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BACKGROUND Children with adolescent idiopathic scoliosis (AIS) have reduced quality of life related to poor self-image, perhaps because of cosmetic concerns. However, there has not been a large-database epidemiologic study on the association between psychiatric disorders and scoliosis. QUESTIONS/PURPOSES Using the Korean National Health Insurance database, we asked: (1) How common are psychiatric disorders among children with AIS? (2) After controlling for gender, age, insurance type, and residential district, are psychiatric disorders more common among children with AIS than among age-matched controls? METHODS A retrospective analysis was conducted using sample datasets from the Health Insurance Review and Assessment Service from 2012 to 2016, which is a 10% randomly extracted sample of total inpatients and outpatients each year. The mean number of total patients in each dataset was 1,047,603 ± 34,534. The mean number of children with AIS was 7409 ± 158 for each year. The age criteria was 10 to 19 years for the matching. Mood disorders, anxiety disorders, and behavioral disorders were selected as disorders possibly associated with AIS. We identified children with AIS who had any of the disorders above, and we obtained the prevalence of these disorders based on diagnostic codes. As an exploratory analysis, clinically meaningful variables were selected among the available codes in the dataset, and a univariable logistic regression test was performed for each variable. A multivariable logistic regression test with advanced variables was performed to identify the adjusted odds ratios of psychiatric disorders in children with AIS. RESULTS The median (range) prevalence of psychiatric disorders in children with AIS from 2012 to 2016 was 7% (6% to 7%). Compared with children who did not have AIS, and after controlling for gender, age, insurance type, and residential district, children with AIS were more likely to have psychiatric disorders in all 5 years. The adjusted ORs of psychiatric disorders in children with AIS compared with children who did not have AIS ranged from 1.47 to 1.74 (2012: OR 1.60 [95% CI 1.46 to 1.75]; p < 0.001; 2013: OR 1.73 [95% CI 1.58 to 1.89]; p < 0.001; 2014: OR 1.74 [95% CI 1.59 to 1.91]; p < 0.001; 2015: OR 1.71 [95% CI 1.56 to 1.88]; p < 0.001; 2016: OR 1.47 [95% CI 1.33 to 1.62]; p < 0.001). CONCLUSION Considering the higher prevalence of psychiatric disorders in children with AIS compared with children who did not have AIS, children with AIS and their parents should be counseled about the increased risk of deteriorating mental health of the patients, and surgeons should provide early referral to pediatric psychiatrists. Further studies should investigate the effect of the factors related to AIS, such as curve type, Cobb angle, and treatment modality. LEVEL OF EVIDENCE Level III, prognostic study.

Patients with lumbar spinal stenosis may exhibit symptoms such as back pain, radiating pain, and neurogenic claudication. Although long-term outcome of treatments manifests similar results for both nonsurgical and surgical treatments, positive effects such as short-term improvement in symptoms and decreased fall risk may be expected with surgery. Surgical treatment is basically decompression, and a combination of treatments can be added depending on the degree of decompression and the accompanying instability. Recently, minimally invasive surgery has been found to result in excellent outcomes in the treatment of lumbar spinal stenosis. Therefore, better treatment effects can be anticipated with an approach aimed at understanding the overall pathophysiology and treatment methods of lumbar spinal stenosis.

G protein-coupled receptor kinase 5 (GRK5) has been considered as a potential target for the treatment of heart failure as it has been reported to be an important regulator of pathological cardiac hypertrophy. To discover novel scaffolds that selectively inhibit GRK5, we have identified a novel small molecule inhibitor of GRK5, KR-39038 [7-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl) amino)-2-(2-chlorophenyl)-6-fluoroquinazolin-4(3H)-one]. KR-39038 exhibited potent inhibitory activity (IC50 value=0.02 μM) against GRK5 and significantly inhibited angiotensin II-induced cellular hypertrophy and HDAC5 phosphorylation in neonatal cardiomyocytes. In the pressure overload-induced cardiac hypertrophy mouse model, the daily oral administration of KR-39038 (30 mg/kg) for 14 days showed a 43% reduction in the left ventricular weight. Besides, KR-39038 treatment (10 and 30 mg/kg/ day, p.o.) showed significant preservation of cardiac function and attenuation of myocardial remodeling in a rat model of chronic heart failure following coronary artery ligation. These results suggest that potent GRK5 inhibitor could effectively attenuate both cardiac hypertrophy and dysfunction in experimental heart failure, and KR-39038 may be useful as an effective GRK5 inhibitor for pharmaceutical applications.

The mortality risk showed a positive correlation as the number of subsequent fractures increased. Hip fracture showed the greatest association with mortality risk, followed by vertebral fracture. For the combination of hip and vertebral fracture, a hip fracture after a vertebral fracture showed the highest mortality risk. It is unclear whether subsequent fractures or a certain location and sequence of subsequent fractures are associated with mortality risk in the elderly. We aimed to investigate the relationship between subsequent fractures and mortality risk. Using the Korean National Health Insurance Research Database, we analyzed the cohort data of 24,756 patients aged > 60 years who sustained fractures between 2002 and 2013. Cox regression was used to assess the mortality risk associated with the number, locations, and sequences of subsequent fractures. Mortality hazard ratios (HRs) for women and men were shown to be associated with the number of subsequent fractures (one, 1.63 (95% confidence interval [CI], 1.48–1.80) and 1.42 (95% CI, 1.28–1.58); two, 1.75 (95% CI, 1.47–2.08) and 2.03 (95% CI, 1.69–2.43); three or more, 2.46(95% CI, 1.92–3.15) and 1.92 (95% CI, 1.34–2.74), respectively). For women, the mortality risk was high when hip (HR, 2.49; 95% CI, 1.80–3.44) or vertebral (HR, 1.40; 95% CI, 1.03–1.90) fracture occurred as a second fracture. Compared with a single hip fracture, there was a high mortality risk in the group with hip fracture after the first vertebral fracture (HR, 2.90; 95% CI, 1.86–4.54), followed by vertebral fracture after the first hip fracture (HR, 1.90; 95% CI, 1.12–3.22). The mortality risk showed a positive correlation as the number of subsequent fractures increased. Hip fracture showed the greatest association with mortality risk, followed by vertebral fracture. For the combination of hip and vertebral fracture, a hip fracture after a vertebral fracture showed the highest mortality risk.

Background: Anterior cervical discectomy and fusion surgery is a common procedure for degenerative cervical spine. This describes allospacer and implant-related outcomes, comparing medium plate–low screw angle and short plate–high screw angle techniques. Methods: From January 2016 to June 2019, 79 patients who underwent ACDF were prospectively enrolled. Patients were divided, depending on the plate–screw system used: medium plate–low screw angle (12.3 ± 2.5 to 13.2 ± 3.2 degrees), and short plate–high screw angle (22.8 ± 5.3 to 23.3 ± 4.7 degrees). Subsidence, ALOD, and sagittal cervical balance were analyzed using lateral cervical X-rays. NDI and VAS scores were also evaluated. Results: Age for medium plate–low-angled screw group is 58.0 ± 11.3 years, and 55.3 ± 12.0 in the short plate–high-angled screw group (p-value = 0.313). Groups were comparable in mean NDI (p-value = 0.347), VAS (p-value = 0.156), C2–C7 SVA, (p-value = 0.981), and lordosis angle (p-value = 0.836) at 1-year post-surgery. Subsidence was higher in the medium plate–low-angled screw than in the short plate–high-angled screw (25% and 8.5%, respectively, p-value = 0.045). ALOD is also more common in the medium plate group (p-value = 0.045). Conclusion: Use of a short plate and insertion of high-angled screws (more than 20 degrees) has less chance of subsidence and occurrence of ALOD than the traditional technique of using medium plate and low angle.

To investigate the epidemiology of congenital scoliosis (CS) and treatment trends. An age-matched, nationwide, population-based study was conducted using the National Health Insurance and Health Insurance Review and Assessment databases from 2010 to 2015. Data regarding the diagnosis and treatment of scoliosis were extracted using International Classifications of Diseases, 10th revision codes. The age-matched normal population was determined from the Korean Statistical Information Service database. We analyzed the incidence rate of CS according to age and sex, as well as the proportion of surgically treated patients. A total of 1664 patients (aged 0–19 years) were diagnosed with CS. The overall average incidence rate of CS over the 5-year period was 3.08 per 100,000 persons, with the highest and second highest rates at 0 years and 12–16 years of age, respectively. The incidence rate stratified by age ranged from 1.5 to 20.1 per 100,000 persons among the age-matched normal population, with peaks at 0 years of age and the second growth spurt in adolescence (12–16 years for males; 10–14 years for females). Anterior surgery was rarely performed; posterior surgery was performed in 92 patients (5.5% of all patients), with the highest prevalence (56.5%) in patients diagnosed at 10–14 years of age. The overall average incidence rate of CS over a 5-year period was 3.08 per 100,000 persons. Only 5.5% of patients underwent surgery within 5 years after the initial diagnosis.

There are a few studies on the postoperative changes in sagittal alignment and corresponding factors, including hand grip strength (HGS) and muscle performance tests for lumbar spinal stenosis (LSS). Thus, we aimed to determine whether HGS can be a surrogate marker for global sagittal alignment changes after decompression with fusion surgery for LSS. This retrospective observational study included 91 patients who underwent spine fusion surgery for LSS. Radiological spinopelvic parameters, including sagittal vertical axis (SVA), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), global tilt (GT), and T1 pelvic angle (T1PA), were analyzed preoperatively and 1 year after posterior decompression and fusion surgery. To assess muscle performance, the 6-m walk (SMT), timed up and go (TUGT), and sit-to-stand (STS) tests were conducted. The relationship between HGS and postoperative SVA was examined through multiple linear regression analysis. Additionally, the relationship between HGS and preoperative/postoperative radiologic spinopelvic parameters and muscle performance test results was analyzed through Pearson's correlation. HGS was significantly correlated with age, preoperative and postoperative SVA, and the muscle performance tests. Furthermore, HGS was a factor that can significantly influence postoperative SVA changes in multiple linear regression analyses. Therefore, HGS may be a good predictor of postoperative SVA change.

BACKGROUND CONTEXT There has been limited research on the association between hand grip strength (HGS) as one of the diagnostic criteria for sarcopenia and surgical outcomes of lumbar spinal stenosis (LSS). PURPOSE We aimed to determine the effect of HGS on surgical outcomes and risk of fall in patients with LSS. STUDY DESIGN This is a retrospective observational study. PATIENT SAMPLE We included 200 patients who underwent spinal surgery for LSS. OUTCOME MEASURES We recorded clinical outcome parameters, including Oswestry Disability Index (ODI), Euro-QOL (EQ-5D), and visual analog scale (VAS) scores for back or leg pain. To assess the risk of fall we used HGS and four functional mobility tests (alternative step test, six-meter walk test, timed up and go test, sit-to-stand test). MATERIALS AND METHODS ODI, EQ-5D, and VAS scores for back and leg pain were assessed preoperatively and 1 year after surgery. The four functional mobility tests were assessed at each time point during the 1-year follow-up period to assess the risk of fall in patients with LSS. We divided the patient cohort according to sex and allocated them into two different groups based on HGS: high HGS (≥26 kg for men, n=26; ≥18 kg for women, n=35), and low HGS ( RESULTS In women and men, HGS correlated with the preoperative/postoperative ODI (r1=−0.217/r2=−0.345 in women, and r1=−0.384/r2=−0.411 in men) and EQ-5D scores (r1=0.190/r2=0.309 in women, and r1=0.373/r2=0.467 in men). HGS also correlated with the four postoperative results for the functional mobility tests: alternative step test (r=−0.238 in women, r=−0.431 in men), six-meter walk test (r=−0.232 in women, r=−0.282 in men), timed up and go test (r=−0.285 in women, r=−0.359 in men), and sit-to-stand test (r=−0.238 in women, r=−0.251 in men). The preoperative and postoperative ODI and EQ-5D scores in the high HGS group were superior to those in the low HGS group. Among the four functional mobility tests, preoperative and postoperative six-meter walk test results showed improvements in the high HGS group. CONCLUSIONS Considering the multifactorial nature of falls, HGS may be a useful surrogate marker for predicting the risk of falls and clinical outcomes in patients with LSS.

Background The Montreal Cognitive Assessment (MoCA) is known to have discriminative power for patients with Mild Cognitive Impairment (MCI). Recently Cognitive Reserve (CR) has been introduced as a factor that compensates cognitive decline. We aimed to assess whether the MoCA reflects CR. Furthermore, we assessed whether there were any differences in the efficacy between the MoCA and the Mini-Mental State Examination (MMSE) in reflecting CR. Methods MoCA, MMSE, and the Cognitive Reserve Index questionnaire (CRIq) were administered to 221 healthy participants. Normative data and associated factors of the MoCA were identified. Correlation and regression analyses of the MoCA, MMSE and CRIq scores were performed, and the MoCA score was compared with the MMSE score to evaluate the degree to which the MoCA reflected CR. Results The MoCA reflected total CRIq score (CRI; B = 0.076, P

Purpose To demonstrate the impact of correcting sagittal balance (SB) on functional outcomes of surgical treatment for degenerative spinal disease and actual falls via utilization of new minimally invasive lumbar fusion techniques via a lateral approach. Materials and methods From November 2011 to March 2015, we enrolled 56 patients who underwent minimally invasive lateral lumbar interbody fusion (LLIF) and matched 112 patients receiving decompression/postero-lateral fusion (PLF) surgery for lumbar spinal stenosis. According to SB status using C7-plumb line-distance (C7PL) and surgery type, patients were divided into three groups: SB PLF, sagittal imbalance (SI) PLF, and LLIF groups. We then compared their outcomes. Results The mean C7PL was 6.2±13.6 mm in the SB PLF group, 72.9±33.8 mm in the SI PLF group, and 74.8±38.2 mm in the LLIF group preoperatively. Postoperatively, C7PL in only the LLIF group improved significantly (p=0.000). Patients in the LLIF group showed greater improvement in fall-related functional test scores than the SI PLF group (p=0.007 for Alternate-Step test, p=0.032 for Sit-to-Stand test). The average number of postoperative falls was 0.4±0.7 in the SB PLF group, 1.1±1.4 in the SI PLF group, and 0.8±1.0 in the LLIF group (p=0.041). Oswestry Disability Index and the Euro-QoL 5 dimension visual analogue scale scores also showed greater improvements in the LLIF group than in the SI PLF group at postoperative 1 year (p=0.003, 0.016). Conclusion Surgical correction of SI in patients with lumbar spinal stenosis using a combination of minimal invasive LLIF and posterior surgery achieved better surgical outcomes and a lower incidence of actual falls than PLF surgery.

The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a cortisol regenerating enzyme that amplifies tissue glucocorticoid levels, plays an important role in diabetes, obesity, and glaucoma and is recognized as a potential therapeutic target for various disease conditions. Moreover, a recent study demonstrated that selective 11β-HSD1 inhibitor can attenuate ischemic brain injury. This prompted us to optimize cyclic sulfamide derivative for aiming to treat ischemic brain injury. Among the synthesized compounds, 6e has an excellent in vitro activivity with an IC50 value of 1 nM toward human and mouse 11β-HSD1 and showed good 11β-HSD1 inhibition in ex vivo study using brain tissue isolated from mice. Furthermore, in the transient middle cerebral artery occlusion model in mice, 6e treatment significantly attenuated infarct volume and neurological deficit following cerebral ischemia/reperfusion injury. Additionally, binding modes of 6e for human and mouse 11β-HSD1 were suggested.

Osteoarthritis (OA) is considered to be one of the most disabling diseases. The intra-articular opioid injection has been widely studied for its simplicity, safety, and efficacy in OA. In this study, however, we suggest a novel method of buprenorphine transdermal patch (BTDP) to painful knee joints of OA patients, instead of intra-articular opioid injection, and subsequently compared the knee application with conventional chest application. We retrospectively enrolled 213 patients with knee OA who did not respond to conventional therapy. The Numeric Rating Scale (NRS), adverse effects, and compliance were recorded before and after the application of the BTDP. All parameters were compared between the knee applied group and the chest applied group. After the BTDP application, the NRS score in the knee applied group was lower than that of the chest applied group (p = 0.007). NRS scores after buprenorphine patch decreased to 2.21 &plusmn, 0.77, and 2.55 &plusmn, 0.71 in the chest applied group and the knee applied group, respectively. The adverse effects were 19.32% in the knee applied group, and 64.00% in the chest applied group. The compliances were 82.95% and 37.60% in the knee applied group and chest applied group, respectively. This novel application of BTDP directly to the painful knee joint of knee OA patients led to a decrease in the NRS score, adverse effects, and an increase in compliance compared with the chest application method.

Background: Few studies have investigated associations between hand grip strength (HGS) and the surgical outcomes of degenerative cervical myelopathy (DCM). Methods: This study was designed as a prospective observational study of 203 patients who had undergone fusion surgery for DCM. We divided the patients according to sex and HGS differences. Clinical outcome parameters, including HGS, a fall diary and four functional mobility tests (alternative step test, six-meter walk test, timed up and go test, and sit-to-stand test) were measured preoperatively, at 3 months and 1 year after surgery. Results: Mean patient ages were 59.93 years in the male group and 67.33 years in the female group (p = 0.000, independent t-test). The mean HGS of both hands improved significantly at postoperative 3 months and 1 year in all patients (p = 0.000 for both, ANOVA). In male patients, preoperative risk of falls was negatively correlated with HGS (p = 0.000). In female patients, pre- and postoperative risk of falls were correlated negatively with HGS (p = 0.000). The postoperative incidence of falls decreased in both groups (p = 0.000) Conclusions: Postoperative HGS in patients with DCM is correlated with postoperative falls and functional outcome differently, when comparing male and female patients, for predicting favorable outcomes and neurologic deficit recovery after surgery in DCM patients.

Tranexamic acid (TXA) protects against endothelial glycocalyx injury in vitro. We aimed to evaluate whether TXA could protect against endothelial glycocalyx degradation in patients undergoing posterior lumbar fusion surgery. Patients aged 30–80 years were enrolled. The TXA group was administered a loading dose of 10 mg/kg, followed by a 1 mg/kg/h infusion. Serum syndecan-1 and heparan sulfate concentrations, which are biomarkers of glycocalyx degradation, were measured at preoperative baseline (T0), immediately post-surgery (T1), and 2 h post-surgery (T2). Postoperative complications were assessed, including hypotension, desaturation, and acute kidney injury. Among the 121 patients who completed the study, 60 received TXA. There were no significant differences in the marker concentrations at each time point. However, the postoperative increase in syndecan-1 levels from baseline was significantly attenuated in the TXA group compared with the control group (median (interquartile range), T1 vs. T0: −1.6 (−5.3–2.6) vs. 2.2 (−0.7–4.8), p = 0.001, T2 vs. T0: 0.0 (−3.3–5.5) vs. 3.6 (−0.1–9.3), p = 0.013). Postoperative complications were significantly associated with the magnitude of the change in syndecan-1 levels (for T2 vs. T0: odds ratio: 1.08, 95% confidence interval: 1.02–1.14, p = 0.006). TXA administration was associated with reduced syndecan-1 shedding in patients undergoing posterior lumbar fusion surgery.

The pathophysiological implications of binding of urotensin II (U-II) to urotensin II receptor (UT) in pulmonary arterial hypertension (PAH) have been proposed recently. Besides high expression of U-II in experimental models and patients with PAH, U-II has been shown to increase proliferation of pulmonary vascular smooth muscle cells and inflammatory responses, which were critical for PAH pathophysiology. However, the direct role of the urotensinergic system in the pathogenesis of PAH is yet to be understood. The aim of the present study was to determine whether a novel UT antagonist, KR36676, attenuates the pathophysiological progression of PAH in an animal model of PAH. PAH was induced by a single subcutaneous injection of monocrotaline (MCT, 60mg/kg) in rats. All the animals received KR36676 (30mg/kg/day) or vehicle by oral gavage. Three weeks after MCT-injection, changes in hemodynamic parameters, extent of right ventricular hypertrophy, fibrosis and pulmonary vascular remodeling, and degree of protein expression were determined. Oral administration of KR36676 effectively decreased the MCT-induced increase in right ventricular systolic pressure, hypertrophy and fibrosis. Furthermore, wall thickness of pulmonary arterioles, proliferation of pulmonary vascular cells, and inflammatory response significantly decreased in the KR36676-treated group following MCT injection compared to that in the MCT-treated vehicle group. These preventive effects of KR36676 are mediated, at least in part, by suppression of ERK1/2 and NF-κB signaling pathways. The novel UT antagonist, KR36676, effectively prevented MCT-induced PAH progression and pulmonary vascular remodeling in rat model. Our findings support the therapeutic efficacy of UT antagonist in PAH prevention and elucidate the possible underlying mechanisms of action.

It has been reported that good spinal sagittal alignment reduces the risk of fall and positive sagittal balance is the radiographic parameter that is most highly correlated with adverse health outcomes. However, no reports have demonstrated a change in risk of falling in patients with lumbar spinal stenosis (LSS) according to sagittal balance status.From September 2013 to October 2014, 141 patients who underwent lumbar spine surgery, including decompression and fusion in-situ for LSS, were enrolled in this study. Based on sagittal balance status, patients were divided into sagittal balance (SB) and sagittal imbalance (SI) groups. Four functional mobility tests were used to evaluate the risk of falling, and a fall diary, Oswestry disability index (ODI), and the Euro-QoL 5D(EQ-5D) visual analogue scale (VAS) were utilized to assess clinical improvement.The mean patient age was 70.1 years in the SB group (N=46) and 70.9 years in the SI group (N=95) (not significant). The mean C7PL was 7.9mm in the SB group and 66.1mm in the SI group preoperatively (p0.05). Among the four functional tests, only postoperative SMT and STS improved significantly in the SB group (p0.05). Patients in the SI group showed significantly improved scores for all four functional tests during postoperative follow-up (p0.05), but their performance was still worse than patients in the SB group. Average number of falls per individual during the follow-up period was 1.1±2.5 in the SB group and 1.9±3.2 in the SI group (p0.05). There was a significant difference in the distribution of non-fallers and fallers (single and multiple fallers) between the two groups postoperatively(p0.05). ODI and the EQ-5D VAS showed greater improvement in the SB group than the SI group. Multiple regression analysis revealed that sagittal balance during follow-up significantly affected ODI, EQ-VAS, functional mobility tests. (p0.05).Therefore, when fusion surgery is planned in patients with LSS, careful consideration of sagittal balance status might be important to attain better surgical and functional outcomes and decrease the incidence of actual falls after surgical treatment.

The mandibular ramus is considered an appropriate choice for reconstruction of maxillofacial defects because of sufficient amounts of material and fewer donor site complications. Although bone harvesting from the mandibular ramus has many advantages, in rare cases it can result in pathologic fracture of the mandible. Here, we present a case of 59-year-old man who suffered a pathologic mandible fracture related to biting hard foods, such as crab shells, after a sinus bone lifting with ramal bone graft procedure performed 2 weeks prior. He underwent closed reduction by intermaxillary fixation with an arch bar over the course of 4 weeks. Three months later, the patients had a stable occlusion with normal mouth opening and sensation. To prevent this complication, the osteotomy should be performed in such a way that it is not too vertical during ramal bone harvesting. Furthermore, we wish to emphasize the importance of patients being instructed to avoid chewing hard foods for at least 4 weeks after ramal bone harvesting.

Rationale: Emphysematous osteomyelitis is a rare disease caused by gas-forming bacteria. But only 45 cases have been reported in the literature since then. Patient concerns: A 72-year-old female presented to our hospital with severe lower back pain that aggravated 4 days ago. Diagnoses: Computed tomography (CT) revealed intraosseous mottled air in the T12 and L1 vertebral bodies and epidural space. The enhanced T1 and T2 magnetic resonance imaging scans showed heterogeneous signal intensity of vertebral bodies, suggestive of emphysematous osteomyelitis. Interventions: Surgery was performed to identify culture strains and to remove emphysematous lesions of the vertebral body using extensive transpedicular irrigation. Outcomes: Escherichia coli (E coli) was identified in the surgical specimen, and intravenous antibiotic therapy was continued with cefotaxime. The patient had a significant decrease in lower back pain after the surgery and the final CT scan before discharge revealed significantly decreased air at T12 and L1 vertebral bodies and no air density in the epidural space. Lessons: We present a patient diagnosed with emphysematous osteomyelitis in vertebral bodies caused by E coli and successfully treated with surgical intervention.

Study design This was a retrospective cohort study. Objective To evaluate the sagittal alignment and T1 slope after multilevel posterior cervical fusion surgery depending on the distal fusion level; C7 or T1, and find out the appropriate distal fusion level. Summary of background data The sagittal balance of the cervical spine is known to be affected by cervical lordosis and T1 slope. However, T1 slope is not a constant parameter that can be frequently changed after the surgery. Furthermore, useful studies to help guide surgeons in decision-making as to the most appropriate distal level of fusion for cervical sagittal balance are very limited. Materials and methods From 2014 to 2015, 50 patients who underwent multilevel posterior cervical fusion surgery were evaluated and followed up for >2 years. Group 1 was composed of 29 patients whose distal fusion level was C7. Group 2 was composed of 21 patients whose distal fusion level was T1. C1-C2 lordosis, C2-C7 lordosis, C2-C7 sagittal vertical axis (SVA), and T1 slope were measured on preoperative and the last follow-up. Results In group 1, C2-C7 SVA (23.1→30.4 mm, P=0.043) was worsened, and T1 slope (22.3→32.9 degrees, P=0.001) was increased after the surgery. In group 2, no significant change occurred in C2-C7 SVA after the surgery (25.3 →23.6 mm, P=0.648). The last follow-up T1 slope was similar with preoperative T1 slope (22.7→21.8 degrees, P=0.04) in group 2. Conclusions This study showed that sagittal alignment became worse after the multilevel posterior cervical surgery when distal fusion level was stopped at C7, which was associated with increase of T1 slope. However, when we extended the distal fusion level to T1, T1 slope was not changed after the surgery. Therefore, sagittal alignment was maintained after the surgery. On the basis of the results of this study, we recommend distal fusion extends to T1. Level of evidence Level III.

Background and Purpose Blockade of the actions of urotensin-II (U-II) mediated by the urotensin (UT) receptor should improve cardiac function and prevent cardiac remodelling in cardiovascular disease. Here, we have evaluated the pharmacological properties of the recently identified UT receptor antagonist, 2-(6,7-dichloro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)-N-methyl-N-(2-(pyrrolidin-1-yl)-1-(4-(thiophen-3-yl)phenyl) ethyl)acetamide (KR36676). Experimental Approach Pharmacological properties of KR36676 were studied in a range of in vitro assays (receptor binding, calcium mobilization, stress fibre formation, cellular hypertrophy) and in vivo animal models such as cardiac hypertrophy induced by transverse aortic constriction (TAC) or myocardial infarction (MI). Key Results KR36676 displayed high binding affinity for the UT receptor (Ki: 0.7 nM), similar to that of U-II (0.4 nM), and was a potent antagonist at that receptor (IC50: 4.0 nM). U-II-induced stress fibre formation and cellular hypertrophy were significantly inhibited with low concentrations of KR36676 (≥0.01 μM). Oral administration of KR36676 (30 mg·kg−1) in a TAC model in mice attenuated cardiac hypertrophy and myocardial fibrosis. Moreover, KR36676 restored cardiac function and myocyte size in rats with MI-induced cardiac hypertrophy. Conclusions and Implications A highly potent UT receptor antagonist exerted anti-hypertrophic effects not only in infarcted rat hearts but also in pressure-overloaded mouse hearts. KR36676 could be a valuable pharmacological tool in elucidating the complicated physiological role of U-II and UT receptors in cardiac hypertrophy.

Study design This was a prospective cohort study. Objectives To find out any differences in clinical outcomes when adding an en bloc total uncinate process resection (TUPR) to conventional anterior cervical discectomy and fusion (ACDF) to relieve an impinged nerve root. Summary of background data There has been a long debate on the extent of cervical decompression needed when ACDF is done for patients with foraminal stenosis. Materials and methods We included 606 patients who underwent ACDF due to foraminal stenosis. Minimum follow-up was 2 years. Patients with a soft disk herniation, myelopathy, anterior-posterior combined surgery or revision surgery were excluded. There were 275 patients (group U) who underwent ACDF with TUPR and 331 patients (group N) who underwent ACDF without TUPR. Clinical outcome measures were neck pain and arm pain, both assessed using Visual Analog Scale (VAS). We also measured Neck Disability Index (NDI) and patient-reported subjective improvement rate (PRSIR) in percentage. These parameters were measured preoperatively, immediately postoperatively, at 6 weeks as well as 3, 6, 9, 12 and 24 months. Statistical analysis was performed using independent sample t test and paired sample t test. Results Preoperative neck and arm pain, and NDI were similar between the 2 groups. All 4 parameters in both groups improved significantly at 6 weeks follow-up and the improved outcomes were maintained up to the 24 month follow-up. There were no significant differences between the 2 groups in overall neck pain VAS, NDI, and PRSIR. There was a significant difference in arm pain VAS statistically all throughout the follow-up period, with group U having lesser arm pain. Conclusions Overall clinical outcomes were significantly improved after the ACDF whether an en bloc uncinate process resection was added or not. However, arm pain VAS was significantly less statistically in the uncinate resection group at all times.

In vitro experiment using degenerated human ligamentum flavum (LF) and herniated intervertebral disk (IVD).To investigate the role and effect of degenerated and herniated IVDs on LF hypertrophy and ossification.Spinal stenosis is caused, in part, by hypertrophy and ossification of the LF, which are induced by aging and degenerative process. It is well known that degenerated IVDs spontaneously produce inflammatory cytokines. Therefore, we hypothesized that degenerated IVD may affect adjacent LF through secreted inflammatory cytokines.LF and herniated lumbar IVD tissues were obtained during surgical spinal procedures. LF fibroblasts were isolated by enzymatic digestion of LF tissue. LF cell cultures were treated with disk supernatant from herniated IVDs. Secreted cytokines from IVD tissue culture were detected by enzyme-linked immunosorbent assay. After analysis of cytotoxicity, DNA synthesis was measured. Reverse transcription-polymerase chain reaction for mRNA expressions of types I, II, III, V, and XI collagen and osteocalcin, and histochemical stains were performed.Supernatant from tissue culture of herniated IVD showed increased production of interleukin-1α, interleukin-6, tumor necrosis factor-α, prostaglandin E2, and nitric oxide compared with disk tissue culture from traumatic condition. There was no cytotoxicity in LF cells treated with disk supernatant from herniated IVDs. There was significant increase in DNA synthesis, upregulation in mRNA expression of types III, XI collagen and osteocalcin, whereas variable expression pattern of type I and V, and strong positive stains for Von Kossa and alkaline phosphatase in LF cultures with disk supernatant.Degenerated and herniated IVDs provide an important pathomechanism in hypertrophy and ossification of the LF through inflammatory cytokines.

Background: While most studies of Duchenne muscular dystrophy scoliosis focus on technical and radiographic indices, functional status is a more important factor to consider in the management of Duchenne muscular dystrophy. The objectives of the current study were to compare the pulmonary function, radiographic outcome, and functional recovery, with use of validated questionnaires, in surgically and nonsurgically treated patients with Duchenne muscular dystrophy who have scoliosis. Methods: Sixty-six patients (forty treated surgically and twenty-six treated nonsurgically) with a minimum follow-up of two years were included in this study. Forced vital capacity, radiographic parameters (the Cobb angle, lordosis, and pelvic obliquity), and functional status, according to the modified Rancho scale and manual muscle test, were measured preoperatively and at the time of the final follow-up. The Muscular Dystrophy Spine Questionnaire (MDSQ) was completed at the final follow-up evaluation. Results: Pulmonary function, functional scores (manual muscle test and modified Rancho scale), and radiographic measurements, except for lordosis, were similar for both groups at the time of the initial consultation (p > 0.05). At the time of the final follow-up, all radiographic parameters were significantly improved in the surgical group compared with the nonsurgical group. The mean score (and standard deviation) on the manual muscle test was not significantly different between the surgical and nonsurgical groups (23.2 ± 8.3 versus 22.8 ± 6.3; p = 0.828). The mean score on the modified Rancho scale also showed similar results in the groups (3.9 ± 0.3 and 4.04 ± 0.3, respectively; p = 0.088). The surgical group had higher mean MDSQ scores than the nonsurgical group (35.1 ± 14.7 and 26.9 ± 9.9, respectively; p = 0.008). Both groups showed a decrease in forced vital capacity at the time of the final follow-up, but the deterioration of forced vital capacity was significantly slower (p = 0.035) in the surgical group (268 ± 361 mL) than in the nonsurgical group (536 ± 323 mL). Conclusions: Surgery in patients who had Duchenne muscular dystrophy with scoliosis improved function and decreased the rate of deterioration of forced vital capacity compared with patients treated conservatively. However, the muscle power and forced vital capacity decreased in both groups. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Background: Hematogeneous infectious spondylodiscitis usually occurs in older immunocompromised patients with other comorbidities. They are usually unable to undergo reconstructive anterior and posterior surgeries. Therefore, an alternative, less aggressive surgical method of transpedicular curettage and drainage was suggested. This study was designed to compare the surgical outcomes for the treatment of hematogeneous infectious spondylodiscitis between transpedicular curettage and drainage technique and conventional combined anterior and posterior surgery. Materials and Methods: Between January 2002 and July 2011, 26 patients underwent surgical treatment for hematogeneous infectious spondylodiscitis. The patients were classified into two groups depending on surgical modality: a transpedicular curettage and drainage (TCD) group and a combined anterior and posterior surgery (CAPS) group. Results: The TCD group consisted of 10 patients (mean age 68.0 years), and the CAPS group consisted of 16 patients (mean age 58.4 years).The mean postoperative followup periods were 36.9 (months) in the TCD group and 69.9 (months) in the CAPS group. The operation time was 180.6 ± 33.6 minutes in the TCD group and 332.7 ± 74.5 minutes in the CAPS group (P < 0.05). Postoperative independent ambulation began at postoperative 4.9 ± 2.4 days in the TCD group but at postoperative 15.1 ± 15.3 days in the CAPS group (P < 0.05). The postoperative hospital stays were 19.9 ± 7.8 days in the TCD group and 35.4 ± 33.3 days in the CAPS group (P < 0.05). The level of C-reactive proteins decreased significantly in both groups after surgery (P < 0.05). Conclusion: Transpedicular curettage and drainage technique proved to be a useful technique for treating hematogeneous infectious spondylodiscitis in patients who were in poor heath with multiple comorbidities unable to undergo the conventional combined anterior and posterior surgery in a single day in terms of earlier ambulation, shorter hospitalization and similar clinical success rate.

Symptoms of intervertebral foraminal stenosis are caused by compression of nerve root exiting the intervertebral foramen. Many attempts to measure the size of the neuromuscular exit have been made; however, only a few studies to compare the area differences between foramens by computed tomography (CT) were done. In this retrospective comparative study, we used the region of interest (ROI) in CT to measure and compare the area of intervertebral foramen between the healthy control group and the patient group. Eighty-one patients who underwent CT of the lumbar spine between May 2014 and December 2017 were enrolled. Using the medical imaging program, the foraminal area between L5 and S1 vertebrae was measured on the sagittal, coronal, and axial planes using ROI. Four groups were established for comparison: those diagnosed with foraminal stenosis by a radiologist and those who were not, those diagnosed with foraminal stenosis by orthopedic surgeons and those who were not. These groups were further divided into subcategories depending on whether the area was operated on for foraminal stenosis. Interobserver and intraobserver agreements were assessed. The mean age of patients was 56.5 years (range 17–84). The foraminal area of the surgical group on sagittal plane was significantly narrower than the control group (P = .005). However, the difference between the 2 groups on axial and coronal planes was not statistically significant (P > .1). Foraminal area 0.9). In this study, we proved that measuring the intervertebral foraminal area using the ROI in CT in the lumbar spine is useful for diagnosing L5-S1 foraminal stenosis, especially on sagittal plane. Furthermore, not only does it provide aid in diagnosis, but it also helps predicting the operability of foraminal stenosis.

Dupuytren's disease is a fibroproliferative connective tissue disorder characterized by contracture of the palmer fascia of the hand. Relaxin (RLN) is a multifunctional factor which contributes to the remodeling of the pelvic ligament by inhibiting fibrosis and inflammatory activities. The aim of this study was to investigate the effect of the RLN gene on the inhibition of fibrosis in myofibroblastic cells. Myofibroblast cells with adenovirus LacZ (Ad-LacZ) as a marker gene or adenovirus relaxin (Ad-RLN) as therapeutic gene showed transgene expressions in beta-galactosidase assay and Western blot analysis. Myofibroblastic cells with Ad-RLN demonstrated a 22% and 48% reduction in collagen I and III mRNA expressions respectively, a 50% decrease in MMP-1, 70% decrease in MMP-2, 80% decrease in MMP-9, and a 15% reduction in MMP-13 protein expression compared with cultures with viral control and saline control. In addition, myofibroblastic cells with Ad-RLN showed a 40% decrease in TIMP 1 and a 15% increase in TIMP 3 protein expression at 48 h compared to cultures with viral control and saline control. Also, myofibroblastic cell with Ad-RLN demonstrated a 74% inhibition of fibronectin and a 52% decrease in total collagen synthesis at 48 h compared with cultures with viral control and saline control. In conclusion, the RLN gene render antifibrogenic effect on myofibroblastic cells from Dupuytren's nodule via direct inhibition of collagen synthesis not through collagenolytic pathway such as MMP-1, -13, TIMP 1, and 3. Therefore relaxin can be an alternative therapeutic strategy in initial stage of Dupuytren's disease by its antifibrogenic effect. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:515–523, 2014.

Background context In the instrumented fusion, adjacent segment facet joint violation or impingement by pedicle screws is unavoidable especially in cephalad segment, despite taking specific intraoperative precautions in terms of surgical approach. In such circumstances, unlike its original purpose, unilateral pedicle screw instrumentation can contribute to reduce the degeneration of cephalad adjacent segment by preventing contralateral cephalad adjacent facet joint from the unavoidable injury by pedicle screw insertion. However, to our knowledge, no long-term follow-up study has compared adjacent segment degeneration (ASD) between unilateral and bilateral pedicle screw instrumented fusion. Purpose To compare ASD after successful posterolateral fusion using either unilateral or bilateral pedicle screw instrumentation for patients with lumbar spinal stenosis and/or Grade 1 spondylolisthesis. Study design Retrospective case-control study. Patient sample One hundred forty-seven patients who had undergone one- or two-level posterolateral fusion with unilateral or bilateral pedicle screw instrumentation for lumbar spinal stenosis with or without low-grade spondylolisthesis and achieved successful fusion, with a minimum 10-year follow-up. Outcome measure The occurrence of radiologic ASD, Oswestry disability index (ODI) scores, and revision rates. Methods A total of 194 consecutive patients were contacted and encouraged to visit our hospital and to participate in our study. Radiologic ASD was evaluated at three motion segments: cephalad adjacent segment (first cephalad adjacent segment), one cephalad to cephalad adjacent segment (second cephalad adjacent segment), and caudal adjacent segment. Clinical outcomes were compared by ODI scores and revision rates. Results In total, 147 of 194 (75.8%) patients were available for at least 10 years of radiologic and clinical follow-up. Adjacent segment degeneration (in first cephalad or caudal adjacent segment) was noted in 55.9% (33 of 59 patients) of the unilateral group and 72.7% (64 of 88 patients) of the bilateral group (p=.035). The occurrence of ASD in each first cephalad and caudal adjacent segment was not significantly different between groups but that in second cephalad adjacent segment was significantly different between groups (p=.004). Clinical outcomes according to ODI showed significant difference between groups (p=.016), especially when ODI scores were compared in patients with ASD (p=.004). Conclusions In a minimum 10-year follow-up retrospective study of posterolateral fusion for lumbar spinal stenosis and/or Grade 1 spondylolisthesis, unilateral pedicle screw instrumentation showed a lower rate of radiologic ASD, especially in second cephalad adjacent segment, and a better clinical outcome by ODI.

Background: Patients with lumbar spinal stenosis (LSS) are at a great risk of a fall and fracture, which vitamin D protects against. Vitamin D deficiency is expected to be highly prevalent in LSS patient, and pain is thought to have a profound effect on vitamin D status by limiting activity and sunlight exposure. Objective: To identify the prevalence of vitamin D deficiency (serum 25-hydroxyvitamin D [25-OHD] < 20ng/mL) and its relationship with pain. Study Design: Nonblinded, cross-sectional clinical study. Setting: University-based outpatient clinic of the Department of Orthopedic Surgery, Yonsei University College of Medicine, Korea. Methods: Consecutive patients who visited the orthopedic outpatient clinic for chronic low back pain and leg pain and were diagnosed as LSS between May 2012 and October 2012 were included. Pain was categorized into 4 groups based on location and severity: 1) mild to moderate back or leg pain; 2) severe back pain; 3) severe leg pain; and 4) severe back and leg pain. Covariates for vitamin D deficiency included age, sex, body mass index, level of education, medical history, season, region of residence, sunlight exposure score and functional disability. 25-OHD level was measured by radioimmunoassay, and bone metabolic status including bone mineral density and bone turnover markers was also measured. Multivariable logistic regression modeling was used to adjust all risk estimates for covariates. Results: The study had 350 patients enrolled. Mean serum 25-OHD level was 15.9 ± 7.1 ng/mL (range, 2.5 ~ 36.6). of the 350 patients, 260 patients out of 350 (74.3%) were vitamin D deficient. Univariate logistic regression analysis showed a significantly higher prevalence of vitamin D deficiency in the following patients: 1) medical comorbidity; 2) urban residence rather than rural; 3) lower score for sunlight exposure; and 4) severe leg pain, or severe back and leg pain rather than mild to moderate pain. Pain category was significantly associated with lower sunlight exposure; however, the association between pain category and vitamin D deficiency remained significant even after adjustment for the sunlight exposure. Furthermore, severe back pain, and severe back and leg pain were also associated with higher incidence of osteoporosis and higher level of bone resorption marker (serum CTx). Limitations: The limitation of our study is that due to its cross-sectional design, causal relationships between pain and vitamin D deficiency could not be established. Conclusion: Vitamin D deficiency was highly prevalent in LSS patients (74.3%), and severe pain was associated with higher prevalence of vitamin D deficiency and osteoporosis which could be potential risk factors or a fall and fracture. As evidenced by the present study, assessment of serum 25-OHD and bone mineral density are recommended in LSS patients with severe pain, and active treatment combining vitamin D, calcium, or bisphosphonate should be considered according to the status of the bone metabolism. Key words: Vitamin D, lumbar spinal stenosis, pain, bone mineral density

Urotensin II and its receptor are thought to be involved in various cardiovascular diseases such as heart failure, pulmonary hypertension and atherosclerosis. Since the regulation of the urotensin II/urotensin II receptor offers a great potential for therapeutic strategies related to the treatment of cardiovascular diseases, the study of selective and potent antagonists for urotensin II receptor is more fascinating. This study was designed to determine the potential therapeutic effects of a newly developed novel urotensin II receptor antagonist, N-(1-(3-bromo-4-(piperidin-4-yloxy)benzyl)piperidin-4-yl)benzo[b]thiophene-3-carboxamide (KR-36996), in experimental models of heart failure. KR-36996 displayed a high binding affinity (Ki=4.44±0.67nM) and selectivity for urotensin II receptor. In cell-based study, KR-36996 significantly inhibited urotensin II-induced stress fiber formation and cellular hypertrophy in H9c2UT cells. In transverse aortic constriction-induced cardiac hypertrophy model in mice, the daily oral administration of KR-36996 (30mg/kg) for 14 days significantly decreased left ventricular weight by 40% (P

Background Hearing loss can lead to a number of disabilities, subsequently reducing the quality of life. In general, hearing thresholds of adolescents are better than adults and the elderly. However, occasionally, adolescents acquire hearing loss for a number of reasons. In this study, our goal was to estimate the prevalence of hearing loss in the Korean population and to investigate the factors related to hearing thresholds in adolescents. Methods A cross-sectional study was conducted using data from the Korean National Health and Nutrition Examination Survey (KNHANES) between 2010 and 2012. We enrolled a total of 1,658 participants, ages 13 to 18 years. We investigated the prevalence of hearing loss and the factors associated with hearing thresholds at various frequencies (0.5, 1, 2, 3, 4, and 6 KHz). Results Weighted prevalence of unilateral and bilateral hearing loss in Korean adolescents was 2.2% and 0.4%, respectively. Weighted prevalence of hearing thresholds ≥ 20 dB at speech and high frequencies were 3.1% and 5.0%, respectively, for unilateral hearing loss and 0.7% and 1.9%, respectively, for bilateral. Age group, tympanometric data, and household income were significantly related to unilateral or bilateral hearing thresholds ≥ 20 dB at speech frequencies. Earphone use in noisy places was associated with bilateral hearing thresholds ≥ 20 dB at high frequencies. Conclusions The prevalence of hearing loss in Korean adolescents was 2.6% using the general standard threshold associated with hearing loss. However, the prevalence of hearing thresholds ≥ 20 dB for speech and high frequencies was much higher. The results from this study provide an estimate of hearing loss in adolescents and suggest the need for early detection and hearing preservation programs among adolescents.

To date, skillful medical management and advanced surgical techniques have provided increased quality of life with less postoperative morbidity in patients with spinal metastasis. We assessed the survival of patients with spinal metastasis according to two treatment modalities: surgery and conservative treatment. From 2005 to 2010, a total of 577 patients (200 surgery, 377 conservative treatment) who had spinal metastasis were enrolled. Prognostic factors and survival were assessed by Cox regression and Kaplan–Meier analyses in patients receiving either surgery or conservative treatment. The mean age was 59.7 (range 21–87) years in the surgery group and 59.9 (range 28–90) years in the conservative treatment group. The major primary cancers were of lung, liver, and colorectal origin in the surgery group and lung, liver, and breast in the conservative group. The mean ± SD Tokuhashi score in the surgery group was 8.12 ± 3.09 and in the conservative group was 8.0 ± 2.8 (not significant). The hazard ratio of the primary cancer group ranged from 1.870 to 3.217 compared to that of the most favorable primary cancer group in all patients. Survival was affected significantly by sex, adjuvant therapy, and postoperative survival in the surgery group and by clinical symptom, metastasis to major internal organ, and primary cancer origin in the conservative group. With this retrospective review of 577 cases of spinal metastasis, different prognostic factors depending on the treatment modality were discovered. Hence, consideration of these factors depending on the treatment modality could be helpful in treating patients with spinal metastasis.

E-mail: kyyi@krict.re.krReceived March 15, 2012, Accepted March 26, 2012Key Words : Melanin concentrating hormone (MCH), MCH-R1 antagonist, 4-Heteroaryl phthalazin-1(2H)-one, ObesityObesity is a chronic disorder in which there is an imbalancebetween energy intake and expenditure. According to arecent World Health Organization (WHO) report, more thanone billion of adults in world population are overweight, and200 million of these individuals are clinically obese.

Background: The objective of this study was to evaluate of prevalence of co-existing spine and hip disease using initial screening kidney-ureter-bladder (KUB) radiograph in patients over 50 who underwent spinal surgery. Materials and Methods: The study subjects were 388 patients (male: female=117:271; mean age 62.0 years) who underwent spinal surgery between 2008 and 2010. We retrospectively reviewed the initial KUB radiographs used to diagnose the spine and hip disease. Depending on the extent of acetabular and hip joint visualization in KUB, we divided the subjects into three groups: Acetabulum, hip joint, and femoral neck visualization. The hip visualization rate was also assessed with respect to patient height. χ 2 and logistic regression test were used for statistical analysis. Results: 126 (32.5%) cases had significant hip pathology including hip osteoarthritis (Kellgren/Lawrence grade 3 in 123 cases, grade 4 in 3 cases) and avascular necrosis (1 case each of Ficat stage IIA and IIB), and 8 cases had other morphologic abnormalities. Regarding acetabulum-hip visualization in KUB, 7 (1.8%) cases had acetabulum visualization only, 16 (4.1%) had hip joint visualization, and 365 (94.1%) had femoral neck including lesser trochanter visualization. Patients were categorized into four groups according to height (less than 150 cm, 150-159 cm, 160-169 cm, greater than 170 cm). The hip visualization rates differed significantly among these four groups ( P Conclusions: The prevalence of discernible hip pathology in patients who underwent spinal surgery was 32.5%. Hip joint visualization was excellent (98.2%) in KUB radiographs. Hence, spinal surgeons should pay attention to hip pathology in surgically indicated spinal patients.

Anticoagulation in CHADS2 Score 1. Background: The revised ACC/AHA/ESC 2006 guideline recommends either aspirin or warfarin for the prevention of ischemic stroke in patients with atrial fibrillation (AF) in CHADS2 score 1. We hypothesized that warfarin is superior to aspirin therapy for the prevention of stroke without increasing bleeding complication in AF patients with CHADS2 score 1. Methods and Results: Among 1,502 patients (mean 62.4 ± 13.8 years old, male 65.4%) who were treated for nonvalvular AF without previous stroke, the number of patients with CHADS2 score 1 was 422 (62.9 ± 10.7 years old, male 290 [68.7%]) and their antithrombotic therapies were as follows: warfarin (n = 143), aspirin (n = 124), other antiplatelet (n = 45), and no antithrombosis (none: n = 110). We reviewed the incidences of ischemic stroke, mortality, and bleeding complications during the follow-up period. Results were: (1) during 22.3 ± 17.8 months of follow-up, the incidence of ischemic stroke was significantly lower in warfarin (6 patients, 4.2%, mean international normalized ratio [INR] 2.0 ± 0.5 IU) than in aspirin (16 patients, 12.9%, P = 0.008) than none (23 patients, 20.9%, P < 0.001) without differences in all-cause mortality. (2) The incidence of major bleeding (decrease in hemoglobin ≥2 g/dL, requiring hospitalization or red blood cell transfusion ≥2 pints) was not different between warfarin (2.1%) and aspirin (0.8%, P = NS), but minor bleeding was more common in warfarin (10.5%) than in aspirin (2.4%, P = 0.007). Conclusion: In AF patients with CHADS2 score 1, warfarin was better to prevent ischemic stroke than aspirin without increasing the incidence of major bleeding complications. However, the incidence of minor bleeding was higher in the warfarin group than the aspirin group. (J Cardiovasc Electrophysiol, Vol. 21, pp. 501-507, May 2010)

BACKGROUND: The purpose of this study was to investigate the relationship between the efficacy of the 2 different ablation techniques of atrial fibrillation (AF) and left atrial (LA) size. METHODS AND RESULTS: A total of 81 patients with paroxysmal AF (n = 58) or persistent AF (n = 23) refractory to antiarrhythmic drugs underwent circumferential pulmonary vein isolation (PVI; n = 45) or PVI (n = 36) without respect to echocardiographic results for LA volume index (LAVI). Of the 81 patients, 41 had less dilated LA (group 1; LAVI < 27 cc/m(2)) and 40 had dilated LA (group 2; LAVI ≥ 27 cc/m(2)). During the 9‐month follow‐up, 33 patients (73.3%) after circumferential PVI and 18 (50%) after PVI (P = .031) were free of arrhythmia. The risk of recurrence was associated with persistent AF, hypertension, LAVI > 27 ml/m(2), PVI, early recurrence of AF, and lower left ventricular (LV) ejection fraction (all P value

The objective of this study was to investigate atrial myocardial properties through two-dimensional (2D) myocardial imaging in patients with atrial fibrillation (AF) and its predictive role for recurrence after catheter ablation. Echocardiographic examinations were performed in 40 patients with paroxysmal AF before catheter ablation and 40 age- and gender-matched healthy control subjects. Using a software package, bidimensional acquisitions were analyzed to measure longitudinal strain and strain rate for the left atrium (LA). Systolic strain and strain rate in all eight segments, and its average values, were significantly reduced in AF patients compared to controls. During 9 months of follow-up after catheter ablation for AF, 11 of 40 AF patients had AF recurrence. AF recurrence was associated with gender, LA volume index, and average values of systolic strain and strain rate. By multivariate analysis, only average strain was an independent predictor of AF recurrence (OR = 0.88, 95% CI 0.79-0.98, p = 0.018). Lower systolic strain of LA was strongly associated with recurrence after catheter ablation. Thus, diverse adjunctive ablation strategies should be considered to reduce recurrence in patients with lower systolic strain.

The objective of this work was to assess the predictive value of pre-procedural N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients undergoing atrial fibrillation (AF) ablation. Seventy-three consecutive patients with AF (paroxysmal n = 49, persistent n = 24) and preserved left ventricular (LV) systolic function (LV ejection fraction > 45%) were prospectively enrolled in this study. All of the enrolled patients underwent catheter ablation after a measurement of their plasma NT-proBNP levels, and an echocardiographic examination with assessment of their LV diastolic function and left atrial(LA) volume. Patients with AF recurrence at 3 months had more persistent AF (P = 0.001), a higher LA volume index (P = 0.002), lesser decelerating times (DT) of mitral inflow (P = 0.014), and higher NT-proBNP levels (P < 0.001), when compared with patients with sinus rhythm restoration. The baseline log NT-proBNP correlated significantly with age (r = 0.26, P = 0.025), LA volume index (r = 0.41, P = 0.001), E/E’ (r = 0.34, P = 0.007), DT (r = −0.34, P = 0.007), and E (r = 0.25, P = 0.04). The log NT-proBNP (HR 7.76, 95% CI 2.95–20.39, P < 0.001) was an independent predictor of AF recurrence. The measurement of NT-proBNP added incremental predictive value to standard indexes of LA size or diastolic function, including LA volume index and DT (P = 0.02). This study suggests the clinical utility of the level of NT-proBNP as an integrating marker of various risk factors, and as an incremental predictive marker for AF catheter ablation.

The cardioprotective effects of KR-31761, a newly synthesized K+ATP opener, were evaluated in rat models of ischemia/reperfusion (I/R) heart injury. In isolated rat hearts subjected to 30-min global ischemia/30-min reperfusion, KR-31761 perfused prior to ischemia significantly increased both the left ventricular developed pressure (% of predrug LVDP: 17.8, 45.1, 54.2, and 62.6 for the control, 1 μM, 3 μM, and 10 μM, respectively) and double product (DP: heart rate × LVDP; % of predrug DP: 17.5, 44.9, 56.2, and 64.5 for the control, 1 μM, 3 μM, and 10 μM, respectively) at 30-min reperfusion while decreasing the left ventricular end-diastolic pressure (LVEDP). KR-31761 (10 μM) significantly increased the time to contracture during the ischemic period, whereas it concentration-dependently decreased the lactate dehydrogenase release during reperfusion. All these parameters were significantly reversed by 5-hydroxydecanoate (5-HD, 100 μM) and glyburide (1 μM), selective and nonselective blockers of the mitochondrial K+ATP (mitoK+ATP) channel and K+ATP channel, respectively. In anesthetized rats subjected to 30-min occlusion of left anterior descending coronary artery/2.5-h reperfusion, KR-31761 administered 15 min before the onset of ischemia significantly decreased the infarct size (72.2%, 55.1%, and 47.1% for the control, 0.3 mg/kg, i.v., and 1.0 mg/kg, i.v., respectively); and these effects were completely and almost completely abolished by 5-HD (10 mg/kg, i.v.) and HMR-1098, a selective blocker of sarcolemmal K+ATP (sarcK+ATP) channel (6 mg/kg, i.v.) administered 5 min prior to KR-31761 (72.3% and 67.9%, respectively). KR-31761 only slightly relaxed methoxamine-precontracted rat aorta (IC50: >30.0 μM). These results suggest that KR-31761 exerts potent cardioprotective effects through the opening of both mitoK+ATP and sarcK+ATP channels in rat hearts with a minimal vasorelaxant effect. Keywords:: KR-31761, cardioprotection, KATP, ischemia/reperfusion, rat heart

The present study was performed to evaluate the cardioprotective effects of KR-33028, a novel Na+/H+ exchanger subtype 1 (NHE-1) inhibitor, in rat and dog models of coronary artery occlusion and reperfusion. In anesthetized rats subjected to a 45-min coronary occlusion and a 90-min reperfusion, KR-33028 at 5 min before occlusion (i.v. bolus) dose-dependently reduced myocardial infarct size from 58.0% to 46.6%, 40.3%, 39.7%, 33.1%, and 27.8% for 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg respectively (P < 0.05). In anesthetized beagle dogs that underwent a 1.0-h occlusion followed by a 3.0-h reperfusion, KR-33028 (3 mg/kg, i.v. bolus) markedly decreased infarct size from 45.6% in vehicle-treated group to 16.4% (P < 0.05), and reduced the reperfusion-induced release in creatine kinase myocardial band isoenzyme (MB), lactate dehydrogenase, troponin-I, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase. In separate experiments to assess the effects of timing of treatment, KR-33028 (1 mg/kg, i.v. bolus) given 10 min before or at reperfusion in rat models also significantly reduced the myocardial infarct size (46.3% and 44.1% respectively) compared with vehicle-treated group. In all studies, KR-33028 caused no significant changes in any hemodynamic profiles. In an isolated rat heart model of hypothermic cardioplegia, KR-33028 (30 mum), which was added to the heart preservation solution (histidin-tryptophan-ketoglutarate) during hypothermic cardioplegic arrest, significantly improved the recovery of left ventricular developed pressure, heart rate and dP/dt(max) after reperfusion. Taken together, these results indicate that KR-33028 significantly reduced the myocardial infarction induced by ischemia and reperfusion in rats and dogs, without affecting hemodynamic profiles.

Internal jugular vein (IJV) is the main pathway of cerebral venous drainage and its valves prevent regurgitation of blood to the brain. IJV valve incompetence (IJVVI) is known to be associated with cerebral dysfunctions. It occurs more often in male over 50 years old, conditions elevating intra-abdominal or intra-thoracic pressure. In robot-assisted laparoscopic radical prostatectomy (RALRP), elderly male undergoes surgery in Trendelenburg position with pneumoperitoneum applied. Therefore, we assessed the IJVVI during RALRP and its influence on postoperative cognitive function. 57 patients undergoing RALRP were enrolled. Neurocognitive tests including Mini-Mental State Examination (MMSE), Auditory Verbal Learning Test, Digit Symbol Substitution Test, Color Word Stroop Test, digit span test, and grooved pegboard test were performed the day before and 2 days after surgery. During surgery, IJVVI was assessed with ultrasonography in supine position with and without pneumoperitoneum, and Trendelenburg position with pneumoperitoneum. 50 patients underwent sonographic assessment and 41 patients completed neurocognitive examination. A total of 27 patients presented IJVVI, 19 patients in supine position without pneumoperitoneum, 7 patients in supine position with pneumoperitoneum and 1 patient in Trendelenburg position with pneumoperitoneum. In neurocognitive tests, patients with IJVVI showed statistically significant decline of score in MMSE postoperatively (p

The present study was performed to evaluate the cardioprotective effects of [5-(2-methoxy-5-chloro-5-phenyl)furan-2-ylcarbonyl]guanidine (KR-32570) in rat and dog models of coronary artery occlusion and reperfusion. In addition, we sought to clarify the efficacy of KR-32570 on reperfusion-induced fatal ventricular arrhythmia. In anesthetized rats subjected to 45-min coronary occlusion and 90-min reperfusion, KR-32570 (i.v. bolus) dose-dependently reduced myocardial infarct size from 58.0% to 50.7%, 35.3%, 33.5% and 27.0% for 0.03, 0.1, 0.3 and 1.0 mg/kg, respectively (P0.05). In anesthetized beagle dogs that underwent 1.2-h occlusion followed by 3.0-h reperfusion, KR-32570 (3 mg/kg, i.v. bolus) markedly decreased infarct size from 28.9% in vehicle-treated group to 8.0% (P0.05), and reduced the reperfusion-induced release in creatine kinase isoenzyme MB, lactate dehydrogenase, Troponin-I and glutamic-oxaloacetic transaminase. KR-32570 dose-dependently decreased the incidence of premature ventricular contraction, ventricular tachycardia or ventricular fibrillation induced by ischemia and reperfusion in rats. Similar results were obtained in dogs with reperfusion-induced arrhythmia. In separate experiments to assess the effects of timing of treatment, KR-32570 given 10 min before or at reperfusion in rat models also significantly reduced the myocardial infarct size (40.9% and 46.1%, respectively) compared with vehicle-treated group. In all studies, KR-32570 caused no significant changes in any hemodynamic profiles. Taken together, these results indicate that KR-32570 significantly reduced the myocardial infarction and incidence of arrhythmias induced by ischemia and reperfusion in rats and dogs, without affecting hemodynamic profiles. Thus, it could be potentially useful in the prevention and treatment of myocardial injuries and lethal ventricular arrhythmias.

A series of 4-substituted (benzo[b]thiophene-2-carbonyl)guanidines was synthesized and evaluated for the NHE-1 inhibitory activity and cardioprotective efficacy both in vitro and in vivo. Several analogs exhibited a strong inhibition on NHE-1, and which was generally well correlated with their cardioprotective efficacy. Especially the 4-nitro 20 and cyano 50 compounds excellently improved the cardiac function and reduced infarct size against ischemia/reperfusion injury.

The present study was performed to evaluate the cardioprotective effects of [5-(2-methoxy-5-chloro-5-phenyl)furan-2-ylcarbonyl]guanidine (KR-32570) on ischemia/reperfusion-induced mechanical and metabolic dysfunction in isolated rat hearts. In addition, the effects of KR-32570 on the Na(+)/H(+)-exchanger (NHE) and lipid peroxidation were also evaluated. KR-32570 strongly inhibited the recovery from acidosis induced by an NH(4)Cl prepulse in PS120 fibroblast cells expressing the human NHE-1 isoform (IC(50): 0.05 and 1.16 microM for KR-32570 and cariporide, respectively). In isolated perfused rat hearts subjected to 30-min ischemia/30-min reperfusion, KR-32570 (1-10 microM) significantly and concentration dependently improved cardiac contractile function and severe contracture in conjunction with causing a marked reduction in lactate dehydrogenase release. Additionally, it (1-10 microM) significantly increased the content of ATP, creatine phosphate and glycogen as well as decreased the tissue lactate content in heart homogenates following ischemia and reperfusion. KR-32570 (1-10 microM) significantly decreased the concentration of 8-iso-prostaglandin F(2 alpha), a reliable marker for oxidant stress, in perfusates from rat hearts subjected to ischemia and reperfusion. In separate experiments, KR-32570 significantly lowered the concentration of malondialdehyde in rat liver homogenate and inhibited Cu(2+)-induced peroxidation of low-density lipoprotein. Taken together, these results suggest that KR-32570 possesses potent cardioprotective effects in perfused rat hearts, and its effects may be mediated by inhibition of NHE-1, preservation of high-energy phosphates, and inhibition of lipid peroxidation.

A novel class of alkoxybenzylcyanoguanidine analogs as the inhibitors of restenosis was discovered, which showed the inhibitory effects on angiotensin II-induced cell proliferation, determined by [ 3 H]thymidine incorporation method. The compound, N'-(4-nitrophenyl)guanidine analog 19, showed 62% inhibition of [ 3 H]thymidine incorporation at 1 μM concentration. In addition, the compound 19 inhibited intimal thickening dose-dependently after balloon injury, which suggests the therapeutic potential for restenosis.

The cardioprotective effects of (2S,3R,4S)-N′-benzyl- N′′-cyano-N-(3,4-dihydro-2-dimethoxymethyl-3-hydro- xy-2-methyl-6-nitro-2H-benzopyran-4-yl)-guanidine (KR-31372) were evaluated against ischemic/reperfusion injury in isolated rat hearts in vitro and in anesthetized rats and dogs in vivo. In isolated perfused rat hearts subjected to a 30-min global ischemia/30-min reperfusion, KR-31372 (1–10 µM) significantly improved severe contracture (end-diastolic pressure and time to contracture), markedly reduced reperfusion lactate dehydrogenase release, and enhanced the recovery of reperfusion contractile function (left ventricular developed pressure and double product) in a concentration-dependent manner compared with the vehicle-treated group. In anesthetized rats subjected to a 45-min coronary occlusion and a 90-min reperfusion, intravenous KR-31372 dose-dependently reduced infarct size from 58.6% to 48.5, 48.1 and 39.6% at 0.3, 1.0 and 3.0 mg/kg, respectively (p < 0.05). In anesthetized beagle dogs that underwent a 1.5-hour occlusion followed by a 5-hour reperfusion, KR-31372 (2 mg/kg, i.v.) markedly reduced infarct size from 57.0% in controls to 28.0% (p < 0.05). The cardioprotective effects of KR-31372 on contractile function in globally ischemic rat hearts and on reperfusion injury in anesthetized rats were significantly reversed by pretreatment with selective adenosine triphosphate-sensitive potassium (KATP) channel blockers, sodium 5-hydroxydecanoate and glibenclamide. Taken together, these results indicate that KR-31372 possesses potent cardioprotective effects in rats and dogs and its effects may be mediated by activation of mitochondrial KATP channels.

PURPOSE Teriparatide markedly increases bone formation and strength, while reducing the incidence of new-onset osteoporotic vertebral compression fractures (OVCFs). In some countries, expenses for teriparatide use are covered by medical insurance for up to 6 months; however, the national medical insurance of the authors' country does not cover these expenses. This retrospective cohort study compared the therapeutic effects of teriparatide on the initial onset of a new OVCF after treatment of osteoporosis and/or related OVCFs with regard to therapeutic durations of longer than 3 months (LT3M) or shorter than 3 months (ST3M). MATERIALS AND METHODS From May 2007 to February 2012, 404 patients who were prescribed and administered teriparatide and who could be followed-up for longer than 12 months were enrolled. They were divided into two groups depending on teriparatide duration: LT3M (n=132) and ST3M (n=272). RESULTS The group with the teriparatide duration of LT3M showed significantly less development of an initial OVCF within 1 year (p=0.004, chi-square). Duration of teriparatide use, body mass index, pre-teriparatide lowest spinal bone mineral density, and severity of osteoporosis significantly affected multiple regression analysis results (p

The functional level of children with progressive neuromuscular disease is a major factor that affects the quality of life (QOL) of parents. However, only a few publications have reported changes in the QOL of parents after correctional spinal surgery.The purpose was to compare changes in QOL for both patients and parents after spinal correctional surgery for better sitting balance and to analyze correlation among radiographic parameters, functional outcome, and QOL questionnaires. Finally, the QOL of patients and parents was compared with the population norm.This study is a retrospective analysis of prospectively gathered data.From 2008 to 2011, 58 patients who underwent correctional surgery for progressive neuromuscular scoliosis and their parents were enrolled.A Muscular Dystrophy Spine Questionnaire (MDSQ) and short-form questionnaire 36 (SF-36) were used.The gathered functional outcome and QOL data using MDSQ and SF-36 for both enrolled patients and parents were compared preoperatively, postoperatively at 3 months, and at 1-year follow-up.Mean age was 15.0±4.1 years. Forty male and 18 female patients were enrolled. Mean follow-up was 38.4±13.7 months. Cobb angle was 61.5°±23.5° preoperatively, 39.0°±20.1° immediately postoperative, and 40.0°±20.2° at the final follow-up. Cobb angle, pelvic obliquity, and lumbar lordosis were significantly improved after surgery (p.001). Among sitting-related questions, answers to questions 15 (sitting comfortably), 16 (change weight in wheelchair), 22 (sit all day), 24 (sit at table for meal), 26 (keep balance while sitting in wheelchair), and 27 (look good while sitting in wheelchair) were significantly improved after correctional surgery (p.001). Regarding the SF-36 scales for patients, bodily pain and social functioning significantly improved postoperatively (p.001).Muscular Dystrophy Spine Questionnaire results indicated that patients had significantly improved sitting balance-related outcomes, whereas the SF-36 indicated improvements only in bodily pain and social functioning scales. For parents, no SF-36 scales improved significantly postoperatively. Accordingly, improved sitting balance and QOL for neuromuscular scoliosis patients after surgery do not necessarily increase parent QOL.

This study tested whether hypocapnic constriction of the rabbit basilar artery in vitro can be triggered by serotonin, and whether the resulting constriction is (1) due to the alkaline pH associated with hypocapnia, and (2) endothelin-1 mediated. Hypocapnic alkaline solution (25 mM NaHCO(3); pH 7.76; pCO(2) 14.2) or isocapnic alkaline solution (50 mM NaHCO(3); pH 7.73; pCO(2) 35.0) rarely altered basal tension. Serotonin (3 microM) challenge in hypocapnic or isocapnic alkaline solution resulted in near maximal tension. Washout of the serotonin did not decrease tension in 54% of the tissues, as plateau tension was maintained for 2-2.5 h. The plateau tension of washed tissues was relaxed by 1-3 microM PD145065 (Ac-D-Bhg-L-Leu-Asp-L-Ile-L-Ile-L-Trp), BQ610 (homopiperidinyl-CO-Leu-D-Trp(CHO)-D-Trp), and BQ788 (N-cis-2, 6-dimethyl-piperidinocarbonyl-L-gamma-MeLeu-D-Trp (COOCH(3))-Nle), endothelin ET(A)/ET(B), endothelin ET(A), and endothelin ET(B) receptor antagonists, respectively. In contrast, serotonin-induced tension in normal solution (25 mM NaHCO(3); pH 7.42; pCO(2) 36.9) was maintained for only 40 min (mean). These results demonstrate that (1) constriction due to hypocapnia in vitro can be triggered by serotonin and is endothelin-1 mediated and (2) alkaline pH in the absence of decreased pCO(2) is sufficient to elicit the constriction triggered by serotonin.

This study tested whether hypocapnic constriction of the rabbit basilar artery in vitro can be triggered by a nitric oxide (NO) synthase inhibitor, and whether the resulting constriction is (1) due to the alkaline pH associated with hypocapnia, and (2) endothelin-1 mediated. Hypocapnic (25 mM NaHCO(3); pH 7.76; pCO(2) 14.2) or isocapnic alkaline solution (50 mM NaHCO(3); pH 7.73; pCO(2) 35.0) rarely altered basal tension. N(G)-monomethyl-L-arginine monoacetate (L-NMMA; 0.1 mM) challenge in hypocapnic or isocapnic alkaline solution resulted in near maximal tension that was maintained for 2-2.5 h even following L-NMMA washout. L-NMMA challenge in normal solution (25 mM NaHCO(3); pH 7. 42; pCO(2) 36.9) also induced near maximal tension, although the tension was maintained for only 25 min (mean). Ac-D-Bhg-L-Leu-Asp-L-Ile-L-Ile-L-Trp (PD145065), homopiperidinyl-CO-Leu-D-Trp(CHO)-D-Trp (BQ610), and N-cis-2, 6-dimethyl-piperidinocarbonyl L-gamma-MeLeu-D-Trp (COOCH(3))-Nle (BQ788; 1-3 microM), endothelin ET(A)/ET(B), endothelin ET(A), and endothelin ET(B) receptor antagonists, respectively, completely relaxed the tension that resulted from L-NMMA challenge in hypocapnic or isocapnic alkaline solution. These results demonstrate that constriction due to hypocapnia in vitro can be triggered by an NO synthase inhibitor and is endothelin-1 mediated. Additionally, alkaline pH in the absence of decreased pCO(2) is sufficient to elicit the constriction.

STUDY DESIGN A retrospective clinical case series. OBJECTIVE To investigate knee osteoarthritis (KOA) and total knee replacement (TKR) status as prognostic factors for surgical outcomes in female patients with lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA There have been many reports on numerous prognostic factors for surgical outcomes in patients with degenerative lumbar conditions; however, there has been no report on the surgical outcome in patients who underwent spinal surgery with coexisting KOA and TKR. METHODS This study included 141 female patients (mean age, 67.6 y) who underwent spinal surgery for LSS between January 2006 and December 2010. At 1 year postoperatively, surgical outcomes were measured using the Oswestry disability index (ODI). Various clinical factors including KOA and TKR were analyzed as prognostic factors for surgical outcomes. RESULTS Mean average scores at preoperative evaluation were 26.1±6.6 in the no KOA group, 23.6±7.9 in the KOA group, and 30.4±6.7 in the TKR group (P