The acute-phase mediator serum amyloid A is associated with symptoms of depression and fatigue.

OBJECTIVE: Establish whether inflammatory biomarkers-serum amyloid A (SAA), C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)-are related to key symptoms of depression, including anxiety and fatigue, in a cross-sectional, out-patient setting to identify biomarkers that reflect psychiatric symptomatology in a naturalistic, real-life population. METHODS: We measured SAA, CRP, IL-6, and TNF-α in plasma samples from 89 adult psychiatric out-patients by multiplex, high-sensitivity electrochemiluminescent assays. Psychiatric symptoms were evaluated using the Hamilton Depression Rating Scale (HAMD-17), the Patient Health Questionnaire (PHQ-9), and the Center for Epidemiological Studies Depression Scale (CES-D). RESULTS: Plasma SAA was most robustly associated with depressive symptoms across diagnostic boundaries in this cohort of out-patients. Elevated SAA was significantly associated with higher total scores on the HAMD-17 scale and correlated with multiple scale items that rated symptoms of fatigue and depressed mood, but not with anxiety-related items. CONCLUSIONS: SAA might constitute a cross-diagnostic marker indicative of depressed mood and fatigue in a naturalistic patient setting. Because SAA activates Toll-like receptors 2 and 4, present on macrophages and glial cells, its association with depression severity could also implicate this inflammatory mediator in the pathogenesis of mood disorders.

An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation.

Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-d-aspartate receptor agonist, are increased. The enzyme amino-ß-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Åsberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single-nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.

Cost reduction of perioperative coagulation management in cardiac surgery: value of "bedside" thrombelastography (ROTEM).

OBJECTIVE: Demographic changes and aggressive platelet inhibition have resulted in a marked increase in blood- and coagulation product expenditure and costs in cardiac surgery. We analyzed "bedside" coagulation test (ROTEM) in order to verify clot forming quality for the purpose of finding a cost-effective treatment path. METHODS: Annual treatment costs of all cardiosurgical patients were analyzed before (729 patients) and after (693 patients) implementation of "bedside" ROTEM. Cumulative numbers and costs of platelet concentrates (PltC), fresh frozen plasma (FFP), red blood cell units (RBC), and coagulation factors: pooled coagulation concentrates (PCC), recombinant factor VIIa (rFVIIa), factor XIII (FXIII), and fibrinogen were assessed. Average monthly numbers and costs were compared. Number of resternotomies and early mortality was assessed and compared in both periods. RESULTS: After ROTEM implementation cumulative RBC expenditure showed 25% decrease while PltC exhibited 50% decrease. FFP expenditure remained unchanged. PCC, FXIII were markedly reduced (-80%) while rFVIIa were entirely omitted. Fibrinogen, however, increased two-fold. Cumulative average monthly costs of all blood products decreased from 66,000 euro to 45,000 euro (-32%). Coagulation factor average monthly costs decreased from 60,000 euro to 30,000 euro (-50%) yielding combined savings of 44%. In contrast, average monthly costs for ROTEM were 1.580 euro. Total number of resternotomies decreased from 6.6% to 5.5% while early mortality (5.9%; 6.0%) remained stable. CONCLUSION: Cumulative costs for treatment of perioperative coagulation disorders can be reduced by "bedside" ROTEM analysis to achieve a selective substitution management. Saved costs for blood- and coagulation products clearly outweighed the expenses of ROTEM. Adequate differential coagulation management can therefore be cost-effective.

Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: a comparative study.

BACKGROUND: Because survival benefits of treatment with radiotherapy are questionable and such treatment can cause substantial damage to the brain over time, the optimum management strategy for low-grade gliomas remains controversial. We aimed to identify the specific effects of radiotherapy on objective and self-reported cognitive function, and on cognitive deterioration over time, in patients with low-grade gliomas treated with early radiotherapy. METHODS: 195 patients with low-grade glioma (of whom 104 had received radiotherapy 1-22 years previously) were compared with 100 low-grade haematological patients and 195 healthy controls. Our analyses aimed to differentiate between the effects of the tumour (eg, disease duration, lateralisation) and treatment effects (neurosurgery, radiotherapy, antiepileptic drugs) on cognitive function and on relative risk of cognitive disability. FINDINGS: Low-grade glioma patients had lower ability in all cognitive domains than did low-grade haematological patients, and did even less well by comparison with healthy controls. Use of radiotherapy was associated with poorer cognitive function; however, cognitive disability in the memory domain was found only in radiotherapy patients who received fraction doses exceeding 2 Gy. Antiepileptic drug use was strongly associated with disability in attentional and executive function. INTERPRETATION: Our findings suggest that the tumour itself has the most deleterious effect on cognitive function and that radiotherapy mainly results in additional long-term cognitive disability when high fraction doses are used. Additionally, the effects of other medical factors, especially antiepileptic drug use, on cognitive function in glioma patients deserve attention.