32 research outputs found
European Position Paper on Rhinosinusitis and Nasal Polyps 2020
The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com
Tumor Transcriptome Sequencing Reveals Allelic Expression Imbalances Associated with Copy Number Alterations
Due to growing throughput and shrinking cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide study of gene expression and copy number alterations in primary tumors. The sequencing of transcripts (RNA-Seq) should offer several advantages over microarray-based methods, including the ability to detect somatic mutations and accurately measure allele-specific expression. To investigate these advantages we have applied a novel, strand-specific RNA-Seq method to tumors and matched normal tissue from three patients with oral squamous cell carcinomas. Additionally, to better understand the genomic determinants of the gene expression changes observed, we have sequenced the tumor and normal genomes of one of these patients. We demonstrate here that our RNA-Seq method accurately measures allelic imbalance and that measurement on the genome-wide scale yields novel insights into cancer etiology. As expected, the set of genes differentially expressed in the tumors is enriched for cell adhesion and differentiation functions, but, unexpectedly, the set of allelically imbalanced genes is also enriched for these same cancer-related functions. By comparing the transcriptomic perturbations observed in one patient to his underlying normal and tumor genomes, we find that allelic imbalance in the tumor is associated with copy number mutations and that copy number mutations are, in turn, strongly associated with changes in transcript abundance. These results support a model in which allele-specific deletions and duplications drive allele-specific changes in gene expression in the developing tumor
Sexual dimorphism in cancer.
The incidence of many types of cancer arising in organs with non-reproductive functions is significantly higher in male populations than in female populations, with associated differences in survival. Occupational and/or behavioural factors are well-known underlying determinants. However, cellular and molecular differences between the two sexes are also likely to be important. In this Opinion article, we focus on the complex interplay that sex hormones and sex chromosomes can have in intrinsic control of cancer-initiating cell populations, the tumour microenvironment and systemic determinants of cancer development, such as the immune system and metabolism. A better appreciation of these differences between the two sexes could be of substantial value for cancer prevention as well as treatment
The Genetic Signatures of Noncoding RNAs
The majority of the genome in animals and plants is transcribed in a developmentally regulated manner to produce large numbers of non–protein-coding RNAs (ncRNAs), whose incidence increases with developmental complexity. There is growing evidence that these transcripts are functional, particularly in the regulation of epigenetic processes, leading to the suggestion that they compose a hitherto hidden layer of genomic programming in humans and other complex organisms. However, to date, very few have been identified in genetic screens. Here I show that this is explicable by an historic emphasis, both phenotypically and technically, on mutations in protein-coding sequences, and by presumptions about the nature of regulatory mutations. Most variations in regulatory sequences produce relatively subtle phenotypic changes, in contrast to mutations in protein-coding sequences that frequently cause catastrophic component failure. Until recently, most mapping projects have focused on protein-coding sequences, and the limited number of identified regulatory mutations have been interpreted as affecting conventional cis-acting promoter and enhancer elements, although these regions are often themselves transcribed. Moreover, ncRNA-directed regulatory circuits underpin most, if not all, complex genetic phenomena in eukaryotes, including RNA interference-related processes such as transcriptional and post-transcriptional gene silencing, position effect variegation, hybrid dysgenesis, chromosome dosage compensation, parental imprinting and allelic exclusion, paramutation, and possibly transvection and transinduction. The next frontier is the identification and functional characterization of the myriad sequence variations that influence quantitative traits, disease susceptibility, and other complex characteristics, which are being shown by genome-wide association studies to lie mostly in noncoding, presumably regulatory, regions. There is every possibility that many of these variations will alter the interactions between regulatory RNAs and their targets, a prospect that should be borne in mind in future functional analyses
Consensus criteria for chronic rhinosinusitis disease control:an international Delphi Study
Background: Chronic rhinosinusitis (CRS) disease control is a global metric of disease status for CRS. While there is broad acceptance that it is an important treatment goal, there has been inconsistency in the criteria used to define CRS control. The objective of this study was to identify and develop consensus around essential criteria for assessment of CRS disease control. Methods: Modified Delphi methodology consisting of three rounds to review a list of 24 possible CRS control criteria developed by a 12-person steering committee. The core authorship of the multidisciplinary EPOS 2020 guidelines was invited to participate. Results: Thirty-two individuals accepted the invitation to participate and there was no dropout of participants throughout the entire study (3 rounds). Consensus essential criteria for assessment of CRS control were: overall symptom severity, need for CRS-related systemic corticosteroids in the prior 6 months, severity of nasal obstruction, and patient-reported CRS control. Near-consensus items were: nasal endoscopy findings, severity of smell loss, overall quality of life, impairment of normal activities and severity of nasal discharge. Participants’ comments provided insights into caveats of, and disagreements related to, near-consensus items. Conclusions: Overall symptom severity, use of CRS-related systemic corticosteroids, severity of nasal obstruction, and patient-reported CRS control are widely agreed upon essential criteria for assessment of CRS disease control. Consideration of near-consensus items to assess CRS control should be implemented with their intrinsic caveats in mind. These identified consensus CRS control criteria, together with evidence-based support, will provide a foundation upon which CRS control criteria with wide-spread acceptance can be developed
Transcranial direct current stimulation in post-stroke aphasia rehabilitation: A systematic review
BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive tool that induces neuromodulation in the brain. Several studies have shown the effectiveness of tDCS in improving language recovery in post-stroke aphasia. However, this innovative technique is not currently used in routine speech and language therapy (SLT) practice. OBJECTIVE: This systematic review aimed to summarise the role of tDCS in aphasia rehabilitation. METHODS: We searched MEDLINE via PubMed and Scopus on October 5, 2018 for English articles published from 1996 to 2018. Eligible studies involved post-stroke aphasia rehabilitation with tDCS combined or not with SLT. RESULTS: We retained 5 meta-analyses and 48 studies. Among the 48 studies, 39 were randomised controlled trials (558 patients), 2 prospective studies (56 patients), and 5 case studies (5 patients). Two articles were sub-analyses of a randomised clinical trial. Methods used in these studies were heterogeneous. Only 6 studies did not find a significant effect of tDCS on language performance. As compared with earlier meta-analyses, the 2 latest found significant effects. CONCLUSION: Evidence from published peer reviewed literature is effective for post-stroke aphasia rehabilitation at the chronic stages. tDCS devices are easy to use, safe and inexpensive. They can be used in routine clinical practice by speech therapists for aphasia rehabilitation. However, further studies should investigate the effectiveness in the subacute post-stroke phase and determine the effect of the lesion for precisely identifying the targeted brain areas. We discuss crucial challenges for future studies
Ann Phys Rehabil Med
Background Aphasia severity is known to affect quality of life (QoL) in stroke patients, as is mood disorders, functional limitations, limitations on activities of daily life, economic status and level of education. However, communication limitation or fatigue has not been explored in this specific population. Objective We aimed to investigate whether these factors were associated with QoL in patients with aphasia after stroke. Methods Patients with aphasia were included from April 2014 to November 2017 after a first stroke and were followed for 2 years post-stroke. QoL was assessed at follow-up by the French Sickness Impact Profile 65 (SIP-65). We explored predictors such as mood disorders, communication impairment, fatigue, limitations on activities of daily life, and aphasia severity in addition to socio-demographic factors. Results We included 32 individuals (22 men; mean age 60.7 [SD 16.6] years) with aphasia after a first stroke. Poor QoL as assessed by the SIP-65 was significantly associated (Pearson correlations) with increased severity of aphasia initially (P = 0.008) and at follow-up (P = 0.01); increased communication activity limitations at follow-up (P < 0.001); increased limitations on activities of daily life at baseline (P = 0.008) and follow-up (P < 0.001); increased fatigue at follow-up (P = 0.001); and increased depression symptoms at follow-up (P = 0.001). On multivariable analysis, QoL was associated with communication activity limitations, limitations on activities of daily life, fatigue and depression, explaining more than 75% of the variance (linear regression R2 = 0.756, P < 0.001). The relative importance in predicting the variance was 32% for limitations on activities of daily life, 21% fatigue, 23% depression and 24% communication activity limitations. Conclusion Aphasia severity, mood disorders and functional limitations may have a negative effect on QoL in patients with aphasia. Also, for the first time, we show that fatigue has an important impact on QoL in this population. Specific management of this symptom might be beneficial and should be explored in future studies