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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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Background

One daily dose of tacrolimus (QDT) improves adherence in kidney transplant (KT) recipients. A switch from twice-daily tacrolimus (BDT) to QDT showed similar efficacy and safety.

Methods

The aim of our study was to demonstrate the long-term efficacy and safety of switching from BDT to QDT in KT recipients. Preliminary results have already been published. Forty-one patients (34 men and 7 women), mean age at KT of 43.9 ± 12.7 years, underwent a 1:1 dose switch from BDT to QDT; the mean time from KT to switch was 36.6 ± 16.1 months. In our study population, 4 patients received a living donor KT and 2 received a second allograft.

Results

The mean follow-up was 86.8 ± 13 months from the switch and 126.2 ± 22.3 months from KT. Graft and patient survival rates were 90.2% and 95.1%, respectively. All patients maintained stable renal function during follow-up. During the first 3 months after the switch we observed a significant decrease in tacrolimus blood level (P = .0001). No significant differences were observed regarding tacrolimus dose before and after QDT introduction (P = not significant [NS]). Fourteen patients who stopped steroids under BDT treatment and 16 patients who stopped steroids after the switch are currently steroid-free.

Conclusion

Our study showed safety and efficacy in switching from BDT to QDT. After early (<1 year) dose adjustment, tacrolimus blood levels remained stable throughout follow-up. Moreover, QDT represented a valid alternative for patients showing steroid side effects.  相似文献   
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Short History of Interventional Neuroradiology What about the Future?   总被引:1,自引:0,他引:1  
1 Short historical background of interventional neuroradiology Even if a number of us were among the pioneers of Interventional Neuroradiology, this specialty has now reached its period of maturity. Schematically, the era of the pioneers began forty years ago and lasted about 15 years, between 1960 and 1975. During that period, on the initiative of Fedor Serbinenko (Russia) and Ren6 Djindjian (France), "intracerebral navigation " using small balloons, which became gradually "detachable", has been invented. At the same time, we discovered how to use these balloons to occlude intracranial vascular lesions, inaccessible or hardly accessible to traditional open skull neurosurgery, for example, carotid cavernous fistulas. Very rapidly, a lot of different embolic particles were successively tested, ranging at first from pieces of muscle, to small glass or silastic beads, gelfoam and dura mater pieces... During this period, parallel progress of hyperselective catheterization and consequently of microangiography allowed to establish new classifications of main vascular pathologies (distinction between brain arteriovenous malformations and dural fistulas ... ). These new classifications allowed a better understanding of physiopathology. This first period was thus primarily devoted to development of very precise diagnosis and techniques of hyperselective endovascular occlusion.  相似文献   
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OBJECTIVE: To investigate whether cardiovascular mortality related to obesity could be modified by physical activity. DESIGN: Mortality follow-up. SETTING: Population study. PARTICIPANTS: Participants in a health survey: 34 868 women and 32 872 men free from known cardiovascular disease or diabetes at baseline. MAIN OUTCOME MEASURES: Total cardiovascular mortality. MAIN RESULTS: During 16 years of follow-up, 3026 women and 3526 men had died from cardiovascular causes. In middle age, obesity [body mass index (BMI) of 30 or higher] was associated with increased risk of cardiovascular death, but the association weakened with age. After 70, there was no association between BMI and cardiovascular death. At all ages, a lower level of physical activity was associated with a higher cardiovascular mortality. In women with high physical activity, indicated by at least 30 min of moderate to vigorous activity more than once a week, cardiovascular mortality was only slightly higher in the obese compared to lean women (adjusted relative risk, 1.27; 95% confidence interval, 0.80-2.00). In men with high physical activity, cardiovascular mortality was, however, significantly higher among the obese (relative risk, 1.62; 95% confidence interval, 1.09-2.40). In both genders cardiovascular mortality was substantially higher in obese people who reported no regular physical activity compared to obese people with a high level of physical activity. CONCLUSION: In obese women, being highly active may, to a large extent, compensate for the risk-increasing effect of being obese, whereas in obese men who engage in a high level of physical activity, the risk of cardiovascular death may be higher than in lean and equally active men.  相似文献   
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Bernard–Soulier syndrome (BSS) is a rare autosomal recessively inherited bleeding disorder. Pregnancy in patients with BSS is characterized by ante‐, intra‐, or postpartum haemorrhage, which may be delayed and severe. There is no consensus in the management of BSS in pregnancy and so far only 16 pregnancies in nine patients have been described. We report a further three pregnancies in two women with the syndrome. We also outline our management of pregnant patients with BSS.  相似文献   
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