Risk Factors for Cervical Disc Arthroplasty Subsidence with Bryan Disc-A Retrospective Observational Analysis.

Background: Cervical disc arthroplasty (CDA) is currently used instead of fusion to preserve cervical spine motion. Cervical implant subsidence is a potential complication after CDA. Methods: Radiological measurements were recorded via patient anteroposterior and lateral radiographs in the neutral position. Subsidence was defined as a decrease of 3 mm or more in functional spinal unit height (FSUH) from which was measured on a post-operative (OP) radiograph. Results: This study included 104 patients who underwent 153 CDA levels with the Bryan Disc. Approximately one-quarter of the implants (22.9%) showed subsidence. Binary logistic regression analysis indicated that pre-OP mean disc height (DH) was identified as an independent risk factor for subsidence in multivariate analysis (0.151, 95% Confidence Interval 0-0.073, p = 0.018). Receiver operating characteristic curve analysis (area under the curve = 0.852, sensitivity 84.7%, specificity 77.1%) revealed a cut-off value of 4.48 mm for pre-OP Mean-DH in the risk for implant subsidence. Conclusions: In this study, the subsidence rate significantly increased when the implants were oversized beyond a pre-OP Mean-DH of approximately >4 mm. Moreover, the implant subsidence incidence was higher than that reported in previous studies. This is possibly due to endplate over-preparation or disc space over-distraction during placement at the same height as the Bryan Disc (8.5 mm).

Incidence and risk factors of heterotopic ossification after cervical Baguera C disc arthroplasty.

OBJECTIVE: This retrospective study was designed to evaluate the incidence and predisposing factors of heterotopic ossification (HO) after cervical disc arthroplasty (CDA) with a specific implant at 1 and 2 levels, and to investigate the biomechanical effects related to HO. The study goal was to identify ways to reduce the likelihood of HO formation after surgery. METHODS: The study included patients who underwent only 1- or 2-level CDA with the Baguera C disc between November 2014 and December 2021 at a single medical center. All patients were operated on by the same neurosurgeon. The surgical indication included 1-level or 2-level disc herniation between C3 and C7 with radiculopathy, myelopathy, or both, with minimal spondylosis. The various factors were assessed by evaluating plain radiographs and cervical CT scans. The presence of HO was evaluated at different intervals postsurgery, and HO severity was graded using the McAfee classification. RESULTS: Of 107 patients who underwent CDA, 47 (43.9%) had HO at 63 of 171 levels (36.8%). Most cases with HO were grade 1, and no grade 4 was observed. Statistically significant risk factors for HO were the length of endplate coverage ratio and inferior anterior residual exposed endplate (AREE); sex, age, implant height and width, shell angle, and pre- and postoperative functional spinal unit (FSU) angle were not significant. More AREE and greater kyphotic postoperative FSU angle in the flexion position were significant factors differentiating HO grades 0 and 1 from grades 2 and 3. Furthermore, the non-HO group showed a trend of higher range of motion at any postoperative time compared to the HO group, especially at 1 month after surgery. CONCLUSIONS: The HO incidence after CDA was correlated with the residual length of endplate coverage and inferior AREE. Additionally, the AREE and kyphotic postoperative FSU angle in the flexion position were associated with HO grade progression. Patients with HO also showed a trend of lower range of motion at 1 month after surgery. Using an adequately sized implant and encouraging neck motion may help prevent HO development and progression.

A Retrospective Observational Study to Evaluate Adjacent Segmental Degenerative Change with the Dynesys-Transition-Optima Instrumentation System.

BACKGROUND: This study evaluates the impact of hybrid dynamic stabilization using the Dynesys-Transition-Optima (DTO) system on adjacent segment disease (ASD) in lumbar spinal stenosis patients with spondylolisthesis. METHODS: From 2012 to 2020, 115 patients underwent DTO stabilization at a single center by a single neurosurgeon. After exclusions for lack of specific stabilization and incomplete data, 31 patients were analyzed. Follow-up was conducted at 6, 12, and 24 months postoperatively, assessing disc height, listhesis distance, and angular motion changes at L2-L3, L3-L4, and L5-S1. RESULTS: L3-L4 segment (the index level), demonstrated a delayed increase in listhesis distance, contrasting with earlier changes in other segments. At two years, L3-L4 exhibited less increase in listhesis distance and less disc height reduction compared to L2-L3 and L5-S1. Notably, the L3-L4 segment showed a significant reduction in angular motion change over two years. CONCLUSIONS: In conclusion, while ASD was not significantly prevented, the study indicates minor and delayed degeneration at the index level. The L3-L4 segment experienced reduced angular change in motion, suggesting a potential benefit of DTO in stabilizing this specific segment.

Cervical Conjoined Nerve Root During Posterior Percutaneous Endoscopic Cervical Diskectomy.

Cervical conjoined nerve root is rare, and medical imaging, such as magnetic resonance imaging and computed tomography, cannot give an accurate preoperative diagnosis.1 Treatment of cervical radiculopathy with root anomaly can be challenging. We report here a case of cervical conjoined nerve root with a 2-dimensional video. A 41-year-old woman without systemic disease presented with a 2-month history of neck and bilateral shoulder pain, upper back tightness, and left upper limb painful numbness, especially of the first to third fingers. The visual analog scale scores of the neck and left upper limb were 4 and 8, respectively. The Neck Disability Index was 26. The diagnosis of retrolisthesis at C5-C6 and cervical disk herniation with severe neuroforaminal narrowing at the left C5-C6 and C6-C7 levels were made with radiographs and magnetic resonance imaging. Posterior percutaneous endoscopic cervical diskectomy at the left C5-C6 and C6-C7 levels via an interlaminar shoulder approach was performed. During operation, a left-sided conjoined nerve root at the C6-C7 level was found (Video 1). Upon removal of a calcified disk and osteophytes at the C6-C7 level, the dura was torn slightly with traction without nerve root exposure or cerebrospinal fluid leakage. The 3-month postoperative follow-up visual analog scale scores of the neck and left upper limb were 0 and 0, respectively. The 3-month postoperative follow-up Neck Disability Index was 1. Posterior percutaneous endoscopic cervical diskectomy has become a favored treatment for cervical disk herniation because it offers sufficient decompression, smaller incisions, minimal blood loss, shorter hospital stay, and less postoperative pain.2,3 Nonetheless, if unexpected variation of the nerve root is noted during decompressive procedures, iatrogenic nerve root injury is a risk. Seven cases of cervical nerve root anomalies have been reported; all were found during posterior cervical surgery, which may indicate that the posterior approach provides better visualization of nerve root variants, especially in endoscopic surgery.4.

Advances in surgical treatment for atlantoaxial instability focusing on rheumatoid arthritis: Analysis of a series of 67 patients.

AIM: An estimated 88% of rheumatoid arthritis (RA) patients experience various degrees of cervical spine involvement. The excessive movement of the atlantoaxial joint, which connects the occiput to the upper cervical spine, results in atlantoaxial instability (AAI). AAI stabilization is usually achieved by C1 lateral mass-to-C2 pedicle screw-rod fixation (LC1-PC2 fixation), which is technically challenging in RA patients who often show destructive changes in anatomical structures. This study aimed to analyze the clinical results and operative experiences of C1-C2 surgery, with emphasis on the advancement of image-guided surgery and augmented reality (AR) assisted navigation. METHODS: We presented our two decades of experience in the surgical management of AAI from April 2004 to November 2022. RESULTS: We have performed surgery on 67 patients with AAI, including 21 traumatic odontoid fractures, 20 degenerative osteoarthritis, 11 inflammatory diseases of RA, 5 congenital anomalies of the os odontoideum, 2 unknown etiologies, 2 movement disorders, 2 previous implant failures, 2 osteomyelitis, 1 ankylosing spondylitis, and 1 tumor. Beginning in 2007, we performed LC1-PC2 fixation under C-arm fluoroscopy. As part of the progress in spinal surgery, since 2011 we used surgical navigation from presurgical planning to intraoperative navigation, using the preoperative computed tomography (CT) -based image-guided BrainLab navigation system. In 2021, we began using intraoperative CT scan and microscope-based AR navigation. CONCLUSION: The technical complexities of C1-C2 surgery can be mitigated by CT-based image-guided surgery and microscope-based AR navigation, to improve accuracy in screw placement and overall clinical outcomes, particularly in RA patients with AAI.

Administration of mRNA-Nanomedicine-Augmented Calvarial Defect Healing via Endochondral Ossification.

Large-area craniofacial defects remain a challenge for orthopaedists, hastening the need to develop a facile and safe tissue engineering strategy; osteoconductive material and a combination of optimal growth factors and microenvironment should be considered. Faced with the unmet need, we propose that abundant cytokines and chemokines can be secreted from the bone defect, provoking the infiltration of endogenous stem cells to assist bone regeneration. We can provide a potent mRNA medicine cocktail to promptly initiate the formation of bone templates, osteogenesis, and subsequent bone matrix deposition via endochondral ossification, which may retard rapid fibroblast infiltration and prevent the formation of atrophic non-union. We explored the mutual interaction of BMP2 and TGFß3 mRNA, both potent chondrogenic factors, on inducing endochondral ossification; examined the influence of in vitro the transcribed polyA tail length on mRNA stability; prepared mRNA nanomedicine using a PEGylated polyaspartamide block copolymer loaded in a gelatin sponge and grafted in a critical-sized calvarial defect; and evaluated bone regeneration using histological and µCT examination. The BMP2 and TGFß3 composite mRNA nanomedicine resulted in over 10-fold new bone volume (BV) regeneration in 8 weeks than the BMP2 mRNA nanomedicine administration alone, demonstrating that the TGFß3 mRNA nanomedicine synergistically enhances the bone's formation capability, which is induced by BMP2 mRNA nanomedicine. Our data demonstrated that mRNA-medicine-mediated endochondral ossification provides an alternative cell-free tissue engineering methodology for guiding craniofacial defect healing.

Recent targets of osteoarthritis research.

Osteoarthritis is one of the most common diseases and poses a significant medical burden worldwide. Currently, the diagnosis and treatment of osteoarthritis primarily rely on clinical symptoms and changes observed in radiographs or other image modalities. However, identification based on reliable biomarkers would greatly improve early diagnosis, help with precise monitoring of disease progression, and provide aid for accurate treatment. In recent years, several biomarkers for osteoarthritis have been identified, including image modalities and biochemical biomarkers such as collagen degradation products, pro- or anti-inflammatory cytokines, micro RNAs, long non-coding RNAs, and circular RNAs. These biomarkers offer new insights in the pathogenesis of osteoarthritis and provide potential targets for further research. This article reviews the evolution of osteoarthritis biomarkers from the perspective of pathogenesis and emphasizes the importance of continued research to improve the diagnosis, treatment, and management of osteoarthritis.

Effectiveness of Teriparatide for Spine Fusion in Osteoporotic Patient: A Systematic Review and Meta-Analysis of Comparative Studies.

OBJECTIVE: Our goal was to assess teriparatide's (TP) effectiveness in improving radiographic and functional outcomes after spinal fusion surgery. This meta-analysis included randomized controlled trials (RCTs) and comparative cohort studies. The findings provide valuable insights and guidance for surgeons treating osteoporotic patients undergoing spinal fusion surgery. METHODS: We conducted a systematic review to assess TP's efficacy in spinal fusion surgery for osteoporosis. Through thorough selection, data extraction, and quality assessment, we employed network meta-analysis to evaluate radiographic outcomes (fusion rate, screw loosening, vertebral fracture) and changes in bone mineral density measured by Hounsfield units. Functional outcomes were assessed using the Oswestry Disability Index scales. Our study aims to comprehensively understand TP's impact and effectiveness in spinal fusion surgery. RESULTS: A total of 868 patients were included in the analysis. All patients underwent thoracolumbar internal fixation fusion surgery and were divided into following 2 groups: the TP treatment group and the control group. The results revealed significant differences in radiological outcomes. The fusion rate showed a significant difference, as well as screw loosening, and bone mineral density measured in Hounsfield units. However, there was no significant difference in vertebral fracture. The TP group demonstrated favorable effects with statistical significance. In terms of functional outcomes, there was no significant difference in the assessment of Oswestry Disability Index scores between the 2 treatment groups. CONCLUSIONS: The meta-analysis demonstrated that the TP group exhibited significantly better outcomes, particularly in radiological measures, when compared to the control group. The use of TP in spinal fusion surgery shows promise in reducing postoperative complications and providing overall benefits.

The residual exposed endplate ratio is predictive of posterior heterotopic ossification after cervical Bryan disc arthroplasty.

OBJECTIVES: Heterotopic ossification (HO), a major cause of dysfunction after disc arthroplasty (CDA). The aim of this study was to determine the cut value of the residual exposed endplate (REE) ratio and to predict the development of posterior HO after Bryan CDA. METHODS: This retrospective study investigated the relationship between the REE ratio and posterior HO formation after Bryan CDA. Consecutive adult patients who underwent 1- or 2-level Bryan CDA by a single neurosurgeon between 2006 and 2016 with at least two years follow-up were included. Postoperative radiographic analysis and measurement were performed to obtain the REE ratio and the HO grade. RESULTS: Of 249 patients with 384 surgical levels who underwent Bryan CDA during the study period, 114 (45.8 %) received 1-level CDA and 135 (54.2 %) received 2-level CDA. Lateral radiographs showed that 169 implants (44 %) had posterior HOs in all grades after two years or more of follow up and 14 implants (3.64 %) had severe HO (McAfee grades 3 and 4). In 329 implants (85.7 %), a comparison of radiographs to CT examination of HO grading showed a substantial relationship. Using area under the curve (AUC) analysis, a REE ratio >9 %, with 65.1 % sensitivity and 86.5 % specificity, was the cut point for posterior HO formation. CONCLUSIONS: REE is highly correlated with the development of postoperative posterior HO after Bryan CDA, regardless of the level of implantation. An undersized implant causing a REE ratio >9 % is a predictor of postoperative posterior HO formation after cervical Bryan CDA.

Anterior Bone Loss after Cervical Baguera C Disc versus Bryan Disc Arthroplasty.

Objectives: The objectives of this study were to identify the risk factors and incidence of anterior bone loss (ABL) after Baguera C cervical disc arthroplasty (CDA) and identify whether design differences in artificial discs affect ABL. Methods: In this retrospective radiological review of patients who underwent single-level Baguera C CDA in a medical center, the extent of ABL and the following radiological parameters were recorded: global and segmental alignment angle, lordotic angle (or functional spinal unit angle), shell angle, global range of motion (ROM), and ROM of the index level. ABL at the index level was grade 0-2. Grade 0 was defined as no remodeling, grade 1 as spur disappearance or mild change in body contour, and grade 2 as obvious bone regression with Baguera C Disc exposure. Results: Combining grade 1 and grade 2, ABL was found in 56 upper adjacent vertebrae and 52 lower adjacent vertebrae of the 77 patients. Only 18 patients (23.4%) had no ABL. Shell angle differed significantly between ABL grades of both the upper and lower adjacent level: 0.0° in grade 0 and 1 ABL vs. 2.0° in grade 2 ABL of the upper adjacent level (p < 0.05); and 0.0° in grade 0 and 1 ABL vs. 3.5° in grade 2 ABL of the lower adjacent level (p < 0.05). A female predominance of ABL was found. Hybrid surgery and artificial disc size were also related to ABL. Conclusions: ABL is more common in Baguera C Disc arthroplasty than Bryan Disc arthroplasty. Larger shell angle was related to ABL after CDA with Baguera C Discs, which may indicate that shell angle is pivotal in determining the incidence of ABL after CDA. Females had more ABL with Baguera C Disc arthroplasty; this might be related to shorter endplate lengths as well as a smaller endplate-implant mismatch.

Percutaneous endoscopic lumbar discectomy for L5-S1 disc herniation based on image analysis and clinical findings: A retrospective review of 345 cases.

The effect of spinal anatomical anomalies on the efficacy of percutaneous endoscopic lumbar discectomy (PELD) for disc herniation repair is unclear. This retrospective review aims to assess the safety and effectiveness of PELD for treating L5-S1 disc herniation with a range of characteristics and to determine the prevalence of lumbosacral transitional vertebrae (LSTV) anatomical anomalies to facilitate pre-surgical planning. From July 2005 to June 2019, 345 patients with L5-S1 disc herniations were treated with PELD. The primary outcome was 1-year postoperative visual analogue scale scores for low back and lower limb pain. The secondary outcomes included the surgical approach used, lumbosacral bony anomalies, presence of a ruptured disc or severely calcified disc, pediatric lumbar disc herniation, recurrent disc herniation management, and the long-term outcome. visual analogue scale scores for most patients were significantly improved after surgery. The prevalence of LSTVs was 4.05% (14/345 patients) in lumbar sacralization and 7.53% (26/345 patients) in sacral lumbarization. The prevalence of ruptured and severely calcified discs was 18.55% (64/345) and 5.79% (20/345), respectively. The prevalence of pediatric lumbar disc herniation was 2.02% (7/345). The recurrence rate was 4.34% (15/345). Two durotomy cases without sequelae and 8 cases of lower limb dysesthesia lasting longer than 3 months postoperatively were reported. PELD is safe and effective for treating L5-S1 disc herniation, including cases complicated by calcified lumbar disc herniation, disc rupture with migration, and the presence of LSTV. Appropriate imaging is essential to identify case-specific factors, including the prevalent LSTV anatomical anomalies, before surgery.

Celecoxib and Etoricoxib may reduce risk of ischemic stroke in patients with rheumatoid arthritis: A nationwide retrospective cohort study.

Background and purpose: Previous studies reported conflicting results about the risk of ischemic stroke associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA). We aimed to investigate two specific COX-2 inhibitors, Celecoxib and Etoricoxib, and their corresponding effects on the risk of ischemic stroke in patients with RA. Patients and methods: 10,857 patients newly diagnosed with RA were identified and sampled from the Taiwanese National Health Insurance Research Database during the period from 2001 to 2009. The identification of RA was based on the criteria of ICD-9-CM diagnosis code 714.0. Patients diagnosed with cerebrovascular disease and those receiving RA treatment prior to the first diagnosis of RA were excluded. Study endpoint was ischemic stroke, defined by ICD-9-CM code. Cox proportional hazard models and Kaplan Meier curves were used to reveal covariates and differences by drugs in the risk of ischemic stroke. Dosages for Celecoxib were defined as ≤ 200 and >200 mg/day; those for Etoricoxib were 0 and >0 mg/day. Results: Among 7,904 RA patients, 6,669 did not take Celecoxib and 564 (8.46%) of them experienced an ischemic stroke event. Of the 597 individuals who took ≤ 200 mg/day of Celecoxib, 58 (9.72%) had strokes. Of the 638 patients who took >200 mg/day of Celecoxib, 38 (5.96%) eventually experienced a stroke. Among the 7,681 patients who did not take Etoricoxib, 654 (8.51%) experienced an ischemic stroke, while 6 (2.69%) in 223 patients who consumed Etoricoxib had a stroke event. Consuming more than 200 mg of Celecoxib per day for <3.5 years lowered the incidence rate for strokes [hazard ratio (HR) 0.67, 95% Confidence Interval (CI) 0.48-0.93 for dosage and HR 0.22, 95% CI 0.10-0.46 for duration, both p < 0.001], while consuming any dosage of Etoricoxib significantly decreases the possibility (HR 0.35, 95% CI 0.16-0.80, p < 0.001). On the other hand, consuming Etoricoxib for 8 years might have a neutral or even a potentially protective effect compared to at 3.8 years. Conclusion: This population-based retrospective cohort study has shown that Celecoxib and Etoricoxib reduce the risk of ischemic stroke in patients with RA in a dose- and time-dependent manner.

Potential Therapeutic Effects of Thiazolidinedione on Malignant Glioma.

Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant tumor of the central nervous system. GBM has a very low 5-year survival rate and reaching merely a median of ~15 months even with aggressive treatments. PPARγ (Peroxisome proliferator- activated receptor gamma) agonists (ciglitazone), while being widely used on patients of type 2 diabetes mellitus, also have approved anticancer effects. Their action mechanisms on malignant glioma are not fully understood. The aim of this study is to investigate the potential therapeutic effect of PPARγ agonists on maligant glioma. Glioma cell line and in-vivo/ex-vivo animal model intervened by ciglitazone were used to assess the associated mechanism and therapeutic effect. Our results from in vivo and ex vivo experiments showed that ciglitazone not only inhibited tumor growth and its associated angiogenesis, but it also reduced colony formation and migration of tumors. Ciglitazone inhibited the phosphorylation of STAT3 (signal transducer and activator of transcription 3) (at the point of tyrosine 705 by increasing both the amount and activity of SHP-2 (Src homology region 2-containing protein tyrosine phosphatase 2) proteins, based on evidence obtained from immunoprecipitation and immunohistochemistry. Furthermore, ciglitazone activated proteasomes and lysosomes to degrade cell-cycle-related proteins like Cyclin D1, Cyclin E, CDK2 (Cyclin-dependent kinase 2), and CDK4 (Cyclin-dependent kinase 4). Ciglitazone triggered expressions of LC3 (Microtubule-associated protein 1A/1B-light chain 3) and formation of acidic vesicular organelles (AVOs), both of which were implicated in the autophagy pathway. In conclusion, ciglitazone showed the multiple actions to regulate the growth of glioma, which appeared to be a potential candidate for treating malignant glioma.

Altered heart rate variability and pulse-wave velocity after spinal cord injury.

BACKGROUND: Heart rate variability (HRV) and pulse-wave velocity (PWV), indicators of cardiac function, are altered in patients with spinal cord injury (SCI), suggesting that autonomic cardiac function and arterial stiffness may underlie the high risk of cardiovascular complications in these patients. No study has simultaneously investigated HRV and PWV in the same patients. AIM: To evaluate cardiovascular complications in SCI patients by comparing HRV and PWV between patients with and without SCI. METHODS: In this cross-sectional pilot study, patients with (n = 60) and without SCI (n = 60) were recruited from December 7, 2019 to January 21, 2020. Each participant received a five-minute assessment of HRV and the cardiovascular system using the Medicore HRV Analyzer SA-3000P. Differences in HRV and PWV parameters between participants with and without SCI were statistically examined. RESULTS: We observed a significant difference between participants with and without SCI with respect to the standard deviation of all normal-to-normal intervals, square root of the mean sum of squared successive risk ratio interval differences, physical stress index, total power, very-low frequency, low frequency, high frequency, and arterial elasticity. CONCLUSION: Patients with SCI have weaker sympathetic and parasympathetic activity as well as lower arterial elasticity compared to those without, suggesting that SCI may increase cardiac function loading.

Allantoin ameliorates amyloid ß-peptide-induced memory impairment by regulating the PI3K/Akt/GSK-3ß signaling pathway in rats.

Alzheimer's disease (AD) is a brain disease that causes problems in memory, thinking, and behavior. Allantoin has been shown to have antioxidant, anti-inflammatory, and neuroprotective effects. In this study, we aimed to investigate the effect and mechanism of action of allantoin on AD-related memory impairment. We investigated the effect of allantoin on an amyloid ß1-42 peptide (Aß1-42)-induced AD model in rats and evaluated its memory-enhancing effect using the Morris water maze test. Pathological changes in the hippocampus and cortex were examined by hematoxylin-eosin staining. The expression of the phosphorylated Tau protein and PI3K/Akt/GSK-3ß signaling pathway was analyzed by western blotting. The results of the water maze test showed that after treatment with allantoin, the rats could reduce their swimming time and travel distances to find the platform. Allantoin treatment also increased the time spent in the quadrant in which the platform was located. Histological assessment showed that Aß1-42 could cause morphological alterations in nerve cells in the hippocampal CA1 region, and that allantoin could repair the damage to these cells. Western blotting revealed that allantoin treatment increased the expression of p-PI3K, p-Akt, and p-GSK-3ß and decreased p-Tau in the hippocampus and cortex of rats. These effects were inhibited by LY294002. These findings showed that allantoin could improve cognitive impairment in Aß1-42-induced rats by activating the PI3K/Akt/GSK-3ß signaling pathway to reduce abnormal hyperphosphorylation of Tau. Thus, allantoin may be a potential therapeutic agent for neurodegenerative diseases.

No increased risk of alopecia in ankylosing spondylitis patients: A population-based cohort study in Taiwan.

AIM: To investigate the association between ankylosing spondylitis (AS) and alopecia. METHODS: In this cohort study, data from over 1 000 000 patients in the Taiwan Longitudinal Health Insurance Database were extracted. We selected newly diagnosed (outpatient department visit three or more times or admission at least once) patients with AS (ICD-9-CM = 720.0) from 2000 to 2012. For the non-AS comparison group, patients never diagnosed with AS were chosen from 1999 to 2013. In all, 3640 AS patients and 14 560 non-AS controls were selected. Cox proportional hazard model and Kaplan-Meier analysis were used to present the results. The adjusted hazard ratio (HR) in the Cox proportional hazard model was adjusted for age, sex, hypertension, hyperlipidemia, diabetes, atopic dermatitis, and mental disorder. RESULTS: No increased risk of alopecia in AS patients was shown in the Cox proportional hazard model (crude HR 1.16, P = 0.595; adjusted HR 1.16, P = 0.599). Negative results are found as well in subgroup analysis of different age, sex (age 20-40 y: HR 1.03, P = 0.925; Age ≥40 y: HR 1.49, P = 0.406; Female: HR 1.17, P = 0.759; Male: HR 1.15, P = 0.667), and phenotypes of alopecia (androgenetic alopecia: HR 1.19, 95% confidence interval [CI] 0.58-2.41; alopecia areata: HR 0.98, 95% CI 0.37-2.62). A significant positive correlation is found between atopic dermatitis and alopecia (adjusted HR 8.05, P = 0.039). CONCLUSION: In this population-based cohort study, we found no association of risk of alopecia and AS.

Percutaneous Endoscopic Surgery Alone to Treat Severe Infectious Spondylodiscitis in the Thoracolumbar Spine: A Reparative Mechanism of Spontaneous Spinal Arthrodesis.

BACKGROUND: Infective spondylodiscitis has been treated solely with antibiotics based on the pathogen identified. Surgical intervention was used in cases of unidentified pathogens, failed antibiotic treatment, neurological deficit, or instability. The standard surgical procedure was debridement and interbody fusion with a bone graft through the anterior approach, followed by posterior instrumentation. Recently, percutaneous endoscopic surgery has been proven to be safe and effective for treating infectious spondylodiscitis. The results of endoscopy surgery treatment alone for infectious spondylodiscitis with severe bony destruction were analyzed in this study. OBJECTIVE: To describe the clinical and radiological outcomes in patients with infectious spondylodiscitis and severe bony destruction, who were treated with minimally invasive endoscopic surgery alone. STUDY DESIGN: Retrospective observational study (Institutional Review Board: CMUH 105-REC2-101). SETTING: An inpatient surgery center. METHODS: The study included 24 patients with infectious spondylodiscitis and severe bony destruction treated with endoscopy surgery. The patients were treated according to the endoscopic surgical protocol and were followed up for at least 5 years. A retrospective chart review was conducted to evaluate the locations, symptoms and signs, comorbidity, pain scale, and functional outcome. Laboratory data, such as erythrocyte sedimentation rate and C-reactive protein level, and clinical outcomes, including the pain scale, visual analogue scale, and functional score of Oswestry disability index, were recorded. All patients underwent a preoperative magnetic resonance imaging (MRI) scan and were carefully reviewed and classified based on the severity, including endplate erosion, bone edema (low T1, high T2), loss of vertebral height, paravertebral inflammation, paravertebral abscess, and epidural abscess. All patients underwent a plain film follow-up at 3, 6, 9, 12, and 18 months after surgery and computed tomography at 12 months postoperatively. RESULTS: The comorbidities of patients were categorized according to the Charlson Comorbidity Index. The results revealed 10 lesions on the thoracic or upper lumbar spine (between T10 and L3) and 14 on the lower lumbar spine (between L3 and S1). Bone destruction as a result of severe infection and loss of disc height was observed in most cases. During the final follow-up, no significant changes were observed in the sagittal alignment, and a kyphotic angle change of less than 10° was observed in 20 cases. Syndesmophyte formation along the anterior longitudinal ligament (ALL), paravertebral syndesmophyte formation, intervertebral bony fusion, and bony ankylosis of the facet joints in the form of osteophyte formation and fusion were noted. No posterior instrumentation surgery was performed for instability in our case series. LIMITATIONS: This was a retrospective observational clinical case series with small sample size. CONCLUSIONS: A trend of spontaneous spinal arthrodesis, including syndesmophyte formation along the ALL, paravertebral ligaments, direct intervertebral bone growth, and bony ankylosis of the facet joint were observed after a minimally invasive endoscopy treatment for infectious spondylodiscitis. The stability of the 3 columns resulted in segmental stability, which prevented the progression of the kyphotic deformity. Percutaneous endoscopic surgery is safe and effective for treating infectious spondylodiscitis even in patients with severe bony destruction.

Runx1 Messenger RNA Delivered by Polyplex Nanomicelles Alleviate Spinal Disc Hydration Loss in a Rat Disc Degeneration Model.

Vertebral disc degenerative disease (DDD) affects millions of people worldwide and is a critical factor leading to low back and neck pain and consequent disability. Currently, no strategy has addressed curing DDD from fundamental aspects, because the pathological mechanism leading to DDD is still controversial. One possible mechanism points to the homeostatic status of extracellular matrix (ECM) anabolism, and catabolism in the disc may play a vital role in the disease's progression. If the damaged disc receives an abundant amount of cartilage, anabolic factors may stimulate the residual cells in the damaged disc to secrete the ECM and mitigate the degeneration process. To examine this hypothesis, a cartilage anabolic factor, Runx1, was expressed by mRNA through a sophisticated polyamine-based PEG-polyplex nanomicelle delivery system in the damaged disc in a rat model. The mRNA medicine and polyamine carrier have favorable safety characteristics and biocompatibility for regenerative medicine. The endocytosis of mRNA-loaded polyplex nanomicelles in vitro, mRNA delivery efficacy, hydration content, disc shrinkage, and ECM in the disc in vivo were also examined. The data revealed that the mRNA-loaded polyplex nanomicelle was promptly engulfed by cellular late endosome, then spread into the cytosol homogeneously at a rate of less than 20 min post-administration of the mRNA medicine. The mRNA expression persisted for at least 6-days post-injection in vivo. Furthermore, the Runx1 mRNA delivered by polyplex nanomicelles increased hydration content by ≈43% in the punctured disc at 4-weeks post-injection (wpi) compared with naked Runx1 mRNA administration. Meanwhile, the disc space and ECM production were also significantly ameliorated in the polyplex nanomicelle group. This study demonstrated that anabolic factor administration by polyplex nanomicelle-protected mRNA medicine, such as Runx1, plays a key role in alleviating the progress of DDD, which is an imbalance scenario of disc metabolism. This platform could be further developed as a promising strategy applied to regenerative medicine.

Dual Regeneration of Muscle and Nerve by Intramuscular Infusion of Mitochondria in a Nerve Crush Injury Model.

BACKGROUND: Peripheral nerve injuries result in muscle denervation and apoptosis of the involved muscle, which subsequently reduces mitochondrial content and causes muscle atrophy. The local injection of mitochondria has been suggested as a useful tool for restoring the function of injured nerves or the brain. OBJECTIVE: To determine outcomes following the administration of isolated mitochondria into denervated muscle after nerve injury that have not been investigated. METHODS: Muscle denervation was conducted in a sciatic nerve crushed by a vessel clamp and the denervated gastrocnemius muscle was subjected to 195 µg hamster green fluorescent protein (GFP)-mitochondria intramuscular infusion for 10 min. RESULTS: The mitochondria were homogeneously distributed throughout the denervated muscle after intramuscular infusion. The increases in caspase 3, 8-oxo-dG, Bad, Bax, and ratio of Bax/Bcl-2 levels in the denervated muscle were attenuated by mitochondrial infusion, and the downregulation of Bcl-2 expression was prevented by mitochondrial infusion. In addition, the decrease in the expression of desmin and the acetylcholine receptor was counteracted by mitochondrial infusion; this effect paralleled the amount of distributed mitochondria. The restoration of the morphology of injured muscles and nerves was augmented by the local infusion of mitochondria. Mitochondrial infusion also led to improvements in sciatic functional indexes, compound muscle action potential amplitudes, and conduction latencies as well as the parameters of CatWalk (Noldus) gait analysis. CONCLUSION: The local infusion of mitochondria can successfully prevent denervated muscle atrophy and augment nerve regeneration by reducing oxidative stress in denervated muscle.