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81.
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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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This article describes early stages in the acquisition of a first vocabulary by infants and young children. It distinguishes two major stages, the first of which operates by a stand‐alone word‐to‐world pairing procedure and the second of which, using the evidence so acquired, builds a domain‐specific syntax‐sensitive structure‐to‐world pairing procedure. As we show, the first stage of learning is slow, restricted in character, and to some extent errorful, whereas the second procedure is determinative, rapid, and essentially errorless. Our central claim here is that the early, referentially based learning procedure succeeds at all because it is reined in by attention‐focusing properties of word‐to‐world timing and related indicants of referential intent.  相似文献   
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OBJECTIVE: A series of nasopharyngeal appliance designs is presented that represents our evolving experience over a 20-year period in the adjunctive use of prosthetic stents in the surgical correction of nasopharyngeal stenosis. DESIGN: Retrospective assessment of effectiveness of two nasopharyngeal stenosis hollow stent designs in a consecutive series of patients for relief of nasal obstructive symptoms. SETTING: Tertiary academic medical center, Craniofacial Program at Children's Hospital. PATIENTS: Four patients with nasopharyngeal stenosis were treated with a preoperatively fabricated stent made from a clasped palatal appliance onto which hollow acrylic conduits were extended through surgically re-created pharyngeal ports. A subsequent set of four patients with nasopharyngeal stenosis were treated with intraoperatively-fashioned silastic grommets, as opposed to palatal appliances. INTERVENTIONS: Postoperative intraoral stenting of nasopharyngeal ports. MAIN OUTCOME MEASURES: Maintenance of pharyngeal port opening after 1 year, improvement in nasal airway obstructive symptoms. RESULTS: The palatal appliance stents were less well tolerated and had a lower maintenance of port patency after device removal (4 of 8, 50%). The silastic grommets provided better retention into the ports and increased patient tolerance, as well as better 1-year port maintenance (6 of 8, 75%). CONCLUSIONS: The grommet stent appliance offers numerous advantages over a conventional dental-clasped appliance for prosthetic nasopharyngeal stenting, including obviation of extensive preoperative preparation, ease of insertion and removal, and exchange of air during the stenting period. Improved nasopharyngeal patency with this device may be due to greater patient tolerance and subsequent longer use.  相似文献   
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Heike  A.  Bischoff-Ferrari  Waiter  C.  Willett  John  B.  Wong  苗峥 《美国医学会杂志》2006,25(4):248-248
背景:对于脊椎以外的骨折而言,补充口服维生素D的预防作用和用量仍无定论。 目的:评估补充维生素D在预防老年髋骨骨折和非脊椎骨折方面的效果。 数据来源:使用MEDLINE、Cochrance对照试验记录(1960~2005年)以及EMBASE(1991-2005年),对英文和非英文文章进行系统回顾。通过与临床专家接触,通过检索美国社会骨和骨矿研究协会提供的参考文献和摘要(1995~2004年).进一步寻找更多的研究。检索词包括随机对照试验(randomized controlled trial,RCT)、临床对照试验、随机分配、双盲法、维生素D3、维生素D2;25-羟基维生素D、骨折、人类、老年、摔倒和骨密度。 研究选取:纳入的研究仅限于口服补充维生素D(维生素D3、维生素D2、补钙或不补钙)与补钙或安慰剂比较的双盲RCTs。试验于检查髋部骨折或非脊椎骨折的老年人(年龄≥60岁)中进行。数据提取:两位作者根据预先规定独立提取相关数据,其中包括研究质量指标。 数据综合:所有的汇总分析均以随机效应模型为基础。5项有关髋部骨折的RCTs(n=9294)和7项有关非脊椎骨折危险的RCTs(n=9820)符合我们的纳入标准。所有试验均使用了维生素D3。对髋部和非脊椎骨折预防研究的异质性亦进行观察,用低剂量(400IU/d)和高剂量(700~800IU/d)分别合并RCTs后异质性消失。与补钙或安慰剂相比,每天服700~800IU的维生素D可使髋部骨折的相对危险(relative risk,aa)下降26%(3项RCTs共计5572人;RR,0.74;95%可信区间[confidence interval,CI],0.61~0.88),使非脊椎骨折的相对危险下降23%(5项RCTs共计6098人;RR,0.77;95%CI,0.68~0.87)。每天服400IU的维生素D(2项RCTs共计3722人;髋部骨折RR,1.15;95%CI,0.88~1.50;非脊椎骨折RR,1.03;95%CI,0.86—1.24)未见明显获益。 结论:口服补充维生素D(700~800IU/d)可以降低尚能活动的老人或慈善机构收容的老年人发生髋部骨折和脊椎以外骨折的危险,每天口服400IU维生素D并不足以预防骨折。  相似文献   
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OBJECTIVE: To illustrate the safety and efficacy of the endoscopic laser approach for cricopharyngeal myotomy (CPM) compared to the traditional transcervical approach. STUDY DESIGN AND SETTING: Retrospective chart review of 22 patients undergoing CPM from 1996 to 2003 at the Mayo Clinic, Jacksonville. RESULTS: The laser CPM technique was used in 14 patients, and an open approach in 8. The mean hospital stay and operative times were shorter for the laser group. Functional outcome analyses showed improvement in both groups. There were no major complications in the laser group, while 1 patient in the transcervical group had a pharyngocutaneous fistula. CONCLUSIONS: The laser technique is at least as effective as the transcervical approach for CPM to improve dysphagia symptoms in the properly selected patient, with a low risk of major complications. SIGNIFICANCE: In this report, we provide the reader with data to support the safety and efficacy of laser CPM. EBM rating: B-3b.  相似文献   
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