Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis

Severe sepsis and septic shock are the primary causes of multiple organ dysfunction syndrome (MODS), which is the most frequent cause of death in intensive care unit patients. Many water-soluble mediators with pro- and anti-inflammatory action such as TNF, IL-6, IL-8, and IL-10 play a strategic role in septic syndrome. In intensive care medicine, blocking any one mediator has not led to a measurable outcome improvement in patients with sepsis. CRRT is a continuously acting therapy, which removes in a nonselective way pro- and anti-inflammatory mediators; "the peak concentration hypothesis" is the concept of cutting peaks of soluble mediators through continuous hemofiltration. Furthermore, there is evidence of increased efficacy of high-volume hemofiltration compared to conventional CVVH, and other blood purification techniques that utilize large-pore membranes or sorbent plasmafiltration are conceptually interesting.     

Peripheral artery disease in type 2 diabetes: the role of fibrinolysis

The aim of the present study is to verify the relationship between peripheral artery disease (PAD) and some coagulation/fibrinolysis parameters in type 2 diabetic patients. Sixty-three type 2 diabetic patients, without PAD, were studied at baseline and after 4 years. Assessments included tissue-Plasminogen Activator (t-PA), Plasminogen Activator Inhibitor-1 antigen (PAI-1 Ag), Plasminogen Activator Inhibitor-1 activity (PAI-1 Act), Plasminogen (Pl), Fibrin peptide A (FPA), Fibrinogen (Fr), and the ankle/brachial pressure index (ABI). We observed a significant difference between diabetic patients and controls as regards tPA (11.8 +/- 5.4 vs. 6.6 +/- 3.0 ng/ml; p <0.05) and PAI-1 Act (17.8 +/- 9.2 vs. 11.7 +/- 6.6 ng/dl; p <0.005). After 4 years 13 diabetic patients became vasculopathic and, at baseline, had significantly lower tPA (8.9 +/- 4.8 vs. 12.5 +/- 5.3; p <0.011), and higher PAI-1 Ag (50.8 +/- 22.2 vs. 32 +/- 22.2; p <0.006), and PAI-1 Act values (24.1 +/- 9.5 vs. 16.1 +/- 8.4; p <0.014), compared with 50 diabetic patients who did not develop PAD after 4 years. These data show that the physiological equilibrium which exists between t-PA and PAI-1 moves towards higher levels in our diabetic patients compared with controls, at baseline, whereas diabetic patients who developed PAD showed a shift towards an antifibrinolytic pathway with diminished t-PA, increased PAI-1 Ag and PAI-1 Act and consequently procoagulant activity. Our study suggests that hypofibrinolysis may be involved in the future onset of PAD in type 2 diabetic patients.     

Bone mineral density in a population of children and adolescents with cerebral palsy and mental retardation with or without epilepsy

Purpose: The present study aimed to assess bone mineral density (BMD) in a population of children and adolescents with cerebral palsy and mental retardation with or without epilepsy. Methods: One hundred thirteen patients (63 male and 50 female) were recruited for evaluation. Patients were divided in three groups: 40 patients (group 1) were affected by cerebral palsy and mental retardation; 47 (group 2) by cerebral palsy, mental retardation, and epilepsy; and 26 (group 3) by epilepsy. The control group consisted of 63 healthy children and adolescents. Patients underwent a dual‐energy x‐ray absorptiometry (DEXA) scan of the lumbar spine (L1–L4), and z‐score was calculated for each patient; t‐score was considered for patients 18 years of age and older. Key Findings: Abnormal BMD by DEXA was found in 17 patients (42.5%) in group 1, in 33 (70.2%) in group 2, and in 3 (11.5%) in group 3. In groups 1 and 2, tetraparesis and severe/profound mental retardation were related to a significantly abnormal BMD (p = 0.003). The multivariate analysis of independent factors on BMD (z‐score) revealed a significant correlation between BMD (z‐score) and age (p = 0.04), body mass index (BMI; p = 0.002), severe/profound mental retardation (p = 0.03), and epilepsy (p = 0.05). Significance: A significantly lower BMD z‐score value was found in patients with cerebral palsy, mental retardation, and epilepsy compared with those without epilepsy. The epileptic disorder appears to be an aggravating factor on bone health when comorbid with cerebral palsy and mental retardation.     

Epstein-Barr virus infections in families: the role of children with infectious mononucleosis

We performed a prospective evaluation of Epstein-Barr virus (EBV) infections in 78 families with a childhood index case of EBV-infectious mononucleosis (EBV-IM). During the acute index episode, adult family (household) contacts, compared with control adults, had a greater rate of oropharyngeal EBV excretion and high serum antibody responses, which suggested a recent antecedent reactivation of an old EBV infection. The increased prevalence of oropharyngeal EBV and acute serological responses found in sibling family contacts during the early surveillance period suggested that these contacts had experienced an increased rate of primary-type EBV infections shortly before or concurrent with the index case. Although nonimmune sibling contacts seroconverted at a slow rate, five of nine manifested IM with their eventual documented primary EBV infection. This study noted significant intrafamilial EBV activity surrounding an episode of childhood EBV-IM. Reactivation of an old EBV infection in adults may be an important source of virus for susceptible children within these families. Siblings of a childhood case of EBV-IM appear to be at increased risk for manifesting IM with their primary EBV infection.