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In terms of harmonic expectancy, compared to an expected dominant-to-tonic and an unexpected dominant-to-supertonic, a dominant-to-submediant is a less unexpected cadence, the perception of which may depend on the subject's musical expertise. The present study investigated how aforementioned 3 different cadences are processed in the networks of bilateral inferior frontal gyri (IFGs) and superior temporal gyri (STGs) with magnetoencephalography. We compared the correct rate and brain connectivity in 9 music-majors (mean age, 23.5 ± 3.4 years; musical training period, 18.7 ± 4.0 years) and 10 non-music-majors (mean age, 25.2 ± 2.6 years; musical training period, 4.2 ± 1.5 years). For the brain connectivity, we computed the summation of partial directed coherence (PDC) values for inflows/outflows to/from each area (sPDCi/sPDCo) in bilateral IFGs and STGs. In the behavioral responses, music-majors were better than non-music-majors for all 3 cadences (p < 0.05). However, sPDCi/sPDCo was prominent only for the dominant-to-submediant in the left IFG. The sPDCi was more strongly enhanced in music-majors than in non-music-majors (p = 0.002, Bonferroni corrected), while the sPDCo was vice versa (p = 0.005, Bonferroni corrected). Our data show that music-majors, with higher musical expertise, are better in identifying a less unexpected cadence than non-music-majors, with connectivity changes centered on the left IFG., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Although health care providers are required to sustain care in difficult circumstances, some patients challenge this principle. Evoking compassion seems likely to be helpful in such situations. This research aimed to evaluate whether inducing compassion in health care providers might mitigate disengagement with patients who have challenging presenting features such as those with disgusting symptoms and/or are to blame for their own health problems., Design: An online experimental study with clinical health care providers., Methods: Medical students (n = 219) and qualified health care professionals (n = 108) took part in an online experiment. Participants were randomized to view a slideshow of either neutral images (control) or compassion-inducing images (compassion condition) and were then presented with a series of patient vignettes where presenting problems systematically varied on patient responsibility and disgusting symptoms. Engagement was assessed by asking participants how caring they felt, how much they would want to help, how challenging it would be, and whether they would wear a mask., Results: Participants reported less engagement with patients who were responsible for their illness and who presented with disgusting symptoms. Induced compassion offset disengagement and qualified health professionals were more caring and willing to help patients than medical students. The compassion induction eliminated some differences between experienced and trainee clinicians., Conclusions: This research demonstrates that disgust and patient responsibility impacts clinical engagement and that medical students are more impacted by such scenarios than qualified health providers. Inducing compassion may help to mitigate these differences, and further investigation into strategies that foster engagement with difficult patients is warranted. Statement of contribution What is already known on the subject? Health care providers are required to sustain care across all patients; however, some patients are more difficult to engage with than others. Clinical engagement appears to be impacted when patients present with disgusting symptoms and/or are to blame for their own health problems. What does this study add? This work reports on a vignette-based study that shows that disgusting symptoms and patient responsibility impact self-reported measures of clinical engagement in response to patient scenarios. Qualified health care providers are less likely to disengage in these situations than medical students. A very brief online induction of compassion has potential to mitigate differences between trained professionals and students., (© 2019 The British Psychological Society.)

Study Design: A retrospective cohort study of a nationwide sample database., Objective: The objective of the present study was to compare the long-term incidence of reoperation for lumbar herniated intervertebral disc disease (HIVD) after major surgical techniques (open discectomy, OD; laminectomy; percutaneous endoscopic lumbar discectomy, PELD; fusion)., Summary of Background Data: HIVD is a major spinal affliction; if the disease is intractable, surgery is recommended. Considering both the aging of patients and the chronicity of lumbar degenerative disease, the effect of surgical treatment for the lumbar spine should be durable for as long as possible., Methods: The National Health Insurance Service-National Sample Cohort (NHIS-NSC) of Republic of Korea was utilized to establish a cohort of adult patients (N = 1856) who underwent first surgery for lumbar HIVD during 2005 to 2007. Patients were followed for 8 to 10 years. Considering death before reoperation as a competing event, reoperation hazards were compared among surgical techniques using the Fine and Gray regression model after adjustment for age, gender, Charlson comorbidity score, osteoporosis, diabetes, the severity of disability, insurance type, and hospital type., Results: The overall cumulative incidences of reoperation were 4% at 1 year, 6% at 2 years, 8% at 3 years, 11% at 5 years, and 16% at 10 years. The cumulative incidences of reoperation were 16%, 14%, 16%, and 10% after OD, laminectomy, PELD, and fusion, respectively, at 10 years postoperation, with no difference among the surgical techniques. However, the distribution of reoperation types was significantly different according to the first surgical technique (P < 0.01). OD was selected as the reoperation surgical technique in 80% of patients after OD and in 81% of patients after PELD., Conclusion: The probability of reoperation did not differ among OD, laminectomy, PELD, and fusion during the 10-year follow-up period. However, OD was the most commonly used technique in reoperation., Level of Evidence: 4.

Objective: Theoretically, the optimal approach is determined by the status of ossification of the posterior longitudinal ligament (OPLL) and sagittal alignment. However, there have long been disputes about the optimum surgical approach of OPLL. This study is to compare risk-effectiveness between anterior decompression and fusion (ADF) and laminoplasty and laminectomy with fusion (LP/LF) for the patient with cervical myelopathy due to multilevel cervical OPLL., Methods: We searched core databases, and compared complication and outcomes between ADF and LP/LF for patients with multiple OPLL for the cervical spine. The incidence of complications such as neurologic deterioration, C5 palsy, and dura tear was assessed. Changes in JOA score between baseline and final evaluations were assessed for 2 groups. The minimal clinically important difference (MCID) was utilized for evaluating clinical significance. We calculated Peto odds ratio (POR) and mean difference for the incidence and continuous variables, respectively., Results: We included data from 21 articles involving 3,872 patients with cervical myelopathy with OPLL. Major neurologic deficits such as paraplegia, quadriplegia developed 2.17% in the ADF group and 1.11% in the LP/LF group, and POR was 2.16. Mean difference of JOA score improvement of 2 groups was 1.30, and the mean difference showed a statistical significance. However, 1.3 points of JOA improvement cannot reach 2.5 points of the MCID., Conclusion: Anterior surgery often led to rare but critical complications, and the difference of neurological improvement between 2 groups was below a clinically meaningful level. Posterior surgeries may be appropriate in the treatment of multilevel cervical myelopathy with OPLL.

Objective: C5 palsy is a severe complication after cervical spine surgery, the pathophysiology of which remains unclear. This multicenter study investigated the incidence of C5 palsy following cervical spine surgery in Korea., Methods: We conducted a retrospective multicenter study involving 21 centers from the Korean Cervical Spine Study Group. The inclusion criteria were cervical spine surgery patients between 2012 and 2016, excluding cases of neck surgery. In patients with C5 palsy, the operative methods, disease category, onset time of C5 palsy, recovery time, C5 manual muscle testing (MMT) grade, and post-C5 palsy management were analyzed., Results: We collected 15,097 cervical spine surgery cases from 21 centers. C5 palsy occurred in 88 cases (0.58%). C5 palsy was more common in male patients (p=0.019) and after posterior approach procedures (p<0.001). C5 palsy usually occurred within 3 days after surgery (77 of 88, 87.5%) and most C5 palsy patients recovered within 6 months (51 of 88, 57.95%). Thirty C5 palsy patients (34.09%) had motor weakness, with an MMT grade≤2. Only four C5 palsy patients (4.5%) did not recover during follow-up. Posterior cervical foraminotomy was performed in 7 cases (7.95%), and steroids were used in 56 cases (63.63%). Twenty-six cases (29.55%) underwent close observation only., Conclusion: The overall incidence of C5 palsy was relatively low (0.58%). C5 palsy was more common after posterior cervical surgery and in male patients. C5 palsy usually developed within 3 days after surgery, and more than half of patients with C5 palsy recovered within 6 months.

Objective: The reoperation rate after lumbar degenerative disease surgery is low. It is difficult to find statistical differences in reoperation rates according to the different diagnoses of lumbar degenerative diseases. National population-based database overcomes the statistical problem by its large cohorts with longitudinal follow-up in a nation. The purpose was to compare the reoperation rates after single-level lumbar spinal posterior decompression and fusion surgeries depending on different preoperative diagnoses of lumbar degenerative disease., Patients and Methods: We used the Korean Health Insurance Review & Assessment Service national database. The study population was the patients with a diagnosis of a degenerative lumbar disease who underwent single-level decompression and fusion from January 1, 2011, to June 30, 2016. We classified the patients into one of three groups based on diagnosis codes of lumbar disc herniation, spondylolisthesis, or spinal stenosis. A reoperation was defined as repeated decompression and fusion. We considered age, sex, the presence of diabetes, osteoporosis, associated comorbidities, and hospital types as potential confounding factors., Results: The reoperation rate was higher in patients with spinal stenosis than in those with lumbar disc herniation. However, there was no difference in the reoperation rate between the patients with lumbar disc herniation and those with spondylolisthesis. Male gender and hospital type were risk factors for reoperation., Conclusion: The incidence of reoperation was dependent on the diagnostic subgroups of lumbar degenerative diseases. This information can help surgeons accurately communicate with their patients and enhance the preoperative informed consent process., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: We aim to investigate using finite element model (FEM) whether the use of a cross-link is a risk factor for rod fracture at the pedicle subtraction osteotomy (PSO) site., Methods: The geometry and dimensions of the FEM were obtained from a high-resolution computed tomography scan data of a 65 years old female patient with spinal sagittal imbalance. The intact model was modified to place PSO on the L4 spine. A cross-link was placed at the PSO site. A multisegment spinal fusion model from L1 to the pelvis was used to compare and analyze the peak von Mises stress (PVMS) values of the implants. A compressive follower load of 400 N was added to the validated intact lumbar spinal model in the follower load path direction., Results: After PSO surgery, the PVMS of the rod was significantly increased during flexion and extension at the PSO site. With the cross-link at the PSO site, the PVMS of the rod was further significantly increased during flexion and extension., Conclusion: The cross-link at the PSO site increased the risk of rod facture, especially during flexion and extension stress., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Objectives: Treatment with mesenchymal stem cells (MSC) in spinal cord injury (SCI) has been highlighted as therapeutic candidate for SCI. Although astrogliosis is a major phenomenon after SCI, the role of astrogliosis is still controversial. In this study, we determined whether acute transplantation of MSC improves the outcome of SCI through modulating astrogliosis., Methods: Bone marrow derived rat MSCs were induced neural differentiation and transplanted after acute SCI rats. Matrix metalloproteinase (MMP) and neuro-inflammatory pathway were analyzed for acute astrogliosis at 1, 3 and 7 d after SCI in RT-PCR- and western blot analysis. Functional outcome was assessed serially at postoperative 1 d and weekly for 4 weeks. Histopathologic analysis was undertaken at 7 and 28 d following injury in immunohistochemistry., Results: Transplantation of MSCs decreased IL-1 α , CXCL-2, CXCL-10, TNF- α and TGF- β in a rat model of contusive SCI. Protein level of NF- κ B p65 was slightly decreased while level of STAT-3 was increased. In immunohistochemistry, MSC transplantation increased acute astrogliosis whereas attenuated scar formation with increased sparing white matter of spinal cord lesions. In RT-PCR analysis, mRNA levels of MMP2 was significantly increased in MSC transplanted rats. In BBB locomotor scale, the rats of MSC treated group exhibited improvement of functional recovery., Conclusions: Transplantation of MSC reduces the inflammatory reaction and modulates astrogliosis via MMP2/STAT3 pathway leading to improve functional recovery after SCI in rats.

Objective: There is a lack of knowledge regarding whether decompression is necessary in treating patients with epidural spinal cord compression (ESCC) grade 2. The purpose of this study was to compare the outcomes of minimally invasive surgery (MIS) without decompression and conventional open surgery (palliative laminectomy) for patients with hepatocellular carcinoma (HCC) spinal metastasis of ESCC grade 2., Methods: Patients with HCC spinal metastasis requiring surgery were retrospectively reviewed. Patients with ESCC grade 2, medically intractable mechanical back pain, a Nurick grade better than 3, 3-6 months of life expectancy, Tomita score ≥5, and Spinal Instability Neoplastic Score ≥7 were included. Patients with neurological deficits, other systemic illnesses and less than 1 month of life expectancy were excluded. Thirty patients were included in the study, including 17 in the open surgery group (until 2008) and 13 in the MIS group (since 2009)., Results: The MIS group had a significantly shorter operative time (94.2±48.2 minutes vs. 162.9±52.3 minutes, p=0.001), less blood loss (140.0±182.9 mL vs. 1534.4±1484.2 mL, p=0.002), and less post-operative intensive care unit transfer (one patient vs. eight patients, p=0.042) than the open surgery group. The visual analogue scale for back pain at 3 months post-operation was significantly improved in the MIS group than in the open surgery group (3.0±1.2 vs. 4.3±1.2, p=0.042). The MIS group had longer ambulation time (183±33 days vs. 166±36 days) and survival time (216±38 days vs. 204±43 days) than the open surgery group without significant difference (p=0.814 and 0.959, respectively)., Conclusion: MIS without decompression would be a good choice for patients with HCC spinal metastasis of ESCC grade 2, especially those with limited prognosis, mechanical instability and no neurologic deficit.

Background: The overall incidence of iatrogenic vertebral artery injury (IVAI) in cervical spine surgeries (CSSs) is reported to be 0.07%-1.4%. Although IVAI occurred during C1-2 fusion, there is no accurate information regarding the surgery-specific risk of IVAI. This study aimed to stratify incidence of IVAI by surgical method and evaluate the correlation between IVAI and its sequelae., Methods: This retrospective, multicenter study involved clinical and radiologic evaluations for IVAI. All CSSs performed between 2012 and 2016 were included; neck mass excision and pain intervention were excluded. Patient characteristics, diagnosis, surgical technique, complications, and presence of IVAI were collected. In IVAI cases, technique details, characteristics, and sequelae were investigated., Results: This study included 14,722 patients with 15,582 CSSs in 21 centers. IVAIs were identified in 13 (0.08%) patients. Surgery-specific incidence of IVAI was 1.35% in cases involving C1-2 posterior fixation and 0.20% in cases involving C3-6 posterior fixation. Common injury mechanisms were screw-in (31%) and high-speed drilling (23%). Screw-related IVAI occurred in 9 (69%) patients, and IVAI of the C1 lateral mass and C2 pedicle screws occurred in 4 and 3 patients, respectively. Of 13 cases of IVAI, 3 (23%) involved cerebellar or stem infarction; the infarction had no substantial correlation with injury grade or dominancy., Conclusions: Overall incidence of IVAI in CSSs was 0.08%. C1-2 posterior fixation had the highest incidence of IVAI (1.35%). Although clinical results of IVAI can be highly variable, controlling risk factors of IVAI is important., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Subsidence of the interbody graft into the vertebral bodies is one of the major complications of direct lateral interbody fusion (DLIF), resulting in pseudoarthrosis and severe pain. Low bone mineral density (BMD) has been known to increase the risk of subsidence. This study aims to determine whether or not the osteopenia should influence the surgical results in DLIF surgery., Methods: We retrospectively reviewed the data collected prospectively on all patients who underwent single-level DLIF at our institution. A total of 84 patients were included in this study, comprised of 41 in the osteopenia group and 43 in the normal BMD group. The clinical and radiologic characteristics were compared at preoperative and postoperative 1 and 2 years., Results: At postoperative two years, there was a statistically significant difference in disc height and intervertebral foramen height at index level between the two groups (p = 0.039, 0.044, respectively), but there was no significant difference in total lumbar lordosis (p = 0.179). At 24-month postoperative, 92.7% of the osteopenia group and 95.3% of the normal BMD group were solidly fused (p = 0.672). All postoperative clinical scores (VAS back pain, VAS leg pain, and ODI) improved similarly in both groups without significant difference. The overall incidence of cage subsidence with >3 mm was 17.1% in the osteopenia group and 9.3% in the normal BMD group (p = 0.345)., Conclusions: Patients with osteopenia who undergo single-level DLIF combined with posterior fixation exhibited comparable clinical and radiological outcomes as patients with normal BMD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

How the brain supports normal episodic memory function without medial temporal lobe (MTL) structures has not been well characterized, which could provide clues for new therapeutic targets for people with MTL dysfunction-related memory impairment. To characterize brain network supporting effective episodic memory function in the absence of unilateral MTL, we investigated the whole-brain cortical interactions during functional magnetic resonance imaging memory encoding paradigms of words and figures in patients who showed a normal range of memory capacity following unilateral MTL resection and healthy controls (HC). Compared to the HC, the patients showed less activation in the left inferior frontal areas and right thalamus together with greater activation in the many cortical areas including the medial prefrontal cortex (mPFC). Task-based functional connectivity (FC) analysis revealed that the mPFC showed stronger interactions with widespread brain areas in both patient groups, including the hippocampus contralateral to the resection. Moreover, the strength of the mPFC FC predicts the individual memory capacity of the patients. Our data suggest that hyperconnectivity of distributed brain areas, especially the mPFC, is a neural mechanism for memory function in the absence of one MTL., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Objectives: To investigate the prevalence and incidence of Parkinson's disease (PD) and provide evidence for preventive strategy of vertebral, hip, and femoral fractures (VF, HF, and FF) in PD patients., Design: Retrospective cohort study., Setting and Participants: Using a nationwide medical service utility database from 2009 to 2014, we enrolled PD patients with diagnosis of G20 as per ICD-10 who used medical services. Overall, the number of PD patients was 97,311, 106,072, 115,762, 127,647, 137,782, and 144,757 through 2009-2014, respectively. We followed 35,663 patients diagnosed with PD in 2010 without prior fracture., Measures: We estimated the annual PD prevalence and incidence and used Cox proportional hazards model to estimate the hazards ratio (HR) for factures based on demographic characteristics, underlying disease, and socioeconomic status according to fracture type (osteoporosis-related fracture, VF, HF/FF). Furthermore, we investigated the cumulative incidence of those fractures by month during the 5-year follow-up., Results: The standardized PD prevalence increased from 238 to 279 between 2009 and 2014, and its incidence decreased from 86 to 72 between 2010 and 2014 per 100,000 population based on 2015 census data. We followed 35,663 PD patients: women, 20,732 (58.1%); aged ≥60 years, 29,264 (82.1%); with osteoporosis, 6542 (18.3%); VF experience, 4242 (11.9%); and HF/FF experience, 2112 (5.9%). Osteoporosis was a significant risk factor for VF [HR 1.75, 95% confidence interval (CI) 1.64-1.87] and HF/FF (HR 1.37, 95% CI 1.24-1.51). The cumulative incidence of VF and HF/FF was the highest at 6 months and increased more than half in the coming 2 years after PD diagnosis., Conclusions/implications: VF and HF/FF are common among PD patients. VF and HF/FF risks were high for female PD patients aged ≥60 years with osteoporosis. Fracture prevention strategies should be focused on older, women, and osteoporosis patients within 3 years of PD diagnosis., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

This study presents a radiofrequency (RF)-energy-harvesting integrated circuit (IC) for powering wireless sensor networks with a wireless transmitter with an industrial, scientific, and medical (ISM) of 915 MHz. The proposed IC comprises an RF-direct current (DC) rectifier, an over-voltage protection circuit, a low-power low-dropout (LDO) voltage regulator, and a charger control circuit. In the RF-DC rectifier circuit, a six-stage Dickson voltage multiplier circuit is used to improve the received RF signal to a DC voltage by using native MOS with a small threshold voltage. The over-voltage protection circuit is used to prevent a high-voltage breakdown phenomenon from the RF front-end circuit, particularly for near-field communication. A low-power LDO regulator is designed to provide stable voltage by using zero frequency compensation and a voltage-trimming feedback. Charging current is amplified N times by using a current mirror to rapidly and stably charge a battery in the proposed charger control circuit. The obtained results revealed that the maximum power conversion efficiency of the proposed RF-energy-harvesting IC was 40.56% at an input power of -6 dBm, an output voltage of 1.5 V, and a load of 30 kΩ. A chip area of the RF-energy-harvesting IC was 0.58 × 0.49 mm 2 , including input/output pads, and power consumption was 42 μW.

Multinodular and vacuolating neuronal tumor (MVNT) of the cerebrum is a recently recognized rare neuronal tumor, and its pathogenesis is unclear. We analyzed 7 cases of histologically typical MVNT: 6 were adults (mean age, 43.0 years [range, 23-56 years]) and 1 was a child (age, 10 years). The most common symptoms were seizures (n = 4) and headache (n = 2). The tumors were supratentorial (temporal, 5; frontal lobes, 2) in origin as reported. Vacuolated tumor cells were robustly positive for α-INA and Olig2 and at least partly positive for synaptophysin and MAP2, but negative for Neu-N, nestin and CD34. GFAP and vimentin were expressed in reactive astrocytes but not in tumor cells. Negative results were obtained for p53, IDH-1, BRAF V600E , H3 K27M, EGFR, Lin28A, and L1CAM. ATRX, BRG1, INI-1, and TMHH were retained. The Ki-67 labeling index was very low (<1%), and pHH3 revealed no mitotic figure. Ultrastructural features of tumor cells were comparable with those of immature neuronal cells, with several intracytoplasmic myelin-like autophagosomes and pericellular vacuolization. No IDH1/IDH2 and BRAF V600E mutations were found upon direct sequencing. Whole-exome sequencing revealed FGFR2-ZMYND11 gene fusion in 1 case. After gross total resection, all patients were alive without seizures. There was no tumor recurrence during an average period of 68 months (range, 23-101 months). The analysis of 7 typical cases of MVNT suggested that these lesions may be clonal tumors because FGFR2-ZMYND11 fusion was found (1 case)., (Copyright © 2018 Elsevier Inc. All rights reserved.)

There is a low incidence of reoperation after surgery. It is difficult to detect statistical differences between reoperation rates of different lumbar fusion surgeries. National population-based databases provide large, longitudinally followed cohorts that may help overcome this challenge. The purpose is to compare the repeat decompression and fusion rate after surgery for degenerative lumbar diseases according to different surgical fusion procedures based on national population-based databases and elucidate the risk factor for repeat decompression and fusions. The Korean Health Insurance Review & Assessment Service database was used. Patients diagnosed with degenerative lumbar diseases and who underwent single-level fusion surgeries between January 1, 2011, and June 30, 2016, were included. They were divided into two groups based on procedure codes: posterolateral fusion or posterior/transforaminal lumbar interbody fusion. The primary endpoint was repeat decompression and fusion. Age, sex, the presence of diabetes, osteoporosis, associated comorbidities, and hospital types were considered potential confounding factors. The repeat decompression and fusion rate was not different between the patients who underwent posterolateral fusion and those who underwent posterior/transforaminal lumbar interbody fusion. Old age, male sex, and hospital type were noted to be risk factors. The incidence of repeat decompression and fusion was independent on the fusion method.

Objective: Ligamentum flavum (LF) is an important anatomical structure for prevention of postoperative adhesions, but the opening of LF is necessary for percutaneous endoscopic lumbar interlaminar discectomy (PEID). Although the defect in LF is small with conventional PEID, the defect could be minimized with LF splitting technique. The objective of this study was to compare clinical outcomes of PEID with opening of LF versus splitting of LF., Methods: A retrospective study was performed for patients underwent PEID for L5-S1. PEID with the opening of LF (open-group) was performed for 55 patients and with splitting of LF (split-group) was performed for 34 patients. The defect of LF in Open-group was 3-5 mm, but the defect was negligible in split-group because the split LF was reapproximated by its elasticity. Clinical outcomes were evaluated with Korean version of the Oswestry Disability Index (K-ODI) and visual analogue pain scores for back (VASB) and leg (VASL). The changes of clinical outcomes during postoperative 24 months between groups were evaluated with linear mixed-effects model., Results: The clinical outcomes were similar between groups for K-ODI (p=0.98), VASB (p=0.52), and VASL (p=0.59). Each outcome demonstrated significant improvement from preoperative baseline throughout the postoperative 24 months (p<0.05). Complications included recurrence in 4 patients and dural tear in 1 in open-group (9.1%), and residual disc herniation in 2 patients and transient weakness in 1 in split-group (8.8%)., Conclusion: Splitting versus opening LF in PEID may be left to the surgeon's discretion. The potential risks and benefits of LF handling should be considered when performing this surgical technique in PEID.

Study Design: A retrospective cohort study., Objective: The objectives of the present study were to examine the changes in the number of surgeries, surgical methods selected, and reoperation rates between the years 2003 and 2008., Summary of Background Data: The selection of the appropriate surgical method between decompression-only (D) and decompression plus fusion (DF) represents a challenging clinical dilemma in patients with degenerative lumbar spinal spondylolisthesis. DF is selected in greater than 90% of patients, mostly due to the associated low reoperation rate. However, the outcomes of D have been improved with minimally invasive decompression surgery techniques., Methods: The Health Insurance Review and Assessment Service database was used to create cohorts of all Korean patients who underwent surgery for degenerative lumbar spinal spondylolisthesis in 2003 (2003 cohort, n = 5624) and 2008 (2008 cohort, n = 11,706). All patients were followed up for at least 5 years. Reoperation was defined as the occurrence of any type of second lumbar surgery during the follow-up period. The probabilities of reoperation were calculated using the Kaplan-Meier method., Results: The number of surgeries increased 2.08-fold in 2008. Patients older than 60 years comprised 38.6% of the 2003 cohort and 52.4% of the 2008 cohort. The proportion of DF surgery was 31.13% in the 2003 cohort but 91.54% in the 2008 cohort. However, the high proportion of fusion surgery failed to reduce the reoperation probability in the 2008 cohort (8.1%) compared with that in the 2003 cohort (6.2%). The cost of DF was US$5264 and that of D was $2719 in 2008. DF decreased the reoperation probability by 1% at the cost of $421/patient in the 2008 cohort., Conclusion: The increased proportion of fusion surgery without improvement in reoperation probability in an aging society may be cautiously addressed in deciding future health policies., Level of Evidence: 4.

Previous studies have reported conflicting results regarding the effect of direct electrical stimulation of the human hippocampus on memory performance. A major function of the hippocampus is to form associations between individual elements of experience. However, the effect of direct hippocampal stimulation on associative memory remains largely inconclusive, with most evidence coming from studies employing non-invasive stimulation. Here, we therefore tested the hypothesis that direct electrical stimulation of the hippocampus specifically enhances hippocampal-dependent associative memory. To test this hypothesis, we recruited surgical patients with implanted subdural electrodes to perform a word pair memory task during which the hippocampus was stimulated. Our results indicate that stimulation of the hippocampus during encoding helped to build strong associative memories and enhanced recollection in subsequent trials. Moreover, stimulation significantly increased theta power in the lateral middle temporal cortex during successful memory encoding. Overall, our findings indicate that hippocampal stimulation positively impacts performance during a word pair memory task, suggesting that successful memory encoding involves the temporal cortex, which may act together with the hippocampus.

Objective: The aim of this nationwide study was to analyze the current state of patients with newly diagnosed metastatic spine tumors according to surgical methods., Methods: Data was extracted from the Korean Health Insurance Review and Assessment Service database. Surgery was categorized into three., Methods: fusion, decompression, and vertebroplasty. Data included patient age, sex, health insurance type, and co-morbidities. Survival rates of metastatic spine tumor patients according to each surgical method were evaluated., Results: Among 1677 patients who had an operation, 823 patients were treated by fusion, 141 patients underwent decompression, and 713 patients were treated by vertebroplasty. The three most prevalent primary tumor sites were the lung, breast, and liver & biliary. On the other hand, the three most prevalent primary tumor sites of patients who underwent surgery were the lung, liver & biliary, and the prostate. The median survival periods for each surgical method in the metastatic spine tumor patients were 228 days for those who underwent surgery, 249 days for decompression, and 154 days for vertebroplasty. Age, sex, and comorbidities significantly affected survival rate., Conclusion: For every primary tumor site, decompression was the least common surgical method during the study period. Although the three surgical methods did not significantly affect the survival period, patients with a poor prognosis tended to undergo vertebroplasty.

Background: Recently, the role of neural modulation in nonauditory cortices via repetitive transcranial magnetic stimulation (rTMS) for tinnitus control has been emphasized. It is now more compelling to consider these nonauditory cortices and the whole "tinnitus network" as targets for tinnitus treatment to achieve a better outcome., Objective: We aimed to investigate the effects of active dual-site rTMS treatment in tinnitus reduction using a double-blind randomized controlled trial., Method: In study 1, the dual-site rTMS treatment group (n = 17) was treated daily for 4 consecutive days. The sham group (n = 13) also visited the clinic for 4 days; they received sham treatment for the same duration as the dual-site rTMS treatment group. In study 2, the rTMS treatment protocol was exactly the same as in study 1. Magnetoencephalography recordings were performed before and 1 week after the last rTMS treatment. The outcome measure was the Tinnitus Handicap Inventory (THI) score and the visual analog scale score. The effects of treatment were assessed 1, 2, 4, and 8 weeks after rTMS treatment in study 1. Then the mean band power and network changes were compared between pre- and post-treatment values after rTMS in study 2., Result: Patients in the dual-site rTMS treatment group exhibited significantly improved THI scores at 2, 4, and 8 weeks after rTMS treatment compared with the pretreatment scores. However, the sham group did not show any significant reduction in THI scores. When the mean band power changes were compared between pre- and post-treatment assessments, an increased oscillation power was observed in the alpha band after rTMS., Conclusion: A beneficial effect of rTMS on tinnitus suppression was found in the dual-site active rTMS group, but not in the sham rTMS group., (© 2019 S. Karger AG, Basel.)

Objective: To determine the prevalence of osteoporosis (OP) and osteoporotic vertebral fracture (OVF) in people with Parkinson's disease (PD) in Korea and its association with socioeconomic status., Methods: Using Health Insurance Review and Assessment Service-National Inpatient Sample (HIRA-NIS) data from 2009 to 2013, we estimated the annual prevalence of PD, OP, and OVF and investigated its association with socioeconomic status using data from National Health Insurance (NHI) beneficiaries and Medical Aid (MA) recipients. This study was supported by research funding from Korean Society for Bone and Mineral Research 2015. There were no study-specific biases related to conflicts of interest., Results: The number of PD patients in the HIRA-NIS increased each year from 2009 to 2013. Among patients with PD, the standardized prevalence rates of OP and OVF increased from 2009 to 2013; from 23.2 to 27.8 and from 2.8 to 4.2, respectively. Among patients with PD with OP, the prevalence of OVF were 12.2% and 15.1% in 2009 and 2013, respectively. The standardized prevalence rates of PD with OP and PD with OVF were significantly higher in MA recipients than in NHI beneficiaries., Conclusion: The prevalence of PD both with OP and with OVF increased and the prevalence was higher in MA recipients than in NHI beneficiaries. These findings may suggest that age over 65 years, female and low income may be a significant factor related to PD occurring with OP and OVF.

Aim: Surgery for spinal metastases can improve symptoms, but sometimes complications can negate the benefits. Operations may have different indications, complexities and risks, and the choice for an individual is a tailor-made personalised decision. Previous prognostic scoring systems are becoming out of date and inaccurate. We designed a risk calculator to estimate survival after surgery, to inform clinicians and patients when making management decisions., Methods: A prospective cohort study was performed, including 1430 patients with spinal metastases who underwent surgery. Of them, 1264 patients from 20 centres were used for model development using a Cox frailty model. Calibration slope, D-statistic and C-index were used for model validation based on 166 patients. Follow-up was to death or minimum of 2 years after surgery. Pre-operative indices (examination findings, pain, Karnofsky physical functioning score, and radiology) were assessed., Results: An algorithm to predict survival was constructed including the tumour type, ambulatory status, analgesic use, American Society of Anesthesiologists score, number of spinal metastases, previous radiotherapy or chemotherapy, presence of visceral metastases, cervical or thoracic spine involvement, as predictors. An Internet-based risk calculator was developed based on this algorithm, with similar or improved accuracy compared to other validated prognostic scoring systems (C-index, 0.68; 95% confidence interval, 0.63--0.73, and calibration slope, 1.00; 95% confidence interval, 0.68--1.32)., Conclusion: A large, prospective, surgical series of patients with symptomatic spinal metastases was used to create a validated risk calculator that can help clinicians to inform patients about the most appropriate treatment plan. The calculator is available at www.spinemet.com., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Study Design: A prospective multicenter cohort study., Objective: To assess the clinical accuracy of six commonly cited prognostic scoring systems for patients with spinal metastases., Summary of Background Data: There are presently several available methods for the estimation of prognosis in metastatic spinal disease, but none are universally accepted by surgeons for clinical use. These scoring systems have not been rigorously tested and validated in large datasets to see if they are reliable enough to inform day-to-day patient management decisions. We tested these scoring systems in a large cohort of patients. A total of 1469 patients were recruited into a secure internet database, and prospectively collected data were analyzed to assess the accuracy of published prognostic scoring systems., Methods: We assessed six prognostic scoring systems, described by the first authors Tomita, Tokuhashi, Bauer, van der Linden, Rades, and Bollen. Kaplan-Meier survival estimates were created for different patient subgroups as described in the original publications. Harrell's C-statistic was calculated for the survival estimates, to assess the concordance between estimated and actual survival., Results: All the prognostic scoring systems tested were able to categorize patients into separate prognostic groups with different overall survivals. However none of the scores were able to achieve "good concordance" as assessed by Harrell's C-statistic. The score of Bollen and colleagues was found to be the most accurate, with a Harrell's C-statistic of 0.66., Conclusion: No prognostic scoring system was found to have a good predictive value. The scores of Bollen and Tomita were the most effective with Harrell's C-statistic of 0.66 and 0.65, respectively. Prognostic scoring systems are calculated using data from previous years, and are subject to inaccuracies as treatments advance in the interim. We suggest that other methods of assessing prognosis should be explored, such as prognostic risk calculation., Level of Evidence: 3.

Background: The causal networks among genes that are commonly expressed in osteoblasts and during bone metastasis (BM) of breast cancer (BC) are not well understood. Here, we developed a machine learning method to obtain a plausible causal network of genes that are commonly expressed during BM and in osteoblasts in BC., Methods: We selected BC genes that are commonly expressed during BM and in osteoblasts from the Gene Expression Omnibus database. Bayesian Network Inference with Java Objects (Banjo) was used to obtain the Bayesian network. Genes registered as BC related genes were included as candidate genes in the implementation of Banjo. Next, we obtained the Bayesian structure and assessed the prediction rate for BM, conditional independence among nodes, and causality among nodes. Furthermore, we reported the maximum relative risks (RRs) of combined gene expression of the genes in the model., Results: We mechanistically identified 33 significantly related and plausibly involved genes in the development of BC BM. Further model evaluations showed that 16 genes were enough for a model to be statistically significant in terms of maximum likelihood of the causal Bayesian networks (CBNs) and for correct prediction of BM of BC. Maximum RRs of combined gene expression patterns showed that the expression levels of UBIAD1 , HEBP1 , BTNL8 , TSPO , PSAT1 , and ZFP36L2 significantly affected development of BM from BC., Conclusions: The CBN structure can be used as a reasonable inference network for accurately predicting BM in BC., Competing Interests: No potential conflict of interest relevant to this article was reported.

This nationwide study of the adult Korean population aimed to compare the survival period between synchronous and metachronous group and to determine recent treatment trends in newly diagnosed spine metastasis patients. Data were extracted from the Korean Health Insurance Review and Assessment Service database. Patients in this study were newly diagnosed with metastatic spine tumors between July 1, 2011 and June 31, 2014. The metachronous group was defined when the primary tumor was diagnosed prior to the diagnosis of spine metastasis, otherwise patients were considered to be the part of the synchronous group. The survival period was calculated from the date of first diagnosis of spine metastasis. In a multivariate analysis, patients in the synchronous group survived significantly longer than those in the metachronous group (P < 0.0001). Median overall survival periods were 273.6 days for the metachronous group and 541.4 days for the synchronous group. Conventional radiation therapy (RT) was the most common treatment modality for metastatic spine tumors, whereas surgery combined with RT was a steadily increasing treatment modality during the study period. Synchronous spine metastasis patients survive significantly longer than metachronous patients. Surgery combined with RT is a recently increasing trend among spine metastasis treatments., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Examining spine surgery patterns over time is crucial to provide insights into variations and changes in clinical decision making. Changes in the number of surgeries, surgical methods, reoperation rates, and cost-effectiveness were analyzed for all patients who underwent surgery for lumbar spinal stenosis without spondylolisthesis in 2003 (2003 cohort) and 2008 (2008 cohort)., Methods: The national health insurance database was used to create the 2003 cohort (n = 10,990) and 2008 cohort (n = 27,942). The surgical methods were classified into decompression and fusion surgery. The cumulative reoperation probability between those surgeries was calculated using the Kaplan-Meier method in the 2003 cohort and 2008 cohort. Comparison of the incremental cost-effectiveness ratios showed the additional direct cost of a 1% change in the reoperation probability., Results: The surgical volume increased 2.54-fold in the 2008 cohort. The age-adjusted number of surgeries per 1 million people increased 2.6-fold (from 154 in the 2003 cohort to 399 in the 2008 cohort) in aged patients and 1.9-fold (from 154 in the 2003 cohort to 291 in the 2008 cohort) in patients 20-59 years old in the 2008 cohort. The proportion of fusion surgeries increased from 20.3% in the 2003 cohort to 37.0% in the 2008 cohort. In total, the 5-year reoperation probabilities increased from 8.1% in the 2003 cohort to 11.2% in the 2008 cohort. Fusion decreased the reoperation probability by 1% at the cost of 1,711 U.S. dollars., Conclusions: The increased numbers of spinal surgeries, fusion surgeries, and surgeries in older patients in a recent cohort were noteworthy. However, the increased surgical volume and fusion surgeries did not reduce the reoperation rate., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: How the brain supports intermediate-term preservation of memory in patients who have undergone unilateral medial temporal lobe resection (MTLR) has not yet been demonstrated. To understand the neural basis of episodic memory in the intermediate term after surgery for temporal lobe epilepsy (TLE), the authors investigated the relationship between the activation of the hippocampus (HIP) during successful memory encoding and individual memory capacity in patients who had undergone MTLR. They also compared hippocampal activation with other parameters, including structural volumes of the HIP, duration of illness, and age at seizure onset., Methods: Thirty-five adult patients who had undergone unilateral MTLR at least 1 year before recruiting and who had a favorable seizure outcome were enrolled (17 left MTLR, 18 right MTLR; mean follow-up 6.31 ± 2.72 years). All patients underwent a standardized neuropsychological examination of memory function and functional MRI scanning with a memory-encoding paradigm of words and figures. Activations of the HIP during successful memory encoding were calculated and compared with standard neuropsychological memory scores, hippocampal volumes, and other clinical variables., Results: Greater activation in the HIP contralateral to the side of the resection was related to higher postoperative memory scores and greater postoperative memory improvement than the preoperative baseline in both patient groups. Specifically, postoperative verbal memory performance was positively correlated with contralateral right hippocampal activation during word encoding in the left-sided surgery group. In contrast, postoperative visual memory performance was positively correlated with contralateral left hippocampal activation during figure encoding in the right-sided surgery group. Activation of the ipsilateral remnant HIP was not correlated with any memory scores or volumes of the HIP; however, it had a negative correlation with the seizure-onset age and positive correlation with the duration of illness in both patient groups., Conclusions: For the first time, a neural basis that supports effective intermediate-term episodic memory after unilateral MTLR has been characterized. The results provide evidence that engagement of the HIP contralateral rather than ipsilateral to the side of resection is responsible for effective memory function in the intermediate term (> 1 year) after surgery in patients who have undergone left MTLR and right MTLR. Engagement of the material-specific contralesional HIP, verbal memory in the left-sided surgery group, and visual memory in the right-sided surgery group were observed.

Background: Although intracranial and spinal ependymomas are histopathologically similar, the molecular landscape is heterogeneous. An urgent need exists to identify differences in the genomic profiles to tailor treatment strategies. In the present study, we delineated differential gene expression patterns between intracranial and spinal ependymomas., Methods: We searched the Gene Expression Omnibus database using the term "ependymoma" and analyzed the raw gene expression profiles of 292 ependymomas (31 spinal and 261 intracranial). The gene expression data were analyzed to find differentially expressed genes (DEGs) between 2 regions. The fold change (FC) and false discovery rate (FDR) were used to assess DEGs after gene integration (|log 2 FC|>2; FDR P < 0.01). Enrichment and pathway analysis was also performed., Results: A total of 201 genes (105 upregulated and 96 downregulated) were significant DEGs in the data sets. The underexpression of NF2 in spinal ependymomas was statistically significant (FDR P = 7.91 × 10 -9 ). However, the FC of NF2 did not exceed the cutoff value (log 2 FC, -1.2). The top 5 ranked upregulated genes were ARX, HOXC6, HOXA9, HOXA5, and HOXA3, which indicated that spinal ependymomas frequently demonstrate overexpression of HOX family genes, which play fundamental roles in specifying anterior/posterior body patterning. Moreover, the gene ontology enrichment analysis specified "anterior/posterior pattern specification" and "neuron migration" in spinal and intracranial ependymomas, respectively., Conclusions: The most substantial magnitude of DEGs in ependymoma might be HOX genes. However, whether the differential expression of these genes is the cause or consequence of the disease remains to be elucidated in a larger prospective study., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Cancer immunotherapy is emerging as a candidate treatment modality for treating post-surgical metastasis and recurrences. Despite the great promises with therapeutic cancer vaccines and checkpoint blocking antibodies in pre-clinical studies, response rates in the clinic still remain unsatisfactory. The evaluation of immunotherapy after surgery in patients could confront significant unexpected hurdles. Surgery itself tends to cause immune suppression, while wound healing factors also stimulate tumor cell outgrowth and metastasis. Regarding the marked changes in the post-surgical tumor microenvironment, one can anticipate that better tumor growth control is attainable by combining cancer vaccines with immune checkpoint blockade. However, it is important that vaccines and checkpoint blocking antibodies are delivered efficiently to their target cells, are released sustained and locally and do not induce cytotoxic effects. The generation of effective anti-tumor immunity and durable response rates could largely depend on these parameters. In the last decade, researchers spend tremendous effort in optimizing the delivery of immunotherapeutic compounds with the use of nanomedicine. Biocompatible nanoparticle based delivery systems demonstrated intriguing results with regard to specific immune cell activation, improved drug delivery, cell targeting, limiting off target toxicity and improving treatment outcome. It therefore makes sense, to speculate on the promises of combined cancer vaccination and immune checkpoint blocking immunotherapy with the aid of nanomedicine. A powerful nanoparticle combination immunotherapy conferring durable therapeutic benefit whilst leaving healthy tissue untouched represents the base for more efficient post-surgical cancer treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A practical synthesis of chiral tryptamines from simple, unprotected indoles has been developed. Indole nucleophiles prepared with MeMgCl in the presence of CuCl reacted with chiral cyclic sulfamidates almost exclusively at the C 3 -position of indole to form a variety of α- and/or β-substituted chiral tryptamines in good yield with excellent regioselectivity. The utility of this simple alkylation process has been demonstrated with the practical synthesis of two biologically active targets, cipargamin and TIK-301, which were completed in three steps, starting from the corresponding indole starting materials.

Background: As survival after treatment for symptomatic spinal metastases increases, the incidence of local tumor recurrence also may increase. However, data regarding incidence and timing of recurrence or duration of survival after second surgeries are not readily available and may help to inform clinicians when to perform second surgeries., Objective: To identify features associated with loss of local control (LLC) at a previously treated or new spinal level., Methods: Clinical and surgical data were collected from a prospective cohort of 1421 patients who had surgery for symptomatic spinal metastases. Patients undergoing repeat spinal surgery for symptomatic LLC at the same or a different level were identified and analyzed., Results: In total, 3.0% patients underwent repeat surgery for symptomatic LLC after a median interval of 184 days from the first surgery; median survival was 6.1 months after second surgery. Factors associated with second surgery for LLC were the primary tumor type, number of spinal levels, Tomita staging, Tokuhashi and Karnofsky scores, anterior surgical approach, more aggressive surgical resection, and postoperative radiotherapy. In total, 1.5% patients were admitted for surgery for a different spinal level than the index operation after median 338 days from the first operation., Conclusions: The likelihood for repeat surgery due to LLC cannot be accurately predicted at the time of initial presentation. Factors associated with second surgery for LLC relate to less aggressive tumor biology and better survival. Most patients had a reasonable duration of survival after second surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

OBJECTIVE In this study, the authors investigated long-term clinical and visual outcomes of patients after occipital lobe epilepsy (OLE) surgery and analyzed the relationship between visual cortical resection and visual function after OLE surgery. METHODS A total of 42 consecutive patients who were diagnosed with OLE and underwent occipital lobe resection between June 1995 and November 2013 were included. Clinical, radiological, and histopathological data were reviewed retrospectively. Seizure outcomes were categorized according to the Engel classification. Visual function after surgery was assessed using the National Eye Institute Visual Functioning Questionnaire 25. The relationship between the resected area of the visual cortex and visual function was demonstrated by multivariate linear regression models. RESULTS After a mean follow-up period of 102.2 months, 27 (64.3%) patients were seizure free, and 6 (14.3%) patients had an Engel Class II outcome. Nineteen (57.6%) of 33 patients had a normal visual field or quadrantanopia after surgery (normal and quadrantanopia groups). Patients in the normal and quadrantanopia groups had better vision-related quality of life than those in the hemianopsia group. The resection of lateral occipital areas 1 and 2 of the occipital lobe was significantly associated with difficulties in general vision, peripheral vision, and vision-specific roles. In addition, the resection of intraparietal sulcus 3 or 4 was significantly associated with decreased social functioning. CONCLUSIONS The authors found a favorable seizure control rate (Engel Class I or II) of 78.6%, and 57.6% of the subjects had good visual function (normal vision or quadrantanopia) after OLE surgery. Lateral occipital cortical resection had a significant effect on visual function despite preservation of the visual field.

Objective: Cervical myelopathy patients sometimes experience concurrent nonspecific moderate to severe low back pain (msLBP). However, postoperative changes in msLBP after cervical myelopathy surgery have rarely been reported. Awareness of postoperative changes in msLBP may be helpful in consultation. Therefore, the objective of this study was to examine postoperative changes in msLBP., Methods: Patients with cervical myelopathy and msLBP (a visual analog pain score ≥5/10) were reviewed prospectively, and 53 patients (male:female ratio, 28:25; mean age, 63.1 years) were enrolled. Cervical myelopathy was assessed with the Japanese Orthopedic Association score. Cervical laminoplasty was performed in 49 patients, and anterior cervical discectomy and fusion were performed in 4 patients. The patients were followed up postoperatively at 1, 3, 6, and 12 months and yearly thereafter. The primary endpoint was improvement of the visual analog scale score for back pain (VAS-B) by greater than 2.6/10. Prognostic factors were analyzed postoperatively at 12 months. The mean follow-up period was 16 ± 9 months., Results: MsLBP improved in 58%, 49%, 53%, 52%, and 59% of the patients at 1, 3, 6, 12, and 24 months postoperatively, respectively. The VAS-B worsened after improvement or vice versa in approximately 30% of the patients during the follow-up period. Lumbar decompression operations were performed in 5 patients at 4, 6, 7, 15, and 16 months postoperatively. The recovery rate of the JOA score was a positive prognostic factor., Conclusions: Although the exact pathophysiology was not demonstrated, cervical myelopathy surgery may directly and indirectly improve msLBP., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Quantitative structure-activity relationships have an extensive history for optimizing drug candidates, yet they have only recently been applied in reaction development. In this report, the predictive power of multivariate parameterization has been explored toward the optimization of a catalyst promoting an aza-Michael conjugate addition for the asymmetric synthesis of letermovir. A hybrid approach combining 2D QSAR and modern 3D physical organic parameters performed better than either approach in isolation. Using these predictive models, a series of new catalysts were identified, which catalyzed the reaction to provide the desired product in improved enantioselectivity relative to the parent catalyst.

Objective: Butyrate exerts metabolic benefits in mice and humans, the underlying mechanisms being still unclear. We aimed to investigate the effect of butyrate on appetite and energy expenditure, and to what extent these two components contribute to the beneficial metabolic effects of butyrate., Design: Acute effects of butyrate on appetite and its method of action were investigated in mice following an intragastric gavage or intravenous injection of butyrate. To study the contribution of satiety to the metabolic benefits of butyrate, mice were fed a high-fat diet with butyrate, and an additional pair-fed group was included. Mechanistic involvement of the gut-brain neural circuit was investigated in vagotomised mice., Results: Acute oral, but not intravenous, butyrate administration decreased food intake, suppressed the activity of orexigenic neurons that express neuropeptide Y in the hypothalamus, and decreased neuronal activity within the nucleus tractus solitarius and dorsal vagal complex in the brainstem. Chronic butyrate supplementation prevented diet-induced obesity, hyperinsulinaemia, hypertriglyceridaemia and hepatic steatosis, largely attributed to a reduction in food intake. Butyrate also modestly promoted fat oxidation and activated brown adipose tissue (BAT), evident from increased utilisation of plasma triglyceride-derived fatty acids. This effect was not due to the reduced food intake, but explained by an increased sympathetic outflow to BAT. Subdiaphragmatic vagotomy abolished the effects of butyrate on food intake as well as the stimulation of metabolic activity in BAT., Conclusion: Butyrate acts on the gut-brain neural circuit to improve energy metabolism via reducing energy intake and enhancing fat oxidation by activating BAT., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: Cervical radiculopathy infrequently presents with motor weakness. Motor weakness was improved in >90% of patients after anterior cervical discectomy and fusion or posterior cervical foraminotomy. Posterior percutaneous endoscopic cervical foraminotomy and discectomy (PECF) is an alternative surgical technique, but the outcome of motor weakness has not been reported. Our objective was to demonstrate the longitudinal outcomes of motor weakness after PECF., Methods: A retrospective review of 106 consecutive patients was performed. Preoperative motor weakness was graded as mild (IV/V strength) or severe (less than III/V strength). The patients visited the outpatient clinic at 1, 3, 6, and 12 months after surgery and yearly thereafter. Improvement was defined as an improved weakness of more than 1 grade, and normalization was defined as the recovery of complete motor strength., Results: Motor weakness preoperatively presented in 76 of 106 (72%) patients (49%, mild weakness; 23%, severe weakness). After PECF, the weakness improved in 72 of 76 (95%) patients and normalized in 65 of 76 (86%) patients. In the patients with mild weakness, the normalization rates were 48%, 81%, 90%, and 96% at postoperative months 1, 3, 6, and 12, respectively. In the patients with severe weakness, the improvement rates were 50%, 71%, 83%, 88%, and 92%, and the normalization rates were 8%, 38%, 58%, 58%, and 63% at postoperative months 1, 3, 6, 12, and 24, respectively., Conclusions: Preoperative motor weakness was improved in 95% of the patients after PECF, but motor weakness was not normalized in 37% of the patients with severe weakness., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Residual disc fragments are observed on immediate postoperative magnetic resonance imaging (MRI) in 2.8-15% of patients after percutaneous endoscopic lumbar discectomy (PELD). Considering the known postoperative longitudinal outcomes in patients with residual disc tissue, a 'watchful waiting' strategy may be preferable to immediate re-operation in patients with asymptomatic residual disc material., Objectives: The aim of the present study was to compare the longitudinal clinical outcomes between PELD patients in whom the complete removal of disc fragments was achieved (complete group) and those in whom residual disc fragments were observed on postoperative MRI (residual group)., Study Design: Retrospective nested case-control study., Methods: A total of 225 patients were included (complete group, n=187 and residual group, n=38). Clinical assessments were performed using the visual analog pain score for the leg (VAS-L, x/10) and back (VAS-B, x/10) and the Korean version of the Oswestry Disability Index (K-ODI, x/45). A linear mixed-effects model was used to analyze changes during the first 24 postoperative months., Results: One month after surgery, significant improvements in the VAS-L, VAS-B and K-ODI values were observed and were maintained during the first 24 postoperative months. No differences in these changes were noted between the groups. Early re-operation (during the first 3 postoperative months) was performed in 3 patients in the residual group (7.9%) and in 4 patients in the complete group (2.1%) (P = 0.10)., Limitations: First, the study design was retrospective. Moreover, the number of patients was relatively small and therefore insufficient to achieve robust statistical power. Second, we did not explore the radiological outcomes in patients with asymptomatic residual disc material because follow-up MRI was only obtained to document symptom recurrence., Conclusion: When residual disc tissue is observed in asymptomatic patients, a 'watchful waiting' strategy may be preferable to immediate re-operation. However, an increased early re-operation rate is expected for patients with residual disc tissue., Key Words: Discectomy, endoscopes, longitudinal studies, patient-reported outcome, percutaneous, reoperation, spine, residual disc.

The objective of this study was to introduce a new machine learning guided by outcome of resective epilepsy surgery defined as the presence/absence of seizures to improve data mining for interictal pathological activities in neocortical epilepsy. Electrocorticographies for 39 patients with medically intractable neocortical epilepsy were analyzed. We separately analyzed 38 frequencies from 0.9 to 800 Hz including both high-frequency activities and low-frequency activities to select bands related to seizure outcome. An automatic detector using amplitude-duration-number thresholds was used. Interictal electrocorticography data sets of 8 min for each patient were selected. In the first training data set of 20 patients, the automatic detector was optimized to best differentiate the seizure-free group from not-seizure-free-group based on ranks of resection percentages of activities detected using a genetic algorithm. The optimization was validated in a different data set of 19 patients. There were 16 (41%) seizure-free patients. The mean follow-up duration was 21 ± 11 mo (range, 13-44 mo). After validation, frequencies significantly related to seizure outcome were 5.8, 8.4-25, 30, 36, 52, and 75 among low-frequency activities and 108 and 800 Hz among high-frequency activities. Resection for 5.8, 8.4-25, 108, and 800 Hz activities consistently improved seizure outcome. Resection effects of 17-36, 52, and 75 Hz activities on seizure outcome were variable according to thresholds. We developed and validated an automated detector for monitoring interictal pathological and inhibitory/physiological activities in neocortical epilepsy using a data-driven approach through outcome-guided machine learning. NEW & NOTEWORTHY Outcome-guided machine learning based on seizure outcome was used to improve detections for interictal electrocorticographic low- and high-frequency activities. This method resulted in better separation of seizure outcome groups than others reported in the literature. The automatic detector can be trained without human intervention and no prior information. It is based only on objective seizure outcome data without relying on an expert's manual annotations. Using the method, we could find and characterize pathological and inhibitory activities.

Background: Indications for surgery for symptomatic spinal metastases have become better defined in recent years, and suitable outcome measures have been established against a changing backdrop of patient characteristics, tumor behavior, and oncologic treatments. Nonetheless, variations still exist in the local management of patients with spinal metastases. In this study, we aimed to review global trends and habits in the surgical treatment of symptomatic spinal metastases, and to examine how these have changed over the last 25 years., Methods: In this cohort study of consecutive patients undergoing surgery for symptomatic spinal metastases, data were collected using a secure Internet database from 22 centers across 3 continents. All patients were invited to participate in the study, except those unable or unwilling to give consent., Results: There was a higher incidence of colonic, liver, and lung carcinoma metastases in Asian countries, and more frequent presentation of breast, prostate, melanoma metastases in the West. Trends in surgical technique were broadly similar across the centers. Overall survival rates after surgery were 53% at 1 year, 31% at 2 years, and 10% at 5 years after surgery (standard error 0.013 for all). Survival improved over successive time periods, with longer survival in patients who underwent surgery in 2011-2016 compared with those who underwent surgery in earlier time periods., Conclusions: Surgical habits have been fairly consistent among countries worldwide and over time. However, patient survival has improved in later years, perhaps due to medical advances in the treatment of cancer, improved patient selection, and operating earlier in the course of disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We aim to characterize the biomechanical properties of a modified iliac screw fixation method compared with the classic iliac screw fixation and the S2 alar iliac screw (S2AI) fixation using a FEM. A three-dimensional, non-linear FEM of lumbosacral spine and pelvis (L1-pelvis) was modified to simulate 3 different iliac screw fixations based on posterior screw fusion. The peak von Mises stress (PVMS) values of the iliac screws in the 3 different iliac screw fixations were recorded in during flexion/extension/axial rotation/lateral bending. The interaction stress which arose between the screw head and the shaft of iliac screws, was also measured for each case. The PVMS values of the 3 different iliac screw fixation techniques were lower than the fatigue strength levels under physiological loadings. PVMS of iliac screws was observed in the screw shaft for S2AI, in the screw neck for the modified iliac screw technique, and in the offset connectors of the classic iliac screw technique. The interaction between the screw head and the neck was compressed in modified iliac screw fixation technique. On the other hand, distraction force was observed in the S2AI technique between the screw head and the screw shaft. This FEM study supports our previous clinical results, which found that the modified iliac screw fixation technique can be an effective alternative sacropelvic fixation technique comparable to the classic iliac screw and the S2AI technique., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To identify the perioperative factors associated with instrument failure in patients undergoing a partial corpectomy with instrumentation (PCI) for spinal metastasis., Methods: We assessed the one hundred twenty-four patients with who underwent PCI for a metastatic spine from 1987 to 2011. Outcome measure was the risk factor related to implantation failure. The preoperative factors analyzed were age, sex, ambulation, American Spinal Injury Association grade, bone mineral density, use of steroid, primary tumor site, number of vertebrae with metastasis, extra-bone metastasis, preoperative adjuvant chemotherapy, and preoperative spinal radiotherapy. The intraoperative factors were the number of fixed vertebrae, fixation in osteolytic vertebrae, bone grafting, and type of surgical approach. The postoperative factors included postoperative adjuvant chemotherapy and spinal radiotherapy. This study was supported by the National Research Foundation grant funded by government. There were no study-specific biases related to conflicts of interest., Results: There were 15 instrumentation failures (15/124, 12.1%). Preoperative ambulatory status and primary tumor site were not significantly related to the development of implant failure. There were no significant associations between insertion of a bone graft into the partial corpectomy site and instrumentation failure. The preoperative and operative factors analyzed were not significantly related to instrumentation failure. In univariable and multivariable analyses, postoperative spinal radiotherapy was the only significant variable related to instrumentation failure ( p =0.049 and 0.050, respectively)., Conclusion: When performing PCI in patients with spinal metastasis followed by postoperative spinal radiotherapy, the surgeon may consider the possibility of instrumentation failure and find other strategies for augmentation than the use of a bone graft for fusion.

Study Design: Retrospective cohort study of a nationwide database., Objective: The primary objective was to summarize the use of surgical methods for lumbar herniated intervertebral disc disease (HIVD) at two different time periods under the national health insurance system. The secondary objective was to perform a cost-effectiveness analysis by utilizing incremental cost-effectiveness ratio (ICER)., Summary of Background Data: The selection of surgical method for HIVD may or may not be consistent with cost effectiveness under national health insurance system, but this issue has rarely been analyzed., Methods: The data of all patients who underwent surgeries for HIVD in 2003 (n = 17,997) and 2008 (n = 38,264) were retrieved. The surgical methods included open discectomy (OD), fusion surgery, laminectomy, and percutaneous endoscopic lumbar discectomy (PELD). The hospitals were classified as tertiary-referral hospitals (≥300 beds), medium-sized hospitals (30-300 beds), or clinics (<30 beds). ICER showed the difference in the mean total cost per 1% decrease in the reoperation probability among surgical methods. The total cost included the costs of the index surgery and the reoperation., Results: In 2008, the number of surgeries increased by 2.13-fold. The number of hospitals increased by 34.75% (731 in 2003 and 985 in 2008). The proportion of medium-sized hospitals increased from 62.79% to 70.86%, but the proportion of surgeries performed at those hospitals increased from 61.31% to 85.08%. The probability of reoperation was highest after laminectomy (10.77%), followed by OD (10.50%), PELD (9.20%), and fusion surgery (7.56%). The ICERs indicated that PELD was a cost-effective surgical method. The proportion of OD increased from 71.21% to 84.12%, but that of PELD decreased from 16.68% to 4.57%., Conclusion: The choice of surgical method might not always be consistent with cost-effectiveness strategies, and a high proportion of medium-sized hospitals may be responsible for this change., Level of Evidence: 4.

Objective: This study aimed to determine the incidence and analyze trends related to spinal diseases based on a national database in the Republic of Korea (ROK) and to elucidate the healthcare burden that will serve as a useful resource for researchers, clinicians, and patients., Methods: This study was a retrospective analysis of data obtained from Healthcare Bigdata Hub, the Korean Statistical Information Service, and Open Data Portal from 2012 through 2016. The main disease codes for spinal diseases (M40-M54) were used for identification of these conditions., Results: The overall annual incidence rates for spinal disease in the ROK was median 15,877 (men, 13,181; women, 18,588) per 100,000 population, and sex ratio was 1:1.41 (p<0.01). The incidence rate and annual costs per patient increased by 7.6% and 14.7% over 5 years continuously, respectively. The age-adjusted incidence rate increased with age; the highest rates were 42.6% in the 75-79 years group. Patients older than 65 years old accounted for median 31.0% of number of patients and 40.1% of medical expenses over 5 years. Lumbar disc herniation (M51) and spinal stenosis (M48) might accounted for both the highest incidence and medical expenses in patients under the age of 60 and over 60 years, respectively., Conclusion: The incidence and medical expenditures of spinal disease increased continuously. As the population of ROK in aging, the incidence and medical expenditures due to spondylosis and stenosis (M48) for the old are also increasing. The social burden of spinal diseases in elder patients needs to be prudently considered in health policy makers.

Objective: A spinal cord subependymoma is an uncommon, indolent, benign spinal cord tumor. It is radiologically similar to a spinal cord ependymoma, but surgical findings and outcomes differ. Gross total resection of the tumor is not always feasible. The present study was done to determine the clinical, radiological and pathological characteristics of spinal cord subependymomas., Methods: We retrospectively reviewed the medical records of ten spinal cord subependymoma patients (M : F=4 : 6; median 38 years; range, 21-77) from four institutions., Results: The most common symptoms were sensory changes and/or pain in eight patients, followed by motor weakness in six. The median duration of symptoms was 9.5 months. Preoperative radiological diagnosis was ependymoma in seven and astrocytoma in three. The tumors were located eccentrically in six and were not enhanced in six. Gross total resection of the tumor was achieved in five patients, whereas subtotal or partial resection was inevitable in the other five patients due to a poor dissection plane. Adjuvant radiotherapy was performed in two patients. Neurological deterioration occurred in two patients; transient weakness in one after subtotal resection and permanent weakness after gross total resection in the other. Recurrence or regrowth of the tumor was not observed during the median 31.5 months follow-up period (range, 8-89)., Conclusion: Spinal cord subependymoma should be considered when the tumor is located eccentrically and is not dissected easily from the spinal cord. Considering the rather indolent nature of spinal cord subependymomas, subtotal removal without the risk of neurological deficit is another option.

Background: For patients with single-level cervical radiculopathy, various types of motion preservation surgeries, such as total disc replacement (TDR), posterior cervical foraminotomy (PCF) and posterior percutaneous endoscopic foraminotomy and discectomy (PECF), are available. In addition to motion preservation, the quality of motion is an important issue. The aim of the present study was to evaluate the influence of these surgeries on cervical motion by comparing the instantaneous axis of rotation (IAR) among PECF, TDR and PCF at the index and superior/inferior adjacent segments., Methods: A retrospective review was performed of patients who underwent index surgery at C5-6 for cervical single-level foraminal disc herniation or foraminal stenosis. Patients with minimal degeneration at the index and other cervical spinal levels and flexion/extension cervical lateral radiographs both preoperatively and 6 months postoperatively were included (PECF, 11 patients; TDR, 11 patients; PCF, 12 patients). The IARs were calculated at the index segment and segments above and below the index segment from the flexion and extension cervical lateral radiographs, which were obtained preoperatively and 6 months postoperatively. A standardized cervical normogram was referenced to qualify shifts in the IAR., Results: Postoperatively, neck pain was significantly decreased, with no difference among the surgical methods. The IARs were not significantly changed after the PECF. Although significant inferior shift occurred at C6-7 after TDR (p = 0.02), the shift occurred within the normal range in the cervical normogram. However, significant inferior shifts in the IARs occurred after PCF at C5-6 (p = 0.02) and C6-7 (p = 0.02), and the IARs moved out of the normal range., Conclusions: The IARs were significantly changed after PCF at either the index segment or the adjacent segment below. The shifts in IAR at the index and adjacent segments were not significant after PECF and TDR. The sample size was too small to allow definitive conclusions, but the present study showed that PECF may be another alternative to motion preservation surgeries.

Study Design: A retrospective cohort study., Objective: The aim of this study was to identify the risk factors for acute progression of myelopathic symptoms (PMS) associated with ossification of the posterior longitudinal ligament (OPLL) after minor trauma and to compare the prognosis between an acute PMS group and a chronic PMS group., Summary of Background Data: Although the prevalence of OPLL among patients with cervical myelopathy is high, few studies have been published regarding the risk factors for acute PMS associated with OPLL after minor trauma., Methods: Patients with OPLL who had histories of minor trauma and had undergone surgery were divided according to clinical course into an acute (within 48 hours, n = 38) and a chronic PMS group (n = 32). The type of trauma and the clinical and radiologic characteristics were compared. The clinical outcomes were also compared at admission and at 1 and 2 years postoperatively., Results: The types of trauma were significantly different between the two groups (P < 0.05). Univariate analysis revealed that older age, a narrower space available for the cord, and a higher rate of stenosis in the spinal canal were associated with acute PMS after minor trauma (P = 0.014, 0.020, and 0.006, respectively). However, the rate of stenosis in the spinal canal was the only risk factor that was identified in a multivariate analysis (P = 0.023; odds ratio, 0.872; 95% confidence interval, 0.774-0.982). The Japanese Orthopedic Association scores at the initial visit and at postoperative years 1 and 2 were significantly lower in the acute PMS group than in the chronic PMS group (P < 0.001, P < 0.001, and P < 0.001, respectively)., Conclusion: One risk factor for acute PMS in patients with OPLL after minor trauma is a higher rate of stenosis of the spinal canal. Patients with acute PMS exhibited unfavorable neurologic outcomes. Preventive surgical treatment may be recommended for patients with significant OPLL with mild cervical myelopathy., Level of Evidence: 3.