Elevated neutrophil to lymphocyte ratio is associated with poor long-term survival and graft failure after lung transplantation

PurposeWe aimed to assess the prognostic value of Neutrophil to Lymphocyte Ratio (NLR) on long-term outcomes and graft dysfunction after lung transplantation.MethodsWe retrospectively reviewed all patients receiving a lung transplant at our institution from 2011 to 2014. The primary exposure was elevated NLR at the time of transplant, defined by NLR>4. The primary outcomes were graft failure and three-year all-cause mortality. Multivariate logistic regression and Kaplan-Meier survival analysis were used to analyze outcomes.Results95 patients were included. 40 patients (42%) had an elevated NLR. Elevated NLR was associated with graft failure (OR: 4.7 [1.2–18.8], p = 0.02), and three-year mortality (OR: 5.4 [1.3–23.2], p = 0.03) on multivariate logistic regression. Patients with elevated NLR demonstrated significantly lower survival on Kaplan-Meier analysis (50% versus 74%, p = 0.02). The c-statistic for our multivariate model was 0.91.ConclusionElevated neutrophil to lymphocyte ratio is associated with poor long-term survival and graft failure after lung transplantation.     

Novel approach to an early assessment of a patient’s potential for neurological remission after acute spinal cord injury: Analysis of hemoglobin concentration dynamics

Context/objective: Examining hemoglobin (Hb) dynamics with regard to the potential of neurological remission in patients with traumatic spinal cord injury (TSCI).Design: Prospective Clinical Observational Study.Setting: BG Trauma Centre Ludwigshafen, Department of Paraplegiology, Rhineland-Palatinate, Germany.Methods: From 2011 to 2017 a total of 80 patients with acute spinal injury were enrolled and divided into three groups: initial neurological impairment either with (G1; n = 33) or without subsequent neurological remission (G0; n = 35) and vertebral fractures without initial neurological impairment as control group (C; n = 12). Blood samples were taken for 3 months at 11 time-points after injury. Analyses were performed using routine diagnostics.Outcome measures: Multiple logistic regression was used to determine the prognostic value of Hb regarding neurological remission respecting clinical covariates.Results: Data showed elevated mean Hb concentrations in G1 from the third day to 1 month compared to G0, Hb levels were significantly higher in G1 after 3 days (P = 0.03, G1 > G0). The final multiple logistic regression model based on this data predicting the presence of neurological remission resulted in an AUC (area under the curve) of 80.5% (CI: 67.8%–93.2%) in the ROC (receiver operating characteristic) analysis.Conclusion: Elevated Hb concentrations are associated with a higher likelihood of neurological remission. Elevated concentrations of Hb in G1 compared to G0 over time might be linked to both a better initial oxygen supply response and a decreased ECM (extracellular matrix) degradation highlighting the role of Hb as a valuable biomarker for neural regeneration after TSCI.     

An assessment of a urinary biomarker for total human environmental exposure to benzo[a]pyrene

Urinary banzo[a]pyrene (BaP) metabolite levels were compared to human environmental exposure to BaP through inhalation and dietary ingestion to assess the predictive validity of the exposure biomarker. These measurements were made for 14 adult volunteers over 14 consecutive days, once during summer/fall, again during winter periods. Based on personal air monitoring, median potential inhalation doses of 11.0 and 2.3 ng/day were estimated for the winter and summer/fall studies, respectively. A median potential ingested dose of 176 ng/day, estimated from duplicate plate sampling, exceeded inhalation by 6-and 122-fold for the winter and summer/fall studies, respectively. Total urinary BaP metabolites were measured using a published reverse metabolism (BaP) method of analysis. Median rates of urinary BaP metabolite elimination for the winter and summer/fall studies were 121 and 129 ng/day, respectively. The changes in inhaled and ingested potential doses were regressed on the change in urinary metabolite elimination from week 1 to week 2 to test the predictive validity of the biomarker measurement. The regression was statistically significant (r = 0.620, p = 0.015, n = 25) when body weight was included and two extreme values were removed. Consistent with the exposure measurements showing diet as the dominant route of exposure, most of the variation in urinary metabolite elimination was explained by the ingested dose. It is concluded that the measurement of urinary BaP by reverse metabolism is qualitative and of marginal predictive validity as an exposure biomarker due to the method's low recoveries and the large unexplained variance.     

Toxicity assessment of environmental pollutant phenanthrene in clam Venerupis philippinarum using oxidative stress biomarkers

The objective of this study was to assess potential toxic effects of phenanthrene (PHE) on tissues of clam Venerupis philippinarum using parameters of antioxidant defenses and oxidative stress. Antioxidant biomarkers including ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), superoxide dismutase (SOD), and glutathione (GSH), as well as DNA damage and lipid peroxidation (LPO) in gills and digestive glands of V. philippinarum, were analyzed after a 1-, 3-, 6-, 10- and 15-day exposure to seawater containing PHE at concentrations of 2, 10, 50 μg/L. The results showed that the activity of most antioxidant enzymes was induced throughout the exposure period, and different trends were detected with time of exposure. The oxidative stress could be obviously caused in the gills and digestive glands under the experimental conditions. Overall, our results show that digestive glands are more sensitive to marine environmental stressors than gills, and GSH is proposed as potential useful biomarker as it showed good correlation with the target contaminant. This could provide useful information for toxic risk assessment of environmental pollutant PHE.     

Cerebrospinal fluid and plasma distribution of anti-α-synuclein IgMs and IgGs in multiple system atrophy and Parkinson's disease

IntroductionUbiquitous naturally occurring autoantibodies (nAbs) against alpha-synuclein (α-syn) may play important roles in the pathogenesis of Multiple System Atrophy (MSA) and Parkinson's disease (PD). Recently, we reported reduced high-affinity/avidity anti-α-syn nAbs levels in plasma from MSA and PD patients, along with distinct inter-group immunoglobulin (Ig)G subclass distributions. The extent to which these observations in plasma may reflect corresponding levels in the cerebrospinal fluid (CSF) is unknown.MethodsUsing competitive and indirect ELISAs, we investigated the affinity/avidity of CSF anti-α-syn nAbs as well as the CSF and plasma distribution of IgG subclasses and IgM nAbs in a cross-sectional cohort of MSA and PD patients.ResultsRepertoires of high-affinity/avidity anti-α-syn IgG nAbs were reduced in CSF samples from MSA and PD patients compared to controls. Furthermore, anti-α-syn IgM nAb levels were relatively lower in CSF and plasma from MSA patients but were reduced only in plasma from PD patients. Interestingly, anti-α-syn IgG subclasses presented disease-specific profiles both in CSF and plasma. Anti-α-syn IgG1, IgG2 and IgG3 levels were relatively increased in CSF of MSA patients, whereas PD patients showed increased anti-α-syn IgG2 and reduced anti-α-syn IgG4 levels.ConclusionsDifferences in the plasma/CSF distribution of anti-α-syn nAbs seem to be a common feature of synucleinopathies. Our data add further support to the notion that MSA and PD patients may have compromised immune reactivity towards α-syn. The differing α-syn-specific systemic immunological responses may reflect their specific disease pathophysiologies. These results are encouraging for further investigation of these immunological mechanisms in neurodegenerative diseases.     

Beclin-1 increases with obstructive sleep apnea severity

Obstructive sleep apnea is a common chronic disorder that leads to chronic intermittent hypoxia described as an important factor contributing to the pathogenesis of OSA-related comorbidities. Besides, recent data suggest that intermittent hypoxia can induce adaptative cardiovascular pathways inducing a relative resistance to ischemic insults. Adaptative pathways induced by hypoxia could implicate autophagic processes and Beclin-1, one of the first mammalian autophagy effectors. Thus, activation of autophagy could protect against cardiovascular events in patients with OSA and could be considered as biomarker of a better prognosis.