Background: Endothelial-to-mesenchymal transition (EndMT) contributes to inflammatory conditions inducing conversion of endothelial cells (ECs) into activated fibroblasts, promoting fibrotic diseases. Pro-inflammatory cytokine is the most potent inducer of EndMT. We investigated inhibition of interleukin-1β (IL-1β)-induced EndMT by gemigliptin, a dipeptidyl peptidase-IV inhibitor. Methods: We exposed human umbilical vein endothelial cells (HUVECs) to 10 ng/mL IL-1β/20 μM gemigliptin and analyzed the expression of endothelial, smooth muscle, mesenchymal, and osteoblastic markers, bone morphogenetic protein (BMP), Smad, and non-Smad signaling pathway proteins. Results: Morphological changes showed gemigliptin blocked IL-1β-induced EndMT, upregulated EC markers, and downregulated smooth muscle and mesenchymal markers. IL-1β activation of HUVECs is initiated by the BMP/Smad and non-smad BMP signaling pathways. Gemigliptin inhibited IL-1β induction of BMP2 and 7, activin receptor type IA, BMP receptor type IA, and BMP receptor type II. Reversal of IL-1β-mediated inhibition of BMP-induced Smad1/5/8, Smad2, and Smad3 phosphorylation by gemigliptin suggests involvement of the Smad pathway in gemigliptin action. In the non-Smad BMP pathway, gemigliptin treatment significantly increased the deactivation of extracellular regulated protein kinase (ERK), p38, and JNK by IL-1β. Gemigliptin treatment suppressed BMP-2-induced expression of key osteoblastic markers including osterix, runt-related transcription factor 2, and hepcidin during IL-1β-induced EndMT. Conclusion We demonstrated a novel protective mechanism of gemigliptin against fibrosis by suppressing IL-1β-induced EndMT.

Objective: : The purpose of this study was to report the results of pedicle subtraction osteotomy (PSO) for fixed sagittal imbalance with a minimum 2-year follow-up. Besides, authors evaluated the effect of adjunctive multi-level posterior column osteotomy (PCO) on achievement of additional lumbar lordosis (LL) during PSO. Methods: : A total of 31 consecutive patients undergoing PSO for fixed sagittal imbalance were enrolled and analyzed. Correction angle of osteotomized vertebra (PSO angle) and other radiographic parameters including pelvic incidence (PI), thoracic kyphosis, LL, and sagittal vertical axis (SVA) were evaluated. Clinical outcomes and surgical complications were also assessed. Results: : The mean age was 66.0±9.3 years with a mean follow-up period of 33.2±10.5 months. The mean number of fused segments was 9.6±3.5. The mean operative time and surgical bleeding were 475.9±160.5 minutes and 1406.1±932.1 mL, respectively. The preoperative SRS-22 score was 2.3±0.7 and improved to 3.2±0.8 at the final follow-up. The mean PI was 54.5±9.5°. LL was changed from 7.0±28.9° to -50.2±13.2°. The PSO angle was 33.7±13.5° (15.6±20.1° preoperatively, -16.1±19.4° postoperatively). The difference of correction angle of LL (57.3°) was greater about 23.6° than which of PSO angle (33.7°). SVA was improved from 189.5±93.0 mm, preoperatively to 12.4±40.8 mm, postoperatively. There occurred six, eight, and 14 cases of complications at intraoperative, early (<2 weeks) postoperative, and late (≥2 weeks) postoperative period, respectively. Additional operations were needed in nine patients due to the complications. Conclusion : PSO could provide satisfactory results for patients with fixed sagittal imbalance regarding clinical and radiographic outcomes. Additional correction of LL could be achieved with conduction of adjunctive multi-level PCOs during PSO.

OBJECTIVE: The purpose of this study was to determine the efficacy of intra-operative cell salvage system (ICS) to decrease the need for allogeneic transfusions in patients undergoing major spinal deformity surgeries.METHODS: A total of 113 consecutive patients undergoing long level posterior spinal segmental instrumented fusion (≥5 levels) for spinal deformity correction were enrolled. Data including the osteotomy status, the number of fused segments, estimated blood loss, intra-operative transfusion amount by ICS (Cell Saver®, Haemonetics©, Baltimore, MA, USA) or allogeneic blood, postoperative transfusion amount, and operative time were collected and analyzed.RESULTS: The number of patients was 81 in ICS group and 32 in non-ICS group. There were no significant differences in demographic data and comorbidities between the groups. Autotransfusion by ICS system was performed in 53 patients out of 81 in the ICS group (65.4%) and the amount of transfused blood by ICS was 226.7 mL in ICS group. The mean intra-operative allogeneic blood transfusion requirement was significantly lower in the ICS group than non-ICS group (2.0 vs. 2.9 units, p=0.033). The regression coefficient of ICS use was -1.036.CONCLUSION: ICS use could decrease the need for intra-operative allogeneic blood transfusion. Specifically, the use of ICS may reduce about one unit amount of allogeneic transfusion in major spinal deformity surgery.
Blood Transfusion ; Blood Transfusion, Autologous ; Comorbidity ; Congenital Abnormalities ; Humans ; Operative Time ; Osteotomy ; Treatment Outcome

BACKGROUND: Waist circumference (WC) is a well-known obesity index that predicts cardiovascular disease (CVD). We studied the relationship between baseline WC and development of incident myocardial infarction (MI) and ischemic stroke (IS) using a nationwide population-based cohort, and evaluated if its predictability is better than body mass index (BMI). METHODS: Our study included 21,749,261 Koreans over 20 years of age who underwent the Korean National Health Screening between 2009 and 2012. The occurrence of MI or IS was investigated until the end of 2015 using National Health Insurance Service data. RESULTS: A total of 127,289 and 181,637 subjects were newly diagnosed with MI and IS. The incidence rate and hazard ratio of MI and IS increased linearly as the WC level increased, regardless of adjustment for BMI. When the analyses were performed according to 11 groups of WC, the lowest risk of MI was found in subjects with WC of 70 to 74.9 and 65 to 69.9 cm in male and female, and the lowest risk of IS in subjects with WC of 65 to 69.9 and 60 to 64.9 cm in male and female, respectively. WC showed a better ability to predict CVD than BMI with smaller Akaike information criterion. The optimal WC cutoffs were 84/78 cm for male/female for predicting MI, and 85/78 cm for male/female for predicting IS. CONCLUSION: WC had a significant linear relationship with the risk of MI and IS and the risk began to increase from a WC that was lower than expected.
Adult ; Body Mass Index ; Cardiovascular Diseases ; Cohort Studies ; Female ; Humans ; Incidence ; Male ; Mass Screening ; Myocardial Infarction ; National Health Programs ; Obesity ; Observational Study ; Stroke ; Waist Circumference

An adrenal incidentaloma is an adrenal mass found in an imaging examination performed for reasons unrelated to suspected adrenal disease. The prevalence of adrenal incidentaloma increases with age; there is no gender difference, but it is often accompanied by obesity, diabetes mellitus, or hypertension. The detection of adrenal incidentaloma is expected to rise with the rapid development of imaging technology and increasing frequency of imaging studies. The Korean Endocrine Society is promoting appropriate practice guidelines to meet the rising incidence of adrenal incidentaloma, in cooperation with the Korean Adrenal Gland and Endocrine Hypertension Study Group. In this paper, we discuss important core issues for treating adrenal incidentaloma, along with the most important factors for healthcare providers who treat and manage affected patients. Initially, we identified 47 recommendations using the Delphi technique, after evaluating core propositions. We reduced these to the 20 most critical recommendations.
Adrenal Glands ; Delphi Technique ; Diabetes Mellitus ; Health Personnel ; Humans ; Hypertension ; Incidence ; Obesity ; Prevalence

An adrenal incidentaloma is an adrenal mass found in an imaging study performed for other reasons unrelated to adrenal disease and often accompanied by obesity, diabetes, or hypertension. The prevalence and incidence of adrenal incidentaloma increase with age and are also expected to rise due to the rapid development of imaging technology and frequent imaging studies. The Korean Endocrine Society is promoting an appropriate practice guideline to meet the rising incidence of adrenal incidentaloma, in cooperation with the Korean Adrenal Gland and Endocrine Hypertension Study Group. In this paper, we discuss important core issues in managing the patients with adrenal incidentaloma. After evaluating core proposition, we propose the most critical 20 recommendations from the initially organized 47 recommendations by Delphi technique.
Adrenal Glands ; Delphi Technique ; Humans ; Hypertension ; Incidence ; Obesity ; Prevalence

Systemic lupus erythematosus is an autoimmune disease for which glucocorticoids are the mainstay of treatment. Cushing's syndrome is caused by glucocorticoid excess, which can be either exogenous or endogenous. Although iatrogenic Cushing's syndrome is the most common form, especially in patients undergoing glucocorticoid treatment, endogenous glucocorticoid excess should be considered because it has a different treatment strategy. We describe a 51-year old woman with a longstanding history of SLE. She was treated with steroid and cytoxan pulse therapy and plasmapheresis. Her lupus activity had been stable for 7 years with low-dose glucocorticoid treatment. She showed excessive weight gain, easy bruising, moon facies, truncal obesity, acne, and menstrual disorder. Given her history of long-term steroid therapy, iatrogenic Cushing's syndrome was considered the most likely diagnosis; however, worsening features of Cushing's syndrome with a minimal dose of glucocorticoid led us to diagnose endogenous Cushing's syndrome due to a left adrenal adenoma. The patient underwent laparoscopic left adrenalectomy. Her SLE was controlled with transient low-dose glucocorticoid treatment, and her lupus activity remained stable without glucocorticoid treatment. This is the first reported case of concomitant endogenous Cushing's syndrome in a patient with preexisting SLE in Korea. This case shows the importance of differential diagnosis including exogenous Cushing's syndrome and endogenous Cushing's syndrome in autoimmune disease patients with glucocorticoid therapy.
Acne Vulgaris ; Adenoma ; Adrenalectomy ; Autoimmune Diseases ; Cushing Syndrome ; Cyclophosphamide ; Diagnosis ; Diagnosis, Differential ; Facies ; Female ; Glucocorticoids ; Humans ; Korea ; Lupus Erythematosus, Systemic ; Moon ; Obesity ; Plasmapheresis ; Weight Gain

OBJECTIVE: Many studies have investigated paraspinal muscle changes after posterior lumbar surgery, including lumbar fusion. However, no study has been performed to investigate back muscle changes after pedicle based dynamic stabilization in patients with degenerative lumbar spinal diseases. In this study, the authors compared back muscle cross sectional area (MCSA) changes after non-fusion pedicle based dynamic stabilization. METHODS: Thirty-two consecutive patients who underwent non-fusion pedicle based dynamic stabilization (PDS) at the L4-L5 level between February 2005 and January 2008 were included in this retrospective study. In addition, 11 patients who underwent traditional lumbar fusion (LF) during the same period were enrolled for comparative purposes. Preoperative and postoperative MCSAs of the paraspinal (multifidus+longissimus), psoas, and multifidus muscles were measured using computed tomographic axial sections taken at the L4 lower vertebral body level, which best visualize the paraspinal and psoas muscles. Measurements were made preoperatively and at more than 6 months after surgery. RESULTS: Overall, back muscles showed decreases in MCSAs in the PDS and LF groups, and the multifidus was most affected in both groups, but more so in the LF group. The PDS group showed better back muscle preservation than the LF group for all measured muscles. The multifidus MCSA was significantly more preserved when the PDS-paraspinal-Wiltse approach was used. CONCLUSION: Pedicle based dynamic stabilization shows better preservation of paraspinal muscles than posterior lumbar fusion. Furthermore, the minimally invasive paraspinal Wiltse approach was found to preserve multifidus muscles better than the conventional posterior midline approach in PDS group.
Humans ; Muscles ; Psoas Muscles ; Retrospective Studies ; Spinal Diseases

BACKGROUND: Although many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated. METHODS: We evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naive type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG) levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels. RESULTS: HbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001), from 7.9% to 7.0% in the metformin group (P<0.001), and from 7.8% to 7.0% (P<0.001) in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group. CONCLUSION: The efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naive Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.
Body Weight ; Diabetes Mellitus, Type 2 ; Diarrhea ; Fasting ; Glucose ; Humans ; Hyperglycemia ; Hypoglycemia ; Hypoglycemic Agents ; Metformin ; Plasma ; Sulfonylurea Compounds ; Thiazolidinediones

OBJECTIVE: The purposes of this study are to estimate postoperative survival and ambulatory outcome and to identify prognostic factors thereafter of metastatic spinal tumors in a single institute. METHODS: We reviewed the medical records of 182 patients who underwent surgery for a metastatic spinal tumor from January 1987 to January 2009 retrospectively. Twelve potential prognostic factors (age, gender, primary tumor, extent and location of spinal metastases, interval between primary tumor diagnosis and metastatic spinal cord compression, preoperative treatment, surgical approach and extent, preoperative Eastern Cooperative Oncology Group (ECOG) performance status, Nurick score, Tokuhashi and Tomita score) were investigated. RESULTS: The median survival of the entire patients was 8 months. Of the 182 patients, 80 (44%) died within 6 months after surgery, 113 (62%) died within 1 year after surgery, 138 (76%) died within 2 years after surgery. Postoperatively 47 (26%) patients had improvement in ambulatory function, 126 (69%) had no change, and 9 (5%) had deterioration. On multivariate analysis, better ambulatory outcome was associated with being ambulatory before surgery (p=0.026) and lower preoperative ECOG score (p=0.016). Survival rate was affected by preoperative ECOG performance status (p<0.001) and Tomita score (p<0.001). CONCLUSION: Survival after metastatic spinal tumor surgery was dependent on preoperative ECOG performance status and Tomita score. The ambulatory functional outcomes after surgery were dependent on preoperative ambulatory status and preoperative ECOG performance status. Thus, prompt decompressive surgery may be warranted to improve patient's survival and gait, before general condition and ambulatory function of patient become worse.
Diagnosis ; Factor Analysis, Statistical* ; Gait ; Humans ; Medical Records ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies ; Spinal Cord Compression ; Survival Rate