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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.

Abstract Survival analyses for malignancies, including renal cell carcinoma (RCC), have primarily been conducted using the Cox proportional hazards (CPH) model. We compared the random survival forest (RSF) and DeepSurv models with the CPH model to predict recurrence-free survival (RFS) and cancer-specific survival (CSS) in non-metastatic clear cell RCC (nm-cRCC) patients. Our cohort included 2139 nm-cRCC patients who underwent curative-intent surgery at six Korean institutions between 2000 and 2014. The data of two largest hospitals’ patients were assigned into the training and validation dataset, and the data of the remaining hospitals were assigned into the external validation dataset. The performance of the RSF and DeepSurv models was compared with that of CPH using Harrel’s C-index. During the follow-up, recurrence and cancer-specific deaths were recorded in 190 (12.7%) and 108 (7.0%) patients, respectively, in the training-dataset. Harrel’s C-indices for RFS in the test-dataset were 0.794, 0.789, and 0.802 for CPH, RSF, and DeepSurv, respectively. Harrel’s C-indices for CSS in the test-dataset were 0.831, 0.790, and 0.834 for CPH, RSF, and DeepSurv, respectively. In predicting RFS and CSS in nm-cRCC patients, the performance of DeepSurv was superior to that of CPH and RSF. In no distant time, deep learning-based survival predictions may be useful in RCC patients.

Post-micturition dribble (PMD) is the involuntary loss of urine immediately after urination. It is classified as a post-micturition symptom and is more common in males. Traditionally, PMD has been considered to be part of the aging process, to have a low prevalence, and to be less bothersome than other lower urinary tract symptoms (LUTS). However, recent evidence suggests that PMD is not less common and does not elicit less discomfort compared with other LUTS in males. Also, PMD seems to commonly overlap with other LUTS and to be associated with erectile dysfunction. Although the etiology of PMD is not fully understood, a weakness or failure of the pelvic floor muscles is considered to be the most important factor. Although bulbar urethral massage and pelvic floor exercises are known to be effective in treating PMD, pharmacologic treatment has not yet been introduced. Recently, the possibility of treating PMD with phosphodiesterase-5 inhibitor has been suggested.

Purpose: Lower urinary tract symptoms (LUTS) are correlated with erectile dysfunction (ED), but research on whether post-micturition dribble (PMD) is related to ED is limited. We assessed the correlation between PMD and ED in middle-aged and older Korean men with LUTS. Materials and Methods: In our prospective, cross-sectional, observational, multicenter study, we enrolled 205 men (age >40 years) with LUTS. LUTS and ED were assessed using the International Prostate Symptom Score (IPSS) and International Index of Erectile Function-5 (IIEF-5), respectively. PMD was assessed using the Hallym PostMicturition Dribble Questionnaire, Question 1, and the PMD volume was calculated in a paper test. Age, prostate volume, serum prostate-specific antigen, maximum urinary flow rate, and postvoid residual urine were also evaluated. Results: There were significant differences in the total and voiding IPSS between men with and without ED (p=0.042 and 0.043, respectively). The Hallym PostMicturition Dribble Questionnaire 1 score was inversely well correlated with the IIEF-5 score (r=-0.388, p

There is no safe and effective standard method for glans penis augmentation. Furthermore, there has been scant research on glans penis augmentation due to a poor understanding of glans anatomy, technical difficulty, and a lack of suitable substances for augmentation. Cross-linked dextran gel is a newly developed filler for soft-tissue augmentation. We evaluated the efficacy and safety of using a novel technique to inject cross-linked dextran gel for glans penis augmentation during a 24-week follow-up study. This prospective, single-arm, multicenter study enrolled twenty healthy adult men who underwent glans penis augmentation between June and August 2013. Cross-linked dextran gel was injected into the glans penis using a simple and easy technique. The sizes of the glans penis and individual satisfaction were assessed. Any adverse event was also reported. A total of 18 individuals were analyzed; two of them were lost to follow-up. The mean procedure time and injected volume were about 30 min and 6.6 ± 0.9 ml, respectively. The mean surface areas of the glans at baseline and 24 weeks were 20.0 ± 3.5 cm2 and 33.6 ± 5.4 cm2 , respectively, representing a mean increase of 68.7% ± 14.0% (P < 0.001). Sixteen individuals (88.9%) were satisfied with the outcomes, and none were dissatisfied. There were no serious adverse events during the study. Cross-linked dextran gel injection for glans penis augmentation was easy and showed a significant augmentative effect on the glans penis, good durability, and was well tolerated without serious adverse events. Therefore, cross-linked dextran gel injection may be an effective, new technique for glans penis augmentation.

ObjectivesPostmicturition dribble (PMD) is a very common symptom in males with lower urinary tract symptoms (LUTS) worldwide, but there is no adequate questionnaire to assess it. Therefore, we developed a questionnaire named the Hallym Post Micturition Dribble Questionnaire (HPMDQ) to assess PMD, and the aim of this study is to validate it.MethodsA series of consecutive male patients newly diagnosed with LUTS and over 40 years of age who visited any of 5 medical institutions were included. LUTS were assessed in all patients using the International Prostate Symptom Score (IPSS), and PMD was assessed using the HPMDQ.ResultsIn total, 2134 male patients aged 40 to 91 years were included in this study. Of these patients, 1088 (51.0%) reported PMD. In the PMD group, the mean values for HPMDQ-Q1, HPMDQ-Q2, HPMDQ-Q3 and HPMDQ total score were 1.39, 1.10, 1.76 and 4.25, respectively. In the non-PMD group, the mean values of these scores were 0, 0.18, 1.52 and 1.58, respectively. The difference in HPMDQ scores between the 2 groups was statistically significant. PMD was significantly associated with the voiding symptoms of LUTS, prostate size and postvoid residual but not with storage symptoms.ConclusionsThe HPMDQ, which consists of 5 questions (frequency, severity, bother, quality of life and response to treatment for PMD), was developed, and its use for assessing PMD is validated in this study. It may be a useful tool for further research and in clinical practice for PMD.

This study is for reporting the outcomes of internal limiting membrane (ILM) peeling on persistent submacular fluid (PSF) after otherwise successful pars plana vitrectomy (PPV) for diabetic tractional retinal detachment (TRD). In this retrospective case series, five consecutive patients (5 eyes) who exhibited PSF following successful repair of diabetic TRD were included. The second operation was performed to remove ILM. The area of ILM peeling was expanded up to the major vascular arcade. Only air tamponade was used. The median interval between the first PPV and the second PPV with ILM peeling was 4.8 months (range: 4–6 months). PSF resolved completely within one (2 eyes) or 2 months after ILM peeling. The median logMAR best-corrected visual acuity (BCVA) was improved from 1.00 (Snellen equivalent 20/200) to 0.70 (Snellen equivalent 20/100). In conclusion, wide ILM peeling is an effective treatment option for PSF subsequent to successful repair of diabetic TRD. ILM peeling might increase the elasticity of retina, thereby allowing the retina to flatten. This procedure can induce faster retinal reattachment in diabetic TRD involving the macula.

In this study, a green chemistry method is reported for the synthesis of Ag2O nanoparticles with the utilization of starch molecules as a stabilizing agent. In particular, by simply adjusting the concentration of starch in the reaction media, the structure of A2O nanoparticles can be engineered in disc and faceted shapes, which has been analyzed by transmission electron microscopy, UV-Vis spectroscopy, and X-ray diffraction technique. In addition, antibacterial activity of the prepared Ag2O nanoparticles had been evaluated against food poisoning and pathogenic bacteria.

Purpose: To evaluate risk factors for deterioration of lower urinary tract symptoms (LUTS) in elderly men in a community-based, prospective longitudinal cohort study. Methods: In a suburban area in Korea, 1,514 subjects aged ≥45 years were randomly selected by systematic sampling. A total of 918 elderly subjects were enrolled in this in-depth clinical study in 2004. Of these, 547 participants were followed up for 3 years and the data was analyzed in 2014. Standard questionnaires were administered face-to-face by trained interviewers. After excluding women, 224 male participants with complete data including transrectal ultrasonography were included in the final analysis. LUTS were diagnosed using the International Prostate Symptom Score (IPSS) questionnaire. Symptom deterioration was defined as a score of ≥8 points during the 3-year follow-up period. Results: LUTS prevalence increased to 13.1% and the mean IPSS increased by 2.6 points during the 3-year period. After adjusting for confounders, a smoking history of ≥50 pack-years was an independent risk factor for deterioration of LUTS and storage subsymptoms compared with no history of smoking (3.1 and 5.1 odds, respectively). Physical activity had a protective effect on voiding subsymptoms. However, high protein diet and alcohol intake were not associated with LUTS deterioration. Conclusions: The LUTS prevalence among elderly men living in a suburban area increased to 13.1% and the IPSS increased by 2.6 points during the 3-year period. A history of heavy smoking, low physical activity, and high protein intake were associated with LUTS deterioration. However, there was no significant association between alcohol intake and LUTS deterioration.

To evaluate the incidence and associated risk factors of massive subretinal hemorrhage (SRH) in patients with retinal angiomatous proliferation (RAP).A total of 187 eyes of 135 treatment-naıve patients diagnosed with RAP were evaluated retrospectively. Clinical records including the time between the initial visit, last anti-vascular endothelial growth factor (VEGF) treatment, last stable examination, and the date of massive SRH were reviewed. Imaging findings including indocyanine green angiography (ICGA) and optical coherence tomography (OCT) were analyzed.Massive SRH developed in 18 eyes (9.6%) a median of 20 months after the initial presentation. Kaplan-Meier survival analysis revealed that the incidence (2.8, 5.8, 13.1, and 21.0% after 1,2,5 and 10 years, respectively) continuously increased. Among 14 eyes with discernable vascular anastomosis on baseline ICGA, 13 (92.8%) showed retinal arteriole involvement. On spectral-domain OCT imaging of the last visit prior to the massive SRH, a layered lamellar tissue complex was noted under the retinal pigment epithelium in 9 of 13 eyes, which was significantly associated with massive SRH[hazard ratio(HR),5.883;P = .010]. The average time between the last stable examination/last injection and the massive SRH was 2 and 5 months, respectively. The patients were treated with anti-VEGF, gas and recombinant tissue plasminogen activator injection; however, all except one eye had visual acuity worse than 20/1000 at the final visit.Massive SRH can occur in RAP in the course of anti-VEGF treatment, resulting in severe vision loss. A proactive dosing regimen may be more appropriate for these RAP eyes.

Purpose To assess the clinical utility of the prostate-specific antigen mass ratio (PSA-MR), a newly developed PSA derivative, simply defined as the (i) PSA density (PSA-D) multiplied by the plasma volume or (ii) total PSA amount in circulation per prostate volume, for predicting prostate cancer (PCa) among men undergoing repeated prostate biopsy (PBx). Materials and Methods Patients (n = 286), who underwent a repeated PBx, were analyzed. The various parameters associated with PCa detection were noted in each patient. PSA-MR was also calculated. Results PCa was detected in 63 (22.0%) of 286 patients. PSA-MR was the independent predictor in the univariate- and multivariate logistic regression analyses (OR = 3.448, p = 0.001 and OR = 13.430, p = 0.033, respectively). A nomogram that incorporated PSA-MR was considered a useful tool (predictive accuracy: 79.2%, 95% CI: 0.726-0.858, p < 0.001). Furthermore, a nomogram that incorporated PSA-MR would have avoided 59.6% of unnecessary repeated PBx. The predictive accuracy of PSA-MR was also superior to that of PSA or PSA-D (p = 0.013 and 0.009, respectively). Conclusions PSA-MR was an independent predictor, and its consideration would have avoided 59.6% of unnecessary repeated PBx for PCa detection. PSA-MR was also superior than PSA or PSA-D. Our results support the use of PSA-MR to facilitate counseling with patients after a negative initial PBx, and use of PSA-MR might reduce further unnecessary biopsies.

BackgroundMacintosh laryngoscopic intubation is a lifesaving procedure, but a difficult skill to learn. The Airtraq optical laryngoscope (AOL) is a novel intubation device with advantages over the direct laryngoscope for untrained personnel in a manikin study. We compared the effectiveness of AOL with Macintosh laryngoscope for tracheal intubation by novice personnel.MethodsWe selected 37 medical students with no prior tracheal intubation experience and educated them on using both laryngoscopes. Seventy-four patients were randomly divided into two groups (group A: AOL, group M: Macintosh laryngoscope). We recorded the tracheal intubation success rate, intubation time, number of attempts, intubation difficulty scale, and adverse effects.ResultsThe total success rate was similar in the two groups, but the success rate at first attempt was higher in group A (P < 0.01). Group A also showed reduced duration and attempts at intubation, as well as adverse effects such as oral cavity injury. Additionally, participant reports indicated that using the AOL was easier than the Macintosh laryngoscope (P < 0.01).ConclusionsThe AOL is a more effective instrument for tracheal intubation than Macintosh laryngoscope when used by novice personnel.

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]