Background: Low back pain (LBP) is the leading global cause of disability and is associated with intervertebral disc degeneration (DD) in some individuals. However, many adults have DD without LBP. Understanding why DD is painful in some and not others may unmask novel therapies for chronic LBP. The objectives of this study were to a) identify factors in human cerebrospinal fluid (CSF) associated with chronic LBP and b) examine their therapeutic utility in a proof-of-concept pre-clinical study. Methods: Pain-free human subjects without DD, pain-free human subjects with DD, and patients with chronic LBP linked to DD were recruited and lumbar MRIs, pain and disability levels were obtained. CSF was collected and analyzed by multiplex cytokine assay. Interleukin-8 (IL-8) expression was confirmed by ELISA in CSF and in intervertebral discs. The SPARC-null mouse model of progressive, age-dependent DD and chronic LBP was used for pre-clinical validation. Male SPARC-null and control mice received systemic Reparixin, a CXCR1/2 (receptors for IL-8 and murine analogues) inhibitor, for 8 weeks. Behavioral signs of axial discomfort and radiating pain were assessed. Following completion of the study, discs were excised and cultured, and conditioned media was evaluated with a protein array. Findings: IL-8 was elevated in CSF of chronic LBP patients with DD compared to pain-free subjects with or without DD. Chronic inhibition with reparixin alleviated low back pain behaviors and attenuated disc inflammation in SPARC-null mice. Interpretation: These studies suggest that the IL-8 signaling pathway is a viable therapy for chronic LBP. Fund: Supported by NIH, MMF, CIHR and FRQS.

All exercises including the novel clip-applying model demonstrated good acceptability and evidence of construct validity (face, content, concurrent and convergent validity) for assessment of basic laparoscopic skill for urologic surgeons.

Simulation-based subtask training shows promise as an effective and reproducible method to teach the complex psychomotor task of airway foreign body retrieval. Completion of the curriculum led to a significant improvement in residents' confidence in and ability to perform bronchoscopic foreign body retrieval in an infant airway mannequin.

Intervertebral disc degeneration (DD) is a cause of low back pain (LBP) in some individuals. However, while >30% of adults have DD, LBP only develops in a subset of individuals. To gain insight into the mechanisms underlying non-painful versus painful DD, human cerebrospinal fluid (CSF) was examined using differential expression shotgun proteomic techniques comparing healthy controls, subjects with non-painful DD, and patients with painful DD scheduled for spinal fusion surgery. Eighty-eight proteins were detected, 27 of which were differentially expressed. Proteins associated with DD tended to be related to inflammation (e.g. cystatin C) regardless of pain status. In contrast, most differentially expressed proteins in DD-associated chronic LBP patients were linked to nerve injury (e.g. hemopexin). Cystatin C and hemopexin were selected for further examination by ELISA in a larger cohort. While Cystatin C correlated with DD severity but not pain or disability, hemopexin correlated with pain intensity, physical disability and DD severity. This study demonstrates that CSF can be used to study mechanisms underlying painful DD in humans, and suggests that while painful DD is associated with nerve injury, inflammation itself is not sufficient to develop LBP.

In this multi-institutional study we successfully demonstrated the construct and internal validity of an objective assessment of cystoscopic and ureteroscopic cognitive and technical skills, including laser lithotripsy.