Acute CSF interleukin-6 trajectories after TBI: associations with neuroinflammation, polytrauma, and outcome.

Traumatic brain injury (TBI) results in a significant inflammatory burden that perpetuates the production of inflammatory mediators and biomarkers. Interleukin-6 (IL-6) is a pro-inflammatory cytokine known to be elevated after trauma, and a major contributor to the inflammatory response following TBI. Previous studies have investigated associations between IL-6 and outcome following TBI, but to date, studies have been inconsistent in their conclusions. We hypothesized that cohort heterogeneity, temporal inflammatory profiles, and concurrent inflammatory marker associations are critical to characterize when targeting subpopulations for anti-inflammatory therapies. Toward this objective, we used serial cerebrospinal fluid (CSF) samples to generate temporal acute IL-6 trajectory (TRAJ) profiles in a prospective cohort of adults with severe TBI (n=114). We examined the impact of injury type on IL-6 profiles, and how IL-6 profiles impact sub-acute (2weeks-3months) serum inflammatory marker load and long-term global outcome 6-12months post-injury. There were two distinct acute CSF IL-6 profiles, a high and low TRAJ group. Individuals in the high TRAJ had increased odds of unfavorable Glasgow Outcome Scale (GOS) scores at 6months (adjusted OR=3.436, 95% CI: 1.259, 9.380). Individuals in the high TRAJ also had higher mean acute CSF inflammatory load compared to individuals in the low TRAJ (p⩽0.05). The two groups did not differ with respect acute serum profiles; however, individuals in the high CSF IL-6 TRAJ also had higher mean sub-acute serum IL-1ß and IL-6 levels compared with the low TRAJ group (p⩽0.05). Lastly, injury type (isolated TBI vs. TBI+polytrauma) was associated with IL-6 TRAJ group (χ(2)=5.31, p=0.02). Specifically, there was 70% concordance between those with TBI+polytrauma and the low TRAJ; in contrast, isolated TBI was similarly distributed between TRAJ groups. These data provide evidence that sustained, elevated levels of CSF IL-6 are associated with an increased inflammatory load, and these increases are associated with increased odds for unfavorable global outcomes in the first year following TBI. Future studies should explore additional factors contributing to IL-6 elevations, and therapies to mitigate its detrimental effects on outcome.

Increased CSF concentrations of myelin basic protein after TBI in infants and children: absence of significant effect of therapeutic hypothermia.

BACKGROUND: The objectives of this study were to determine effects of severe traumatic brain injury (TBI) on cerebrospinal fluid (CSF) concentrations of myelin basic protein (MBP) and to assess relationships between clinical variables and CSF MBP concentrations. METHODS: We measured serial CSF MBP concentrations in children enrolled in a randomized controlled trial evaluating therapeutic hypothermia (TH) after severe pediatric TBI. Control CSF was obtained from children evaluated, but found not to be having CNS infection. Generalized estimating equation models and Wilcoxon Rank-Sum test were used for comparisons of MBP concentrations. RESULTS: There were 27 TBI cases and 57 controls. Overall mean (± SEM) TBI case MBP concentrations for 5 days after injury were markedly greater than controls (50.49 ± 6.97 vs. 0.11 ± 0.01 ng/ml, p < 0.01). Mean MBP concentrations were lower in TBI patients <1 year versus >1 year (9.18 ± 1.67 vs. 60.22 ± 8.26 ng/ml, p = 0.03), as well as in cases with abusive head trauma (AHT) versus non-abusive TBI (14.46 ± 3.15 vs. 61.17 ± 8.65 ng/ml, p = 0.03). TH did not affect MBP concentrations. CONCLUSIONS: Mean CSF MBP increases markedly after severe pediatric TBI, but is not affected by TH. Infancy and AHT are associated with low MBP concentrations, suggesting that age-dependent myelination influences MBP concentrations after injury. Given the magnitude of MBP increases, axonal injury likely represents an important therapeutic target in pediatric TBI.

Rhabdomyolysis associated with infection by Mycoplasma pneumoniae: a case report.

BACKGROUND: Mycoplasma pneumoniae is responsible for approximately 20% of the cases of community-acquired pneumonia. The onset of respiratory symptoms is gradual and systemic complaints such as headache, malaise, arthalgias, and low-grade fever are frequently prominent. Extrapulmonary manifestations of M pneumoniae are common and hematologic (thrombocytopenia, splenomegaly, disseminated intravascular coagulation, hemolytic anemia), dermatologic (Stevens-Johnson syndrome), gastrointestinal (vomiting, diarrhea, pancreatitis), renal (interstitial nephritis, glomerulonephritis), cardiac (pericarditis, myocarditis, pericardial effusion) and central nervous system (meningitis, transverse myelitis, polyradiculopathy, cerebellar ataxia, sensorineural hearing loss) complications can occur. OBSERVATION: We describe the case of an adolescent girl with massive rhabdomyolysis associated with an infection caused by M pneumoniae. We briefly review the differential diagnosis of a patient presenting with acute rhabdomyolysis and discuss the use of a new polymerase chain reaction-based assay for direct detection of M pneumoniae in throat swab specimens. CONCLUSION: Clinicians should be aware of a possible association between rhabdomyolysis and infection with M pneumoniae and should consider testing for M pneumoniae when they are presented with a patient with idiopathic rhabdomyolysis. The new polymerase chain reaction-based assay for detection of M pneumoniae is a more accurate and more efficient method than traditional culture.

A study of solder investment setting expansion and thermal contraction: Part 2.

In this study, which won the NBC Fellowship Project, the author measured expansion and contraction in two soldering and six casting investments to determine which are most accurate (defined as marginal gap less than 50 micrometers and lack of movement with alternating finger pressure) under a number of manipulated parameters, including water/powder ratio, setting time, span length and burnout temperature. It was determined that all investments demonstrated slight expansion between initial and final set. Substantial contraction occurred in all investments when subjected to heat. Vestra, CB-30 and Cera-Fina demonstrated the greatest contraction at 1500 degrees F. Hi-Heat (soldering), Quick Set, High Span, Vivest, and Hi-Temp (casting) demonstrated greatest contraction at 2000 degrees F. The purpose of the study and the methods and materials used were explained in part one, published in March. The results and conclusions are presented here. An introduction to elevated fixturing and a verification of the study results will be presented in part three.

A study of solder investment setting and thermal contraction: Part 1.

In this study, which won the NBC Fellowship Project, the author measured expansion and contraction in two soldering and six casting investments to determine which are most accurate (defined as marginal gap less than 50 micrometers and lack of movement with alternating finger pressure) under a number of manipulated parameters, including water/powder ratio, setting time, span length and burnout temperature. It was determined that all investments demonstrated slight expansion between initial and final set. Substantial contraction occurred in all investments when subjected to heat. Vestra, CB-30 and Cera-Fina demonstrated the greatest contraction at 1500 degrees F. Hi-Heat [corrected] (soldering), Quick Set, High Span, Vivest, and Hi-Temp (casting) demonstrated greatest contraction at 2000 degrees F. The purpose of the study and the methods and materials used are explained in part 1. The results and conclusions will be presented in part 2. An introduction to elevated fixturing and a verification of the study results will be presented in part 3.