Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Colorectal cancer risk assessment and screening recommendation: a community survey of healthcare providers' practice from a patient perspective

<p>Abstract</p> <p>Background</p> <p>Family history is a common risk factor for colorectal cancer (CRC), yet it is often underused to guide risk assessment and the provision of risk-appropriate CRC screening recommendation. The aim of this study was to identify from a patient perspective health care providers' current practice relating to: (i) assessment of family history of CRC; (ii) notification of "increased risk" to patients at "moderately/potentially high" familial risk; and (iii) recommendation that patients undertake CRC screening.</p> <p>Methods</p> <p>1592 persons aged 56-88 years randomly selected from the Hunter Community Study (HCS), New South Wales, Australia were mailed a questionnaire. 1117 participants (70%) returned a questionnaire.</p> <p>Results</p> <p>Thirty eight percent of respondents reported ever being asked about their family history of CRC. Ever discussing family history of CRC with a health care provider was significantly more likely to occur for persons with a higher level of education, who had ever received screening advice and with a lower physical component summary score. Fifty one percent of persons at "moderately/potentially high risk" were notified of their "increased risk" of developing CRC. Thirty one percent of persons across each level of risk had ever received CRC screening advice from a health care provider. Screening advice provision was significantly more likely to occur for persons who had ever discussed their family history of CRC with a health care provider and who were at "moderately/potentially high risk".</p> <p>Conclusions</p> <p>Effective interventions that integrate both the assessment and notification of familial risk of CRC to the wider population are needed. Systematic and cost-effective mechanisms that facilitate family history collection, risk assessment and provision of screening advice within the primary health care setting are required.</p

Defining left ventricular remodeling following acute ST-segment elevation myocardial infarction using cardiovascular magnetic resonance.

The assessment of post-myocardial infarction (MI) left ventricular (LV) remodeling by cardiovascular magnetic resonance (CMR) currently uses criteria defined by echocardiography. Our aim was to provide CMR criteria for assessing LV remodeling following acute MI.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Evaluation of capture ELISA for detection of antineutrophil cytoplasmic antibodies directed against proteinase 3 in Wegener's granulomatosis: first results from a multicentre study

Objective: To evaluate the performance characteristics of direct and capture ELISA for the detection of PR3-ANCA in Wegener's granulomatosis (WG) in international ANCA reference laboratories. Methods: Serum samples were derived from patients with histological and clinical diagnosis of WG (n = 60), rheumatoid arthritis (RA) (n = 30) and healthy controls (n = 30). Each of them was tested for the presence of ANCA by indirect immunofluorescence technique (IFT), direct and capture ELISA in six international reference laboratories (Massachusetts General Hospital, Boston; Wieslab AB, Lund; University of Maastricht; University Hospital Groningen; Mayo Clinic, Rochester; Rheumaklinik Bad Bramstedt/University of Schleswig-Holstein Campus Lubeck). Each centre tested the sera according to their house protocols of IFT and ELISA. The diagnostic performance of each test was estimated by receiver operating characteristic curve analysis and sensitivity and specificity in detection of ANCA/PR3-ANCA were calculated for the respective methods. Results: In patients histologically and clinically known as WG, the detection of ANCA by IFT varied between 52 and 83% among the participating centres. PR3-ANCA positivity with the different ELISAs ranged from 53 to 80% in direct ELISA and from 72 to 76% in capture ELISA. While most capture ELISAs successfully detected PR3-ANCA, there were significant differences between IFT and direct ELISA results between laboratories. ROC curve analysis demonstrated that in five of six laboratories the overall diagnostic performance of capture ELISA was superior to IFT and direct ELISA, respectively. Conclusion: Capture ELISA is a highly sensitive assay for detection of PR3-ANCA in WG and should be used in conjunction with compatible clinical picture and histological evidence