Association Between High Blood Folate Levels and Glaucoma in a Representative Korean Population.

Purpose: This study aimed to investigate the association between folate levels and the prevalence of glaucoma. Methods: This nationwide population-based cross-sectional study included 1790 participants aged ≥40 years. We analyzed data regarding the participants obtained in the 2016-2018 Korean National Health and Nutrition Examination Survey. The diagnosis of glaucoma was defined according to the International Society of Geographical and Epidemiological Ophthalmology criteria. Logistic regression analyses were used to investigate the relationship between blood folate levels and glaucoma. Results: There was a significantly lower prevalence of glaucoma in the highest quartile of blood folate levels than in the lowest quartile, after adjusting for confounding factors such as age, sex, systemic hypertension, diabetes, hypercholesterolemia, and smoking (odds ratio [OR] = 0.470; 95% confidence interval [CI], 0.291-0.759; P for trend = 0.017). There was a significantly lower risk of glaucoma in the highest quartile of blood folate levels than in the lowest quartile among women (OR = 0.188; 95% CI, 0.099-0.357; P for trend <0.001) and younger participants (OR =0.443; 95% CI, 0.229-0.856; P for trend = 0.045). Conclusions: Our findings indicate a strong inverse correlation between blood folate levels and glaucoma.

Association of glaucoma and lifestyle with incident cardiovascular disease: a longitudinal prospective study from UK Biobank.

The shared pathophysiological features of the cerebrovascular disease (CVD) and glaucoma suggest an association between the two diseases. Using the prospective UK Biobank cohort, we examined the associations between glaucoma and incident CVD and assessed the extent to which a healthy lifestyle reduced the CVD risk in subjects with glaucoma, using a scoring system consisting of four factors: current smoking, obesity, regular physical activity, and a healthy diet. During a mean follow-up time of 8.9 years, 22,649 (4.9%) incident CVD cases were documented. Multivariable Cox regression analyses revealed that subjects with glaucoma were significantly more likely to exhibit incident CVD (hazard ratio [HR]:1.19, 95% confidence interval [CI] 1.03-1.37; p = 0.016) than controls. In the further subgroup analyses, glaucoma increased incident CVD risk both in the young (40-55 years) and the old (56-70 years) and in both sexes, with higher risk in the young (HR: 1.33, CI 1.02-1.74) and female subjects (HR: 1.32, CI 1.14-1.52). When we analyze the associations between glaucoma and incident CVD by lifestyle factors, the highest absolute risks were observed in individuals with both glaucoma and an unhealthy lifestyle (HR: 2.66, CI 2.22-3.19). In conclusion, glaucoma was an independent risk factor for incident CVD. A healthy lifestyle was associated with a substantially lower risk for CVD incidence among adults with glaucoma.

Anti-inflammatory effect of glucagon-like Peptide-1 receptor agonist on the neurosensory retina in an acute optic nerve injury rat model.

PURPOSE: To explore the possibility of using glucagon-like peptide-1 receptor agonist (GLP-1RA) as a new treatment for neuroinflammation, by analyzing retinal pathological changes in an optic nerve crush rat model. METHODS: Eight-week-old male Sprague-Dawley rats were divided into lixisenatide (LIX, n = 10), traumatic control (T-CON, n = 10), and normal control (n = 5) groups. The optic nerves of left eyes in the LIX and T-CON groups were crushed in a standardized manner. The LIX group was treated with subcutaneous injections of lixisenatide (200 µg/kg/day) for 5 days. One week after initiating treatment, quantitative polymerase chain reaction, Western blot, and immunohistochemistry analyses were performed on the retinal tissues of each group to identify inflammatory markers. RESULTS: The LIX group showed significantly lower mRNA levels of interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), thioredoxin interacting protein (TXNIP), and glial fibrillary acidic protein (GFAP) than the T-CON group. Also, the LIX group exhibited decreased TXNIP and GFAP expression compared with the T-CON group, and similar expression to the normal control group, according to Western blot analysis. Significantly increased immunohistochemistry staining of Brn3a and decreased TUNEL staining were seen in the LIX group compared with the T-CON group, indicating that lixisenatide contributes to retinal ganglion cell survival in cases of acute optic nerve injury. CONCLUSIONS: Neuroinflammation was significantly reduced in lixisenatide-treated retinas compared with untreated retinas in our acute optic nerve injury rat model. The neuroprotective effect of lixisenatide indicates that it can serve a new treatment option against clinically intractable traumatic optic neuropathy.

Increased Complement-Associated Inflammation in Cytomegalovirus-Positive Hypertensive Anterior Uveitis Patients Based on the Aqueous Humor Proteomics Analysis.

Herpetic anterior uveitis-associated ocular inflammation is commonly manifested with ocular hypertension and glaucoma. Relative to other viruses, cytomegalovirus (CMV) positive hypertensive anterior uveitis is associated with high recurrences of uveitis, as well as with uncontrolled intraocular pressure (IOP) and a subsequent higher requirement for future glaucoma surgery. To gain novel insights into the pathogenesis of ocular hypertension in these patients, we investigated the proteome changes of the aqueous humor (AH) derived from the CMV hypertensive anterior uveitis (CMV-HAU; n = 10) patients and non-glaucoma (cataract; n = 10) patients using liquid chromatography with tandem mass spectrometry. Among a total of 562 proteins identified, fifty and fifteen proteins were significantly elevated and decreased, respectively, in the AH of CMV-HAU patients compared to the control subjects by ≥2 fold. Gene ontology (GO) enrichment and network analyses of elevated proteins revealed that the enrichment of protein was involved in the complement activation, the humoral immune response mediated by the circulating immunoglobulins, proteolysis, and platelet degranulation. In the AH of CMV-HAU, GDF (growth/differentiation factor)-15, the inflammatory marker belonging to the TGF-ß superfamily proteins, was significantly increased, while vasorin, an anti-TGF-ß protein, levels were decreased. The trabecular meshwork cells infected with CMV exhibited a significantly increased expression of inflammatory markers. Collectively, these data indicate increased complement factor associated inflammation and humoral immunity in CMV-HAU associated ocular hypertension.

Role of vasorin, an anti-apoptotic, anti-TGF-ß and hypoxia-induced glycoprotein in the trabecular meshwork cells and glaucoma.

Glaucoma, one of the leading causes of irreversible blindness, is commonly associated with elevated intraocular pressure due to impaired aqueous humour (AH) drainage through the trabecular meshwork. The aetiological mechanisms contributing to impaired AH outflow, however, are poorly understood. Here, we identified the secreted form of vasorin, a transmembrane glycoprotein, as a common constituent of human AH by mass spectrometry and immunoblotting analysis. ELISA assay revealed a significant but marginal decrease in vasorin levels in the AH of primary open-angle glaucoma patients compared to non-glaucoma cataract patients. Human trabecular meshwork (HTM) cells were confirmed to express vasorin, which has been shown to possess anti-apoptotic and anti-TGF-ß activities. Treatment of HTM cells with vasorin induced actin stress fibres and focal adhesions and suppressed TGF-ß2-induced SMAD2/3 activation in HTM cells. Additionally, cobalt chloride-induced hypoxia stimulated a robust elevation in vasorin expression, and vasorin suppressed TNF-α-induced cell death in HTM cells. Taken together, these findings reveal the importance of vasorin in maintenance of cell survival, inhibition of TGF-ß induced biological responses in TM cells, and the decreasing trend in vasorin levels in the AH of glaucoma patients suggests a plausible role for vasorin in the pathobiology of ocular hypertension and glaucoma.

The Enhanced Inhibitory Effect of Estrogen on PD-L1 Expression Following Nrf2 Deficiency in the AOM/DSS Model of Colitis-Associated Cancer.

Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a dual role in carcinogenesis. We previously reported that Nrf2 deficiency enhances the anti-tumorigenic effect of 17ß-estradiol (E2) in an azoxymethane (AOM)/dextran sodium sulfate (DSS) model of colitis-associated cancer (CAC). Herein, we aimed to determine a possible explanation for our recent work and investigated the immune microenvironment represented by programmed death-ligand 1 (PD-L1) expression. One week after the AOM injection, mice were administered with DSS in drinking water for seven days; daily E2 injections were intraperitoneally administered during this period. The mice were sacrificed 16 weeks after AOM injection and analyzed for PD-L1 expression in the distal colon tissues using Western blotting and immunohistochemistry (IHC). Based on Western blotting results, PD-L1 expression was reduced in Nrf2 knockout (KO) female and E2-treated male mice when compared with their wild-type counterparts, following AOM/DSS treatment; this supports the association of PD-L1 expression with tumor progression. Additionally, this finding was in good agreement with the IHC results for PD-L1. Furthermore, we observed that PD-L1 is predominantly expressed in stromal cells rather than on epithelial cells in the colon. Western blotting revealed that PD-L1 expression in the colon positively correlates with expressions of inducible nitric oxide synthase (iNOS) (male, P = 0.002; female, P <0.001) and cyclooxygenase-2 (COX-2) (male, P <0.001; female, P <0.001). Collectively, our findings indicate that estrogen ameliorates the immune microenvironment represented by PD-L1 expression and enhances its effect in the absence of Nrf2.

Long-term prognosis for glaucoma in patients with Posner-Schlossman syndrome.

BACKGROUND: The aim of this study is to investigate the long-term prognosis for glaucoma in patients with Posner-Schlossman syndrome (PSS). METHODS: In this retrospective case series study, a total of 98 patients with PSS from January 2014 to February 2019 were included in this study. Initial presentations and follow-up data were obtained from medical records. Vision-related quality of life (VR-QoL) was assessed using the 25-item National Eye Institute Visual Functioning Questionnaire. RESULTS: Of the 98 patients included in the study, 66 (67%) presented with glaucoma, and among them, 21 (32%) required glaucoma surgery. The mean follow-up time was 50.1 months (range 1-263 months). Iris involvement was noted in 46 (46.9%) eyes; 26 (26.5%) had sectoral iris changes and 20 (20.4%) showed diffuse iris changes. Eyes with iris involvement had a significantly higher number of acute attacks of uveitis than those without (p = 0.010). The 5-year glaucoma surgery-free interval was 77.8% according to Kaplan-Meier analysis. Significant predictors of glaucoma surgery included iris involvement (hazard ratio [HR] = 5.215; confidence interval [CI] = 1.387-19.610), highest number of anti-glaucoma agents (HR = 5.069; CI = 1.848-13.905), baseline average retinal nerve fiber layer thickness (RNFLT) thickness (HR = 0.949; CI = 0.917-0.982), and disease duration (HR = 0.977; CI = 0.957-0.996). Overall complete surgical success and qualified success at 2 years was 35.3% and 75.5%, respectively. Patients with iris involvement, glaucoma surgery, and thinner average RNFLT had significantly poorer VR-QoL (all, p < 0.05). CONCLUSIONS: Patients with PSS and glaucoma required glaucoma surgery in a high rate. Iris involvement increased the probability of surgical treatment and lowered the VR-QoL of PSS patients.

Association Between Chronic Renal Disease and the Risk of Glaucoma Development: A 12-year Nationwide Cohort Study.

Purpose: The purpose of this study was to present the results of our investigation into the risk of glaucoma development in patients with chronic renal disease (CRD). Methods: The present retrospective cohort study used the Korean National Health Insurance Service data, which consisted of 1,025,340 random subjects who were tracked from 2002 to 2013. Newly diagnosed glaucoma and CRD were included on the basis of the Korean Classification of Disease codes. The CRD group consisted of patients who received an initial CRD diagnosis between January 2003 and December 2007 as an index period (n = 3640). The control group (n = 17,971) was selected using 1:5 propensity-score matching using social and demographic factors, along with the year of enrollment. Each group subject was followed until 2013. We used multivariate Cox proportional hazard regression analysis to compare the risk of glaucoma development between the two groups. Results: Glaucoma consecutively developed in 4.3% in the CRD group and 2.8% in the control group (P < 0.0001). CRD increased the risk of glaucoma development (hazard ratio [HR] = 1.63, 95% confidence interval [CI] = 1.34-1.98] after adjusting for age, sex, comorbidities, residence, household income, and the year of enrollment. In multivariate Cox regression analysis, patients with comorbidity of hypertension, diabetes mellitus, or aged ≥ 50 years showed a significantly higher risk of glaucoma development (all P < 0.008). Conclusions: A significant association between CRD and following development of glaucoma was revealed after adjusting the potential confounding factors.

Fasting plasma glucose level and the risk of open angle glaucoma: Nationwide population-based cohort study in Korea.

BACKGROUND: The level of fasting plasma glucose (FPG) is positively associated with intraocular pressure. Diabetes causes early structural changes of retina, especially on ganglion cell layer. In this regard, the FPG level itself may also show an independent association with open angle glaucoma (OAG) development in general population. Herein, we investigate the association of the FPG level with the incidence of OAG. METHODS: Using nationally representative data from the Korean National Health Insurance System, 374,376 subjects ≥40 years of age without OAG who underwent health examinations from 2009 to 2013 were enrolled and followed to the end of 2014. Incident cases of OAG using the International Classification of Diseases 10 codes and medication information were analyzed based on the levels of FPG. RESULTS: Subjects with the highest FPG level (≥160 mg/dL), compared with the lowest level (<80 mg/dL), showed a higher hazard ratio (HR) [2.189; 95% confidence interval (CI): 1.779-2.695; P for trend < 0.001] for OAG after adjustments for age and sex. This result persisted after further adjustments for the presence of type 2 diabetes, current smoking, drinking, and exercise habits, diastolic blood pressure, body mass index (BMI), and total cholesterol level (HR: 1.588; 95% CI: 1.268-1.989; P for trend < 0.001). The positive association between the FPG level and the incidence of OAG was distinct in subjects 40-64 years of age, those with a BMI <25 kg/m2, and those without hypertension (HR 2.022; 95% CI: 1.494-2.736; P for trend <0.001: HR 1.817; 95% CI: 1.372-2.407; P for trend < 0.001: HR 1.706; 95% CI: 1.180-2.467; P for trend <0.001, respectively). CONCLUSIONS: This nationwide population-based cohort study showed that the fasting glucose was associated with an increased risk of OAG. These findings suggest that subjects with high FPG levels require special attention when screening for glaucoma.

The cost-effectiveness of medication, laser trabeculoplasty, and trabeculectomy for treatment of open-angle glaucoma in South Korea.

OBJECTIVES: Open-angle glaucoma (OAG) imposes high disease burden in South Korea. Although various effective interventions are available to manage the progression of OAG, there is limited data on the cost-effectiveness of these treatment strategies in South Korea. METHODS: Using a Markov cohort model, we evaluated the cost-effectiveness of 3 major treatment strategies (medication, laser trabeculoplasty, and trabeculectomy) for South Korean patients with OAG. We projected a 25-year time horizon to study a hypothetical cohort of 10,000 patients of age 40 with mild OAG. The outcome measures were quality-adjusted life-years (QALYs) gained, cost from the societal perspective, and the incremental cost-effectiveness ratio (ICER) of medication, laser trabeculoplasty, and trabeculectomy. Interventions were evaluated at a willingness-to-pay (WTP) threshold of 30,000,000 KRW ($29,152) per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to address the model uncertainty. RESULTS: The mean costs for medication, laser trabeculoplasty, and trabeculectomy were 29,661,740 KRW, 17,34,1342 KRW, and 22,275,438 KRW, respectively. The mean QALYs gained were 15.7, 15.3, and 14.8 for medication, laser trabeculoplasty, and trabeculectomy, respectively. Surgery was strongly dominated because it generated fewer expected QALYs but incurred greater expected cost than laser. The ICER was 30,885,179 KRW per QALY for medication versus laser trabeculoplasty. Laser was cost-effective, however, at a lower WTP threshold of 21,000,000 KRW per QALY gained or below. The results were most sensitive to the progression rates from mild to moderate glaucoma under laser treatment. CONCLUSION: Under the WTP threshold of 30,000,000 KRW per QALY, medication was cost-effective compared with laser trabeculoplasty and trabeculectomy for treating mild OAG in South Korean population. Laser, however, can be a cost-effective alternative in more resource-limited settings.

The cost-effectiveness of systematic screening for age-related macular degeneration in South Korea.

BACKGROUND: Interventions that can facilitate early diagnosis of age-related macular degeneration (AMD) will facilitate early treatment and improve clinical outcomes but there has been concerns about additional medical costs to the health care system. An examination through a retina fundus photography by a non-specialist has been suggested as a potential cost-effective alternative to a direct examination by a specialist, but limited scientific data exists on the cost-effectiveness of screening strategies for AMD. Our objective is to conduct an economic evaluation of various population-wide screening strategies for AMD among the South Korean population. METHODS AND FINDINGS: Using a Markov cohort model, we evaluated the cost-effectiveness of four AMD screening strategies (opportunistic examination, opportunistic treatment, systematic photography, and systematic examination) in comparison with status quo (no screening) for South Korean adults. We projected a life time horizon to study a hypothetical cohort of 100,00 persons of age 40 with and without AMD at baseline. The outcome measures were quality-adjusted life-years (QALYs) gained, cost from the societal perspective, and the incremental cost-effectiveness ratio (ICER) of each strategy. Interventions were evaluated at a willingness-to-pay (WTP) threshold of 30,000,000 KRW ($27,538) per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to address the model uncertainty. Opportunistic examination was strongly dominated because it generated fewer expected QALYs but incurred greater expected cost than the other screening strategies. The mean lifetime expected costs were 289,013 KRW, 363,692 KRW, 9,351,964 KRW, and 12,309,783 KRW, and the mean QALYs gained were 37.73, 37.75, 40.47, 40.68, for no screening, opportunistic treatment, systematic photography, and systematic examination, respectively. The results were most sensitive to the utility weight of mild AMD, the probability of complication from treatment, the cost of being in mild AMD, and the probability of recovery from complication. After eliminating the two weakly dominated strategies, systematic photography was cost-effective at the ICER of 3,310,448 KRW per QALY in comparison to status quo. CONCLUSIONS: Under the WTP threshold of 30,000,000 KRW per QALY, systematic photography is cost-effective for screening AMD in South Korean adults. Systematic examination by ophthalmologists generates more expected QALY and cost compared to systematic photography.

Patterns of care for glaucoma patients in Korea from 2002 to 2013 using the national health insurance service claims data.

Due to the rapidly increasing life-expectancy, the prevalence of glaucoma has increased steadily in recent years. We aimed to evaluate the patterns of care and primary treatment strategy patterns in Korea according to glaucoma subtypes to assess the quality of care for glaucoma patients.In this serial cross-sectional survey, the claims data from the Korean National Health Insurance Service was used to identify and group glaucoma patients into primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACG), other types of glaucoma, and ocular hypertension from 2002 to 2013. Records for outpatient visits, hospitalizations, drug prescriptions, admissions, and surgical interventions were used to determine the patterns of care and identify primary treatment strategies.Both the prevalence (0.11% in 2002 to 0.43% in 2013) and incidence rates (0.06% in 2003 to 0.11% in 2013) for glaucoma increased over time. The mean number of outpatient visits increased (4.9-6.0 visits per year), while the proportion of hospitalized patients (2.3-1.0% of patients) and duration of hospital stay (4.5-3.4 days among hospitalized patients) decreased between 2002 and 2013 for patients with POAG. The proportion of patients not being managed by medication or surgery decreased, with POAG and PACG patients receiving medications increasing from 70.9% and 59.2% in 2002 to 88.4% and 63.3% in 2013, respectively. Finally, while the proportion of trabeculectomy decreased (22.2% to 10.0% of surgical procedures in 2002 and 2013, respectively), more patients with PACG have received iridectomy (59.3% to 86.0% of surgical procedures in 2002 and 2013, respectively).Between 2002 and 2013, the pattern of care for both patients with POAG and PACG has shifted toward management by outpatient visits and intervention with anti-glaucoma medications in Korea.

Primary Imaging Test and Appropriate Biopsy Methods for Thyroid Nodules: Guidelines by Korean Society of Radiology and National Evidence-Based Healthcare Collaborating Agency.

The Korean Society of Radiology and the National Evidence-based Healthcare Collaborating Agency developed guidelines for primary imaging tests and appropriate biopsy methods for thyroid nodules. These guidelines were developed using an adaptation process by collaboration between the development committee and the working group. The development committee, composed of research methodology experts, established the overall plan and provided support about methodological strategies. The working group, composed of radiologist experts in thyroid imaging, wrote the proposals. The guidelines recommend neck ultrasound (US) as a first-line imaging modality for the diagnosis of thyroid nodules in patients with suspected nodules, and US-guided fine-needle aspiration as a primary method for histologic examination of thyroid nodules.

Factors affecting the clinical relevance of Corynebacterium striatum isolated from blood cultures.

This study aimed to identify clinical or microbiological factors affecting the clinical relevance of Corynebacterium striatum isolated from blood cultures. A total of 64 isolates from 51 patients identified as C. striatum by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing were assessed. More than two blood cultures were positive in 25 (48.1%) patients. Diabetes, solid tumor, and a history of previous exposure to antibiotics were more common in patients with multiple positive blood cultures. Charlson comorbidity scores were also higher, and more isolates were recovered after 48 hours of hospital stay in patients with multiple positive blood cultures. Strains recovered from patients with multiple positive blood cultures produced significantly more biofilm. Based on multilocus sequence typing (MLST), sequence type (ST) 20 (31.3%) was the most dominant, followed by ST2 (20.3%) and ST23 (10.9%). There was no relationship between the number of positive blood culture sets and sequence typing. In multivariate analyses, Carlson comorbidity score (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.09-3.36; P = 0.03) and biofilm formation were associated with multiple positive blood cultures (OR, 17.43; 95% CI, 3.71-81.91; P = 0.03). This study provides evidence that the biofilm phenotype could contribute to determining the clinical significance of C. striatum in patients with severe underlying conditions. The predominance of certain STs suggests the relatedness of C. striatum infection and the nosocomial environment.

Identification of a Novel GLA Mutation (L206 P) in a Patient with Fabry Disease.

We report a new α-Galactosidase A (αGal-A) mutation in a 39-year-old Korean born, male Fabry disease patient. Fabry disease is a devastating, progressive inborn error of metabolism caused by X-linked genetic mutations. In this case, the first clinical symptom to occur was in childhood consisting of a burning pain originating in the extremities then radiating inwards to the limbs. This patient also stated to have ringing in his ears, angiokeratomas on his trunk, and cornea verticillata. He visited an outpatient cardiologist due to intermittent and atypical chest discomfort at the age of 39. Electrocardiographic and echocardiographic examination showed left ventricular hypertrophy. A physical examination revealed proteinuria without hematuria. The patient's plasma αGal-A activity was markedly lower than the mean value of the controls. After genetic counseling and obtaining written informed consent, we identified one hemizygous mutation in exon 4 of galactosidase alpha, c.617T>C (p.Leu206 Pro). He was eventually diagnosed as having Fabry disease.

Association between metformin use and mortality in patients with type 2 diabetes mellitus and localized resectable pancreatic cancer: a nationwide population-based study in korea.

BACKGROUND: Preclinical studies support an antitumor effect of metformin. However, clinical studies have conflicting results and metformin's effect remains controversial. The aim of this study was to evaluate metformin's effect on clinical outcomes in diabetic patients with pancreatic cancer treated with curative resection. RESULTS: A total of 764 patients underwent curative resection, met none of the exclusion criteria, and were prescribed oral hypoglycemic agents. The cancer-specific survival (5-year, 31.9% vs. 22.2%, p < 0.001) was significantly higher in the 530 metformin users than in the 234 diabetic metformin non-users. After multivariable adjustments, metformin users had significantly lower cancer-specific mortality as compared with metformin non-users (hazard ratio, 0.727; 95% confidence interval, 0.611-0.868). Cubic spline regression analysis demonstrated significantly decreased cancer-specific mortality with increasing dose of metformin (p = 0.0047). MATERIALS AND METHODS: Data were provided from the Korea Central Cancer Registry and the National Health Insurance Service in the Republic of Korea. The study cohort consisted of 28,862 patients newly diagnosed with pancreatic cancer between 2005 and 2011. Metformin exposure was determined from prescription information from 6 months before the first diagnosis of pancreatic cancer to last follow-up. The main outcome was cancer-specific survival. CONCLUSIONS: This large study indicates that metformin might decrease cancer-specific mortality rates in localized resectable pancreatic cancer patients with pre-existing diabetes, independently of other factors, with a dose-response relationship.

Association between Metformin Use and Survival in Nonmetastatic Rectal Cancer Treated with a Curative Resection: A Nationwide Population Study.

PURPOSE: Metformin is associated with an anticancer effect. However, the effects of metformin in rectal cancer are controversial. This study investigated the impact of metformin on the survival of patients with diabetes mellitus and nonmetastatic rectal cancer who underwent curative surgery. MATERIALS AND METHODS: The database was provided by the Korea Center Cancer Registry and National Health Insurance Service of the Republic of Korea. A cohort of patients with newly diagnosed rectal cancer between 2005 and 2011 was identified. Drug exposure was defined as receiving the oral hypoglycemic agent for at least 90 days over the period from 6 months before the initial diagnosis of rectal cancer to the last follow-up. RESULTS: A total of 4,503 patients were prescribed oral hypoglycemic agents and classified as the diabetic group, of which 3,694 patients received metformin for at least 90 days. Unadjusted analyses showed a significantly higher overall survival (hazard ratio, 0.596; 95% confidence interval, 0.506 to 0.702) and rectal cancer-specific survival (hazard ratio, 0.621; 95% confidence interval, 0.507 to 0.760) in the metformin group than in the nonmetformin group. The adjusted overall survival (hazard ratio, 0.631; 95% confidence interval, 0.527 to 0.755) and cancer-specific survival (hazard ratio, 0.598; 95% confidence interval, 0.479 to 0.746) in the group with a medication possession ratio of 80% or greater was significantly higher than in the group with a medication possession ratio of less than 80%. CONCLUSION: Metformin use is associated with overall and cancer-specific survival in diabetic patients with a nonmetastatic rectal cancer treated with a curative resection.

Associations of sleep duration with open angle glaucoma in the Korea national health and nutrition examination survey.

The aim of this study is to investigate the relationship between sleep duration and glaucoma, stratified by obesity status.This study was conducted using data from the Korean National Health and Nutrition Examination Survey V 2010 to 2012. Open-angle glaucoma was diagnosed according to the International Society of Geographical and Epidemiological Ophthalmology criteria. Subjects were divided into subgroups based on those who were overweight (body mass index ≥25 kg/m or <25 kg/m) or with abdominal obesity (based on waist circumference). Multiple logistic regression analysis was done to estimate the magnitude of the association between sleep duration (<7 h, 7-<9, or ≥9 hours) and prevalence of glaucoma in the total population and in the subgroups.Individuals who slept <5 hours per night had the highest prevalence of glaucoma (5.55 ±â€Š1.09%), followed by those who slept ≥9 hours per night (4.56 ±â€Š0.10%), and then by those who slept 5 to <6 hours per night (4.15 ±â€Š0.68%), which revealed a U-shaped pattern (P for trend = 0.072). Among overweight individuals, subjects who slept <7 hours and those who slept ≥9 hours were significantly more likely to have glaucoma compared with subjects who slept 7 to <9 hours after adjusting for survey year, age, sex, smoking, drinking, exercise, education level, household income, hypertension, intraocular pressure, stress, and depression (odds ratio, 2.41; 95% confidence interval, 1.14-5.03). Unlike for overweight individuals, sleep duration in nonoverweight individuals was not statistically significantly associated with glaucoma.Our results reveal a U-shaped association between sleep duration and the prevalence of glaucoma. An effect of sleep duration on glaucoma was present in the subgroup of overweight patients.

Effect of trapping vascular endothelial growth factor-A in a murine model of dry eye with inflammatory neovascularization.

AIM: To evaluate whether trapping vascular endothelial growth factor A (VEGF-A) would suppress angiogenesis and inflammation in dry eye corneas in a murine corneal suture model. METHODS: We established two groups of animals, one with non-dry eyes and the other with induced dry eyes. In both groups, a corneal suture model was used to induce inflammation and neovascularization. Each of two groups was again divided into three subgroups according to the treatment; subgroup I (aflibercept), subgroup II (dexamethasone) and subgroup III (phosphate buffered saline, PBS). Corneas were harvested and immunohistochemical staining was performed to compare the extents of neovascularization and CD11b+ cell infiltration. Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and VEGF-A in the corneas. RESULTS: Trapping VEGF-A with aflibercept resulted in significantly decreased angiogenesis and inflammation compared with the dexamethasone and PBS treatments in the dry eye corneas (all P<0.05), but with no such effects in non-dry eyes. The anti-inflammatory and anti-angiogenic effects of VEGF-A trapping were stronger than those of dexamethasone in both dry eye and non-dry eye corneas (all P<0.05). The levels of RNA expression of VEGF-A, TNF-alpha, and IL-6 in the aflibercept subgroup were significantly decreased compared with those in the PBS subgroup in the dry eye group. CONCLUSION: Compared with non-dry eye corneas, dry eye corneas have greater amounts of inflammation and neovascularization and also have a more robust response to anti-inflammatory and anti-angiogenic agents after ocular surface surgery. Trapping VEGF-A is effective in decreasing both angiogenesis and inflammation in dry eye corneas after ocular surface surgery.

Cytomegalovirus as a cause of hypertensive anterior uveitis in immunocompetent patients.

BACKGROUND: The aims of this study are to investigate the clinical characteristics of patients with anterior hypertensive uveitis and to compare the characteristics between patients in cytomegalovirus (CMV)-positive and CMV-negative groups in their aqueous humor samples. Immunocompetent patients (n = 42) with a history of chronic and/or recurrent hypertensive anterior uveitis underwent ophthalmic examination and serological tests. Among the 42 patients with hypertensive anterior uveitis, aqueous humor sampling was performed in 21, and they were analyzed for viral deoxyribonucleic acids using the polymerase chain reaction (PCR). RESULTS: The average age of the 42 patients with hypertensive anterior uveitis was 57.6 years, and 29 (69.0 %) of the subjects were males. Of the patients, 22 (52.4 %) underwent glaucoma surgery, and the average corneal endothelial cell counts were 1908 cells/mm(2). Among the 21 patients who underwent an aqueous sampling, 6 were positive for CMV-DNA, while 15 were negative. The frequency of glaucoma surgery was similar between groups (CMV positive vs. CMV negative, 66.0 vs. 66.0 %, P = 0.701). However, 66.7 % of the CMV-positive group underwent glaucoma tube shunt surgery, whereas 80 % of the CMV-negative group underwent trabeculectomy or received an ExPRESS glaucoma filtration device (Alcon, Fort Worth, TX) for glaucoma surgery (P = 0.095). The corneal endothelial cell counts were significantly lower in the CMV-positive group (CMV positive vs. CMV negative, 1245 ± 560 vs. 1981 ± 387 cells/mm(2); P = 0.009). CONCLUSIONS: CMV was found to be an etiological factor in patients with hypertensive anterior uveitis in Korea. Special caution is needed for patients with CMV-induced hypertensive anterior uveitis, considering its adverse effect on the corneal endothelium.