Enhanced Intervertebral Disc Repair via Genetically Engineered Mesenchymal Stem Cells with Tetracycline Regulatory System.

The therapeutic potential of Mesenchymal stem cells (MSCs) for the treatment of Intervertebral disc (IVD) degeneration can be enhanced by amplifying specific cytokines and proteins. This study aimed to investigate the therapeutic potential of tetracycline-off system-engineered tonsil-derived mesenchymal stem cells (ToMSC-Tetoff-TGFß1-IGF1-BMP7) for treating intervertebral disc (IVD) degeneration. ToMSCs were isolated from a tonsillectomy patient and genetically modified with four distinct plasmids via CRISPR/Cas9-mediated knock-in gene editing. Transgene expression was confirmed through immunofluorescence, western blots, and an enzyme-linked immunosorbent assay for transforming growth factor beta 1 (TGFß1) protein secretion, and the effect of MSC-TetOff-TGFß1-IGF1-BMP7 on disc injury was assessed in a rat model. The ToMSC-Tetoff-TGFß1-IGF1-BMP7 treatment exhibited superior therapeutic effects compared to ToMSC-TGFß1, and ToMSC-SDF1α implantation groups, stimulating the regeneration of nucleus pulposus (NP) cells crucial for IVD. The treatment showed potential to restore the structural integrity of the extracellular matrix (ECM) by upregulating key molecules such as aggrecan and type II collagen. It also exhibited anti-inflammatory properties and reduced pain-inducing neuropeptides. ToMSC-Tetoff-TGFß1-IGF1-BMP7 holds promise as a novel treatment for IVD degeneration. It appears to promote NP cell regeneration, restore ECM structure, suppress inflammation, and reduce pain. However, more research and clinical trials are required to confirm its therapeutic potential.

Unsubtracted Roadmap Technique for Preventing Cement Leakage During Percutaneous Vertebroplasty: A Retrospective Cohort Study.

OBJECTIVE: To determine the effectiveness of the unsubtracted roadmap technique (USRT) for decreasing cement leakage (CL) during percutaneous vertebroplasty (PVP). METHODS: In this retrospective cohort study, patients who underwent PVP between January and November 2018 were included. Patients were divided into the unsubtracted roadmap (UR) (n = 20) and conventional venography (CV) (n = 22) groups. USRT was performed before cement injection in the UR group. Computed tomography was performed on the first day after PVP in both groups to assess the CL. The vertebral height restoration rate was confirmed by radiography before and after the procedure. The CL location was classified as basivertebral vein (type B), segmental vein (type S), or cortical defect (type C). Visual analog scale and Oswestry Disability Index scores before and after surgery were calculated to confirm clinical outcomes. RESULTS: Based on the computed tomography images, CL occurred in 7 (34.78%) and 15 (63.64%) cases in the UR and CV groups, respectively. Number of CL type B, S, and C in the UR and CV groups were 2 and 6, 3 and 6, and 2 and 3, respectively. The injected cement volume was not significantly different between the UR (4.86 mL) and the CV (4.75 mL) groups (P = 0.450). Regarding vertebral body height restoration (P = 0.856) and clinical outcomes, there were no significant differences between both groups. Radiation exposure was significantly less in the UR group (P = 0.019). CONCLUSIONS: USRT is an effective method for reducing CL and radiation exposure during PVP.

Does Diabetes Affect the Surgical Outcomes in Cases With Cervical Ossification of the Posterior Longitudinal Ligament? A Multicenter Study From Asia Pacific Spine Study Group.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To evaluate the surgical outcomes of cervical ossification of the posterior longitudinal ligament (OPLL) in diabetes mellitus (DM) patients. METHODS: Approximately 253 cervical OPLL patients who underwent surgical decompression with or without fixation were registered at 4 institutions in 3 Asian countries. They were followed up for at least 2 years. Demographics, imaging, and surgical information were collected, and cervical Japanese Orthopaedic Association (JOA) scores and the visual analog scale (VAS) for the neck were used for evaluation. RESULTS: Forty-seven patients had DM, showing higher hypertension and cardiovascular disease prevalence. Although they presented worse preoperative JOA scores than non-DM patients (10.5 ± 3.1 vs. 11.8 ± 3.2; P = 0.01), the former showed comparable neurologic recovery at the final follow-up (13.9 ± 2.9 vs. 14.2 ± 2.6; P = 0.41). No correlation was noted between the hemoglobin A1c level in the DM group and the pre- and postoperative JOA scores. No significant difference was noted in VAS scores between the groups at pre- and postsurgery. Regarding perioperative complications, DM patients presented a higher C5 palsy frequency (14.9% vs. 5.8%; P = 0.04). A similar trend was observed when surgical procedure was limited to laminoplasty. CONCLUSIONS: This is the first multicenter Asian study to evaluate the impact of DM on cervical OPLL patients. Surgical results were favorable even in DM cases, regardless of preoperative hemoglobin A1c levels or operative procedures. However, caution is warranted for the occurrence of C5 palsy after surgery.

Association of frailty with regional sagittal spinal alignment in the elderly.

The degenerative changes in the spine of the frail elderly gradually exacerbate the alignment of the spine as the degeneration progresses. This study was conducted to assess the relationship between frailty and spine sagittal alignment measured in terms of global, cervical, thoracic, and lumbo-pelvic parameters. In total, 101 patients aged 75 years and older hospitalized for spine surgery were prospectively enrolled. We evaluated spinal sagittal parameters by dividing them into global (C7 sagittal vertical axis [SVA] and T1 pelvic angle [T1PA]), cervical (the C2-7 Cobb angle, Jackson line, and C2-7 plumb line), thoracic (thoracic kyphosis [TK]), and lumbo-pelvic (pelvic tilt [PT] and pelvic incidence minus lumbar lordosis value [PI-LL]). Patient characteristics; the Fatigue, Resistance, Ambulation, Illness, Loss of Weight (FRAIL) scale; and sagittal spinal parameters were included in the analysis. Multiple regression analysis was performed to identify associations between the FRAIL scale and sagittal spinal parameters. The FRAIL scale showed correlations with global sagittal parameters (C7 SVA [ß = 0.225, p = 0.029] and T1PA [ß = 0.273, p = 0.008]) and lumbo-pelvic parameters (PT [ß = 0.294, p = 0.004] and PI-LL [ß = 0.323, p = 0.001). Cervical and thoracic parameters were not directly associated with the FRAIL scale. LL and PI-LL were associated with TK, and TK was associated with cervical parameters (the C2-7 Cobb angle, Jackson line and C2-7 plumb line). In conclusion, frailty status could be an important factor that influences sagittal spinal alignment in the elderly. In this study, it was found that frailty mainly affected the balance of lumbo-pelvic alignment, and consequently affected the balance of the whole spine.

Laminectomy with instrumented fusion vs. laminoplasty in the surgical treatment of cervical ossification of the posterior longitudinal ligament: A multicenter retrospective study.

Laminectomy with instrumented fusion (LF) has demonstrated better prevention of ossification of posterior longitudinal ligament (OPLL) growth compared to laminoplasty (LP). There remains uncertainty, however, as to which surgical approach is more beneficial with respect to clinical outcomes and complications. We retrospectively reviewed 273 cervical OPLL patients of more than 3 levels, from the two institutions' databases, who underwent LF or LP between January 1998 and January 2016. Each 273 patient (85 with LF, 188 with LP) was assessed for postoperative neurologic and radiologic outcomes, complications and reoperations. The mean length of follow-up was 40.11 months. There were baseline differences between cohorts. Overall, postoperative JOA recovery rate at last follow up was significantly better in the LP group with similar improvement in visual analog neck score. Postoperative C2-7 Cobb angle was decreased compared to baseline for both LF and LP cohorts, but there was no significant difference between groups. Complications occurred in 19 (22.35%) LF patients, and 11 (5.85%) LP patients, with higher incidence of C5 palsy and instrumentation failure in the LF group. Four LF patients (4.71%) and five LP patients (2.66%) underwent reoperation during the follow up period.

Predictors of neurologic outcome after surgery for cervical ossification of the posterior longitudinal ligament differ based on myelopathy severity: a multicenter study.

OBJECTIVE: The purpose of this retrospective multicenter study was to compare prognostic factors for neurological recovery in patients undergoing surgery for cervical ossification of the posterior longitudinal ligament (OPLL) based on their presenting mild, moderate, or severe myelopathy. METHODS: The study included 372 consecutive patients with OPLL who underwent surgery for cervical myelopathy between 2006 and 2016 in East Asian countries with a high OPLL prevalence. Baseline and postoperative clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA) myelopathy score and recovery ratio. Radiographic assessment included occupying ratio, cervical range of motion, and sagittal alignment parameters. Patient myelopathy was classified as mild, moderate, or severe based on the preoperative JOA score. Linear and multivariate regression analyses were performed to identify patient and surgical factors associated with neurological recovery stratified by baseline myelopathy severity. RESULTS: The mean follow-up period was 45.4 months (range 25-140 months). The mean preoperative and postoperative JOA scores and recovery ratios for the total cohort were 11.7 ± 3.0, 14.5 ± 2.7, and 55.2% ± 39.3%, respectively. In patients with mild myelopathy, only age and diabetes correlated with recovery. In patients with moderate to severe myelopathy, older age and preoperative increased signal intensity on T2-weighted imaging were significantly correlated with a lower likelihood of recovery, while female sex and anterior decompression with fusion (ADF) were associated with better recovery. CONCLUSIONS: Various patient and surgical factors are correlated with likelihood of neurological recovery after surgical treatment for cervical OPLL, depending on the severity of presenting myelopathy. Older age, male sex, intramedullary high signal intensity, and posterior decompression are associated with less myelopathy improvement in patients with worse baseline function. Therefore, myelopathy-specific preoperative counseling regarding prognosis for postoperative long-term neurological improvement should include consideration of these individual and surgical factors.

Clinical and radiological outcomes of multilevel cervical laminoplasty versus three-level anterior cervical discectomy and fusion in patients with cervical spondylotic myelopathy.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is one of the most common causes of spinal cord impairment in elderly patients. However, a consensus has yet to be reached on the ideal method of surgical intervention. In this study, we investigated serial changes of radiological findings after three-level anterior cervical discectomy and fusion (ACDF) and multilevel laminoplasty and attempted to identify the radiological parameters affecting long-term clinical outcomes in CSM. METHODS: Of the 152 patients with multilevel CSM treated with three-level ACDF and multilevel laminoplasty, 42 had complete radiological parameters both before and 2 years after surgery (three-level ACDF, 22 patients; multilevel laminoplasty, 20 patients). Radiological parameters included spinal cord signal intensity (SI) changes on magnetic resonance imaging (MRI). Clinical outcomes including the Japanese Orthopaedic Association (JOA) score, neck disability index (NDI), Oswestry disability index (ODI), and 36-Item Short Form Health Survey score were measured. RESULTS: The ACDF group showed significant restoration of segmental lordosis postoperatively (preoperatively: 2.21°, 6 months: 8.37°, P=0.026), and segmental and cervical range of motion (ROM) was markedly reduced and well maintained until the final follow-up (preoperatively: 25.48°, 24 months: 4.35°, P<0.001; preoperatively: 41.71°, 24 months: 20.18°, P<0.001). The recovery rates of the JOA score were 42.85% and 57.40% in the ACDF and laminoplasty groups, respectively, although this difference was not statistically significant. Multivariate regression analysis demonstrated that signal change on MRI significantly affected the recovery rate (P=0.003). The visual analog scale (VAS) score and NDI decreased considerably only in the laminoplasty group, and device complications were confirmed only in the ACDF group (incidence rate =36.5%). CONCLUSIONS: Multilevel laminoplasty showed better radiological and similar clinical outcomes. ACDF had more surgical complications. Spinal cord SI change on preoperative MRI was the independent risk factor for poor clinical outcomes. We recommend laminoplasty instead of three-level ACDF to treat multilevel CSM.

Surgical Strategies for Cervical Deformities Associated With Neuromuscular Disorders.

Neuromuscular disorders (NMDs) are diseases involving the upper and lower motor neurons and muscles. In patients with NMDs, cervical spinal deformities are a very common issue; however, unlike thoracolumbar spinal deformities, few studies have investigated these disorders. The patients with NMDs have irregular spinal curvature caused by poor balance and poor coordination of their head, neck, and trunk. Particularly, cervical deformity occurs at younger age, and is known to show more rigid and severe curvature at high cervical levels. Muscular physiologic dynamic characteristics such as spasticity or dystonia combined with static structural factors such as curvature flexibility can result in deformity and often lead to traumatic spinal cord injury. In addition, postoperative complication rate is higher due to abnormal involuntary movement and muscle tone. Therefore, it is important to control abnormal involuntary movement perioperatively along with strong instrumentation for correction of deformity. Various methods such as botulinum toxin injection, physical therapy, muscle division technique, or intrathecal baclofen pump implant may help control abnormal involuntary movements and improve spinal stability. Surgical management for cervical deformities associated with NMDs requires a multidisciplinary effort and a customized strategy.

Impact of Time Interval between Index Event and Stenting on Periprocedural Risk in Patients with Symptomatic Carotid Stenosis.

OBJECTIVE: The purpose of this study was to evaluate the impact of time interval between index event and stenting on the periprocedural risk of stenting for symptomatic carotid stenosis and to determine the optimal timing of stenting. METHODS: This retrospective study included 491 (322 symptomatic [65.6%] and 169 asymptomatic [34.4%]) patients undergoing carotid stenting. The symptomatic patients were categorized into Day 0-3, 4-7, 8-10, 11-14, 15-21, and >21 groups according to the time interval between index event and stenting. Periprocedural (≤30 days) risk for clinical (any neurological deterioration) and radiological (new infarction on postprocedural diffusion-weighted imaging) events of stenting in each time interval versus asymptomatic stenosis was calculated with logistic regression analysis adjusted for confounders, and provided as odds ratio (OR) and 95% confidence interval (CI). RESULTS: Overall clinical event rate (4.3%) of stenting for symptomatic carotid stenosis was higher than that for asymptomatic stenosis (1.2%; OR, 3.979 [95% CI, 1.093-14.489]; p=0.036). Stenting in Day 0-3 (13.2%; OR, 10.997 [95% CI, 2.333-51.826]; p=0.002) and Day 4-7 (8.3%; OR, 6.775 [95% CI, 1.382-33.227]; p=0.018) was associated with high risk for clinical events. However, the clinical event rates in stenting after 7 days from index event (Day 8-10, 1.8%; Day 11-14, 2.5%; Day 15-21, 0%; Day >21, 2.9%) were not different from that in stenting for asymptomatic stenosis. Overall radiological event rate (55.6%) in symptomatic stenosis was also higher than that in asymptomatic stenosis (35.5%; OR, 2.274 [95% CI, 1.553-3.352]; p<0.001). The high risk for radiological events was maintained in all time intervals (Day 0-3 : 55.3%; OR, 2.224 [95% CI, 1.103-4.627]; p=0.026; Day 4-7 : 58.3%; OR, 2.543 [95% CI, 1.329-4.949]; p=0.005; Day 8-10 : 53.6%; OR, 2.096 [95% CI, 1.138-3.889]; p=0.018; Day 11-14 : 57.5%; OR, 2.458 [95% CI, 1.225-5.021]; p=0.012; Day 15-21 : 55.6%; OR, 2.271 [95% CI, 1.099-4.764]; p=0.028; Day >21 : 54.8%; OR, 2.203 [95% CI, 1.342-3.641]; p=0.002). CONCLUSION: This study showed that as stenting was delayed, the periprocedural risk for clinical events decreased. The clinical event risk was high only in stenting within 7 days and comparable with that for asymptomatic stenosis in stenting after 7 days from index event, although the radiological event risk was not affected by stenting timing. Therefore, our results suggest that delayed stenting after 7 days from symptom onset is a safe strategy for symptomatic stenosis.

Feasibility of the Epiduroscopy Simulator as a Training Tool: A Pilot Study.

Epiduroscopy is a type of spinal intervention that visualizes the epidural space through the sacral hiatus using a fiberoptic scope. However, it is technically difficult to perform compared to conventional interventions and susceptible to complications. Surgery simulator has been shown to be a promising modality for medical education. To develop the epiduroscopy simulator and prove its usefulness for epiduroscopy training, we performed a case-control study including a total of 20 physicians. The participants were classified as the expert group with more than 30 epiduroscopy experiences and the beginner group with less experience. A virtual simulator (EpiduroSIM™, BioComputing Lab, KOREATECH, Cheonan, Republic of Korea) for epiduroscopy was developed by the authors. The performance of the participants was measured by three items: time to reach a virtual target, training score, and number of times the dura and nerve are violated. The training score was better in the expert group (75.00 vs. 67.50; P < 0.01). The number of violations was lower in the expert group (3.50 vs. 4.0; P < 0.01). The realism of the epidural simulator was evaluated to be acceptable in 40%. Participants improved their simulator skills through repeated attempts. The epiduroscopy simulator helped participants understand the anatomical structure and actual epiduroscopy.

Upper Cervical Surgery, Increased Signal Intensity of the Spinal Cord, and Hypertension as Risk Factors for Dyspnea After Multilevel Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Retrospective study. OBJECTIVE: To investigate the associated risk factors for acute respiratory distress after multilevel anterior cervical discectomy and fusion (ACDF) with a focus on the subjective symptom, dyspnea. SUMMARY OF BACKGROUND DATA: Acute respiratory distress after ACDF is a relatively common adverse event, the cause of which is usually soft tissue swelling or hematoma. It can result in serious morbidity and requires careful, focused treatment. METHODS: We reviewed the records of 532 patients (from January 2014 to August 2018) who had undergone multilevel ACDF surgery. Acute respiratory distress was defined as a complaint of dyspnea within 5 postoperative days. We investigated the patients' demographic parameters, comorbidities, and surgical procedure details. We also investigated radiologic parameters, including magnetic resonance imaging (MRI), with special attention to the prevertebral soft tissue thickness at C3 and C6. Statistical analysis was performed using the Student's t test and multiple logistic regression analysis. RESULTS: Out of a total of 484 patients studied after exclusion criteria were applied, 31 patients (6.6%) experienced dyspnea after surgery. We selected 92 patients from the non-dyspnea group and compared them with 31 patients from the dyspnea group. On univariate analysis, upper cervical surgery involving C3, increased cord signal intensity on T2-weighted imaging (T2WI) magnetic resonance imaging (MRI), hypertension, smoking, and prevertebral soft tissue swelling at C3 level on postoperative day 1 were statistically significant factors associated with dyspnea. On logistic regression analysis, upper cervical surgery involving C3, increased cord signal intensity on T2WI MRI, and hypertension were found to be statistically significant variables (P < 0.05). CONCLUSION: Patients undergoing upper cervical surgery involving C3, and having increased cord signal intensity on T2WI MRI and hypertension need to be monitored more carefully for acute respiratory distress after multilevel ACDF. LEVEL OF EVIDENCE: 4.

Extensor muscle-preserving laminectomy in treating multilevel cervical spondylotic myelopathy compared with laminoplasty.

BACKGROUND: Laminectomy and laminoplasty are popularly used in posterior cervical spine surgery but still have involved complications. We aimed to compare the clinical outcomes of microscope-assisted extensor muscle-preserving laminectomy (MA-EMPL) and open-door laminoplasty (ODLP) in treating multilevel cervical spondylotic myelopathy (MCSM). METHODS: A prospective study was designed to enroll twenty patients with MCSM underwent MA-EMPL, and recruit twenty-four patients with MCSM received ODLP (control). Radiographic measurements, outcome indicators including Japanese Orthopedic Association (JOA) score and visual analogue score (VAS) were used to evaluate technical effectiveness. Surgical complications were documented to assess technical safety. RESULTS: Postoperative cervical curvature index and range of neck motion (ROM) were not significantly changed except ROM in ODLP group. Postoperative JOA score and VAS in both groups showed improvements at final follow-up. There was no statistical difference in postoperative neurological recovery rates between two groups (67.6%±17.8% vs. 70.15%±19.6%, P=0.632). However, VAS was significantly lower at postoperative 1 month in MA-EMPL group compared with ODLP group (P<0.001). The incidences of C5 palsy were 0 vs. 16.7% between MA-EMPL group and ODLP group. There was no axial symptom occurred in MA-EMPL group while six patients in ODLP group (0 vs. 25%, P=0.049). In addition, the mean blood loss and hospital stay were lesser in MA-EMPL group compared with ODLP group (P<0.001, P=0.002, respectively). CONCLUSIONS: MA-EMPL is an effective, safe and minimally invasive method in treatment of MCSM. Compared with ODLP, MA-EMPL has advantage to decrease intraoperative blood loss, hospital stay, postoperative VAS and axial symptom, as well as preserve postoperative ROM.

An Epiduroscopy Simulator Based on a Serious Game for Spatial Cognitive Training (EpiduroSIM): User-Centered Design Approach.

BACKGROUND: Performing high-level surgeries with endoscopy is challenging, and hence, an efficient surgical training method or system is required. Serious game-based simulators can provide a trainee-centered educational environment unlike traditional teacher-centered education environments since serious games provide a high level of interaction (feedback that induces learning). OBJECTIVE: This study aimed to propose an epiduroscopy simulator, EpiduroSIM, based on a serious game for spatial cognitive training. METHODS: EpiduroSIM was designed based on a serious game. For spatial cognitive training, the virtual environment of EpiduroSIM was modeled based on a cognitive map. RESULTS: EpiduroSIM was developed considering user accessibility to provide various functions. The experiment for the validation of EpiduroSIM focused on psychological fidelity and repetitive training effects. The experiments were conducted by dividing 16 specialists into 2 groups of 8 surgeons. The group was divided into beginner and expert based on their epiduroscopy experience. The psychological fidelity of EpiduroSIM was confirmed through the training results of the expert group rather than the beginner group. In addition, the repetitive training effect of EpiduroSIM was confirmed by improving the training results in the beginner group. CONCLUSIONS: EpiduroSIM may be useful for training beginner surgeons in epiduroscopy.

Evaluating the differences between 1D, 2D, and 3D occupying ratios in reflecting the JOA score in cervical ossification of the posterior longitudinal ligament.

BACKGROUND: To compare the differences between the one-dimensional (1D) length, two-dimensional (2D) area, and three-dimensional (3D) volume occupying ratios, and to assess the difference between the central and peripheral types of ossification of the posterior longitudinal ligament (OPLL). METHODS: In total, 60 patients were included in this study, and 1D and 2D occupying ratios were obtained using Centricity PACS (GE Healthcare), while a 3D model was created using MIMICS® (Materialise, Leuven, Belgium). Clinical symptoms were measured preoperatively by the modified Japanese Orthopedic Association (JOA) score, short-form health survey (SF-36), and neck disability index. The increased signal intensity (ISI) in T2-weighted MRI was divided into three groups: grade 0, none; grade1, limited to one disc level; or grade2, beyond one disc level. The axial view of spinal canal in CT was vertically divided into three equal parts. Then, the OPLL was categorized by central and peripheral type according to the location of most protruded tip. RESULTS: The 1D, 2D, and 3D occupying ratios had a significantly negative relationship with JOA score (r=-0.503; -0.506; -0.516, respectively). There was little difference in the JOA score between the central and peripheral types (17.15 vs. 17.12, P=0.785). The relationship with MR ISI, according to the central and peripheral type, showed no significant difference. In each multiple regression analysis, the 1D, 2D, and 3D occupying ratios were determined to have more influence on the JOA score (Beta: -0.364, -0.411, -0.462, respectively) than age, sex, most severe level, OPLL type, location type, and MR ISI. CONCLUSIONS: There was no difference between 1D, 2D, and 3D occupying ratios in reflecting the JOA score in cervical OPLL. Also, it is sufficient to reflect the occupying ratio in the clinical outcome without distinguishing between central and peripheral type.

Analysis of Risk Factors Associated with Hospital Readmission Within 360 Days After Degenerative Lumbar Spine Surgery in Elderly Patients.

OBJECTIVE: There is a paucity of studies on readmission rates in elderly patients over a period of 360 days after spinal surgery. METHODS: We identified 1248 patients older than 70 years who underwent degenerative lumbar spinal surgery from November 2005 to April 2015. We reviewed the patients who were readmitted within 360 days and compared them by univariate and multivariate analysis with the nonreadmitted patients for each period of 0-30, 30-90, 90-180, and 180-360 days postoperatively to determine risk factors for hospital readmission. RESULTS: A total of 1248 patients (733 female, 58.7%) were enrolled in the study. The number of readmitted patients was 37 (2.96%), 94 (7.53%), 145 (11.62%), 182 (14.58%), and 213 (17.07%) at 30, 90, 180, 270, and 360 days, respectively. Surgical site-related problems decreased gradually in the first 0-90 days and slightly increased after then. Non-surgical site-related problems gradually increased with time. Logistic multiple regression analysis showed that electrocardiographic abnormalities, male sex, low hemoglobin levels, asthma, heart disease, intensive care unit admission, low alanine aminotransferase level, high body mass index, and high platelet level were risk factors for readmission. CONCLUSIONS: We found that electrocardiographic abnormalities, male sex, low hemoglobin levels, asthma, heart disease, intensive care unit admission, low aspartate aminotransferase level, high body mass index, and high platelet level were risk factors for readmission. As the postoperative observational period became longer, the reasons for readmission tended to be more related to non-surgical site-related problems than to surgical-related problems.

CTCF Regulates Otic Neurogenesis via Histone Modification in the Neurog1 Locus.

The inner ear is a complex sensory organ responsible for hearing and balance. Formation of the inner ear is dependent on tight regulation of spatial and temporal expression of genes that direct a series of developmental processes. Recently, epigenetic regulation has emerged as a crucial regulator of the development of various organs. However, what roles higher-order chromatin organization and its regulator molecules play in inner ear development are unclear. CCCTC-binding factor (CTCF) is a highly conserved 11-zinc finger protein that regulates the three-dimensional architecture of chromatin, and is involved in various gene regulation processes. To delineate the role of CTCF in inner ear development, the present study investigated inner ear-specific Ctcf knockout mouse embryos (Pax2-Cre; Ctcffl/fl ). The loss of Ctcf resulted in multiple defects of inner ear development and severely compromised otic neurogenesis, which was partly due to a loss of Neurog1 expression. Furthermore, reduced Neurog1 gene expression by CTCF knockdown was found to be associated with changes in histone modification at the gene's promoter, as well as its upstream enhancer. The results of the present study demonstrate that CTCF plays an essential role in otic neurogenesis by modulating histone modification in the Neurog1 locus.

Effect of posterior instrumented fusion on three-dimensional volumetric growth of cervical ossification of the posterior longitudinal ligament: a multiple regression analysis.

BACKGROUND CONTEXT: Despite the fact that ossification of posterior longitudinal ligament (OPLL) is a three-dimensional disease, conventional studies have focused mainly on a two-dimensional measurement, and it is difficult to accurately determine the volume of OPLL growth and analyze the factors affecting OPLL growth after posterior decompression (laminoplasty or laminectomy and fusion). PURPOSE: The present study aimed to investigate the factors affecting OPLL volume growth using a three-dimensional measurement. STUDY DESIGN/SETTING: This was a retrospective case study. PATIENT SAMPLE: Eighty-three patients with cervical OPLL who were diagnosed as having multilevel cervical OPLL of more than three levels on cervical computed tomography (CT) scans were retrospectively reviewed from June 1, 1998, to December 31, 2015. OUTCOME MEASURES: The OPLL volume from the C1 vertebrae to the C7 vertebrae was measured on preoperative and the most recent follow-up CT scans. METHODS: Eighty-three patients were retrospectively examined for age, gender, body mass index, hypertension, diabetes, type of OPLL, surgical method, preoperative cervical curvature, and preoperative and postoperative cervical range of motion. Preoperative cervical CT and the most recent follow-up cervical CT scans were converted to Digital Imaging and Communications in Medicine data, and the OPLL volume was three-dimensionally measured using the Mimics program (Materialise, Leuven, Belgium). The OPLL volume growth was analyzed using univariate and multivariate analyses. RESULTS: The average follow-up period was 32.36 (±23.39) months. Patients' mean age was 54.92 (±8.21) years. In univariate analysis, younger age (p=.037) and laminoplasty (p=.012) were significantly associated with a higher mean annual growth rate of OPLL (%/y). In multivariate analysis, only laminoplasty (p=.027) was significantly associated with a higher mean annual growth rate of OPLL (%/y). The mean annual growth rate of OPLL was about seven times faster with laminoplasty (8.00±13.06%/y) than with laminectomy and fusion (1.16±9.23%/y). CONCLUSIONS: Posterior instrumented fusion has the effect of reducing OPLL growth rate compared with motion-preserving laminoplasty. Patients' age and the surgical method need to be considered in surgically managing the multilevel OPLL.

Steroid intracochlear distribution differs by administration method: Systemic versus intratympanic injection.

OBJECTIVE: Steroids have been widely used to treat inner-ear diseases such as sudden sensorineural hearing loss, tinnitus, and Meniere's disease. They can be given via either systemic or intratympanic (IT) injection. The purpose of the present study was to explore differences in intracochlear steroid distribution by the administration method employed (systemic vs. IT injection). STUDY DESIGN: Animal study. METHODS: Twenty-three Sprague-Dawley rats were given fluorescein isothiocyanate-labeled dexamethasone (FITC-DEX) three times (on successive days) via intraperitoneal (IP) or IT injection. Cochlear uptake of FITC-DEX was evaluated via immunohistochemistry and flow cytometry at 6 hours, and 3 and 7 days after the final injection. RESULTS: FITC-DEX uptake was evident in spiral ganglion cells (SGs), the organ of Corti (OC), and the lateral walls (LWs), the basal turns of which were stained relatively prominently in both groups. Animals receiving IP injections exhibited higher FITC-DEX uptakes by the SGs and OC, whereas IT injection triggered higher-level FITC-DEX accumulation by the OC and LWs. Flow cytometry revealed that intracochlear FITC-DEX uptake by IT-injected animals was higher and more prolonged than in animals subjected to IP injections. CONCLUSION: We thus describe differences in cochlear steroid distributions after systemic and IT injections. This finding could help our understanding of the pharmacokinetics of steroids in the cochlea. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:189-194, 2018.

Effect of Iris registration on visual outcome in wavefront-guided LASEK for myopic astigmatism.

PURPOSE: This study aimed to investigate the effect of iris registration (IR) on visual outcomes in wavefront-guided LASEK for myopic astigmatism. METHODS: The retrospective chart review was performed for wavefront-guided LASEK using VISX Star S4 in patients with myopic astigmatism (cylinder ≥ 1.00 diopter[D]). Eyes were divided into IR group (LASEK with IR at the time of surgery) and Non-IR group (LASEK without IR system + failed-IR engagement during LASEK). Visual acuity (VA), astigmatism, higher-order aberration (HOA), and contrast sensitivity were assessed preoperatively and 3 months postoperatively. The IR and Non-IR groups were subcategorized depending on the spherical equivalent (lower myopia ≤-5.00 D vs. higher myopia >-5.00 D) for the comparison of HOA changes. RESULTS: Postoperative uncorrected VAs showed no differences between IR (n = 30) and Non-IR (n = 46). In astigmatic vector analyses, no differences were noted in the mean magnitude of error and the mean angle of error between two groups. There were no differences in postoperative total HOA, spherical aberration (SA), coma, and trefoil between the groups, either. The total HOA and SA increased in both groups, while coma increased only in Non-IR. In higher myopia, ΔRMS of coma was smaller in IR. Preoperative and postoperative total HOA were linearly correlated in Non-IR, but not for IR. Contrast sensitivity of 12 cycles per degree improved in both groups. CONCLUSION: IR had similar outcomes to conventional trackers in wavefront-guided LASEK, with less tendency of inducing coma, especially in higher myopia.

Tumor Necrosis Factor-producing T-regulatory Cells Are Associated With Severe Liver Injury in Patients With Acute Hepatitis A.

BACKGROUND AND AIMS: CD4+CD25+Foxp3+ T-regulatory (Treg) cells control immune responses and maintain immune homeostasis. However, under inflammatory conditions, Treg cells produce cytokines that promote inflammation. We investigated production of tumor necrosis factor (TNF) by Treg cells in patients with acute hepatitis A (AHA), and examined the characteristics of these cells and association with clinical factors. METHODS: We analyzed blood samples collected from 63 patients with AHA at the time of hospitalization (and some at later time points) and 19 healthy donors in South Korea. Liver tissues were collected from patients with fulminant AHA during liver transplantation. Peripheral blood mononuclear cells were isolated from whole blood and lymphocytes were isolated from liver tissues and analyzed by flow cytometry. Cytokine production from Treg cells (CD4+CD25+Foxp3+) was measured by immunofluorescence levels following stimulation with anti-CD3 and anti-CD28. Epigenetic stability of Treg cells was determined based on DNA methylation patterns. Phenotypes of Treg cells were analyzed by flow cytometry and an RORγt inhibitor, ML-209, was used to inhibit TNF production. Treg cell suppression assay was performed by co-culture of Treg-depleted peripheral blood mononuclear cells s and isolated Treg cells. RESULTS: A higher proportion of CD4+CD25+Foxp3+ Treg cells from patients with AHA compared with controls produced TNF upon stimulation with anti-CD3 and anti-CD28 (11.2% vs 2.8%). DNA methylation analysis confirmed the identity of the Treg cells. TNF-producing Treg cells had features of T-helper 17 cells, including up-regulation of RORγt, which was required for TNF production. The Treg cells had reduced suppressive functions compared with Treg cells from controls. The frequency of TNF-producing Treg cells in AHA patients' blood correlated with their serum level of alanine aminotransferase. CONCLUSIONS: Treg cells from patients with AHA have altered functions compared with Treg cells from healthy individuals. Treg cells from patients with AHA produce higher levels of TNF, gain features of T-helper 17 cells, and have reduced suppressive activity. The presence of these cells is associated with severe liver injury in patients with AHA.