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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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Coronary magnetic resonance angiography (CMRA) is a technique in clinical evolution. Current clinical applications include assessment for coronary anomalies, aneurysms, bypass graft patency, and, in experienced centers, the exclusion of proximal and multivessel coronary artery disease (CAD). As local expertise increases and more extensive multicenter data become available, additional applications will be established. CMRA promises to supplement and in some cases obviate the need for X-ray contrast angiography, and to expand our understanding of the pathophysiology of CAD. Zusammenfassung Die Magnetresonanzangiographie der Koronargefäße (CMRA) ist eine sich ständig weiterentwickelnde Technik. Etablierte Anwendungen sind zurzeit die Beurteilung von koronaren Anomalien, Aneurysmen und der Durchgängigkeit von Bypasses. Auch der Ausschluss proximaler Koronarstenosen und einer koronaren Mehrgefäßerkrankung ist in einigen spezialisierten Zentren möglich. Mit zunehmender Erfahrung der jeweiligen Anwender und der Verfügbarkeit von Ergebnissen großer multizentrischer Studien können zukünftig weitere klinische Anwendungen etabliert werden. In der Zukunft könnte die CMRA ergänzende Informationen zur Indikationsstellung einer konventionellen Röntgenangiographie bringen und in einigen Fällen diese Untersuchung sogar ersetzen. Die CMRA wird unseren Einblick in die Pathophysiologie der koronaren Herzerkrankung sicher erweitern.  相似文献   
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PURPOSE: Angiotensin converting enzyme inhibitors (ACEIs) are a group of drugs used to treat hypertension and heart failure, with additional benefits, such as cardiovascular and renal protection, in patients with diabetes. However, angioedema as a complication of ACEI therapy is under-recognized. As there are important implications for anesthesiologists and emergency medicine physicians, a review was undertaken to document the scope of the problem of ACEI-induced angioedema.. METHODS: A review of the published literature (identified by searching Medline, EMBASE and CINAHL) was undertaken, addressing the clinical uses of ACEIs and the incidence, risk factors, pathophysiology, clinical presentation and management of angioedema associated with the use of these drugs. PRINCIPAL FINDINGS: The incidence of ACEI related angioedema has increased from 0.1-0.2% to 1% over the last decade. Patients who are receiving ACEIs are predisposed to developing angioedema which may be triggered by trauma, airway instrumentation, infection, and irritant fumes, particularly in those who are at increased risk. Cases of acute facial and airway oedema, due to ACEI drug administration, may be misdiagnosed as an anaphylactic reaction, and the association with ACEIs may be ignored. Some cases of intraoperative and postoperative airway edema may be precipitated by airway instrumentation in patients receiving ACEI drugs. The severity of airway compromise ranges from mild facial edema to severe laryngeal or subglottic edema which may prove life-threatening. CONCLUSION: In view of the widespread clinical indications and ever-increasing use of ACEI drugs, the potentially life-threatening adverse reaction of ACEI-associated angioedema, and its treatment, must be recognized by anesthesiologists and all clinicians involved in airway management.  相似文献   
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BACKGROUND: Little is known about the health-related quality of life (HRQOL) of nonclinical samples of people with irritable bowel syndrome (IBS) in Canada. In a pilot survey, the impact of IBS on HRQOL using a population-based, urban sample was examined. METHODS: A random sample of Calgary residents (18 years of age or older), selected by random digit dialing (n=1521), completed a structured questionnaire including ROME II Criteria and Medical Outcomes Study Short-Form 12-Item Health Survey, version 2 (SF-12v2). The mean scale and summary scores of SF-12v2 for those who did and did not meet ROME II criteria and for those who met ROME II criteria with and without visiting a physician in past three months were determined and compared using multiple regression analyses. RESULTS: Of the 951 households successfully contacted, 590 (62%) were willing to participate, of which 437 (74%) individuals were recruited. One hundred ten IBS cases (81 of which were women) and 327 non-IBS controls (180 of which were women) were identified. All of the eight mean scale scores and the two mean summary scores were significantly lower in people with IBS than in those without, whether or not adjusting for demographics. Forty-four of the 110 IBS cases (40%) sought medical help. Significantly lower mean physical component score and three scale scores (general health, social functioning and role physical) were found in those who sought medical help than in those who did not. CONCLUSIONS: People with IBS experience significant impairment in HRQOL, including both physical and mental well-being. People with IBS who seek medical help report worse physical health than those who do not, but their mental health is no different.  相似文献   
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