Treatment with IgM-enriched immunoglobulin in sepsis: a matched case-control analysis.

The therapeutic potential of IgM-enriched immunoglobulin preparations (IgGAM) in sepsis remains a field of debate. The use of polyclonal immunoglobulins as adjuvant therapy (Esen & Tugrul, 2009; Kaukonen et al., 2014; Molnár et al., 2013; Taccone et al., 2009) has been shown to improve clinical outcomes in terms of mortality. This study analyze the impact of IgM-enriched IgG (IgGM) as additional immunomodulation. Patients and methods: This is a retrospective registry of 1196 patients with severe sepsis and septic shock from nine Intensive Care Units in Colombia, from routine clinical practice; 220 patients treated with IgGAM were registered. Fully matched comparators for severity and type of infection selected among patients non-treated with IgGAM. Mortality after 28 days was 30.5% among IgGAM-treated patients and 40.5% among matched comparators. Results: Multivariate Cox regression analysis showed IgGAM treatment to be the only variable protective from death after 28 days (hazard ratio 0.62; 0.45-0.86; p: 0.004). Results reinforce the importance of IgGAM treatment for favorable outcome after septic shock and are in line with recent published meta-analyses. This study showed that treatment with IgGM in patients with sepsis was an independent modulator of the 28-day associated with a lower mortality.

Diabetes-Related Neurological Implications and Pharmacogenomics.

Diabetes mellitus (DM) is the most commonly occurring cause of neuropathy around the world and is beginning to grow in countries where there is a risk of obesity. DM Type II, (T2DM) is a common age-related disease and is a major health concern, particularly in developed countries in Europe where the population is aging. T2DM is a chronic disease which is characterised by hyperglycemia, hyperinsulinemia and insulin resistance, together with the body's inability to use glucose as energy. Such metabolic disorder produces a chronic inflammatory state, as well as changes in lipid metabolism leading to hypertriglyceridemia, thereby producing chronic deterioration of the organs and premature morbidity and mortality. The pathology's effects increase cerebral damage, leading to the rapid onset of neurodegenerative diseases. Hyperglycemia causes oxidative stress in tissues which are susceptible to the complications involved in diabetes, including peripheral nerves. Other additional mechanisms include activation of polyol aldose reductase signalling accompanied by protein kinase C (PKC)-ß activation, poly(ADP ribose) polymerase activation, cyclooxygenase (COX) 2 activation, endothelial dysfunction, altered Na+/K+ ATPase pump function, dyslipidaemia and perturbation of calcium balance. All the forgoing has an impact on neuron activity, mitochondrial function, membrane permeability and endothelial function. These biochemical processes directly affect the neurons and endothelial tissue, thereby accelerating cerebral aging by means of peroxidation of the polyunsaturated fatty acids and thus injuring cell membrane integrity and inducing apoptosis in the glial cells. The Central Nervous System (CNS) includes two types de glial cells: microglia and macroglia (astrocytes, oligodendrocytes and radial cells which include Bergmann cells and Müller cells). Glial cells constitute more than 90% of the CNS cell population. Human studies have shown that some oral antidiabetic drugs can improve cognition in patients suffering mild cognitive impairment (MCI) and dementia [1, 2]. While it is still unclear whether diabetes management will reduce MCI and Alzheimer's disease (AD), incidence, emerging evidence suggests that diabetes therapies may improve cognitive function. This review focuses three aspects: the clinical manifestation of diabetes regarding glial and neuronal cells, the association between neurodegeneration and diabetes and summarises some of the pharmacogenomic data obtained from studies of T2DM treatment, focusing on polymorphisms in genes affecting pharmacokinetics, pharmacodynamics and treatment outcome of the most commonly-prescribed oral anti-diabetic drugs (OADs).