The iterative implementation of a comprehensive enhanced recovery after surgery protocol in all spinal surgery in Korea: a comparative analysis of clinical outcomes and medical costs between primary spinal tumors and degenerative spinal diseases.

OBJECTIVE: Most studies on the enhanced recovery after surgery (ERAS) protocol in spine surgery have focused on patients with degenerative spinal diseases (DSDs), resulting in a lack of evidence for a comprehensive ERAS protocol applicable to patients with primary spine tumors (PSTs) and other spinal diseases. The authors had developed and gradually adopted components of the comprehensive ERAS protocol for all spine surgical procedures from 2003 to 2011, and then the current ERAS protocol was fully implemented in 2012. This study aimed to evaluate the impact and the applicability of the comprehensive ERAS protocol across all spine surgical procedures and to compare outcomes between the PST and DSD groups. METHODS: Adult spine surgical procedures were conducted from 2003 to 2021 at the Seoul National University Hospital Spine Center and data were retrospectively reviewed. The author divided the study periods into the developing ERAS (2003-2011) and post-current ERAS (2012-2021) periods, and outcomes were compared between the two periods. Surgical procedures for metastatic cancer, infection, and trauma were excluded. Interrupted time series analysis (ITSA) was used to assess the impact of the ERAS protocol on medical costs and clinical outcomes, including length of stay (LOS) and rates of 30-day readmission, reoperation, and surgical site infection (SSI). Subgroup analyses were conducted on the PST and DSD groups in terms of LOS and medical costs. RESULTS: The study included 7143 surgical procedures, comprising 1494 for PSTs, 5340 for DSDs, and 309 for other spinal diseases. After ERAS protocol implementation, spine surgical procedures showed significant reductions in LOS and medical costs by 22% (p = 0.008) and 22% (p < 0.001), respectively. The DSD group demonstrated a 16% (p < 0.001) reduction in LOS, whereas the PST group achieved a 28% (p < 0.001) reduction, noting a more pronounced LOS reduction in PST surgical procedures (p = 0.003). Medical costs decreased by 23% (p < 0.001) in the DSD group and 12% (p = 0.054) in the PST group, with a larger cost reduction for DSD surgical procedures (p = 0.021). No statistically significant differences were found in the rates of 30-day readmission, reoperation, and SSI between the developing and post-current ERAS implementation periods (p = 0.65, p = 0.59, and p = 0.52, respectively). CONCLUSIONS: Comprehensive ERAS protocol implementation significantly reduced LOS and medical costs in all spine surgical procedures, while maintaining comparable 30-day readmission, reoperation, and SSI rates. These findings suggest that the ERAS protocol is equally applicable to all spine surgical procedures, with a more pronounced effect on reducing LOS in the PST group and on reducing medical costs in the DSD group.

Surgical treatment of spondylolisthesis by oblique lumbar interbody fusion and transpedicular screw fixation: Comparison between conventional double position versus navigation-assisted single lateral position.

BACKGROUND AND OBJECTIVES: Oblique lumbar interbody fusion (OLIF) procedures involve anterior insertion of interbody cage in lateral position. Following OLIF, insertion of pedicle screws and rod system is performed in a prone position (OLIF-con). The location of the cage is important for restoration of lumbar lordosis and indirect decompression. However, inserting the cage at the desired location is difficult without reduction of spondylolisthesis, and reduction after insertion of interbody cage may limit the amount of reduction. Recent introduction of spinal navigation enabled both surgical procedures in one lateral position (OLIF-one). Therefore, reduction of spondylolisthesis can be performed prior to insertion of interbody cage. The objective of this study was to compare the reduction of spondylolisthesis and the placement of cage between OLIF-one and OLIF-con. METHODS: We retrospectively reviewed 72 consecutive patients with spondylolisthesis for this study; 30 patients underwent OLIF-one and 42 underwent OLIF-con. Spinal navigation system was used for OLIF-one. In OLIF-one, the interbody cage was inserted after reducing spondylolisthesis, whereas in OLIF-con, the cage was inserted before reduction. The following parameters were measured on X-rays: pre- and postoperative spondylolisthesis slippage, reduction degree, and the location of the cage in the disc space. RESULTS: Both groups showed significant improvement in back and leg pains (p < .05). Transient motor or sensory changes occurred in three patients after OLIF-con and in two patients after OLIF-one. Pre- and postoperative slips were 26.3±7.7% and 6.6±6.2% in OLIF-one, and 23.1±7.0% and 7.4±5.8% in OLIF-con. The reduction of slippage was 74.4±6.3% after OLIF-one and 65.4±5.7% after OLIF-con, with a significant difference between the two groups (p = .04). The cage was located at 34.2±8.9% after OLIF-one and at 42.8±10.3% after OLIF-con, with a significant difference between the two groups (p = .004). CONCLUSION: Switching the sequence of surgical procedures with OLIF-one facilitated both the reduction of spondylolisthesis and the placement of the cage at the desired location.

Is laminectomy necessary for C1-C2 epidural schwannomas?

PURPOSE: Spinal schwannomas often require laminectomy for gross total resection. However, laminectomy may not be necessary due to the unique anatomy of epidural schwannomas at the C1-2 level, even with the intradural part. This study aimed to determine the need for laminectomy by comparing factors between patients who underwent laminectomy and those who did not and to identify the benefits of not performing laminectomy. METHODS: Fifty patients with spinal epidural schwannoma confined to C1-C2 level were retrospectively collected and divided into groups based on whether laminectomy was intended and performed. In all cases where laminectomy was conducted, patients underwent laminoplasty using microplate-and-screws, which deviates from the conventional laminectomy approach. Tumor characteristics were compared, and a cut-off value for laminectomy was determined. Outcomes were compared between groups, and factors influencing laminectomy were identified. Postoperative changes in cervical curves were measured. RESULTS: The diameter of the intradural part of the tumor was significantly longer in the laminectomy performed group, with a 14.86 mm cut-off diameter requiring laminectomy. Recurrence rates did not differ significantly between groups. Surgery time was substantially longer for the laminectomy performed group. No significant changes were observed in Cobb's angles of Oc-C2, C1-C2, and Oc-C1 before and after surgery. CONCLUSION: The study showed that the diameter of the intradural part of the tumor influenced the decision to perform laminectomy for removing epidural schwannomas at C1-C2. The cut-off value of the diameter of the intradural part of the tumor for the laminectomy was 14.86 mm. Not performing laminectomy can be a viable option with no significant differences in removal and complication rates.

Impact of C3 laminectomy on cervical sagittal alignment in cervical laminoplasty: a prospective, randomized controlled trial comparing clinical and radiological outcomes between C3 laminectomy with C4-C6 laminoplasty and C3-C6 laminoplasty.

BACKGROUND CONTEXT: C3 laminectomy in cervical laminoplasty is a modified laminoplasty technique that can preserve the semispinalis cervicis muscle attached to the C2 spinous process. Several previous studies have shown that this technique can lead to better outcomes of postoperative axial neck pain and C2-C3 range of motion (ROM) than conventional cervical laminoplasty. However, there is still a lack of understanding of total and proportional postoperative cervical sagittal alignment outcomes. PURPOSE: To assess the effects of C3 laminectomy in cervical laminoplasty on postoperative cervical alignment and clinical outcomes. DESIGN: A single-center, patient-blinded, randomized controlled trial. PATIENT SAMPLE: We included consecutive 126 patients diagnosed with cervical spondylotic myelopathy (CSM) or ossification of posterior longitudinal ligament (OPLL) who were scheduled for cervical laminoplasty from March 2017 to January 2020. OUTCOME MEASURES: The primary outcome measures were C2-C7 Cobb angle (CA) and neck disability index (NDI). Secondary outcomes measures included other clinical outcomes and radiographic parameters including segmental Cobb angle and presence of C2-C3 interlaminar fusion. METHODS: Patients were randomly allocated to either the C3 laminectomy with C4-C6 laminoplasty group (LN group) or the C3-C6 laminoplasty group (LP group) at a 1:1 ratio. Laminoplasty was performed using a unilateral open-door technique and stabilized with titanium mini plates. A linear mixed model analysis was employed to examine the longitudinal data from postoperative 1-year through 3-year. Additional analysis between three types of cervical sagittal alignment morphology was done. RESULTS: Among 122 patients who were randomly allocated to one of two groups (LN group, n=61; LP group, n=61), modified intent-to-treat analysis was done for 109 patients (LN group, n=51, LP group, n=58) who had available at least a year of postoperative data. Postoperative C2-C7 CA was not significantly different between the two groups. However, NDI was significantly different between the two groups (12.8±1.0 in the LN group vs 8.6±1.0 in LP group, p=.005), which exceeded the minimum clinically important difference (MCID). The postoperative C2-C3 CA was significantly greater in the LN group (7.1±0.5° in LN group vs 3.2±0.5° in LP group, p<.001) while C4-C7 CA was significantly smaller in the LN group (3.9±0.8° in LN group vs 7.7±0.7° in LP group, p<.001) with greater cSVA in the LN group (31.6±1.4 mm in LN group vs 25.5±1.3 mm in LP group at postoperative 3-year, p=.002). Postoperative Euro-Quality of Life-5 Dimension (EQ-5D), numerical rating scores for neck pain (NRS-N) were significantly better in the LP group than in the LN group (all p<.05) and only EQ-5D surpassed the MCID. The C2-C3 fusion rate was significantly different between the LN group (9.8%) and the LP group (44.8%) (p<.001). The LN group showed a higher prevalence of a specific cervical alignment morphology characterized by a sigmoid shape with proximal lordosis and distal kyphosis (S curve). This S curve demonstrated significantly unfavorable outcomes across multiple outcome variables. CONCLUSION: The impact of C3 laminectomy in cervical laminoplasty on postoperative kyphosis among patients with CSM or OPLL did not significantly differ from that of C3-C6 laminoplasty. However, C3 laminectomy in cervical laminoplasty might result in an unfavorable clinical outcome with an unbalanced cervical sagittal alignment characterized by a sigmoid shape with proximal lordosis and distal kyphosis.

The Optimal Time between Embolization and Surgery for Hypervascular Spinal Metastatic Tumors : A Systematic Review and Meta-Analysis.

OBJECTIVE: Preoperative transarterial embolization (TAE) of tumor feeders in hypervascular spine metastasis is known to reduce intraoperative estimated blood loss (EBL) during surgery. The effect of TAE varies for several reasons, and one controllable factor is the timing between embolization and surgery. However, the adequate timing remains unclear. This study aimed to evaluate the timing and other factors that reduce EBL in spinal metastasis surgery through a meta-analysis. METHODS: A comprehensive database search was performed to identify direct comparative studies of EBL stratified by the timing of surgery after TAE for spinal metastasis. EBL was analyzed according to the timing of surgery and other factors. Subgroup analyses were also performed. The difference in EBL was calculated as the mean difference (MD) and 95% confidence interval (CI). RESULTS: Among seven studies, 196 and 194 patients underwent early and late surgery after TAE, respectively. The early surgery was defined as within 1-2 days after TAE, while the late surgery group received surgery later. Overall, the MD in EBL was not different according to the timing of surgery (MD, 86.3 mL; 95% CI, -95.5 to 268.1 mL; p=0.35). A subgroup analysis of the complete embolization group demonstrated that patients who underwent early surgery within 24 hours after TAE had significantly less bleeding (MD, 233.3 mL; 95% CI, 76.0 to 390.5 mL; p=0.004). In cases of partial embolization, EBL was not significantly different regardless of the time interval. CONCLUSION: Complete embolization followed by early spinal surgery within 24 hours may reduce intraoperative bleeding for the patients with hypervascular spinal metastasis.

Nationwide sample data analysis of additional surgery rate after anterior or posterior cervical spinal surgery.

Surgical outcomes of degenerative cervical spinal disease are dependent on the selection of surgical techniques. Although a standardized decision cannot be made in an actual clinical setting, continued education is provided to standardize the medical practice among surgeons. Therefore, it is necessary to supervise and regularly update overall surgical outcomes. This study aimed to compare the rate of additional surgery between anterior and posterior surgeries for degenerative cervical spinal disease using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) nationwide patient database. The NHIS-NSC is a population-based cohort with about a million participants. This retrospective cohort study included 741 adult patients (> 18 years) who underwent their first cervical spinal surgery for degenerative cervical spinal disease. The median follow-up period was 7.3 years. An event was defined as the registration of any type of cervical spinal surgery during the follow-up period. Event-free survival analysis was used for outcome analysis, and the following factors were used as covariates for adjustment: location of disease, sex, age, type of insurance, disability, type of hospital, Charles comorbidity Index, and osteoporosis. Anterior cervical surgery was selected for 75.0% of the patients, and posterior cervical surgery for the remaining 25.0%. Cervical radiculopathy due to foraminal stenosis, hard disc, or soft disc was the primary diagnosis in 78.0% of the patients, and central spinal stenosis was the primary diagnosis in 22.0% of them. Additional surgery was performed for 5.0% of the patients after anterior cervical surgery and 6.5% of the patients after posterior cervical surgery (adjusted subhazard ratio, 0.83; 95% confidence interval, 0.40-1.74). The rates of additional surgery were not different between anterior and posterior cervical surgeries. The results would be helpful in evaluating current practice as a whole and adjusting the health insurance policy.

Long-term Follow-up Results of Reconstructive Laminoplasty With L-shaped Leibinger Mini-plate for Posterior Approach in the Treatment of Intraspinal Tumor Surgery.

OBJECTIVE: Laminoplasty using mini-plates is one of the most common surgical techniques in surgery for intraspinal pathologies. However, limited are present in the literature. The aim of this study was to determine its long-term clinical and radiologic outcome, specifically using an L-shaped mini-plate. METHODS: Patients who underwent surgery for spinal intradural pathology from January 2008 to December 2019 were retrospectively reviewed. Those who received laminoplasty using the Leibinger mini-plate and were followed for more than 2 years were included. Patient demographics and clinical and radiographic data were reviewed and analyzed. A total of 117 patients (male:female = 47:70; mean age 50.9 years, range 16-92 years) were included, and mean follow-up period was 50.3 months (range 24-151 months). RESULTS: The most common pathology was schwannoma (n = 66, 56.4%) followed by meningioma (n = 30, 25.6%). Gross total resection was achieved in 82.9% (n = 97). Clinical outcomes at last follow-up were mostly good and excellent (n = 95, 81.2%). Computed tomography at the postoperative 1-year follow-up were available in 32 patients (27.4%) and the overall fusion rate was 89.3% (50 of 56 laminae). The fusion rate was significantly lower in the cervical spine compared to other locations (50% vs. thoracic [100%], lumbar [85.7%], P < 0.002). No displacement of laminae or postoperative spinal deformity were observed throughout the follow-up. CONCLUSIONS: Laminoplasty using L-shape Leibinger mini-plates had an 89.3% fusion rate, and no displacement of the re-attached laminae was observed. We think it is a safe and feasible option in surgeries for intraspinal pathologies.

Involvement of the vertebral artery in hemifacial spasm: clinical features and surgical strategy.

The vertebral artery (VA)-involved hemifacial spasm (HFS) has distinctive clinical features and performing microvascular decompression (MVD) is challenging. We described the clinical presentations of VA-involved HFS and the outcomes of MVD using the interposition method. Between January 2008 and March 2015, MVD was performed in 271 patients with VA-involved HFS. Demographic characteristics, preoperative severity, intraoperative findings, spasm-free outcome, and complications were retrospectively evaluated. A control group of 1500 consecutive patients with non-VA-involved HFS was enrolled. VA-involved HFS was associated with older age (p < 0.001), less female predominance (p < 0.001), more left-sided predominance (p < 0.001), and rapid symptom progression before MVD (p < 0.001). The Teflon Fulcrum method allowed intraoperative identification of the neurovascular compression site in 92.6% of the cases, and showed more severe indentation on the facial nerve (p < 0.001). Changes in the brainstem auditory evoked potentials during MVD (p < 0.001) and postoperative non-serviceable hearing loss (p < 0.001) were more frequent in patients with VA-involved than in non-VA-involved HFS. The spasm-free outcome and overall complication rates after MVD were not significantly different between the groups. VA-involved HFS has distinctive clinical features and poses a major surgical challenge for MVD success. The interposition method is a feasible surgical strategy in VA-involved HFS.

Screening for Normal Cognition, Mild Cognitive Impairment, and Dementia with the Korean Dementia Screening Questionnaire.

OBJECTIVE: The Korean Dementia Screening Questionnaire (KDSQ) is an informant-based instrument used to screen for cognitive dysfunction. However, its ability to only dichotomously discriminate between dementia and normal cognition has been previously investigated. This study investigated the ability of the KDSQ to classify not only dichotomous but also multiple stages of cognitive dysfunction. METHODS: We examined 582 participants. Receiver operating characteristic (ROC) curves were used to determine dichotomous classification parameters. Multi-category ROC surfaces were evaluated to classify the three stages of cognitive dysfunction. RESULTS: Dichotomous classification using the ROC curve analyses showed that the area under the curve was 0.92 for dementia for subjects without dementia and 0.96 for dementia in controls. Simultaneous multi-category classification analyses showed that the volume under the ROC surface (VUS) was 0.57 and that the derived optimal cut-off points were 2 and 8 for controls, MCI, and dementia. The estimated Youden index for the KDSQ was 0.48, and the derived optimal cut-off points were 5 and 10. The overall classification accuracy of the VUS and Youden index was 61.2% and 58.6%, respectively. CONCLUSION: The KDSQ is useful for classifying dichotomous and multi-category stages of cognitive dysfunction.

C-H activation guided by aromatic N-H ketimines: synthesis of functionalized isoquinolines using benzyl azides and alkynes.

Aromatic N-H ketimines were in situ generated from various benzylic azides by ruthenium catalysis for the subsequent Rh-catalyzed annulation reaction with alkynes to give the corresponding isoquinolines. In contrast to conventional synthetic methods for aromatic N-H ketimines, our protocol works under mild and neutral conditions, which enabled the synthesis of isoquinolines having various functionalities such as carbonyl, ester, alkenyl, and ether groups. In addition, the imidates generated from α-azido ethers were successfully used for the synthesis of 1-alkoxyisoquinolines.

Novel catalyst system for hydrostannation of alkynes.

A catalyst system was developed for the highly regio- and stereoselective hydrostannation of a range of alkynes with tributylstannane under mild conditions. The active catalytic species was generated from a stable diruthenium complex by illuminating household fluorescent light (30 W) at room temperature.

An atlas of combinatorial transcriptional regulation in mouse and man.

Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.

The folding and evolution of multidomain proteins.

Analyses of genomes show that more than 70% of eukaryotic proteins are composed of multiple domains. However, most studies of protein folding focus on individual domains and do not consider how interactions between domains might affect folding. Here, we address this by analysing the three-dimensional structures of multidomain proteins that have been characterized experimentally and observe that where the interface is small and loosely packed, or unstructured, the folding of the domains is independent. Furthermore, recent studies indicate that multidomain proteins have evolved mechanisms to minimize the problems of interdomain misfolding.

Divergence of interdomain geometry in two-domain proteins.

For homologous protein chains composed of two domains, we have determined the extent to which they conserve (1) their interdomain geometry and (2) the molecular structure of the domain interface. This work was carried out on 128 unique two-domain architectures. Of the 128, we find 75 conserve their interdomain geometry and the structure of their domain interface; 5 conserve their interdomain geometry but not the structure of their interface; and 48 have variable geometries and divergent interface structure. We describe how different types of interface changes or the absence of an interface is responsible for these differences in geometry. Variable interdomain geometries can be found in homologous structures with high sequence identities (70%).