26 research outputs found
Concentration of meropenem in patients with sepsis and acute kidney injury before and after initiation of continuous renal replacement therapy : a prospective observational trial
Background The effect of renal replacement therapy on drug concentrations in patients with sepsis has not been fully elucidated because the pharmacokinetic properties of many antimicrobials are influenced by both pathophysiological and treatment-related factors. The aim of this study was to determine meropenem concentrations in patients with sepsis before and after the initiation of continuous venovenous hemodialysis with regional citrate anticoagulation (RCA-CVVHD). Methods The study included 15 critically ill patients undergoing RCA-CVVHD due to sepsis-induced acute kidney injury. All participants received 2 g of meropenem every 8 h in a prolonged infusion lasting 3 h. Meropenem concentrations were measured in blood plasma using high-performance liquid chromatography coupled with tandem mass spectrometry. Blood samples were obtained at six-time points prior to and at six-time points after introducing RCA-CVVHD.
Results The median APACHE IV and SOFA scores on admission were 118 points (interquartile range [IQR] 97-134 points) and 19.5 points (IQR 18-21 points), respectively. There were no significant differences in the plasma concentrations of meropenem measured directly before RCA-CVVHD and during the first 450 min of the procedure. The drug concentration reached its peak 2 h after initiating the infusion and then steadily declined. Conclusions The concentration of high-dose meropenem (2 g every 8 h) administered in a prolonged infusion was similar before and after the introduction of RCA-CVVHD in patients with sepsis who developed acute kidney injury
Aspirin desensitization in patients with aspirin-induced and aspirin-tolerant asthma : a double-blind study
Background: Numerous open trials have demonstrated the
beneficial clinical effects of aspirin desensitization (AD) in
patients with aspirin-induced asthma (AIA). These beneficial
effects might be attributable to aspirin’s potent antiinflammatory properties, but that supposition requires further
corroboration.
Objective: We sought to compare the clinical and biochemical
responses to chronic oral AD in 20 patients with AIA and 14
patients with aspirin-tolerant asthma (ATA). All of the patients
had chronic rhinosinusitis and nasal polyposis, and these
responses were investigated in a pilot, double-blind, placebocontrolled study.
Methods: Twelve patients with AIA and 6 patients with ATA
were randomly assigned to receive 624 mg of aspirin, and 8
patients with AIA and 8 patients with ATA received placebo.
Both aspirin and placebo were administered once daily for 6
months. Nasal symptoms, Sino-Nasal Outcome Test (SNOT20)
scores, peak nasal inspiratory flows, Asthma Control
Questionnaire scores, spirometric parameters, peak expiratory
flows, blood eosinophilia, and corticosteroid doses were assessed
on a monthly basis. Levels of urinary leukotriene E4 and the
stable plasma prostaglandin (PG) D2 metabolite 9a,11b-PGF2
were evaluated at baseline and after 1, 3, 5, and 6 months.
Results: Only the patients with AIA subjected to AD reported
improvements in smell and reductions in sneezing and nasal
blockade. The SNOT20 and Asthma Control Questionnaire
scores of these patients decreased, and their peak nasal
inspiratory flows increased. The dosages of inhaled
corticosteroids were reduced. There were no changes in
leukotriene E4 or 9a,11b-PGF2 levels after AD.
Conclusion: The clinically beneficial effects of AD on nasal
and bronchial symptoms occurred only in the patients with AIA
Subphenotypes of nonsteroidal antiinflammatory diseaseexacerbated respiratory disease identified by latent class analysis
Background
Induced sputum (IS) allows to measure mediators of asthmatic inflammation in bronchial secretions. NSAID‐exacerbated respiratory disease (NERD) is recognized as a distinct asthma phenotype, usually with a severe course, eosinophilic airway inflammation, and increased production of pro‐inflammatory eicosanoids. A more insightful analysis of NERD patients has shown this phenotype to be nonhomogeneous.
Objective
We aimed to identify possible subphenotypes in a cohort of NERD patients with the means of latent class analysis (LCA).
Methods
A total of 95 asthma patients with aspirin hypersensitivity underwent sputum induction. High‐performance liquid chromatography or gas chromatography coupled with mass spectrometry was used to profile eicosanoids in induced sputum supernatant (ISS). Sixteen variables covering clinical characteristics, IS inflammatory cells, and eicosanoids were considered in the LCA.
Results
Three classes (subphenotypes) were distinguished within the NERD cohort. Class 1 subjects had mild‐to‐moderate asthma, an almost equal distribution of inflammatory cell patterns, the lowest concentrations of eicosanoids, and logLTE4/logPGE2 ratio. Class 2 represented severe asthma with impaired lung function despite high doses of steroids. High sputum eosinophilia was in line with higher pro‐inflammatory LTE4 in ISS and the highest logLTE4/logPGE2 ratio. Class 3 subjects had mild‐to‐moderate asthma and were also characterized by eosinophilic airway inflammation, yet increased production of pro‐ (LTE4, PGD2 and 11‐dehydro‐TBX2) was balanced by anti‐inflammatory PGE2. The value of logLTE4/logPGE2 was between values calculated for classes 1 and 3, similarly to disease control and severity.
Conclusions
LCA revealed three distinct NERD subphenotypes. Our results support a more complex pathobiology of aspirin hypersensitivity. Considering NERD heterogeneity, the relationship between inflammatory pathways and clinical manifestations of asthma may lead to more individualized treatment in difficult to treat patients in the future
Influence of dietary fatty acids on differentiation of human stromal vascular fraction preadipocytes
Nasal versus bronchial and nasal response to oral aspirin challenge : clinical and biochemical differences between patients with aspirin-induced asthma/rhinitis
Background: Aspirin-induced asthma/rhinitis (AIAR) is characterized by the altered metabolism of leukotrienes and proinflammatory prostaglandins. The basal and postchallenge levels
of eicosanoids might reflect the clinical and biochemical characteristics of patients with distinct types of hypersensitive
responses to aspirin.
Objective: We compared clinical and eicosanoid profiles of
patients with AIAR showing both bronchial and nasal versus
isolated nasal responses to aspirin challenge.
Methods: Twenty-three patients with AIAR underwent the single-blind, oral, placebo-controlled aspirin challenge. The
bronchial response (BR) was evidenced by dyspnea and
spirometry, whereas the nasal response (NR) was evidenced by
nasal symptoms and acoustic rhinometry and/or rhinomanometry. Urinary leukotriene E4 (uLTE4), serum and urinary stable prostaglandin D2 metabolite, and 9α,11β-prostaglandin F2
(9α,11β-PGF2), were determined at baseline and after the
aspirin challenge.
Results: Fifteen subjects showed BR and NR (BNR), whereas 8
showed NR only. Basal uLTE4 in the BNR group was significantly higher than in the NR group. After aspirin challenge, it
increased significantly in both groups. Serum 9α,11β-PGF2
increased after aspirin challenge in the BNR group only. The
patients with BNR had more severe AIAR.
Conclusions: BNR to aspirin in AIAR indicates a more
advanced disease and more profound underlying eicosanoid
metabolism disturbances