Dysregulation of Inflammatory Pathways in Adult Spinal Deformity Patients with Frailty.

Background/Objectives: An important aspect of the pathophysiology of frailty seems to be the dysregulation of inflammatory pathways and the coagulation system. However, an objective assessment of the impact of frailty on the recovery from surgery is not fully studied. This study sought to assess how frailty affects the recovery of adult spinal deformity (ASD) surgery using blood biomarkers. Methods: 153 consecutive ASD patients (age 64 ± 10 yr, 93% female) who had corrective spine surgery in a single institution and reached 2y f/u were included. The subjects were stratified by frailty using the modified frailty index-11 (robust [R] group or prefrail and frail [F] group). Results of commonly employed laboratory tests at baseline, 1, 3, 7, and 14 post-operative days (POD) were compared. Further comparison was performed in propensity-score matched-39 paired patients between the groups by age, curve type, and baseline alignment. A correlation between HRQOLs, major complications, and biomarkers was performed. Results: Among the propensity-score matched groups, CRP was significantly elevated in the F group at POD1,3(POD1; 5.3 ± 3.1 vs. 7.9 ± 4.7 p = 0.02, POD3; 6.6 ± 4.6 vs. 8.9 ± 5.2 p = 0.02). Transaminase was also elevated in the F group at POD3(ASD: 36 ± 15 vs. 51 ± 58 U/L, p = 0.03, ALT: 32 ± 16 vs. 47 ± 55 U/L, p = 0.04). Interestingly, moderate correlation was observed between transaminase at POD1 and 2 y SRS22 (AST; function r = -0.37, mental health r = -0.39, satisfaction -0.28, total r = -0.40, ALT; function r = -0.37, satisfaction -0.34, total r = -0.39). Conclusions: Frailty affected the serum CRP and transaminase differently following ASD surgery. Transaminase at early POD was correlated with 2 y HRQOLs. These findings support the hypothesis that there is a specific physiological basis to the frailty that is characterized in part by increased inflammation and that these physiological differences persist.

Human-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury.

The transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) has shown promise in spinal cord injury (SCI) model animals. Establishing a functional synaptic connection between the transplanted and host neurons is crucial for motor function recovery. To boost therapeutic outcomes, we developed an ex vivo gene therapy aimed at promoting synapse formation by expressing the synthetic excitatory synapse organizer CPTX in hiPSC-NS/PCs. Using an immunocompromised transgenic rat model of SCI, we evaluated the effects of transplanting CPTX-expressing hiPSC-NS/PCs using histological and functional analyses. Our findings revealed a significant increase in excitatory synapse formation at the transplantation site. Retrograde monosynaptic tracing indicated extensive integration of transplanted neurons into the surrounding neuronal tracts facilitated by CPTX. Consequently, locomotion and spinal cord conduction significantly improved. Thus, ex vivo gene therapy targeting synapse formation holds promise for future clinical applications and offers potential benefits to individuals with SCI.

Influence of thoracolumbar kyphosis on postoperative spinal alignment in patients with Lenke type 5C adolescent idiopathic scoliosis.

PURPOSE: This study aimed to examine the changes in thoracolumbar kyphosis (TLK) following correction surgery in patients with Lenke type 5C adolescent idiopathic scoliosis (AIS) and to evaluate its influence on postoperative spinal alignment and clinical outcomes. METHODS: Sixty-six patients with Lenke type 5C AIS were included and followed up for a minimum of 5 years after surgery. First, the patients were divided into two groups according to the preoperative TLK angle (Study 1; Kyphosis and Lordosis group). The patients were further classified into two groups according to the presence or absence of postoperative changes in TLK (Study 2; Changed and Maintained groups). Finally, the outcome variables were compared between these groups and analyzed for spinal alignment and clinical outcomes. RESULTS: In Study 1, patients demonstrated a significant kyphotic change in the Lordosis group and a significant lordotic change in the Kyphosis group postoperatively. No statistically significant differences were found between the two groups when comparing the pre- and postoperative coronal and sagittal alignment. In Study 2, there were no statistically significant differences between the Changed and the Maintained groups in each spinal alignment pre- and postoperatively. Each domain of the Scoliosis Research Society 22-item questionnaire remained unchanged at 5 years postoperation. CONCLUSION: In many patients with Lenke type 5C AIS, TLK changed significantly and approached 0° after surgery. However, the magnitude of the preoperative TLK and the presence or absence of improvement did not affect postoperative spinal alignment. Furthermore, the patients had satisfactory clinical outcomes irrespective of TLK modification. LEVEL OF EVIDENCE: III.

How coronal malalignment affects the surgical outcome in corrective spine surgery for adult symptomatic lumbar deformity.

PURPOSE: The importance of coronal alignment is unclear, while the importance of sagittal alignment in the treatment of adult patients with spinal deformities is well described. This study sought to elucidate the impact of global coronal malalignment (GCMA) in surgically treated adult symptomatic lumbar deformity (ASLD) patients. METHODS: A multicentre retrospective analysis of a prospective ASD database. GCMA was defined as GCA (C7PL-CSVL) ≥ 3 cm. GCMA is categorized based on the Obeid-Coronal Malalignment Classification (O-CM). Demographic, surgical, radiographic, HRQOL, and complication data were analysed. The risk for postoperative GCMA was analysed by univariate and multivariate analyses. RESULTS: Of 230 surgically treated ASLD patients, 96 patients showed GCMA preoperatively and baseline GCA was correlated with the baseline SRS-22 pain domain score (r = - 30). Postoperatively, 62 patients (27%, O-CM type 1: 41[18%], type 2: 21[9%]) developed GCMA. The multivariate risk analysis indicated dementia (OR 20.1[1.2-304.4]), diabetes (OR 5.9[1.3-27.3]), and baseline O-CM type 2 (OR 2.1[1.3-3.4]) as independent risk factors for postoperative GCMA. The 2-year SRS-22 score was not different between the 2 groups, while 4 GCMA patients required revision surgery within 1 year after surgery due to coronal decompensation (GCMA+ vs. GCMA- function: 3.6 ± 0.6 vs. 3.7 ± 0.7, pain: 3.7 ± 0.8 vs. 3.8 ± 0.8, self-image: 3.6 ± 0.8 vs. 3.6 ± 0.8, mental health: 3.7 ± 0.8 vs. 3.8 ± 0.9, satisfaction: 3.9 ± 0.9 vs. 3.9 ± 0.8, total: 3.7 ± 0.7 vs. 3.7 ± 0.7). Additionally, the comparisons of 2-yr SRS-22 between GCMA ± showed no difference in any UIV and LIV level or O-CM type. CONCLUSIONS: In ASLD patients with corrective spine surgery, GCMA at 2 years did not affect HRQOL or major complications at any spinal fusion extent or O-CM type of malalignment, whereas GCA correlated with pain intensity before surgery. These findings may warrant further study of the impact of GCMA on HRQOL in the surgical treatment of ASLD patients.

Hepatocyte growth factor pretreatment boosts functional recovery after spinal cord injury through human iPSC-derived neural stem/progenitor cell transplantation.

BACKGROUND: Human induced pluripotent stem cell-derived neural stem/progenitor cell (hiPSC-NS/PC)-based cell transplantation has emerged as a groundbreaking method for replacing damaged neural cells and stimulating functional recovery, but its efficacy is strongly influenced by the state of the injured spinal microenvironment. This study evaluates the impact of a dual therapeutic intervention utilizing hepatocyte growth factor (HGF) and hiPSC-NS/PC transplantation on motor function restoration following spinal cord injury (SCI). METHODS: Severe contusive SCI was induced in immunocompromised rats, followed by continuous administration of recombinant human HGF protein into the subarachnoid space immediately after SCI for two weeks. Acute-phase histological and RNA sequencing analyses were conducted. Nine days after the injury, hiPSC-NS/PCs were transplanted into the lesion epicenter of the injured spinal cord, and the functional and histological outcomes were determined. RESULTS: The acute-phase HGF-treated group exhibited vascularization, diverse anti-inflammatory effects, and activation of endogenous neural stem cells after SCI, which collectively contributed to tissue preservation. Following cell transplantation into a favorable environment, the transplanted NS/PCs survived well, facilitating remyelination and neuronal regeneration in host tissues. These comprehensive effects led to substantial enhancements in motor function in the dual-therapy group compared to the single-treatment groups. CONCLUSIONS: We demonstrate that the combined therapeutic approach of HGF preconditioning and hiPSC-NS/PC transplantation enhances locomotor functional recovery post-SCI, highlighting a highly promising therapeutic strategy for acute to subacute SCI.

Reinstrumentation for progressive hyper-kyphotic deformity after implant removal despite obtaining physiological alignment by posterior corrective surgery for adolescent idiopathic scoliosis with flat back: a case report.

This case report describes a 13-year-old female patient with adolescent idiopathic scoliosis (AIS) and flat back who experienced progressive kyphotic deformity after implant removal despite obtaining physiological alignment postoperatively. The patient underwent multiple surgeries, and a late-developing infection complicated her treatment course. Despite hard bracing to prevent kyphotic change, the kyphosis progressed to 74° within a year after implant removal, leading to a decrease in patient height and back pain. Revision surgery was eventually necessary. Possible factors for the kyphotic progression include injury to paraspinal back muscles due to multiple surgeries or insufficient bony fusion from late-developing infection. This case highlights the importance of thorough evaluation and follow-up for optimal patient outcomes after implant removal in AIS patients, particularly those with flat back.

Impact of Surgical Resection Without Spinal Fusion for Thoracic Dumbbell Tumors on Postoperative Global Spinal Sagittal Alignment and Clinical Outcomes.

STUDY DESIGN: A retrospective comparative study. OBJECTIVES: This study investigated radiographical changes in global spinal sagittal alignment (GSSA) and clinical outcomes after tumor resection without spinal fusion in patients with thoracic dumbbell tumors. METHODS: Thirty patients with thoracic dumbbell tumors who were followed up for at least 3 years were included in this study. Variations in the outcome variables were analyzed using individual GSSA parameters measured on radiography. Clinical outcomes were assessed using the modified McCormick scale (MMCS), Japan Orthopaedic Association (JOA) score, and visual analog scale (VAS). To assess the impact of the affected levels on these outcomes, we divided the patients into three groups according to the location of the tumor (upper [T1-4], middle [T5-8], or lower [T9-12] thoracic spine). RESULTS: The GSSA parameters (cervical lordosis, T1 slope, thoracic kyphosis [global, upper, middle, and lower], thoracolumbar kyphosis, lumbar lordosis, sacral slope, pelvic incidence, and pelvic tilt) of all the patients did not change significantly after surgery. Eleven of thirty patients had preoperative gait disturbances but they could walk without support (MMCS grade I or II) at the final follow-up. The JOA score and VAS showed significant postoperative improvements. No statistically significant differences were observed in each postoperative sagittal profile or clinical outcome between the upper, middle, and lower groups. CONCLUSIONS: Tumor resection without spinal fusion did not affect the various GSSA parameters and resulted in satisfactory clinical outcomes, indicating that spinal fusion may not always be necessary when resecting thoracic dumbbell tumors.

The Effect of Age-adjusted Sagittal Alignment on the Result of Posterior Decompression Surgery for Lumbar Spinal Canal Stenosis.

STUDY DESIGN: Retrospective case series. OBJECTIVE: The aim of this study was to compare the outcomes of posterior decompression surgery for lumbar spinal canal stenosis (LSS) in patients with preoperative sagittal malalignment to those without, after adjusting for age and sex. SUMMARY OF BACKGROUND DATA: Sagittal balance is an important factor in spine surgery and is thought to affect postoperative outcomes following LSS. However, the relationship between sagittal malalignment and postoperative outcomes has not been thoroughly examined. METHODS: We included 533 patients who underwent surgical treatment for LSS and also achieved two-year follow-up. Patients were categorized into either a malalignment (MA+) group (69 patients) or a matched-alignment (MA-) group (348 patients) based on age-adjusted preoperative sagittal alignment. We compared the baseline and two-year postoperative health-related quality of life (HRQOL) using the Visual Analog Scale and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) scores. We also calculated clinical efficacy using the minimal clinically important difference (MCID) based on JOABPEQ scores, and age- and sex-adjusted JOABPEQ scores two years after surgery. Differences between groups were examined using the Mann‒Whitney U test and χ 2 analysis, where applicable. RESULTS: Both groups showed an improved HRQOL after decompression surgery. Similar proportions of patients showed substantial improvement, as estimated by the MCID, in four out of five subdomains of the JOABPEQ. A significantly smaller proportion of patients in the MA+ group showed substantial improvement in lumbar function. The age- and sex-adjusted HRQOL scores two years after surgery were lower in the MA+ group, particularly in the lumbar function and social life function subdomains of the JOABPEQ. CONCLUSION: The effects of posterior decompression surgery alone can still be observed at least two years postoperatively for patients with LSS and concomitant sagittal malalignment. Patients with sagittal malalignment may experience lower HRQOL than those without this type of malalignment.

10-year Longitudinal MRI Study of Intervertebral Disk Degeneration in Patients With Lumbar Spinal Canal Stenosis After Posterior Lumbar Decompression Surgery.

STUDY DESIGN: A prospective longitudinal magnetic resonance imaging (MRI) study. OBJECTIVE: The objective of this study was to describe the progression of intervertebral disk (IVD) degeneration in patients who underwent posterior decompression surgery for lumbar spinal canal stenosis (LSS). SUMMARY OF BACKGROUND DATA: IVD degeneration contributes to the pathogenesis of LSS; however, the long-term consequences of degenerative changes after decompression surgery remain unknown. MATERIALS AND METHODS: Of 258 consecutive patients who underwent posterior lumbar decompression surgery for LSS, 62 who underwent MRI at their 10-year follow-up were included; 17 age-matched asymptomatic volunteers were analyzed as controls. Three MRI findings representing IVD degeneration were graded on their severity: decrease in signal intensity, posterior disk protrusion (PDP), and disk space narrowing (DSN). Clinical outcome was assessed using the low back pain (LBP) score from the Japanese Orthopaedic Association scoring system. We examined the association between the progression of degenerative changes on MRI and LBP/associated factors using logistic regression adjusting for age at baseline and sex. RESULTS: The severity of IVD degeneration tended to be higher in patients with LSS than asymptomatic volunteers at both baseline and follow-up. IVD degeneration progressed in all patients during the 10-year follow-up period. Progression of decrease in signal intensity and PDP was observed at L1/2 in 73% and at L2/3 in 34%, respectively (the highest frequencies in the lumbar spine). Progression of DSN was highest at L4/5 in 42%. The rates of PDP and DSN progression during the 10-year follow-up period tended to be greater in patients with LSS than in asymptomatic volunteers. No significant difference in the proportion of LBP deterioration was evident for individuals with and without MRI findings of progression. CONCLUSIONS: Our study reveals a natural history of the long-term postoperative course of IVD degeneration after posterior decompression surgery for LSS. Compared with healthy controls, patients with LSS seemed to be predisposed to IVD degeneration. Lumbar decompression surgery may promote the progression of DSN; however, progression of IVD degeneration after lumbar decompression surgery was not associated with worsening LBP scores.

Long-Term Clinical, Radiographic, and Cost Analysis of Corrective Spine Surgery for Adult Symptomatic Lumbar Deformity With a Mean of 7.5 years Follow-Up.

STUDY DESIGN: Multicenter retrospective study. OBJECTIVE: This study reports long-term clinical and radiographic outcomes in surgically treated patients with adult symptomatic lumbar deformity (ASLD). SUMMARY OF BACKGROUND DATA: The short-term results of corrective spinal surgery for ASLD are often favorable despite a relatively high complication profile. However, long-term outcomes have not been completely characterized. METHODS: A total of 169 surgically treated consecutive ASLD patients (≥50 yr) who achieved minimum 5 year follow-up were included (average 7.5 yr observation window, average age 67±8 yr, 96% female). The subjects were stratified by current age (50s, 60s, and 70s) and compared. Kaplan-Meier analysis was used to estimate the cumulative incidence of unplanned reoperation stratified by age group. Initial and overall direct costs of surgery were also analyzed. RESULTS: The SRS-22 at final follow-up was similar among the three groups (50s, 60s, and 70s; 4.0±0.5 vs. 3.8±0.7 vs. 3.8±0.7, respectively). The overall major complication rate was 56%, and 12% experienced late complications. The cumulative reoperation rate was 23%, and 4% required late reoperation. Patients in their 70s had a significantly higher reoperation rate (33%) and overall complication rate (65%). However, the late complication rate was not significantly different between the three groups (9% vs. 12% vs. 13%). Sagittal alignment was improved at two years and maintained to the final follow-up, whereas reciprocal thoracic kyphosis developed in all age groups. The direct cost of initial surgery was $45K±9K and increased by 13% ($53K±13K) at final follow-up. CONCLUSIONS: Long-term surgical outcomes for ASLDs were favorable, with a relatively low rate of late-stage complications and reoperations, as well as reasonable direct costs. Despite the higher reoperation and complication rate, ASLD patients of more advanced age achieved similar improvement to those in the younger age groups.

Risk factors of AIS C incomplete cervical spinal cord injury for poor prognosis-The significance of anorectal evaluation.

BACKGROUND: Although the prognosis of incomplete cervical spinal cord injury (SCI) diagnosed as American Spinal Injury Association Impairment Scale grade C (AIS C) is generally favorable, some patients remain non-ambulatory. The present study explored the clinical factors associated with the non-ambulatory state of AIS C patients. METHODS: This study was a single-center retrospective observational study. Seventy-three participants with AIS C on admission were enrolled and divided into two groups according to ambulatory ability after one year. Prognostic factors of SCI were compared in ambulatory (A-group) and non-ambulatory participants (NA-group). Univariable and multivariable logistic regression analyses were performed on demographic information, medical history, mechanism of injury, presence of fracture, ASIA motor scores (MS) of the extremities, neurological findings, including an anorectal examination on admission, and imaging findings. RESULTS: Forty-one patients were included in the A-group and 32 in the NA-group. Univariable analysis revealed that the following factors were related to poor outcomes (p < 0.05): older age, history of cerebrovascular disorder, impairment/absence of S4-5 sensory score, deep anal pressure (DAP) (-), voluntary anal contraction (VAC) (-), anorectal tone (-), anal wink reflex (-), and low MS of the upper and lower extremities. In the multivariable analysis using age, presence or absence of sacral abnormality, and history of cerebrovascular disorders (adjusted for these three factors), older age and presence of sacral abnormality on admission were independent risk factors for a non-ambulatory state at the 1-year follow-up. CONCLUSIONS: Incomplete AIS C SCI individuals with older age and/or impairment of anorectal examination could remain non-ambulatory at 1-year follow-up.

Impact of pleural effusion at an early period after posterior spinal fusion for adolescent idiopathic scoliosis on future pulmonary function and lung volume.

Background: Posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) has a potential risk for postoperative pleural effusion. Although pleural effusion at an early period after PSF for AIS occurs with a relatively high frequency and occasionally requires some treatments, the impact of postoperative pleural effusion on future pulmonary function or lung volume (LV) has not been clarified to date. The aim of this study was to evaluate the effect of pleural effusion after PSF for AIS on the postoperative pulmonary function and LV. Methods: A total of 114 consecutive patients who underwent PSF for AIS followed up greater than 2 years at our institute were retrospectively reviewed. We evaluated postoperative pleural effusion by computed tomography (CT) at the 1-week follow-up and divided patients into the pleural effusion (PF) and non-pleural effusion (NP) groups. We investigated spirometry parameters recorded for testing included vital capacity (VC), forced expiratory volume in the first second (FEV1), %VC, and FEV1% and measured the LV using CT images and a workstation at baseline and 2 years after surgery. Results: A total of 87 (76.3%) patients with postoperative pleural effusion were identified, but all patients were asymptomatic and did not require additional treatment for postoperative pleural effusion. All pulmonary function parameters at the 2-year follow-up exhibited no significant differences between the two groups. Although preoperative left LV (1.21±0.30 L vs. 1.36±0.34 L; p=.022) and total LV (2.68±0.62 L vs. 2.99±0.73 L; p=.031) were significantly lower in the PF group than in the NP group, all postoperative LV parameters were similar between the two groups. Conclusions: Pleural effusion at an early period after PSF for AIS was a postoperative occurrence without an impact on future pulmonary function and LV.

Temporary Monosegmental Fixation Using Multiaxial Percutaneous Pedicle Screws for Surgical Management of Bony Flexion-Distraction Injuries of the Thoracolumbar Spine: A Technical Note.

Introduction: The efficacy of minimally invasive surgeries for thoracolumbar flexion-distraction injuries (FDIs) has been reported, but those surgeries were monosegmental fusion surgeries of two adjacent vertebrae with bone grafts or temporary fixations using percutaneous pedicle screws (PPSs) that were at least bisegmental. Our idea was to fuse the fracture itself, not to fuse the fractured vertebra with an adjacent vertebra or to stabilize the fractured vertebra by bridging rostrally/caudally adjacent intact vertebrae, specifically when the displacement is minimal. This study aimed to present the surgical techniques of reduction and temporary monosegmental fixation of neurologically intact thoracolumbar bony FDIs using multiaxial PPSs, which can minimize the surgical invasiveness and preserve all motion segments, as well as report three cases treated with this procedure. Technical Note: When the fracture extended from the vertebral body to the spinous process at the same level, screws were placed into the fractured vertebra rostrally to the fracture along the rostral endplate, and the caudally adjacent vertebra was instrumented beyond the fracture line. When the fracture extended from the vertebral body to the spinous process of the rostrally adjacent vertebra, screws were placed into the fractured vertebra caudally to the fracture line, and the rostrally adjacent vertebra was instrumented. The kyphotic deformity was reduced through ligamentotaxis by using MPPSs in the rostral vertebra as rigid joysticks to apply direct buttress leverage to the rostral endplate. Intraoperative blood loss was minimal. The correction of kyphotic deformity and its durability were acceptable, and the segmental range of motion of the two affected vertebrae from flexion to extension was maintained after implant removal. Conclusions: This surgery can act as the least-invasive option for the management of thoracolumbar bony FDIs to allow early ambulation without external bracing and to preserve all the motion segments.

Clinical and Imaging Characteristics of Non-Neoplastic Spinal Lesions: A Comparative Study with Intramedullary Tumors.

The features of non-neoplastic lesions are often similar to those of intramedullary tumors, and a differential diagnosis is challenging to obtain in some cases. A surgical biopsy, which is performed on highly invasive tumors, should be avoided in cases of non-neoplastic lesions. Therefore, an accurate diagnosis is important prior to treatment. We evaluated 43 patients suspected of having spinal cord tumors and, finally, were diagnosed with non-neoplastic intramedullary lesions via magnetic resonance imaging. The patients commonly presented with myelitis. The patients with non-neoplastic neurological diseases had a significantly shorter symptom duration than those with intramedullary astrocytomas. The proportion of patients with non-neoplastic neurological diseases who presented with lesions at the cervical spinal level and focal lesions on axial imaging but without a spinal cord enlargement was significantly higher than that of patients with intramedullary astrocytomas. The current study aimed to distinguish spinal cord tumors from non-neoplastic intramedullary lesions based on their distinct features.

In Vivo Imaging Analysis of an Inner Ear Drug Delivery in Mice: Comparison of Inner Ear Drug Concentrations Over Time.

Treatment for inner ear regeneration and protection needs local injection of steroid or new drug for inner ear regeneration into the round window membrane (RWM) in cochlea, but a systemic injection is not available due to its systemic side effects. However, pharmacokinetics of therapeutic agents or steroid locally injected into the inner ear is not well known. Hence, we introduce a new method for the real-time observation of drug delivery in transgenic animals in vivo. We exemplify mice which contain a firefly luciferase (FLuc) gene expression cassette regulated by the murine glial fibrillary acidic protein (GFAP) promoter. Luciferin delivered into the inner ear of those mice reacts with FLuc that is expressed in the GFAP-expressing cells in the cochlear nerve and spiral ganglion, and the resulting bioluminescence is detected by a camera. Using this system, we show the imaging of pharmacokinetic differences between local and systemic (intravenous and subcutaneous) injections of the inner ear.

Risk factors for early-onset radiographical adjacent segment disease in patients with spondylolytic spondylolisthesis after single-level posterior lumbar interbody fusion.

BACKGROUND CONTEXT: The risk factors for radiographical adjacent segment disease (ASD) in patients with degenerative spondylolisthesis have been previously reported. However, there are only few reports on patients with spondylolytic spondylolisthesis who underwent single-level posterior lumbar interbody fusion (PLIF). PURPOSE: The study aimed to investigate the risk factors for radiographical ASD in patients with L5-S1 spondylolytic spondylolisthesis who underwent single-level PLIF. STUDY DESIGN/SETTING: A retrospective study PATIENT SAMPLE: This study retrospectively reviewed 135 consecutive patients (91 men and 44 women) with symptomatic L5-S1 spondylolytic spondylolisthesis who underwent single-level PLIF. OUTCOME MEASURES: The pre- and postoperative (at the final follow-up) spinopelvic parameters, % slip, sacral slope, lumbar lordosis (LL), pelvic tilt, pelvic incidence (PI), PI minus LL (PI - LL), lumbosacral angle, C7 sagittal vertical axis, and thoracic kyphosis were measured using standing radiographs. METHODS: Radiographical ASD was defined as disc height loss (>3 mm), increase of posterior angulation (>5°), or progression of spondylolisthesis (>3 mm) between the pre- and postoperative radiographs. Pfirrmann's classification was used to evaluate disc degeneration. The radiographical parameters and changes between the pre- and postoperative values were evaluated and compared for the non-ASD and ASD groups. Binary logistic regression analysis was performed to evaluate the adjusted associations between each potential explanatory variable and ASD development. RESULTS: The radiographical ASD incidence was 11%. Additionally, 60% of the patients with ASD had radiographical ASD at 1 year and all cases of radiographical ASD in this follow-up period occurred within 3 years after the initial surgery. The mean period of ASD occurrence after initial surgery was 21.7 ± 12.6 months. No patients required reoperation for radiographical ASD. Multivariate analysis revealed that a preoperative (odds ratio [OR], 5.9; 95% confidence interval [CI], 1.2-28.9; p=.03) and a postoperative (OR, 6.5; 95% CI, 1.2-34.5; p=.03) PI - LL of ≥15° were risk factors for radiographical ASD. CONCLUSIONS: Pre- and postoperative PI - LL value mismatch was identified as significant independent risk factors for radiographical ASD in patients with L5-S1 spondylolytic spondylolisthesis. Obtaining larger lordosis at L5-S1 may be the key to preventing radiographical ASD.

Comparison of Drug Availability in the Inner Ear After Oral, Transtympanic, and Combined Administration.

Although combination of oral and transtympanic drug therapy (CT) has been proved more effective and safer for idiopathic sudden sensorineural hearing loss (ISSNHL) by some clinical trials, there are few laboratory researches on the pharmacokinetics in the inner ear following CT on account of structural limitations of the inner ear. The aim of the present study was to investigate the pharmacokinetic behaviors of CT in the inner ear of mice. Eighteen transgenic GFAP-Luc mice which express luciferase in cochlear spiral ganglion cells were divided into oral administration (OR) group, transtympanic injection route (TT) group and CT group, and luciferin was delivered into the inner ear of these mice through oral, transtympanic or combined routes, respectively. A new in vivo imaging system was used to observe luciferin/luciferase signals and the compare the pharmacokinetics of different administration routes in the inner ear of mice. Bioluminescence signals were observed in the inner ear 3.3 ± 2.6 min after CT, significantly earlier than that of OR group (15.8 ± 7.4 min). CT owned the longest reaching-peak time and largest area under the curve (AUC) among three groups. Compared to TT, CT had longer biological half-life and higher AUC value, but did not displayed stronger peak value. There were significant differences in the peak values between OR group and TT group and between OR group and CT group. This study suggests that the OR route is less effective than the TT or CT route, and combination of OR and TT can deliver more drugs into the inner ear and confer a longer therapeutic window, but cannot increase drug intensity.

Serum C-reactive protein is an early, simple and inexpensive prognostic marker for the progression of intramedullary lesion on magnetic resonance imaging from acute to subacute stage in patients with spinal cord injury.

STUDY DESIGN: Retrospective chart audit. OBJECTIVES: This study aimed to identify conventional routine blood testing biomarkers associated with the progression of intramedullary injured area in patients with spinal cord injury (SCI). SETTING: A spinal cord injury center in Hokkaido, Japan. METHODS: We retrospectively reviewed 71 consecutive adults with acute SCI who were admitted within 24 h after injury and diagnosed as American Spinal Injury Association Impairment Scale Grade A or B at admission. Participants were divided into the progression (P group) and no progression group (NP group) based on the change of the hyperintense signal abnormality in the spinal cord on magnetic resonance imaging from the time of admission to 4 weeks after injury. Individual characteristics and blood testing data obtained in the first 4 weeks after injury were compared between groups. RESULTS: The P and NP groups were comprised of 16 and 55 participants, respectively. In univariate analyses, white blood cell (WBC) count on day 3 was significantly higher in group P than group NP (P = 0.021), as was serum C-reactive protein (CRP) level on day 3 (P = 0.015) and day 7 (P = 0.047). Multivariable analysis identified serum CRP level on day 3 as a significant independent prognostic factor for the progression of secondary SCI (OR, 1.138; 95% confidence interval, 1.01-1.28; P = 0.034). CONCLUSIONS: Serum CRP level on day 3 after injury was a good predictor for the progression of intramedullary signal intensity change on MRI from acute to subacute stage in patients with SCI.

Predictive factors for irreversible motor paralysis following cervical spinal cord injury.

STUDY DESIGN: A retrospective observational study. OBJECTIVES: To elucidate predictive clinical factors associated with irreversible complete motor paralysis following traumatic cervical spinal cord injury (CSCI). SETTING: Hokkaido Spinal Cord Injury Center, Japan. METHODS: A consecutive series of 447 traumatic CSCI persons were eligible for this study. Individuals with complete motor paralysis at admission were selected and divided into two groups according to the motor functional outcomes at discharge. Initial findings in magnetic resonance imaging (MRI) and other clinical factors that could affect functional outcomes were compared between two groups of participants: those with and those without motor recovery below the level of injury at the time of discharge. RESULTS: Of the 73 consecutive participants with total motor paralysis at initial examination, 28 showed some recovery of motor function, whereas 45 remained complete motor paralysis at discharge, respectively. Multivariate logistic regression analysis showed that the presence of intramedullary hemorrhage manifested as a confined low intensity changes in diffuse high-intensity area and more than 50% of cord compression on MRI were significant predictors of irreversible complete motor paralysis (odds ratio [OR]: 8.4; 95% confidence interval [CI]: 1.2-58.2 and OR: 14.4; 95% CI: 2.5-82.8, respectively). CONCLUSION: The presence of intramedullary hemorrhage and/or severe cord compression on initial MRI were closely associated with irreversible paralysis in persons with motor complete paralysis following CSCI. Conversely, subjects with a negligible potential for recovery could be identified by referring to these negative findings.