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
The aetiology of vitiligo has not been fully elucidated, and several hypotheses have been investigated; among them, the most explored assumes an autoimmune basis for the disease. Supporting this hypothesis is the frequent co-occurrence of autoimmune diseases with vitiligo. In addition, various genetic loci associated with vitiligo harbour key immune response genes. Our general hypothesis is that autoimmunity-associated genes participate in the control of vitiligo susceptibility. To investigate this hypothesis, we tested for association between vitiligo and genes CYP27B1, REL, TNFAIP3 and IL2/IL21, all previously related to autoimmune diseases associated with vitiligo. The study was performed using two independent population samples: a family-based discovery set (211 trios) and a replication set (131 cases/119 controls). Statistically significant association with vitiligo was detected between markers of the REL and IL2 gene in the family-based sample. Both association signals were concentrated among patients displaying autoimmune comorbidity and non-segmental vitiligo. Evidence for validation was detected for IL2 marker. Our findings suggest REL and IL2 as new vitiligo susceptibility genes and reinforce the hypothesis of a shared genetic mechanism controlling vitiligo and other autoimmune diseases. 相似文献
Objective: To examine (i) the associations between physical activity dimensions, cardiorespiratory fitness and body composition and, (ii) the associations between physical activity dimensions, cardiorespiratory fitness, body composition and biomarkers of cardiometabolic health in persons with spinal cord injury (SCI).
Methods: A cross-sectional prospective cohort study with 7-day follow-up was conducted. Body composition, cardiorespiratory fitness and biomarkers of cardiometabolic health were measured in thirty-three participants with SCI (> 1 year post injury). Physical activity dimensions were objectively assessed over 7-days.
Results: Activity energy expenditure (r =.43), physical activity level (r =.39), and moderate-to-vigorous physical activity (MVPA) (r =.48) were significantly (P < 0.001) associated with absolute (L/min) peak oxygen uptake (?O2 peak). ?O2 peak was significantly higher in persons performing ≥150 MVPA minutes/week compared to <40 minutes/week (P?=?0.003). Individual physical activity dimensions were not significantly associated with biomarkers of cardiometabolic health. However, body composition characteristics (BMI, waist and hip circumference) showed significant (P < 0.04), moderate (r >.30) associations with parameters of metabolic regulation, lipid profiles and inflammatory biomarkers. Relative ?O2 peak (ml/kg/min) was moderately associated with only insulin sensitivity (r?=?0.37, P?=?0.03).
Conclusions: Physical activity dimensions are associated with cardiorespiratory fitness; however, stronger and more consistent associations suggest that poor cardiometabolic health is associated with higher body fat content. Given these findings, the regulation of energy balance should be an important consideration for researchers and clinicians looking to improve cardiometabolic health in persons with SCI. 相似文献
Background and study aimsThe COVID-19 outbreak has reorganized surgical team conditions regarding endoscopy. The number of interventions has been reduced, the number of healthcare professionals must be limited, and both the patients and physicians are more protected than ever.Patients and MethodsIn the highest peak of contagion in Colombia, endoscopy, colonoscopy, and esophagogastroduodenoscopy were performed using a low-cost disposable device. A total of 1388 procedures were performed. Every patient was assessed for symptoms via a telephone call, at the health center, and after the procedure, following specific attention routes.ResultsAfter procedure follow-up, no positive cases of COVID-19 were noted.ConclusionThe methodology reduced the risk of infection during the COVID-19 pandemic. 相似文献
OBJECTIVE: To investigate whether cardiovascular mortality related to obesity could be modified by physical activity. DESIGN: Mortality follow-up. SETTING: Population study. PARTICIPANTS: Participants in a health survey: 34 868 women and 32 872 men free from known cardiovascular disease or diabetes at baseline. MAIN OUTCOME MEASURES: Total cardiovascular mortality. MAIN RESULTS: During 16 years of follow-up, 3026 women and 3526 men had died from cardiovascular causes. In middle age, obesity [body mass index (BMI) of 30 or higher] was associated with increased risk of cardiovascular death, but the association weakened with age. After 70, there was no association between BMI and cardiovascular death. At all ages, a lower level of physical activity was associated with a higher cardiovascular mortality. In women with high physical activity, indicated by at least 30 min of moderate to vigorous activity more than once a week, cardiovascular mortality was only slightly higher in the obese compared to lean women (adjusted relative risk, 1.27; 95% confidence interval, 0.80-2.00). In men with high physical activity, cardiovascular mortality was, however, significantly higher among the obese (relative risk, 1.62; 95% confidence interval, 1.09-2.40). In both genders cardiovascular mortality was substantially higher in obese people who reported no regular physical activity compared to obese people with a high level of physical activity. CONCLUSION: In obese women, being highly active may, to a large extent, compensate for the risk-increasing effect of being obese, whereas in obese men who engage in a high level of physical activity, the risk of cardiovascular death may be higher than in lean and equally active men. 相似文献
The aim of the study was to evaluate differences in the relationship between peripheral diabetic neuropathy and microvascular reactivity in type 1 and type 2 diabetic patients. Twenty-eight type 1 and 37 type 2 diabetic patients were included in the study. Control groups consisted of 18 and 25, age and body mass index matched healthy persons. The presence of peripheral neuropathy was estimated by vibration perception threshold higher than 20 V evaluated by biothesiometry. Microvascular reactivity was examined by laser doppler fluxmetry using postocclusive reactive hyperemia and thermal hyperemia. The following variables of vascular reactivity were examined: peak flow after occlusion as a difference between maximal and basal perfusion (PORH (max)), mean velocity increase during postocclusive hyperemia (PORH (max)/t (1)), peak flow during thermal hyperemia (TH (max)) and the mean velocity increase in the perfusion during thermal hyperemia (TH (max)/t (2)). These parameters are expressed in perfusion units (PU) or in perfusion units per second (PU . s (-1)). The microvascular reactivity in type 1 diabetic patients without evidence of peripheral neuropathy was comparable with that in healthy persons and it was significantly higher than in type 1 diabetic patients with peripheral neuropathy in all tested parameters (PORH (max): 64 [40; 81] PU vs. 24 [17; 40] PU, p < 0.001, PORH (max)/t (1): 5.41 [2.69; 8.18] PU/s vs. 1.21 [0.69; 2.5] PU/s, p < 0.001, TH (max): 105 [77; 156] PU vs. 56 [46; 85] PU, p < 0.001 and TH (max)/t (2): 2.48 [1.67; 3.33] PU/s vs. 0.87 [0.73; 1.06] PU/s, p < 0.001). On the contrary, no difference in the microvascular reactivity parameters was found between type 2 diabetic patients with and without neuropathy (PORH (max): 48 [30; 60] PU vs. 49 [36; 57] PU, NS, PORH (max)/t (1): 3.46 [2.15; 5.19] PU/s vs. 3.29 [2.45; 4.8] PU/s, NS, TH (max): 95 [78; 156] PU vs. 97 [73; 127] PU, NS and TH (max)/t (2): 1.45 [0.95; 2.84] PU/s vs. 1.37 [1.12; 1.95] PU/s, NS). In both these groups microvascular reactivity was comparable with that estimated in the age and BMI matched healthy persons. An inverse relationship was observed between microvascular reactivity and vibratory perception threshold in type 1 diabetic patients, but it was not true in type 2 diabetic patients. We suppose that the pathogenesis of neuropathy and impaired microvascular reactivity may be differently influenced by metabolic factors in type 1 and type 2 diabetic patients. 相似文献
OBJECTIVE: Alveolar distraction is a relatively novel procedure by which alveolar bone and underlying mucosa are regenerated. The low predictability of other vertical or horizontal bone regeneration methods has increased interest in this promising technique. This article was designed to review published clinical and experimental results on alveolar distraction, including basic research in other disciplines (maxillofacial and orthopedic distraction) related to or with influence on alveolar distraction. STUDY DESIGN: A review of the international literature was performed to summarize results of clinical and experimental studies on alveolar distraction and on distraction at other anatomical sites that contribute important findings on tissue biology, molecular mechanisms, and other factors that influence and participate in the alveolar distraction process. RESULTS: Research into alveolar distraction has addressed the latency phase, distraction phase, and consolidation phase, yielding highly variable results. Little experimental research has been carried out on this procedure, and most publications are clinical studies with a short follow-up period. Published studies have reported a high rate of complications, attributable to our current lack of understanding of the process. CONCLUSIONS: Definitive conclusions on alveolar distraction are hampered by the lack of clinical and experimental studies to date. Greater knowledge of the factors that influence the distraction process will lead to a more predictable and efficacious distraction technique and a better distractor design. 相似文献
Eye drops contain several ophthalmic medications which can produce allergic reactions. We report the case of a patient with contact dermatitis from neomycin and a probable fixed exanthema after parenteral administration of tobramycin who tolerated topical tobramycin and other aminoglycosides. 相似文献