Intervertebral disc (IVD) degeneration (IVDD) is a leading cause of chronic low backpain. There is a strong clinical demand for more effective treatments for IVDD as conventional treatments provide only symptomatic relief rather than arresting IVDD progression. This study shows that senolytic therapy with local drug delivery can inhibit IVDD and restore IVD integrity. ABT263, a senolytic drug, is loaded in poly(lactic-co-glycolic acid) nanoparticles (PLGA-ABT) and intradiscally administered into injury-induced IVDD rat models. The single intradiscal injection of PLGA-ABT may enable local delivery of the drug to avascular IVD, prevention of potential systemic toxicity caused by systemic administration of senolytic drug, and morbidity caused by repetitive injections of free drug into the IVD. The strategy results in the selective elimination of senescent cells from the degenerative IVD, reduces expressions of pro-inflammatory cytokines and matrix proteases in the IVD, inhibits progression of IVDD, and even restores the IVD structure. This study demonstrates for the first time that local delivery of senolytic drug can effectively treat senescence-associated IVDD. This approach can be extended to treat other types of senescence-associated degenerative diseases.

Neuromuscular disorders (NMDs) are diseases involving the upper and lower motor neurons and muscles. In patients with NMDs, cervical spinal deformities are a very common issue; however, unlike thoracolumbar spinal deformities, few studies have investigated these disorders. The patients with NMDs have irregular spinal curvature caused by poor balance and poor coordination of their head, neck, and trunk. Particularly, cervical deformity occurs at younger age, and is known to show more rigid and severe curvature at high cervical levels. Muscular physiologic dynamic characteristics such as spasticity or dystonia combined with static structural factors such as curvature flexibility can result in deformity and often lead to traumatic spinal cord injury. In addition, postoperative complication rate is higher due to abnormal involuntary movement and muscle tone. Therefore, it is important to control abnormal involuntary movement perioperatively along with strong instrumentation for correction of deformity. Various methods such as botulinum toxin injection, physical therapy, muscle division technique, or intrathecal baclofen pump implant may help control abnormal involuntary movements and improve spinal stability. Surgical management for cervical deformities associated with NMDs requires a multidisciplinary effort and a customized strategy.

Study Design. Retrospective study. Objective. To investigate the associated risk factors for acute respiratory distress after multilevel anterior cervical discectomy and fusion (ACDF) with a focus on the subjective symptom, dyspnea. Summary of Background Data. Acute respiratory distress after ACDF is a relatively common adverse event, the cause of which is usually soft tissue swelling or hematoma. It can result in serious morbidity and requires careful, focused treatment. Methods. We reviewed the records of 532 patients (from January 2014 to August 2018) who had undergone multilevel ACDF surgery. Acute respiratory distress was defined as a complaint of dyspnea within 5 postoperative days. We investigated the patients’ demographic parameters, comorbidities, and surgical procedure details. We also investigated radiologic parameters, including magnetic resonance imaging (MRI), with special attention to the prevertebral soft tissue thickness at C3 and C6. Statistical analysis was performed using the Student's t test and multiple logistic regression analysis. Results. Out of a total of 484 patients studied after exclusion criteria were applied, 31 patients (6.6%) experienced dyspnea after surgery. We selected 92 patients from the non-dyspnea group and compared them with 31 patients from the dyspnea group. On univariate analysis, upper cervical surgery involving C3, increased cord signal intensity on T2-weighted imaging (T2WI) magnetic resonance imaging (MRI), hypertension, smoking, and prevertebral soft tissue swelling at C3 level on postoperative day 1 were statistically significant factors associated with dyspnea. On logistic regression analysis, upper cervical surgery involving C3, increased cord signal intensity on T2WI MRI, and hypertension were found to be statistically significant variables (P < 0.05). Conclusion. Patients undergoing upper cervical surgery involving C3, and having increased cord signal intensity on T2WI MRI and hypertension need to be monitored more carefully for acute respiratory distress after multilevel ACDF. Level of Evidence: 4