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1.  Optical Coherence Tomography Reflects Brain Atrophy in Multiple Sclerosis: A Four-Year Study 
Annals of neurology  2015;78(5):801-813.
Objective
The aim of this work was to determine whether atrophy of specific retinal layers and brain substructures are associated over time, in order to further validate the utility of optical coherence tomography (OCT) as an indicator of neuronal tissue damage in patients with multiple sclerosis (MS).
Methods
Cirrus high-definition OCT (including automated macular segmentation) was performed in 107 MS patients biannually (median follow-up: 46 months). Three-Tesla magnetic resonance imaging brain scans (including brain-substructure volumetrics) were performed annually. Individual-specific rates of change in retinal and brain measures (estimated with linear regression) were correlated, adjusting for age, sex, disease duration, and optic neuritis (ON) history.
Results
Rates of ganglion cell + inner plexiform layer (GCIP) and whole-brain (r = 0.45; p<0.001), gray matter (GM; r = 0.37; p<0.001), white matter (WM; r = 0.28; p = 0.007), and thalamic (r = 0.38; p < 0.001) atrophy were associated. GCIP and whole-brain (as well as GM and WM) atrophy rates were more strongly associated in progressive MS (r = 0.67; p<0.001) than relapsing-remitting MS (RRMS; r = 0.33; p = 0.007). However, correlation between rates of GCIP and whole-brain (and additionally GM and WM) atrophy in RRMS increased incrementally with step-wise refinement to exclude ON effects; excluding eyes and then patients (to account for a phenotype effect), the correlation increased to 0.45 and 0.60, respectively, consistent with effect modification. In RRMS, lesion accumulation rate was associated with GCIP (r = −0.30; p = 0.02) and inner nuclear layer (r = −0.25; p = 0.04) atrophy rates.
Interpretation
Over time GCIP atrophy appears to mirror whole-brain, and particularly GM, atrophy, especially in progressive MS, thereby reflecting underlying disease progression. Our findings support OCT for clinical monitoring and as an outcome in investigative trials.
doi:10.1002/ana.24487
PMCID: PMC4703093  PMID: 26190464
2.  Discovery of Inhibitors for the Ether Lipid-Generating Enzyme AGPS as Anti-Cancer Agents 
ACS chemical biology  2015;10(11):2589-2597.
Dysregulated ether lipid metabolism is an important hallmark of cancer cells. Previous studies have reported that lowering ether lipid levels by genetic ablation of the ether lipid-generating enzyme alkyl-glycerone phosphate synthase (AGPS) lowers key structural and oncogenic ether lipid levels and alters fatty acid, glycerophospholipid, and eicosanoid metabolism to impair cancer pathogenicity, indicating that AGPS may be a potential therapeutic target for cancer. In this study, we have performed a small-molecule screen to identify candidate AGPS inhibitors. We have identified several lead AGPS inhibitors and have structurally characterized their interactions with the enzyme and show that these inhibitors bind to distinct portions of the active site. We further show that the lead AGPS inhibitor 1a selectively lowers ether lipid levels in several types of human cancer cells and impairs their cellular survival and migration. We provide here the first report of in situ-effective pharmacological tools for inhibiting AGPS, which may provide chemical scaffolds for future AGPS inhibitor development for cancer therapy.
doi:10.1021/acschembio.5b00466
PMCID: PMC4703096  PMID: 26322624
3.  Yes-Associated Protein 1 Is Activated and Functions as an Oncogene in Meningiomas 
Molecular cancer research : MCR  2012;10(7):904-913.
The Hippo signaling pathway is functionally conserved in Drosophila melanogaster and mammals, and its proposed function is to control tissue homeostasis by regulating cell proliferation and apoptosis. The core components are composed of a kinase cascade that culminates with the phosphorylation and inhibition of Yes-associated protein 1 (YAP1). Phospho-YAP1 is retained in the cytoplasm. In the absence of Hippo signaling, YAP1 translocates to the nucleus, associates with co-activators TEAD1-4, and functions as a transcriptional factor promoting the expression of key target genes. Components of the Hippo pathway are mutated in human cancers, and deregulation of this pathway plays a role in tumorigenesis. Loss of the NF2 tumor suppressor gene is the most common genetic alteration in meningiomas, and the NF2 gene product, Merlin, acts upstream of the Hippo pathway. Here, we show that primary meningioma tumors have high nuclear expression of YAP1. In meningioma cells, Merlin expression is associated with phosphorylation of YAP1. Using an siRNA transient knockdown of YAP1 in NF2-mutant meningioma cells, we show that suppression of YAP1 impaired cell proliferation and migration. Conversely, YAP1 overexpression led to a strong augment of cell proliferation and anchorage-independent growth and restriction of cisplatin-induced apoptosis. In addition, expression of YAP1 in nontransformed arachnoidal cells led to the development of tumors in nude mice. Together, these findings suggest that in meningiomas, deregulation of the Hippo pathway is largely observed in primary tumors and that YAP1 functions as an oncogene promoting meningioma tumorigenesis.
doi:10.1158/1541-7786.MCR-12-0116
PMCID: PMC4703097  PMID: 22618028
4.  Small Retailer Perspectives of the 2009 Women, Infants and Children Program Food Package Changes 
Objective
To understand vendor perspectives regarding changes made in 2009 to the Special Supplemental Nutrition Program for Women, Infant, and Children (WIC) food package.
Methods
Fifty-two in-depth, qualitative interviews with owners or managers of small stores in 8 urban areas across 7 states conducted 6-12 months after the changes.
Results
Store owners experienced implementation challenges, but felt the changes increased the number of customers, sales, and profits.
Conclusion
This research provides vendor perspectives on the 2009 WIC policy changes and may enhance policy implementation directed at increasing healthy food availability, particularly in urban communities.
doi:10.5993/AJHB.36.5.8
PMCID: PMC4703098  PMID: 22584093
WIC; qualitative research; storeowner perspectives; food policy; sales
5.  The Dynamic Process of Drug-GPCR Binding at Either Orthosteric or Allosteric Sites Evaluated by Metadynamics 
Major advances in G Protein-Coupled Receptor (GPCR) structural biology over the past few years have yielded a significant number of high-resolution crystal structures for several different receptor subtypes. This dramatic increase in GPCR structural information has underscored the use of automated docking algorithms for the discovery of novel ligands that can eventually be developed into improved therapeutics. However, these algorithms are often unable to discriminate between different, yet energetically similar, poses because of their relatively simple scoring functions. Here, we describe a metadynamics-based approach to study the dynamic process of ligand binding to/unbinding from GPCRs with a higher level of accuracy and yet satisfying efficiency.
doi:10.1007/978-1-4939-2914-6_18
PMCID: PMC4703114  PMID: 26260607
Molecular dynamics; Ligand binding; Receptor; Simulations; Enhanced sampling algorithms; Free energy
6.  The impact of criminalization of HIV non-disclosure on the healthcare engagement of women living with HIV in Canada: a comprehensive review of the evidence 
Introduction
In 2012, the Supreme Court of Canada ruled that people living with HIV (PLWH) must disclose their HIV status to sexual partners prior to sexual activity that poses a “realistic possibility” of HIV transmission for consent to sex to be valid. The Supreme Court deemed that the duty to disclose could be averted if a person living with HIV both uses a condom and has a low plasma HIV-1 RNA viral load during vaginal sex. This is one of the strictest legal standards criminalizing HIV non-disclosure worldwide and has resulted in a high rate of prosecutions of PLWH in Canada. Public health advocates argue that the overly broad use of the criminal law against PLWH undermines efforts to engage individuals in healthcare and complicates gendered barriers to linkage and retention in care experienced by women living with HIV (WLWH).
Methods
We conducted a comprehensive review of peer-reviewed and non-peer-reviewed evidence published between 1998 and 2015 evaluating the impact of the criminalization of HIV non-disclosure on healthcare engagement of WLWH in Canada across key stages of the cascade of HIV care, specifically: HIV testing and diagnosis, linkage and retention in care, and adherence to antiretroviral therapy. Where available, evidence pertaining specifically to women was examined. Where these data were lacking, evidence relating to all PLWH in Canada or other international jurisdictions were included.
Results and discussion
Evidence suggests that criminalization of HIV non-disclosure may create barriers to engagement and retention within the cascade of HIV care for PLWH in Canada, discouraging access to HIV testing for some people due to fears of legal implications following a positive diagnosis, and compromising linkage and retention in healthcare through concerns of exposure of confidential medical information. There is a lack of published empirical evidence focused specifically on women, which is a concern given the growing population of WLWH in Canada, among whom marginalized and vulnerable women are overrepresented.
Conclusions
The threat of HIV non-disclosure prosecution combined with a heightened perception of surveillance may alter the environment within which women engage with healthcare services. Fully exploring the extent to which HIV criminalization represents a barrier to the healthcare engagement of WLWH is a public health priority.
doi:10.7448/IAS.18.1.20572
PMCID: PMC4689876  PMID: 26701080
HIV; criminalization; HIV non-disclosure; women; Canada
7.  Urinary Nucleic Acid TSPAN13-to-S100A9 Ratio as a Diagnostic Marker in Prostate Cancer 
Journal of Korean Medical Science  2015;30(12):1784-1792.
The potential use of urinary nucleic acids as diagnostic markers in prostate cancer (PCa) was evaluated. Ninety-five urine samples and 234 prostate tissue samples from patients with PCa and benign prostatic hyperplasia (BPH) were analyzed. Micro-array analysis was used to identify candidate genes, which were verified by the two-gene expression ratio and validated in tissue mRNA and urinary nucleic acid cohorts. Real-time quantitative polymerase chain reaction (qPCR) was used to measure urinary nucleic acid levels and tissue mRNA expression. The TSPAN13-to-S100A9 ratio was selected to determine the diagnostic value of urinary nucleic acids in PCa (P = 0.037) and shown to be significantly higher in PCa than in BPH in the mRNA and nucleic acid cohort analyses (P < 0.001 and P = 0.013, respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.898 and 0.676 in tissue mRNA cohort and urinary nucleic acid cohort, respectively. The TSPAN13-to-S100A9 ratio showed a strong potential as a diagnostic marker for PCa. The present results suggest that the analysis of urine supernatant can be used as a simple diagnostic method for PCa that can be adapted to the clinical setting in the future.
Graphical Abstract
doi:10.3346/jkms.2015.30.12.1784
PMCID: PMC4689822  PMID: 26713053
Prostatic Neoplasms; Cell-free Nucleic Acid; Urine; Two-gene Expression Ratio; S100A9; TSPAN13; Diagnostic Marker
8.  Prognostic Inflammation Score in Surgical Patients with Colorectal Cancer 
Journal of Korean Medical Science  2015;30(12):1793-1799.
Several inflammatory markers have been investigated as prognostic parameters in a variety of cancer population with mostly favorable results. This study aimed to verify the significance of common inflammatory markers as prognostic variables and assess whether a selective combination of them as prognostic inflammation score (PIS) could further improve their prognostic values in surgical patients with colorectal cancer (CRC). A total of 265 patients who had undergone curative resection of CRC were reviewed retrospectively. Preoperative levels of inflammatory markers such as serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), and neutrophil/lymphocyte ratio (NLR) were assessed by uni- and multivariate survival analysis with disease-free (DFS) and disease-specific survival (DSS). PIS was constructed with a selective combination of inflammatory markers which were independently significant. On univariate analysis, CRP, ESR, and NLR were significantly associated with DFS and DSS. On multivariate analysis, CRP and NLR were independently significant prognostic variables for DSS and DFS respectively (P=0.013, P=0.021). When PIS was constructed with combination of CRP and NLR, it was independently and significantly associated with both DFS and DSS (P=0.006, P=0.010). Furthermore, PIS was superior to CRP for DSS (HR=15.679 vs. HR=5.183), and NLR for DFS in terms of prognosticating power (HR=4.894 vs. HR=2.687). When PIS is constructed with combination of CRP and NLR, it is a potentially significant prognostic variable associated with poor survival regardless pathologic prognostic variables in patients with CRC after curative resection.
Graphical Abstract
doi:10.3346/jkms.2015.30.12.1793
PMCID: PMC4689823  PMID: 26713054
Colorectal Neoplasms; Inflammation; C-reactive Protein, Erythrocyte Sedimentation Rate; White Blood Cell Count; Neutrophi/Lymphocyte Ratio
9.  Persistence with Antihypertensive Medications in Uncomplicated Treatment-Naïve Patients: Effects of Initial Therapeutic Classes 
Journal of Korean Medical Science  2015;30(12):1800-1806.
We aimed to assess one-year persistence with antihypertensive therapy (AHT) among newly treated uncomplicated hypertensive patients in Korea and to evaluate the effect of initial therapeutic classes on persistence. We retrospectively analyzed a random sample of 20% of newly treated uncomplicated hypertensive patients (n = 45,787) in 2012 from the National Health Insurance claims database. This group was classified into six cohorts based on initial AHT class. We then measured treatment persistence, allowing a prescription gap of 60 days. Adherence to AHT was assessed with the medication possession ratio. Calcium channel blockers (CCB, 43.7%) and angiotensin receptor blockers (ARB, 40.3%) were most commonly prescribed as initial monotherapy. Overall, 62.1% and 42.0% were persistent with any AHT and initial class at one year, respectively, and 64.2% were adherent to antihypertensive treatment. Compared with ARBs, the risk of AHT discontinuation was significantly increased with initial use of thiazide diuretics (hazard ratio [HR], 3.16; 95% confidence interval [CI] 2.96-3.74) and beta blockers (HR, 1.86; CI, 1.77-1.95) and was minimally increased with CCBs (HR, 1.12; CI, 1.08-1.15). In conclusion, persistence and adherence to AHT are suboptimal, but the differences are meaningful in persistence and adherence between initial AHT classes.
Graphical Abstract
doi:10.3346/jkms.2015.30.12.1800
PMCID: PMC4689824  PMID: 26713055
Uncomplicated Hypertension; Persistence; Adherence; Therapeutic Class
10.  Renal Complications and Their Prognosis in Korean Patients with Middle East Respiratory Syndrome-Coronavirus from the Central MERS-CoV Designated Hospital 
Journal of Korean Medical Science  2015;30(12):1807-1814.
Some cases of Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) infection presented renal function impairment after the first MERS-CoV patient died of progressive respiratory and renal failure. Thus, MERS-CoV may include kidney tropism. However, reports about the natural courses of MERS-CoV infection in terms of renal complications are scarce. We examined 30 MERS-CoV patients admitted to National Medical Center, Korea. We conducted a retrospective analysis of the serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urine dipstick tests, urinary protein quantitation (ACR or PCR), and other clinical parameters in all patients. Two consecutive results of more than trace (or 1+) of albumin and blood on dipstick test occurred in 18 (60%) (12 [40%]) and 22 (73.3%) (19 [63.3%]) patients, respectively. Fifteen (50.0%) patients showed a random urine ACR or PCR more than 100 mg/g Cr. Eight (26.7%) patients showed acute kidney injury (AKI), and the mean and median durations to the occurrence of AKI from symptom onset were 18 and 16 days, respectively. Old age was associated with a higher occurrence of AKI in the univariate analysis (HR [95% CI]: 1.069 [1.013-1.128], P = 0.016) and remained a significant predictor of the occurrence of AKI after adjustment for comorbidities and the application of a mechanical ventilator. Diabetes, AKI, and the application of a continuous renal replacement therapy (CRRT) were risk factors for mortality in the univariate analysis (HR [95% CI]: diabetes; 10.133 [1.692-60.697], AKI; 12.744 [1.418-114.565], CRRT; 10.254 [1.626-64.666], respectively). Here, we report renal complications and their prognosis in 30 Korean patients with MERS-CoV.
doi:10.3346/jkms.2015.30.12.1807
PMCID: PMC4689825  PMID: 26713056
Middle; East Respiratory Syndrome-Coronavirus; Prognosis; Renal Complication
11.  Clinical Features of Drug-induced Liver Injury According to Etiology 
Journal of Korean Medical Science  2015;30(12):1815-1820.
Drug-induced liver injury (DILI) is an increasingly common cause of acute hepatitis. We examined clinical features and types of liver injury of 65 affected patients who underwent liver biopsy according DILI etiology. The major causes of DILI were the use of herbal medications (43.2%), prescribed medications (21.6%), and traditional therapeutic preparations and dietary supplements (35%). DILI from herbal medications, traditional therapeutic preparations, and dietary supplements was associated with higher elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels than was DILI from prescription medications. The types of liver injury based on the R ratio were hepatocellular (67.7%), mixed (10.8%), and cholestatic (21.5%). Herbal medications and traditional therapeutic preparations were more commonly associated with hepatocellular liver injury than were prescription medications (P = 0.002). Herbal medications and traditional therapeutic preparations induce more hepatocellular DILI and increased elevations in AST and ALT than prescribed medications.
Graphical Abstract
doi:10.3346/jkms.2015.30.12.1815
PMCID: PMC4689826  PMID: 26713057
Drug-induced Liver Injury; Hepatotoxicity; Etiology; Plants, Medicinal; Traditional Therapy; Prescribed Medicines
12.  Vitamin D Status and Bone Mineral Density in Obese Children with Nonalcoholic Fatty Liver Disease 
Journal of Korean Medical Science  2015;30(12):1821-1827.
Whether nonalcoholic fatty liver disease (NAFLD) is related to vitamin D and bone health in obese children is unknown. The aim of this study was to evaluate vitamin D status and bone mineral density (BMD) in obese children according to their condition within the NAFLD spectrum. Anthropometric data, laboratory tests, and abdominal ultrasonography were obtained from 94 obese children. The subjects were divided into three groups according to NAFLD spectrum: normal liver, simple steatosis, and nonalcoholic steatohepatitis (NASH). Although there were no differences in vitamin D levels between the three groups, these groups showed significant differences in highly sensitive C-reactive protein (P=0.044), homeostasis model assessment of insulin resistance (HOMA-IR) (P=0.02), hepatic fibrosis scores (P<0.05), and trunk fat percentage (P=0.025). Although there were significant differences in BMDs, the age-matched BMD z-scores were not significantly different between the three groups. Serum vitamin D levels were negatively correlated with age (r=-0.368, P=0.023), serum uric acid levels (r=-0.371, P=0.022), fibrosis 4 (FIB4) (r=-0.406, P=0.011), and HOMA-IR (r=-0.530, P=0.001) in obese children with NASH. Multiple regression analysis for vitamin D in the NASH group revealed age and HOMA-IR as significant factors. In conclusion, inflammatory markers, hepatic fibrosis scores, trunk fat, and insulin resistance may reflect the spectrum of NAFLD in obese children, whereas vitamin D levels and BMD may not. In patients with NASH, however, low serum vitamin D is associated with hepatic fibrosis and insulin resistance, but not with bone health status.
Graphical Abstract
doi:10.3346/jkms.2015.30.12.1821
PMCID: PMC4689827  PMID: 26713058
Obesity; Vitamin D; Bone Density; Insulin Resistance; Body Composition; Nonalcoholic Fatty Liver Disease; Child
13.  Early Caffeine Use in Very Low Birth Weight Infants and Neonatal Outcomes: A Systematic Review and Meta-Analysis 
Journal of Korean Medical Science  2015;30(12):1828-1835.
The use of caffeine citrate for treatment of apnea in very low birth weight infants showed short-term and long-term benefits. A systematic review and meta-analysis of the literature was undertaken to document the effect providing caffeine early (0-2 days of life) compared to providing caffeine late (≥3 days of life) in very low birth weight infants on several neonatal outcomes, including bronchopulmonary dysplasia (BPD). We searched MEDLINE, the EMBASE database, the Cochrane Library, and KoreaMed for this meta-analysis. The quality of the included studies was assessed using the Newcastle-Ottawa Scale and Jadad's scale. Studies were included if they examined the effect of the early use of caffeine compared with the late use of caffeine. Two reviewers screened the candidate articles and extracted the data from the full-text of all of the included studies. We included a total of 59,136 participants (range 58,997-59,136; variable in one study) from a total of 5 studies. The risk of death (odds ratio [OR], 0.902; 95% confidence interval [CI], 0.828 to 0.983; P=0.019), bronchopulmonary dysplasia (BPD) (OR, 0.507; 95% CI, 0.396 to 0.648; P<0.001), and BPD or death (OR, 0.526; 95% CI, 0.384 to 0.719; P<0.001) were lower in the early caffeine group. Early caffeine use was not associated with a risk of necrotizing enterocolitis (NEC) and NEC requiring surgery. This meta-analysis suggests that early caffeine use has beneficial effects on neonatal outcomes, including mortality and BPD, without increasing the risk of NEC.
doi:10.3346/jkms.2015.30.12.1828
PMCID: PMC4689828  PMID: 26713059
Caffeine; Very Low Birth Weight; Bronchopulmonary Dysplasia; Infant, Newborn; Outcome
14.  Characteristics of Children with Acute Carbon Monoxide Poisoning in Ankara: A Single Centre Experience 
Journal of Korean Medical Science  2015;30(12):1836-1840.
The purpose of the study was to define characteristics of children with acute carbon monoxide poisoning. Eighty children hospitalized with acute carbon monoxide poisoning were recruited prospectively over a period of 12 months. Sociodemographic features, complaints and laboratory data were recorded. When the patient was discharged, necessary preventive measures to be taken were explained to parents. One month later, the parents were questioned during a control examination regarding the precautions that they took. The ages of the cases were between one month and 16 yr. Education levels were low in 86.2% of mothers and 52.6% of fathers. All families had low income and 48.8% did not have formal housing. The source of the acute carbon monoxide poisoning was stoves in 71.2% of cases and hot-water heaters in 28.8% of cases. Three or more people were poisoned at home in 85.1% of the cases. The most frequent symptoms of poisoning were headache and vertigo (58.8%). Median carboxyhemoglobin levels at admission to the hospital and discharge were measured as 19.5% and 1.1% (P < 0.001). When families were called for re-evaluation, it was determined that most of them had taken the necessary precautions after the poisoning incident (86.3%). This study determined that children with acute childhood carbon monoxide poisoning are usually from families with low socioeconomic and education levels. Education about prevention should be provided to all people who are at risk of carbon monoxide poisoning before a poisoning incident occurs.
doi:10.3346/jkms.2015.30.12.1836
PMCID: PMC4689829  PMID: 26713060
Child; Carbon Monoxide; Poisoning; Prevention; Education; Ankara
15.  Postpartum Glucose Testing Rates Following Gestational Diabetes Mellitus and Factors Affecting Testing Non-compliance from Four Tertiary Centers in Korea 
Journal of Korean Medical Science  2015;30(12):1841-1846.
The purpose of this study was to investigate postpartum glucose testing rates in patients with gestational diabetes mellitus (GDM) and to determine factors affecting testing non-compliance in the Korean population. This was a retrospective study of 1,686 patients with GDM from 4 tertiary centers in Korea and data were obtained from medical records. Postpartum glucose testing was conducted using a 2-hr 75-g oral glucose tolerance, fasting glucose, or hemoglobin A1C test. Test results were categorized as normal, prediabetic, and diabetic. The postpartum glucose testing rate was 44.9% (757/1,686 patients); and of 757 patients, 44.1% and 18.4% had pre-diabetes and diabetes, respectively. According to the multivariate analysis, patients with a high parity, larger weight gain during pregnancy, and referral from private clinics due to reasons other than GDM treatment were less likely to receive postpartum glucose testing. However, patients who had pharmacotherapy for GDM were more likely to be screened. In this study, 55.1% of patients with GDM failed to complete postpartum glucose testing. Considering the high prevalence of diabetes (18.4%) at postpartum, clinicians should emphasize the importance of postpartum diabetes screening to patients with factors affecting testing noncompliance.
Graphical Abstract
doi:10.3346/jkms.2015.30.12.1841
PMCID: PMC4689830  PMID: 26713061
Diabetes, Gestational; Postpartum Glucose Screening; Referral
16.  Cerebral Angiographic Findings of Cosmetic Facial Filler-related Ophthalmic and Retinal Artery Occlusion 
Journal of Korean Medical Science  2015;30(12):1847-1855.
Cosmetic facial filler-related ophthalmic artery occlusion is rare but is a devastating complication, while the exact pathophysiology is still elusive. Cerebral angiography provides more detailed information on blood flow of ophthalmic artery as well as surrounding orbital area which cannot be covered by fundus fluorescein angiography. This study aimed to evaluate cerebral angiographic features of cosmetic facial filler-related ophthalmic artery occlusion patients. We retrospectively reviewed cerebral angiography of 7 patients (4 hyaluronic acid [HA] and 3 autologous fat-injected cases) showing ophthalmic artery and its branches occlusion after cosmetic facial filler injections, and underwent intra-arterial thrombolysis. On selective ophthalmic artery angiograms, all fat-injected patients showed a large filling defect on the proximal ophthalmic artery, whereas the HA-injected patients showed occlusion of the distal branches of the ophthalmic artery. Three HA-injected patients revealed diminished distal runoff of the internal maxillary and facial arteries, which clinically corresponded with skin necrosis. However, all fat-injected patients and one HA-injected patient who were immediately treated with subcutaneous hyaluronidase injection showed preserved distal runoff of the internal maxillary and facial arteries and mild skin problems. The size difference between injected materials seems to be associated with different angiographic findings. Autologous fat is more prone to obstruct proximal part of ophthalmic artery, whereas HA obstructs distal branches. In addition, hydrophilic and volume-expansion property of HA might exacerbate blood flow on injected area, which is also related to skin necrosis. Intra-arterial thrombolysis has a limited role in reconstituting blood flow or regaining vision in cosmetic facial filler-associated ophthalmic artery occlusions.
Graphical Abstract
doi:10.3346/jkms.2015.30.12.1847
PMCID: PMC4689831  PMID: 26713062
Retinal Artery Occlusion; Hyaluronic Acid; Autologous Fat; Facial Filler; Cerebral Angiography
17.  The Toxicity of Nonsteroidal Anti-inflammatory Eye Drops against Human Corneal Epithelial Cells in Vitro 
Journal of Korean Medical Science  2015;30(12):1856-1864.
This study investigated the toxicity of commercial non-steroid anti-inflammatory drug (NSAID) eye solutions against corneal epithelial cells in vitro. The biologic effects of 1/100-, 1/50-, and 1/10-diluted bromfenac sodium, pranoprofen, diclofenac sodium, and the fluorometholone on corneal epithelial cells were evaluated after 1-, 4-, 12-, and 24-hr of exposure compared to corneal epithelial cell treated with balanced salt solution as control. Cellular metabolic activity, cellular damage, and morphology were assessed. Corneal epithelial cell migration was quantified by the scratch-wound assay. Compared to bromfenac and pranoprofen, the cellular metabolic activity of diclofenac and fluorometholone significantly decreased after 12-hr exposure, which was maintained for 24-hr compared to control. Especially, at 1/10-diluted eye solution for 24-hr exposure, the LDH titers of fluorometholone and diclofenac sodium markedly increased more than those of bromfenac and pranoprofen. In diclofenac sodium, the Na+ concentration was lower and amount of preservatives was higher than other NSAIDs eye solutions tested. However, the K+ and Cl- concentration, pH, and osmolarity were similar for all NSAIDs eye solutions. Bromfenac and pranoprofen significantly promoted cell migration, and restored wound gap after 48-hr exposure, compared with that of diclofenac or fluorometholone. At 1/50-diluted eye solution for 48-hr exposure, the corneal epithelial cellular morphology of diclofenac and fluorometholone induced more damage than that of bromfenac or pranoprofen. Overall, the corneal epithelial cells in bromfenac and pranoprofen NSAID eye solutions are less damaged compared to those in diclofenac, included fluorometholone as steroid eye solution.
Graphical Abstract
doi:10.3346/jkms.2015.30.12.1856
PMCID: PMC4689832  PMID: 26713063
Bromfenac Sodium; Corneal Epithelial Cells; Diclofenac Sodium; Fluorometholone; Pranoprofen; Cytotoxicity
18.  Clinical Performance of the 1st American Academy of Orthopaedic Surgeons Clinical Guideline on Prevention of Symptomatic Pulmonary Embolism after Total Knee Arthroplasty in Korean Patients 
Journal of Korean Medical Science  2015;30(12):1865-1873.
We sought to document the clinical performance of the 1st American Academy of Orthopaedic Surgeons (AAOS) guideline on the prevention of symptomatic pulmonary embolism (PE) after total knee arthroplasty (TKA) in Korean patients, in terms of the proportions of the each risk-stratified group, efficacy and safety. Consecutive 328 patients underwent TKA were preoperatively assessed for the risks of PE and bleeding and categorized into 4 groups: 1) standard risk, 2) high risk for PE, 3) high risk for bleeding, and 4) high risks both for PE and bleeding. One of three options was administered according to the groups (aspirin in group 1 or 4; enoxaparin and following aspirin in group 2; antithrombotic stocking in group 3). Incidences of symptomatic deep vein thrombosis (DVT) and PE, and major or minor bleeding complications were evaluated. Majority of the patients (86%) were assessed to be with standard risks both for PE and bleeding. No patient experienced symptomatic DVT or PE and major bleeding. Eleven percent of the patients discontinued chemoprophylaxis because of bleeding-related wound complication. In conclusion, the 1st AAOS guideline functions successfully in Korean patients undergoing TKA in terms of prevention of symptomatic DVT and PE while avoiding major bleeding complications.
Graphical Abstract
doi:10.3346/jkms.2015.30.12.1865
PMCID: PMC4689833  PMID: 26713064
Arthroplasty, Replacement, Knee; Venous Thromboembolism; Pulmonary Embolism; Venous Thrombosis; Hemorrhage; Chemoprevention; Aspirin; Enoxaparin; AAOS Guideline
19.  Vitamin C Deficiency of Korean Homeless Patients Visiting to Emergency Department with Acute Alcohol Intoxication 
Journal of Korean Medical Science  2015;30(12):1874-1880.
Vitamins are essential micronutrients for maintenance of tissue functions. Vitamin deficiency is one of the most serious and common health problems among both chronic alcoholics and the homeless. However, the vitamin-level statuses of such people have been little studied. We evaluated the actual vitamin statuses of alcoholic homeless patients who visited an emergency department (ED). In this study the blood levels of vitamins B1, B12, B6, and C of 217 alcoholic homeless patients were evaluated retrospectively in a single urban teaching hospital ED. Vitamin C deficiency was observed in 84.3% of the patients. The vitamin B1, B12, and B6 deficiency rates, meanwhile, were 2.3%, 2.3%, and 23.5%, respectively. Comparing the admitted patients with those who were discharged, only the vitamin C level was lower. (P=0.003) In fact, the patients' vitamin C levels were markedly diminished, vitamin C replacement therapy for homeless patients should be considered in EDs.
Graphical Abstract
doi:10.3346/jkms.2015.30.12.1874
PMCID: PMC4689834  PMID: 26713065
Vitamin B Complex; Ascorbic Acid Deficiency; Homeless Persons; Alcoholics
20.  Preventive Effects of Seat Belt on Clinical Outcomes for Road Traffic Injuries 
Journal of Korean Medical Science  2015;30(12):1881-1888.
Proper seat belt use saves lives; however, the use rate decreased in Korea. This study aimed to measure the magnitude of the preventive effect of seat belt on case-fatality across drivers and passengers. We used the Emergency Department based Injury In-depth Surveillance (EDIIS) database from 17 EDs between 2011 and 2012. All of adult injured patients from road traffic injuries (RTI) in-vehicle of less than 10-seat van were eligible, excluding cases with unknown seat belt use and outcomes. Primary and secondary endpoints were in-hospital mortality and intracranial injury. We calculated adjusted odds ratios (AORs) of seat belt use and driving status for study outcomes adjusting for potential confounders. Among 23,698 eligible patients, 15,304 (64.6%) wore seat belts. Driver, middle aged (30-44 yr), male, daytime injured patients were more likely to use seat belts (all P < 0.001). In terms of clinical outcome, no seat belt group had higher proportions of case-fatality and intracranial injury compared to seat belt group (both P < 0.001). Compared to seat belt group, AORs (95% CIs) of no seat belt group were 10.43 (7.75-14.04) for case-fatality and 2.68 (2.25-3.19) for intracranial injury respectively. In the interaction model, AORs (95% CIs) of no seat belt use for case-fatality were 11.71 (8.45-16.22) in drivers and 5.52 (2.83-14.76) in non-driving passengers, respectively. Wearing seat belt has significantly preventive effects on case-fatality and intracranial injury. Public health efforts to increase seat belt use are needed to reduce health burden from RTIs.
Graphical Abstract
doi:10.3346/jkms.2015.30.12.1881
PMCID: PMC4689835  PMID: 26713066
Mortality; Accident Prevention; Motor Vehicles; Seat Belts
21.  The Relationship between Clinical Outcome in Subarachnoidal Hemorrhage Patients with Emergency Medical Service Usage and Interhospital Transfer 
Journal of Korean Medical Science  2015;30(12):1889-1895.
Prompt diagnosis and appropriate transport of patients with subarachnoid hemorrhage (SAH) is critical. We aimed to study differences in clinical outcomes by emergency medical services (EMS) usage and interhospital transfer in patients with SAH. We analyzed the CAVAS (CArdioVAscular disease Surveillance) database which is an emergency department-based, national cohort of cardiovascular disease in Korea. Eligible patients were adults with non-traumatic SAH diagnosed between January 2007 and December 2012. We excluded those whose EMS use and intershopital transfer data was unknown. The primary and secondary outcomes were mortality and neurologic status at discharge respectively. We compared the outcomes between each group using multivariable logistic regressions, adjusting for sex, age, underlying disease, visit time and social history. Of 5,461 patients with SAH, a total of 2,645 were enrolled. Among those, 258 used EMS and were transferred from another hospital, 686 used EMS only, 1,244 were transferred only, and 457 did not use EMS nor were transferred. In the regression analysis, mortality was higher in patients who used EMS and were transferred (OR 1.40, 95% CI 1.02-1.92), but neurologic disability was not meaningfully different by EMS usage and interhospital transfer. In Korea, SAH patients' mortality is higher in the case of EMS use or receiving interhospital transfer.
Graphical Abstract
doi:10.3346/jkms.2015.30.12.1889
PMCID: PMC4689836  PMID: 26713067
Subarachnoid Haemorrhage; Emergency Medical Services; Interhospital Transfer; Mortality
22.  CT Findings in People Who Were Environmentally Exposed to Asbestos in Korea 
Journal of Korean Medical Science  2015;30(12):1896-1901.
Asbestos related pleuropulmonary disease has been emerging health problem for recent years. It can cause variable clinical symptoms and radiological abnormalities. However, there has been no report for their characteristics in subjects who were environmentally exposed to asbestos. We reviewed the CT images of 35 people who were environmentally exposed to asbestos in Chungnam province, Korea. The study result showed high incidence of pleural plaque and pulmonary fibrosis on chest CT (94% and 77%, respectively). The common CT findings of lung parenchymal lesions were as follows: centrilobular opacities (94%), subpleural dot-like or branching opacities (80%), interlobular septal thickening (57%), intralobular interstitial thickening (46%), parenchymal bands (43%) and subpleural curvilinear line (29%). There were no significant differences in the prevalence of pulmonary fibrosis and pleural plaques according to sex, age and duration of exposure. In conclusion, pleural plaque and pulmonary fibrosis are common asbestos-related CT finding in the exposed people. Asbestos related lung parenchymal CT findings in the participants with environmental exposure show similar to those observed in the occupational exposure.
Graphical Abstract
doi:10.3346/jkms.2015.30.12.1896
PMCID: PMC4689837  PMID: 26713068
Asbestos; Environmental Exposure; Pulmonary Fibrosis; Asbestosis; Plaque; Multidetector Computed Tomography
23.  Changes in the Expressions of Iba1 and Calcitonin Gene-Related Peptide in Adjacent Lumbar Spinal Segments after Lumbar Disc Herniation in a Rat Model 
Journal of Korean Medical Science  2015;30(12):1902-1910.
Lumbar disc herniation is commonly encountered in clinical practice and can induce sciatica due to mechanical and/or chemical irritation and the release of proinflammatory cytokines. However, symptoms are not confined to the affected spinal cord segment. The purpose of this study was to determine whether multisegmental molecular changes exist between adjacent lumbar spinal segments using a rat model of lumbar disc herniation. Twenty-nine male Sprague-Dawley rats were randomly assigned to either a sham-operated group (n=10) or a nucleus pulposus (NP)-exposed group (n=19). Rats in the NP-exposed group were further subdivided into a significant pain subgroup (n=12) and a no significant pain subgroup (n=7) using mechanical pain thresholds determined von Frey filaments. Immunohistochemical stainings of microglia (ionized calcium-binding adapter molecule 1; Iba1), astrocytes (glial fibrillary acidic protein; GFAP), calcitonin gene-related peptide (CGRP), and transient receptor potential vanilloid 1 (TRPV1) was performed in spinal dorsal horns and dorsal root ganglions (DRGs) at 10 days after surgery. It was found immunoreactivity for Iba1-positive microglia was higher in the L5 (P=0.004) dorsal horn and in the ipsilateral L4 (P=0.009), L6 (P=0.002), and S1 (P=0.002) dorsal horns in the NP-exposed group than in the sham-operated group. The expression of CGRP was also significantly higher in ipsilateral L3, L4, L6, and S1 segments and in L5 DRGs at 10 days after surgery in the NP-exposed group than in the sham-operated group (P<0.001). Our results indicate that lumbar disc herniation upregulates microglial activity and CGRP expression in many adjacent and ipsilateral lumbar spinal segments.
Graphical Abstract
doi:10.3346/jkms.2015.30.12.1902
PMCID: PMC4689838  PMID: 26713069
Multisegmental; Neural Pathways; Lumbar Disc Herniation; Microglia; Calcitonin Gene-Related Peptide; Neuropathic Pain
24.  The Use of Extracorporeal Circulation in Suspected Brain Dead Organ Donors with Cardiopulmonary Collapse 
Journal of Korean Medical Science  2015;30(12):1911-1914.
Donor shortage is a major limitation in organ transplantation. Several studies have reported that extracorporeal membrane oxygenation (ECMO)-assisted organ donation can be successfully completed without inducing warm ischemia in patients with brain death. The present report described clinical experience of three patients (23-yr old man, 32-yr old man, and 41-yr old woman) who underwent ECMO for the evaluation of brain death and organ donation. They donated six kidneys, three livers, and one both lungs without warm ischemia by ECMO. Six kidney recipients successfully recovered normal status without hemodialysis and two liver recipients survived with normal liver functions, but one liver recipient and one lung recipient died 3 and 15 days after transplantation. Our report strongly encourages ECMO-assisted organ donation from brain death patients with refractory cardiopulmonary collapse to achieve improved organ transplantation.
doi:10.3346/jkms.2015.30.12.1911
PMCID: PMC4689839  PMID: 26713070
Extracorporeal Membrane Oxygenation; Brain Death; Tissue Organ Procurement
25.  Thyroid Cancer: We Need a Carcinogen-specific Genome Study 
Journal of Korean Medical Science  2015;30(12):1920-1921.
doi:10.3346/jkms.2015.30.12.1920
PMCID: PMC4689841  PMID: 26713072

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