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71.

Background and aims

Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors.

Methods and results

In a cross-sectional study, atherosclerosis burden was compared between 112 female SLE patients and 31 controls. Plaque number and carotid intima-media wall thickness (cIMT) were assessed by ultrasonography. In a retrospective study, BMD determinations obtained 5-years before the ultrasonography assessment were analyzed in a subgroup of 62 patients. Plaque frequency was increased in SLE, even in patients without CV events or carotid wall thickening. cIMT was increased in patients with CVD, positively correlated with body mass index (BMI). Interestingly, a paradoxical effect of BMI on carotid parameters was observed. Whereas underweight patients (BMI < 20) showed increased prevalence of carotid plaques with low cIMT, those with BMI > 30 showed higher cIMT and plaque burden. Overweight patients (25 < BMI<30) exhibited both elevated cIMT and plaque number. BMI was an independent predictor of BMD. In our retrospective study, patients with either clinical or subclinical CVD exhibited lower BMD levels than their CV-free counterparts. A low lumbar spine BMD independently predicted CVD development after adjusting for confounders.

Conclusion

SLE was associated with a higher subclinical atherosclerosis burden, a bimodal effect being observed for BMI. Decreased BMD can be a CV risk biomarker in SLE.  相似文献   
72.

Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.

Objective

To assess the accuracy of available tools to predict LNI and to develop a novel model for men diagnosed via MRI-targeted biopsies.

Design, setting, and participants

A total of 497 patients diagnosed via MRI-targeted biopsies and treated with RP and extended pelvic lymph node dissection (ePLND) at five institutions were retrospectively identified.

Outcome measurements and statistical analyses

Three available models predicting LNI were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses. A nomogram predicting LNI was developed and internally validated.

Results and limitations

Overall, 62 patients (12.5%) had LNI. The median number of nodes removed was 15. The AUC for the Briganti 2012, Briganti 2017, and MSKCC nomograms was 82%, 82%, and 81%, respectively, and their calibration characteristics were suboptimal. A model including PSA, clinical stage and maximum diameter of the index lesion on multiparametric MRI (mpMRI), grade group on targeted biopsy, and the presence of clinically significant PCa on concomitant systematic biopsy had an AUC of 86% and represented the basis for a coefficient-based nomogram. This tool exhibited a higher AUC and higher net benefit compared to available models developed using standard biopsies. Using a cutoff of 7%, 244 ePLNDs (57%) would be spared and a lower number of LNIs would be missed compared to available nomograms (1.6% vs 4.6% vs 4.5% vs 4.2% for the new nomogram vs Briganti 2012 vs Briganti 2017 vs MSKCC).

Conclusions

Available models predicting LNI are characterized by suboptimal accuracy and clinical net benefit for patients diagnosed via MRI-targeted biopsies. A novel nomogram including mpMRI and MRI-targeted biopsy data should be used to identify candidates for ePLND in this setting.

Patient summary

We developed the first nomogram to predict lymph node invasion (LNI) in prostate cancer patients diagnosed via magnetic resonance imaging-targeted biopsy undergoing radical prostatectomy. Adoption of this model to identify candidates for extended pelvic lymph node dissection could avoid up to 60% of these procedures at the cost of missing only 1.6% patients with LNI.  相似文献   
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Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Methods

In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6?months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).

Results

After 1?month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6?months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r?=??0.5376; P?<?.001 and r?=??0.3285; P?<?.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β?=??0.57, P?=?.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581–0.863]; P?=?.029) were used as classifier, especially in the first 2?months of treatment (0.806 [95% CI 0.665–0.947]; P?<?.001).

Conclusions

This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy.  相似文献   
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