Effect of a Pericardium Graft Inserted Adjacent to the Endplate in the Ahmed Glaucoma Valve Implantation.

The surface area of encapsulation around the Ahmed glaucoma valve (AGV) endplate is a critical factor in the surgical outcome as it is associated with the degree of IOP reduction. We investigated the surgical outcome of AGV implantation with an additional pericardium graft inserted adjacent to the endplate, with the intent of expanding the surface area of encapsulation. We enrolled 92 patients (92 eyes) who underwent AGV implantation. Of them, 50 patients underwent conventional surgery (termed the without-expansion group), and 42 received an additional an 8 × 6 mm pericardium graft inserted adjacent to the AGV endplate at the sub-Tenon's space (with-expansion). The hypertensive phase was classified as mild (>21 mmHg), moderate (>25 mmHg), and severe (>30 mmHg). Six months post-surgery, the with-expansion group exhibited a lower IOP (14.90 ± 4.27 mmHg) and lower peak IOP (22.29 ± 4.95 mmHg) than the without-expansion group (17.56 ± 4.88 mmHg and 25.06 ± 6.18 mmHg, p = 0.008 and p = 0.021, respectively). The with-expansion group exhibited a relatively low rate of moderate (16.7%) and severe (4.8%) hypertensive phases compared to the without-expansion group (40.0% and 20.0%, with p = 0.014 and p = 0.031, respectively). The additional pericardium graft was associated with a reduced occurrence of moderate hypertensive phase in both univariate and multivariate analysis logistic regression analyses (p = 0.017 and p = 0.038, respectively). Endplate surface area expansion using an additional pericardium graft reduced the occurrence of moderate and severe hypertensive phases, and lower postoperative 6-month IOP could be achieved.

Harnessing dendritic cell diversity in cancer immunotherapy.

Dendritic cells (DCs) are ubiquitous immune cells endowed with a unique capacity to initiate antigen-specific immunity and tolerance. Owing to their unique functional attributes, DCs have long been considered ideal candidates for the induction of effective antitumour responses. At the forefront of the cancer-immunity cycle, attempts to harness DC natural adjuvant properties in the clinic have resulted so far in suboptimal antitumour responses. A better understanding of the heterogeneity of the DC network and its dynamics within the tumour microenvironment will provide a blueprint to fully capitalise on their functional properties to achieve more effective antitumour responses. In this review, we will briefly summarise the origin and heterogeneity of the DC network, their roles in shaping antitumour immunity and in modulating the response to immune checkpoint blockade therapies.

Incidence and risk factors of tuberculosis in patients following gastrectomy or endoscopic submucosal dissection: a cohort analysis of country-level data.

BACKGROUND: Gastric cancer adversely affects nutrition and immunity, while increasing the risk of tuberculosis (TB). This study investigated the incidence and risk factors for TB in gastric cancer patients who had undergone gastrectomy or endoscopic submucosal dissection (ESD). METHODS: This retrospective cohort study was conducted using Korean national insurance claims data. We defined three study groups (total gastrectomy, subtotal gastrectomy, and ESD) of patients diagnosed with gastric cancer plus a cancer-free control group. The latent TB infection (LTBI) screening status, TB incidence, and potential confounders in each cohort were analyzed, and the risk of TB was analyzed using a Cox proportional hazard model. RESULTS: LTBI tests were performed in less than 1% of all patients, and the TB incidence rates were 473.8, 287.4, 199.4, 111.1 events/100,000 person-years in the total gastrectomy, subtotal gastrectomy, ESD, and control cohorts, respectively. Compared to the control cohort, the total gastrectomy cohort showed the highest hazard ratio (HR) for TB incidence (HR: 2.896, 95% CI: 2.559-2.337), while the ESD cohort showed a significantly increased risk (HR: 1.578, 95% CI: 1.957-1.980). Age, body mass index, and lack of exercise were risk factors in all cohorts. Comorbidities were also considered risk factors, depending on the cohort type. CONCLUSIONS: Patients who underwent gastrectomy or ESD had an increased risk of TB, and this risk was correlated with the scope of gastrectomy. Considering the low rate of LTBI diagnostic tests and increased risk of TB in the study cohorts, more specific and practical guidelines for TB management are required for gastric cancer patients.

Factors Associated with Elevated Tumor Necrosis Factor-α in Aqueous Humor of Patients with Open-Angle Glaucoma.

Tumor necrosis factor-alpha (TNF-α) is an important modulator of neuroinflammation, secreted from activated glial cells in response to intraocular stress. The purpose of this study was to investigate the clinical factors associated with elevated TNF-α and its level in aqueous humor of patients with open-angle glaucoma (OAG). Aqueous humor was collected from 73 OAG eyes, and TNF-α level was analyzed using the singleplex bead immunoassay method. Patients were divided into TNF-α-positive and TNF-α-negative groups according to the TNF-α level of 10 pg/mL, and baseline clinical characteristics were compared. The TNF-α-positive group showed higher baseline IOP, greater IOP fluctuation, and higher systolic blood pressure than the TNF-α-negative group (p = 0.007, p < 0.001, and p = 0.009, respectively). In the multivariate logistic regression analysis, IOP fluctuation (p = 0.037) and systolic blood pressure (p = 0.016) were all independently associated with positive TNF-α level. In normal-tension glaucoma (NTG) patients, presence of central scotoma (p = 0.029) was significantly associated with positive TNF-α level. In conclusion, positive TNF-α level in OAG patients was associated with greater IOP fluctuation and higher systolic blood pressure. In NTG patients, positive TNF-α level was associated with the presence of central scotoma. IOP factors and vascular factors, including blood pressure and presence of central scotoma, may indicate glaucoma pathogenesis related to TNF-α elevation in OAG patients.

TGFß and CIS Inhibition Overcomes NK-cell Suppression to Restore Antitumor Immunity.

Antibodies targeting "immune checkpoints" have revolutionized cancer therapy by reactivating tumor-resident cytotoxic lymphocytes, primarily CD8+ T cells. Interest in targeting analogous pathways in other cytotoxic lymphocytes is growing. Natural killer (NK) cells are key to cancer immunosurveillance by eradicating metastases and driving solid tumor inflammation. NK-cell antitumor function is dependent on the cytokine IL15. Ablation of the IL15 signaling inhibitor CIS (Cish) enhances NK-cell antitumor immunity by increasing NK-cell metabolism and persistence within the tumor microenvironment (TME). The TME has also been shown to impair NK-cell fitness via the production of immunosuppressive transforming growth factor ß (TGFß), a suppression which occurs even in the presence of high IL15 signaling. Here, we identified an unexpected interaction between CIS and the TGFß signaling pathway in NK cells. Independently, Cish- and Tgfbr2-deficient NK cells are both hyperresponsive to IL15 and hyporesponsive to TGFß, with dramatically enhanced antitumor immunity. Remarkably, when both these immunosuppressive genes are simultaneously deleted in NK cells, mice are largely resistant to tumor development, suggesting that combining suppression of these two pathways might represent a novel therapeutic strategy to enhance innate anticancer immunity.

Angiotensin II related glial cell activation and necroptosis of retinal ganglion cells after systemic hypotension in glaucoma.

The purpose of this study was to design an animal model mimicking glaucoma with hemodynamic instability and to identify involvement of angiotensin II (AngII) and associated changes of the retina. Systemic hypotension was induced in Sprague-Dawley rats by oral hydrochlorothiazide administration. Rats were sacrificed at 4, 8, and 12-week time points. AngII and receptor levels were examined in the serum and retina. To examine the relationship between glia activation and associated RGC death, biochemical analysis of GFAP, Iba-1, and necroptosis associated factors such as TNFα, receptor-interacting protein (RIP) 1, 3, and inactive caspase 8 were explored. To investigate the difference in RGC death mechanism, JNK inhibitor or RIP3 inhibitor were given intraperitoneally to rats with ocular hypertension and systemic hypotension both to identify the pathway mainly involved. AngII and receptors were increased in the serum and retina of systemic hypotensive rat. At 4, 8, and 12 weeks after hypotension induction, glial activation was increased as indicated by GFAP and Iba-1 staining. TNFα, RIP3 were elevated. and downregulation of inactive caspase 8 was apparent in the retina of hypotensive rat. Electron microscopy revealed that necroptosis of RGC was gradually increased after systemic hypotension. Following intraperitoneal JNK inhibitor or RIP3 inhibitor administration, RGC loss was attenuated in systemic hypotensive rats but not in ocular hypertensive rats. In conclusion, AngII is involved in glial activation and associated RGC necroptosis following systemic hypotension. This pathway represents a novel and distinct cell death mechanism when compared to that involved in elevated intraocular pressure.

Survival and medical costs of melanoma patients with subsequent cancer diagnoses: A South Korean population-based retrospective cohort study.

AIM: Subsequent cancers (SCs) after melanoma diagnosis further increases the risks of mortality and medical costs. This population-based analysis aimed to evaluate risk factors for SC, mortality, and medical costs of melanoma patients with SC. METHODS: A retrospective cohort analysis was conducted using a nationwide claims database during 2002-2017 in South Korea. SC was defined as having other types of cancer diagnoses other than subsequent melanoma during-up to 5 years after melanoma diagnosis. Melanoma patients were divided into patients with and without SC, and the overall and subgroup survival rates, the risk of developing SC, and the total medical costs were analyzed using a Kaplan-Meier method and regressions. RESULTS: A total of 3740 melanoma patients were included in the analysis (mean age, 62.3 ± 15.4 y; 47.2% men), and 2273 patients (1157 within 2 months, 756 after 2 months of melanoma diagnosis) had SC. Higher Charlson comorbidity index score and male sex significantly increased the risk of developing SC. Five-year survival rate and cumulative medical costs were 62.3% (95% confidence interval [CI], 60.8-63.9) and $21,413, respectively, in all patients. Patients with SC diagnosed after 2 months showed the lowest survival rate of 47.8% (95% CI, 44.3-51.4) and the highest costs of $27,081, showing a mortality hazard ratio of 1.65 (range, 1.46-1.86) and a cost ratio of 1.189 (range, 1.112-1.271) compared with those without SC. CONCLUSION: This study presented survival outcomes and medical costs in melanoma patients and confirmed that SC after the first diagnosis of melanoma significantly increased disease burden in terms of mortality and medical costs.

Microvasculature Recovery Detected Using Optical Coherence Tomography Angiography and the Rate of Visual Field Progression After Glaucoma Surgery.

Purpose: We evaluated microvascular changes using optical coherence tomography angiography (OCT-A) in glaucoma patients who underwent glaucoma surgery. Methods: The macula and optic nerve head were imaged using an OCT-A device at one day before surgery and at one week, one month, three months, and six months after surgery. Measurements of vessel density (VD) were made in the intradisc region and macula, and the area of the foveal avascular zone (FAZ) was measured in both superficial and deep vascular layers. A mean deviation (MD) slope value of < -1.0 decibel/y was considered to be indicative of VF progression. Results: A significant increase in VD was observed postoperatively in the deep vascular layer of the intradisc area (P < 0.001), and a significant decrease in the FAZ area was evident in the deep vascular layer (P = 0.018). An increase in the intradisc deep VD (17.48% ± 5.63%) was statistically significant in glaucoma eyes without progression, compared with those with progression (-1.27% ± 2.19%). Worse preoperative MD of the VF (P = 0.006), lower preoperative intradisc VD (P < 0.001), and fewer changes in the intradisc deep VD after surgery (P < 0.001) were significantly associated with MD slope. Conclusions: We found deep VD changes in the laminar region of the optic nerve head and the macular area at up to postoperative one month after glaucoma surgery. An increase in the deep VD in the laminar region was beneficial to VF progression in glaucoma patients after surgery.

Lifetime survival and medical costs of lung cancer: a semi-parametric estimation from South Korea.

BACKGROUND: It is essential to have information on the disease burden of lung cancer at an individual level throughout the life; however, few such results have been reported. Thus, this study aimed to assess the lifetime disease burden in patients with lung cancer by assessing various factors, such as survival, years of life lost (YLL) and medical expenditure in South Korea based on real-world data and extrapolation. METHODS: Newly diagnosed lung cancer patients (n = 2919) in 2004-2010 were selected and observed until the end of 2015 using nationwide reimbursement claim database. The patients were categorised into the Surgery group, Chemo and/or Radiotherapy group (CTx/RTx), and Surgery+CTx/RTx according to their treatment modality. Age- and sex-matched control subjects were selected from among general population using the life table. The survival and cost data after diagnosis were analysed by a semi-parametric method, the Kaplan-Meier analysis for the first 100 months and rolling extrapolation algorithm for 101-300 months. YLL were derived from the difference in survival between patients and controls. RESULTS: Lifetime estimates (standard error) were 4.5 (0.2) years for patients and 14.5 (0.1) years for controls and the derived YLL duration was 10.0 (0.2) years. Lifetime survival years showed the following trend: Surgery (14.2 years) > Surgery+CTx/RTx (8.5 years) > CTx/RTx group (3.0 years), and YLL were increased as lifetime survival years decreased (2.3, 8.7, 12.2 years, respectively). The mean lifetime medical cost was estimated at 30,857 USD/patient. Patients in the Surgery group paid higher treatment cost in first year after diagnosis, but the overall mean cost per year was lower at 4359 USD compared with 7075USD of Surgery+CTx/RTx or 7626USD of CTx/RTx group. CONCLUSIONS: Lung cancer has resulted in about 10 years of life lost in overall patients. The losses were associated with treatment modality, and the results indicated that diagnosing lung cancer in patients with low stage disease eligible for surgery is beneficial for reducing disease burden in terms of survival and treatment cost per year throughout the life.

Risk Factors for Choroidal Detachment After Ahmed Valve Implantation in Glaucoma Patients.

PURPOSE: To assess the incidence and risk factors related to choroidal detachment after glaucoma drainage device (Ahmed valve) implantation. DESIGN: Retrospective case-control study. METHODS: A total of 188 eyes of 188 glaucoma patients were enrolled who underwent Ahmed valve implantation surgery. Patients were divided into 2 groups according to the presence or absence of choroidal detachment. The data were analyzed for factors associated with choroidal detachment. Separately, we divided eyes with choroidal detachment into 2 subgroups according to severity and conducted a subanalysis. In addition, we also analyzed the factors associated with chamber collapse. RESULTS: The incidence of choroidal detachment was 35.1% according to wide-field fundus photography and 16.9% according to 45-degree fundus photography. The current study showed that age, central corneal thickness, axial length, etiology of glaucoma, history of cataract or glaucoma, hypertension, diabetes, and severity of the visual field (MD) were different between the choroidal detachment and nonchoroidal detachment groups. A multivariate analysis showed significant differences in age (P = .035), etiology of glaucoma (pseudoexfoliation; PEX) (P = .028), lens status (pseudophakia) (P = .011), and hypertension (P = .011). The greater the intraocular pressure difference before and after surgery, the greater the size of the choroidal detachment. Chamber collapse risk was associated with only short axial length. CONCLUSION: The detection of choroidal detachment after Ahmed valve implantation can be increased according to the introduction of wide fundus photography. The risk of choroidal detachment is associated with the etiology of glaucoma (PEX), older age, pseudophakia (lens status), and hypertension.

Cost-effectiveness of Bariatric Surgery for People with Morbid Obesity in South Korea.

OBJECTIVE: This study aimed to evaluate the cost-effectiveness of bariatric surgery (BS) compared to non-surgical treatment (NST) in Korean people with morbid obesity according to comorbidities and body mass index (BMI) severity. METHODS: The target cohort was people with morbid obesity, defined as BMI of ≥ 35 kg/m2, or obese people with BMI of 30-34.9 kg/m2 having obesity-related comorbidities. A decision-tree model for 1-year obesity treatment and Markov model for the rest of life were used. In the decision-tree model, the comorbidity remission rate and BMI change after 1-year treatment were decided based on a prospective clinical trial. In the Markov model, the transition probabilities were calculated considering the BMI level and age. The starting age of 20 years, a cycle length of 1 year, a time horizon of 80 years, and a 5% discount rate were applied for the base case from the healthcare system perspective. RESULTS: In the base case, BS improved quality-adjusted life years (QALYs) and was the cost-effective option in total cohort (incremental cost-effectiveness ratio of BS vs. NST was 674 USD/QALY). It was shown to be cost-effective in all subgroup analyses based on BMI level. In particular, BS was a dominant alternative for the subgroup with basal BMI of 35.0-37.4 kg/m2. Various sensitivity analyses showed the robustness of results indicating the cost-effectiveness of BS. CONCLUSION: BS at BMI of > 30 kg/m2 was more effective than NST for a reduction in BMI and remission of obesity-related comorbidities and was cost-effective in Korea.

Increased levels of synaptic proteins involved in synaptic plasticity after chronic intraocular pressure elevation and modulation by brain-derived neurotrophic factor in a glaucoma animal model.

The dendrites of retinal ganglion cells (RGCs) synapse with the axon terminals of bipolar cells in the inner plexiform layer (IPL). Changes in the RGC dendrites and synapses between the bipolar cells in the inner retinal layer may critically alter the function of RGCs in glaucoma. The present study attempted to discover changes in the synapse using brain-derived neurotrophic factor (BDNF) after glaucoma induction by chronic intraocular pressure elevation in a rat model. Immunohistochemical staining revealed that the BDNF-injected group had a significant increase in the level of synaptophysin, which is a presynaptic vesicle protein, in the innermost IPL compared with the phosphate-buffered saline (PBS)-injected group. SMI-32, which is a marker of RGCs, was colocalized with synaptophysin in RGC dendrites, and this colocalization significantly increased in the BDNF-injected group. After the induction of glaucoma, the BDNF-injected group exhibited increases in the total number of ribbon synapses, as seen using electron microscopy. Expression of calcium/calmodulin-dependent protein kinase II (CaMKII), cAMP-response element binding protein (CREB) and F-actin, which are key molecules involved in synaptic changes were upregulated after BDNF injection. These initial findings show the capability of BDNF to induce beneficial synaptic changes in glaucoma.

Economic burden of lung cancer: A retrospective cohort study in South Korea, 2002-2015.

We evaluated the survival rates and medical expenditure in patients with lung cancer using a nationwide claims database in South Korea. A retrospective observational cohort study design was used, and 2,919 lung cancer patients and their matched controls were included. Medical expenditures were analyzed with the Kaplan-Meier sample average method, and patients were categorized into 4 groups by operation and primary treatment method (i.e. Patients with operation: OP = surgery, OP+CTx/RTx = surgery with anti-cancer drugs or radiotherapy; Patients without operation: CTx/RTx = anti-cancer drugs or radiotherapy, Supportive treatment). The 5-year medical expenditure per case was highest in the OP+CTx/RTx group ($36,013), followed by the CTx/RTx ($23,134), OP ($22,686), and supportive treatment group ($3,700). Lung cancer-related anti-cancer drug therapy was the major cost driver, with an average 53% share across all patients. Generalized linear regression revealed that monthly medical expenditure in lung cancer patients, after adjustment for follow-up month, was approximately 3.1-4.3 times higher than that in the control group (cost ratio for OP = 3.116, OP+CTx/RTx = 3.566, CTx/RTx = 4.340, supportive treatment = 4.157). The monthly medical expenditure at end of life was estimated at $2,139 for all decedents, and approximately a quarter of patients had received chemotherapy in the last 3 months. In conclusion, this study presented the quantified treatment costs of lung cancer on various aspects compared with matched controls according to the treatment of choice. In this study, patients with operation incurred lower lifetime treatment costs than patients with CTx/RTx or supportive treatment, indicating that the economic burden of lung cancer was affected by treatment method. Further studies including both cancer stage and treatment modality are needed to confirm these results and to provide more information on the economic burden according to disease severity.

The Association between Polypharmacy and Hip Fracture in Osteoporotic Women: A Nested Case-Control Study in South Korea.

BACKGROUND AND OBJECTIVE: Polypharmacy, regarded as an indicator of potentially inappropriate medications (PIMs), may lead to a higher risk of serious health consequences in elderly patients with osteoporosis. Thus, this study aimed to analyze the association between polypharmacy and hip fracture in patients with osteoporosis because only a limited number of studies have reported on this association, with inconsistent results to date. METHODS: In this nested case-control study using a population-based sample cohort, the target cases were female patients with hip fracture diagnosed with osteoporosis and aged ≥ 50 years. Polypharmacy (prescription of an average of five or more daily drugs), PIMs for hip fracture (such as benzodiazepines and glucocorticoids), Charlson Comorbidity Index (CCI) score, and other comorbidities were analyzed during the year preceding the diagnosis of hip fracture. Adjusted odds ratios (ORs) for hip fracture for the variables were also analyzed. RESULTS: The cases (n = 1003) showed higher exposure rates to polypharmacy, glucocorticoids, and benzodiazepines, and had more severe comorbidity statuses compared with the controls. The ORs for hip fracture adjusted for confounders increased with polypharmacy level, with persistent statistical significance in most analyses. The ORs (95% confidence intervals), with reference to the 0 to < 1 drug group, were 1.65 (1.31-2.08) and 2.11 (1.12-3.96) for the 5 to < 10 and 10 + drug groups, respectively, with adjustment for PIMs, and 1.34 (1.04-1.72) and 1.45 (0.76-2.80) for the 5 to < 10 and 10 + drug groups, respectively, with adjustment for PIMs and CCI score. CONCLUSIONS: The results suggest that polypharmacy is associated with an increased risk of hip fracture after adjustment for confounders in patients with osteoporosis. These results highlight the importance of polypharmacy management in preventing hip fractures in patients with osteoporosis.

Effects of Early Postoperative Intraocular Pressure after Ahmed Glaucoma Valve Implantation on Long-term Surgical Outcomes.

PURPOSE: To evaluate the long-term effects of early postoperative intraocular pressure (IOP) after Ahmed glaucoma valve (AGV) implantation on long-term surgical outcomes. METHODS: This retrospective, non-randomized study included 100 eyes of 100 patients who underwent AGV surgery. We divided the enrolled patients into four groups according to the presence of transient hypotony within the first postoperative week or the presence of a hypertensive phase during the first three postoperative months. Postoperative IOP, the number of glaucoma medications, and cumulative success rate were compared among the groups. RESULTS: There was significantly better IOP control and a better success rate in the non-hypertensive phase group 2 years postoperatively. However, no significant difference was found in the IOP or success rate at 2 years postoperatively between the transient hypotony and non-hypotony groups. Further subgroup analysis showed that the non-hypotony, non-hypertensive phase group had a significantly higher success rate (100%) at 2 years postoperatively. CONCLUSIONS: We can predict the long-term prognosis after AGV implantation by considering the early postoperative IOP state and the presence of a hypertensive phase.

Different contributions of autophagy to retinal ganglion cell death in the diabetic and glaucomatous retinas.

Diabetes mellitus and glaucoma are the two major causes of selective retinal ganglion cell (RGC) death. To determine the relationship between autophagy and RGC death, we compared autophagy and the related molecular pathways in diabetic and glaucomatous retinas and examined their effect on RGC survival. Biochemical analysis of microtubule-associated protein light chain 3 (LC3)-II and beclin-1 were observed. To determine the pathways involved in autophagy induction, adenosine monophosphate-activated protein kinase (AMPK) and the mechanistic target of rapamycin (mTOR) were also explored. Beclin-1 and the LC3B-II to LC3B-I ratio significantly elevated at 4 and 8 weeks after glaucoma induction; however, only a slight increase was apparent in the diabetic retina. Significant upregulation of phosphorylated AMPK and downregulation of phosphorylated mTOR was evident in the diabetic retina. After autophagy was inhibited with 3-methyladenine (3-MA), apoptosis of RGCs was significantly increased in the diabetic retinas. However, 3-MA inhibition of autophagy decreased the apoptosis of RGCs in glaucomatous retinas. Therefore, our results suggest that RGC death is differentially regulated by autophagy and that the pathways involved differ depending on the triggering injury.

Transverse Separation of the Outer Retinal Layer at the Peripapillary in Glaucomatous Myopes.

Glaucoma specialists often overlook the outer retinal changes because the glaucomatous optic neuropathy typically involves retinal nerve fiber layer (RNFL). By detailed inspection of the outer retina in myopic eyes, we observed a separation of the inner nuclear layer (INL) from the outer nuclear layer (ONL) at the peripapillary sclera (pp-sclera). Therefore, we conducted a retrospective observation of 108 eyes of 108 Korean subjects with myopia assessed by swept-source optical coherence tomography (SSOCT) and divided into normal and glaucomatous eyes. Mean subject age, refractive error and axial length difference between 2 groups were insignificant, respectively. To quantify the ONL-INL separation, straight-line distance from ONL endpoint to INL endpoint was measured at the center of the optic disc by SSOCT horizontal scan. The glaucomatous group had significantly large ONL-INL separation than the non-glaucomatous group (p = 0.027) but had no significant difference in INL - Anterior scleral canal opening (ASCO) separation. The width of ONL-INL separation were associated with ß-peripapillary atrophy (ß-PPA), degree of horizontal tilt of the optic disc and worse glaucomatous RNFL defect by Pearson's correlation analysis (all p < 0.001, respectively). In conclusion, we demonstrate transverse separation of INL from ONL at the peripapillary region, which was significantly associated with glaucomatous optic nerve damage. These observations may be of interest to elucidate the role of PPA in glaucoma pathogenesis and a clinical index to take notice for myopic subjects.

Correction: A genetic variant in SLC28A3, rs56350726, is associated with progression to castration-resistant prostate cancer in a Korean population with metastatic prostate cancer.

[This corrects the article DOI: 10.18632/oncotarget.18298.].

A genetic variant in SLC28A3, rs56350726, is associated with progression to castration-resistant prostate cancer in a Korean population with metastatic prostate cancer.

Background: Genetic variation which related with progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT) has not been elucidated in patients with metastatic prostate cancer (mPCa). Therefore, we assessed the association between genetic variats in mPCa and progession to CRPC. Results: Analysis of exome genotypes revealed that 42 SNPs were significantly associated with mPCa. The top five polymorphisms were statistically significantly associated with metastatic disease. In addition, one of these SNPs, rs56350726, was significantly associated with time to CRPC in Kaplan-Meier analysis (Log-rank test, p = 0.011). In multivariable Cox regression, rs56350726 was strongly associated with progression to CRPC (HR = 4.172 95% CI = 1.223-14.239, p = 0.023). Materials and Methods: We assessed genetic variation among 1000 patients with PCa with or without metastasis, using 242,221 single nucleotide polymorphisms (SNPs) on the custom HumanExome BeadChip v1.0 (Illuminam Inc.). We analyzed the time to CRPC in 110 of the 1000 patients who were treated with ADT. Genetic data were analyzed using unconditional logistic regression and odds ratios calculated as estimates of relative risk of metastasis. We identified SNPs associated with metastasis and analyzed the relationship between these SNPs and time to CRPC in mPCa. Conclusions: Based on a genetic variation, the five top SNPs were observed to associate with mPCa. And one (SLC28A3, rs56350726) of five SNP was found the association with the progression to CRPC in patients with mPCa.

Association of Parkinsonism or Parkinson Disease with Polypharmacy in the Year Preceding Diagnosis: A Nested Case-Control Study in South Korea.

INTRODUCTION: Published studies on the association between polypharmacy and parkinsonism or Parkinson disease are very limited. OBJECTIVE: The objective of this study was to investigate whether polypharmacy is associated with parkinsonism or Parkinson disease in elderly patients. METHODS: From a South Korean national health insurance sample cohort database for 2002-2013, we matched parkinsonism cases (defined by diagnosis codes for parkinsonism/Parkinson disease) and Parkinson disease cases (patients who had records for both Parkinson disease diagnosis and anti-Parkinson disease drug prescriptions) with controls. Logistic regression analysis evaluated the associations of parkinsonism/Parkinson disease with polypharmacy (i.e., five or more prescribed daily drugs) during the year preceding parkinsonism/Parkinson disease diagnosis, medications potentially associated with parkinsonism, and comorbidity status (using the Charlson Comorbidity Index score and hospitalization records). RESULTS: The study population included 6209 cases and 24,836 controls for parkinsonism and 1331 cases and 5324 controls for Parkinson disease. In univariate logistic regression, odds ratios for parkinsonism/Parkinson disease increased significantly with increased polypharmacy, medications potentially associated with parkinsonism, Charlson Comorbidity Index score, or prior hospitalizations. In multiple logistic regression, odds ratios for parkinsonism/Parkinson disease (adjusted for medications potentially associated with parkinsonism and comorbidities) also increased with increased polypharmacy. Odds ratios (95% confidence interval) for Parkinson disease were higher than those for parkinsonism with stronger statistical significance: 1.41 (1.28-1.55) and 2.17 (1.84-2.57) for parkinsonism and 2.87 (2.30-3.58) and 4.75 (3.39-6.66) for Parkinson disease for between five and ten prescribed daily drugs and ten or more drugs, respectively. CONCLUSIONS: Polypharmacy in the year preceding diagnosis may be associated with an increased risk for parkinsonism/Parkinson disease. Medications potentially associated with parkinsonism were assumed to increase the risk for parkinsonism/Parkinson disease, but more studies are required to confirm this relationship.