Effect of species, concentration and volume of local anesthetics on intervertebral disk degeneration in rats with discoblock.

PURPOSE: Discoblock is effective in relieving discogenic low back pain, but it can also cause intervertebral disk degeneration (IDD). The effect of species, concentration and volume of local anesthetics on IDD with discoblock have not been reported. The purpose was to study the effect of species, concentration and volume of local anesthetics on IDD in rats undergoing discoblock. METHODS: The effects of local anesthetics on nucleus pulposus cell (NPC) viability in vitro were studied. NPCs were exposed to lidocaine, bupivacaine and ropivacaine at different concentrations. NPC viability was measured. The least cytotoxic local anesthetic was used in vivo. The concentration and volume of local anesthetics on IDD in rat with discoblocks were tested in vivo. Detection indicators included X-ray, MRI, water content of the disk and histological changes. RESULTS: The toxicity of local anesthetics to NPCs was dose and time dependent, and the cytotoxicity of different local anesthetics was different. Among the three local anesthetics, ropivacaine was the least toxic to NPCs. The effect of ropivacaine concentration on IDD was not significant, as detected by X-ray, MRI, disk water content and histology (P < 0.05). The volume of ropivacaine has a significant effect on IDD, as supported by X-ray, MRI, disk water content and histology (P < 0.05). Acupuncture itself significantly increased IDD, as detected by MRI, disk water content and histology (P < 0.05). CONCLUSION: Ropivacaine should be selected for its low cytotoxicity. A lower volume and slow injection speed should be used to reduce IDD during discoblock.

Does Focal Kyphotic Deformity at Non-responsible Levels Affect the Outcomes of Anterior Cervical Decompression and Fusion?

OBJECTIVE: Focal cervical kyphotic deformity (FCK) without neurologic compression is not uncommon in patients with cervical spondylotic myelopathy (CSM) who underwent anterior cervical decompression and fusion (ACDF) surgery. It remains unclear whether FCK at non-responsible levels needs to be treated simultaneously. This study aims to investigate whether FCK at non-responsible levels is the prognostic factor for CSM and elucidate the surgical indication for FCK. METHODS: Patients with CSM who underwent ACDF between January 2016 and April 2021 were included. Patients were divided into two groups according to the presence of FCK and two classifications according to global cervical sagittal alignment. Clinical outcomes were compared using Japanese Orthopaedic Association (JOA) scores and recovery rate (RR) of neurologic function. Univariate and multivariate analysis based on RR assessed the relationship between various possible prognostic factors and clinical outcomes. The receiver operating characteristic curve (ROC) was used to determine the optimal cutoff value of the focal Cobb angle to predict poor clinical outcomes. RESULTS: A total of 94 patients were included, 41 with FCK and 53 without. Overall, the RR of neurologic function was significantly lower in the FCK than in the non-FCK group. Further analysis showed that the RR difference between the two groups was only observed in hypo-lordosis classification (kyphotic and sigmoid alignment), but not in the lordosis classification. Multivariate analysis showed that the preoperative focal Cobb angle in the FCK level (OR = 0.42; 95% CI = 0.18-0.97) was independently associated with clinical outcomes in the hypo-lordosis classification. The optimal cutoff point of the preoperative focal kyphotic Cobb angle was calculated at 4.05°. CONCLUSION: For CSM with hypo-lordosis, FCK was a risk factor for poor postoperative outcomes. Surgeons may consider treating the FCK simultaneously if the focal kyphotic Cobb angle of FCK is greater than 4.05° and is accompanied by cervical global kyphotic or sigmoid deformity.

TMEM135 maintains the equilibrium of osteogenesis and adipogenesis by regulating mitochondrial dynamics.

BACKGROUND: Disturbance in the differentiation process of bone marrow mesenchymal stem cells (BMSCs) leads to osteoporosis. Mitochondrial dynamics plays a pivotal role in the metabolism and differentiation of BMSCs. However, the mechanisms underlying mitochondrial dynamics and their impact on the differentiation equilibrium of BMSCs remain unclear. METHODS: We investigated the mitochondrial morphology and markers related to mitochondrial dynamics during BMSCs osteogenic and adipogenic differentiation. Bioinformatics was used to screen potential genes regulating BMSCs differentiation through mitochondrial dynamics. Subsequently, we evaluated the impact of Transmembrane protein 135 (TMEM135) deficiency on bone homeostasis by comparing Tmem135 knockout mice with their littermates. The mechanism of TMEM135 in mitochondrial dynamics and BMSCs differentiation was also investigated in vivo and in vitro. RESULTS: Distinct changes in mitochondrial morphology were observed between osteogenic and adipogenic differentiation of BMSCs, manifesting as fission in the late stage of osteogenesis and fusion in adipogenesis. Additionally, we revealed that TMEM135, a modulator of mitochondrial dynamics, played a functional role in regulating the equilibrium between adipogenesis and osteogenesis. The TMEM135 deficiency impaired mitochondrial fission and disrupted crucial mitochondrial energy metabolism during osteogenesis. Tmem135 knockout mice showed osteoporotic phenotype, characterized by reduced osteogenesis and increased adipogenesis. Mechanistically, TMEM135 maintained intracellular calcium ion homeostasis and facilitated the dephosphorylation of dynamic-related protein 1 at Serine 637 in BMSCs. CONCLUSIONS: Our findings underscore the significant role of TMEM135 as a modulator in orchestrating the differentiation trajectory of BMSCs and promoting a shift in mitochondrial dynamics toward fission. This ultimately contributes to the osteogenesis process. This work has provided promising biological targets for the treatment of osteoporosis.

Clinical Outcomes of Percutaneous Endoscopic Lumbar Discectomy Assisted With Sequential SNRB in Treating Lumbosacral Contiguous Double-Level Disc Herniation.

BACKGROUND: For patients with lumbosacral contiguous double-level disc herniation, there has been no consensus on which level(s) should be treated. Selective nerve root block (SNRB) can identify the pain-generating nerve root; however, its diagnostic accuracy remains controversial due to potential spread of the injectate. Sequential SNRB from S1 to L5 may improve the diagnostic specificity. OBJECTIVES: To examine the clinical and radiographic outcomes of percutaneous endoscopic lumbar discectomy (PELD) assisted with sequential SNRB from S1 to L5 in patients who had lumbosacral contiguous double-level disc herniation. STUDY DESIGN: A retrospective design was used. SETTING: This study was conducted in a university-affiliated tertiary hospital in Shanghai, China. METHODS: Fifty-eight consecutive patients with lumbosacral contiguous double-level disc herniation were included (January 2018 to January 2021). Sequential SNRB from S1 to L5 was performed to identify the symptomatic level(s), followed by PELD based on the results of sequential SNRB. Clinical outcomes were assessed by the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and modified Macnab criteria. Pre- and post-operation radiologic and clinical parameters were evaluated. Demographics were retrieved from medical records. RESULTS: Patients were followed-up with an average duration of 18.6 months. Among the 58 patients, 21 received surgical treatment at L4/L5 level, 25 at L5/S1 level, and 12 at both levels based on the results of sequential SNRB from S1 to L5. Compared with preoperative values, mean VAS scores for leg and back pain, as well as the ODI score, improved significantly after the surgery. There were no significant differences in the clinical outcomes between patients receiving surgical treatment at L4/L5, L5/S1, or both levels. According to the Macnab criteria, 49 patients (84.5%) had excellent or good results. LIMITATIONS: This study used a retrospective design with relatively small sample size and medium follow-up duration. CONCLUSIONS: Sequential SNRB from S1 to L5 was an effective approach to guide PELD treatment for patients with lumbosacral contiguous double-level disc herniation. Health care providers may consider using this approach to facilitate future clinical practice.

The Ability of Biodegradable Thermosensitive Hydrogel Composite Calcium-Silicon-Based Bioactive Bone Cement in Promoting Osteogenesis and Repairing Rabbit Distal Femoral Defects.

Osteoporotic vertebral compression fractures are a global issue affecting the elderly population. To explore a new calcium silicate bone cement, polylactic acid (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel was compounded with tricalcium silicate (C3S)/dicalcium silicate (C2S)/plaster of Paris (POP) to observe the hydration products and test physical and chemical properties. The cell compatibility and osteogenic capability were tested in vitro. The rabbit femoral condylar bone defect model was used to test its safety and effectiveness in vivo. The addition of hydrogel did not result in the formation of a new hydration product and significantly improved the injectability, anti-washout properties, and in vitro degradability of the bone cement. The cholecystokinin octapeptide-8 method showed significant proliferation of osteoblasts in bone cement. The Alizarin red staining and alkaline phosphatase activity test showed that the bone cement had a superior osteogenic property in vitro. The computed tomography scan and gross anatomy at 12 weeks after surgery in the rabbit revealed that PLGA-PEG-PLGA/C3S/C2S/POP was mostly degraded, with the formation of new bone trabeculae and calli at the external orifice of the defect. Thus, PLGA-PEG-PLGA/C3S/C2S/POP composite bone cement has a positive effect on bone repair and provides a new strategy for the clinical application of bone tissue engineering materials.

Oblique lateral interbody fusion stand-alone vs. combined with percutaneous pedicle screw fixation in the treatment of discogenic low back pain.

Objective: Oblique lateral interbody fusion (OLIF) has unique advantages in the treatment of discogenic low back pain (DBP). However, there are few studies in this area, and no established standard for additional posterior internal fixation. The purpose of this study was to investigate the efficacy of OLIF stand-alone vs. combined with percutaneous pedicle screw fixation (PPSF) in the treatment of DBP. Methods: This retrospective case-control study included forty patients. All patients were diagnosed with DBP by discography and discoblock. Perioperative parameters (surgery duration, blood loss, and muscle damage), complications, Visual analog scale (VAS), and Oswestry Disability Index (ODI) were assessed. Imaging data including cage subsidence, cage retropulsion, fusion rate, and adjacent spondylosis degeneration (ASD) were analyzed. Results: There were 23 patients in the OLIF stand-alone group and 17 patients in the OLIF + PPSF group. The mean surgery duration, blood loss, and muscle damage in the OLIF stand-alone group were significantly better than those in the OLIF + PPSF group (P < 0.05). However, there was no significant difference in the average hospitalization time between the two groups (P > 0.05). There was no significant difference in the VAS and ODI scores between the two groups before surgery (P > 0.05), and VAS and ODI scores significantly improved after surgery (P < 0.05). The VAS and ODI scores in the OLIF stand-alone group were significantly better than those in the OLIF + PPSF group at 1 month (P < 0.05), While there was no significant difference between the two groups at 12 months and last follow up (P > 0.05). At the last follow-up, there was no significant difference in cage subsidence, fusion rate, ASD and complication rate between the two groups (P > 0.05). Conclusion: OLIF stand-alone and OLIF + PPSF are both safe and effective in the treatment of DBP, and there is no significant difference in the long-term clinical and radiological outcomes. OLIF stand-alone has the advantages of surgery duration, blood loss, muscle damage, and early clinical effect. More clinical data are needed to confirm the effect of OLIF stand-alone on cage subsidence and ASD. This study provides a basis for the clinical application of standard DBP treatment with OLIF.