PSORIASIS INCREASES RETINAL VEIN OCCLUSION RISK IN DIABETIC PATIENTS: A Nationwide Population-Based Study.

PURPOSE: The objective of this research was to explore how psoriasis is linked to the occurrence of retinal vein occlusion (RVO) in diabetic population. METHODS: This was a retrospective, nationwide, population-based cohort study that examined medical records from January 2009 to December 2012. The study focused on patients ≥20 years of age who had been diagnosed with Type 2 diabetes mellitus (DM). The authors compared the incidence rate of RVO between a group of patients with psoriasis and a group of patients without psoriasis until December 2018 in all subjects. RESULTS: Of the 2,745,689 Type 2 DM patients, 23,725 patients were classified in the psoriasis group and the rest of the 2,547,121 individuals in the control group. A total of 497 RVO cases occurred in the psoriasis group (3.14/1,000 person-years) and 42,388 RVO cases in the control group (2.44/1,000 person-years). According to multivariable Cox proportional hazard models, individuals with psoriasis had a significantly greater risk of developing RVO compared with control subjects (hazard ratio: 1.216, 95% confidence interval: 1.11-1.33) after adjustments for covariates. CONCLUSION: This study demonstrated that psoriasis was an independent risk factor for developing RVO in DM patients. Therefore, physicians need to be vigilant for the occurrence of RVO in DM patients who also have psoriasis.

Visual prognosis and surgical timing of Ahmed glaucoma valve implantation for neovascular glaucoma secondary to diabetic vitrectomy.

BACKGROUND: Evaluate the visual outcomes of Ahmed glaucoma valve implantation (AGVI) in patients with neovascular glaucoma (NVG) who underwent diabetic vitrectomy and suggest appropriate AGVI timing. METHODS: Medical records of patients who underwent AGVI due to NVG after diabetic vitrectomy were reviewed. Successful intraocular pressure (IOP) control was defined as an IOP between 6 and 21 mmHg. Visual outcome was compared before NVG diagnosis and after AGVI, and the "favorable" visual outcome was defined as a postoperative deterioration in BCVA of less than 0.3 logMAR units compared to those before the development of NVG. Various factors including surgical timing were evaluated to identify the risk factors associated with unfavorable visual outcome. RESULTS: A total of 35 eyes were enrolled and divided into group 1(medically uncontrolled NVG group, IOP more than 30mmHg, 16 eyes) and group 2(NVG group responded well to the initial non-surgical treatment but eventually required AGVI, 19 eyes). Despite the favorable rate of normalization of post-AGVI IOP (85.7%), 43.8% in Group 1 and 26.3% in Group 2 showed unfavorable visual outcomes. In group 1, delayed surgical timing more than 1 week from the NVG diagnosis showed a significant association with unfavorable visual outcomes (P = 0.041). In group 2, poor patient compliance (follow up loss, refuse surgery) was the main factor of unfavorable visual outcomes. CONCLUSION: When NVG occurs in patients with proliferative diabetic retinopathy after vitrectomy, physicians should be cautious not to delay the surgical intervention, especially in patients with IOP of 30 or more despite non-surgical treatment. Early AGVI within six days might be necessary to preserve useful vision in these patients.

Behçet's Disease Is Associated with Multiple Sclerosis and Rheumatoid Arthritis: A Korean Population-Based Study.

BACKGROUND: No epidemiologic study has previously reported on the associations among Behçet's disease (BD) and autoimmune disorders. OBJECTIVES: To investigate the association between BD and the autoimmune disorders multiple sclerosis and rheumatoid arthritis. METHODS: Medical records of patients newly diagnosed with BD (n = 6,214) in 2012-2017 were analyzed using data entered into a large, nationwide database from 2007 to 2017. An age- and sex-matched control population of individuals without BD was sampled at a ratio of controls:BD cases of 3:1 (n = 18,642). Both cohorts were analyzed for the presence of multiple sclerosis or rheumatoid arthritis within a minimum of 5 years prior to their BD diagnosis. RESULTS: Patients with BD had significantly higher odds ratios (ORs) for multiple sclerosis (8.85 [95% CI 2.36-33.17]) and rheumatoid arthritis (4.62 [95% CI 3.35-6.35]) than the control group after adjustment for diabetes mellitus, hypertension, and dyslipidemia. BD patients aged <40 years had a higher proportion of rheumatoid arthritis (OR 23.91, 95% CI 5.50-103.9) than older patients (OR 3.96, 95% CI 2.83-5.54). CONCLUSION: Our results suggest that BD is associated with multiple sclerosis and rheumatoid arthritis.

Association between Retinal Vein Occlusion and Psoriasis in Korea: A Nationwide Population-based Prospective Cohort Study.

Psoriasis is a chronic inflammatory skin disease imparting increased risk of cardiovascular diseases. Until now, few studies have reported an increased incidence of ophthalmological retinal vasculopathy in individuals with psoriasis. This study aimed to investigate the association between psoriasis and retinal vein occlusion in the Korean population. Data collected by the National Health Insurance Service between 2009 and 2015 in Korea were analysed. Participants who underwent national health examinations from 2009 to 2012 were enrolled in this study and were divided into either the psoriasis group (n = 3,088) or the control group (n = 465,205). All occurrences of retinal vein occlusion were observed, and the incidence rate of retinal vein occlusion was compared between the psoriasis and control groups. A Cox proportional hazards regression analysis was used to assess the association between psoriasis and newly developed retinal vein occlusion. During a mean 4.37-year follow-up period, 2,034 patients developed retinal vein occlusion. According to multivariable Cox proportional hazard models, individuals with psoriasis had a significantly higher risk of retinal vein occlusion compared with controls (hazard ratio 1.72, 95% confidence interval 1.18-2.51) after adjustments for covariates. This study found that psoriasis was positively associated with retinal vein occlusion.

Neuroprotective Effects of Green Tea Seed Isolated Saponin Due to the Amelioration of Tauopathy and Alleviation of Neuroinflammation: A Therapeutic Approach to Alzheimer's Disease.

Tauopathy is one of the major causes of neurodegenerative disorders and diseases such as Alzheimer's disease (AD). Hyperphosphorylation of tau proteins by various kinases leads to the formation of PHF and NFT and eventually results in tauopathy and AD; similarly, neuroinflammation also exaggerates and accelerates neuropathy and neurodegeneration. Natural products with anti-tauopathy and anti-neuroinflammatory effects are highly recommended as safe and feasible ways of preventing and /or treating neurodegenerative diseases, including AD. In the present study, we isolated theasaponin E1 from ethanol extract of green tea seed and evaluated its therapeutic inhibitory effects on tau hyper-phosphorylation and neuroinflammation in neuroblastoma (SHY-5Y) and glioblastoma (HTB2) cells, respectively, to elucidate the mechanism of the inhibitory effects. The expression of tau-generating and phosphorylation-promoting genes under the effects of theasaponin E1 were determined and assessed by RT- PCR, ELISA, and western blotting. It was found that theasaponin E1 reduced hyperphosphorylation of tau and Aß concentrations significantly, and dose-dependently, by suppressing the expression of GSK3 ß, CDK5, CAMII, MAPK, EPOE4(E4), and PICALM, and enhanced the expression of PP1, PP2A, and TREM2. According to the ELISA and western blotting results, the levels of APP, Aß, and p-tau were reduced by treatment with theasaponin E1. Moreover, theasaponin E1 reduced inflammation by suppressing the Nf-kB pathway and dose-dependently reducing the levels of inflammatory cytokines such as IL-1beta, IL-6, and TNF-alpha etc.

Investigation of Genetic Mutations in High-risk and Low-risk Basal Cell Carcinoma in a Non-Caucasian Population by Whole Exome Sequencing.

This study analysed genomic mutations in basal cell carcinoma using whole exome sequencing of DNA specimens obtained from 20 Korean patients. Histological evaluation determined that 15 (75%) were low-risk basal cell carcinomas, and 5 (25%) were high-risk basal cell carcinomas. Seventy-five percent of the basal cell carcinomas harboured somatic mutations in hedge-hog pathway genes (PTCH1, 40% and SMO, 50%) and 45% harboured mutations in TP53. LRP1B was the most frequently mutated gene in high-risk basal cell carcinomas, SMO was the most frequently mutated gene in low-risk basal cell carcinomas. Specifically, LRP1B, ROS1, PTCH1, KMT2C, NSD1 and ARID1A mutations were more frequent in high-risk basal cell carcinomas than in low-risk basal cell carcinomas. However, copy number gains of the ROS1 gene were observed only in low-risk basal cell carcinomas. Other basal cell carcinoma related genes found in this study include: KDR, KMT2D, FAT1, FAT4, GRIN2A, ERBB4, NOTCH2, PDE4DIP, TET1, ZFHX3 and PREX2. These results provide insight into basal cell carcinoma in non-Caucasians.

Association of Actinic Keratosis with Rheumatoid Arthritis and Psoriasis: A Nationwide Population-Based Study in Korea.

There have been no epidemiological studies identifying associations between systemic inflammatory diseases and actinic keratosis. This study used a large nationwide database to investigate the associations between actinic keratosis and systemic inflammatory diseases. Records of patients over 20 years of age newly diagnosed with actinic keratosis (n = 64,659) from 2012 to 2017 were analysed. A control population of individuals without actinic keratosis, matched for age, sex, and year of claim, who visited an outpatient clinic, was sampled at a ratio of 1:1 (n = 64,659). Both cohorts were analysed for the presence of systemic inflammatory diseases within at least 5 years prior to diagnosis of actinic keratosis. Patients with actinic keratosis exhibited higher odds ratios for rheumatoid arthritis (1.336; 95% confidence interval (95% CI) 1.161-1.537)) and psoriasis (1.513; 95% CI 1.435-1.595) compared with the control group on multivariate analysis. However, the proportions of Behçet's disease, Crohn's disease, ulcerative colitis, and multiple sclerosis in the actinic keratosis group were not statistically significant.

Raman Scattering Study on the Influence of E-Beam Bombardment on Si Electron Lens.

Microcolumns have a stacked structure composed of an electron emitter, electron lens (source lens), einzel lens, and a deflector manufactured using a micro electro-mechanical system process. The electrons emitted from the tungsten field emitter mostly pass through the aperture holes. However, other electrons fail to pass through because of collisions around the aperture hole. We used Raman scattering measurements and X-ray photoelectron spectroscopy analyses to investigate the influence of electron beam bombardment on a Si electron lens irradiated by acceleration voltages of 0, 20, and 30 keV. We confirmed that the crystallinity was degraded, and carbon-related contamination was detected at the surface and edge of the aperture hole of the Si electron lens after electron bombardment for 24 h. Carbon-related contamination on the surface of the Si electron lens was verified by analyzing the Raman spectra of the carbon-deposited Si substrate using DC sputtering and a carbon rod sample. We report the crystallinity and the origin of the carbon-related contamination of electron Si lenses after electron beam bombardment by non-destructive Raman scattering and XPS analysis methods.

Cancer risk in patients with Behçet disease: A nationwide population-based dynamic cohort study from Korea.

BACKGROUND: Many studies have shown a link between inflammation and cancer development. However, there are few studies regarding the correlation between Behçet disease (BD) and cancer. OBJECTIVES: To determine the overall cancer risk and risk for specific cancers in patients with BD. METHODS: Patients with BD (n = 14,137; mean age, 44.2 ± 12.5 years; male patients, 32.4%) without known previous cancer were selected from the Korean National Health Insurance Database between 2007 and 2014. An age- and sex-matched control population of individuals without BD was randomly sampled at a ratio of 10:1. Both cohorts were followed for incident cancer until 2015. RESULTS: Overall, cancer was newly diagnosed in 451 patients with BD (3.19%) and 3975 controls (2.81%) during the follow-up period. Patients with BD showed a significantly higher risk for cancer compared with the controls (hazard ratio [HR], 1.134; 95% confidence interval [CI], 1.029-1.25), leukemia (HR, 5.801; 95% CI, 3.24-10.385), lymphoma (HR, 2.584; 95% CI, 1.559-4.283), oral cavity and pharyngeal cancer (HR, 2.113; 95% CI, 1.102-4.052), thyroid cancer (HR, 1.256; 95% CI, 1.05-1.501), and prostate cancer (HR, 1.784; 95% CI, 1.141-2.791). LIMITATIONS: The treatment or severity of diseases in each individual was not examined. CONCLUSIONS: Patients with BD had a higher risk for overall cancer compared with controls without BD. Physicians should carefully monitor patients with BD for the potential development of malignancies.

Early postoperative changes of motor alignment after surgery for intermittent exotropia.

PURPOSE: To evaluate the early postoperative changes of the angle of deviation after surgery for intermittent exotropia. METHODS: We retrospectively reviewed the medical records of 114 patients who had been surgically treated for intermittent exotropia and followed-up on postoperatively for 1 month or more. Patients were observed at postoperative 6 h, 1 day, 1 week, and 1 month. The main outcome measure was the change of the angle of deviation during the early postoperative period (from 6 h to 1 day postoperatively). RESULTS: The mean preoperative angle of exodeviation was 26.3 ± 7.6 PD at distance and 25.4 ± 10.3 PD at near. The angle of deviation was -3.3 (esodeviation) ± 7.0 PD at distance and -0.7 ± 7.1 PD at near at postoperative 6 h, and -3.7 ± 6.9 PD and -0.8 ± 6.8 PD at postoperative 1 day. Neither of these sets represented a significant change from 6 h to 1 day postoperatively (p = 0.300 at distance, p = 0.945 at near). However, in 25 patients (21.9%) the angle of deviation changed 5 PD or more from 6 h to 1 day. Among them, ten showed exodrift and 15 esodrift. At postoperative 1 month, the deviations became significantly more exotropic compared with postoperative 1 day (p < 0.001). CONCLUSIONS: The mean angle of deviation showed no significant change from 6 h to 1 day postoperatively, but 21.9% of patients showed a change of 5 PD or more in this period. These results should be considered in determining the time and the target angle of adjustment in adjustable strabismus surgery for exotropia.

The effects of different hinge positions on posterior tibial slope in medial open-wedge high tibial osteotomy.

PURPOSE: The purpose of this study was to determine the standard hinge position to minimize effects from medial open-wedge high tibial osteotomy (HTO) on the posterior tibial slope. METHODS: Sixteen cadaveric knees underwent medial open-wedge osteotomy using either the standard or the low hinge position. To define the standard hinge position, a line 3 cm inferior to the medial tibial plateau towards the fibular head and located its intersection with a longitudinal line 1 cm medial to the fibular shaft was drawn. Low hinge position was defined as the point 1 cm inferior to the standard position. After tibial osteotomy, computed tomography scans of each knee were taken and three-dimensional models were constructed to characterize hinge position orientation and measure the osteotomy site effects on posterior tibial slope, medial proximal tibial angle, and gap ratio (the ratio of the anterior to posterior gap in the opened wedge). RESULTS: In two low hinge position specimens, the tibial lateral cortex hinge fracture occurred. Osteotomy through the low hinge position resulted in significantly greater posterior tibial slope compared to the standard hinge position (mean ± standard deviation) (11.2 ± 3.0° and 5.6 ± 2.5°, respectively; p < 0.001). Medial proximal tibial angle was also significantly greater for low compared to standard hinge position (95.4 ± 3.5° and 88.0 ± 3.5°, respectively; p < 0.001). Gap ratio was not significantly different between the two groups. CONCLUSION: Hinge position significantly affects the posterior tibial slope and medial proximal tibial angle following medial open-wedge HTO. Accurate hinge position is crucial to prevent complications from changes in posterior tibial slope and medial proximal tibial angle after surgery.

Inflammatory bowel disease is associated with an increased risk of inflammatory skin diseases: A population-based cross-sectional study.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract attributed to aberrant activity of the immune system. Increasing evidence suggests that patients with IBD are at an increased risk of inflammatory skin diseases (ISDs). OBJECTIVE: We sought to clarify the association between IBD and ISDs using a nationwide health claims database maintained in Korea. METHODS: We interrogated Korean health claim database data from 2009 to 2013. We enrolled all patients with IBD, and age- and sex-matched control subjects, and evaluated the risks of ISDs, including psoriasis, rosacea, and atopic dermatitis, and the risks of autoimmune skin diseases, including vitiligo and alopecia areata. We used multivariable logistic regression to this end. RESULTS: ISDs including rosacea, psoriasis, and atopic dermatitis were significantly associated with IBD, whereas the associations between IBD and autoimmune skin diseases including vitiligo and alopecia areata were less marked or nonexistent. Ulcerative colitis and Crohn's disease were both associated with ISDs. LIMITATIONS: We were unable to distinguish phenotypes and severities of skin diseases. CONCLUSION: IBD was significantly associated with ISDs, but less so or not at all with autoimmune skin diseases.

Subsequent vitiligo after hematopoietic stem cell transplantation: A nationwide population-based cohort study from Korea.

BACKGROUND: Subsequent vitiligo after hematopoietic stem cell transplantation (HSCT) has been described sporadically in case series. OBJECTIVE: To investigate the incidence and risk factors of subsequent vitiligo after HSCT. METHODS: A nationwide, population-based cohort study was performed using the Korean National Health Insurance Claims Database from 2009 to 2013. All HSCT recipients who had undergone HSCT between 2010 and 2011 and not treatment for vitiligo in 2009 (to exclude preexisting active vitiligo) were included in the HSCT recipient group, and an age- and sex-matched control group without HSCT was also established. RESULTS: A total of 2747 HSCT recipients and 8241 controls were enrolled. Newly acquired vitiligo occurred in 1.06% of HSCT recipients between 2010 and 2013, and there was a significant increase (OR 3.130, 95% CI 1.859-5.271) in cases of vitiligo in HSCT recipients compared with controls (0.34%). Allogeneic HSCT (OR 5.593, 95% CI 1.628-19.213) and bone marrow-sourced stem cells (as compared with peripheral blood-sourced stem cells; OR 2.492, 95% CI 1.114-5.576) were independently associated with the development of vitiligo after HSCT. LIMITATIONS: Medical record review was not available. CONCLUSION: Vitiligo developed at a significantly increased rate after HSCT compared with controls. Allogeneic HSCT and bone marrow-sourced stem cells were independent risk factors.

Comparison of outcomes of unilateral recession-resection as primary surgery and reoperation for intermittent Exotropia.

BACKGROUND: The aim of this study was to compare the primary surgery and reoperation outcomes of unilateral lateral rectus recession and medial rectus resection (R&R) for intermittent exotropia. METHODS: We retrospectively reviewed the medical records of 80 patients, all of whom had undergone unilateral R&R for intermittent exotropia as a primary surgery or reoperation and been followed-up on postoperatively for 6 months or more. The patients were divided into two groups: unilateral R&R as primary surgery (group A, 44 patients) and unilateral R&R as reoperation (group B, 36 patients). The outcome measures were postoperative angle of deviation, surgical success rate, and mean dose-effect ratio (PD/mm, corrected angle of deviation / sum of amount of recession of lateral rectus and of resection of medial rectus). Surgical success was defined as exo- or esodeviation within 8 PD. RESULTS: The mean postoperative follow-up duration was 49.91 ± 14.83 months in group A and 43.17 ± 26.91 months in group B (p = 0.160). The mean angles of deviation at postoperative 1 day were -5.18 PD (overcorrection) in group A and -5.28 PD in group B (p = 0.932). However, there was a significant difference in the mean angle of deviation between the two groups at each visit from postoperative 3 months to final follow-up (p < 0.05): in short, group A had become more exotropic than group B. And the surgical success rate was higher in group B than in group A at each visit from postoperative 12 months to final follow-up (47.7% in group A and 83.3% in group B at final follow-up) (p < 0.05). The mean dose-effect ratio at 6 months after surgery was 1.89 ± 0.58 PD/mm in group A and 2.26 ± 0.32 PD/mm in group B (p = 0.001). CONCLUSIONS: Unilateral R&R as reoperation presented better results for the surgical treatment of recurrent exotropia, showing a smaller exodrift pattern and higher surgical success rates compared with R&R as a primary surgery. The mean effect per millimeter (the mean dose-effect ratio, PD/mm) of R&R as reoperation was significantly greater than that of R&R as primary surgery at postoperative 6 months. These results could serve as useful guidelines in the planning of surgical correction for primary and recurrent exotropia.

Erratum to: Betulin suppressed interleukin-1b-induced gene expression, secretion and proteolytic activity of matrix metalloproteinase in cultured articular chondrocytes and production of matrix metalloproteinase in the knee joint of rat.

[This corrects the article on p. 19 in vol. 21, PMID: 28066137.].

Betulin suppressed interleukin-1ß-induced gene expression, secretion and proteolytic activity of matrix metalloproteinase in cultured articular chondrocytes and production of matrix metalloproteinase in the knee joint of rat.

We investigated whether betulin affects the gene expression, secretion and proteolytic activity of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as in vivo production of MMP-3 in the rat knee joint to evaluate the potential chondroprotective effect of betulin. Rabbit articular chondrocytes were cultured and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure interleukin-1ß (IL-1ß)-induced gene expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), ADAMTS-5 and type II collagen. Effect of betulin on IL-1ß-induced secretion and proteolytic activity of MMP-3 was investigated using western blot analysis and casein zymography, respectively. Effect of betulin on MMP-3 protein production was also examined in vivo. The results were as follows: (1) betulin inhibited the gene expression of MMP-3, MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5, but increased the gene expression of type II collagen; (2) betulin inhibited the secretion and proteolytic activity of MMP-3; (3) betulin suppressed the production of MMP-3 protein in vivo. These results suggest that betulin can regulate the gene expression, secretion, and proteolytic activity of MMP-3, by directly acting on articular chondrocytes.

Combination treatment of low-fluence Q-switched Nd:YAG laser and oral tranexamic acid for post-inflammatory hyperpigmentation due to allergic contact dermatitis to henna hair dye.

A 64-year-old female presented with facial hyperpigmentation. She had dyed her hair monthly with pure henna powder for the past seven months. After patch tests, the patient was diagnosed as post-inflammatory hyperpigmentastion due to allergic contact dermatitis to pure henna that has rarely been reported. The patient underwent Q-switched Nd:YAG laser treatment and was treated with oral tranexamic acid for 10 weeks. The hyperpigmentation on her forehead demonstrated substantial improvement.

A Novel Anti-Cancer Agent, 1-(3,5-Dimethoxyphenyl)-4-[(6-Fluoro-2-Methoxyquinoxalin-3-yl)Aminocarbonyl] Piperazine (RX-5902), Interferes With ß-Catenin Function Through Y593 Phospho-p68 RNA Helicase.

1-(3,5-Dimethoxyphenyl)-4-[(6-fluoro-2-methoxyquinoxalin-3-yl)aminocarbonyl] piperazine (RX-5902) exhibits strong growth inhibition in various human cancer cell lines with IC50 values ranging between 10 and 20 nM. In this study, we demonstrate that p68 RNA helicase is a cellular target of RX-5902 by the drug affinity responsive target stability (DARTS) method, and confirmed the direct binding of (3) H-labeled RX-5902 to Y593 phospho-p68 RNA helicase. We further demonstrated RX-5902 inhibited the ß-catenin dependent ATPase activity of p68 RNA helicase in an in vitro system. Furthermore, we showed that treatment of cancer cells with RX-5902 resulted in the downregulation of the expression of certain genes, which are known to be regulated by the ß-catenin pathway, such as c-Myc, cyclin D1 and p-c-Jun. Therefore, our study indicates that the inhibition of Y593 phospho-p68 helicase - ß-catenin interaction by direct binding of RX-5902 to Y593 phospho-p68 RNA helicase may contribute to the anti-cancer activity of this compound.