24 research outputs found
Outcome of HIV-1-associated cryptococcal meningitis, Denmark 1988-2008
No full textIntroduction: The risk of HIV-1-associated Cryptococcus neoformans meningitis (CM) has decreased and the outcome has improved with the use of combination antiretroviral therapy (cART). Outcome has not been reported in Denmark in the cART era. Methods: A review of all cases of HIV-1-associated CM treated at 2 hospitals in Denmark was carried out. Survival was compared by time-updated Cox proportional hazards analysis. Results: A total of 45 cases were evaluated. Six individuals (13.3%) died within 30 days of being diagnosed with CM. cART was initiated a median of 15 days (range 3–53) after a diagnosis of CM for 12 individuals and did not affect 30-day outcome. Older age, however, was associated with an increased risk of death at 30 days (mortality rate ratio (MMR) 1.16 (95% confidence interval (95% CI) 1.05–1.30) per y increment). Twenty-four (55.8%) of 43 individuals (2 had emigrated) died within the 1st y. Initiation of cART significantly improved 1-y outcome (MMR 0.22, 95% CI 0.06–0.77). Mental status, CD4 T cell count, and antifungal did not affect short- or long-term outcome. Conclusions: We found that long-term survival after HIV-1-associated CM has improved significantly with the use of cART. Short-term mortality was not affected by initiation of cART and remained high. Read More: http://informahealthcare.com/doi/abs/10.3109/00365548.2011.611168Abstract Introduction: The risk of HIV-1-associated Cryptococcus neoformans meningitis (CM) has decreased and the outcome has improved with the use of combination antiretroviral therapy (cART). Outcome has not been reported in Denmark in the cART era. Methods: A review of all cases of HIV-1-associated CM treated at 2 hospitals in Denmark was carried out. Survival was compared by time-updated Cox proportional hazards analysis. Results: A total of 45 cases were evaluated. Six individuals (13.3%) died within 30 days of being diagnosed with CM. cART was initiated a median of 15 days (range 3?53) after a diagnosis of CM for 12 individuals and did not affect 30-day outcome. Older age, however, was associated with an increased risk of death at 30 days (mortality rate ratio (MMR) 1.16 (95% confidence interval (95% CI) 1.05?1.30) per y increment). Twenty-four (55.8%) of 43 individuals (2 had emigrated) died within the 1(st) y. Initiation of cART significantly improved 1-y outcome (MMR 0.22, 95% CI 0.06?0.77). Mental status, CD4 T cell count, and antifungal did not affect short- or long-term outcome. Conclusions: We found that long-term survival after HIV-1-associated CM has improved significantly with the use of cART. Short-term mortality was not affected by initiation of cART and remained high
Increased sputum lactate during oral glucose tolerance test in cystic fibrosis
No full textBlood glucose levels exceeding 8 mM are shown to increase glucose levels in airway surface in cystic fibrosis (CF). Moreover, high levels of endobronchial glucose are proposed to increase the growth of common CF bacteria and feed the neutrophil-driven inflammation. In the infected airways, glucose may be metabolized by glycolysis to lactate by both bacteria and neutrophils. Therefore, we aimed to investigate whether increased blood glucose may fuel the glycolytic pathways of the lung inflammation by determining sputum glucose and lactate during an oral glucose tolerance test (OGTT). Sputum from 27 CF patients was collected during an OGTT. Sputum was collected at fasting and one and two hours following the intake of 75 g of glucose. Only participants able to expectorate more than one sputum sample were included. Glucose levels in venous blood and lactate and glucose content in sputum were analyzed using a regular blood gas analyzer. We collected 62 sputum samples: 20 at baseline, 22 after 1 h, and 20 after 2 h. Lactate and glucose were detectable in 30 (48.4%) and 43 (69.4%) sputum samples, respectively. The sputum lactate increased significantly at 2 h in the OGTT (p = 0.024), but sputum glucose was not changed. As expected, plasma glucose level significantly increased during the OGTT (p < 0.001). In CF patients, sputum lactate increased during an OGTT, while the sputum glucose did not reflect the increased plasma glucose. The increase in sputum lactate suggests that glucose spills over from plasma to sputum where glucose may enhance the inflammation by fueling the anaerobic metabolism in neutrophils or bacteria.</p
Osteoporosis Is Associated with Deteriorating Clinical Status in Adults with Cystic Fibrosis
No full textBackground. Cystic fibrosis (CF) patients are in increased risk of osteoporosis. We aimed to determine the osteoporosis prevalence in an adult CF cohort and investigate calcium metabolic parameters and clinical status’ association with bone mineral density evaluated by dual X-ray absorptiometry scan. Methods. We performed a cross section database study of adults at a tertiary CF Center. Z scores were applied for patients 50 years of age. Results. One hundred twenty-five patients were included. Compared to nonosteoporotic patients, osteoporotic patients (15%) had significantly lower percent predicted forced expiratory volume in 1 second (ppFEV1), lower body mass index, higher frequency of CF-related diabetes and chronic lung infection, and higher high-sensitive C-reactive protein and glycated hemoglobin levels. Vitamin D was not associated with any outcome. In multivariate analyses, only ppFEV1 and female gender were independently associated with Z scores. Conclusions. Osteoporosis in CF occurs with deteriorating clinical status while the role of calcium metabolism seems minor. Gender specific and dysglycemic impact on bone status should be investigated further
Changes in RANKL during the first two years after cART initiation in HIV-infected cART naïve adults
No full textAbstract Background By assessing the changes in concentration of soluble receptor activator of nuclear factor κ B ligand (RANKL) and osteoprotegrin (OPG) after initiation of combination antiretroviral therapy (cART) in treatment-naïve HIV-infected patients we aimed to evaluate whether the initial accelerated bone loss could be mediated by increased soluble RANKL (sRANKL) levels associated with CD4+ T cell recovery. Methods We used multiplex immunoassays to determine sRANKL and OPG concentrations in plasma from 48 HIV patients at baseline and 12, 24, 48 and 96 weeks after cART initiation. Results Soluble RANKL changed significantly over time (overall p = 0.02) with 25% decrease (95% CI: -42 to −5) at week 24 compared to baseline and stabilized at a lower level thereafter. We found no correlation between CD4+ T cell count increment and changes in sRANKL or between percentage change in BMD and changes in sRANKL. Conclusion In this study there was no indication that the accelerated bone loss after cART initiation was mediated by early changes in sRANKL due to CD4+ T cell recovery. Future studies should focus on the initial weeks after initiation of cART. Trial registration Clinical-Trial.gov . id NCT00135460 , August 25, 2005. The study was approved by the Danish Data Protection Agency, Danish Medicines Agency and Regional Ethics Committee
Comparing the harmful effects of nontuberculous mycobacteria and Gram negative bacteria on lung function in patients with cystic fibrosis
No full textBACKGROUND: To better understand the relative effects of infection with nontuberculous mycobacteria and Gram negative bacteria on lung function decline in cystic fibrosis, we assessed the impact of each infection in a Danish setting. METHODS: Longitudinal registry study of 432 patients with cystic fibrosis contributing 53,771 lung function measures between 1974 and 2014. We used a mixed effects model with longitudinally structured correlation, while adjusting for clinically important covariates. RESULTS: Infections with a significant impact on rate of decline in %FEV1 were Mycobacterium abscessus complex with -2.22% points per year (95% CI -3.21 to -1.23), Burkholderia cepacia complex -1.95% (95% CI -2.51 to -1.39), Achromobacterxylosoxidans -1.55% (95% CI -2.21 to -0.90), and Pseudomonas aeruginosa -0.95% (95% CI -1.24 to -0.66). Clearing M. abscessus complex was associated with a change to a slower decline, similar in magnitude to the pre-infection slope. CONCLUSIONS: In a national population we have demonstrated the impact on lung function of each chronic CF pathogen. M. abscessus complex was associated with the worst impact on lung function. Eradication of M. abscessus complex may significantly improve lung function
Patients with cystic fibrosis and advanced lung disease benefit from lumacaftor/ivacaftor treatment
No full textA cross-sectional study in adiponectin, glucose metabolism, and body composition in cystic fibrosis
No full textObjectiveWe hypothesized that the insulin-sensitizing adipokine adiponectin (ADP) is upregulated in cystic fibrosis (CF) related diabetes (CFRD) and underweight adults with CF. We aimed to assess correlations between glucose metabolism, body composition and ADP in CF.MethodsWe performed a cross-sectional study among adults with CF at the Copenhagen CF Center. The study included a fasting level of ADP, an oral glucose tolerance test (OGTT), and a dual energy-x-ray absorptiometry scan.ResultsIn total, 115 patients were included of whom 104 had an OGTT performed. Glucose intolerance was not correlated with ADP in multivariable analysis, while increased hepatic insulin resistance (i.e., HOMA-IR) was correlated with reduced ADP levels. ADP declined by 4% (eβ 0.96, 95% CI: 0.94, 0.98), 5% (eβ 0.95, 95% CI: 0.93, 0.98), 9% (eβ 0.91, 95% CI: 0.87, 0.95), and 83% (eβ 0.17, 95% CI: 0.08, 0.37) for each one unit (kg/m2) increase in body mass index, fat mass index, muscle mass index, and bone mineral content index, respectively.ConclusionsIn CF, ADP was negatively correlated with hepatic insulin resistance as well as low fat, muscle, and bone mass, but not with glucose intolerance. This suggests that malnutrition leads to higher ADP levels in CF
Changes in glucose tolerance in people with cystic fibrosis after initiation of first‐generation CFTR modulator treatment
No full textBackground: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been shown to have a beneficial effect on pulmonary function and nutritional status in patients with cystic fibrosis (CF), but the extent to which they affect glucose tolerance is not fully understood. In the current study, we evaluated the change in glucose tolerance and insulin secretion after first-generation CFTR modulator treatment in adults with CF.Methods: We performed a longitudinal observational study with an oral glucose tolerance test performed at baseline and after three and a half years of follow-up. The test comprised glucose, C-peptide and insulin measured at fasting, 1 h, and 2 h, and HbA1c at fasting. We compared changes in parameters of glucose tolerance and insulin secretion from baseline to follow-up.Results: Among 55 participants, 37 (67%) were treated with a first-generation CFTR modulator for a median of 21 months. Glucose levels were unchanged in both the treated and untreated group. In the treated group, C-peptide levels declined, yet no significant differences in glucose, insulin, and C-peptide levels were observed between the groups. HbA1c increased in both groups, while no significant change in the insulin sensitivity indices was detected in either group. However, homeostatic model assessment for insulin resistance tended to decline in the treated group, whilst tending towards an increase in the untreated group. The difference between the groups reached statistical significance (p = 0.040).Conclusion: Treatment with first-generation CFTR modulators, mainly tezacaftor/ivacaftor, did not seem to be associated with glucose tolerance nor insulin secretion in adults with CF. However, CFTR modulators may still have a beneficial effect on insulin sensitivity.</p
Neutrophil count in sputum is associated with increased sputum glucose and sputum L-lactate in cystic fibrosis
No full textBackground: Markers of lung inflammation measured directly in expectorated sputum have the potential of improving the timing of antibiotic treatment in cystic fibrosis (CF). L-Lactate might be a marker of inflammation, as it is produced from glucose by polymorphonuclear neutrophils (PMNs) in CF lungs. We aimed to investigate changes in and associations between PMNs, glucose and L-lactate in sputum during antibiotic treatment. In addition, the effect of hemoglobin A1c and plasma glucose on these biomarkers were investigated.Methods: We sampled non-induced sputum at day 0, 7, 14 and 42 in 27 chronically infected CF patients electively treated with 14 days of intravenous antibiotic. To analyze sputum samples, we used flowcytometry to count PMNs and colorimetric assays to estimate lactate and glucose.Results: No changes in levels of PMNs, glucose and lactate were detected in sputum during the antibiotic treatment. Sputum PMNs were positively associated with both glucose (log coefficient = 0.20, p = 0.01) and L-lactate (log coefficient = 0.34, p<0.001). In multivariate analyses, hemoglobin A1c was negatively associated with sputum PMNs (log coefficient = -1.68, p<0.001) and plasma glucose was negatively associated with sputum glucose (log coefficient = -0.09, p = 0.02).Conclusions: In CF sputum PMNs, glucose and lactate were unchanged during elective antibiotic treatment. However, sputum PMNs were associated with both sputum glucose and sputum lactate. Surprisingly, hyperglycemia seemed to be associated with less PMNs infiltration and less glucose in CF sputum.</p
