The Utility and Feasibility of Smart Glasses in Spine Surgery: Minimizing Radiation Exposure During Percutaneous Pedicle Screw Insertion.

OBJECTIVE: Spine surgeons are often at risk of radiation exposure due to intraoperative fluoroscopy, leading to health concerns such as carcinogenesis. This is due to the increasing use of percutaneous pedicle screw (PPS) in spinal surgeries, resulting from the widespread adoption of minimally invasive spine stabilization. This study aimed to elucidate the effectiveness of smart glasses (SG) in PPS insertion under fluoroscopy. METHODS: SG were used as an alternative screen for fluoroscopic images. Operators A (2-year experience in spine surgery) and B (9-year experience) inserted the PPS into the bilateral L1-5 pedicles of the lumbar model bone under fluoroscopic guidance, repeating this procedure twice with and without SG (groups SG and N-SG, respectively). Each vertebral body's insertion time, radiation dose, and radiation exposure time were measured, and the deviation in screw trajectories was evaluated. RESULTS: The groups SG and N-SG showed no significant difference in insertion time for the overall procedure and each operator. However, group SG had a significantly shorter radiation exposure time than group N-SG for the overall procedure (109.1 ± 43.5 seconds vs. 150.9 ± 38.7 seconds; p = 0.003) and operator A (100.0 ± 29.0 seconds vs. 157.9 ± 42.8 seconds; p = 0.003). The radiation dose was also significantly lower in group SG than in group N-SG for the overall procedure (1.3 ± 0.6 mGy vs. 1.7 ± 0.5 mGy; p = 0.023) and operator A (1.2 ± 0.4 mGy vs. 1.8 ± 0.5 mGy; p = 0.013). The 2 groups showed no significant difference in screw deviation. CONCLUSION: The application of SG in fluoroscopic imaging for PPS insertion holds potential as a useful method for reducing radiation exposure.

Predictors of Persistent Postoperative Numbness Following Lumbar Fusion in Patients Older Than 75 Years: A Minimum 2-Year Follow-up.

OBJECTIVE: To evaluate the preoperative and perioperative predictors of persistent leg numbness following lumbar fusion in patients aged ≥ 75 years. METHODS: This single-center retrospective study examined 304 patients aged ≥ 75 years who underwent lumbar fusion for lumbar degenerative disease (102 men, 202 women; mean age, 79.2 [75-90] years). The visual analogue scale (VAS) score for leg numbness was examined preoperatively and at 2 years postoperatively. The persistent leg numbness group included patients with a 2-year postoperative VAS score for leg numbness ≥ 5 points. The demographic data were also reviewed. A multivariate stepwise logistic regression analysis was performed for variables with univariate analysis values of p < 0.2 on univariate analysis. RESULTS: In total, 71 patients (23.4%) experienced persistent postoperative leg numbness. Multivariate logistic regression analysis revealed that a history of lumbar decompression, longer symptom duration, and a preoperative VAS score for leg numbness ≥ 5 points were associated with greater postoperative persistent leg numbness following lumbar fusion. In contrast, other factors, such as sex, body mass index, vertebral fracture, diabetes mellitus, depression, symptom duration, dural injury, operative time, and estimated blood loss, were not. CONCLUSION: A history of preoperative lumbar decompression, longer symptom duration, and greater preoperative VAS scores for leg numbness were preoperative predictors of persistent postoperative leg numbness following lumbar fusion in older patients. Although lumbar fusion is expected to improve leg numbness, surgeons should consider the surgical history, duration, and preoperative numbness intensity and explain the potential postoperative persistent leg numbness in advance.

Clinical Features and Therapeutic Process of Sacral Fatigue Fractures in Adolescents.

BACKGROUND: Sacral fatigue fractures are a rare injury but should be considered as a differential diagnosis for low back and buttock pain in young adults. Collective reports are limited, most of which have focused on long-distance runners. PURPOSE: To investigate the characteristics of sacral fatigue fractures in adolescents. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: We analyzed patient background characteristics, physical examination and imaging findings, and treatment courses of those diagnosed with sacral fatigue fractures using magnetic resonance imaging. RESULTS: Among 34 patients with sacral fatigue fractures, 15 and 19 were male and female patients, respectively, with an age range of 11 to 19 years (mean age, 15.0 years). Almost all patients were athletes, and 29 patients performed their sport ≥5 times a week. Long-distance runners were the most commonly affected, comprising 7 patients, and participants in other common sports such as baseball (6 patients), basketball (4 patients), and soccer (3 patients) were also affected. Physical examination revealed tension sign (Lasègue test) on the affected side in 6 patients and tight hamstrings in 24 patients. Imaging findings included 18 patients with right-side involvement, 12 with left-side involvement, and 4 with involvement on both sides. In 11 patients, spina bifida occulta was observed at S1 and 8 patients had a history of lumbar spondylolysis with 4 patients having concurrent sacral fatigue fractures. Physical therapy was performed concurrently with the cessation of exercise, and return to exercise was permitted if the pain had been relieved after 1 month. All patients returned to sports at a median of 48 days (range, 20-226 days) after symptom onset. However, 2 patients experienced recurrence (1 patient on the ipsilateral side and 1 patient on the contralateral side). CONCLUSION: Sacral stress fractures are not limited to long-distance runners in this population and can manifest as lower back pain or buttock pain in athletes participating in a variety of sports. Although the course of treatment was generally good, the possibility of recurrence must always be considered.

Clinical Characteristics, Surgical Outcomes, and Risk Factors for Emergency Surgery in Patients With Spinal Metastases: A Prospective Cohort Study.

OBJECTIVE: To elucidate the patient characteristics and outcomes of emergency surgery for spinal metastases and identify risk factors for emergency surgery. METHODS: We prospectively analyzed 216 patients with spinal metastases who underwent palliative surgery from 2015 to 2020. The Eastern Cooperative Oncology Group performance status, Barthel index, EuroQol-5 dimension (EQ5D), and neurological function were assessed at surgery and at 1, 3, and 6 months postoperatively. Multivariate analysis was performed to identify risk factors for emergency surgery. RESULTS: In total, 146 patients underwent nonemergency surgery and 70 patients underwent emergency surgery within 48 hours of diagnosis of a surgical indication. After propensity score matching, we compared 61 patients each who underwent nonemergency and emergency surgery. Regardless of matching, the median performance status and the mean Barthel index and EQ5D score showed a tendency toward worse outcomes in the emergency than nonemergency group both preoperatively and 1 month postoperatively, although the surgery greatly improved these values in both groups. The median survival time tended to be shorter in the emergency than nonemergency group. The multivariate analysis showed that lesions located at T3-10 (p = 0.002; odds ratio [OR], 2.92; 95% confidence interval [CI], 1.48-5.75) and Frankel grades A-C (p < 0.001; OR, 4.91; 95% CI, 2.45-9.86) were independent risk factors for emergency surgery. CONCLUSION: Among patients with spinal metastases, preoperative and postoperative subjective health values and postoperative survival are poorer in emergency than nonemergency surgery. Close attention to patients with T3-10 metastases is required to avoid poor outcomes after emergency surgery.

Rapamycin mitigates inflammation-mediated disc matrix homeostatic imbalance by inhibiting mTORC1 and inducing autophagy through Akt activation.

Background: Low back pain is a global health problem that originated mainly from intervertebral disc degeneration (IDD). Autophagy, negatively regulated by the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway, prevents metabolic and degenerative diseases by removing and recycling damaged cellular components. Despite growing evidence that autophagy occurs in the intervertebral disc, the regulation of disc cellular autophagy is still poorly understood. Methods: Annulus fibrosus (rAF) cell cultures derived from healthy female rabbit discs were used to test the effect of autophagy inhibition or activation on disc cell fate and matrix homeostasis. Specifically, different chemical inhibitors including rapamycin, 3-methyladenine, MK-2206, and PP242 were used to modulate activities of different proteins in the PI3K/Akt/mTOR signaling pathway to assess IL-1ß-induced cellular senescence, apoptosis, and matrix homeostasis in rAF cells grown under nutrient-poor culture condition. Results: Rapamycin, an inhibitor of mTOR complex 1 (mTORC1), reduced the phosphorylation of mTOR and its effector p70/S6K in rAF cell cultures. Rapamycin also induced autophagic flux as measured by increased expression of key autophagy markers, including LC3 puncta number, LC3-II expression, and cytoplasmic HMGB1 intensity and decreased p62/SQSTM1 expression. As expected, IL-1ß stimulation promoted rAF cellular senescence, apoptosis, and matrix homeostatic imbalance with enhanced aggrecanolysis and MMP-3 and MMP-13 expression. Rapamycin treatment effectively mitigated IL-1ß-mediated inflammatory stress changes, but these alleviating effects of rapamycin were abrogated by chemical inhibition of Akt and mTOR complex 2 (mTORC2). Conclusions: These findings suggest that rapamycin blunts adverse effects of inflammation on disc cells by inhibiting mTORC1 to induce autophagy through the PI3K/Akt/mTOR pathway that is dependent on Akt and mTORC2 activities. Hence, our findings identify autophagy, rapamycin, and PI3K/Akt/mTOR signaling as potential therapeutic targets for IDD treatment.

Imaging Characteristics of Non-Rheumatoid Arthritis Patients With Retro-Odontoid Pseudotumor: A Multicenter Case-Control Study.

STUDY DESIGN: Multicenter case-control study. OBJECTIVE: To identify imaging characteristics of the cervical spine in patients with retro-odontoid pseudotumor (ROP) without rheumatoid arthritis (RA) and determine the pathogenesis of ROP. SUMMARY OF BACKGROUND DATA: ROP results from proliferative changes in the soft tissue of the atlantoaxial junction surrounding the region of the transverse ligament, and is commonly seen in RA patients. However, the pathogenesis of ROP caused by mechanical instability of the upper cervical spine in patients without RA is yet to be explained. METHODS: We collected imaging data (preoperative radiographs, magnetic resonance imaging [MRI], and computed tomography [CT]) of patients who underwent surgery between April 2011 and March 2022 at the three university hospitals for ROP (cases) and cervical spondylotic myelopathy (as age, sex, and institution matched controls). The two groups were compared for different parameters on cervical dynamic radiographs, MRI, and CT. RESULTS: The ROP group consisted of 42 patients, and the control group comprised 168 patients. C2-C7 range of motion was significantly smaller in the ROP group (25.8 ± 2.6°) compared to the control group (33.0 ± 1.0°). C2-C7 sagittal vertical axis was significantly larger in the ROP group than the control group (39.3 ± 3.6 mm versus 32.2 ± 1.3 mm). MRI and CT assessment showed progressive degeneration at all intervertebral levels in the ROP group. A significant positive correlation was observed between the thickness of the soft tissue posterior to the dental process and the atlantodental interval in the flexion position (r = 0.501). CONCLUSION: The development of ROP was associated with degeneration of facet joints and intervertebral discs in the middle and lower cervical spine. Our findings suggest that decreased mobility of the middle and lower cervical spine may cause instability in the upper cervical spine, leading to the formation of ROP.

Effect of Bone Metastasis Cancer Board on Spinal Surgery Outcomes: A Retrospective Study.

Background and Objectives: Bone metastasis cancer boards (BMCBs) focusing on the management of bone metastases have been gathering much attention. However, the association of BMCBs with spinal surgery in patients with spinal metastases remains unclear. In this retrospective single-center observational study, we aimed to clarify the effect of a BMCB on spinal metastasis treatment. Materials and Methods: We reviewed consecutive cases of posterior decompression and/or instrumentation surgery for metastatic spinal tumors from 2008 to 2019. The BMCB involved a team of specialists in orthopedics, rehabilitation medicine, radiation oncology, radiology, palliative supportive care, oncology, and hematology. We compared demographics, eastern cooperative oncology group performance status (ECOGPS), Barthel index (BI), number of overall versus emergency surgeries, and primary tumors between patients before (2008-2012) and after (2013-2019) BMCB establishment. Results: A total of 226 patients including 33 patients before BMCB started were enrolled; lung cancer was the most common primary tumor. After BMCB establishment, the mean patient age was 5 years older (p = 0.028), the mean operating time was 34 min shorter (p = 0.025), the mean hospital stay was 34.5 days shorter (p < 0.001), and the mean BI before surgery was 12 points higher (p = 0.049) than before. Moreover, the mean number of surgeries per year increased more than fourfold to 27.6 per year (p < 0.01) and emergency surgery rates decreased from 48.5% to 29.0% (p = 0.041). Patients with an unknown primary tumor before surgery decreased from 24.2% to 9.3% (p = 0.033). Postoperative deterioration rates from 1 to 6 months after surgery of ECOGPS and BI after BMCB started were lower than before (p = 0.045 and p = 0.027, respectively). Conclusion: The BMCB decreased the emergency surgery and unknown primary tumor rate despite an increase in the overall number of spinal surgeries. The BMCB also contributed to shorter operation times, shorter hospital stays, and lower postoperative deterioration rates of ECOGPS and BI.

Development and Validation of the 17-Point Brazilian Portuguese Translated Version of the Modified Japanese Orthopedic Association Score (mJOA-BR17).

BACKGROUND: Cervical spondylotic myelopathy (CSM) is the most common degenerative dysfunction of the spinal cord in the cervical spine in patients older than 55 years. The Japanese Orthopedic Association developed a scoring system to quantify clinical impairment of CSM patients, allocate them according to the degree of impairment, and suggest best timing for surgery. The original version evaluates the upper limb motor function through the ability of feeding with chopsticks, which are not intrinsic in western populations. To compare severity and treatment improvement of any diseases, it is preferable to have modified and translated versions of questionnaires and scores closest to the original ones. The authors present a prospective cohort study to validate the 17-point Brazilian Portuguese translated version of the modified Japanese Orthopedic Association (mJOA-BR17) survey. METHODS: Patients with CSM (n = 36) were allocated to the disease group, while age- and sex-matched healthy volunteers (n = 34) were recruited for the control group. Comparison of statistical analysis of mJOA-BR17 domains for each group was established. After the translation and adaptation of mJOA-BR17, the validation was made through application to the 2 groups. RESULTS: There were statistical differences between groups in total mJOA-BR17 score (CSM, 14.14 ± 2.92; control, 16.68 ± 0.59: P < 0.001), lower limbs motor function (CSM, 3.25 ± 1.02; control, 3.91 ± 0.29: P < 0.001), upper limbs sensory function (CSM, 1.17 ± 0.81; control, 1.86 ± 0.36: P < 0.001), lower limbs sensory function (CSM, 1.62 ± 0.64; control, 2.0 ± 0.0: P < 0.001), and bladder function (CSM, 2.69 ± 0.52; control, 2.97 ± 0.17: P = 0.005). The receiver operating characteristic curve was 0.81, indicating usefulness of the mJOA-BR17 score to identify patients with CSM from healthy controls. CONCLUSIONS: The mJOA-BR17 demonstrated similarity, applicability, and good understanding in comparison to the English-modified version of 17-point JOA score for CSM, becoming a valuable tool to quantify and differentiate CSM patients from healthy individuals.

Concepts of Regeneration for Spinal Diseases in 2023.

It is our pleasure to announce the publication of the Special Issue "Regeneration for Spinal Diseases 3.0" in the International Journal of Molecular Sciences (ISSN 1422-0067) [...].

Rate and Duration of Bone Union for Conservative Treatment in Pediatric Lumbar Spondylolysis.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To report the detailed bone fusion rates and duration of treatment in unilateral and bilateral cases of pediatric lumbar spondylolysis (LS). SUMMARY OF BACKGROUND DATA: Early diagnosis and optimal conservative management for LS are crucial for achieving bony healing without surgery. However, existing research on the conservative treatment of pediatric LS, particularly regarding bone union rates and treatment duration for each stage of bilateral spondylolysis, is limited. METHODS: We retrospectively analyzed 590 pediatric patients (522 boys and 68 girls) under 18 years of age diagnosed with LS and treated conservatively from 2015 to 2021. Diagnosis was based on computed tomography scans and magnetic resonance imaging findings, with stages classified as very early, early, progressive, or terminal. Patient background, sports history, level and stage of spondylolysis, presence of spina bifida occulta, bone union rate, duration of conservative treatment, and recurrence rate were retrospectively analyzed. RESULTS: The overall bone union rate was 81.9%, with a mean conservative treatment duration of 53.7 days. Unilateral LS cases showed decreased bone union rates with stage advancement (very early; 98.2%, early; 96.0%, progressive; 64.3%). Bilateral LS cases with progressive or terminal stage demonstrated low bone union rates (very early/very early; 100%, early/very early; 94.1%, progressive/very early; 66.7%, early/early; 82.9%, progressive/early; 32.3%, progressive/progressive; 23.7%, very early/terminal; 0%, early/terminal; 50.0%, progressive/terminal; 11.1%). The duration of conservative treatment extended as the stage of the main and contralateral lesions progressed, ranging from 39.1 days (very early/none) to 105 days (progressive/terminal). Recurrence rate after bone fusion was 16.6%, with no differences based on lesion stage. CONCLUSION: In this series of 590 patients, conservative treatment yielded high bone union rates for pediatric LS. However, union rates decreased with stage advancement, especially in bilateral cases. These findings provide valuable insights for prognosticating natural history and outcome regarding LS treatment, bone union and return to activity.

Cytokine Inhibitors Upregulate Extracellular Matrix Anabolism of Human Intervertebral Discs under Alginate Beads and Alginate-Embedded Explant Cultures.

We investigated the effects of the cytokine inhibitors IL-1 receptor antagonist (IL-1Ra) and soluble tumor necrosis factor receptor-1 (sTNFR1) on the extracellular matrix metabolism of human intervertebral discs (IVDs) and the roles of IL-1ß and TNF in the homeostasis of IVD cells. The 1.2% alginate beads and the explants obtained from 35 human lumbar discs were treated with cytokine inhibitors. Extracellular matrix metabolism was evaluated by proteoglycan (PG) and collagen syntheses and IL-1ß, TNF, and IL-6 expressions after three days of culture in the presence or absence of IL-1Ra, sTNFR1, and cycloheximide. Simultaneous treatment with IL-1Ra and sTNFR1 stimulated PG and collagen syntheses in the NP and AF cells and explants. The IL-1ß concentration was significantly correlated to the relative increase in PG synthesis in AF explants after simultaneous cytokine inhibitor treatment. The relative increase in PG synthesis induced by simultaneous cytokine treatment was significantly higher in an advanced grade of MRI. Expressions of IL-1ß and TNF were upregulated by each cytokine inhibitor, and simultaneous treatment suppressed IL-1ß and TNF productions. In conclusion, IL-1Ra and sTNFR1 have the potential to increase PG and collagen synthesis in IVDs. IL-1ß and TNF have a feedback pathway to maintain optimal expression, resulting in the control of homeostasis in IVD explants.

Preoperative Low Back Pain Affects Postoperative Patient Satisfaction Following Minimally Invasive Transforaminal Lumbar Interbody Fusion Surgery.

STUDY DESIGN: A single-center retrospective study. PURPOSE: To research the predictive factors associated with postoperative patient satisfaction 1 year after minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF), a minimally invasive procedure for lumbar degenerative disease. OVERVIEW OF LITERATURE: There have been reports of numerous variables influencing patient satisfaction with lumbar surgery; however, there have been few investigations on MIS are limited. METHODS: This study included 229 patients (107 men and 122 women; mean age, 68.9 years) who received one or two levels of MISTLIF, and the patient's age, gender, disease, paralysis, preoperative physical functions, duration of symptom(s), and surgery-associated factors (waiting for surgery, number of surgical levels, surgical time, and intraoperative blood loss) were studied. Radiographic characteristics and clinical outcomes such as Oswestry Disability Index (ODI) scores and Visual Analog Scale (VAS; 0-100) ODI scores for low back pain, leg pain, and numbness were studied. One year following surgery, patient satisfaction (defined as satisfaction for surgery and for present condition; 0-100) was assessed using VAS and its relationships with investigation factors were examined. RESULTS: The mean VAS scores of satisfaction for surgery and for present condition were 88.6 and 84.2, respectively. The results of multiple regression analysis showed that preoperative adverse factors of satisfaction for surgery were being elderly (ß =-0.17, p =0.023), high preoperative low back pain VAS scores (ß =-0.15, p =0.020), and postoperative adverse factors were high postoperative ODI scores (ß =-0.43, p <0.001). In addition, the preoperative adverse factor of satisfaction for present condition was high preoperative low back pain VAS scores (ß =-0.21, p =0.002), and postoperative adverse factors were high postoperative ODI scores (ß =-0.45, p <0.001) and high postoperative low back pain VAS scores (ß =-0.26, p =0.001). CONCLUSIONS: According to this study, significant preoperative low back pain and high postoperative ODI score after surgery are linked to patient unhappiness.

Clinical Characteristics and Surgical Outcomes of Metastatic Spine Tumors in the Very Elderly: A Prospective Cohort Study in a Super-Aged Society.

The number of advanced-age patients with spinal metastases is rising. This study was performed to clarify the characteristics and surgical outcomes of spinal metastases in advanced-age patients. We prospectively analyzed 216 patients with spinal metastases from 2015 to 2020 and divided them into three age groups: <70 years (n = 119), 70-79 years (n = 73), and ≥80 years (n = 24). Although there were no significant intergroup differences in preoperative characteristics and surgery-related factors except for age, patients aged ≥80 years tended to have a worse performance status (PS), Barthel index, and EuroQol-5 dimension (EQ-5D) before and after surgery than the other two groups. Although the median PS, mean Barthel index and mean EQ-5D greatly improved postoperatively in each group, the median PS and mean Barthel index at 6 months and the mean EQ-5D at 1 month postoperatively were significantly poorer in the ≥80-year group than the 70-79-year group. The rates of postoperative complications and re-deterioration of the EQ-5D were significantly higher in the oldest group than in the other two groups. Although surgery for spinal metastases improved the PS, Barthel index, and EQ-5D regardless of age, clinicians should be aware of the poorer outcomes and higher complication rates in advanced-age patients.

Preoperative Base Excess as a Predictor of Perioperative Complications in Patients with Nonidiopathic Scoliosis who Have High Risk Associated with General Anesthesia.

Introduction: Patients with nonidiopathic scoliosis often have a high risk associated with general anesthesia because of cardiac or pulmonary dysfunction secondary to underlying diseases. Base excess has been reported as a predictor in the management of trauma and cancer, although not yet in scoliosis. This study was performed to clarify the surgical outcomes and the association of perioperative complications with base excess in patients with nonidiopathic scoliosis who have a high risk associated with general anesthesia. Methods: Patients with nonidiopathic scoliosis who were referred to our institution from 2009 to 2020 because of their high risk associated with general anesthesia were retrospectively enrolled. High-risk factors for anesthesia were determined by a senior anesthesiologist and categorized into circulatory or pulmonary dysfunction. Perioperative complications were analyzed using the Clavien-Dindo classification; severe complications were defined as grade ≥III. We investigated high-risk factors for anesthesia, underlying diseases, preoperative and postoperative Cobb angle, surgery-related factors, base excess, and postoperative management. These variables were statistically compared between patients with and without complications. Results: Thirty-six patients (mean age, 17.9 years old; range, 11-40 years old) were enrolled (two patients declined surgery). High-risk factors were circulatory dysfunction in 16 patients and pulmonary dysfunction in 20 patients. The mean Cobb angle improved from 85.1° (36°-128°) preoperatively to 43.6° (9°-83°) postoperatively. Three intraoperative complications and 23 postoperative complications occurred in 20 (55.6%) patients. Severe complications occurred in 10 (27.8%) patients. All patients underwent postoperative intensive care unit management after posterior all-screw construction. A large preoperative Cobb angle (p=0.021) and base excess outliers (>3 or <-3 mEq/L) (p=0.005) were significant risk factors for complications. Conclusions: Patients with nonidiopathic scoliosis who have a high risk associated with general anesthesia have a higher complication rate. Preoperative large deformity and base excess (>3 or <-3 mEq/L) could be predictors of complications.

Anti-Inflammatory Effects of Adiponectin Receptor Agonist AdipoRon against Intervertebral Disc Degeneration.

Adiponectin, a hormone secreted by adipocytes, has anti-inflammatory effects and is involved in various physiological and pathological processes such as obesity, inflammatory diseases, and cartilage diseases. However, the function of adiponectin in intervertebral disc (IVD) degeneration is not well understood. This study aimed to elucidate the effects of AdipoRon, an agonist of adiponectin receptor, on human IVD nucleus pulposus (NP) cells, using a three-dimensional in vitro culturing system. This study also aimed to elucidate the effects of AdipoRon on rat tail IVD tissues using an in vivo puncture-induced IVD degeneration model. Analysis using quantitative polymerase chain reaction demonstrated the downregulation of gene expression of proinflammatory and catabolic factors by interleukin (IL)-1ß (10 ng/mL) in human IVD NP cells treated with AdipoRon (2 µM). Furthermore, western blotting showed AdipoRon-induced suppression of p65 phosphorylation (p < 0.01) under IL-1ß stimulation in the adenosine monophosphate-activated protein kinase (AMPK) pathway. Intradiscal administration of AdipoRon was effective in alleviating the radiologic height loss induced by annular puncture of rat tail IVD, histomorphological degeneration, production of extracellular matrix catabolic factors, and expression of proinflammatory cytokines. Therefore, AdipoRon could be a new therapeutic candidate for alleviating the early stage of IVD degeneration.

The Combination of Separation Surgery and Intensity Modulated Radiation Therapy (IMRT) for a Primary Osteosarcoma of the Spine: A Case Report and Literature Review.

Background: Primary spinal osteosarcoma is a rare and intractable disease. Although en bloc resection is favorable for longer survival, it is not always achievable. Separation surgery, a partial resection with circumferential separation to safely deliver high-dose irradiation including intensity-modulated radiation therapy (IMRT), has been recently indicated for patients with spinal cord compression secondary to solid tumor metastases. However, little evidence regarding this combination approach to spinal osteosarcoma exists. Case presentation: We report a 55-year-old male patient with a T1 tumor who underwent urgent decompression surgery for epidural spinal cord compression. Pathological findings revealed primary osteosarcoma. Separation surgery, IMRT, and adjuvant chemotherapy were applied to reduce the symptoms of epidural spinal cord compression. The patient was alive without local recurrence at the 5-year follow-up. Conclusions: Separation surgery with IMRT can be a relatively safe and effective treatment option in patients with osteosarcoma adjacent to spinal cord when en-bloc resection is challenging.

Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy.

Background: Degenerative disc disease, a major cause of low back pain and associated neurological symptoms, is a global health problem with the high morbidity, workforce loss, and socioeconomic burden. The present surgical strategy of disc resection and/or spinal fusion results in the functional loss of load, shock absorption, and movement; therefore, the development of new biological therapies is demanded. This achievement requires the understanding of intervertebral disc cell fate during aging and degeneration. Methods: Literature review was performed to clarify the current concepts and future perspectives of disc cell fate, focused on apoptosis, senescence, and autophagy. Results: The intervertebral disc has a complex structure with the nucleus pulposus (NP), annulus fibrosus (AF), and cartilage endplates. While the AF arises from the mesenchyme, the NP originates from the notochord. Human disc NP notochordal phenotype disappears in adolescence, accompanied with cell death induction and chondrocyte proliferation. Discs morphologically and biochemically degenerate from early childhood as well, thereby suggesting a possible involvement of cell fate including age-related phenotypic changes in the disease process. As the disc is the largest avascular organ in the body, nutrient deprivation is a suspected contributor to degeneration. During aging and degeneration, disc cells undergo senescence, irreversible growth arrest, producing proinflammatory cytokines and matrix-degradative enzymes. Excessive stress ultimately leads to programmed cell death including apoptosis, necroptosis, pyroptosis, and ferroptosis. Autophagy, the intracellular degradation and recycling system, plays a role in maintaining cell homeostasis. While the incidence of apoptosis and senescence increases with age and degeneration severity, autophagy can be activated earlier, in response to limited nutrition and inflammation, but impaired in aged, degenerated discs. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is a signal integrator to determine disc cell fate. Conclusions: Cell fate and microenvironmental regulation by modulating PI3K/Akt/mTOR signaling is a potential biological treatment for degenerative disc disease.