Does diabetes modify the effect of FRAX risk factors for predicting major osteoporotic and hip fracture?

Summary

In an observational study population of 62,413 individuals (6,455 [10 %] with diabetes), diabetes was independently associated with major osteoporotic fractures (MOFs) but did not significantly modify the effect of FRAX^TM risk factors or prior fracture site. However, the presence of diabetes exerted a much stronger effect on hip fracture risk in younger versus older individuals.

Introduction

Diabetes mellitus increases fracture risk independent of risk factors that comprise the WHO FRAX^TM tool. We explored whether diabetes modifies the effect of FRAX clinical risk factors on MOF and hip fracture risk.

Methods

Using a registry of clinical dual-energy X-ray absorptiometry (DXA) results for Manitoba, Canada, we identified women and men aged 40 years and older undergoing baseline DXA in 1996–2011. Health services data were used to identify diabetes diagnosis, FRAX risk factors and incident fractures using previously validated algorithms. Prior fracture was stratified as clinical vertebral, hip, humerus, forearm, pelvis and ‘other’. Cox proportional hazards models were used to test for statistical interactions of diabetes with FRAX clinical risk factors and prior fracture site.

Results

During a mean follow-up of 6 years, there were 4,218 MOF and 1,108 hip fractures. Diabetes was a significant independent risk factor for MOF adjusted for FRAX risk factors including bone mineral density (BMD) (adjusted hazard ratio [aHR] 1.32 [95 % confidence interval (CI) 1.20–1.46]). No significant interactions of FRAX risk factors or prior fracture site with diabetes were identified in analyses of MOF. For predicting hip fractures, age significantly modified the effect of diabetes (aHR age <60, 4.67 [95 % CI 2.76–7.89], age 60–69, 2.68 [1.77–4.04], age 70–79, 1.57 [1.20–2.04], age >80, 1.42 [1. 10–1.99]; pinteraction <0.001).

Conclusions

Diabetes is an independent risk factor for MOFs and does not significantly modify the effect of FRAX risk factors or prior fracture site. However, diabetes exerts a much stronger effect on hip fracture risk in younger than older individuals which needs to be considered in hip fracture prediction.     

Perivascular Neuropilin-1 expression is an independent marker of improved survival in renal cell carcinoma

Renal cell carcinoma (RCC) treatment has improved in the last decade with the introduction of drugs targeting tumor angiogenesis. However, the 5-year survival of metastatic disease is still only 10–15%. Here, we explored the prognostic significance of compartment-specific expression of Neuropilin 1 (NRP1), a co-receptor for vascular endothelial growth factor (VEGF). NRP1 expression was analyzed in RCC tumor vessels, in perivascular tumor cells, and generally in the tumor cell compartment. Moreover, complex formation between NRP1 and the main VEGF receptor, VEGFR2, was determined. Two RCC tissue microarrays were used; a discovery cohort consisting of 64 patients and a validation cohort of 314 patients. VEGFR2/NRP1 complex formation in cis (on the same cell) and trans (between cells) configurations was determined by in situ proximity ligation assay (PLA), and NRP1 protein expression in three compartments (endothelial cells, perivascular tumor cells, and general tumor cell expression) was determined by immunofluorescent staining. Expression of NRP1 in perivascular tumor cells was explored as a marker for RCC survival in the two RCC cohorts. Results were further validated using a publicly available gene expression dataset of clear cell RCC (ccRCC). We found that VEGFR2/NRP1 trans complexes were detected in 75% of the patient samples. The presence of trans VEGFR2/NRP1 complexes or perivascular NRP1 expression was associated with a reduced tumor vessel density and size. When exploring NRP1 as a biomarker for RCC prognosis, perivascular NRP1 and general tumor cell NRP1 protein expression correlated with improved survival in the two independent cohorts, and significant results were obtained also at the mRNA level using the publicly available ccRCC gene expression dataset. Only perivascular NRP1 expression remained significant in multivariable analysis. Our work shows that perivascular NRP1 expression is an independent marker of improved survival in RCC patients, and reduces tumor vascularization by forming complexes in trans with VEGFR2 in the tumor endothelium. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

In vitro study of continuous wave Doppler spectral changes resulting from stenoses and bulbs

Quantitative analysis of continuous wave (CW) Doppler spectra by measurements of peak frequency and spectral broadening is an important non-invasive method for detecting disturbed flow caused by carotid arterial stenosis. It is known that severe stenoses can be detected; however, the spectral changes associated with minor or moderate stenoses may not be detected or can potentially be confused with those produced by flow disturbances in the normal carotid bulb. In order to determine if the flow disturbances in a normal bulb and those associated with a minor stenosis produce significant spectral changes, Doppler spectra were recorded from straight tubes with bulbs or stenoses in an in vitro model with steady flow rates of 400, 600, and 800 cc/min (Reynolds numbers of 1700, 2600, and 3500). Stenoses greater than approximately 30% cross-sectional area were associated with an increased peak frequency and increased spectral broadening as measured by spectral broadening index (SBI), coefficient of variation (CV), coefficient of skewedness (CS) and coefficient of kurtosis (CK). Stenoses less than 30% were not detected. With flow rates of 400 and 600 cc/min, the presence of a bulb did not affect peak frequency or the extent of spectral broadening. With a higher flow rate (800 cc/min), there was an increase in SBI, CV and CS but no increase in peak frequency. Based on the results of these in vitro steady flow experiments in straight tubes, we conclude that increased peak frequency and spectral broadening are the result of a stenosis greater than 30% cross-sectional area.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrochemical evidence of the adsorption of alkanethiols on two sites on Ag(111)

We present spectroscopic and electrochemical results consistent with the adsorption of alkanethiols on two sites and the formation of a very densely packed, stable, monolayer on Ag(111). A surface coverage of alkanethiols of 8.5 (±0.4)×10^?10 mol cm^?2 was calculated from the charge associated with the reduction of a monolayer of alkanethiols. Alkanethiol modified Ag(111) electrodes were found to have lower capacitances than the alkanethiol modified Au(111) electrodes. The lower capacitances are due to the higher surface concentration of alkanethiols on Ag(111). The very low intensity of the methylene CH stretching bands of alkanethiols with alkane chains of four to nine carbons chemisorbed on Ag(111) suggests a vertical orientation of all-trans alkane chains. No vibrational evidence of oxidation of the chemisorbed alkanethiols was found after exposure to air for up to 6 weeks. A fine structure consisting of two current peaks was observed in all cyclic voltammograms of the reduction of chemisorbed alkanethiols. This revealed that the reduction of chemisorbed alkanethiols occurs in two steps on Ag(111). Chronoamperometric measurements also support a two-step reductive desorption of alkanethiols. The high surface concentration of alkanethiols and the orientation of the alkane chains suggest that the fine structure in the voltammograms is due to the reduction of the alkanethiols from two adsorption sites.     

Surrogate markers for atherosclerosis in overweight subjects with atherogenic dyslipidemia: the GEMS project

Metabolic syndrome is a constellation of major risk factors for cardiovascular disease. In affected individuals with this syndrome, the independent contribution of low high-density lipoprotein-cholesterol and increased triglyceride levels to the development of atherosclerosis remains to be clarified. We assessed the relationship between these 2 parameters and several surrogate markers for atherosclerosis. One hundred and twenty overweight cases, defined as having high-density lipoprotein-cholesterol (or=75 percentile) were compared with 120 discordant overweight controls defined on lipid values (high-density lipoprotein-cholesterol >or=50 percentile and triglycerides 相似文献   

Chronic insomnia, quality-of-life, and utility scores: comparison with good sleepers in a cross-sectional international survey

Background

Chronic insomnia has a recognized impact on health-related quality-of-life (HRQoL) but data on utility scores across countries are lacking. The objective of the present study was to assess health related quality of life (HRQoL) and utility scores in individuals from three different countries (USA, France, and Japan), comparing sufferers of chronic insomnia to good sleepers.

Methods

A cross-sectional survey (SLEEPI-i) of 4067 persons in the US (n = 1298; 478 good sleepers and 820 patients with insomnia), France (n = 1858; 998 good sleepers and 860 patients with insomnia) and Japan (n = 911; 506 good sleepers and 405 patients with insomnia). Enrollment and data collection using consumer panels were web-based in the US and France, and gathered via a postal survey in Japan. People with chronic insomnia (>6 months) were selected based on Insomnia Severity Index scores (ISI). Severity of insomnia was assessed using the ISI score and HRQoL was assessed using the self-administered Short-Form SF-36 Health Survey. Utility scores were derived using the algorithm developed by Brazier et al. Multivariate analyses were used to adjust for potential confounding factors.

Results

In all countries, people with chronic insomnia (40% treated) reported lower SF-36 scores in each of eight domains compared with good sleepers (P < .0001). Chronic insomnia was associated with significantly lower utility scores compared with good sleepers (mean scores 0.63 versus 0.72 in the US, 0.57 versus 0.67 in France, and 0.67 versus 0.77 in Japan, P < .0001).

Conclusions

This survey suggests that chronic insomnia is associated with significant impairment of HRQoL and decreased utilities across the different geographical regions studied.