IL-8 correlates with reduced baseline femoral neck bone mineral density in adults with cystic fibrosis: a single center retrospective study.

Cystic fibrosis (CF) is a multi-system disease that is characterized by lung disease due to recurrent airway infection and inflammation. Endocrine complications, such as CF bone disease (CFBD), are increasingly identified as patients are living longer. The cause of CFBD is multifactorial with chronic systemic inflammation theorized to be a contributing factor. Thus, we attempted to identify inflammatory biomarkers that are associated with CFBD. We conducted a retrospective observational study of 56 adult patients with CF with an average percentage predictive forced expiratory volume in one second (ppFEV1) of 73.7% (standard deviation: 30.0) who underwent baseline serum analysis for osteoprotegerin (OPG) and pro-inflammatory biomarkers (IL-1ß, IL-6, IL-8 and TNF-α), and had repeated dual-energy x-ray absorptiometry (DXA) scans separated by at least 2 years to examine correlations between serum biomarkers and bone mineral density (BMD) measurements. Univariate linear regression model analysis demonstrated that serum IL-1ß and IL-8, but not other pro-inflammatory markers, were negatively correlated with baseline BMD results. However, after accounting for confounding variables, only the relationship between IL-8 and left femoral neck BMD remained statistically significant. Additionally, IL-8 level was associated with BMD decline over time. These results suggest that IL-8 might play a unique role in the pathophysiology of CFBD relative to other pro-inflammatory cytokines but further study is warranted before firm conclusions can be made.

Factors influencing clinical trial participation for adult and pediatric patients with cystic fibrosis.

There remains a limited understanding of the factors influencing clinical trial participation for individuals with Cystic Fibrosis (CF). A comprehensive survey was developed to examine the interests, preferences, and barriers/facilitators to research and clinical trial participation for CF patients. A consecutive sample of 198 CF adults attending the St. Paul's Hospital CF Clinic and parents of children with CF attending the BC Children's Hospital CF Clinic from Vancouver, Canada were surveyed. Parents of pediatric patients were less comfortable with blood collection, required more safety data prior to participating, and were more concerned about potential side effects. Very few respondents (<10%) appeared able/willing to fulfill the typical requirements to participate in a phase 1 clinical trial. Overall, there were more similarities than differences between the responses of adult and parents of pediatric CF patients. The patient-centered information can be used to inform the design of future clinical trials to enhance feasibility.

A Cervical Spinal Cord Hemi-Contusion Injury Model Based on Displacement Control in Non-Human Primates (Macaca fascicularis).

Non-human primate (NHP) spinal cord injury (SCI) models can be informative in the evaluation of treatments that show promise in rodent models prior to translation to humans. In the present study, we aimed to establish a cervical spinal hemi-contusion model with controlled displacement and evaluate the abnormalities in behavior, electrophysiology, histology, and magnetic resonance imaging. Twelve adult NHPs were divided into an SCI group (n = 8, 24 and 48 weeks) and a control group (n = 4). An impactor (Φ = 4 mm) was driven to compress the left C5 cord at 800 mm/sec. The contusion displacement and peak force was 4.08 ± 0.17 mm and 19.8 ± 4.6 N. The behavioral assessment showed a consistent dysfunction below the wrist and spontaneous recovery of limb function after injury. Lesion length and lesion area at the epicenter based on T2 hyperintensity were 5.68 ± 0.47 mm and 5.99 ± 0.24 mm2 at 24 weeks post-injury (wpi), and 5.29 ± 0.17 mm and 5.95 ± 0.24 mm2 at 48 wpi. The spared spinal cord area immuno-positive for glial fibrillary acidic protein was significantly reduced, while the staining intensity increased at 24 wpi and 48 wpi, compared with the sham group. Ipsilateral somatosensory and motor evoked potentials were dynamic, increasing in latency and decreasing in amplitude compared with pre-operative values or the contralateral values, and correlated to varying degrees with behavioral outcomes. A shift in size-frequency distribution of sensory neurons of the dorsal root ganglia (DRG) was consistent with a loss of large-diameter cells. The present study demonstrated that the NHP SCI model resulted in consistent unilateral limb dysfunction and potential plasticity in the face of loss of spinal cord and DRG tissue.