Impact of microscopic extrathyroidal extension on differentiated thyroid cancer post-surgical risk of recurrence: a retrospective analysis.

PURPOSE: In the last edition of the American Joint Committee on Cancer (AJCC) staging system, differentiated thyroid cancers (DTC) showing microscopic extrathyroidal extension (mETE) are considered comparable to intrathyroidal cancers for their clinical behavior and prognosis. The aim of the study is to evaluate the impact of this updated assessment of T, when applied to the postoperative recurrence risk stratification, according to the American Thyroid Association Guidelines (ATA-RR). METHODS: One-hundred DTC patients who underwent total thyroidectomy were retrospectively evaluated. The downstaging of mETE was introduced in the definition of T, and the updated classification defined as modified ATA-RR (ATAm-RR). For each patient, post-surgical basal and stimulated thyroglobulin (Tg) levels, neck ultrasound (US) and post-ablative 131-I whole body scan (WBS) reports were considered. The predictive performance (PP) of disease recurrence was calculated both for each single parameter, as well as for all of them. RESULTS: According to ATAm-RR classification, 19/100 patients (19%) were downstaged. ATA-RR proved a significant PP for disease recurrence (DR) (sensitivity 75.0%, specificity 63.0%, p = 0.023). However, ATAm-RR performed slightly better due to an increased specificity (sensitivity 75.0%, specificity 83.7%, p < 0.001). For both classifications, the PP was optimal when all the above-mentioned predictive parameters were considered. CONCLUSION: Our results suggest that the new assessment of T considering mETE resulted in a downgrading of ATA-RR class in a significant number of patients. This provides a better PP for disease recurrence, and the best PP was obtained when considering the whole predictive variables together.

Detección precoz de la ambliopía en Atención Primaria / Early detection of amblyopia in Primary Care

Introducción: la detección precoz de alteraciones visuales en la infancia tiene importancia ya que pueden causar problemas en el desarrollo visual, el rendimiento escolar o, incluso, suponer un riesgo vital como el retinoblastoma. El objetivo de este estudio es realizar una revisión bibliográfica sobre las actividades diagnósticas que puede realizar el pediatra de Atención Primaria (PAP) para mejorar el cribaje de la ambliopía, e identificar la edad más adecuada para este cribado. Material y métodos: se ha realizado una búsqueda bibliográfica de textos científicos en inglés y español publicados en los últimos 20 años en bases de datos como PubMed y Google Académico. Algunas de las palabras clave fueron: “amblyopia”, “vision screening”, “pediatric”, “retinoscopy” y “photoscreener”. Resultados: se encontraron 376 resultados, seleccionándose 29 artículos y dos libros que incluían métodos diagnósticos de ambliopía realizados por el PAP (Bruckner, Hirschberg, Cover test, estereopsis y agudeza visual) y otros más avanzados (retinoscopia, autorrefractómetros, fotorrefractómetros y potenciales evocados). Los programas de cribado y derivación al oftalmólogo realizados por el PAP están basados en métodos tradicionales, siendo en general poco objetivos y heterogéneos. Conclusiones: los resultados encontrados no definen la edad óptima para el cribado, ni la prueba o combinación de pruebas más adecuadas para evitar derivaciones innecesarias o que una alteración pase inadvertida. Sin embargo, este cribado puede realizarse sencilla y rápidamente a partir de los 6 meses de vida mediante métodos avanzados como fotorrefractometría. Aumentar los recursos disponibles del PAP y conocer su aplicabilidad real y sus beneficios clínicos puede precisar posteriores investigaciones (AU)

Introduction: early detection of visual alterations in childhood has special relevance since it can cause problems in visual development, school performance, or even pose a vital risk such as retinoblastoma. The aim of this study was to conduct a traditional review about the diagnostic procedures that can be performed by the Primary Care Pediatrician (PCP) to improve the screening of amblyopia and to identify the most appropriate age for this screening.Material and methods: a bibliographic search of scientific texts in English and Spanish published in the last 20 years in databases such as PubMed and Google Scholar has been carried out. Some of the key words were: “amblyopia”, “vision screening”, “pediatric”, “retinoscopy” and “photoscreener”.Results: 376 results were found. 29 articles and 2 books were selected covering diagnostic methods of amblyopia performed by the PCP (Bruckner, Hirschberg, Cover test, stereopsis and visual acuity assessment) and others more advanced (retinoscopy, autorefractometry, photorefractometry and evoked potentials). The screening and ophthalmologist referral programs performed by the PCP are based on traditional methods and are generally not very objective and heterogeneous.Conclusions: the evidence does not allow to define the optimal age to amblyopia screening or which test or combination of tests could be the most appropriate to avoid unnecessary referrals or unnoticed alterations. However, this screening can be performed easily and quickly from the age of 6 months using diagnostic methods such as photorefractometry. Increasing the available resources in PCP clinic and knowing its applicability and clinical benefits may require further research. (AU)

Evaluation of adequacy of levo-thyroxine dosage in patients with differentiated thyroid carcinoma: correlation between morning and afternoon TSH determination.

PURPOSE: The aim of this study was to judge the reliability of evaluating thyroid-stimulating hormone (TSH) and free thyroxine (f-T4) in the morning and afternoon in differentiated thyroid carcinoma (DTC) patients. METHODS: We evaluated 153 DTC patients, aged 61 ± 13 years, in active follow-up in our center after primary treatments and under stabilized levo-thyroxine (L-T4) posology. In each patient, morning and afternoon examinations were performed 1-3 months apart. Blood samples were collected at 08:00-09:00 h and 15:00-16:00 h. TSH and f-T4 were evaluated in both samples. Thyroglobulin (Tg), Tg-antibodies and neck ultrasonography were also evaluated. RESULTS: According to clinical and laboratory examinations, 92% of patients were disease-free, 6% had biochemical disease, and 2% structural disease. L-T4 dosages (1.64 ± 0.38 µg/kg b.w.) proved the same on both occasions, despite slight changes in body weight or L-T4 posology in 15% of patients. Free-T4 values were significantly higher in the afternoon (21.5 ± 0.3 pmol/L) than in the morning (18.8 ± 0.4 pmol/L; P < 0.0001), whereas TSH values were statistically unchanged (morning 0.85 ± 0.25 mIU/L; afternoon 0.72 ± 0.20 mIU/L). There was a significant correlation (P < 0.0001) between the two TSH determinations in the same patients. CONCLUSIONS: In DTC patients, follow-up examination consists of clinical and laboratory evaluations. The majority of patients have good disease control. Our study suggests that the adequacy of L-T4 therapy can be monitored equally well either in the morning or in the afternoon. Afternoon examinations can alleviate crowding in hospital ambulatories in the morning.

An innovative long final year assistantship in general practice: description and evaluation.

We describe and evaluate an innovative immersive 15 week final year assistantship in general practice. Evaluation data was taken from five years of routinely collected School data and available national comparative data. The assistantship aims to enable students to consolidate knowledge and hone their skills through central participation in the care of large numbers of patients with acute and long term conditions. We estimate that most students consulted with over 450 patients during the assistantship. Students report that they became useful to their practice teams, had multiple episodes of feedback on their performance which they found useful and, in the school exit survey, reported that they were highly prepared for practice. 9.4 per cent of students reported that the assistantship was 'too long' and, especially those who completed the assistantship in the second semester, they were out of hospital for too long before F1. Some described a learning 'plateau' after the 10th week which was addressed by modifications to the assistantship. Nevertheless, in national surveys, our graduates' self-reported preparedness for practice is high, a perception shared by their F1 supervisors. General practice can make a valuable contribution to the education of senior medical students and contribute to their preparedness for practice.

Nanoshaping field emitters from glassy carbon sheets: a new functionality induced by H-plasma etching.

This paper reports on the morphological and electrical characterization at the nanometer scale and the investigation of the field emission characteristics of glassy carbon (GC) plates which underwent H-induced physical/chemical processes occurring in a dual-mode MW-RF plasma reactor. Plasma treatment produced on the GC surface arrays of vertically aligned conically shaped nanostructures, with density and height depending on the plasma characteristics. Two kinds of samples obtained under two different bias regimes have been deeply analyzed using an AFM apparatus equipped with tools for electric forces and surface potential measurements. The features of electron emission via the Field Emission (FE) mechanism have been correlated with the morphology and the structure at the nanoscale of the treated glassy carbon samples. The measured current density and the characteristics of the emission, which follow the Fowler-Nordheim law, indicate that the plasma-based methodology utilized for the engineering of the GC surfaces is able to turn conventional GC plates into efficient emission devices. The outstanding properties of GC suggest the use of such nanostructured materials for the assembling of cold cathodes to be used in a harsh environment and under extreme P/T conditions.

A novel long non-coding RNA in the rheumatoid arthritis risk locus TRAF1-C5 influences C5 mRNA levels.

Long non-coding RNAs (lncRNAs) can regulate the transcript levels of genes in the same genomic region. These locally acting lncRNAs have been found deregulated in human disease and some have been shown to harbour quantitative trait loci (eQTLs) in autoimmune diseases. However, lncRNAs linked to the transcription of candidate risk genes in loci associated to rheumatoid arthritis (RA) have not yet been identified. The TRAF1 and C5 risk locus shows evidence of multiple eQTLs and transcription of intergenic non-coding sequences. Here, we identified a non-coding transcript (C5T1lncRNA) starting in the 3' untranslated region (UTR) of C5. RA-relevant cell types express C5T1lncRNA and RNA levels are further enhanced by specific immune stimuli. C5T1lncRNA is expressed predominantly in the nucleus and its expression correlates positively with C5 mRNA in various tissues (P=0.001) and in peripheral blood mononuclear cells (P=0.02) indicating transcriptional co-regulation. Knockdown results in a concurrent decrease in C5 mRNA levels but not of other neighbouring genes. Overall, our data show the identification of a novel lncRNA C5T1lncRNA that is fully located in the associated region and influences transcript levels of C5, a gene previously linked to RA pathogenesis.

Intrafamilial variability of ZRS-associated syndrome: characterization of a mosaic ZRS mutation by pyrosequencing.

During limb development, the spatio-temporal expression of sonic hedgehog (SHH) is driven by the Zone of polarizing activity Regulatory Sequence (ZRS), located 1 megabase upstream from SHH. Gain-of-function mutations of this enhancer, which cause ectopic expression of SHH, are known to be responsible for congenital limb malformations with variable expressivity, ranging from preaxial polydactyly or triphalangeal thumbs to polysyndactyly, which may also be associated with mesomelic deficiency. In this report, we describe a patient affected with mirror-image polydactyly of the four extremities and bilateral tibial deficiency. The proband's father had isolated preaxial polydactyly type II (PPD2). Using Sanger sequencing, a ZRS point mutation (NC_000007.14, g.156584153A>G, UCSC, Build hg.19) was only identified in the patient. However, pyrosequencing analysis enabled the detection of a 10% somatic mosaic in the blood and saliva from the father. To our knowledge, this is the first description of a ZRS mosaic mutation. This report highlights the complexity of genotype-phenotype correlation in ZRS-associated syndromes and the importance of detecting somatic mosaicism for accurate genetic counselling.

[Epigenetics in inflammatory systemic diseases]. / Epigenetik bei entzündlichen Systemerkrankungen.

In addition to analysis of the genetic code, in recent years more and more studies have concentrated on changes in the epigenetic code. Epigenetic mechanisms determine which genes in a cell are transcribed and thus form the phenotype of a cell. The epigenetic code can be changed by environmental influences, which allows cells to adapt to longstanding changes in the environment. Therefore, it is feasible to assume that epigenetic changes are the molecular basis for long-term effects of the environment on disease development. In particular in tumors and chronic inflammatory diseases epigenetic changes were found to correlate with disease severity and progression. Knowledge about these epigenetic changes might help that epigenetic modifications can be used in the future as biomarkers, prognostic factors and therapeutic targets.

[Assessment of an educational maze for major trauma care teaching]. / Évaluation d'un labyrinthe pédagogique pour l'enseignement de la traumatologie grave.

BACKGROUND: Assess efficacy, satisfaction and usefulness of an educational maze based on posters and audioguide for major trauma care teaching to medical students. The educational maze consists of posters with audio comments recorded in an audioguide. This tool was part of a larger educational program including medical simulation. STUDY DESIGN: Prospective, interventional, observational, monocentric study. STUDENT: Medical student of Grenoble University Hospital, in the four last years of medical school, following a training course in anesthesia, emergency medical services and intensive care units. METHOD: Forty essentials key messages for major trauma management were included in 10 posters and audioguides. A first assessment with short opened answers was handed to the students at the end of the educational maze to assess their memorization. A second assessment with simple choice answers regarding satisfaction and usefulness of this new educational tool was realized at the end of the entire program. RESULT: One hundred and eighty-four medical students attending the major trauma program were included in this study. On the first test, 75% of essential knowledge on major trauma management was memorized by more than 50% of the medical students. On the second test, 94% of medical students had a high satisfaction level of this educational maze. CONCLUSION: An educational maze based on posters and audioguides seems to be an efficient, useful tool for teaching essential knowledge on major trauma management to medical students.

[Normobaric hyperoxia therapy for patients with traumatic brain injury]. / Hyperoxie normobarique chez le patient traumatisé crânien.

Cerebral ischaemia plays a major role in the outcome of brain-injured patients. Because brain oxygenation can be assessed at bedside using intra-parenchymal devices, there has been a growing interest about whether therapeutic hyperoxia could be beneficial for severely head-injured patients. Normobaric hyperoxia increases brain oxygenation and may improve glucose-lactate metabolism in brain regions at risk for ischaemia. However, benefits of normobaric hyperoxia on neurological outcome are not established yet, that hinders the systematic use of therapeutic hyperoxia in head-injured patients. This therapeutic option might be proposed when brain ischemia persists despite the optimization of cerebral blood flow and arterial oxygen blood content.

DNA methylation regulates the expression of CXCL12 in rheumatoid arthritis synovial fibroblasts.

In the search for specific genes regulated by DNA methylation in rheumatoid arthritis (RA), we investigated the expression of CXCL12 in synovial fibroblasts (SFs) and the methylation status of its promoter and determined its contribution to the expression of matrix metalloproteinases (MMPs). DNA was isolated from SFs and methylation was analyzed by bisulfite sequencing and McrBC assay. CXCL12 protein was quantified by enzyme-linked immunosorbent assay before and after treatment with 5-azacytidine. RASFs were transfected with CXCR7-siRNA and stimulated with CXCL12. Expression of MMPs was analyzed by real-time PCR. Basal expression of CXCL12 was higher in RASFs than osteoarthritis (OA) SFs. 5-azacytidine demethylation increased the expression of CXCL12 and reduced the methylation of CpG nucleotides. A lower percentage of CpG methylation was found in the CXCL12 promoter of RASFs compared with OASFs. Overall, we observed a significant correlation in the mRNA expression and the CXCL12 promoter DNA methylation. Stimulation of RASFs with CXCL12 increased the expression of MMPs. CXCR7 but not CXCR4 was expressed and functional in SFs. We show here that RASFs produce more CXCL12 than OASFs due to promoter methylation changes and that stimulation with CXCL12 activates MMPs via CXCR7 in SFs. Thereby we describe an endogenously activated pathway in RASFs, which promotes joint destruction.

[Epigentics in rheumatic diseases]. / Epigenetik in der Rheumatologie.

The human genome comprises approximately 30000 genes needed for the formation and function of approximately 1 Million proteins in the human body. Differentiation leads to the deactivation of genes that are not needed in the specific tissues or cells. To regulate the cell specific gene expression in normal cells epigenetic modifications work in concert with genetic mechanisms. In contrast to genetic mutations, epigenetics encompasses the wide range of heritable changes in gene expression that do not result from alteration in the DNA sequence itself. A dysregulation of epigenetic modifications results in diseases such as cancer or autoimmune diseases. Since these epigenetic modifications of the DNA and the histones are reversible they are good targets for novel therapeutic intervention.

[miRNA in epigenetics of rheumatic diseases]. / miRNA in der Epigenetik rheumatischer Erkrankungen.

Epigenetic modifications are heritable changes in genome function that occur without a change in DNA sequence. They turn genes on or off by small chemical modifications. Thereby, they change the structure of the DNA making them accessible or not for transcription factors or other DNA binding molecules. MicroRNAs are a new class of regulatory non-coding RNAs that modulate gene expression and influences epigenetic mechanisms. miRNAs offer novel mechanisms of therapeutic strategies for cancer and autoimmune diseases. Here, we summarize which miRNAs play a role in rheumatic diseases and their biological function.

Intrathecal baclofen in cerebral palsy. A retrospective study of 25 wheelchair-assisted adults.

OBJECTIVE: To study the efficacy and safety of intrathecal baclofen therapy (ITB) in wheelchair-dependent adults with cerebral palsy. PATIENTS AND METHODS: A retrospective analysis and clinical examination of 25 wheelchair-assisted adults with cerebral palsy receiving ITB initiated between 1999 and 2009 in three different cities in western France. RESULTS: ITB improves spasticity and facilitates wheelchair comfort and nursing care. The therapy has an effect on motor disorders and pain. Eighty percent of the ITB patients were satisfied. Dissatisfaction was related to complications or adverse events and not lack of efficacy. Complications occurred in 32% of the patients and transient interruption of the treatment or surgical removal of the ITB pump was necessary in 16% of cases. DISCUSSION AND CONCLUSION: Wider use of ITB in this indication is likely and should lead to a better understanding of the drug's pharmacological effects on motor disorders and pain. Use of the Goal Attainment Assessment Scale or Caregiver Questionnaire can help us.