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Abstract We investigated the regulation of histone deacetylases (HDACs) by miR-2861 in the osteoblastic differentiation of human mesenchymal stem cells (MSCs) and miR-2861 binding site by CRISPR activation (CRISPRa). Transfection of miR-2861 into human MSCs was performed and the effect on osteoblast differentiation was analyzed. Using catalytically inactive Cas12a, the CRISPRa system induced targeted overexpression of endogenous miRNA and repressed the luciferase activities of reporters that contained functional miRNA target sites. The delivery of miR-2861 into MSCs enhanced osteoblast differentiation by decreased expressions of the HDAC1, 4 and 5 genes. The mechanism of HDAC5 repression by miR-2861 in humans has not been fully elucidated. To this end, the HDAC5 mRNA sequence was analyzed and a putative primate-specific miR-2861 binding site was identified in the 3’ untranslated region (3’-UTR). CRISPRa was applied to validate the putative binding site and an increase in endogenous miR-2861 was found to repress the expression of a reporter that contained the novel miR-2861 binding site. The delivery of miR-2861 to human MSCs enhanced osteoblast differentiation. In the 3’-UTR, the HDAC5 repression was mediated by the miR-2861 binding site, and miR-2861 promoted osteoblast differentiation via the inhibition of HDAC5 through a primate-specific miRNA binding site. Therefore, miRNAmiR-2861 with the CRISPRa methods might be a good biomaterial for osteogenesis augmentation.

Objective We investigated the clinical efficacy of anabolic agents compared with bisphosphonates (BPs) for the incidence of new osteoporotic vertebral fracture (OVF) and fracture healing of OVF in the patients with OVF via meta-analyses of randomized controlled trials (RCTs). Methods Electronic databases, including PubMed, Embase, and Cochrane Library were searched for published RCTs till December 2022. The RCTs that recruited participants with osteoporosis at high-/very high-risk of fracture (a history of osteoporotic vertebral or hip fracture) or fresh OVF were included in this study. We assessed the risk of bias on every included RCTs, estimated relative risk (RR) for the incidence of new OVF and fracture healing of OVF, and overall certainty of evidence. Meta-analyses were performed by Cochrane review manager (RevMan) ver. 5.3. Cochrane risk of bias 2.0 and GRADEpro/GDT were applied for evaluating methodological quality and overall certainty of evidence, respectively. Results Five hundred eighteen studies were screened, and finally 6 eligible RCTs were included in the analysis. In the patients with prevalent OVF, anabolic agents significantly reduced the incidence of new OVF (teriparatide and romosozumab vs. alendronate and risedronate [RR, 0.57; 95% confidence interval, 0.45–0.71; p < 0.00001; high-certainty of evidence]; teriparatide vs. risedronate [RR, 0.50; 95% confidence interval, 0.37–0.68; p < 0.0001; high-certainty of evidence]). However, there was no evidence of teriparatide compared to alendronate in fracture healing of OVF (RR, 1.23; 95% confidence interval, 0.95–1.60; p = 0.12; low-certainty of evidence). Conclusion In the patients with prevalent OVF, anabolic agents showed a significant superiority for preventing new OVF than BPs, with no significant evidence for promoting fracture healing of OVF. However, considering small number of RCTs in this study, additional studies with large-scale data are required to obtain more robust evidences.

BackgroundWith the progressive increase in aging populations, the use of opportunistic computed tomography (CT) scanning is increasing, which could be a valuable method for acquiring information on both muscles and bones of aging populations. ObjectiveThe aim of this study was to develop and externally validate opportunistic CT-based fracture prediction models by using images of vertebral bones and paravertebral muscles. MethodsThe models were developed based on a retrospective longitudinal cohort study of 1214 patients with abdominal CT images between 2010 and 2019. The models were externally validated in 495 patients. The primary outcome of this study was defined as the predictive accuracy for identifying vertebral fracture events within a 5-year follow-up. The image models were developed using an attention convolutional neural network–recurrent neural network model from images of the vertebral bone and paravertebral muscles. ResultsThe mean ages of the patients in the development and validation sets were 73 years and 68 years, and 69.1% (839/1214) and 78.8% (390/495) of them were females, respectively. The areas under the receiver operator curve (AUROCs) for predicting vertebral fractures were superior in images of the vertebral bone and paravertebral muscles than those in the bone-only images in the external validation cohort (0.827, 95% CI 0.821-0.833 vs 0.815, 95% CI 0.806-0.824, respectively; P

Abstract This study aims to identify healthcare costs indicators predicting secondary surgery for degenerative lumbar spine disease (DLSD), which significantly impacts healthcare budgets. Analyzing data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database of Republic of Korea (ROK), the study included 3881 patients who had surgery for lumbar disc herniation (LDH), lumbar spinal stenosis without spondylolisthesis (LSS without SPL), lumbar spinal stenosis with spondylolisthesis (LSS with SPL), and spondylolysis (SP) from 2006 to 2008. Patients were categorized into two groups: those undergoing secondary surgery (S-group) and those not (NS-group). Surgical and interim costs were compared, with S-group having higher secondary surgery costs ($1829.59 vs $1618.40 in NS-group, P = 0.002) and higher interim costs ($30.03; 1.86% of initial surgery costs vs $16.09; 0.99% of initial surgery costs in NS-group, P

AbstractBackground Probabilistic graphical modelling (PGM) can be used to predict risk at the individual patient level and show multiple outcomes and exposures in a single model.Objective To develop PGM for the prediction of clinical outcome in patients with degenerative cervical myelopathy (DCM) after posterior decompression and to use PGM to identify causal predictors of the outcome.Methods We included data from 59 patients who had undergone cervical posterior decompression for DCM. The candidate predictive parameters were age, sex, body mass index, trauma history, symptom duration, preoperative and last Japanese Orthopaedic Association (JOA) scores, gait impairment, claudication, bladder dysfunction, Nurick grade, American Spinal Injury Association (ASIA) grade, smoking, diabetes mellitus, cardiopulmonary disorders, hypertension, stroke, Parkinson’s disease, dementia, psychiatric disorders, arthritis, ossification of the posterior longitudinal ligament, cord signal change, postoperative kyphosis and the cord compression ratio.Results In regression analyses, preoperative JOA (PreJOA) score, presence of a psychiatric disorder, and ASIA grade were identified as significant factors associated with the last JOS score. Dementia, sex, PreJOA score and gait impairment were causal factors in the PGM. Sex, dementia and PreJOA score were direct causal factors related to the last follow-up JOA (LastJOA) score. Being female, having dementia, and having a low PreJOA score were significantly related to having a low LastJOA score.Conclusions The causal predictors of surgical outcome for DCM were sex, dementia and PreJOA score. Therefore, PGM may be a useful personalized medicine tool for predicting the outcome of patients with DCM.

Abstract 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.

Polylactide (PLA) is an alternative to traditional petroleum-based polymers; however, its brittleness and tendency to produce rustling in the film form limit its applications in deep freeze packaging and at quiet public facilities. Herein, a PLA-based biodegradable packaging material was prepared by blending transparent flexible PLA (TF-PLA) with various lactic acid-based ester precursors (LAEPs), which were synthesized using l-lactic acid, poly (tetrahydrofuran), sebacic acid, and 1,4-butanediol, thereby producing TF-PLAs with good transparency and biodegradability, low-level migration, low rustling, and improved mechanical properties. The glass transition temperature (Tg) values and chemical structures of the synthesized LAEPs were studied using differential scanning calorimetry (DSC) with the Gordon–Taylor equation and proton nuclear magnetic resonance (1H NMR) spectroscopy. The obtained TF-PLA showed better elongation at room temperature as well as flexibility, with a bending angle comparable to that of neat PLA at extremely low temperatures. The evaluated barrier property and migration level of the TF-PLA film indicated the untapped market potential of TF-PLA. The biodegradability test of sorted TF-PLAs over eight weeks indicated good biodegradability, similar to that of neat PLA. Therefore, TF-PLAs have a high potential for deep freeze packaging applications.

Abstract Background The restoration of the functional ability of mesenchymal stem cells (MSCs) using epigenetic modification is very promising for patients with weak osteogenesis ability. This study focused on the acceleration of osteogenesis from MSCs using microRNA (miRNA)2861 and a cell-penetrating peptide (CPP), LK. Methods We performed MSCs penetration test of complex between the LK peptides and miRNA 2861. Three different experiments were performed to investigate the effects of miRNA 2861 on osteogenic differentiation in MSCs: 1) intensity of alizarin red staining, which reflects the status of mineralization by osteoblasts; 2) gene expression related to osteoblast differentiation; and 3) confirmation of corresponding protein translation for comparison with RNA expression levels. Results We found that cLK effectively delivered miRNA 2861 into the cytoplasm of human MSCs and accelerated osteogenic differentiation from MSCs, as well as mineralization. Conclusion The complex of miRNA 2861 with LK may have a positive effect on the osteogenic differentiation from MSCs and mineralization. Therapies using miRNAs combined with LK may be good candidates for the augmentation of osteogenesis in patients.

Abstract Lumbar spinal stenosis (LSS) and sagittal imbalance are relatively common in elderly patients. Although the goals of surgery include both functional and radiological improvements, the criteria of correction may be too strict for elderly patients. If the main symptom of patients is not forward-stooping but neurogenic claudication or pain, lumbar decompression without adding fusion procedure may be a surgical option. We performed cost-utility analysis between lumbar decompression and lumbar fusion surgery for those patients. Elderly patients (age > 60 years) who underwent 1–2 levels lumbar fusion surgery (F-group, n = 31) or decompression surgery (D-group, n = 40) for LSS with sagittal imbalance (C7 sagittal vertical axis, C7-SVA > 40 mm) with follow-up ≥ 2 years were included. Clinical outcomes (Euro-Quality of Life-5 Dimensions, EQ-5D; Oswestry Disability Index, ODI; numerical rating score of pain on the back and leg, NRS-B and NRS-L) and radiological parameters (C7-SVA; lumbar lordosis, LL; the difference between pelvic incidence and lumbar lordosis, PI-LL; pelvic tilt, PT) were assessed. The quality-adjusted life year (QALY) and incremental cost-effective ratio (ICER) were calculated from a utility score of EQ-5D. Postoperatively, both groups attained clinical and radiological improvement in all parameters, but NRS-L was more improved in the F-group (p = 0.048). ICER of F-group over D-group was 49,833 US dollars/QALY. Cost-effective lumbar decompression may be a recommendable surgical option for certain elderly patients, despite less improvement of leg pain than with fusion surgery.

Objective Total en bloc spondylectomy (TES) is a curative surgical method for spinal tumors. After resecting the 3 spinal columns, reconstruction is of paramount importance. We present cases of mechanical failure and suggest strategies for salvage surgery. Methods The medical records of 19 patients who underwent TES (9 for primary tumors and 10 for metastatic tumors) were retrospectively reviewed. Previously reported surgical techniques were used, and the surgical extent was 1 level in 16 patients and 2 levels in 3 patients. A titanium-based mesh-type interbody spacer filled with autologous and cadaveric bone was used for anterior support, and a pedicle screw/rod system was used for posterior support. Radiotherapy was performed in 11 patients (pre-TES, 5; post-TES, 6). They were followed up for 59 ± 38 months (range, 11–133 months). Results During follow-up, 8 of 9 primary tumor patients (89%) and 5 of 10 metastatic tumor patients (50%) survived (mean survival time, 124 ± 8 months vs. 51 ± 13 months; p=0.11). Mechanical failure occurred in 3 patients (33%) with primary tumors and 2 patients (20%) with metastatic tumors (p=0.63). The mechanical failure-free time was 94.4 ± 14 months (primary tumors, 95 ± 18 months; metastatic tumors, 68 ± 16 months; p=0.90). Revision surgery was performed in 4 of 5 patients, and bilateral broken rods were replaced with dual cobalt-chromium alloy rods. Repeated rod fractures occurred in 1 of 4 patients 2 years later, and the third operation (with multiple cobalt-chromium alloy rods) was successful for over 6 years. Conclusion Considering the difficulty of reoperation and patients’ suffering, preemptive use of a multiple-rod system may be advisable.

IntroductionFull-endoscopic lumbar discectomy (FELD) is a type of minimally invasive spinal surgery for lumbar disc herniation (LDH). Sufficient evidence exists to recommend FELD as an alternative to standard open microdiscectomy, and some patients prefer FELD due to its minimally invasive nature. However, in the Republic of Korea, the National Health Insurance System (NHIS) controls the reimbursement and use of supplies for FELD, but FELD is not currently reimbursed by the NHIS. Nonetheless, FELD has been performed upon patients' request, but providing FELD for patients' sake is inherently an unstable arrangement in the absence of a practical reimbursement system. The purpose of this study was to conduct a cost-utility analysis of FELD to suggest appropriate reimbursements.MethodThis study was a subgroup analysis of prospectively collected data including 28 patients who underwent FELD. All patients were NHIS beneficiaries and followed a uniform clinical pathway. Quality-adjusted life years (QALYs) were assessed with a utility score using the EuroQol 5-Dimension (EQ-5D) instrument. The costs included direct medical costs incurred at the hospital for 2 years and the price of the electrode ($700), although it was not reimbursed. The costs and QALYs gained were used to calculate the cost per QALY gained.ResultPatients' mean age was 43 years and one-third (32%) were women. L4-5 was the most common surgical level (20/28, 71%) and extrusion was the most common type of LDH (14, 50%). Half of the patients (15, 54%) had jobs with an intermediate level of activity. The preoperative EQ-5D utility score was 0.48±0.19. Pain, disability, and the utility score significantly improved starting 1 month postoperatively. The average EQ-5D utility score during 2 years after FELD was estimated as 0.81 (95% CI: 0.78-0.85). For 2 years, the mean direct costs were $3,459 and the cost per QALY gained was $5,241.ConclusionThe cost-utility analysis showed a quite reasonable cost per QALY gained for FELD. A comprehensive range of surgical options should be provided to patients, for which a practical reimbursement system is a prerequisite.

ObjectivePosterior full-endoscopic cervical foraminotomy (PECF) is one of minimally invasive surgical techniques for cervical radiculopathy. Because of minimal disruption of posterior cervical structures, such as facet joint, cervical kinematics was minimally changed. However, a larger resection of facet joint is required for cervical foraminal stenosis (FS) than disc herniation (DH). The objective was to compare the cervical kinematics between patients with FS and DH after PECF.MethodsConsecutive 52 patients (DH, 34 vs. FS, 18) who underwent PECF for single-level radiculopathy were retrospectively reviewed. Clinical parameters (neck disability index, neck pain and arm pain), and segmental, cervical and global radiological parameters were compared at postoperative 3, 6, and 12 months, and yearly thereafter. A linear mixed-effect model was used to assess interactions between groups and time. Any occurrence of significant pain during follow-up was recorded during a mean follow-up period of 45.5 months (range 24-113 months).ResultsClinical parameters improved after PECF, with no significant differences between groups. Recurrent pain occurred in 6 patients and surgery (PECF, anterior discectomy and fusion) was performed in 2 patients. Pain-free survival rate was 91% for DH and 83% for FS, with no significant difference between the groups (P = 0.29). Radiological changes were not different between groups (P > 0.05). Segmental neutral and extension curvature became more lordotic. Cervical curvature became more lordotic on neutral and extension X-rays, and the range of cervical motion increased. The mismatch between T1-slope and cervical curvature decreased. Disc height did not change, but the index level showed degeneration at postoperative 2 years.ConclusionClinical and radiological outcomes after PECF were not different between DH and FS patients and kinematics were significantly improved. These findings may be informative in a shared decision-making process.

Abstract Among plastic items, single‐use straws are particularly detrimental to marine ecosystems because such straws, including those made of poly(lactic acid) (PLA), are sharp and extremely slowly degradable in the ocean. While paper straws are promising alternatives, they exhibit hydration‐induced swelling even when coated with a non‐degradable plastic coating and promote effervescence (fizzing) in soft drinks owing to their surface heterogeneities. In this study, upgraded paper straw is coated with poly(butylene succinate) cellulose nanocrystal (PBS/CNC) composites. CNC increases adhesion to paper owing to their similar chemical structures, optimizes crystalline PBS spherulites through effective nucleation, and reinforces the matrix through its anisotropic and rigid features. The straws are not only anti‐fizzing when used with soft drinks owing to their homogeneous and seamless surface coatings, but also highly water‐resistant and tough owing to their watertight surfaces. All degradable components effectively decompose under aerobic composting and in the marine environment. This technology contributes to United Nations Sustainable Development Goal 14 (Life Below Water).

Abstract Radiotherapy has played an important role in the treatment of spinal metastases. One of the major complications of radiotherapy is vertebral compression fracture (VCF). Although the spinal instability neoplastic score (SINS) was developed for evaluating spinal instability in patients with spinal metastases, it is also commonly used to predict VCF after radiotherapy in patients with spinal metastases. However, its accuracy for predicting radiotherapy-induced VCF and precision remain controversial. The aim of this study was to clarify the diagnostic value of the SINS to predict radiotherapy-induced VCF and to make recommendations for improving its diagnostic power. We searched core databases and identified 246 studies. Fourteen studies were analyzed, including 7 studies (with 1269 segments) for accuracy and 7 studies (with 280 patients) for precision. For accuracy, the area under the summary receiver operating characteristic curve was 0.776. When a SINS cut-off value of 7 was used, as was done in the included studies, the pooled sensitivity was 0.790 and the pooled specificity was 0.546. For precision, the summary estimate of interobserver agreement was the highest dividing 2 categories based on a cut-off value of 7, and the value was 0.788. The body collapse showed moderate relationship and precision with the VCF. The lytic tumor of bone lesion showed high accuracy and fair reliability, while location had excellent reliability, but low accuracy. The SINS system can be used to predict the occurrence of VCF after radiotherapy in spinal metastases with moderate accuracy and substantial reliability. Increasing the cut-off value and revising the domains may improve the diagnostic performance to predict the VCF of the SINS.

Abstract Physicians often encounter surgical candidates with lumbar disc herniation (LDH) who request non-surgical management even though surgery is recommended. However, second opinions may differ among doctors. Therefore, a prospective comprehensive cohort study (CCS) was designed to assess outcomes of nonsurgical treatment for surgical candidates who were recommended to undergo surgery for LDH but requested a second opinion. The CCS includes both randomized and observational cohorts, comprising a nonsurgery cohort and surgery cohort, in a parallel fashion. Crossover between the nonsurgery and surgery cohorts was allowed at any time. The present study was an as-treated interim analysis of 128 cases (nonsurgery cohort, n = 71; surgery cohort, n = 57). Patient-reported outcomes included visual analogue scores for the back (VAS-B) and leg (VAS-L), the Oswestry Disability Index, the EuroQol 5-Dimension instrument, and the 36-Item Short-Form Health Survey (SF-36), which were evaluated at baseline and at 1, 3, 6, 12, and 24 months. At baseline, age and SF-36 physical function were significantly lower in the surgery cohort than in the nonsurgery cohort (p 0.01). Nonsurgical management may be a negotiable option even for surgical candidates in the shared decision-making process.

Background : Cytomegalovirus (CMV) infection is a crucial infection in kidney transplant recipients (KTRs) despite advancements in diagnostic and treatment methods. There are still many controversies about the ways to prevent CMV infection. Methods : We retrospectively analyzed 153 KTRs who underwent kidney transplantation (KT) between September 2013 and January 2016. We classified KTRs into two groups: valacyclovir prophylaxis group (intravenous ganciclovir for 2 weeks after KT, followed by oral valacyclovir for 3 months) and historical control group (only intravenous ganciclovir for 2 weeks after KT). We evaluated the incidence of CMV infection, clinical outcomes, CMV-free survival rate between the two groups and risk factors for the development of CMV infection. Results : Mean time between KT and diagnosis of CMV infection was 4.5±3.3 months. The valacyclovir prophylaxis group showed lower incidence of CMV infection than the historical control group (21.7% vs. 43.9%, P=0.011). The valacyclovir prophylaxis group showed higher CMV-free survival rate than the control group (P=0.011). In multivariable- adjusted analysis, independent risk factors for the development of CMV infection were no valacyclovir prophylaxis, older age at KT, thymoglobulin induction, and delayed graft function. Conclusions: Valacyclovir prophylaxis for 3 months showed significant reduction in the incidence of CMV infection in KTRs. Therefore, we suggest valacyclovir prophylaxis for 3 months in KTRs with risk factors such as old age, thymoglobulin induction, and delayed graft function.

Composite materials have been extensively studied to optimize properties such as lightness and strength, which are the advantages of plastics. We prepared a highly concentrated (30 wt %) nylon/chitosan nanowhisker (CSW) masterbatch by blending nylon 6,10 and CSW by solvent casting to achieve high dispersion efficiency while considering an industrial setting. Subsequently, 0.3 wt % nylon/CSW nanocomposites were prepared with a large quantity of nylon 6,10 via melt blending. During preparation, the materials were stirred in the presence of formic acid at different times to investigate the effect of stirring time on the structure of the CSW and the physical properties of the composite. The formation of nanocomposites by the interactions between nylon and CSW was confirmed by observing the change in hydrogen bonding using FT-IR spectroscopy and the rise in melting temperature and melting enthalpy through differential scanning calorimetry. The results demonstrated increases in complex viscosity and shear thinning. The rheological properties of the composites changed due to interactions between CSW and nylon, as indicated by the loss factor. The mechanical properties produced by the nanocomposite stirred for 1.5 h were superior, suggesting that formic acid caused minimal structural damage, thus verifying the suitability of the stirring condition.

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.

Background Although kidney transplantation outcomes have improved dramatically after using calcineurin inhibitors (CNIs), CNI toxicity continues to be reported and the mechanism remains uncertain. Here, we investigated the neurotoxicity of CNIs by focusing on the viability of glioma cells. Methods Glioma cells were treated with several concentrations of CNIs for 24 hours at 37℃ and their cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Results Exposure to 0, 0.25, 0.5, 2.5, 5.0, and 10.0 mM concentrations respectively showed 100%, 64.3%, 61.3%, 68.1%, 62.4%, and 68.6% cell viability for cyclosporine and 100%, 38.6%, 40.8%, 43.7%, 37.8%, and 43.0% for tacrolimus. The direct toxic effect of tacrolimus on glioma cell viability was stronger than that of cyclosporine at the same concentration. Conclusion CNIs can cause neurological side effects by directly exerting cytotoxic effects on brain cells. Therefore, we should carefully monitor the neurologic symptoms and level of CNIs in kidney transplant patients.

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

Fabry disease (FD) is an X-linked, recessively inherited, rare, progressive, disorder of glycosphingolipid metabolism affecting multiple organs resulting in organ dysfunction. It is rare to find only one FD affected subject with a de novo mutation. Here we report a case of a 41-year-old Asian male diagnosed with de novo FD. Comprehensive ophthalmological evaluation was performed using slit lamp, color fundus photography, optical coherence tomography, fluorescein angiography, and indocyanine green angiography. On slit lamp examination, cornea verticillata and slightly tortuous, and aneurysmal dilatation of inferior bulbar conjunctival vessels were observed. Other imaging modalities showed unremarkable findings. Cornea verticillata and inferior bulbar conjunctival vascular abnormalities may be detected earlier than other ocular abnormalities in de novo FDs like hereditary FDs.

ObjectiveThe demand for treating degenerative lumbar spinal disease has been increasing, leading to increased utilization of medical resources. Thus, we need to understand how the budget of insurance is currently used. The objective of the present study is to overview the utilization of the National Health Insurance Service (NHIS) by providing the direct insured cost between patients receiving surgery and patients receiving nonsurgical treatment for degenerative lumbar disease.MethodsThe NHIS-National Sample Cohort was utilized to select patients with lumbar disc herniation, spinal stenosis, spondylolisthesis or spondylolysis. A matched cohort study design was used to show direct medical costs of surgery (n = 2,698) and nonsurgical (n = 2,698) cohorts. Non-surgical treatment included medication, physiotherapy, injection, and chiropractic. The monthly costs of the surgery cohort and nonsurgical cohort were presented at initial treatment, posttreatment 1, 3, 6, 9, and 12 months and yearly thereafter for 10 years.ResultsThe characteristics and matching factors were well-balanced between the matched cohorts. Overall, surgery cohort spent $50.84/patient/month, while the nonsurgical cohort spent $29.34/patient/month (pConclusionSurgical treatment initially led to more government reimbursement than nonsurgical treatment, but the charges during follow-up period were not different. The results of the present study should be interpreted in light of the costs of medical services, indirect costs, societal cost, quality of life and societal willingness to pay in each country. The monetary figures are implied to be actual economic costs but those in the reimbursement system instead reflect reimbursement charges from the government.

We reviewed charts and radiologic studies of 30 patients operated upon by ADR with Mobi-C® in single level since 2006. All patients had healthy cervical facet joints (less than or equal to grade 1 according to grading systems for cervical facet joint degeneration) preoperatively. We assessed clinical outcomes with NDI and VAS on neck and arm over follow-up and also measured ROM at implanted segment on dynamic radiographs during follow-up. The mean follow-up period was 42.4 ± 15.9 months. We then assessed the linearity of changes in ROM at implanted segment through linear mixed model. All patients showed significantly improved clinical outcomes. ROMs at implanted segment were maintained at slightly increased levels until 24 months postoperatively (P = 0.529). However, after 24 months, ROMs at implanted segment decreased significantly until last follow-up (P = 0.001). In addition, the decreasing pattern after 24 months showed a regular regression (P = 0.001). This decline was correlated with decline of extension angle at implanted segment. Based on this regular regression, we estimated that ROMs at implanted segments would be less than 2 degrees at 10.24 years postoperatively. Even though implanted segment maintains its motion for some length of time, we could assume that an artificial disc would have limited life expectancy correlated with the decline of extension angle.

Background : The long-term prognosis of BK virus-associated nephropathy (BKVAN) in kidney transplant recipients (KTRs) is uncertain. We evaluated the long-term prognosis in KTRs with BKVAN and the clinical significance of BKVAN on post-transplant clinical outcome. Methods : We retrospectively analyzed the medical records of 582 patients who underwent kidney transplant (KT) between 2001 and 2014. We divided the patients into a BKVAN group (15 patients) diagnosed by allograft biopsy and a control group (356 patients). Results : The incidence of BKVAN was 4.0%, and the mean follow-up duration was 93.1 ± 52.3 months. Median time from KT to BKVAN diagnosis was 5.9 months (interquartile range [IQR], 4.4-8.7). In the BKVAN group, 9 (60.0%) KTRs with combined acute rejection progressed to graft failure, and the median time from BKVAN diagnosis to graft failure was 36.2 months (IQR, 9.7-65.5). Death-censored graft survival rate and patient survival rate in the BKVAN group were significantly lower than those in the control group. BKVAN and rejection were independent risk factors for graft failure. In the subgroup analysis, death-censored graft survival rate of KTRs with BKVAN with acute rejection was significantly worst in comparison with similar patients without BKVAN regardless of acute rejection (P ＜ 0.001). Conclusion : The long-term prognosis of BKVAN with acute rejection was very poor because of graft failure caused by inadequate treatment for acute rejection considering BKVAN. Therefore, we should carefully monitor the allograft status of KTRs through regular surveillance tests after treatment for BKVAN with acute rejection.

Background. A multicenter, randomized, open-label, parallel group, pilot, 52-week study in Asian countries that assessed the renal function, efficacy, and safety of reduced-exposure versus standard-exposure prolonged-release tacrolimus (PR-T) in adult kidney transplant recipients (KTRs). Methods. Posttransplantation, KTRs received PR-T from weeks 0 to 4 (initial dose, 0.2–0.3 mg/kg; target trough level, 6–10 ng/mL). At week 4, KTRs were randomized (1:1) to receive reduced-exposure PR-T (target 4–6 ng/mL, weeks 4–12; 3–5 ng/mL, weeks 12–52) or standard-exposure PR-T (target: 6–10 ng/mL, weeks 4–52). Primary end point: estimated glomerular filtration rate (eGFR) over 52 weeks. Secondary end points (week 52) included creatinine clearance, serum creatinine, graft/patient survival, biopsy-confirmed acute rejection (AR), composite of graft loss/patient death/biopsy-confirmed AR, and steroid-resistant AR. Treatment-emergent adverse events were recorded. Results. Sixty-six KTRs received PR-T (reduced-exposure, n = 32; standard-exposure, n = 34) and were analyzed. After per-protocol dose adjustment, mean ± standard deviation tacrolimus trough level was lower with reduced- versus standard-exposure PR-T (week 52, 4.5 ± 1.1 ng/mL vs 8.0 ± 2.2 ng/mL). In the reduced- versus standard-exposure group, eGFR was similar at weeks 8 to 52 (overall least-square mean difference, –2.82; 95% confidence interval, −7.91 to 2.27; P = 0.272). At week 52, there was no significant difference in creatinine clearance (P = 0.375) or serum creatinine (P = 0.547) between groups. All grafts/patients survived, no steroid-resistant AR was reported, and 4 and 3 patients had AR in reduced- and standard-exposure groups, respectively. Drug-related treatment-emergent adverse events were reported in 34.4% and 38.2% of patients, respectively. Conclusions. Reducing exposure to PR-T resulted in a clinically acceptable short-term safety profile and was generally as effective as standard tacrolimus exposure for Asian patients.

Objective Posterior percutaneous endoscopic cervical foraminotomy (P-PECF) is a minimally invasive surgical technique for treatment of cervical radiculopathies. Application of P-PECF to patients with preexisting loss of cervical curvature (

Epithelioid angiomyolipoma (EAML) is an uncommon, variant type of angiomyolipoma with a possibility of metastatic transformation and distant spread. Angiomyolipomas, including epithelioid variant type, are mostly renal in origin. EAML originating from extrarenal location is very rare and imaging findings are not well described. Herein, we reported a very rare case of EAML arising from the perirenal space that mimicked a malignant retroperitoneal tumor, in a 39-year-old female.

Background: Kidney transplantation (KT) is the treatment of choice for end-stage renal disease patients. The spouse is a major donor in living KT. Clinical outcomes of spousal donor KT are not inferior to those of living related donor KT. In this study, we compared clinical outcomes between ABO-compatible (ABOc) and ABO-incompatible (ABOi) spousal donor KTs. Methods: Thirty-two cases of spousal donor KT performed from January 2011 to August 2013 were analyzed retrospectively. Twenty-one ABOc KTs and 11 ABOi KTs were performed. We investigated patient survival, graft survival, acute rejection, graft function, and complications. Results: During follow-up, patient and graft survival rates were 100% in both groups. There were no significant differences in the incidence of delayed graft function, acute rejection, and the change in graft function between the 2 groups. Medical and surgical complications were not significantly different between the groups. Conclusion: The clinical outcomes of ABOc and ABOi spousal donor KTs were equivalent. In ABOi KT, an emotionally motivated spousal donor KT may be a good alternative to the problem of the absolute shortage of kidney donations.

Category: Bunion Introduction/Purpose: The scarf osteotomy has gained in popularity for the treatment of a symptomatic hallux valgus deformity due to its inherent stability, versatility of correction and early mobilization. We have reported parallel-shaped modified scarf osteotomy(PSMSO) with good functional outcomes and no complication as stress fracture or troughing. However, we encountered second transfer metatarsalgia after the osteotomy. The scarf osteotomy can be shortened, but there was no specific amount of shortening that will produce transfer metatarsalgia in limitation of our literature review. In this study, we measured the shortening of first metatarsal length and investigated the relation of first metatarsal length and second transfer metatarsalgia after PSMSO for hallux valgus deformity. Methods: We retrospectively reviewed 168 consecutive PSMSOs performed in 124 patients with hallux valgus deformity between March 2009 and August 2015. Concomitant other pathologies of foot or previous second metatarsalgia were excluded. After excluding 45 cases, 123 cases in 88 patients were included. For clinical assessment, VAS, the AOFAS Hallux Metatarsophalangeal-Interphalangeal (AOFAS Hallux MTP-IP) Scale were obtained. The hallux valgus angle (HVA), the intermetatarsal angle (IMA), the distal metatarsal articular angle (DMAA), the first metatarsal length measured by a modified Davies and Saxby’s method and the protrusion of second metatarsal relative to first metatarsal using the Maestro’s method were assessed on standard weight bearing radiographs of the foot. For evaluation of the development of second transfer metatarsalgia, callosity or tenderness beneath the second metatarsal head was investigated. After identifying the lesion, we divided two groups with and without second transfer metatarsalgia and compared the variables after propensity score matching. Results: Mean follow-up period was 20.6±7.8 (12-66) months. The mean VAS and AOFAS Hallux MTP-IP score improved significantly (p

Objective : The use of indocyanine green videoangiography (ICG-VA) to assess blood flow in the brain during cerebrovascular surgery has been increasing. Clinical studies on ICG-VA have predominantly focused on qualitative analysis. However, quantitative analysis numerical modelling for time profiling enables a more accurate evaluation of blood flow kinetics. In this study, we established a multiple exponential modified Gaussian (multi-EMG) model for quantitative ICG-VA to understand accurately the status of cerebral hemodynamics. Methods : We obtained clinical data of cerebral blood flow acquired the quantitative analysis ICG-VA during cerebrovascular surgery. Varied asymmetric peak functions were compared to find the most matching function form with clinical data by using a nonlinear regression algorithm. To verify the result of the nonlinear regression, the mode function was applied to various types of data. Results : The proposed multi-EMG model is well fitted to the clinical data. Because the primary parameters—growth and decay rates, and peak center and heights—of the model are characteristics of model function, they provide accurate reference values for assessing cerebral hemodynamics in various conditions. In addition, the primary parameters can be estimated on the curves with partially missed data. The accuracy of the model estimation was verified by a repeated curve fitting method using manipulation of missing data. Conclusion : The multi-EMG model can possibly serve as a universal model for cerebral hemodynamics in a comparison with other asymmetric peak functions. According to the results, the model can be helpful for clinical research assessment of cerebrovascular hemodynamics in a clinical setting. [ABSTRACT FROM AUTHOR]