio vascular, como las enfermedades reumáticas.

SUMMARY The child's skin microcirculation (MCC) undergoes changes from the first days of life until adolescence. Through video capillaroscopy (VC), in vivo and non-invasive visualization of the CCM is accessed in children of any age. The site of the election is the nail fold of the fingers of the hands. The capillary loops arranged in a crown over the nail matrix and the superficial vascular plexus are observed. The newborns present a primitive network, which later evolves reaching around 10 years the parameters similar to the adult. There are structural differences in MCC if the findings in children are compared with those of adults. In children the capillary density per linear millimeter is lower, the tortuosity index is higher, the superficial vascular plexus is more visible and bizarre capillary forms are found Knowledge of the parameters of MCC preserved in children will be of great importance in the diagnostic exploration of pathologies that affect this vascular territory such as rheumatic diseases.

Bayesian pharmacokinetic-guided prophylaxis with recombinant factor VIII in severe or moderate haemophilia A.

INTRODUCTION: Personalised pharmacokinetics (PK) using Bayesian analysis with limited sampling is assumed to help to optimise prophylaxis in haemophilia A (HA) patients. MATERIALS AND METHODS: Our prospective, observational study analysed the influence of PK parameters on clinical variables (bleeding rates, joint status, adherence, and consumption) using myPKFiT® in a cohort of twenty-one severe and moderate HA patients on prophylaxis with recombinant FVIII (Advate®) in two periods of one year, the first before PK-based tailoring and the second after PK-guided prophylaxis. Intra-individual and inter-individual coefficients of variation (CV) of half-life (t1/2) were calculated. RESULTS: A total of 73 PK estimations were performed in both periods, resulting in 17.2% inter-individual CV in mean t1/2, and 4.9% intra-individual CV. Before PK-based tailoring a significant association between joint bleeds and t1/2 was found (P = 0.010), especially in patients with short t1/2. This finding was reproduced (P = 0.013) after withdrawal of two patients with bleeding phenotype related to their advanced arthropathy but normal t1/2 and trough levels. Patients with joint bleeds weighed less (P = 0.039) and required higher doses (P = 0.032) than patients with zero joint bleeds. These associations were not observed in the second period after the adoption of PK-guided prophylaxis. There were no differences between the two periods, although a tendency to fewer spontaneous bleeds was suggested after PK-based tailoring. CONCLUSIONS: PK-guided prophylaxis facilitates an adequate level of bleeding control in patients with HA, maintaining clinical variables and patient convenience in an integrative manner, without increasing FVIII consumption.

Diagnostic accuracy of serum inflammatory markers in late fracture-related infection: a systematic review and meta-analysis.

AIMS: To assess the diagnostic value of C-reactive protein (CRP), leucocyte count (LC), and erythrocyte sedimentation rate (ESR) in late fracture-related infection (FRI). MATERIALS AND METHODS: PubMed, Embase, and Cochrane databases were searched focusing on the diagnostic value of CRP, LC, and ESR in late FRI. Sensitivity and specificity combinations were extracted for each marker. Average estimates were obtained using bivariate mixed effects models. RESULTS: A total of 8284 articles were identified but only six were suitable for inclusion. Sensitivity of CRP ranged from 60.0% to 100.0% and specificity from 34.3% to 85.7% in all publications considered. Five articles were pooled for meta-analysis, showing a sensitivity and specificity of 77.0% and 67.9%, respectively. For LC, this was 22.9% to 72.6%, and 73.5% to 85.7%, respectively, in five articles. Four articles were pooled for meta-analysis, resulting in a 51.7% sensitivity and 67.1% specificity. For ESR, sensitivity and specificity ranged from 37.1% to 100.0% and 59.0% to 85.0%, respectively, in five articles. Three articles were pooled in meta-analysis, showing a 45.1% sensitivity and 79.3% specificity. Four articles analyzed the value of combined inflammatory markers, reporting an increased diagnostic accuracy. These results could not be pooled due to heterogeneity. CONCLUSION: The serum inflammatory markers CRP, LC, and ESR are insufficiently accurate to diagnose late FRI, but they may be used as a suggestive sign in its diagnosis.

High diagnostic accuracy of white blood cell scintigraphy for fracture related infections: Results of a large retrospective single-center study.

INTRODUCTION: White blood cell (WBC) scintigraphy for diagnosing fracture-related infections (FRIs) has only been investigated in small patient series. Aims of this study were (1) to establish the accuracy of WBC scintigraphy for diagnosing FRIs, and (2) to investigate whether the duration of the time interval between surgery and WBC scintigraphy influences its accuracy. PATIENTS AND METHODS: 192 consecutive WBC scintigraphies with 99mTc-HMPAO-labelled autologous leucocytes performed for suspected peripheral FRI were included. The golden standard was based on the outcome of microbiological investigation in case of surgery, or - when these were not available - on clinical follow-up of at least six months. The discriminative ability of the imaging modalities was quantified by several measures of diagnostic accuracy. A multivariable logistic regression analysis was performed to identify predictive variables of a false-positive or false-negative WBC scintigraphy test result. RESULTS: WBC scintigraphy had a sensitivity of 0.79, a specificity of 0.97, a positive predicting value of 0.91, a negative predicting value of 0.93 and a diagnostic accuracy of 0.92 for detecting an FRI in the peripheral skeleton. The duration of the interval between surgery and the WBC scintigraphy did not influence its diagnostic accuracy; neither did concomitant use of antibiotics or NSAIDs. There were 11 patients with a false-negative (FN) WBC scintigraphy, the majority of these patients (n = 9, 82%) suffered from an infected nonunion. Four patients had a false-positive (FP) WBC scintigraphy. CONCLUSIONS: WBC scintigraphy showed a high diagnostic accuracy (0.92) for detecting FRIs in the peripheral skeleton. Duration of the time interval between surgery for the initial injury and the WBC did not influence the results which indicate that WBC scintigraphy is accurate shortly after surgery.

Transfection of bovine fetal fibroblast with polyethylenimine (PEI) nanoparticles: effect of particle size and presence of fetal bovine serum on transgene delivery and cytotoxicity.

The development of efficient transfection protocols for livestock cells is crucial for implementation of cell-based transgenic methods to produce genetically modified animals. We synthetized fully deacylated linear 22, 87 and 217 kDa polyethylenimine (PEI) nanoparticles and compared their transfection efficiency and cytotoxicity to commercial branched 25 kDa PEI and linear 58 kDa poly(allylamine) hydrochloride. We studied the effect of PEI size and presence of serum on transfection efficiency on primary cultures of bovine fetal fibroblasts and established cells lines (HEK 293 and Hep G2). We found that transfection efficiency was affected mainly by polymer/pDNA ratio and DNA concentration and in less extent by PEI MW. In bovine fibroblast, preincubation of PEI nanoparticles with fetal bovine serum (FBS) greatly increased percentage of cells expressing the transgene (up to 82%) while significantly decreased the polymer cytotoxic effect. 87 and 217 kDa PEI rendered the highest transfection rates in HEK 293 and Hep G2 cell lines (>50% transfected cells) with minimal cell toxicity. In conclusion, our results indicate that fully deacylated PEI of 87 and 217 kDa are useful DNA vehicles for non-viral transfection of primary cultures of bovine fetal fibroblast and HEK 293 and Hep G2 cell lines.

Hallazgos capilaroscópicos patológicos previos al desarrollo de lupus eritematoso sistémico / Pathologic capillaroscopic findings before systemic lupus erythematous development

La capilaroscopía periungular es una técnica de estudio, de la microcirculación cutánea in vivo. Es de elección en el diagnóstico diferencial entre Raynaud primario y secundario. Presentamos la descripción de los hallazgos capilaroscópicos mediante imágenes, en una adolescente que padece fenómeno de Raynaud. Se hallan alteraciones estructurales y funcionales de los capilares. En los meses posteriores la paciente desarrolla lupus eritematoso sistémico. La presencia de estos hallazgos previos al desarrollo de enfermedad lúpica, no es frecuente.

Nailfold capillaroscopy is a technique to visualize the skin microcirculation in vivo. This is of the utmost importance to establish the differential diagnosis between primary and secondary Raynaud. We hereby present the capillaroscopic image of the alterations, both structural and functional, detected in a female adolescent with Raynaud's phenomenon. In the next months the patient developed a systemic lupus erythematosus. The presence of these prior to the development of lupus disease is rare findings.

Simultaneous Measurement of Fluorescence, Conversion and Physical/mechanical Properties for Monitoring Bulk and Localized Photopolymerization Reactions in Heterogeneous Systems.

An FT-NIR spectrometer, rheometer and fluorescence spectrophotometer were coupled for the real-time monitoring of polymerization reactions, allowing the simultaneous tracking of polymerization kinetics, storage modulus as well as fluorescence. In this study, a methacrylate functionalized dansyl chromophore (DANSMA) was synthesized and two different nanogels were made from urethane dimethacrylate and isobornyl methacrylate. Two series of resin formulations were prepared using the DANSMA probe, ethoxylated bisphenol A dimethacrylate as the matrix monomer, Irgacure® 651 as the initiator and the dispersed, monomer-swollen nanogels to give clear UV-curable resins. Placement of the fluorescent probe either throughout the resin or linked into the nanogel before its dispersion in the matrix provides a tool to study how the nanogel structure affects local network development by means of fluorescence from the DANSMA probe. We demonstrate the potential of this new technique using a composite as the two phase system (resin and polymerizable nanogel) including a dansyl derivative as a polymerizable probe to follow the reactions that are taking places in both phases.

mRNA and microRNA analysis reveals modulation of biochemical pathways related to addiction in the ventral tegmental area of methamphetamine self-administering rats.

BACKGROUND: Methamphetamine is a highly addictive central nervous system stimulant with increasing levels of abuse worldwide. Alterations to mRNA and miRNA expression within the mesolimbic system can affect addiction-like behaviors and thus play a role in the development of drug addiction. While many studies have investigated the effects of high-dose methamphetamine, and identified neurotoxic effects, few have looked at the role that persistent changes in gene regulation play following methamphetamine self-administration. Therefore, the aim of this study was to identify RNA changes in the ventral tegmental area following methamphetamine self-administration. We performed microarray analyses on RNA extracted from the ventral tegmental area of Sprague-Dawley rats following methamphetamine self-administration training (2 h/day) and 14 days of abstinence. RESULTS: We identified 78 miRNA and 150 mRNA transcripts that were differentially expressed (fdr adjusted p < 0.05, absolute log2 fold change >0.5); these included genes not previously associated with addiction (miR-125a-5p, miR-145 and Foxa1), loci encoding receptors related to drug addiction behaviors and genes with previously recognized roles in addiction such as miR-124, miR-181a, DAT and Ret. CONCLUSION: This study provides insight into the effects of methamphetamine on RNA expression in a key brain region associated with addiction, highlighting the possibility that persistent changes in the expression of genes with both known and previously unknown roles in addiction occur.

Euroforgen-NoE collaborative exercise on LRmix to demonstrate standardization of the interpretation of complex DNA profiles.

There has been very little work published on the variation of reporting practices of mixtures between laboratories, but it has been previously demonstrated that there is little consistency. This is because there is no current uniformity of practice, so different laboratories will operate using different rules. The interpretation of mixtures is not solely a matter of using some software to provide 'an answer'. An assessment of a case will usually begin with a consideration of the circumstances of a crime. Assumptions made about the numbers of contributors follow from an examination of the electropherogram(s)--and these may differ between the prosecution and the defence hypotheses. There may be a necessity to evaluate several sets of hypotheses for any given case if the circumstances are uncertain. Once the hypotheses are formulated, the mathematical analysis is complex and can only be accomplished by the use of specialist software. In order to obtain meaningful results, it is essential that scientists are trained, not only in the use of the software, but also in the methodology to understand the likelihood ratio concept that is used. The Euroforgen-NoE initiative has developed a training course that utilizes the LRmix program to carry out the calculations. This software encompasses the recommendations of the ISFG DNA commissions on mixture interpretation and is able to interpret samples that may come from two or more contributors and may also be partial profiles. Recently, eighteen different laboratories were trained in the methodology. Afterwards they were asked to independently analyze two different cases with partial mixture DNA evidence and to write a statement court-report. We show that by introducing a structured training programme, it is possible to demonstrate, for the first time, that a high degree of standardization, leading to uniformity of results can be achieved by participating laboratories.

Lipid peroxidation affects red blood cells membrane properties in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune, chronic inflammatory, non-organ specific disease with an important morbimortality affecting several organs and systems. Oxidative stress is a well documented mechanism of red blood cells (RBC) mechanical impairment. Free radicals could produced, through lipid peroxidation, physical and chemical alterations in the cellular membrane properties modifying its composition, packing and lipid distribution on the membrane erythrocyte. The aim of the present work is to study the lipid peroxidation in the RBC membrane in SLE patients (n = 42) affecting so far the lipid membrane fluidity and erythrocyte deformability in comparison with healthy controls (n = 52). Malonildialdehyde (MDA) is a subrogate assessing lipidic peroxidation, rigidity index estimating erythrocyte deformability and the anisotropy coefficient estimating lipid membrane fluidity were used. Our results show that MDA values are increased, while erythrocyte deformability and membrane fluidity are significantly decreased in erythrocyte membrane from SLE patients in comparison with normal controls. The association of thiobarbituric acid reactive substances (TBARS) with membrane lipid fluidity and erythrocyte deformability confirms that the damage of membrane properties is produced by lipid peroxidation.

Comparaciones indirectas, respuesta de los autores / Indirect comparisons, author response

No disponible