Plasma metabolomics and clinical predictors of survival differences in COPD patients.

BACKGROUND: Plasma metabolomics profile (PMP) in COPD has been associated with clinical characteristics, but PMP's relationship to survival has not been reported. We determined PMP differences between patients with COPD who died an average of 2 years after enrollment (Non-survivors, NS) compared to those who survived (S) and also with age matched controls (C). METHODS: We studied prospectively 90 patients with severe COPD and 30 controls. NS were divided in discovery and validation cohorts (30 patients each) and the results compared to the PMP of 30 S and C. All participants completed lung function tests, dyspnea scores, quality of life, exercise capacity, BODE index, and plasma metabolomics by liquid and gas chromatography / mass spectometry (LC/MS, LC/MS2, GC/MS). Statistically, we used Random Forest Analysis (RFA) and Support Vector Machine (SVM) to determine metabolites that differentiated the 3 groups and compared the ability of metabolites vs. clinical characteristics to classify patients into survivors and non-survivors. RESULTS: There were 79 metabolites statistically different between S and NS [p < 0.05 and false discovery rate (q value) < 0.1]. RFA and SVM classification of COPD survivors and non-survivors had a predicted accuracy of 74 and 85% respectively. Elevation of tricyclic acid cycle intermediates branched amino acids depletion and increase in lactate, fructose and xylonate showed the most relevant differences between S vs. NS suggesting alteration in mitochondrial oxidative energy generation. PMP had similar predictive power for risk of death as information provided by clinical characteristics. CONCLUSIONS: A plasma metabolomic profile characterized by an oxidative energy production difference between survivors and non-survivors was observed in COPD patients 2 years before death.

Comparative analysis of COPD associated with tobacco smoking, biomass smoke exposure or both.

BACKGROUND: Exposure to noxious gases and particles contained in both tobacco smoking (TS) and biomass smoke (BS) are well recognized environmental risk factors for chronic obstructive pulmonary disease (COPD). COPD is characterized by an abnormal inflammatory response, both in the pulmonary and systemic compartments. The differential effects of TS, BS or their combined exposure have not been well characterized yet. This study sought to compare the lung function characteristics and systemic inflammatory response in COPD patients exposed to TS, BS or their combination. METHODS: Sociodemographic, clinical and lung functional parameters were compared across 49 COPD patients with a history of smoking and no BS exposure (TS COPD), 31 never-smoker COPD patients with BS exposure (BS COPD), 46 COPD patients with a combined exposure (TS + BS COPD) and 52 healthy controls (HC) who have never been exposed neither to TS or BS. Blood cell counts, C-reactive protein (CRP), fibrinogen and immunoglobulin E (IgE) levels were quantified in all four groups. RESULTS: TS + BS COPD patients exhibited significantly lower oxygen saturation than the rest of groups (p < 0.01). Spirometry and diffusing capacity were significantly higher in BS than in TS or TS + BS patients. CRP levels were significantly higher in TS COPD patients than in BS COPD group (p < 0.05), whereas fibrinogen was raised in COPD patients with a history of smoking (TS and TS + BS) when compared to control subjects (p < 0.01). Finally, COPD patients with BS exposure (BS and BS + TS groups) showed higher IgE levels than TS and HC (p < 0.05). CONCLUSIONS: There are significant physiological and inflammatory differences between COPD patients with TS, BS and TS + BS exposures. The latter had worse blood oxygenation, whereas the raised levels of IgE in BS exposed patients suggests a differential Th2 systemic inflammatory pattern triggered by this pollutant.

Correction to: Comparative analysis of COPD associated with tobacco smoking, biomass smoke exposure or both.

In the original publication [1] is an error in table 1. The correct version can be found in this Erratum.

Randomized effectiveness trial of a brief course of acupuncture for posttraumatic stress disorder.

BACKGROUND: Initial posttraumatic stress disorder (PTSD) care is often delayed and many with PTSD go untreated. Acupuncture appears to be a safe, potentially nonstigmatizing treatment that reduces symptoms of anxiety, depression, and chronic pain, but little is known about its effect on PTSD. METHODS: Fifty-five service members meeting research diagnostic criteria for PTSD were randomized to usual PTSD care (UPC) plus eight 60-minute sessions of acupuncture conducted twice weekly or to UPC alone. Outcomes were assessed at baseline and 4, 8, and 12 weeks postrandomization. The primary study outcomes were difference in PTSD symptom improvement on the PTSD Checklist (PCL) and the Clinician-administered PTSD Scale (CAPS) from baseline to 12-week follow-up between the 2 treatment groups. Secondary outcomes were depression, pain severity, and mental and physical health functioning. Mixed model regression and t test analyses were applied to the data. RESULTS: Mean improvement in PTSD severity was significantly greater among those receiving acupuncture than in those receiving UPC (PCLΔ=19.8±13.3 vs. 9.7±12.9, P<0.001; CAPSΔ=35.0±20.26 vs. 10.9±20.8, P<0.0001). Acupuncture was also associated with significantly greater improvements in depression, pain, and physical and mental health functioning. Pre-post effect-sizes for these outcomes were large and robust. CONCLUSIONS: Acupuncture was effective for reducing PTSD symptoms. Limitations included small sample size and inability to parse specific treatment mechanisms. Larger multisite trials with longer follow-up, comparisons to standard PTSD treatments, and assessments of treatment acceptability are needed. Acupuncture is a novel therapeutic option that may help to improve population reach of PTSD treatment.

Immunological markers and Helicobacter pylori in patients with stomach cancer: Expression and correlation.

Programmed death-ligand 1 (PD-L1) and ICOS-L (also referred to as B7 homolog 1 and 2, respectively) modulate the immune inflammatory response. The aim of the present study was to examine the expression levels of these inflammatory mediators in two groups of patients with an Helicobacter pylori (H. pylori) infection; patients with and without gastric cancer. The association between bacterial virulence factors, CagA and VacA, was also examined, as well as their correlation with the inflammatory profile. Endoscopy analysis indicated that 18 patients suffered from cancer and 28 patients suffered from other gastric pathologies. PCR and reverse transcription-quantitative PCR were used to analyze gastric biopsies and determine the expression levels of the inflammatory modulators PD-L1 and ICOS-L, transcription factors, cytokines and other genes associated with inflammation and pathogenicity. All 46 patients were determined positive for markers of H. pylori. Patients with stomach cancer had lower levels of ICOS-L (P<0.05) and GATA3 (P<0.01), a negative correlation between CagA and IL-17 (P<0.05), a positive correlation between CagA and IL-10 (P<0.05), a negative correlation between vacA-m1 and retinoid orphan receptor γt (RORγt) (P<0.001), and a positive correlation between RORγt and ICOS-L (P<0.001). The reduced levels of ICOS-L and GATA3 along with the negative correlation between CagA and IL-17, and between vacA-m1 and RORγt were all associated with an increased risk of gastric cancer in the present cohort.

Excitotoxicity in the pathogenesis of neurological and psychiatric disorders: Therapeutic implications.

Neurological and psychiatric disorders are leading contributors to the global disease burden, having a serious impact on the quality of life of both patients and their relatives. Although the molecular events underlying these heterogeneous diseases remain poorly understood, some studies have raised the idea of common mechanisms involved. In excitotoxicity, there is an excessive activation of glutamate receptors by excitatory amino acids, leading to neuronal damage. Thus, the excessive release of glutamate can lead to a dysregulation of Ca2+ homeostasis, triggering the production of free radicals and oxidative stress, mitochondrial dysfunction and eventually cell death. Although there is a consensus in considering excitotoxicity as a hallmark in most neurodegenerative diseases, increasing evidence points to the relevant role of this pathological mechanism in other illnesses affecting the central nervous system. Consequently, antagonists of glutamate receptors are used in current treatments or in clinical trials in both neurological and psychiatric disorders. However, drugs modulating other aspects of the excitotoxic mechanism could be more beneficial. This review discusses how excitotoxicity is involved in the pathogenesis of different neurological and psychiatric disorders and the promising strategies targeting the excitotoxic insult.