Spinal cord injury in high-risk complex adult spinal deformity surgery: review of incidence and outcomes from the Scoli-RISK-1 study.

STUDY DESIGN: Clinical case series. OBJECTIVE: To describe the cause, treatment and outcome of 6 cases of perioperative spinal cord injury (SCI) in high-risk adult deformity surgery. SETTING: Adult spinal deformity patients were enrolled in the multi-center Scoli-RISK-1 cohort study. METHODS: A total of 272 patients who underwent complex adult deformity surgery were enrolled in the prospective, multi-center Scoli-RISK-1 cohort study. Clinical follow up data were available up to a maximum of 2 years after index surgery. Cases of perioperative SCI were identified and an extensive case review was performed. RESULTS: Six individuals with SCI were identified from the Scoli-RISK-1 database (2.2%). Two cases occurred intraoperatively and four cases occurred postoperatively. The first case was an incomplete SCI due to a direct intraoperative insult and was treated postoperatively with Riluzole. The second SCI case was caused by a compression injury due to overcorrection of the deformity. Three cases of incomplete SCI occurred; one case of postoperative hematoma, one case of proximal junctional kyphosis (PJK) and one case of adjacent segment disc herniation. All cases of post-operative incomplete SCI were managed with revision decompression and resulted in excellent clinical recovery. One case of incomplete SCI resulted from infection and PJK. The patient's treatment was complicated by a delay in revision and the patient suffered persistent neurological deficits up to six weeks following the onset of SCI. CONCLUSION: Despite the low incidence in high-risk adult deformity surgeries, perioperative SCI can result in devastating consequences. Thus, appropriate postoperative care, follow up and timely management of SCI are essential.

Prediction of Proximal Junctional Kyphosis and Failure After Corrective Surgery for Adult Spine Deformity: An MRI-Based Model Combining Bone and Paraspinal Muscle Quality Metrics.

BACKGROUND: Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) are common complications observed after adult spinal deformity (ASD) surgery and major cause for unplanned reoperations. In addition to spinal alignment, osteoporosis and paraspinal muscle (PSM) degeneration are reportedly indispensable factors that account for PJK/PJF. PURPOSE: To investigate the utility of the preoperative risk assessment model using MRI-based skeletomuscular metrics in predicting PJK and/or PJF(PJK/PJF) after ASD correction. STUDY DESIGN: Retrospective Case-Control study. PATIENT SAMPLE: Consecutive series of 149 patients at a single academic institution. OUTCOME MEASURES: MRI based measurements of vertebral bone quality at upper instrumented vertebra (VBQ-U) score and fat infiltration rate (FI%) of paraspinal muscle (PSM). METHODS: We performed a retrospective analysis of patients with ASD who underwent ≥5-segment fusion. The vertebral bone quality (VBQ) scoring system was used to assess the bone quality. The PSM quality including FI% and cross-sectional area (CSA) were evaluated. Multivariate logistic regression was performed to determine potential risk factors of PJK/PJF. RESULTS: Of 149 patients who underwent ASD surgery, PJK/PJF was found in 45(30.2%). Mean VBQ-U scores were 3.45 ± 0.64 and 3.00 ± 0.56 for patients with and without PJK/PJF (P<0.001). Mean FI% of PSM(L3/L4) was 27.9 ± 12.8 and 20.7 ± 13.3 for patients with and without PJK/PJF (P<0.001). On multivariate analysis, the VBQ-U score and FI% of PSM were significant independent predictors of PJK/PJF. The AUC for the novel risk assessment model is 0.806, with a predictive accuracy of 86.7%. CONCLUSION: In patients undergoing ASD correction, paraspinal muscle and vertebral bone quality significantly outweigh radiographic alignment parameters in predicting PJK/PJF. The MRI-based risk assessment model offers a valuable tool for early assessing individualized risk information for PJK/PJF.

Posterior-only approach cervical hemivertebrectomy and short fusion with pedicle screws in young children with cervical scoliosis: case report and technical note.

PURPOSE: Cervical hemivertebrae (C3-6) causing significant osseous torticollis, head tilt and facial asymmetry are rare and complicated. Cervical hemivertebrectomy (CHVE) by a posterior-only approach was never reported because it is highly risky and its efficacy remains controversial. This study is to evaluate the feasibility and preliminary clinical outcomes of posterior-only approach for CHVE and torticollis correction in young children. METHODS: Four young children aged 5-9 years old with significant torticollis caused by cervical hemivertebrae underwent deformity correction consisting of cervical pedicle screw (CPS) placement with O-arm-based intraoperative navigation, CHVE using ultrasonic bone scalpel and short-segmental posterior instrumentation and fusion. Details of this novel technique were presented. The preliminary short-term clinical and radiographic outcomes were assessed. RESULTS: On average, the operative time was 312.5 ± 49.9 min, and the surgical blood loss was 375.0 ± 150.0 ml. The structural cervical scoliosis was corrected from 31.5 ± 7.3° to 11.0 ± 4.1°, and the average correction rate was 64.9%. Head tilt was favorably corrected from 11.0 ± 4.2° to 3.5 ± 2.6°. The shoulder balance improved from 6.3 ± 1.3° to 1.5 ± 1.9°. One case with C6 CHVE had convex side radiating nerve root pain but no sign of muscle power weakness. Full recovery was achieved one month after surgery. No other complication occurred. CONCLUSIONS: CHVE by a posterior-only approach was a feasible alternative option for the treatment of congenital cervical scoliosis. It could resect the CHV effectively and achieve satisfactory torticollis correction without additional anterior access surgery. Successful CPS placement in this child population was essentially important to enable reliable osteotomy closure and firm posterior instrumentation.

Acute changes in hippocampal metabolism after anesthesia and surgery: Implications for perioperative neurocognitive disorder.

BACKGROUND: The risk of developing dementia is higher in individuals who suffer from perioperative neurocognitive disorder (PND), including postoperative cognitive dysfunction (POCD) and delirium. Recent studies have indicated correlations between anesthesia, surgery and PND. Acute metabolic changes induced by anesthesia and surgery may be related to cognitive impairments. Despite a paucity of research on acute metabolic changes in the hippocampus during surgery, there are conflicting about specific metabolites. METHODS: We developed a mouse model of cognitive impairment induced by isoflurane anesthesia and unilateral nephrectomy. Cognition was evaluated by Y maze and fear conditioning test (FCT). The hippocampus was harvested after the surgery. LC-MS (liquid chromatography-mass spectrometry) was performed. The differential metabolites involved in lipid, amino acid, nucleotide, carbohydrate metabolism were analyzed. RESULTS: Anesthesia and surgery exposure induced cognition decline. A total of 49 metabolites were significantly up-regulated and 122 down-regulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the metabolites identified purine, glutathione, nicotinate and nicotinamide metabolism. Metabolites involved in lipid, amino acid, nucleotide, carbohydrate metabolism were identified including nicotinamide adenine dinucleotide (NAD), 1-Methylnicotinamide, propionic acid, histidine, adenosine, and guanosine cyclic monophosphate. Some metabolites exhibited a consistent change trend in the hippocampus of aging mice. CONCLUSIONS: The study indicates that anesthesia and surgery can induce acute alterations in hippocampal metabolomics, including metabolites involved in lipid, amino acid, nucleotide, and carbohydrate metabolism. These metabolites may play a role in modulating PND through the regulation of neuroinflammation, oxidative stress, blood-brain barrier (BBB) permeability.

Coronal deformity in ankylosing spondylitis with concomitant thoracolumbar kyphosis: patterns, manifestations and surgical strategies.

PURPOSE: To evaluate different patterns of coronal deformity secondary to ankylosing spondylitis (AS), to propose relevant treatment strategies, and to assess efficacy of asymmetrical pedicle subtraction osteotomy (APSO). METHODS: Coronal deformity was defined as coronal Cobb angle over 20º or coronal balance distance (CBD) more than 3 cm. 65 consecutive AS patients with concomitant coronal and sagittal deformity who underwent PSO were included. The average follow-up time was 40.4 months. Radiographic evaluation included coronal Cobb angle and CBD. Furthermore, sagittal parameters were used to assess magnitude and maintenance of kyphosis correction. RESULTS: Based on curve characteristics, coronal deformity caused by AS included four different radiologic patterns: Pattern I: lumbar scoliosis; Pattern II: C-shaped thoracolumbar curve; Pattern III: trunk shift without major curve; Pattern IV: proximal thoracic scoliosis. APSO was performed for patients in Pattern I to III while conventional PSO was applied for patients in Pattern IV. Significant improvement in all the sagittal parameters were noted in 65 patients without obvious correction loss at the last follow-up. Besides, significant and sustained correction of coronal mal-alignment was identified in 59 APSO-treated patients. Rod fracture occurred in four cases and revision surgery was performed for one case. CONCLUSION: According to radiologic manifestations, coronal deformity caused by AS could be categorized into four patterns. APSO proved to be a feasible and effective procedure for correction of Pattern I to III patients. Coronal deformity pattern, apex location, sagittal profile of lumbar spine and preoperative hip function should be considered for osteotomy level selection in APSO.

Regulating the activity of GABAergic neurons in the ventral pallidum alters the general anesthesia effect of propofol.

The full mechanism of action of propofol, a commonly administered intravenous anesthetic drug in clinical practice, remains elusive. The focus of this study was the role of GABAergic neurons which are the main neuron group in the ventral pallidum (VP) closely associated with anesthetic effects in propofol anesthesia. The activity of VP GABAergic neurons following propofol anesthesia in Vgat-Cre mice was observed via detecting c-Fos immunoreactivity by immunofluorescence and western blotting. Subsequently, chemogenetic techniques were employed in Vgat-Cre mice to regulate the activity of VP GABAergic neurons. The role of VP GABAergic neurons in generating the effects of general anesthesia induced by intravenous propofol was further explored through behavioral tests of the righting reflex. The results revealed that c-Fos expression in VP GABAergic neurons in Vgat-Cre mice dramatically decreased after propofol injection. Further studies demonstrated that chemogenetic activation of VP GABAergic neurons during propofol anesthesia shortened the duration of anesthesia and promoted wakefulness. Conversely, the inhibition of VP GABAergic neurons extended the duration of anesthesia and facilitated the effects of anesthesia. The results obtained in this study suggested that regulating the activity of GABAergic neurons in the ventral pallidum altered the effect of propofol on general anesthesia.

Prediction Model for Lumbar Curve Correction after Selective Thoracic Fusion in Lenke 1 and 2 Adolescent Idiopathic Scoliosis.

STUDY DESIGN: A retrospective study. OBJECTIVE: To identify independent risk factors and construct a prediction model for lumbar curve correction (LCC) after selective thoracic fusion (STF) in patients with Lenke 1 and 2 adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: STF has been widely applied in Lenke 1 and 2 AIS patients. However, LCC after STF is still controversial. METHODS: 128 patients undergoing STF with at least 2 years follow-up were included. Cases were divided into high-LCC group and low-LCC group according to a rounded-up median of 65%. 49 variables were taken into account. Logistic regression was applied to identify independent predictive factors. Prediction model was established by backward stepwise regression, and its evaluation was implemented on R. RESULTS: Five parameters showed independent predictive value for low LCC: Right shoulder higher before surgery [right shoulder higher vs. balanced: odds ratio (OR)=0.244, P=0.014], postoperative Cobb angle of lumbar curve (LC) (OR=1.415, P=0.001, cut-off value=11°), lowest instrumented vertebra (LIV) distal to end vertebra (no vs. yes: OR=4.587, P=0.013), postoperative LIV tilt (OR=0.686, P=0.010, cut-off value=6.85°) and postoperative LIV+1 tilt (OR=1.522, P=0.005, cut-off value=6.25°). The prediction model included six variables: lumbar modifier, preoperative shoulder balance, postoperative Cobb angle of LC, LIV position, postoperative LIV tilt and postoperative LIV+1 tilt. Model evaluation demonstrated satisfactory capability and stability [area under curve=0.890, 10-fold cross-validation accuracy=0.782]. CONCLUSION: Preoperative shoulder balance, Cobb angle of LC, LIV position, postoperative LIV and LIV+1 tilt could be used to prognosticate LCC after STF. A model with solid prediction ability was established, which could further our understanding of LCC and assist in making clinical decisions.

Opioid Use Prior to Adult Spine Deformity Correction Surgery is Associated With Worse Pre- and Postoperative Back Pain and Prolonged Opioid Demands.

STUDY DESIGN: Prospective multicenter database post-hoc analysis. OBJECTIVES: Opioids are frequently prescribed for painful spinal conditions to provide pain relief and to allow for functional improvement, both before and after spine surgery. Amidst a current opioid epidemic, it is important for providers to understand the impact of opioid use and its relationship with patient-reported outcomes. The purpose of this study was to evaluate pre-/postoperative opioid consumption surrounding ASD and assess patient-reported pain outcomes in older patients undergoing surgery for spinal deformity. METHODS: Patients ≥60 years of age from 12 international centers undergoing spinal fusion of at least 5 levels and a minimum 2-year follow-up were included. Patient-reported outcome scores were collected using the Numeric Rating Scale for back and leg pain (NRS-B; NRS-L) at baseline and at 2 years following surgery. Opioid use, defined based on a specific question on case report forms and question 11 from the SRS-22r questionnaire, was assessed at baseline and at 2-year follow-up. RESULT: Of the 219 patients who met inclusion criteria, 179 (81.7%) had 2-year data on opioid use. The percentages of patients reporting opioid use at baseline (n = 75, 34.2%) and 2 years after surgery (n = 55, 30.7%) were similar (P = .23). However, at last follow-up 39% of baseline opioid users (Opi) were no longer taking opioids, while 14% of initial non-users (No-Opi) reported opioid use. Regional pre- and postoperative opioid use was 5.8% and 7.7% in the Asian population, 58.3% and 53.1% in the European, and 50.5% and 40.2% in North American patients, respectively. Baseline opioid users reported more preoperative back pain than the No-Opi group (7.0 vs 5.7, P = .001), while NRS-Leg pain scores were comparable (4.8 vs 4, P = .159). Similarly, at last follow-up, patients in the Opi group had greater NRS-B scores than Non-Opi patients (3.2 vs 2.3, P = .012), but no differences in NRS-Leg pain scores (2.2 vs 2.4, P = .632) were observed. CONCLUSIONS: In this study, almost one-third of surgical ASD patients were consuming opioids both pre- and postoperatively world-wide. There were marked international variations, with patients from Asia having a much lower usage rate, suggesting a cultural influence. Despite both opioid users and nonusers benefitting from surgery, preoperative opioid use was strongly associated with significantly more back pain at baseline that persisted at 2-year follow up, as well as persistent postoperative opioid needs.

Hyper-Selective Posterior Fusion is Recommended When the Modified S-Line is Positive in Lenke 5C Adolescent Idiopathic Scoliosis.

OBJECTIVE: Postoperative coronal decompensation and less fusion level are dilemmas and the proper selective posterior fusion (SPF) strategy should be investigated. We proposed a parameter, modified S-line, and aimed to investigate if the modified S-line could predict postoperative coronal decompensation in patients with Lenke 5C adolescent idiopathic scoliosis (AIS). METHODS: This is a retrospective radiographic study and Lenke 5C AIS patients undergoing SPF during the period from September 2017 to June 2021 were included. The modified S-line was defined as the line linking the centers of the concave-side pedicles of the upper end vertebra (UEV) and lower end vertebra (LEV) at baseline. A modified S-line tilt to the right is established as modified S-line+ (UEV being to the right of the LEV). The patients were further categorized into two groups: the Cobb to Cobb fusion group and the Cobb-1 to Cobb fusion group. Outcomes including thoracic Cobb angle, TL/L Cobb angle, coronal balance, upper instrumented vertebra (UIV) translation, lower instrumented vertebra (LIV) translation, UIV tilt, LIV tilt, LIV disc angle, thoracic apical vertebral translation, lumbar apical vertebral translation (L-AVT), L-T AVT ratio, L-T Cobb were measured at baseline, immediately after surgery, and the last follow-up. Radiographic parameters and the incidence of both proximal and distal decompensation between the two groups were compared by chi-square test. RESULTS: Among 92 patients, 48 were modified S-line+ and 44 were modified S-line-. Modified S-line+ status was identified as a risk factor for postoperative proximal decompensation (p = 0.005) during follow-up. In Cobb to Cobb group, a higher occurrence of proximal decompensation in individuals with modified S-line+ status (p = 0.001) was confirmed. Also, in the Cobb to Cobb group with baseline modified S-line+ status, patients presenting decompensation showed a significantly larger baseline of the UIV tilt and postoperative disc angle below the lower instrumented vertebra. However, In Cobb-1 group, the incidence of decompensation after surgery showed no association with baseline modified S-line tilt status (p = 0.815 and 0.540, respectively). CONCLUSION: The modified S-line could serve as an important parameter in surgical decision-making for Lenke 5C AIS patients. Cobb to Cobb SPF is not recommended with a modified S-line+ status, and the Cobb-1 to Cobb fusion may serve as a potential alternative.

Posterior Corrective Surgery for Type II Congenital Kyphosis: SRS-Schwab Grade 4 Osteotomy or Vertebral Column Resection?

OBJECTIVE: Surgical decision-making for congenital kyphosis (CK) with failure of anterior segmentation (type II) has been contradictory regarding the trade-off between the pursuit of correction rate and the inherent risk of the osteotomy procedure. This study was designed to compare the clinical and radiographic measurement in type II CK underwent SRS-Schwab Grade 4 osteotomy and vertebral column resection (VCR), the most-adapted osteotomy techniques for CK, and to propose the strategy to select between the two procedures. METHODS: This retrospective observational comparative study evaluated surgical outcomes in type II CK patients underwent VCR or SRS-Schwab Grade 4 osteotomy at our institution between January 2015 and January 2020. Patients operated with VCR and SRS-Schwab Grade 4 osteotomy were allocated to Group 1 and Group 2 respectively. Radiographic parameters and SRS-22 quality of life metrics were assessed at pre-operation, post-operation, and during follow-up visits for both groups, allowing for a comprehensive comparison of surgical outcomes. RESULTS: Thirty-one patients (19 patients in Group 1 and 12 patients in Group 2) aged 16.3 ± 10.4 years were recruited. Correction of segmental kyphosis was similar between groups (51.1 ± 17.6° in Group 1 and 48.4 ± 19.8° in Group 2, p = 0.694). Group 1 had significantly longer operation time (365.9 ± 81.2 vs 221.4 ± 78.9, p < 0.001) and more estimated blood loss (975.2 ± 275.8 ml vs 725.9 ± 204.3 mL, p = 0.011). Alert event of intraoperative sensory and motor evoked potential (SEP and MEP) monitoring was observed in 1 patient of Group 2. Both groups had 1 transient post operative neurological deficit respectively. CONCLUSION: SRS-Schwab Grade 4 osteotomy was suitable for kyphotic mass when its apex is the upper unsegmented vertebrae or the neighboring disc, or when the apical vertebrae with an anterior/posterior (A/P) height ratio of vertebral body higher than 1/3. VCR is suitable when the apex is located within the unsegmented mass with its A/P height ratio lower than 1/3. Proper selection of VCR and SRS-Schwab Grade 4 osteotomy according to our strategy, could provide satisfying radiographic and clinical outcomes in type II CK patients during a minimum of 2 years follow-up. Patients undergoing VCR procedure might have longer operation time, more blood loss and higher incidence of peri- and post-operative complications.

Dynamic microphysiological system chip platform for high-throughput, customizable, and multi-dimensional drug screening.

Spheroids and organoids have attracted significant attention as innovative models for disease modeling and drug screening. By employing diverse types of spheroids or organoids, it is feasible to establish microphysiological systems that enhance the precision of disease modeling and offer more dependable and comprehensive drug screening. High-throughput microphysiological systems that support optional, parallel testing of multiple drugs have promising applications in personalized medical treatment and drug research. However, establishing such a system is highly challenging and requires a multidisciplinary approach. This study introduces a dynamic Microphysiological System Chip Platform (MSCP) with multiple functional microstructures that encompass the mentioned advantages. We developed a high-throughput lung cancer spheroids model and an intestine-liver-heart-lung cancer microphysiological system for conducting parallel testing on four anti-lung cancer drugs, demonstrating the feasibility of the MSCP. This microphysiological system combines microscale and macroscale biomimetics to enable a comprehensive assessment of drug efficacy and side effects. Moreover, the microphysiological system enables evaluation of the real pharmacological effect of drug molecules reaching the target lesion after absorption by normal organs through fluid-based physiological communication. The MSCP could serves as a valuable platform for microphysiological system research, making significant contributions to disease modeling, drug development, and personalized medical treatment.

Sagittal Imbalance in Degenerative Kyphosis: Prevalence and Implication on Postoperative Mechanical Failure.

BACKGROUND AND OBJECTIVES: To explore the patterns of sagittal imbalance in patients with lumbar or thoracolumbar degenerative kyphosis (DK) and determine its implication for the risk of mechanical complication (MC) after corrective surgery. METHODS: A total of 137 patients with DK who underwent corrective surgery were reviewed. The patients were divided into L group (with a kyphotic apex at L2 and below) and TL group (with kyphotic apex at L1 and above). Then, sacral slope (SS) (defined as S1 if SS > 0 in TL, or SS > 10 in L group) and sagittal vertical axis ≥ 5 cm (defined as +) were used as modifier sagittal balance. The Scoliosis Research Society (SRS)-22 questionnaire scores were analyzed, and the risk of mechanical failure was compared across groups. RESULTS: The distribution of subgroups was 38 (27.7%) in TLS1(-) group, 36 (26.3%) in TLS1(+) group, 16 (11.7%) in TLS0(-) group, and 5 (3.6%) in TLS0(+) group. For L group, the figure was 5 (3.6%) in LS1(-), 22 (16.1%) in LS1(+), 7 (5.2%) in LS0(-), and 8 (5.8%) in LS0(+). Patients in L group had significantly higher regional kyphosis, lower lumbar lordosis, and higher sagittal vertical axis, indicating a higher risk of global decompensation. The SRS function scores and pain scores were also lower in the L group compared with the TL group. At a minimum of 2 years of follow-up, χ2 test showed that the incidence of TLS0 (+), LS0 (-), and LS0 (+) had significantly higher rates of MC (>40%). In both TL and L groups, patients with MC were found to have significantly lower bone mineral density than those without. CONCLUSION: The findings decipher the distinct patterns of sagittal imbalance in severe DK patients with kyphotic apex at thoracolumbar or lumbar spine. Patients with kyphotic apex apex at L2 or below, low SS, and global imbalance showed the highest risk of postoperative mechanical failure.

Impaired synaptic plasticity and decreased glutamatergic neuron excitability induced by SIRT1/BDNF downregulation in the hippocampal CA1 region are involved in postoperative cognitive dysfunction.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia/surgery, especially among elderly patients, and poses a significant threat to their postoperative quality of life and overall well-being. While it is widely accepted that elderly patients may experience POCD following anesthesia/surgery, the exact mechanism behind this phenomenon remains unclear. Several studies have indicated that the interaction between silent mating type information regulation 2 homologue 1 (SIRT1) and brain-derived neurotrophic factor (BDNF) is crucial in controlling cognitive function and is strongly linked to neurodegenerative disorders. Hence, this research aims to explore how SIRT1/BDNF impacts cognitive decline caused by anesthesia/surgery in aged mice. METHODS: Open field test (OFT) was used to determine whether anesthesia/surgery affected the motor ability of mice, while the postoperative cognitive function of 18 months old mice was evaluated with Novel object recognition test (NORT), Object location test (OLT) and Fear condition test (FC). The expressions of SIRT1 and other molecules were analyzed by western blot and immunofluorescence staining. The hippocampal synaptic plasticity was detected by Golgi staining and Long-term potentiation (LTP). The effects of SIRT1 and BDNF overexpression as well as chemogenetic activation of glutamatergic neurons in hippocampal CA1 region of 18 months old vesicular glutamate transporter 1 (VGLUT1) mice on POCD were further investigated. RESULTS: The research results revealed that older mice exhibited cognitive impairment following intramedullary fixation of tibial fracture. Additionally, a notable decrease in the expression of SIRT1/BDNF and neuronal excitability in hippocampal CA1 glutamatergic neurons was observed. By increasing levels of SIRT1/BDNF or enhancing glutamatergic neuron excitability in the CA1 region, it was possible to effectively mitigate synaptic plasticity impairment and ameliorate postoperative cognitive dysfunction. CONCLUSIONS: The decline in SIRT1/BDNF levels leading to changes in synaptic plasticity and neuronal excitability in older mice could be a significant factor contributing to cognitive impairment after anesthesia/surgery.

Association between vertebral endplate defects and patient-reported symptoms: an immunohistochemical study investigating the COX-2/PGE-2/EP-4 axis.

BACKGROUND CONTEXT: Vertebral endplate defects are often implicated in degenerative disc disorders, yet their connection to patient-reported symptoms remains unclear. COX-2 and PGE-2 are known for their roles in inflammation and pain, with EP-4 receptor involvement in pain signaling. Examining their expression in vertebral endplate tissues may provide insights into pathomechanism of low back pain. PURPOSE: To investigate the association between endplate defects and patient-reported symptoms and to further clarify the role of the COX-2/PGE-2/EP-4 axis in the pathogenesis of chronic low back pain. STUDY DESIGN/SETTING: Retrospective study. PATIENT SAMPLE: A total of 71 patients who had undergone single-level L4/5 or L5/S1 modified laminectomy decompression preserving proximal upper laminae and transforaminal lumbar interbody fusion surgery were included in this study, including 18 patients diagnosed with lumbar disc herniation, 19 with lumbar disc herniation accompanied by degenerative lumbar spinal stenosis, and 34 with degenerative spondylolisthesis. OUTCOME MEASURES: Demographic data, Pfirrmann grade, Modic changes, endplate defect score, visual analog scale (VAS) for back and leg pain, and Oswestry Disability Index (ODI) before surgery, 3-month and 6-month follow-up, and the percentage of immune-positive cells (COX-2, PGE-2, and EP-4) in endplate tissue sections. METHODS: Patients were divided into defect and nondefect groups according to endplate morphology on lumbar MR. All intraoperative endplate specimens were immediately fixed in 10% formaldehyde, and then embedded in paraffin 3 days later for tissue sections. The outcome measures were compared between the defect group and nondefect group. Data were analyzed using independent t-tests and χ² tests. Pearson's rank correlation test was used to assess correlations between patient-reported symptoms and the percentage of immune-positive cells in the groups. Multivariable logistic regression models using the forward stepwise likelihood ratio method were used to identify the factors that were independently associated with endplate defects. RESULTS: The age of Defect group was significantly higher than that of nondefect group (52.5±7.7 vs 57.2±9.1. p=.024). There were no significant differences in gender, diagnosis, BMI, comorbidities, or surgical level between the two groups. Modic changes (Type Ⅱ/Type Ⅲ) were more common in patients of Defect group than nondefect group (38.5% vs 11.1%, p<.001), and so was disc degeneration (Pfirrmann grade Ⅳ/Ⅴ) (69.2% vs 33.3%, p<.001). Defect group had significantly higher VAS-Back (6.5±2.0 vs 4.9±1.6, p<.001) and ODI scores (62.9±10.7 vs 45.2±14.8, p<.001) than nondefect group, while there was no significant differences between the two groups during the 3 and 6-month follow-up after surgery. Histologically, Defect group was characterized by upregulation of COX-2, PGE-2, and EP-4 in endplate tissue sections. Both in defect and nondefect groups, VAS-Back showed moderate positive correlations with the expressions of COX-2 (r=0.643; r=0.558, p both<.001), PGE-2 (r=0.611; r=0.640, p both<.001), and EP-4 (r=0.643; r=0.563, p both<.001). Multivariate regression analyses reveled that percentage of COX-2-positive cells was associated with endplate defects (OR=1.509, 95%CI [1.048-2.171], p=.027), as well as percentage of PGE-2-positive (OR=1.291, 95%CI [1.106-1.508], p=.001) and EP-4-positive cells (OR=1.284, 95%CI [1.048∼2.171], p=.003). CONCLUSIONS: Patients with endplate defects had worse quality of life, more severe disc degeneration and Modic changes, and up-regulated COX-2/PGE-2/EP-4 axis expression in cartilage endplates in patients with defected endplates. Inflammatory factors may significantly contribute to the onset and progression of chronic low back pain in patients with endplate defects, consequently impacting patient-reported symptoms.

The Influence of Radiographic Parameter on the S2 Alar-Iliac Screw Virtual Trajectory in Degenerative Lumbar Scoliosis Patients: A Computed Tomography Study.

OBJECTIVE: S2 alar-iliac (S2AI) screw had been widely used in the pelvic fusion for degenerative lumbar scoliosis (DLS) patients. However, whether S2AI screw trajectory was influenced by sagittal profile in DLS patients had not been comprehensively investigated. The objective of this study was to evaluate the associations between the optimal S2 alar-iliac (S2AI) screw trajectory and sagittal spinopelvic parameters in DLS patients. METHODS: Computed tomography (CT) scans of pelvis were performed in 47 DLS patients for three-dimensional reconstruction of S2AI screw trajectory from September 2019 to November 2021. Five S2AI screw trajectory parameters were measured in CT reconstruction images, including: 1) angle in the transverse plane (Tsv angle); 2) angle in the sagittal plane (Sag angle); 3) maximal screw length; 4) screw width; and 5) skin distance. The lumbar Cobb angle, lumbar apical vertebral translation (AVT); global kyphosis (GK); thoracic kyphosis (TK); lumbar lordosis (LL); sagittal vertical axis (SVA); sacral slope (SS); pelvic tilt (PT); and pelvic incidence (PI) were measured in standing X-ray films of the whole spine and pelvis. RESULTS: Both Tsv angle and Sag angle had significant positive associations with SS (p < 0.05) but negative associations with both PT (p < 0.05) and LL (p < 0.05) in all cases. Patients with SS less than 15° had both smaller Tsv angle and Sag angle than those with SS equal to or more than 15° (p < 0.05). The decreased LL would lead to the backward rotation of the pelvis, resulting in a more cephalic and less divergent trajectory of S2AI screw in DLS patients. CONCLUSIONS: For DLS patients with lumbar kyphosis, spine surgeons should avoid both excessive Tsv and Sag angles for S2AI screw insertion, especially when using free-hand technique.

Optimal timing of starting growing rod treatment for early-onset scoliosis.

BACKGROUND CONTEXT: Growing rod (GR) systems require periodical surgical intervention and may cause associated complications, as well as worsened sagittal plane deformity. Generally, the risk of complications decreases with an increment in age at the time of the index surgery with GR construct placement. However, the optimal timing to begin GR treatment has not reached a consensus yet. PURPOSE: This study was performed to investigate the effect of age at the index GR surgery on the complication rates and formulate clinical guidelines for the optimal timing to begin GR treatment for EOS patients. STUDY DESIGN: Kaplan-Meier analysis was used to determine complication occurrence as a function of the age at the index surgery and to determine the survival rates for the procedures. The receiver operator characteristic (ROC) curve was used to determine optimal cut-off values for the optimal timing of index surgery based on whether complications occurred or not. PATIENT SAMPLE: 54 patients who met the criteria were enrolled in this study. OUTCOME MEASURES: The following spinal parameters were measured: major coronal Cobb angle, global kyphosis (GK), and coronal balance (CB). CB was defined as the horizontal distance from the C7 plumb line to the center sacral vertical line. METHODS: All patients had completed GR treatment and had a minimum 1-year follow-up duration after the final surgical intervention. Patient data were collected as follows: age at the index surgery, gender, diagnosis, type of GR construct, and the number of lengthening procedures. The standing full-spine radiographs were obtained before and after the index surgery, before and after each lengthening procedure, before and after the final surgical intervention, and at the latest follow-up. Complications were categorized as implant, alignment, and general. RESULTS: Kaplan-Meier analysis of complications demonstrated a declining trend in complication rates with increasing age at the index surgery. The absence of perioperative complications was targeted, we constructed the ROC curve and the cut-off value was 71.0 months. Age at the index surgery was therefore categorized into two groups: younger-age group (≤ 71.0 months) and advanced-age group (> 71.0 months). There was a higher complication rate for the younger-age group than versus the advanced-age group (61.5% vs 22.0%, p=.011). PJK as a major alignment-related complication, was more frequent in the younger-age group than in the advanced-age group (30.8% vs 4.9%, p=.025). But the advanced-age group exhibited significantly more severe deformities before GR surgery compared to the younger-age group. CONCLUSIONS: This study shows that the elevated risk of complications observed in the younger-age group, which can be attributed to the younger age at the index surgery and the increased number of lengthening procedures during treatment. We suggest deferring the initiation of GR treatment until after the age of six years for EOS patients. We hope it will serve as a basis for GR technique in the treatment of EOS, with the ultimate goal of enhancing treatment outcomes for this challenging disorder.

Preoperative supine pelvic incidence predicts standing pelvic incidence following S2AI fixation in patients with adult spinal deformity: a prospective study.

STUDY DESIGN: A prospective study. OBJECTIVE: The aim of this study was to investigate the PI change in different postures and before and after S2­alar­iliac (S2AI) screw fixation, and to investigate whether pre-op supine PI could predict post-op standing PI. Previous studies have reported PI may change with various positions. Some authors postulated that the unexpected PI change in ASD patients could be due to sacroiliac joint laxity, S2-alar-iliac (S2AI) screw placement, or aggressive sagittal cantilever technique. However, there was a lack of investigation on how to predict post-op standing PI when making surgical strategy. METHODS: A prospective case series of ASD patients undergoing surgical correction with S2AI screw placement was conducted. Full-spine X-ray films were obtained at pre-op standing, pre-op supine, pre-op prone, as well as post-op standing postures. Pelvic parameters were measured. Spearman correlation analysis was used to determine relationships between each parameter. RESULTS: A total of 83 patients (22 males, 61females) with a mean age of 58.4 ± 9.5 years were included in this study. Pre-op standing PI was significantly lower than post-op standing PI (p = 0.004). Pre-op prone PI was significantly lower than post-op standing PI (p = 0.001). By contrast, no significant difference was observed between pre-op supine and post-op standing PI (p = 0.359) with a mean absolute difference of 2.2° ± 1.9°. Correlation analysis showed supine PI was significantly correlated with post-op standing PI (r = 0.951, p < 0.001). CONCLUSION: This study revealed the PI changed after S2AI screw fixation. The pre-op supine PI can predict post-op standing PI precisely, which facilitates to provide correction surgery strategy with a good reference for ideal sagittal alignment postoperatively.

Nrf-2/ROS/NF-κB pathway is modulated by cynarin in human mesenchymal stem cells in vitro from ankylosing spondylitis.

Ankylosing spondylitis (AS) is an immune chronic inflammatory disease, resulting in back pain, stiffness, and thoracolumbar kyphotic deformity. Based on the reported anti-inflammatory and antioxidant capacities of cynarin (Cyn), this study explored its protective role and molecular mechanisms in mesenchymal stem cells (MSCs) from AS. The target pathways and genes were verified using Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescent staining, while molecular docking analysis was conducted. In AS-MSCs, we found that the expression levels of p-NF-κB, IL-6, IL-1ß, and TNF-α were higher and IκB-α, Nrf-2, and HO-1 were lower compared with healthy control (HC)-MSCs. With molecular docking analysis, the biding affinities between Cyn and Keap1-Nrf-2 and p65-IκB-α were predicted. The mRNA and protein expression of p-NF-κB, IL-6, IL-1ß, and TNF-α and the reactive oxygen species (ROS) generation were downregulated following Cyn administration. Meanwhile, the expression level of IκB-α, Nrf-2, and HO-1 were significantly increased after Cyn pretreatment. The results suggested that the protective mechanisms of Cyn in AS-MSCs were based on enhancing the antioxidation and suppression of excessive inflammatory responses via Nrf-2/ROS/NF-κB axis. Our findings demonstrate that Cyn is a potential candidate for alleviating inflammation in AS.

[Binocular loupe assisted mini-lateral and medial incisions in lateral position for release of elbow stiffness].

Objective: To analyze the effectiveness of binocular loupe assisted mini-lateral and medial incisions in lateral position for the release of elbow stiffness. Methods: The clinical data of 16 patients with elbow stiffness treated with binocular loupe assisted mini-internal and external incisions in lateral position release between January 2021 and December 2022 were retrospectively analyzed. There were 9 males and 7 females, aged from 19 to 57 years, with a median age of 33.5 years. Etiologies included olecranon fracture in 6 cases, elbow dislocation in 4 cases, medial epicondyle fracture in 2 cases, radial head fracture in 4 cases, terrible triad of elbow joint in 2 cases, supracondylar fracture of humerus in 1 case, coronoid process fracture of ulna in 1 case, and humerus fracture in 1 case, with 5 cases presenting a combination of two etiologies. The duration of symptoms ranged from 5 to 60 months, with a median of 8 months. Preoperatively, 12 cases had concomitant ulnar nerve numbness, and 6 cases exhibited ectopic ossification. The preoperative range of motion for elbow flexion and extension was (58.63±22.30)°, the visual analogue scale (VAS) score was 4.3±1.6, and the Mayo score was 71.9±7.5. Incision lengths for both lateral and medial approaches were recorded, as well as the occurrence of complications. Clinical outcomes were evaluated using Mayo scores, VAS scores, and elbow range of motion both preoperatively and postoperatively. Results: The lateral incision lengths for all patients ranged from 3.0 to 4.8 cm, with an average of 4.1 cm. The medial incision lengths ranged from 2.4 to 4.2 cm, with an average of 3.0 cm. The follow-up duration ranged from 6 to 19 months and a mean of 9.2 months. At last follow-up, 1 patient reported moderate elbow joint pain, and 3 cases exhibited residual mild ulnar nerve numbness. The other patients had no complications such as new heterotopic ossification and ulnar nerve paralysis, which hindered the movement of elbow joint. At last follow-up, the elbow range of motion was (130.44±9.75)°, the VAS score was 1.1±1.0, and the Mayo score was 99.1±3.8, which significantly improved when compared to the preoperative ones ( t=-12.418, P<0.001; t=6.419, P<0.001; t=-13.330, P<0.001). Conclusion: The binocular loupe assisted mini-lateral and medial incisions in lateral position integrated the advantages of traditional open and arthroscopic technique, which demonstrated satisfying safety and effectivity for the release of elbow contracture, but it is not indicated for patients with posterior medial heterolateral heterotopic ossification.