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Abstract Introduction The EVEREST II study previously reported that intravitreally administered ranibizumab (IVR) combined with photodynamic therapy (PDT) achieved superior visual gain and polypoidal lesion closure compared to IVR alone in patients with polypoidal choroidal vasculopathy (PCV). This follow-up study reports the long-term outcomes 6 years after initiation of the EVEREST II study. Methods This is a non-interventional cohort study of 90 patients with PCV from 16 international trial sites who originally completed the EVEREST II study. The long-term outcomes were assessed during a recall visit at about 6 years from commencement of EVEREST II. Results The monotherapy and combination groups contained 41 and 49 participants, respectively. The change in best-corrected visual acuity (BCVA) from baseline to year 6 was not different between the monotherapy and combination groups; − 7.4 ± 23.0 versus − 6.1 ± 22.4 letters, respectively. The combination group had greater central subfield thickness (CST) reduction compared to the monotherapy group at year 6 (− 179.9 vs − 74.2 µm, p = 0.011). Fewer eyes had subretinal fluid (SRF)/intraretinal fluid (IRF) in the combination versus monotherapy group at year 6 (35.4% vs 57.5%, p = 0.032). Factors associated with BCVA at year 6 include BCVA (year 2), CST (year 2), presence of SRF/IRF at year 2, and number of anti-VEGF treatments (years 2–6). Factors associated with presence of SRF/IRF at year 6 include combination arm (OR 0.45, p = 0.033), BCVA (year 2) (OR 1.53, p = 0.046), and presence of SRF/IRF (year 2) (OR 2.59, p = 0.042). Conclusion At 6 years following the EVEREST II study, one-third of participants still maintained good vision. As most participants continued to require treatment after exiting the initial trial, ongoing monitoring and re-treatment regardless of polypoidal lesion status are necessary in PCV. Trial Registration ClinicalTrials.gov identifier, NCT01846273.

Abstract Background Neurogenic differentiation factor 1 (NEUROD1) is frequently overexpressed in small‐cell lung cancer (SCLC). NEUROD1 plays an important role in promoting malignant behavior and survival. Methods In this study, we evaluated the association between putative functional polymorphisms in 45 NEUROD1 target genes and chemotherapy response and survival outcomes in 261 patients with SCLC. Among the 100 single nucleotide polymorphisms (SNPs) studied, two were significantly associated with both chemotherapy response and overall survival (OS) of patients with SCLC. Results The SNP rs3806915C>A in semaphorin 6A (SEMA6A) gene was significantly associated with better chemotherapy response and OS (p = 0.04 and p = 0.04, respectively). The SNP rs11265375C>T in nescient helix–loop helix 1 (NHLH1) gene was also associated with better chemotherapy response and OS (p = 0.04 and p = 0.02, respectively). Luciferase assay showed a significantly higher promoter activity of SEMA6A with the rs3806915 A allele than C allele in H446 lung cancer cells (p = 4 × 10−6). The promoter activity of NHLH1 showed a significantly higher with the rs11265375 T allele than C allele (p = 0.001). Conclusion These results suggest that SEMA6A rs3806915C>A and NHLH1 rs11265375C>T polymorphisms affect the promoter activity and expression of the genes, which may affect the survival outcome of patients with SCLC.

Purpose: Several studies have shown that zinc has a significant influence on erectile function. However, no studies evaluating the cellular distribution of free zinc in penile erectile tissue have been performed. Therefore, this study aimed to test whether free zinc is present in penile tissue and whether it may be involved in the electrical stimulation (ES)-induced penile erection. Materials and Methods: The subjects for this study were 26 young (8-week-old) male C57BL/6J mice. After the cavernous nerve was exposed through a midline stomach incision, 14 mice received ES of the cavernous nerve (ES group), whereas 12 mice did not (control group). Intracavernous pressure (ICP) (consisting of 10 V at a duration of 1 min, frequency of 12 Hz and a pulse width of 1 m/s) was recorded during ES. Immediately after ICP was recorded, penile tissues were harvested for histological and biochemical analysis, including analysis of zinc transporter 3 (ZnT3) and intracellular free zinc levels. Results: The expression of neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) in penile tissue was significantly greater in the ES group than in the control group (p=0.036 and 0.016, respectively). And then, ZnT3 and intracellular free zinc were present in the penile tissue of both groups. However, ZnT3 immunofluorescence in the ES group was more intense in the dorsal nerve bundle (22% increase, p=0.032). The ES group also showed higher intensity N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) fluorescence signals indicative of intracellular free zinc level in the penile tissue compared to the control group (49% increase in dorsal nerve bundle, p=0.001; 50% increase in corpus cavernosum, p=0.001). Conclusions: The results of the study supported the expression and distribution of free zinc in penile tissue and increased levels after penile erection. Therefore, this study provides anatomical evidence for the potential role of free zinc in penile erection.

Purpose To describe the optical coherence tomography features of pachyvitelliform maculopathy (PVM), an acquired vitelliform lesion (AVL) associated with pachychoroid disease. Methods This study was a retrospective, multicentre, observational analysis. Medical records and multimodal imaging were reviewed in all patients with pachychoroid disease and AVL. Visual acuity, central choroidal thickness (CCT), AVL dimensions, total choroidal area, luminal choroidal area, stromal choroidal area and choroidal vascular index were measured in all eyes with PVM and compared with normal age-matched control eyes. Results Mean age of the PVM group (17 eyes of 17 patients) was 71.41 years. Average follow-up was 33.15 months. Baseline VA was 20/40 in the PVM group and declined to 20/100 (p=0.006). AVLs were all detected overlying pachyvessels with optical coherence tomography and were all hyperautofluorescent with fundus autofluorescent imaging. Mean CCT in the PVM group was significantly greater (352.35 µm) than the CCT in the control group (226.88 µm, p<0.001). Retinal pigment epithelium (RPE) disruption was present in 64.71% of eyes with PVM at baseline and 41.18% developed macular atrophy at the end of follow-up. Conclusions PVM, defined by the presence of AVL associated with pachychoroid features, is a distinct novel entity of the pachychoroid disease spectrum. This study suggests a possible pathogenesis of RPE dysfunction secondary to a thick choroid, leading to accumulation of undigested photoreceptor outer segments and AVL. Clinicians should be aware of this common cause of vitelliform lesions and the poor visual prognosis due to the high risk of atrophy development. [ABSTRACT FROM AUTHOR]

Background: The Chinese visceral adiposity index (CVAI) and new visceral adiposity index (NVAI) are novel indices of visceral adiposity used to predict metabolic and cardiovascular diseases in Asian populations. However, the relationships of CVAI and NVAI with chronic kidney disease (CKD) have not been investigated. We aimed to characterize the relationships of CVAI and NVAI with the prevalence of CKD in Korean adults. Methods: A total of 14,068 participants in the 7th Korea National Health and Nutrition Examination Survey (6,182 men and 7,886 women) were included. Receiver operating characteristic (ROC) analyses were employed to compare the associations between indices of adiposity and CKD, and a logistic regression model was used to characterize the relationships of CVAI and NVAI with CKD prevalence. Results: The areas under the ROC curves for CVAI and NVAI were significantly larger than for the other indices, including the visceral adiposity index and lipid accumulation product, in both men and women (all P<0.001). In addition, high CVAI or NVAI was significantly associated with a high CKD prevalence in both men (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.31 to 3.48 in CVAI and OR, 6.47; 95% CI, 2.91 to 14.38 in NVAI, P<0.05) and women (OR, 4.87; 95% CI, 1.85 to 12.79 in CVAI and OR, 3.03; 95% CI, 1.35 to 6.82 in NVAI, P<0.05); this association remained significant after adjustment for multiple confounding factors in men and women. Conclusion: CVAI and NVAI are positively associated with CKD prevalence in a Korean population. CVAI and NVAI may be useful for the identification of CKD in Asian populations, including in Korea. [ABSTRACT FROM AUTHOR]

Purpose To compare the efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy (PCV) over 96 weeks in the HAWK study. Design HAWK was a global, 2-year, randomised, double-masked, multicentre phase III trial in participants with neovascular age-related macular degeneration. Methods Of the Japanese participants with PCV, 39 received brolucizumab 6 mg and 30 received aflibercept 2 mg. After 3 monthly loading doses, brolucizumab-treated eyes received an injection every 12 weeks (q12w) but were adjusted to q8w if disease activity was detected. Aflibercept-treated eyes received fixed q8w dosing. Mean change in best-corrected visual acuity (BCVA), the proportion of participants on q12w, retinal thickness, retinal fluid changes and safety were assessed to Week 96. Results Mean change in BCVA (early treatment diabetic retinopathy study (ETDRS) letters) from baseline to week 48/week 96 was+10.4/+11.4 for brolucizumab and +11.6/+11.1 for aflibercept. For brolucizumab-treated eyes, the probability of only q12w dosing after loading through week 48 was 76%, and 68% through week 96. Fluid resolution was greater with brolucizumab than aflibercept: respective proportions of eyes with intraretinal fluid and/or subretinal fluid were 7.7% and 30% at week 48% and 12.8% and 16.7% at week 96. Brolucizumab exhibited an overall well-tolerated safety profile despite a higher rate of intraocular inflammation compared with aflibercept. Conclusion In Japanese eyes with PCV, brolucizumab q12w/q8w monotherapy resulted in robust and consistent BCVA gains that were comparable to q8w aflibercept dosing. Anatomical outcomes favoured brolucizumab over aflibercept, with 76% of brolucizumab participants maintained on q12w dosing after loading to week 48. [ABSTRACT FROM AUTHOR]

Background/Aims To analyse the long-term anatomic and visual outcomes of patients with peripapillary pachychoroid syndrome (PPS), a recently described entity in the pachychoroid disease spectrum. Methods This study retrospectively included patients from several retina centres worldwide. Visual acuity (VA), retinal thickness and choroidal thickness at baseline, 6 months and final follow-up were assessed. Temporal trends in VA and anatomic characteristics were evaluated. Visual and anatomic outcomes in eyes that were observed versus those that were treated were analysed. Results Fifty-six eyes of 35 patients were included with mean follow-up of 27±17 months. Median VA was 20/36 at baseline and remained stable through follow-up (p=0.77). Retinal thickness significantly decreased subfoveally (p=0.012), 1.5 mm nasal to the fovea (p=0.002) and 3.0 mm nasal to the fovea (p=0.0035) corresponding to areas of increased thickening at baseline. Choroidal thickness significantly decreased subfoveally (p=0.0030) and 1.5 mm nasal to the fovea (p=0.0030). Forty-three eyes were treated with modalities including antivascular endothelial growth factor injection, photodynamic therapy, and others. VA remained stable in treated eyes over follow-up (p=0.67). An isolated peripapillary fluid pocket in the outer nuclear layer was characteristic of PPS. Conclusion Patients with PPS experienced decreased retinal oedema and decreased choroidal thickening throughout the course of disease. While some patients experienced visual decline, the overall visual outcome was relatively favourable and independent of trends in retinal or choroidal thickening. [ABSTRACT FROM AUTHOR]

Among biodegradable polymers, polylactides (PLAs) have attracted considerable interest because the monomer can be produced from renewable resources. Since their initial degradability strongly affects commercial application fields, it is necessary to manage the degradation properties of PLAs to make them more commercially attractive. To control their degradability, poly(lactide-co-glycolide) (PLGA) copolymers of glycolide and isomer lactides (LAs) were synthesized, and their enzymatic and alkaline degradation rates of PLGA monolayers as functions of glycolide acid (GA) composition were systematically investigated by the Langmuir technique. The results showed that the alkaline and enzymatic degradations of PLGA monolayers were faster than those of l-polylactide (l-PLA), even though proteinase K is selectively effective in the l-lactide (l-LA) unit. Alkaline hydrolysis was strongly affected by their hydrophilicity, while the surface pressure of monolayers for enzymatic degradations was a major factor.