SUMO-specific protease 2 regulates lipid droplet size through ERRα-mediated CIDEA expression in adipocytes.

Lipid droplets are not only lipid storage sites but also are closely related to lipid metabolism. Lipid droplet growth increases lipid storage capacity and suppresses lipolysis via lipase associated with the lipid droplet surface. The cell death-inducing DFF45-like effector (CIDE) family of proteins mediates lipid droplet fusion, which mainly contributes to lipid droplet growth. We previously demonstrated small ubiquitin-like modifier (SUMO)-specific protease 2 (SENP2) plays important roles in lipid metabolism and induction/maintenance of adipogenesis. In this study, we determined whether SENP2 regulates lipid droplet size in adipocytes. Overexpression of SENP2 increased lipid droplet size in differentiated 3T3-L1 adipocytes and facilitated CIDEA transcription. We found SENP2 increased CIDEA expression mainly through desumoylation of estrogen-related receptor α (ERRα), which acted in coordination with peroxisome proliferator-activated receptor γ-coactivator α. In addition, palmitate treatment increased SENP2 and CIDEA mRNA levels. Specific small interfering RNA-mediated knockdown of SENP2, as well as ERRα knockdown, eliminated palmitate-induced CIDEA expression. These results suggest SENP2 enhances CIDEA expression by modulating ERRα when SENP2 is upregulated, such as after palmitate treatment, to increase lipid droplet size in adipocytes.

Direct Differentiation of Bone Marrow Mononucleated Cells Into Insulin-Producing Cells Using 4 Specific Soluble Factors.

Bone marrow-derived stem cells are self-renewing and multipotent adult stem cells that differentiate into several types of cells. Here, we investigated a unique combination of 4 differentiation-inducing factors (DIFs), including putrescine (Put), glucosamine (GlcN), nicotinamide, and BP-1-102, to develop a differentiation method for inducing mature insulin-producing cells (IPCs) and apply this method to bone marrow mononucleated cells (BMNCs) isolated from mice. BMNCs, primed with the 4 soluble DIFs, were differentiated into functional IPCs. BMNCs cultured under the defined conditions synergistically expressed multiple genes, including those for PDX1, NKX6.1, MAFA, NEUROG3, GLUT2, and insulin, related to pancreatic beta cell development and function. They produced insulin/C-peptide and PDX1, as assessed using immunofluorescence and flow cytometry. The induced cells secreted insulin in a glucose-responsive manner, similar to normal pancreatic beta cells. Grafting BMNC-derived IPCs under kidney capsules of mice with streptozotocin (STZ)-induced diabetes alleviated hyperglycemia by lowering blood glucose levels, enhancing glucose tolerance, and improving glucose-stimulated insulin secretion. Insulin- and PDX1-expressing cells were observed in the IPC-bearing graft sections of nephrectomized mice. Therefore, this study provides a simple protocol for BMNC differentiation, which can be a novel approach for cell-based therapy in diabetes mellitus.

Role of SUMO-Specific Protease 2 in Leptin-Induced Fatty Acid Metabolism in White Adipocytes.

BACKGROUND: Leptin is a 16-kDa fat-derived hormone with a primary role in controlling adipose tissue levels. Leptin increases fatty acid oxidation (FAO) acutely through adenosine monophosphate-activated protein kinase (AMPK) and on delay through the SUMO-specific protease 2 (SENP2)-peroxisome proliferator-activated receptor δ/γ (PPARδ/γ) pathway in skeletal muscle. Leptin also directly increases FAO and decreases lipogenesis in adipocytes; however, the mechanism behind these effects remains unknown. Here, we investigated the role of SENP2 in the regulation of fatty acid metabolism by leptin in adipocytes and white adipose tissues. METHODS: The effects of leptin mediated by SENP2 on fatty acid metabolism were tested by siRNA-mediated knockdown in 3T3-L1 adipocytes. The role of SENP2 was confirmed in vivo using adipocyte-specific Senp2 knockout (Senp2-aKO) mice. We revealed the molecular mechanism involved in the leptin-induced transcriptional regulation of carnitine palmitoyl transferase 1b (Cpt1b) and long-chain acyl-coenzyme A synthetase 1 (Acsl1) using transfection/reporter assays and chromatin immunoprecipitation. RESULTS: SENP2 mediated the increased expression of FAO-associated enzymes, CPT1b and ACSL1, which peaked 24 hours after leptin treatment in adipocytes. In contrast, leptin stimulated FAO through AMPK during the initial several hours after treatment. In white adipose tissues, FAO and mRNA levels of Cpt1b and Acsl1 were increased by 2-fold 24 hours after leptin injection in control mice but not in Senp2-aKO mice. Leptin increased PPARα binding to the Cpt1b and Acsl1 promoters in adipocytes through SENP2. CONCLUSION: These results suggest that the SENP2-PPARα pathway plays an important role in leptin-induced FAO in white adipocytes.

SENP2 suppresses browning of white adipose tissues by de-conjugating SUMO from C/EBPß.

The adipose tissue is a key site regulating energy metabolism. One of the contributing factors behind this is browning of white adipose tissue (WAT). However, knowledge of the intracellular determinants of the browning process remains incomplete. By generating adipocyte-specific Senp2 knockout (Senp2-aKO) mice, here we show that SENP2 negatively regulates browning by de-conjugating small ubiquitin-like modifiers from C/EBPß. Senp2-aKO mice are resistant to diet-induced obesity due to increased energy expenditure and heat production. Senp2 knockout promotes beige adipocyte accumulation in inguinal WAT by upregulation of thermogenic gene expression. In addition, SENP2 knockdown promotes thermogenic adipocyte differentiation of precursor cells isolated from inguinal and epididymal WATs. Mechanistically, sumoylated C/EBPß, a target of SENP2, suppresses expression of HOXC10, a browning inhibitor, by recruiting a transcriptional repressor DAXX. These findings indicate that a SENP2-C/EBPß-HOXC10 axis operates for the control of beige adipogenesis in inguinal WAT.

SENP2 regulates mitochondrial function and insulin secretion in pancreatic ß cells.

Increasing evidence has shown that small ubiquitin-like modifier (SUMO) modification plays an important role in metabolic regulation. We previously demonstrated that SUMO-specific protease 2 (SENP2) is involved in lipid metabolism in skeletal muscle and adipogenesis. In this study, we investigated the function of SENP2 in pancreatic ß cells by generating a ß cell-specific knockout (Senp2-ßKO) mouse model. Glucose tolerance and insulin secretion were significantly impaired in the Senp2-ßKO mice. In addition, glucose-stimulated insulin secretion (GSIS) was decreased in the islets of the Senp2-ßKO mice without a significant change in insulin synthesis. Furthermore, islets of the Senp2-ßKO mice exhibited enlarged mitochondria and lower oxygen consumption rates, accompanied by lower levels of S616 phosphorylated DRP1 (an active form of DRP1), a mitochondrial fission protein. Using a cell culture system of NIT-1, an islet ß cell line, we found that increased SUMO2/3 conjugation to DRP1 due to SENP2 deficiency suppresses the phosphorylation of DRP1, which possibly induces mitochondrial dysfunction. In addition, SENP2 overexpression restored GSIS impairment induced by DRP1 knockdown and increased DRP1 phosphorylation. Furthermore, palmitate treatment decreased phosphorylated DRP1 and GSIS in ß cells, which was rescued by SENP2 overexpression. These results suggest that SENP2 regulates mitochondrial function and insulin secretion at least in part by modulating the phosphorylation of DRP1 in pancreatic ß cells.

Effects of an Individualized Educational Program for Korean Patients With Chronic Low Back Pain: A Randomized Controlled Trial.

BACKGROUND: Most patients with low back pain prefer to ignore symptoms and avoid medical management because of incorrect perceptions about this condition. However, over 90% of patients with chronic low back pain are hardly unable to perform daily activities, with 50% reporting that their daily activities have been severely impeded. PURPOSE: In this study, an individualized educational program was developed and implemented in a sample of Korean patients with chronic low back pain, and the effectiveness of this program was evaluated. METHODS: This study was conducted as a randomized controlled trial with outpatients (n = 43) in an orthopedic clinic. The Analysis, Design, Development, Implementation, and Evaluation model was applied to develop the educational program. The experimental group was provided with an educational booklet and contacted via biweekly personalized telephone and face-to-face counseling sessions. The control group was provided the educational booklet only. SAS Version 9.4 was used to analyze collected data using the χ2 test, t test, Fisher's exact test, Wilcoxon test, linear regression analysis, and Spearman partial correlation analysis. RESULTS: After 8 weeks, the experimental group demonstrated a significantly greater reduction in maximum, average, and current low back pain experienced within the immediately preceding 24 hours than the control group (p = .001, p = .002, and p = .014, respectively). In addition, daily living disability showed a greater reduction, and average back muscle strength showed a more significant improvement in the experimental group than in the control group (p = .001 and p = .035). The difference in medication adherence between the groups was not statistically significant (p = .089). The experimental group rated an average of 4.3 out of 5.0 points on the program satisfaction scale, indicating an 86% rate of satisfaction. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: In this study, the individualized educational program was shown to be effective in helping alleviate symptoms in patients with chronic low back pain, decrease daily living disability, and improve average back muscle strength. It was further demonstrated that following up with expert medical staffs can motivate patients to incorporate the recommendations of the program into their daily routine, leading to higher patient satisfaction.

An Essential Role of the N-Terminal Region of ACSL1 in Linking Free Fatty Acids to Mitochondrial ß-Oxidation in C2C12 Myotubes.

Free fatty acids are converted to acyl-CoA by long-chain acyl-CoA synthetases (ACSLs) before entering into metabolic pathways for lipid biosynthesis or degradation. ACSL family members have highly conserved amino acid sequences except for their N-terminal regions. Several reports have shown that ACSL1, among the ACSLs, is located in mitochondria and mainly leads fatty acids to the ß-oxidation pathway in various cell types. In this study, we investigated how ACSL1 was localized in mitochondria and whether ACSL1 overexpression affected fatty acid oxidation (FAO) rates in C2C12 myotubes. We generated an ACSL1 mutant in which the N-terminal 100 amino acids were deleted and compared its localization and function with those of the ACSL1 wild type. We found that ACSL1 adjoined the outer membrane of mitochondria through interaction of its N-terminal region with carnitine palmitoyltransferase-1b (CPT1b) in C2C12 myotubes. In addition, overexpressed ACSL1, but not the ACSL1 mutant, increased FAO, and ameliorated palmitate-induced insulin resistance in C2C12 myotubes. These results suggested that targeting of ACSL1 to mitochondria is essential in increasing FAO in myotubes, which can reduce insulin resistance in obesity and related metabolic disorders.

Is allograft a more reliable treatment option than autograft in 2-level anterior cervical discectomy and fusion with plate fixation?

This study aimed to assess the efficacy of allograft in 2-level anterior cervical discectomy and fusion (ACDF) with plate fixation by comparing its clinical and radiological outcomes to those of autograft.Thirty five patients with femur cortical allografts and 32 patients with tricortical iliac autografts were evaluated. All surgeries were performed by a single senior surgeon. During routine follow-up (at 3 months, 6 months, and annually after the surgery), the fusion rate, subsidence rate, and fused segmental lordosis angle were assessed by radiologic evaluation. Clinical outcomes were assessed using the visual analog scale (VAS), neck disability index (NDI) scores, and Odom criteria. This study was conducted using the results of the 2-year postoperative follow-up.Among 67 patients, 62 (92.5%) showed successful bone fusion at 2 years postoperatively: 91.4% (32/35) in the allograft group and 93.8% (30/32) in the autograft group. The fusion rate was 37.1% (13/35) in the allograft group and 68.8% (23/32) in the autograft group at 6 months and 68.5% (24/35) in the allograft group and 93.8% (30/32) in autograft group at 1 year. Eight (72.7%) of the remaining 11 patients with allograft achieved bone fusion without any intervention at the 2-year follow-up. The fusion was achieved faster in the autograft group than in the allograft group (P = .003). There was no significant difference in the subsidence rate or change in the fused segmental lordosis angle between the 2 groups; there was also no significant difference in clinical outcomes (NDI scores, VAS scores, Odom criteria) between the 2 groups. However, the intraoperative blood loss was significantly greater in the autograft group, and the operative time was also significantly longer in the autograft group (P < .001). In the autograft group, 6 patients (18.8%) had minor complications at the donor site.In 2-level ACDF with plate fixation, the radiologic and clinical outcomes of autograft and allograft were similar at 2-year follow-up, although fusion was observed earlier in the autograft group.

Metformin Ameliorates Lipotoxic ß-Cell Dysfunction through a Concentration-Dependent Dual Mechanism of Action.

BACKGROUND: Chronic exposure to elevated levels of free fatty acids contributes to pancreatic ß-cell dysfunction. Although it is well known that metformin induces cellular energy depletion and a concomitant activation of AMP-activated protein kinase (AMPK) through inhibition of the respiratory chain, previous studies have shown inconsistent results with regard to the action of metformin on pancreatic ß-cells. We therefore examined the effects of metformin on pancreatic ß-cells under lipotoxic stress. METHODS: NIT-1 cells and mouse islets were exposed to palmitate and treated with 0.05 and 0.5 mM metformin. Cell viability, glucose-stimulated insulin secretion, cellular adenosine triphosphate, reactive oxygen species (ROS) levels and Rho kinase (ROCK) activities were measured. The phosphorylation of AMPK was evaluated by Western blot analysis and mRNA levels of endoplasmic reticulum (ER) stress markers and NADPH oxidase (NOX) were measured by real-time quantitative polymerase chain reaction analysis. RESULTS: We found that metformin has protective effects on palmitate-induced ß-cell dysfunction. Metformin at a concentration of 0.05 mM inhibits NOX and suppresses the palmitate-induced elevation of ER stress markers and ROS levels in a AMPK-independent manner, whereas 0.5 mM metformin inhibits ROCK activity and activates AMPK. CONCLUSION: This study suggests that the action of metformin on ß-cell lipotoxicity was implemented by different molecular pathways depending on its concentration. Metformin at a usual therapeutic dose is supposed to alleviate lipotoxic ß-cell dysfunction through inhibition of oxidative stress and ER stress.

Direct differentiation of bone marrow mononucleated cells into insulin producing cells using pancreatic ß-cell-derived components.

Transplantation of stem cell-derived insulin producing cells (IPCs) has been proposed as an alternative to islet transplantation for the treatment of diabetes mellitus. However, current IPC differentiation protocols are focused on generating functional cells from the pluripotent stem cells and tend to rely on multistep, long-term exposure to various exogenous factors. In this study, we addressed the observation that under stress, pancreatic ß-cells release essential components that direct the differentiation of the bone marrow nucleated cells (BMNCs) into IPCs. Without any supplementation with known differentiation-inducing factors, IPCs can be generated from BMNCs by in vitro priming for 6 days with conditioned media (CM) from the ß-cells. In vitro primed BMNCs expressed the ß-cell-specific transcription factors, as well as insulin, and improved hyperglycemia and glucose intolerance after transplantation into the streptozotocin-induced diabetic mice. Furthermore, we have found that components of the CM which trigger the differentiation were enclosed by or integrated into micro particles (MPs), rather than being secreted as soluble factors. Identification of these differentiation-directing factors might enable us to develop novel technologies required for the production of clinically applicable IPCs.

SUMO-specific protease 2 mediates leptin-induced fatty acid oxidation in skeletal muscle.

BACKGROUND AND PURPOSE: In addition to the central nervous system-mediated action, leptin also directly induces fatty acid oxidation in skeletal muscle. Rapid induction of FAO by leptin is mediated by the AMP-activated protein kinase (AMPK) pathway, but the mechanism of prolonged FAO by leptin was previously unknown. In an earlier study, we showed that free fatty acids increase transcription of small ubiquitin-like modifier (SUMO) specific protease 2 (SENP2) in skeletal muscle, and that SENP2 stimulates expression of FAO-associated enzymes by deSUMOylating peroxisome proliferator-activated receptors, PPARδ and PPARγ. In this study, we examine whether SENP2 is involved in prolonged stimulation of FAO by leptin. METHODS: The Effect of leptin on expression of SENP2 and on SENP2-mediated FAO was investigated by using western blotting and real time qPCR of C2C12 myotubes, and of C2C12 myotubes in which expression of specific genes was knocked down using siRNAs. Additionally, muscle-specific SENP2 knockout mice were generated to test the involvement of SENP2 in leptin-induced FAO in vivo. RESULTS: We show that leptin treatment of C2C12 myotubes causes signal transducer and activator of transcription 3 (STAT3) to bind to the Senp2 promoter, inducing SENP2 expression. We also show that leptin increases the binding of PPARδ and PPARγ to PPRE sites in the promoters of two FAO-associated genes: long-chain acyl-CoA synthetase 1 (Acsl1) or carnitine palmitoyl transferase 1b (Cpt1b). When SENP2 is knocked down in myotubes, leptin-induced expression of FAO-associated enzymes and prolonged increase of FAO are suppressed, but rapid increase of FAO is unaffected. In addition, leptin-induced expression of FAO-associated enzymes was not observed in muscle tissue of SENP2 knockout mice. CONCLUSIONS: We demonstrate that the peripheral actions of leptin on FAO are mediated by two different pathways: AMPK causes a rapid increase in FAO, and SENP2 of the STAT3 pathway causes a slow, prolonged increase in FAO.

Re-highlighting the action of PPARγ in treating metabolic diseases.

Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor family and plays an important role in adipocyte differentiation, glucose homeostasis, and insulin sensitivity. Thiazolidinediones (TZDs), synthetic ligands of PPARγ, have been used for the treatment of diabetes mellitus for two decades. TZDs were expected to be amazing drugs not only for type 2 diabetes but also for metabolic syndrome and atherosclerotic vascular disease because they can reduce both insulin resistance and inflammation in experimental studies. However, serious unwanted effects pushed TZDs back to an optional second-tier drug for type 2 diabetes. Nevertheless, PPARγ is still one of the most important targets for the treatment of insulin resistance and diabetes mellitus, and novel strategies to modulate PPARγ activity to enhance its beneficial effects and reduce unwanted adverse effects are anticipated. Recent studies showed that post-translational modification (PTM) of PPARγ regulates PPARγ activity or stability and may be a novel way to optimize PPARγ activity with reduced adverse effects. In this review, we will focus on recent advances in PTM of PPARγ and the mechanisms regulating PPARγ function as well as in the development of PPARγ modulators or agonists.

Analgesic Efficacy and Safety of Prolonged-Release Oxycodone/Naloxone in Korean Patients with Chronic Pain from Spinal Disorders.

BACKGROUND: A prolonged-release formulation of oxycodone/naloxone has been shown to be effective in European populations for the management of chronic moderate to severe pain. However, no clinical data exist for its use in Korean patients. The objective of this study was to assess efficacy and safety of prolonged-release oxycodone/naloxone in Korean patients for management of chronic moderate-to-severe pain. METHODS: In this multicenter, single-arm, open-label, phase IV study, Korean adults with moderate-to-severe spinal disorder-related pain that was not satisfactorily controlled with weak opioids and nonsteroidal anti-inflammatory drugs received prolonged-release oral oxycodone/naloxone at a starting dose of 10/5 mg/day (maximum 80/40 mg/day) for 8 weeks. Changes in pain intensity and quality of life (QoL) were measured using a numeric rating scale (NRS, 0-10) and the Korean-language EuroQol-five dimensions questionnaire, respectively. RESULTS: Among 209 patients assessed for efficacy, the mean NRS pain score was reduced by 25.9% between baseline and week 8 of treatment (p < 0.0001). There was also a significant improvement in QoL from baseline to week 8 (p < 0.0001). The incidence of adverse drug reactions was 27.7%, the most common being nausea, constipation, and dizziness; 77.9% of these adverse drug reactions had resolved or were resolving at the end of the study. CONCLUSIONS: Prolonged-release oxycodone/naloxone provided significant and clinically relevant reductions in pain intensity and improved QoL in Korean patients with chronic spinal disorders. (ClinicalTrials.gov identifier: NCT01811238).

Carnitine induces autophagy and restores high-fat diet-induced mitochondrial dysfunction.

OBJECTIVE: Autophagy is suppressed in skeletal muscle and the liver with insulin resistance induced by a high-fat diet. Autophagy is essential for maintaining mitochondrial function, and dysfunctional mitochondria are associated with insulin resistance. As carnitine treatment is well known to improve insulin resistance by promoting mitochondrial function, we investigated if carnitine affects autophagy in the skeletal muscle of a high-fat diet-induced rodent model of obesity. RESULTS: After 6weeks on a high-fat diet (48kcal% fat), mice developed glucose intolerance, and the gastrocnemius muscle showed a decrease in insulin signaling and mitochondrial function, which was reversed after carnitine (100mg/kg/day) treatment by oral gavage for 2weeks. Swollen mitochondria with destroyed cristae were observed in the skeletal muscle of high-fat diet-fed mice but were not there after carnitine treatment. High-fat diet decreased LC3B-II, a marker of autophagosome formation, and increased sequestosome 1 (SQSTM1), expression of which was reversed after carnitine treatment. In C2C12 myotubes, prolonged treatment with palmitate suppressed autophagy, which was relieved by carnitine treatment. However, the induction of autophagy by carnitine in C2C12 myotubes was not observed after knock-down of peroxisome proliferator-activated receptor γ (PPARγ), which is known to regulate autophagy. CONCLUSION: We conclude that the removal of dysfunctional mitochondria by induction of autophagy through PPARγ may be a novel mechanism by which carnitine improves insulin resistance and mitochondrial dysfunction in obesity.

Radiological and clinical long-term results of heterotopic ossification following lumbar total disc replacement.

BACKGROUND: The long-term results of heterotopic ossification (HO) following lumbar total disc replacement (TDR) and the corresponding clinical and radiological outcomes are unclear. PURPOSE: This study aimed to report the long-term results of HO following lumbar TDR and to analyze the clinical and radiological outcomes. STUDY DESIGN/SETTING: A retrospective case review was performed for the consecutive patients who underwent lumbar TDR. PATIENT SAMPLE: The study included 48 patients (60 segments) who underwent lumbar TDR. OUTCOME MEASURES: The time and location of HO development, segmental range of motion (ROM) of index level, the visual analog scale (VAS), and the Oswestry Disability Index (ODI) were analyzed. METHODS: Forty-eight patients (60 segments) were divided into HO and non-HO groups, and radiographs were used to measure the time and location of HO development. We compared segmental ROM between two groups using flexion-extension radiographs. Clinical outcomes were assessed using the VAS and the ODI. Furthermore, the segmental ROM, VAS, and ODI scores of each HO class were compared with those of the non-HO group. RESULTS: The mean follow-up duration was 104.4 months. Heterotopic ossification was detected in 30 of 60 segments following lumbar TDR, and HO progression was noted in six segments. The mean segmental ROM was significantly lower in the HO group than in the non-HO group. The mean VAS and ODI scores were not significantly different between the two groups. Segmental ROM was significantly lower in the class III and IV of the HO group than in the non-HO group. The VAS and ODI scores were not significantly different among the different classes. CONCLUSIONS: We found that the incidence of HO is the highest within 12 months after lumbar TDR, and the incidence might increase 5 years after surgery. Furthermore, HO progressed over time. Segmental ROM was decreased in the HO groups; however, the limitation in motion might have little clinical influence.

Stereotactic ablative body radiotherapy for spinal metastasis from hepatocellular carcinoma: its oncologic outcomes and risk of vertebral compression fracture.

Spinal metastases from hepatocellular carcinoma (HCC) require high-dose irradiation for durable pain and tumor control. Stereotactic ablative body radiotherapy (SABR) enables the delivery of high-dose radiation. However, but vertebral compression fracture (VCF) can be problematic. The aim of his study is to evaluate the outcome and risk of VCF after SABR for spinal metastasis from HCC. We retrospectively reviewed 33 lesions in 42 spinal segments from 29 patients who received SABR with 1 fraction (16-20 Gy), or 3 fractions (18-45 Gy) from September 2009 to January 2015. The 1-year local control (LC) rate was 68.3%. Radiographic grade of cord compression (RGCC) was the only independent prognostic factor associated with LC (P = 0.007). The 1-year ultimate LC rate including the outcome of salvage re-irradiation was 87.2%. The pain response rate was 73.3% according to the categories of the International Bone Metastases Consensus Group. The 1-year VCF-free rate was 71.5%. Pre-existing VCF (P < 0.001) and only-lytic change (P = 0.017) were associated with a higher post-SABR VCF rate. One-third of post-SABR VCFs required interventions. SABR for spinal metastases from HCC provided efficacious LC, especially for lesions with RGCC ≤ II, and showed effective and durable pain relief. As VCF after SABR occurred frequently for vertebral segments with pre-existing VCF and only-lytic change, early preventive vertebroplasty is considerable for those high-risk vertebral segments.

Characteristics and Efficacy of a New 3-Dimensional Printed Mesh Structure Titanium Alloy Spacer for Posterior Lumbar Interbody Fusion.

This study evaluated the characteristics of a newly developed 3-dimensional printed mesh structure titanium spacer and its efficacy for posterior lumbar interbody fusion. Posterior lumbar interbody fusion with this spacer was performed at 53 segments (40 patients; mean age, 64 years; range, 51-73 years). Data were collected prospectively. Radiographic characteristics were analyzed with changes in interbody height, instability of the segments, formation of bone bridges around the implants, and pseudarthrosis, as determined by dynamic radiographs and postoperative computed tomography scans. Clinical outcomes were evaluated with the visual analog scale for the low back and extremities, the Oswestry Disability Index, and the 36-Item Short Form Survey. Radiographically, preoperative anterior and posterior interbody height was significantly increased immediately postoperatively (P<.05), and this increase was maintained until the last follow-up. No segmental motion of 3° or greater was noted at the last follow-up. Sagittal computed tomography images showed complete anterior bone bridges for 94.3% of cases and complete posterior bone bridges for 86.7% of cases. Coronal computed tomography images showed bilateral complete bone bridges for 94.3% of cases and unilateral bone bridges for 5.7% of cases without incomplete bilateral bone bridges. No pseudarthrosis or revision, particularly including posterior lumbar interbody fusion at L5-S1, was noted. Compared with preoperative values, the visual analog scale score for the low back and extremities, the Oswestry Disability Index, and the 36-Item Short Form Survey score showed significant improvement at the last follow-up (P<.05). Posterior lumbar interbody fusion with a newly developed 3-dimensional printed mesh structure titanium spacer showed satisfactory radiographic and clinical results, with no cases of pseudarthrosis or revision, including posterior lumbar interbody fusion at L5-S1. [Orthopedics. 2017; 40(5):e880-e885.].

Different Risk Factors of Proximal Junctional Kyphosis and Proximal Junctional Failure Following Long Instrumented Fusion to the Sacrum for Adult Spinal Deformity: Survivorship Analysis of 160 Patients.

Background: The failure modes, time to development, and clinical relevance are known to differ between proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). However, there are no reports that study the risk factors of PJK and PJF separately. Objective: The aim of this study was to investigate the risk factors for PJK and PJF separately. Methods: A retrospective study of 160 consecutive patients who underwent a long instrumented fusion to the sacrum for adult spinal deformity with a minimum follow-up of 2 years was conducted. A separate survivorship analysis of PJK and PJF was performed using the Cox proportional hazards model for the 3 categorical parameters of surgical, radiographic, and patient factors. Results: PJK developed in 27 patients (16.9%) and PJF in 29 patients (18.1%). The median survival time was 17.0 months for PJK and 3.0 months for PJF. Multivariate analyses revealed that a high body mass index was an independent risk factor for PJK (hazard ratio [HR] = 1.179), whereas the significant risk factors for PJF were older age, the presence of osteoporosis, the uppermost instrumented vertebra level at T11-L1, and a greater preoperative sagittal vertical axis (HR = 1.082, 6.465, 5.236, and 1.017, respectively). A large correction of sagittal deformity was shown to be a risk factor for PJF on univariate analyses, but not on multivariate analyses. Conclusion: PJK developed at a median of 17 months and PJF at a median of 3 months. A high body mass index was an independent risk factor for PJK, whereas older age, osteoporosis, uppermost instrumented vertebra level at the thoracolumbar junction, and greater preoperative sagittal vertical axis were risk factors for PJF.

How does back muscle strength change after posterior lumbar interbody fusion?

OBJECTIVE There is a lack of evidence of how back muscle strength changes after lumbar fusion surgery and how exercise influences these changes. The aim of this study was to evaluate changes in back muscle strength after posterior lumbar interbody fusion (PLIF) and to measure the effects of a postoperative exercise program on muscle strength and physical and mental health outcomes. METHODS This prospective study enrolled 59 women (mean age 58 years) who underwent PLIF at 1 or 2 spinal levels. To assess the effects of a supervised lumbar stabilization exercise (LSE), the authors allocated the patients to an LSE (n = 26) or a control (n = 33) group. The patients in the LSE group performed the LSEs between 3 and 6 months postoperatively. Back extensor strength, visual analog scale (VAS) scores in back pain, and physical component summary (PCS) and mental component summary (MCS) scores on the 36-Item Short Form Health Survey were determined for the both groups. RESULTS Mean strength of the back muscles tended to slightly decrease by 7.5% from preoperatively to 3 months after PLIF (p = 0.145), but it significantly increased thereafter and was sustained until the last follow-up (38.1%, p < 0.001). The mean back muscle strength was similar in the LSE and control groups preoperatively, but it increased significantly more in the LSE group (64.2%) than in the control group (21.7%) at the last follow-up 12 months after PLIF (p = 0.012). At the last follow-up, decreases in back pain VAS scores were more significant among LSE group patients, who had a pain reduction on average of 58.2%, than among control group patients (reduction of 26.1%) (p = 0.013). The patients in the LSE group also had greater improvement in both PCS (39.9% improvement) and MCS (20.7% improvement) scores than the patients in the control group (improvement of 18.0% and 1.1%, p = 0.042 and p = 0.035, respectively). CONCLUSIONS After PLIF, strength in back muscles decreased until 3 months postoperatively but significantly increased after that period. The patients who regularly underwent postoperative LSE had significantly improved back strength, less pain, and less functional disability at 12 months postoperatively.

The Ideal Cage Position for Achieving Both Indirect Neural Decompression and Segmental Angle Restoration in Lateral Lumbar Interbody Fusion (LLIF).

STUDY DESIGN: A prospective radiographic analysis. OBJECTIVE: To assess the ideal cage position for lateral lumbar interbody fusion (LLIF) together. SUMMARY OF BACKGROUND DATA: Achieving both indirect decompression and restoration of the segmental angle (SA) appear to be contrary to one another because the anteriorly located cage might be advantageous for restoring the SA, and posteriorly located cage might be favorable for achieving the indirect decompression effect. Little has been known about the significance of cage position in LLIF. METHODS: Forty-one patients who underwent LLIF followed by percutaneous pedicle screw fixation for 94 levels were evaluated. Postoperative plain radiographs and magnetic resonance images were obtained 3 days after surgery. The cage position was determined by the anterior, middle, and posterior portions. The anterior and posterior disk heights, SA, cross-sectional area of the thecal sac (CSA), and the foraminal area (FA) were compared according to the cage position. RESULTS: The cage was placed in the anterior area for 31 levels and middle for 63 levels. The cage height was 13.0±1.3 degrees. The increases in anterior disk height and SA were significantly greater in the anterior group (9.1 mm, 6.1 degrees) than those of the middle group (6.7 mm, 2.4 degrees). Posterior disk height increased by a mean of 4.5 mm, but its change did not differ according to the cage position. CSA and FA increased by 36.5% and 69.6%, respectively. There were no significant differences in the CSA and FA increases with respect to the cage position. Regression analysis showed that the increase of SA was affected by cage position, but the increase ratios of CSA and FA were not affected. CONCLUSIONS: The cage position within the anterior 1/3 of disk space is better for achieving the restoration of the SA without compromising the indirect neural decompression, if the height of cage is large enough.