The Established and Evolving Role of Nailfold Capillaroscopy in Connective-Tissue Disease

Nailfold capillaroscopy (NFC) is a low-cost, non-invasive, rapid, highly specific and reproducible investigation well established in the diagnosis of systemic sclerosis and related conditions. This chapter will detail the relevant underlying scientific principles that underpin the investigation, the methods for performing NFC, the range of abnormalities that can be present and the currently available classification criteria before moving on to discuss the various established and emerging applications as relevant to the connective tissue diseases. In addition to its role in the diagnosis of SSc, highlighted by its inclusion in the most recent ACR/EULAR consensus classification criteria, NFC has been shown to predict disease activity, many organ-specific complications such as digital ulcers, pulmonary hypertension and interstitial lung disease, and even mortality. It is emerging as a useful investigation in other CTDs characterised by microvasculopathy, such as in the idiopathic inflammatory myopathies and mixed connective tissue disease, as well as being studied as a serial investigation in patients to act as a potential biomarker and measure of treatment efficacy. NFC can contribute to the earlier identification of patients with CTDs with clinically important complications and if applied accurately, therefore, can help improve outcomes in these often challenging diseases

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

Baseline risk markers and visit-to-visit variability in relation to kidney outcomes - A post-hoc analysis of the PERL study.

BACKGROUND: Baseline risk variables and visit-to-visit variability (VV) of systolic blood pressure (SBP), HbA METHODS: Post-hoc analysis of a double-blind randomized placebo-controlled clinical trial investigating allopurinol\u27s effect on iohexol-derived glomerular filtration rate (iGFR) in type 1 diabetes with elevated UA. Primary outcome was iGFR change over three years. Linear regression with backwards selection of baseline clinical variables was performed to identify an optimized model forecasting iGFR change. Furthermore, VVs of SBP, HbA RESULTS: 404 participants were included in the primary analyses. In the optimized baseline variable model, higher HbA CONCLUSIONS: We identified several risk markers for faster iGFR decline in a high-risk population with type 1 diabetes. While further research is needed, our results indicate possible new and clinically feasible measures to risk stratify for DKD in type 1 diabetes