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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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A 20-month-old Kuwaiti girl had manifestations of lipoid proteinosis, a rare autosomal recessive disorder seen more commonly in Caucasians. This condition is diagnosed based on clinical, histopathologic, and ultrastructural criteria. Its biochemical and genetic aspects are still poorly understood.  相似文献   
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The present study sought to investigate the moderating function that social problem-solving effectiveness serves in relation to negative stressful life events and depressive symptomatology. It was also hypothesized that knowledge of problem solving would improve upon the prediction of level of depressive symptoms beyond the assessment of stressful events. Results involving 462 undergraduate students provide support for both predictions. Specifically, findings from a multiple regression analysis indicated that (1) differences in reported depressive mood between subjects under high and low stress levels were minimal for individuals characterized as effective problem-solvers, relative to those persons with problem-solving scores reflective of ineffective problem solving; and (2) assessment of problem-solving scores and their interaction with stress level provided for an additional three times the amount of explained variance in predicting depression scores beyond life stress scores. Additionally, a cross-validation of the regression analysis was conducted and found to result in a minimal amount of shrinkage that could be due to samplespecific characteristics.We would like to extend our appreciation to two anonymous reviewers for their helpful comments on an earlier draft of this article. The study was supported in part by a grant funded by Fairleigh Dickinson University to the first author.  相似文献   
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This paper presents some of the findings from the Smoking in Pregnancy study of attitudes towards smoking among pregnant women, mothers of young children and their partners in East Surrey. As part of the study, respondents completed a General Health Questionnaire to identify mental health difficulties and, if they were smoking at the time of the study, they also completed the Fagerstrom nicotine addiction test. Eleven female respondents had high scores on the General Health Questionnaire, suggesting symptoms of depression, anxiety and/or social dysfunction for these women. There was no evidence that smokers were suffering from greater mental health difficulties than ex-smokers or non-smokers. However, the General Health Questionnaire scores of smokers were positively associated with their level of nicotine dependence. Furthermore, when General Health Questionnaire scores of all respondents were compared with self-reported health status there was a marked discrepancy suggesting under-reporting of symptoms by women.  相似文献   
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We report seven cases of primary cutaneous phaeohyphomycosis. There were five males and two females, ranging in age from 42–65 years (mean 57.7 years). Two patients were otherwise healthy, but five were immunocompromised. One patient had rheumatoid arthritis and was on oral prednisone; two were renal transplant recipients, one was a heart transplant recipient, and the fifth had dermatomyositis. No history of trauma was elicited from any of the patients, but in two cases, foreign material was seen in the tissue sections. All lesions were oil the extremities. In two cases, tissues were cultured, and these grew Exophiala jean-selmei . The others were not cultured because fungal infection was not clinically suspected. No systemic disease developed in any of the cases, and all were cured by the simple, complete excision of the lesions.  相似文献   
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Background/Aims: This study was designed to assess changes in: (a) neuropsychological tests, measures of memory, quality of life and scores for anxiety and depression; (b) liver function tests; and (c) the relationship between these following transjugular intrahepatic portosystemic stent-shunt.Methods: Twenty-nine patients undergoing transjugular intrahepatic portosystemic stent-shunt for recurrent variceal haemorrhage, 12 matched patients with cirrhosis and variceal haemorrhage manage with variceal band ligation and 16 normal controls were studied. Patients in any of the groups who were clinically encephalopathic were excluded from the study. Serial changes in the conventional liver function tests and Indocyanine green clearance, and psychometric function (Hospital Anxiety Depression Scale, Rivermead Behavioral Memory Test, Quality of Life and the memory and reaction sub-tests of the Cambridge Automated Neuropsychological Test Assessment Battery) were measured prior to and 1, 3, 9 and 15 months following transjugular intrahepatic portosystemic stent-shunt.Results: Over a mean follow up of 9.1 months in the transjugular intrahepatic portosystemic stent-shunt group (range 3–28), one patient (3%) developed clinically detectable encephalopathy. Sixty-seven percent of patients with cirrhosis showed evidence of subclinical encephalopathy as compared with the control population. Significant deterioration occurred in the reaction sub-tests of the Cambridge Automated neuropsychological Test Assessment Battery in patients, both in the transjugular intrahepatic portosystemic stent-shunt group and the controls with cirrhosis, during follow up. Transjugular intrahepatic portosystemic stent-shunt was followed by significant deterioration in levels of anxiety and psychological component of the quality of life. The Rivermead Behavioural Memory Test and the memory sub-test of the Cambridge Automated Neurpsychological Test Assessment Battery did, however, improve significantly at 1 and 15 months after transjugular intrahepatic portosystemic stent-shunt, respectively. Serum alanine aminotransferase, bilirubin and indocyanine green clearance deteriorated significantly following transjugular intrahepatic portosystemic stent-shunt (p<0.001, p<0.001 and p<0.0001, respectively). Significant correlation was observed between changes in the indocyanine green clearance and changes in the complex and simple reaction time subtests of the Cambridge Automated Neuropsychological Test Assessment Battery (r=0.6 and r=0.66, respectively).Conclusions: The results of this study showed that about 67% of patients with cirrhosis were subclinically encephalopathic and that temporary deterioration occurred in the Cambridge Automated Neuropsychological Test Assessment Battery during follow up, both in patients having transjugular intrahepatic portosystemic stent-shunt and in the controls with cirrhosis. These parallel the changes in the liver function tests and indocyanine green clearance. Temporary deterioration was also observed in the Quality of Life and Hospital Anxiety Depression Scale in the transjugular intrahepatic portosystemic stent-shunt group, although the measures of memory improved. Further studies should address the biochemical mechanisms of these changes and the role of prophylactic measures.  相似文献   
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