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21.

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   
22.
Chronic transplant dysfunction is a complex dynamic pathogenic process. Clinically, a decrease in glomerular filtration rate (GFR) becomes apparent leading to chronic renal insufficiency and dialysis or death from cardiovascular events. Chronic transplant dysfunction can develop into a chronic alIograft nephropathy (CAN) as a specific entity with dynamic progression. CAN includes a collection of immunologic and non-immunologic factors, rejection, ischemia time, donor and recipient characteristics and toxicity of calcineurin inhibitors. Despite improvements in immunosuppression, the long-range prognosis of renal allografts has not improved. Whether modern immunosuppressive concepts with reduction or avoidance of calcineurin inhibitors and a therapy based on antimetabolites, such as mycophenolate or mTOR-inhibitors could lead to a prolongation of transplant survival, remains to be seen.  相似文献   
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Multi-day signals, generally with duration of 2-10 days, are a prominent temporal variation type of radon (Rn) in geogas in the unsaturated zone. Rare multi-day Rn signals have been found which are characterized by: (a) a declining limb lasting up to 10 days which conforms to the radioactive decay of Rn, (b) recurs at the same location and (c) is recorded in diverse situations-volcanic and seismogenic. It suggested that a Rn blob is injected at a lower level on a steady upward flow of geogas whereby the rise and final fall of the signal are attributed to the edges of the blob while the central Rn-decay segment records the passing of the decaying blob itself. Rn-decay signals are a small subset of multi-day Rn signals which are considered as highly irregular and unusable for the understanding of geophysical processes. In difference, it is concluded that multi-day Rn signals are probably proxies of subtle geodynamic processes at upper crustal levels and are therefore significant for studying such processes.  相似文献   
25.
We study the image formation of vibro-acoustography systems based on a concave sector array transducer taking into account depth-of-field effects. The system point-spread function (PSF) is defined in terms of the acoustic emission of a point-target in response to the dynamic radiation stress of ultrasound. The PSF on the focal plane and the axis of the transducer are presented. To extend the obtained PSF to the 3D-space, we assume it is a separable function in the axial direction and the focal plane of the transducer. In this model, an image is formed through the 3D convolution of the PSF with an object function. Experimental vibro-acoustography images of a breast phantom with lesion-like inclusions were compared with simulated images. Results show that the experimental images are in good agreement with the proposed model.  相似文献   
26.
目的:通过对21例髋臼爆裂性骨折伴股骨头脱位的手术治疗,探讨处理此类损伤应注意的几个问题。方法:术前 X片及CT片明确骨折及脱位类型,采用患侧扩大的髂股入路或Langenbeck-Kocher入路,显露髂骨内外板及小骨盆内壁、髋臼前后柱,必要时显露坐骨大切迹,保持股骨头于脱位状态,直视下复位各骨折块尽量达到髓关节内软骨面光滑圆弧,在骨折复位状态下行内固定,之后使股骨头复位入髋臼,术后皮牵引,早期锻炼。结果:术后21例随访12~36个月, 骨折均愈合好,髋臼内壁形态光滑,元再脱位或创伤性关节炎症状出现。结论:髋臼爆裂性骨折伴股骨头脱位的病例,早期手术恢复髋臼内壁软骨面光滑圆弧可最大限度的恢复患肢功能,能有效地防止髓关节创伤性关节炎的发生,手术切口的选择是复位成功的关键,同时深静脉栓塞、坐骨神经的损伤及异位骨化的预防应予以重视。  相似文献   
27.
BACKGROUND: The laparoscopic resection of rectal cancer shows morbidity and oncological safety comparable to the open approach, but morbidity increases after conversion to open resection. No oncological long-term results are available for the latter patients. METHODS: From 01/01/2000-31/12/2002, patients with curatively resected rectal cancer enrolled in a observational study were evaluated for morbidity, mortality, tumor- and local recurrence rate, paying attention to patients with conversion from laparoscopic to open resection. RESULTS: 237 (3.3%) of 7,189 patients underwent laparoscopic resection (ITT). These patients showed significantly more T1/2 tumors (P<0.001) in earlier UICC stages (P<0.001) than open resected patients. 35 (14.8%) of 237 laparoscopic procedures were converted. Compared with patients receiving complete laparoscopic or open resection, these patients showed significantly higher frequencies of intraoperative (P<0.001) and general postoperative complications (P=0.003) as well as the highest overall morbidity (P=0.031). After a median follow-up of 30.1 months, the highest 5-year local recurrence rate was found in the converted group (16.0%). The laparoscopically resected patients showed a local recurrence rate of 3.3%, patients with open resection of 12.4% (P=0.082). The disease-free survival rate did not differ between the groups (P=0.585). CONCLUSION: Laparoscopic resection of rectal cancer provides oncological results similar to open resection. After conversion, the short and oncological long-term outcomes were worse. Considering a conversion rate of 15%, only a strict indication for the laparoscopic approach can be allowed, and laparoscopic resection should be performed at centers.  相似文献   
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