123 research outputs found
Increased Indoleamine-2,3-Dioxygenase Activity Is Associated With Poor Clinical Outcome in Adults Hospitalized With Influenza in the INSIGHT FLU003Plus Study
BACKGROUND: Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections.
METHODS: We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression.
RESULTS: We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M; IQR, 0.13–0.40) than controls (0.12; IQR, 0.09–0.17; P ≤ .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21–0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25–43.90).
CONCLUSIONS: High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration.
CLINICALTRIALS.GOV IDENTIFIER: NCT01056185
Increased indoleamine-2,3-dioxygenase activity is associated with poor clinical outcome in adults hospitalized with influenza in the INSIGHT FLU003Plus study
BACKGROUND:
Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections.
METHODS:
We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression.
RESULTS:
We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M; IQR, 0.13-0.40) than controls (0.12; IQR, 0.09-0.17; P ≤ .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21-0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25-43.90).
CONCLUSIONS:
High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration.
CLINICALTRIALSGOV IDENTIFIER:
NCT01056185
Pathogenesis of the eosinophilic pleural effusions
Purpose of review
Eosinophilic pleural effusions (EPE) are defined as those that contain
at least 10% eosinophils. EPEs account for 5 to 16% of exudative
pleural effusions. However, their pathogenesis is poorly understood. The
purpose of this review is to discuss the mechanisms that lead to
eosinophilic pleural inflammation.
Recent findings
Eosinophilic pleural effusions are caused by the presence of air or
blood or both in the pleural space, infectious or other inflammatory
diseases, malignancy, pulmonary emboli, asbestos exposure, and drug
reactions. Differences in the clinical features suggest that a variety
of mechanisms operate to induce eosinophilic pleural inflammation and
pleural fluid accumulation. Human and animal studies indicate that
interleukin (IL)-5 is an important common contributor of different
pathogenetic pathways. The possible role of other cytokines, chemokines,
and adhesion molecules in the development of EPE is under investigation.
Summary
Understanding the pathogenesis of EPE will permit the development of
novel therapies for the persistent, symptomatic, posttraumatic and
idiopathic EPE. Anti-IL-5 treatment is an interesting option that
requires further research
Can pharmacologic agents speed the rate of resorption of pleural fluid?
Purpose of review Pleural effusion is a common clinical problem resulting from a wide range of diseases. Treatment options include targeting the primary cause or, in persistent cases, invasive removal of the excess fluid from the pleural cavity. In this review, we summarize the experimental data concerning pharmacological agents that influence pleural fluid resorption and examine their potential as a novel noninvasive treatment strategy. Recent findings Recently published evidence indicates that adrenergic agents and corticosteroids can increase pleural fluid clearance from the cavity. On the contrary, paracetamol and certain nonsteroid anti-inflammatory drugs can impede fluid outflow. These concepts are based on data extracted by in-vivo studies using provoked hydrothoraces in rabbits and mice, as well as by ex-vivo electrophysiological experiments using sheep and human pleural tissue. Summary In conclusion, the available experimental data indicate that certain pharmacological agents may impact fluid resorption, thus affecting pleural fluid accumulation and the rate of pleural effusion resolution. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved
Malignant pleural effusion: Tumor-host interactions unleashed
Malignant pleural effusion (MPE) poses a significant clinical problem. Current nonetiologic management is suboptimal in terms of efficacy and safety. In light of recent research progress, we propose herein a new view of MPE development, which may rapidly translate into meaningful changes in therapeutics. In addition to tumor-induced impairment of pleural fluid drainage, pertinent findings point toward another pathway to MPE formation: a vicious loop of interactions between pleural-based tumor cells and the host vasculature and immune system that results in increased net fluid production via enhanced plasma extravasation into the pleural space. The ability of tumor cells to trigger this cascade likely rests on a specific and distinct transcriptional repertoire, which results in important vasoactive events in the pleural space. Although the characterization of tumor-derived factors responsible for MPE development is in the making, an additional, indirect path to MPE was recently demonstrated: tumor cells recruit and co-opt host cells and mediators, which, in turn, amplify tumor cell-primed fluid leakage and impact tumor cell functions. Importantly, recent evidence suggests that the biologic events that culminate in clinical MPE are likely amenable to therapeutic inhibition and even prevention. In this perspective, the scientific basis for an update of current concepts of MPE formation is highlighted. Key questions for future research are posed. Finally, a vision for novel, effective, safe, and convenient treatment modalities that can be offered to outpatients with MPE is set forth. Copyright © 2012 by the American Thoracic Society
Pleurotoxic Drugsan Update: Someone Else to Blame?
Purpose of ReviewTo provide an updated summary of the pleurotoxic drugs
and their manifestations.Recent FindingsNovel antineoplastic agents for
the treatment of hematologic and non-hematologic malignancies have been
associated with the induction of pleural disorders. Moreover, the list
of agents that have been associated with drug-induced lupus pleuritis is
steadily increasing.SummaryPleurotoxic medications are agents that may
cause pleural disorders, most commonly pleural effusions. Connecting a
pleural disorder to a specific drug requires the exclusion of other
potential causes combined with resolution of the disorder after drug
discontinuation while previous literature reports on similar cases may
be of assistance. The incorporation of new therapies into clinical
practice over the last few years has exposed medical professionals to
areas devoid of a historic evidence base. Thus, drug-induced
pleurotoxicity should be always included in the diagnostic approach to
the patient with a pleural effusion
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