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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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The objective of this study is to test the luminous efficiency functions V(lambda), V'(lambda), V(10)(lambda) and their linear combinations on the basis of a data set gained from a simulated mesopic night-time driving experiment. Another aim is to provide 'real-world' data for the 'X framework' or 'linear combination model', and to find out its limits in a practical situation. Human performance was measured by the reaction time method. Results show that the single parameter of the linear combination of photopic and scotopic luminous efficiency functions can be determined analytically with little variation for a given mesopic background luminance level and a given visual target colour, but the computation leads to considerable deviations comparing all three target colours (red, green and blue) used in the experiment. The conclusion for the given experimental conditions is that the single parameter of the linear combination model has an increasing deviation for lower background luminance levels.  相似文献   
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Minimally invasive surgery is rapidly becoming the desired surgical standard, especially for pediatric patients. Infants and children are a particular technical challenge, however, because of the small size of target anatomical structures and the small surgical workspace. Computer-assisted robot-enhanced surgical telemanipulators may overcome these challenges by facilitating surgery in a small workspace. We studied the feasibility of performing robotic endoscopic neck surgery on a porcine model of the human infant neck. The study design was a prospective, feasibility pilot study of a small cohort for proof of concept and for a survival model. Sixteen non-survival piglets weighing 4.5–10 kg were used to develop the surgical approach and operative technique. Eight piglets aged 3–6 weeks old and weighing 4.0–9.1 kg underwent survival thyroidectomy by a cervical endoscopic approach using the Zeus surgical robot, which includes the Aesop endoscope holder and “Microwrist” microdissecting instruments. We succeeded in performing endoscopic robotic neck surgery on a piglet as small as 4 kg, in an operative pocket as small as 2 cm3. Total incision length for all three ports was ≤23 mm. There were no major complications, no major robotic instrument malfunctions or breakages, and no procedures required conversion to open surgery. These results support the feasibility of robotic endoscopic neck surgery on a neck the size of a human infant’s. Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users.  相似文献   
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Intradiscal Thermal Annuloplasty for Discogenic Pain: An Outcome Study   总被引:3,自引:1,他引:2  
Objectives: Published studies of intradiscal thermal annuloplasty (IDTA) have shown at most 50% pain relief as an improved outcome with little focus on functional improvement in the treatment of discogenic pain. Previous studies have used a number of criteria for patient selection including low back pain unresponsive to conservative care, no compressive radiculopathy, positive provocative discography and absence of previous surgery at the same symptomatic level. The purpose of present study is to examine the hypothesis that additional inclusion criteria for patient selection such as disc height, absence of degenerative disc disease (DDD) in untreated discs, absence of herniated nucleus pulposus or lumbar canal stenosis may improve the outcome of treatment. Methods: In this prospective case‐series study additional criteria of patient selection were introduced, namely disc height of at least 50%, no lumbar canal stenosis, one or two levels of DDD, no evidence of nucleus pulposus herniation on magnetic resonance image. Thirty‐four patients were enrolled in the study and 32 of them were followed over a period of 12 months. The visual analog scale (VAS) pain score and seven activities of daily living (ADLs) were followed and reported on a scale from 0 to 10. Results: Sustained decrease of the VAS pain scores was observed from 3 to 12 months following IDTA. ADLs improved in all patients between 3 and 12 months post‐treatment. Patients in the Bureau of Workers Compensation (BWC) group had a higher VAS score but showed the same level of improvement in ADLs as compared to commercial insurance or self‐pay patients. In the non‐BWC patient group an average VAS pain score decrease of more than 6 points on a 10‐point scale was reported at 6 to 12 months following IDTA. Conclusions: We found dramatic improvement of pain scores and ADLs following IDTA when strict patient selection was applied. We believe that IDTA is an effective, minimally invasive treatment for discogenic pain in properly selected patients.  相似文献   
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PURPOSE: To study efficacy and toxicity of radiochemotherapy in esophageal cancer including initial endoluminal high-dose-rate brachytherapy (HDR-BT). PATIENTS AND METHODS: Between 01/1995 and 06/2005, 61 patients with esophageal cancer were treated preoperatively with definitive and palliative intent. Treatment started with intraluminal HDR-BT for recanalization of the esophagus (single fraction size of 8 Gy in 0.5 cm depth, three times, q7d) followed by external-beam radiation therapy (50 Gy total dose, 5 x 2 Gy/week, 25 fractions in 5 weeks). Chemotherapy was started simultaneously with external irradiation (three courses of cisplatin and 5-fluorouracil, q21d). RESULTS: Swallowing function improved in 55/61 patients (dysphagia classification according to the RTOG), and worsened in 6/61 patients, respectively. Median duration of symptomatic improvement was 11 months, median follow-up 12 months (range 3-68 months). Following simultaneous radiochemotherapy, tumor resectability was achieved in 7/25 patients of the neoadjuvant group, and the histological specimen showed complete remission in 6/7 patients. CONCLUSION: These results indicate a favorable effect of simultaneous radiochemotherapy starting with endoluminal HDR-afterloading-( AL-)BT in esophageal cancer.  相似文献   
9.
股骨干骨折--扩髓和不扩髓髓内钉比较   总被引:4,自引:0,他引:4  
治疗股骨干骨折,采用不扩髓髓内钉比扩髓髓内钉手术时间明显缩短,而且失血也少。但是,扩髓钉的骨愈合更快,延迟愈合更少。两者都没有显著增加包括肺损害等其它并发症的风险。功能结果不能确定。  相似文献   
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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently described familial cerebrovascular disorder shown to map to chromosome 19q12. Familial hemiplegic migraine has also been shown in some families to map close to the CADASIL locus. The fully developed CADASIL phenotype consists of recurrent strokes developing in the fourth decade, progressing to a pseudobulbar palsy, spastic quadriparesis, and subcortical dementia. In an Irish family 15 members were fully investigated by magnetic resonance scanning; 10 had typical magnetic resonance features of CADASIL. Five members of this family had familial hemiplegic migraine and 4 of these had magnetic resonance evidence of CADASIL. Two other members had migraine with and without aura as a presenting clinical symptom of CADASIL. This disorder has been shown by linkage analysis to map to the CADASIL locus at chromosome 19. The phenotype at presentation of CADASIL in this family was variable and age related and included familial hemiplegic migraine, migraine with and without aura, transient ischemic attacks, strokes, and spinal cord infarction. This family study increases our understanding of the spectrum of clinical manifestations of this underrecognized familial cerebrovascular disorder.  相似文献   
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