Despite the clinical relevance of back pain and intervertebral disc herniation, the lack of reliable models has strained their molecular understanding. We characterized the lumbar spinal phenotype of C57BL/6 and SM/J mice during aging. Interestingly, old SM/J lumbar discs evidenced accelerated degeneration, associated with high rates of disc herniation. SM/J AF's and degenerative human's AF transcriptomic profiles showed altered immune cell, inflammation, and p53 pathways. Old SM/J mice presented increased neuronal markers in herniated discs, thicker subchondral bone, and higher sensitization to pain. Dorsal root ganglia transcriptomic studies and spinal cord analysis exhibited increased pain and neuroinflammatory markers associated with altered extracellular matrix regulation. Immune system single-cell and tissue level analysis showed distinctive T-cell and B-cell modulation and negative correlation between mechanical allodynia and INF-α, IL-1β, IL2, and IL4, respectively. This study underscores the multisystemic network behind back pain and highlights the role of genetic background and the immune system in disc herniation disease.

Acknowledgments: This study is supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R01AR055655, R01AR064733, R01AR074813 to MVR.

Purpose: Resection of pelvic sarcoma with limb preservation (internal hemipelvectomy) is a major undertaking. Resection requires large areas of soft-tissue to be removed. Because of wound complications, we manage these defects with immediate tissue transfer (ITT) at the time of resection when a large defect is anticipated. This study compares the outcomes of ITT with primary wound closure (PWC).

Method: Twenty patients undergoing 22 separate procedures (1995–2007) were identified in our prospectively maintained database. Demographics, tumour type, operative data and complications, and functional scores (MSTS-1993, TESS) were collected.

Results: Twelve defects were managed with ITT, nine with pedicled myocutaneous vertical rectus abdominis (VRAM) flaps (one received double VRAM flaps due to the large defect), two with tensor fascia lata (TFL) rotation flaps (one augmented by local V-Y advancement, the other with gluteus maximus rotation flap) and one received latissimus dorsi free tissue transfer. Four wound complications necessitated operative intervention in this group: two debrided VRAM flaps went on to heal and the two TFL flaps required revision: one to VRAM flap and the other to a latissimus dorsi free flap which ultimately suffered chronic infection and hindquarter amputation was performed. Ten defects were managed with PWC, and 5 wound complications occurred, all five suffered infection, one developed hematoma and one dehisced. One wound resolved with debridement, two healed after revision to pedicled gracilis and gluteus maximus myocutaneous flaps. Two patients were converted to hindquarter amputation due to chronic infection. Functional scores were collected on 8 of 12 living patients, at time of writing. The mean TESS scores were 83 and 73 in the ITT and PWC groups. Five patients in the ITT and 3 in the PWC group were deceased.

Conclusion: Soft-tissue closure following pelvic sarcoma resection remains a difficult challenge, and our experience reflects that. There were fewer wound complications (33% v 50%) and slightly better function with ITT than PWC, but this was not statistically significant due to the small size of our study. Although small, this study suggests ITT should be considered whenever a large soft tissue defect is anticipated.