Differential Disruption of Blood–Brain Barrier in Severe Traumatic Brain Injury

Background

Traumatic brain injury (TBI) is a significant cause of death and disability in young adults, but not much is known about the incidence and characteristics of blood–brain barrier (BBB) dysfunction in this group. In this proof of concept study, we sought to quantify the incidence of BBB dysfunction (defined as a cerebrospinal fluid (CSF)–plasma albumin quotient of ≥0.007) and examine the relationship between plasma and CSF levels of proteins and electrolytes, in patients with severe TBI.

Methods

We recruited 30 patients, all of whom were receiving hypertonic 20 % saline infusion for intracranial hypertension and had external ventricular drains in situ. Simultaneous CSF and blood samples were obtained. Biochemical testing was performed for sodium, osmolality, potassium, glucose, albumin, immunoglobulin-G, and total protein.

Results

Eleven patients (37 %) showed evidence of impairment of passive BBB function, with a CSF–plasma albumin quotient of ≥0.007. There were strong positive correlations seen among CSF–plasma albumin quotient and CSF–plasma immunoglobulin-G quotient and CSF–plasma total protein quotient (r = 0.967, P < 0.001 and r = 0.995, P < 0.001, respectively). We also found a higher maximum intracranial pressure (24 vs. 21 mmHg, P = 0.029) and a trend toward increased mortality (27 vs. 11 %, P = 0.33) in patients with BBB disruption.

Conclusions

In summary, passive BBB dysfunction is common in patients with severe TBI, and may have important implications for effectiveness of osmotherapy and long-term outcomes. Also, our results suggest that the CSF–plasma total protein quotient, a measurement which is readily available, can be used instead of the CSF–plasma albumin quotient for evaluating BBB dysfunction.     

A genetic risk score predicts coronary artery disease in familial hypercholesterolaemia: enhancing the precision of risk assessment

Familial hypercholesterolaemia (FH) is associated with increased risk of coronary artery disease (CAD); however, risk prediction and stratification remain a challenge. Genetic risk scores (GRS) may have utility in identifying FH patients at high CAD risk. The study included 811 patients attending the lipid disorders clinic at Royal Perth Hospital with mutation-positive (n = 251) and mutation-negative (n = 560) FH. Patients were genotyped for a GRS previously associated with CAD. Associations between the GRS, clinical characteristics, and CAD were assessed using regression analyses. The average age of patients was 49.6 years, and 44.1% were male. The GRS was associated with increased odds of a CAD event in mutation-positive [odds ratio (OR) = 3.3; 95% confidence interval (CI) = 1.3-8.2; P = .009] and mutation-negative FH patients (OR = 1.8; 95% CI = 1.0-3.3; P = .039) after adjusting for established predictors of CAD risk. The GRS was associated with greater subclinical atherosclerosis as assessed by coronary artery calcium score (P = .039). A high GRS was associated with CAD defined clinically and angiographically in FH patients. High GRS patients may benefit from more intensive management including lifestyle modification and aggressive lipid-lowering therapy. Further assessment of the utility of the GRS requires investigation in prospective cohorts, including its role in influencing the management of FH patients in the clinic.     

Perioperative consultative hematology: can you clear my patient for a procedure?

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Methionine epimerization in cyclic peptides

Bioactive flax cyclic octa- and nona-peptides containing single methionine (Met) and its oxidized forms were treated under mild alkaline conditions to perform regio-selective epimerization. Cyclic peptide epimerization at the Met α-proton in a single chemical step has not been reported previously. The epimerization rate varies among Met oxidation states and ring size. These d-amino isomers along with the developed Met alkylation strategy will enable an approach to novel chemical functionalization of biomolecules. The amino acid configurations were confirmed by Marfey derivatizations, and cytotoxicity studies show the difference among the isomers. These d-amino analogs can act as a potential biomarker in plant protein processing and biomedical applications.

One step regioselective methionine epimerization in cyclic peptides followed by selective functionalization leads to chemical novelty.