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Brusselle G.G.,Ghent University | VanderStichele C.,Ghent University | Jordens P.,OLV Ziekenhuis | Deman R.,AZ Groeninge | And 14 more authors.

Background: Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases may benefit from macrolides. Methods: We performed a randomised double-blind placebo-controlled trial in subjects with exacerbationprone severe asthma. Subjects received low-dose azithromycin (n=55) or placebo (n=54) as add-on treatment to combination therapy of inhaled corticosteroids and long-acting β2 agonists for 6 months. The primary outcome was the rate of severe exacerbations and LRTI requiring treatment with antibiotics during the 26-week treatment phase. Secondary efficacy outcomes included lung function and scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ). Results: The rate of primary endpoints (PEPs) during 6 months was not significantly different between the two treatment groups: 0.75 PEPs (95% CI 0.55 to 1.01) per subject in the azithromycin group versus 0.81 PEPs (95% CI 0.61 to 1.09) in the placebo group (p=0.682). In a predefined subgroup analysis according to the inflammatory phenotype, azithromycin was associated with a significantly lower PEP rate than placebo in subjects with noneosinophilic severe asthma (blood eosinophilia ≤200/ml): 0.44 PEPs (95% CI 0.25 to 0.78) versus 1.03 PEPs (95% CI 0.72 to 1.48) (p=0.013). Azithromycin significantly improved the AQLQ score but there were no significant between-group differences in the ACQ score or lung function. Azithromycin was well tolerated, but was associated with increased oropharyngeal carriage of macrolide-resistant streptococci. Conclusions Azithromycin did not reduce the rate of severe exacerbations and LRTI in patients with severe asthma. However, the significant reduction in the PEP rate in azithromycin-treated patients with non-eosinophilic severe asthma warrants further study. ClinicalTrials.gov number NCT00760838. Source

Mathys V.,Scientific Institute of Public Health | Van De Vyvere M.,Ziekenhuis Netwerk Antwerpen ZNA Stuivenberg | De Droogh E.,ZNA Middelheim | Soetaert K.,Scientific Institute of Public Health | Groenen G.,Belgian Lung and Tuberculosis Association
International Journal of Tuberculosis and Lung Disease

The Xpert®MTB/RIF assay detects the presence of Mycobacterium tuberculosis and its resistance to rifampicin (RMP) directly in sputum samples. Discrepant results were observed in a case of smear-positive pulmonary tuberculosis that was Xpert-resistant but phenotypically susceptible to RMP. Complementary investigations (repeat Xpert, Genotype®MTBDRplus assay and sequencing of the rpoB gene) revealed the presence of a silent mutation in the rpoB gene, leading to the conclusion of a false-positive Xpert result. As misinterpretation of Xpert results may lead to inappropriate treatment, the presence of rpoB mutations should be confirmed by sequencing the rpoB gene. © 2014 The Union. Source

Slieker J.C.,Erasmus Medical Center | Komen N.,Erasmus Medical Center | Mannaerts G.H.,St. Franciscus Gasthuis | Karsten T.M.,Reinier de Graaf Groep | And 4 more authors.
Archives of Surgery

Objective: To determine the risk factors for symptomatic anastomotic leakage (AL) after colorectal resection. Design: Review of records of patients who participated in the Analysis of Predictive Parameters for Evident Anastomotic Leakage study. Setting: Eight health centers. Patients: Two hundred fifty-nine patients who underwent left-sided colorectal anastomoses. Intervention: Corticosteroids taken as long-term medication for underlying disease or perioperatively for the prevention of postoperative pulmonary complications. Main OutcomeMeasures: Prospective evaluations for risk factors for symptomatic AL. Results: In 23% of patients, a defunctioning stoma was constructed. The incidence of AL was 7.3%. The clinical course of patients with AL showed that in 21% of leaks, the drain indicated leakage; in the remaining patients, computed tomography or laparotomy resulted equally often in the detection of AL. In 50% of patients with AL, a Hartmann operation was needed. The incidence of AL was significantly higher in patients with pulmonary comorbidity (22.6% leakage), patients taking corticosteroids as longterm medication (50% leakage), and patients taking corticosteroids perioperatively (19% leakage). Perioperative corticosteroids were prescribed in 8% of patients for the prevention of postoperative pulmonary complications. Conclusions: We found a significantly increased incidence of AL in patients treated with long-term corticosteroids and perioperative corticosteroids for pulmonary comorbidity. Therefore, we recommend that in this patient category, anastomoses should be protected by a diverting stoma or a Hartmann procedure should be considered to avoid AL. Trial Registration: trialregister.nl Identifier: NTR1258. Source

De Greve J.,Oncologisch Centrum UZ Brussel | Teugels E.,Oncologisch Centrum UZ Brussel | Geers C.,Oncologisch Centrum UZ Brussel | Decoster L.,Oncologisch Centrum UZ Brussel | And 6 more authors.
Lung Cancer

Human epidermal growth factor receptor (HER)2/neu kinase domain mutations are found in approximately 1-4% of lung adenocarcinomas with a similar phenotype to tumors with epidermal growth factor receptor (EGFR) mutations. Afatinib is a potent irreversible ErbB family blocker. We determined the tumor genomic status of the EGFR and HER2 genes in non- or light smokers with lung adenocarcinoma in patients who were entered into an exploratory Phase II study with afatinib. Five patients with a non-smoking history and metastatic lung adenocarcinomas bearing mutations in the kinase domain of HER2 gene were identified, three of which were evaluable for response. Objective response was observed in all three patients, even after failure of other EGFR- and/or HER2-targeted treatments; the case histories of these patients are described in this report. These findings suggest that afatinib is a potential novel treatment option for this subgroup of patients, even when other EGFR and HER2 targeting treatments have failed. © 2012 Elsevier Ireland Ltd. Source

Van den Wyngaert T.,University of Antwerp | Huizing M.T.,University of Antwerp | Fossion E.,ZNA Middelheim | Vermorken J.B.,University of Antwerp
Oral Oncology

Bisphosphonates (BP) have been associated with the occurrence of osteonecrosis of the jaw (ONJ), possibly by causing an excessive bone turnover inhibition. However, little in vivo evidence exists to support this theory. The 99mTc-medronate scintigrams of patients with skeletal metastases and BP use (n = 40) were individually matched with cancer patients without BP exposure (n = 40) and controls with neither malignancy nor BP use (n = 40). Patients with established ONJ or intense focal abnormalities in the studied regions were excluded. Mandibular (MBT) bone turnover was quantified relative to the femur by defining regions-of-interest with correction for background activity. The patients with BP exposure (34 female, 6 male) had a median age of 63 years (range 25-81) and received a median number of 11 zoledronic acid administrations (range 1-44). Most patients suffered from breast cancer (n = 30). The mean ratio of the MBT in cancer patients with BP use over non-users was 0.88 (95% CI 0.80-0.96; p = 0.003), and 0.83 (95% CI 0.73-0.94; p = 0.001) when BP using oncological patients were compared with controls without malignancy or BP use. The ratio of MBT's between BP naive patients was 0.95 (95% CI 0.83-1.07; p = 0.8). No dose-response effect between the number of BP administrations and MBT could be demonstrated (r = 0.02; p = 0.9). These findings suggest that, relative to the femur, BP exert a stronger effect on mandibular bone turnover, which strengthens the hypothesis that the inhibition of bone turnover may be important in the pathophysiology of ONJ. © 2010 Elsevier Ltd. All rights reserved. Source

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