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Purpose: This study aimed to evaluate changes in intraocular pressure following intravitreal dexamethasone implant injection, specifically in patients undergoing glaucoma filtration surgery. Methods: The degree of increase in intraocular pressure was compared retrospectively among three groups. Group 1 comprised patients who underwent prior glaucoma filtration surgery (54 eyes). Group 2 included patients with or suspected glaucoma without such surgical history (20 eyes). Group 3 included patients without glaucoma (33 eyes). Pressure measurements were taken before the injection and at 1, 2, 3, and 6 months post-injection. A subgroup analysis was performed for pressure > 35 mmHg, > 30 mmHg, > 25 mmHg, and a difference > 10 mmHg between the peak and baseline pressure. Results: Group 1 consistently displayed lower pressures compared with Group 2, with significant difference at both 1- and 6-month post-injections (15.09 mmHg vs. 18.10 mmHg, P = 0.042 and 13.91 mg vs. 17.25 mmHg, P = 0.040). The proportion of patients in Group 1 and Group 3 with pressures > 25 mmHg, > 30 mmHg, and a difference > 10 mmHg did not significantly differ (15.6% vs. 9.5%, P = 0.231; 3.1% vs. 2.3%, P = 0.867; and 17.1% vs. 7.1%, P = 0.231). Notably, Group 2 exhibited a significantly higher proportion within each category (> 25 mmHg, 24.0%; > 30 mmHg, 20.0%; > 10 mmHg difference, 28.0%). Conclusion: Intravitreal dexamethasone implant did not increase the risk of elevated intraocular pressure in patients with a history of glaucoma filtration surgery compared with patients with suspected glaucoma; the risk was similar to those without glaucoma. [ABSTRACT FROM AUTHOR]

Background and Objectives: The European Association of Urology guidelines on urolithiasis highlight the limited evidence supporting the superiority of percutaneous nephrostomy (PCN) over retrograde ureteral stent placement for the primary treatment of infected hydronephrosis secondary to urolithiasis. We, therefore, conducted a systematic review and meta-analysis comparing the effects of PCN and retrograde ureteral stent in patients with severe urinary tract infections secondary to obstructive urolithiasis. Materials and Methods: Meta-analyses were performed to compare four outcomes: time for the temperature to return to normal; time for the white blood cell (WBC) count to return to normal; hospital length of stay; and procedure success rate. After a full-text review, eight studies were identified as relevant and included in our systematic review and meta-analysis. Results: No significant difference was detected between PCN and retrograde ureteral stenting for the time for the temperature to return to normal (p = 0.13; mean difference [MD] = −0.74; 95% confidence interval [CI] = −1.69, 0.21; I2 = 96%) or the time for the WBC count to return to normal (p = 0.24; MD = 0.46; 95% CI = −0.30, 1.21; I2 = 85%). There was also no significant difference between methods for hospital length of stay (p = 0.78; MD = 0.45; 95% CI = −2.78, 3.68; I2 = 96%) or procedure success rate (p = 0.76; odds ratio = 0.86; 95% CI = 0.34, 2.20; I2 = 47%). Conclusions: The clinical outcomes related to efficacy did not differ between PCN and retrograde ureteral stenting for severe urinary tract infection with obstructive urolithiasis. Thus, the choice between procedures depends mainly on the urologist's or patient's preferences. [ABSTRACT FROM AUTHOR]

We develop a numerically stable sequential formulation of thermoporomechanics for largely deformable gas hydrate deposits, extended from the fixed stress split of infinitesimal transformation. Constitutive equations are based on the total Lagrangian approach for both flow and geomechanics, including dynamic full tensor permeability and thermal conductivity updated from the deformation gradient. For space discretization, we take the cell‐centered finite volume and node‐based finite element method for flow and geomechanics, respectively. Then, we propose a sequential implicit method for all‐way coupled thermoporomechanics, where the nonisothermal multiphase flow problem of gas hydrates is solved implicitly first and then the geomechanics problem is solved implicitly at the next step. During solution of the flow problem, we fix the rate of first Pioal total stress for numerical stability as well as apply porosity correction and entropy correction to account for geomechanical effects. We test numerical examples where flow and geomechanics parameters are based on deep oceanic gas hydrate deposits. When applying depressurization, even though the results between the infinitesimal transformation and finite strain geomechanics are similar in the early stages due to small deformation, we find differences between them in the late times as deformation becomes large. Accordingly, permeability and thermal conductivity tensors become nonisotropic full tensors although they are initially isotropic. We identify numerical stability of the developed sequential method from the test cases that exhibit the highly complex coupled gas hydrate systems with large deformation. Thus, the proposed sequential formulation can be applied in largely deformable gas hydrate systems. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening viral zoonosis. The causative agent of this disease is the Dabie bandavirus, which is usually known as the SFTS virus (SFTSV). Although the role of vertebrates in SFTSV transmission to humans remains uncertain, some reports have suggested that dogs could potentially transmit SFTSV to humans. Consequently, preventive measures against SFTSV in dogs are urgently needed. In the present study, dogs were immunized three times at two-week intervals with formaldehyde-inactivated SFTSV with two types of adjuvants. SFTSV (KCD46) was injected into all dogs two weeks after the final immunization. Control dogs showed viremia from 2 to 4 days post infection (dpi), and displayed white pulp atrophy in the spleen, along with a high level of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay (TUNEL) positive area. However, the inactivated SFTSV vaccine groups exhibited rare pathological changes and significantly reduced TUNEL positive areas in the spleen. Furthermore, SFTSV viral loads were not detected at any of the tested dpi. Our results indicate that both adjuvants can be safely used in combination with an inactivated SFTSV formulation to induce strong neutralizing antibodies. Inactivated SFTSV vaccines effectively prevent pathogenicity and viremia in dogs infected with SFTSV. In conclusion, our study highlighted the potential of inactivated SFTSV vaccination for SFTSV control in dogs. [ABSTRACT FROM AUTHOR]

Background and Objectives: Urolithiasis occurrence is uncommon in kidney transplantation patients, though it has serious implications, including acute kidney injury in the transplanted kidney. This study investigates the leading causes of urolithiasis in kidney transplantation patients, the diagnostic process, and the outcomes of multimodal management. Materials and Methods: Data collection spanned from January 1997 to December 2021, involving kidney transplantation patients with urolithiasis from the database of the Korean Society of Endourology and Robotics (KSER) research committee. Analysis encompassed factors triggering urolithiasis, the diagnostic process, stone attributes, treatment methods, and outcomes. Results: Our analysis included 58 kidney transplantation patients with urolithiasis from eight medical centers. Of these patients, 37 were male and 4 had previous urolithiasis diagnoses. The mean age was 59.09 ± 10.70 years, with a mean duration from kidney transplantation to diagnosis of 76.26 ± 183.14 months. The most frequent method of stone detection was through asymptomatic routine check-ups (54.7%). Among the 58 patients, 51 underwent stone treatment. Notably, 95.3% of patients with ureter stones received treatment, a significantly higher rate than the 66.7% of patients with renal stones (p = 0.010). Success rates showed no significant differences between renal (70%) and ureter stone (78.0%) groups (p = 0.881). Conclusions: Urolithiasis in transplanted kidneys constitutes an acute condition requiring emergency intervention. Endo-urological interventions are effective for kidney transplantation patients with urolithiasis. To ensure prevention and early detection, diligent follow-up and routine imaging tests are necessary. [ABSTRACT FROM AUTHOR]

Elevated intraocular pressure (IOP) in glaucoma causes retinal ganglion cell (RGC) loss and damage to the optic nerve. Although IOP is controlled pharmacologically, no treatment is available to restore retinal and optic nerve function. In this paper, we aimed to develop a novel gene therapy for glaucoma using an AAV2-based thioredoxin 2 (Trx2)-exoenzyme C3 transferase (C3) fusion protein expression vector (scAAV2-Trx2-C3). We evaluated the therapeutic effects of this vector in vitro and in vivo using dexamethasone (DEX)-induced glaucoma models. We found that scAAV2-Trx2-C3-treated HeLa cells had significantly reduced GTP-bound active RhoA and increased phosphor-cofilin Ser3 protein expression levels. scAAV2-Trx2-C3 was also shown to inhibit oxidative stress, fibronectin expression, and alpha-SMA expression in DEX-treated HeLa cells. NeuN immunostaining and TUNEL assay in mouse retinal tissues was performed to evaluate its neuroprotective effect upon RGCs, whereas changes in mouse IOP were monitored via rebound tonometer. The present study showed that scAAV2-Trx2-C3 can protect RGCs from degeneration and reduce IOP in a DEX-induced mouse model of glaucoma, while immunohistochemistry revealed that the expression of fibronectin and alpha-SMA was decreased after the transduction of scAAV2-Trx2-C3 in murine eye tissues. Our results suggest that AAV2-Trx2-C3 modulates the outflow resistance of the trabecular meshwork, protects retinal and other ocular tissues from oxidative damage, and may lead to the development of a gene therapeutic for glaucoma. [ABSTRACT FROM AUTHOR]

Birefringence, an inherent characteristic of optically anisotropic materials, is widely utilized in various imaging applications ranging from material characterizations to clinical diagnosis. Polarized light microscopy enables high-resolution, high-contrast imaging of optically anisotropic specimens, but it is associated with mechanical rotations of polarizer/analyzer and relatively complex optical designs. Here, we present a form of lens-less polarization-sensitive microscopy capable of complex and birefringence imaging of transparent objects without an optical lens and any moving parts. Our method exploits an optical mask-modulated polarization image sensor and single-input-state LED illumination design to obtain complex and birefringence images of the object via ptychographic phase retrieval. Using a camera with a pixel size of 3.45 μm, the method achieves birefringence imaging with a half-pitch resolution of 2.46 μm over a 59.74 mm2 field-of-view, which corresponds to a space-bandwidth product of 9.9 megapixels. We demonstrate the high-resolution, large-area, phase and birefringence imaging capability of our method by presenting the phase and birefringence images of various anisotropic objects, including a monosodium urate crystal, and excised mouse eye and heart tissues. [ABSTRACT FROM AUTHOR]

Background and Objectives: Percutaneous nephrolithotomy (PCNL) is still the gold-standard treatment for large and/or complex renal stones. Endoscopic combined intrarenal surgery (ECIRS) was developed with the goal of minimizing the number of access tracts of PCNL while simultaneously improving the one-step stone-free rate (SFR). The aim of this study was to share the experience of the consecutive 200 cases of ECIRS in one institute and analyze surgical outcomes of mini-ECIRS and standard ECIRS. Materials and Methods: We performed ECIRS for 200 adult patients between July 2017 and January 2020. An ECIRS was performed with the patient under general anesthesia in the intermediate-supine position. Surgeries were finished using a tubeless technique with a simple ureteral stent insertion. Results: There were significant differences in the mean maximal stone length (MSL), the variation coefficient of stone density (VCSD), the linear calculus density (LCD), the Seoul National University Renal Stone Complexity (S-ReSC), and the modified S-ReSC scores in stone characteristics, and estimated blood loss (EBL) and operation time in peri-operative outcomes between conventional and mini-ECIRS. After propensity-score matching, there was only a difference in EBL between the two groups. In logistic regression models, MSL [odds ratio (OR) 0.953; 95% confidence interval (CI) 0.926–0.979; p < 0.001], LCD (OR 4.702; 95% CI 1.613–18.655; p = 0.013) were significant factors for the success rate after ECIRS. Conclusions: In patients who underwent a mini-ECIRS, the stones were relatively smaller and less complex, and the operation time was shorter. However, if the size of stones was similar, there was no difference in the success rate, but EBL was lower in mini-ECIRS than in standard surgery. [ABSTRACT FROM AUTHOR]

Cystinuria is a known genetic disorder. To date, two genes, SLC3A1 and SLC7A9, have been identified as causes of cystinuria. In this study of 10 patients with cystinuria, which is the largest Korean cohort ever studied, we examined the patients' phenotypes, clinical courses, and genetic analyses. A total of 10 patients with cystinuria diagnosed with cystine stones in a single tertiary medical center (Severance Hospital, Seoul, Republic of Korea) from April 2000 to July 2023 were included in the study. All of the patients participated in mutational studies, and the clinical presentation and consecutive laboratory findings of the patients were analyzed retrospectively. After the initial stone-related surgery or procedure at our hospital, 6 of the 10 patients underwent additional surgery at least once for recurrent stones. Genetic analyses identified six new mutations, of which only two patients had type B mutations. The most common genotype was compound heterozygous type A. We investigated the genotypes and clinical courses of 10 Korean patients with cystinuria who had not been previously reported. More data are needed to statistically analyze the genotype and phenotype of cystinuria. [ABSTRACT FROM AUTHOR]

Background and Objectives: Analysis of urine stone composition is one of the most important factors in urolithiasis treatment. This study investigated whether a convolutional neural network (CNN) can show decent results in predicting urinary stone composition even in single-use flexible ureterorenoscopic (fURS) images with relatively low resolution. Materials and Methods: This study retrospectively used surgical images from fURS lithotripsy performed by a single surgeon between January 2018 and December 2021. The ureterorenoscope was a single-use flexible ureteroscope (LithoVue, Boston Scientific). Among the images taken during surgery, a single image satisfying the inclusion and exclusion criteria was selected for each stone. Cases were divided into two groups according to whether they contained any calcium oxalate (the Calcium group) or none (the Non-calcium group). From 506 total cases, 207 stone surface images were finally included in the study. In the CNN model, the transfer learning method using Resnet-18 as a pre-trained model was used, and only endoscopic digital images and stone classification data were input to achieve minimally supervised learning. Results: There were 175 cases in the Calcium group and 32 in the Non-calcium group. After training and validation, the model was tested using the test set, and the total accuracy was 81.8%. Recall and precision of the test results were 88.2% and 88.2% in the Calcium group and 60.0% and 60.0% in the Non-calcium group, respectively. The area under the receiver operating characteristic curve of the model, which represents its classification performance, was 0.82. Conclusions: Single-use flexible ureteroscopes have financial benefits but low vision quality compared with reusable digital flexible ureteroscopes. As far as we know, this is the first artificial intelligence study using single-use fURS images. It is meaningful that the CNN performed well even under these difficult conditions because these results can further expand the possibilities of its use. [ABSTRACT FROM AUTHOR]

This retrospective study evaluated the real-world safety and effectiveness of switching to intravitreal brolucizumab for refractory neovascular age-related macular degeneration (nAMD). A total of 81 patients who received brolucizumab injections as switch therapy were followed for more than 3 months. A good response was defined as better anatomical improvement or extended injection intervals compared with previous anti-vascular endothelial growth factor (VEGF) treatment over a mean follow-up period of 41.4 weeks. Approximately 82.7% of patients showed a good response after switching. After 1 year, patients showed significant visual gains (+ 6.6 letters, p = 0.006) and central retinal thickness reductions (− 112.6 µm, p < 0.001), with 30.8% having injection intervals extended over 12 weeks. In the poor-response group, visual acuity and anatomical outcomes worsened soon after switching. More previous injections, thinner baseline central retina, and the presence of prechoroidal cleft or polypoidal lesion resulted in a better response (p < 0.05). Adverse effects occurred in eight eyes (9.9%), including one retinal vascular occlusion and seven intraocular inflammation cases, which were unrelated to the response. Most patients with nAMD refractory to anti-VEGF treatment demonstrated anatomical improvement or extended injection intervals after switching. This study shows that identified structural biomarkers may predict treatment response and select an appropriate therapeutic strategy. [ABSTRACT FROM AUTHOR]

Background: The natural course of polypoid lesions in the ureter during ureteroscopic stone surgery was not yet clarified. Methods: Patient data were collected prospectively from six teaching hospitals between 2019 and 2021. Patients with polypoid lesions in the ureter distal to ureteral stones were included during ureteroscopy. Computed tomography was performed on all enrolled patients three months after the procedure. Follow-up ureteroscopy was performed only if the patient consented, due to the need for general anesthesia and ethical considerations. Results: Among the 35 patients who were followed up, 14 had fibroepithelial polyps and 21 had inflammatory polyps. Twenty of the followed-up patients underwent ureteroscopy, and nine of them had fibroepithelial polyps. Although fibroepithelial polyps did not disappear in the follow-up ureteroscopy (p = 0.002), the rate of postoperative hydronephrosis was not higher in the fibroepithelial group than in the inflammatory group. Postoperative ureteral stricture and moderate-to-severe hydronephrosis were found to be closely related to the number of resected polyps, regardless of the type of polyp (p = 0.014 and 0.006, respectively). Conclusion: Fibroepithelial polyps in the ureter may persist after treatment of adjacent ureter stones. However, conservative management may be preferable to active removal of ureteral polyps because fibroepithelial polyps may not contribute to clinically significant hydronephrosis after surgery, and inflammatory polyps disappear spontaneously. Hasty resections of polyps may increase the risk of ureteral stricture. [ABSTRACT FROM AUTHOR]

Background: The authors intend to compare the effects of each targeted therapy (TT) in the treatment of patients with metastatic renal cell carcinoma (mRCC) using big data based on the Korean National Health Insurance System (NHIS) and determine the optimal treatment sequence. Methods: Data on the medical use of patients with kidney cancer were obtained from the NHIS database from January 1, 2002, to December 31, 2020. Patient variables included age, sex, income level, place of residence, prescribing department, and duration from diagnosis to the prescription date. The primary outcome was overall survival (OS) for each drug and sequencing. We performed propensity score matching (PSM) according to age, sex, and Charlson Comorbidity Index based on the primary TTs. Results: After 1:1 PSM, the sunitinib (SUN) (n = 1,214) and pazopanib (PAZ) (n = 1,214) groups showed a well-matched distribution across the entire cohort. In the primary treatment group, PAZ had lower OS than SUN (HR, 1.167; p = 0.0015). In the secondary treatment group, axitinib (AXI) had more favorable OS than cabozantinib (CAB) (HR, 0.735; p = 0.0118), and everolimus had more adverse outcomes than CAB (HR, 1.544; p < 0.0001). In the first to second TT sequencing, SUN–AXI had the highest OS; however, there was no statistically significant difference when compared with PAZ–AXI, which was the second highest (HR, 0.876; p = 0.3312). The 5-year survival rate was calculated in the following order: SUN–AXI (51.44%), PAZ–AXI (47.12%), SUN–CAB (43.59%), and PAZ–CAB (34.28%). When the four sequencing methods were compared, only SUN–AXI versus PAZ–CAB (p = 0.003) and PAZ–AXI versus PAZ–CAB (p = 0.017) were statistically significant. Conclusions: In a population-based RWD analysis of Korean patients with mRCC, SUN-AXI sequencing was shown to be the most effective among the first to second TT sequencing methods in treatment, with a relative survival advantage over other sequencing combinations. To further support the results of this study, risk-stratified analysis is needed. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to determine the short-term real-world safety and efficacy of intravitreal brolucizumab injections in Korean patients with neovascular age-related macular degeneration (nAMD). Methods: This multicenter retrospective study involved 294 eyes (treatment naïve 20 eye [6.8%] and nontreatment naïve 274 eyes [93.2%]) of 290 patients from 13 hospitals or retinal centers in South Korea. Patients with nAMD who received brolucizumab injection(s) between April 1 and November 30, 2021, with a follow-up ≥1 month, were included. Primary outcomes were safety, incidence of intraocular inflammation (IOI), and potential risk factors. The secondary outcome was efficacy, i.e., change in best-corrected visual acuity (BCVA) and optical coherence tomography-measured macular thickness and retinal fluid. Results: The mean age was 71.63 ± 8.66. The follow-up period was 2.38 ± 0.79 months. The mean number of brolucizumab injections during the follow-up was 1.52 ± 0.58. The overall incidence of IOI was 13.9% (n = 41 eyes). Most IOI cases were of anterior uveitis (8.8%, 26 eyes), followed by retinal vasculitis (2.4%, seven eyes) and occlusive retinal vasculitis (0.3%, one eye). Most eyes showed IOI resolution (n = 40, 97.5%) and BCVA restoration (n = 39, 95.1%) with or without corticosteroid treatment during the follow-up. Age, sex, IOI history, or other anti-vascular endothelial growth factor injection histories were not associated with the occurrence of IOI. However, only thin subfoveal choroidal thickness (SFCT) was associated with the occurrence of IOI (odds ratio = 0.995, p = 0.020). BCVA at 1 month improved from baseline (baseline 0.518 ± 0.356 vs. 1 month 0.503 ± 0.383, p = 0.023), but the improvement was not maintained. Anatomical improvement was significant after 3 months. Conclusion: In Korean patients with nAMD, the incidence of IOI following brolucizumab injections was 13.9%. IOI was well-controlled with or without steroid treatment. Most IOI eyes (95.1%) were restored to the level of vision before. IOI occurrence and occlusive vasculitis was rare. In the short term, brolucizumab injection effectively improved vision at 1 month and dried retinal fluid for 3 months. [ABSTRACT FROM AUTHOR]

Retinal pigmentosa (RP) patients lose vision due to the loss of photoreceptors. Retinal prostheses bypass the dead photoreceptors by electrically stimulating surviving retinal neurons, such as bipolar cells or retinal ganglion cells (RGCs). In previous studies, stimulus charge has been mainly optimized to maximize the RGC response to electrical stimulation. This study aimed to investigate the effect of amplitude and duration even under the same charge condition on eliciting RGC spikes in the wild-type and degenerate retinas. Wild-type (WT) Sprague–Dawley rats were used as the normal retinal model, and Pde6b knockout rats were used as a retinal degeneration (RD) model. Electrically-evoked RGC spikes were recorded from isolated rat retinas using an 8 × 8 multielectrode array. The same charge was maintained (10 or 20 nC), and electrical stimulation was applied to WT and RD retinas, adjusting the amplitude and duration of the 1st phase of biphasic pulses. In the pulse modulation of the 1st phase, high amplitude (short duration) pulses induced more RGC spikes than low amplitude (long duration) pulses. Both WT and RD retinas showed a significant reduction in the number of RGC spikes upon stimulation with lower amplitude (longer duration) pulses. In clinical trials where stimulus charges are delivered to the degenerate retina of blind patients, high amplitude (short duration) pulses would help elicit more RGC spikes. [ABSTRACT FROM AUTHOR]

Background and Objectives: Ureteral stent insertion passively dilates the ureter. Therefore, it is sometimes used preoperatively before flexible ureterorenoscopy to make the ureter more accessible and facilitate urolithiasis passage, especially when ureteroscopic access has failed or when the ureter is expected to be tight. However, it may cause stent-related discomfort and complications. This study aimed to assess the effect of ureteral stenting prior to retrograde intrarenal surgery (RIRS). Materials and Methods: Data from patients who underwent unilateral RIRS for renal stone with the use of a ureteral access sheath from January 2016 to May 2019 were retrospectively analyzed. Patient characteristics, including age, sex, BMI, presence of hydronephrosis, and treated side, were recorded. Stone characteristics in terms of maximal stone length, modified Seoul National University Renal Stone Complexity score, and stone composition were evaluated. Surgical outcomes, including operative time, complication rate, and stone-free rate, were compared between two groups divided by whether preoperative stenting was performed. Results: Of the 260 patients enrolled in this study, 106 patients had no preoperative stenting (stentless group), and 154 patients had stenting (stenting group). Patient characteristics except for the presence of hydronephrosis and stone composition were not statistically different between the two groups. In surgical outcomes, the stone-free rate was not statistically different between the two groups (p = 0.901); however, the operation time for the stenting group was longer than that of the stentless group (44.8 ± 24.2 vs. 36.1 ± 17.6 min; p = 0.001). There were no differences in the complication rate between the two groups (p = 0.523). Conclusions: Among surgical outcomes for RIRS with a ureteral access sheath, preoperative ureteral stenting does not provide a significant advantage over non-stenting with respect to the stone-free rate and complication rate. [ABSTRACT FROM AUTHOR]

To investigate angiographic characteristic features of diabetic choroidopathy, as well as choroidal vascular density (CVD) and fractal dimension (CFD) in diabetic eyes and controls using ultra-widefield (UWF) indocyanine green angiography (ICGA). All patients underwent UWF fluorescein angiography and ICGA. Using imageJ software, CVD and CFD was analyzed. SFCT was assessed using spectral-domain optical coherence tomography. The image parameters were compared based on the DR stage and the presence of diabetic macular edema (DME). One-hundred six eyes from 63 patients (59.11 ± 16.31 years; male [%]: 23 [36.5%]) were included in the DM group, and 40 eyes from 22 subjects were included in the control group. The DM group had a mean age of 59.11 ± 16.31 years and a mean HbA1c percentage of 7.72 ± 1.28%. The most common ICGA findings of DC were choroidal hyperpermeability (57.5%), hypofluorescent spots (48.1%). Salt and pepper pattern (19.8%), inverted inflow phenomenon (3.8%), choroidal arterial tortuosity (24.5%), and late choroidal non-perfusion (6.6%) were more common in advanced DR. The CVD, CFD, and SFCT increased as the DR severity progressed. The DME group had a significantly higher CFD and SFCT than the non-DME group (P < 0.001 and P = 0.019, respectively). The qualitative and quantitative UWF ICGA image analysis revealed that choroidal blood vessels became dilated, complex, and hyperpermeable as the DR progressed. These features of diabetic choroidopathy (DC) were more severe in eyes with DME than the non-DME eyes. [ABSTRACT FROM AUTHOR]

Microbiota are ecological communities of commensal, symbiotic, and pathogenic microorganisms. The microbiome could be involved in kidney stone formation through hyperoxaluria and calcium oxalate supersaturation, biofilm formation and aggregation, and urothelial injury. Bacteria bind to calcium oxalate crystals, which causes pyelonephritis and leads to changes in nephrons to form Randall's plaque. The urinary tract microbiome, but not the gut microbiome, can be distinguished between cohorts with urinary stone disease (USD) and those without a history of the disease. In the urine microbiome, the role is known of urease-producing bacteria (Proteus mirabilis, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Providencia stuartii, Serratia marcescens, and Morganella morganii) in stone formation. Calcium oxalate crystals were generated in the presence of two uropathogenic bacteria (Escherichia coli and K. pneumoniae). Non-uropathogenic bacteria (S. aureus and Streptococcus pneumoniae) exhibit calcium oxalate lithogenic effects. The taxa Lactobacilli and Enterobacteriaceae best distinguished the healthy cohort from the USD cohort, respectively. Standardization is needed in urine microbiome research for urolithiasis. Inadequate standardization and design of urinary microbiome research on urolithiasis have hampered the generalizability of results and diminished their impact on clinical practice. [ABSTRACT FROM AUTHOR]

To investigate angiographic characteristic features of diabetic choroidopathy, as well as choroidal vascular density (CVD) and fractal dimension (CFD) in diabetic eyes and controls using ultra-widefield (UWF) indocyanine green angiography (ICGA). All patients underwent UWF fluorescein angiography and ICGA. Using imageJ software, CVD and CFD was analyzed. SFCT was assessed using spectral-domain optical coherence tomography. The image parameters were compared based on the DR stage and the presence of diabetic macular edema (DME). One-hundred six eyes from 63 patients (59.11 ± 16.31 years; male [%]: 23 [36.5%]) were included in the DM group, and 40 eyes from 22 subjects were included in the control group. The DM group had a mean age of 59.11 ± 16.31 years and a mean HbA1c percentage of 7.72 ± 1.28%. The most common ICGA findings of DC were choroidal hyperpermeability (57.5%), hypofluorescent spots (48.1%). Salt and pepper pattern (19.8%), inverted inflow phenomenon (3.8%), choroidal arterial tortuosity (24.5%), and late choroidal non-perfusion (6.6%) were more common in advanced DR. The CVD, CFD, and SFCT increased as the DR severity progressed. The DME group had a significantly higher CFD and SFCT than the non-DME group (P < 0.001 and P = 0.019, respectively). The qualitative and quantitative UWF ICGA image analysis revealed that choroidal blood vessels became dilated, complex, and hyperpermeable as the DR progressed. These features of diabetic choroidopathy (DC) were more severe in eyes with DME than the non-DME eyes. [ABSTRACT FROM AUTHOR]

Background and Objectives: Non-contrast computed tomography (NCCT) is widely used to evaluate urolithiasis. The NCCT attenuation, measured in Hounsfield units (HU), has been evaluated to predict stone characteristics. We propose a novel parameter, linear calculus density (LCD), and analyze variables from NCCT imaging to predict calcium oxalate (CaOx) stones, which are common and challenging to fragment. Materials and Methods: We retrospectively reviewed the medical records of patients with urolithiasis between 2014 and 2017. Among those, 790 patients were included. Based on the NCCT pre-treatment, the maximal stone length (MSL), mean stone density (MSD), and stone heterogeneity index (SHI) were obtained. In addition, the variation coefficient of stone density (VCSD = SHI/MSD × 100) and linear calculus density (LCD = VCSD/MSL) were calculated. In accordance with the stone analysis, the patients were divided into two groups (CaOx and non-CaOx groups). The logistic regression model and receiver operating characteristic (ROC) curve were used for predictive modeling. Results: In the CaOx group, the SHI, VCSD, and LCD were more significant than in the non-CaOx group (all p < 0.001). SHI (OR 1.002, 95% CI 1.001–1.004, p < 0.001), VCSD (OR 1.028, 95% CI 1.016–1.041, p < 0.001), and LCD (OR 1.352, 95% CI 1.270–1.444, p < 0.001) were significant independent factors for CaOx stones in the logistic regression models. The areas under the ROC curve for predicting CaOx stones were 0.586 for SHI, 0.66 for VCSD, and 0.739 for LCD, with a cut-point of 2.25. Conclusions: LCD can be a useful new parameter to provide additional information to help discriminate CaOx stones before treatment. [ABSTRACT FROM AUTHOR]

Background: To identify factors associated with microvascular recovery after intravitreal bevacizumab or panretinal photocoagulation (PRP) in diabetic retinopathy (DR). Methods: We retrospectively reviewed 320 eyes/patients with DR treated with intravitreal bevacizumab and/or PRP. Two consecutive fluorescein angiographies (FAs) of each eye were compared. The number of microaneurysms and the area of capillary non-perfusion were calculated automatically using ImageJ software. Microvascular recovery was defined as a marked reduction in the numbers of microaneurysms (< 20%) or a marked reduction in the area of capillary non-perfusion (< 50%) in 45-degree fields or a complete regression of new vessels in ETDRS 7 standard fields. Baseline FA findings and changes in the ocular and systemic factors were analyzed. Results: Twenty-eight (8.8%) of the 320 total eyes were found to meet the criteria of microvascular recovery after the treatments. Multivariate analysis revealed the presence of diffuse capillary telangiectasis (P =.003) and late disc leaking (P =.007) on baseline FA and a reduction of glycated hemoglobin (P =.005) during the follow-up period were predictive factors of microvascular recovery after the treatments. Although the microvascular recovery group presented with a significant improvement of BCVA after the treatments, the baseline BCVA could not predict the microvascular recovery after the treatments. Conclusions: Diffuse capillary telangiectasis or late disc leaking on baseline FA and improved glycemic control positively predicted the microvascular recovery after treatments for DR. [ABSTRACT FROM AUTHOR]

Purpose: To test the safety and feasibility of laser lithotripsy for midsize renal stones using a newly developed robotic retrograde intrarenal surgery (RIRS) system (easyUretero) in a porcine model. Materials and Methods: Three urologic surgeons representing three different RIRS experience levels (beginner, intermediate, and expert) participated. Four female pigs (aged 6 months) underwent manual or robotic RIRS. Under general anesthesia, a nephrostomy tract was created ventrally, and calcium stones (diameter, 1.0–1.5 cm) were inserted at renal calices. For manual RIRS, surgeons operated a flexible ureteroscope. For robotic RIRS, the ureteroscope was attached to the robotic slave device. The Auriga XL™ Holmium laser was used for lithotripsy. Lasering and stone retrieval time were measured. Kidneys and ureters were inspected for injury at the end of each session. Results: For the expert, both lasering and stone retrieval by manual RIRS were quicker than by robotic RIRS (22.8 ± 11.0 s/stone vs 234.5 ± 102.5 s/stone, p = 0.02; 41.5 ± 0.5 s/stone vs 79.3 ± 8.1 s/stone, p = 0.02). For the intermediate and beginner, lasering and stone retrieval times were not significantly different between manual and robotic procedures (127.8 ± 93.2 s/stone vs 284.8 ± 112.3 s/stone, p = 0.08; 86.0 ± 30.5 s/stone vs 84.1 ± 21.4 s/stone, p = 0.92). All stones were removed. Grade 1 ureteral and renal injuries occurred in both manual RIRS and robotic RIRS. Conclusions: The laser lithotripsy using the easyUretero robotic system is safe and feasible in a porcine model, even for less-experienced surgeons. [ABSTRACT FROM AUTHOR]

Background and Objectives: This systematic review and meta-analysis of randomized controlled trials was performed to compare the therapeutic effects and safety profiles of silodosin and tamsulosin for medical expulsive therapy (MET) of ureteral stones. Materials and Methods: We searched PubMed, EMBASE, the Cochrane Library, and Web of Science to identify articles published before July 2022 that described randomized controlled trials comparing silodosin and tamsulosin for MET of ureteral stones. Endpoints were stone expulsion rate, stone expulsion time, and total complication rate. Results: In total, 14 studies were included in our analysis. The size of ureteral stones was <1 cm. Compared with tamsulosin, silodosin resulted in a significantly higher stone expulsion rate (p < 0.01, odds ratio (OR) = 2.42, 95% confidence interval (CI) = 1.91 to 3.06, I2 = 0%) and significantly shorter stone expulsion time (p < 0.01, mean difference = −3.04, 95% CI = −4.46 to −1.63, I2 = 89%). The total complication rate did not significantly differ between silodosin and tamsulosin (p = 0.33, OR = 1.15, 95% CI = 0.87 to 1.52, I2 = 7%). Conclusions: Compared with tamsulosin, silodosin resulted in significantly better expulsion of ureteral stones <1 cm. The total complication rate did not significantly differ between silodosin and tamsulosin. Thus, silodosin may be superior to tamsulosin for MET of ureter stones <1 cm. [ABSTRACT FROM AUTHOR]

Purpose: To investigate long‐term visual outcomes of patients with polypoidal choroidal vasculopathy (PCV) and typical neovascular age‐related macular degeneration (nAMD) in the real‐world setting. Methods: Retrospective, multicenter, noninterventional consecutive cohort study. Two hundred eighty‐five eyes of 261 patients with PCV and 902 eyes of 877 patients with typical nAMD, who could be followed up 1 year or longer from 2005 to 2018, were included. Mean changes in best‐corrected visual acuity (BCVA) from baseline in the PCV and the typical nAMD groups were compared. Results: Mean follow‐up period of total patients was 4.3 ± 2.8 (1–10) years. Baseline BCVA was better in the PCV group than that in the typical nAMD group (0.59 ± 0.52 versus 0.79 ± 0.63 logMAR, p < 0.001). The mean changes in BCVA from baseline in the PCV and nAMD group were +2.1 and −0.1 letters at 1 year, −0.2 and −3.7 letters at 3 years, −3.9 and −10.5 letters at 5 years and − 8.7 and − 12.1 letters at 7 years, respectively. Before 2006, the initial BCVA was sustained for approximately 1 year in eyes with PCV and for less than half year in eyes with typical nAMD. However, after 2007, when anti‐VEGF agents were available, the initial BCVA was sustained for 4 years in eyes with PCV, while it was sustained for 1 year in eyes with typical nAMD. Conclusion: In the real‐world, long‐term BCVA deteriorated in both PCV and typical nAMD groups, but the PCV group showed better visual outcomes than the typical nAMD group. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopamine(DA)rgic neurons in the substantia nigra of the midbrain, and primarily causes motor symptoms. While the pathological cause of PD remains uncertain, oxidative damage, neuroinflammation, and energy metabolic perturbation have been implicated. Pyruvate has been shown neuroprotective in animal models for many neurological disorders, presumably owing to its potent anti-oxidative, anti-inflammatory, and energy metabolic properties. We therefore investigated whether exogenous pyruvate could also protect nigral DA neurons from degeneration and reverse the associated motor deficits in an animal model of PD using the DA neuron-specific toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP (20 mg/kg) was injected four times every 2 h into the peritoneum of mice, which resulted in a massive loss of DA neurons as well as an increase in neuronal death and cytosolic labile zinc overload. There were rises in inflammatory and oxidative responses, a drop in the striatal DA level, and the emergence of PD-related motor deficits. In comparison, when sodium pyruvate was administered intraperitoneally at a daily dose of 250 mg/kg for 7 days starting 2 h after the final MPTP treatment, significant relief in the MPTP-induced neuropathology, neurodegeneration, DA depletion, and motor symptoms was observed. Equiosmolar dose of NaCl had no neuroprotective effect, and lower doses of sodium pyruvate did not have any statistically significant effects. These findings suggest that pyruvate has therapeutic potential for the treatment of PD and related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background and Objectives: During the coronavirus disease 2019 (COVID-19) outbreak, the European Association of Urology (EAU) Guidelines Office Rapid Reaction Group (GORRG) recommended that patients with clinical stage I (CSI) seminoma be offered active surveillance (AS). This meta-analysis aimed to evaluate the efficacy of AS versus adjuvant treatment with chemotherapy or radiotherapy for improving the overall survival (OS) of CSI seminoma patients. Materials and Methods: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed/Medline, EMBASE, and Cochrane Library databases were searched. The primary outcome was 5-year OS, and the secondary outcome was the 5-year relapse-free survival (RFS). The outcomes were analyzed as odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 14 studies were included. Overall, the quality scores were relatively high, and little publication bias was noted. In terms of the 5-year OS, 7 studies were analyzed; there was no significant difference between AS and adjuvant treatment (OR, 0.99; 95% CI, 0.41–2.39; p = 0.97). In terms of 5-year RFS, 12 studies were analyzed. Adjuvant treatment reduced the risk of 5-year recurrence by 85% compared with AS (OR, 0.15; 95% CI, 0.08–0.26; p < 0.001). Conclusions: In terms of the OS in CSI seminoma patients, no intergroup difference was noted, so it is reasonable to offer AS, as recommended by the EAU GORRG until the end of the COVID-19 pandemic. However, since there is a large intergroup difference in the recurrence rate, further research on the long-term (>5 years) outcomes is warranted. [ABSTRACT FROM AUTHOR]

In addition to laser photocoagulation, currently used therapeutic interventions for diabetic retinopathy (DR) include relatively short-lived anti-VEGF drugs targeting vascular endothelial growth factor (VEGF). The latter requires frequent administration via intravitreal injections to effect long-term VEGF suppression. However, due to the patient burden associated with this treatment modality, gene therapy may represent a preferable alternative, providing long-lasting yet patient-friendly effects. Here, we explore the therapeutic efficacy of rAAV2-sVEGFRv-1, a recombinant adeno-associated virus encoding a soluble variant of VEGF receptor-1, upon early DR processes. Bevacizumab, an anti-VEGF agent often prescribed off label to treat DR, was used as an experimental comparator. Administered by intravitreal injection to a streptozotocin-induced diabetic mouse model, rAAV2-sVEGFRv-1 was shown to effectively transduce the mouse retinas and express its transgene therein, leading to significant reductions in pericyte loss and retinal cell layer thinning, two processes that play major roles in DR progression. Acellular capillary formation, vascular permeability, and apoptotic activity, the latter being the cell death mechanism by which retinal neurodegeneration occurs, were also shown to be reduced by the therapeutic virus vector. Immunohistochemistry was used to visualize that rAAV2-sVEGFRv-1 has an effect on cell types important to DR pathophysiology, particularly the ganglion cell layer and glial cells. Combined with our previous work showing that the therapeutic virus vector reduces neovascularization, our current results reveal that rAAV2-sVEGFRv-1 addresses the early aspects of DR as well, thereby demonstrating its potential as a human gene therapeutic versus the condition as a whole. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) aggregates in the brain. Clusterin (CLU), also known as apolipoprotein J, is a potent risk factor associated with AD pathogenesis, in which Aβ aggregation is essentially involved. We observed close colocalization of CLU and Aβ(1–42) (Aβ42) in parenchymal amyloid plaques or vascular amyloid deposits in the brains of human amyloid precursor protein (hAPP)-transgenic Tg2576 mice. Therefore, to elucidate the binding interaction between CLU and Aβ42 and its impact on amyloid aggregation and toxicity, the two synthetic proteins were incubated together under physiological conditions, and their structural and morphological variations were investigated using biochemical, biophysical, and microscopic analyses. Synthetic CLU spontaneously bound to different possible variants of Aβ42 aggregates with very high affinity (Kd = 2.647 nM) in vitro to form solid CLU–Aβ42 complexes. This CLU binding prevented further aggregation of Aβ42 into larger oligomers or fibrils, enriching the population of smaller Aβ42 oligomers and protofibrils and monomers. CLU either alleviated or augmented Aβ42-induced cytotoxicity and apoptosis in the neuroblastoma-derived SH-SY5Y and N2a cells, depending on the incubation period and the molar ratio of CLU:Aβ42 involved in the reaction before addition to the cells. Thus, the effects of CLU on Aβ42-induced cytotoxicity were likely determined by the extent to which it bound and sequestered toxic Aβ42 oligomers or protofibrils. These findings suggest that CLU could influence amyloid neurotoxicity and pathogenesis by modulating Aβ aggregation. [ABSTRACT FROM AUTHOR]

Background and Objectives: Disposable flexible ureteroscopes have been widely used because of their cost-effectiveness and higher sterility potential compared with reusable flexible ureteroscopes. This study aimed to compare the surgical outcomes and complication rates in patients who undergo reusable or disposable flexible ureteroscopic stone surgeries (fURS) for urinary stone disease. Materials and Methods: A systematic review and meta-analysis were conducted under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. This systematic review was registered with PROSPERO (CRD42022331291). Clinical trials comparing reusable and disposable fURS for stone disease were found from PubMed, EMBASE, Cochrane Library, and the Web of Science up to March 2022. Participants were patients with upper urinary tract stones; the interventions were reusable or disposable fURS. Outcomes, including stone-free rate, operation time, length of hospital stay, and complication rate, were compared for analysis. Results: Overall, 111 studies were identified, but after removing duplicate studies, 75 studies remained. Thirty-two of these studies were excluded. Of the 43 screened studies, 11 met the eligibility criteria. There was no difference in the stone-free rate (SFR) between disposable and reusable fURS (p = 0.14; OR = 1.36; 95% CI, 0.9 to 2.04). For operation time, no difference was identified between reusable and disposable fURS groups (p = 0.12; MD = −5.31; 95% CI, −12.08 to 1.46). For hospital stay, there was also no difference between the two groups (p = 0.61; MD = −0.03; 95% CI, −0.17 to 0.10). There was no significant difference in complication rate between the two groups (p = 0.85; OR = 0.95; 95% CI, 0.56 to 1.61). Conclusions: There were no differences in the SFR, operation time, length of hospital stay, and complication rate between reusable and disposable fURS. Disposable fURS may be a comparable alternative to reusable fURS. [ABSTRACT FROM AUTHOR]

Purpose: During the coronavirus disease 2019 (COVID-19) pandemic, the European Association of Urology (EAU) recommended that courses of intravesical bacillus Calmette-Guérin (BCG) therapy lasting more than 1 year could be safely terminated for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Thus, we conducted a systematic review and network meta-analysis according to EAU's COVID-19 recommendations. Materials and methods: A systematic review was performed following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We conducted a network meta-analysis of recurrence rate in patients with NMIBC receiving induction therapy (M0) and those receiving maintenance therapy lasting 1 year (M1) and more than 1 year (M2). Results: Nineteen studies of 3,957 patients were included for the network meta-analysis. In a node-split forest plot using Bayesian Markov Chain Monte Carlo (MCMC) modeling, there were no differences between the M1 and M2 groups in recurrence rate [odds ratio (OR) 0.95 (0.73–1.2)]. However, recurrence rate in the M0 group was higher than that in the M1 [OR 1.9 (1.5–2.5)] and M2 [OR 2.0 (1.7–2.4)] groups. P-score tests using frequentist inference to rank the treatments in the network demonstrated that the therapy used in the M2 group (P-score 0.8701) was superior to that used in the M1 (P-score 0.6299) and M0 groups (P-score 0). In rank-probability tests using MCMC modeling, the M2 group showed the highest rank, followed by the M1 and M0 groups. Conclusion: In the network meta-analysis, there were no differences between those receiving BCG maintenance therapies in terms of recurrence rate. In the rank tests, therapy lasting more than 1-year appears to be most effective. During the COVID-19 pandemic, 1-year maintenance therapy can be used, but after the COVID-19 pandemic, therapy lasting more than 1-year could be beneficial. [ABSTRACT FROM AUTHOR]

Histone deacetylase 6 (HDAC6), a deacetylase of p53, has emerged as a privileged inhibitory target for cancer therapy because of its deacetylating activity for p53 at K120 and K373/382. However, intricate roles of HDAC6 in hepatocellular carcinogenesis have been suggested by recent evidence, namely that HDAC6 ablation suppresses innate immunity, which plays critical roles in tumor immunosurveillance and antitumor immune responses. Therefore, it is valuable to determine whether HDAC6 ablation inhibits hepatocellular carcinogenesis using in vivo animal models. Here, we firstly showed that HDAC6 ablation increased K320 acetylation of p53, known as pro‐survival acetylation, in all tested animal models but did not always increase K120 and K373/382 acetylation of p53, known as pro‐apoptotic acetylation. HDAC6 ablation induced cellular senescence in primary MEFs and inhibited cell proliferation in HepG2 cells and liver regeneration after two‐thirds partial hepatectomy. However, the genetic ablation of HDAC6 did not inhibit hepatocarcinogenesis, but instead slightly enhanced it in two independent mouse models (DEN + HFD and DEN + TAA). Notably, HDAC6 ablation significantly promoted hepatocarcinogenesis in a multiple DEN treatment hepatocellular carcinoma (HCC) mouse model, mimicking chronic DNA damage in the liver, which correlated with hyperacetylation at K320 of p53 and a decrease in inflammatory cytokines and chemokines. Our data from three independent in vivo animal HCC models emphasize the importance of the complex roles of HDAC6 ablation in hepatocellular carcinogenesis, highlighting its immunosuppressive effects. We provide the first evidence that HDAC6 is a p53 deacetylase at K320, which is especially important for cancer cell survival in chronic DNA damage conditions. Contrary to the general assumption that HDAC6 inhibition leads to hyperacetylation of p53 at K120, resulting in tumor suppression, our findings from in vivo animal HCC modelsemphasize the importance of the opposing roles of HDAC6 ablation in hepatocellular carcinogenesis by highlighting the K320 acetylation of p53 and immunosuppressive effects. [ABSTRACT FROM AUTHOR]

Due to the heterogeneity of carbonate rocks, some small pores partially undertaking flows are unresolved in X-ray CT images, therefore have been not appropriately considered in direct flow simulation. By the data fusion of two non-destructive measurements from X-ray CT imaging and nuclear magnetic resonance measurement, this study proposes the construction of ternary-phase domain including resolved apparent-pore, unresolved gray-pore, and resolved solid voxels. Gray-pore voxel containing the unresolved pore is characterized as a microporous structure with equivalent local hydraulic properties according to CT number and pore size distribution. From X-ray CT images of reservoir carbonate rocks from Abu Dhabi, ternary-phase domains are constructed consistently to figure out local and overall flow behaviors despite the different image resolutions. Stokes–Brinkman flow simulation shows that although some apparent-pore volumes are disconnected from each other due to limited resolution, fluid flow can be passed by the gray-pore region. Additionally, a modified hydraulic tortuosity model is proposed to evaluate the tortuosity of the ternary-phase domain because the conventional hydraulic tortuosity model for the binary-phase domain underestimates the tortuosity of the ternary-phase domain. [ABSTRACT FROM AUTHOR]

In addition to laser photocoagulation, therapeutic interventions for diabetic retinopathy (DR) have heretofore consisted of anti-VEGF drugs, which, besides drawbacks inherent to the treatments themselves, are limited in scope and may not fully address the condition's complex pathophysiology. This is because DR is a multifactorial condition, meaning a gene therapy focused on a target with broader effects, such as the mechanistic target of rapamycin (mTOR), may prove to be the solution in overcoming these concerns. Having previously demonstrated the potential of a mTOR-inhibiting shRNA packaged in a recombinant adeno-associated virus to address a variety of angiogenic retinal diseases, here we explore the effects of rAAV2-shmTOR-SD in a streptozotocin-induced diabetic mouse model. Delivered via intravitreal injection, the therapeutic efficacy of the virus vector upon early DR processes was examined. rAAV2-shmTOR-SD effectively transduced mouse retinas and therein downregulated mTOR expression, which was elevated in sham-treated and control shRNA-injected (rAAV2-shCon-SD) control groups. mTOR inhibition additionally led to marked reductions in pericyte loss, acellular capillary formation, vascular permeability, and retinal cell layer thinning, processes that contribute to DR progression. Immunohistochemistry showed that rAAV2-shmTOR-SD decreased ganglion cell loss and pathogenic Müller cell activation and proliferation, while also having anti-apoptotic activity, with these effects suggesting the therapeutic virus vector may be neuroprotective. Taken together, these results build upon our previous work to demonstrate the broad ability of rAAV2-shmTOR-SD to address aspects of DR pathophysiology further evidencing its potential as a human gene therapeutic strategy for DR. [ABSTRACT FROM AUTHOR]

Background: Robotic‐assisted radical prostatectomy(RARP) is widely used to surgically treat of localized prostate cancer. Among RARP, retzius-sparing techniques(RS-RARP) are implemented through douglas pouch, not the existing conventional approach(C-RARP). We conducted an updated systematic review and meta-analysis including recent published papers. Materials & methods: Systematic review was performed following the PRISMA guideline. PubMed, EMBASE, and Cochrane Library were searched up to August 2021. We conducted meta-analysis as follows; Participants, patients with biopsy-proven PCa; Interventions, Patients underwent C-RARP or RS-RALP; Outcomes, comparison of continence recovery rate, positive surgical margins(PSM), complication, operation time and estimated blood loss(EBL) included for analysis. Results: Thirteen studies with a total of 2917 patients were included for meta-analysis. Among them, three were randomized controlled trials (RCT) studies and the rest were non-RCT studies. Incontinence was analyzed with zero pad and safety pad, respectively. There showed a statistically significant advantage for RS-RARP in terms of continence recovery at 1 month(0 pad; OR 0.28, (0.16–0.47), safety-pad; OR 0.12 (0.07–0.22), p<0.001), as well as at 3 months(0 pad; OR 0.31 (0.18–0.53), safety-pad; OR 0.23 (0.14–0.40) p<0.001), 6 months(0 pad; OR 0.29 (0.17–0.51), safety-pad; OR 0.13 (0.06–0.27), p<0.001). And after 12 months, RS-RARP showed better results only in the safety-pad(0 pad; OR 0.64 (0.35–1.18), p = 0.15, safety-pad; OR 0.12 (0.04–0.36), p<0.001). In PSM, there was no statistical difference between two group at overall stage, but RS-RARP was observed to be higher than C-RARP in pT3 subgroup analysis(OR 0.74 (0.55–0.99), p = 0.047) (Fig 1). Whereas, there was no significant difference between the two groups in complication, operation time, and EBL. Conclusions: Our analysis showed that RS-RARP is superior about early continence recovery than C-RARP. However, RS-RARP showed relatively high PSM in locally advanced PCa of pT3 or above. Therefore, although RS-RARP has few advantages about functional outcomes, we think that caution should be exercised when approaching patients with high-risk local diseases. [ABSTRACT FROM AUTHOR]

We investigate the feasibility of electromagnetic (EM) geophysics methods to detect the dissociation of gas hydrate specifically from a gas hydrate deposit located in the Ulleung Basin, East Sea, Korea via an integrated flow-geomechanics-EM geophysics simulation. To this end, coupled flow and geomechanics simulation is first performed with the multiple porosity model employed, where a mixed formulation with the finite volume (FV) and finite element (FE) methods are taken for the flow and geomechanics, respectively. From the saturation and porosity fields obtained from the coupled flow and geomechanics, the electrical conductivity model is established for the EM simulation. Solving the partial differential equation of electrical diffusion which is linearized using the 3D finite element method (FEM), the EM fields are then computed. For numerical experiments, particularly two approaches in the configuration for the EM methods are compared in this contribution: the surface-to-surface and the surface-to-borehole methods. When the surface-to-surface EM method is employed, the EM is found to be less sensitive, implying low detectability. Especially for the short term of production, the low detectability is attributed to the similarity of electrical resistivity between the dissociated gas (CH 4 ) and hydrate as well as the specific dissociation pattern within the intercalated composites of the field. On the other hand, when the surface-to-borehole EM method is employed, its sensitivity to capture the produced gas flow is improved, confirming its detectability in monitoring gas flow. Hence, the EM geophysics simulation integrated with coupled flow and geomechanics can be a potential tool for monitoring gas hydrate deposits. [ABSTRACT FROM AUTHOR]

Purpose: In the context of the COVID-19 outbreak, the European Association of Urology (EAU) guidelines Rapid Reaction Group provided recommendations to manage muscle invasive bladder cancer (MIBC) based on priority levels: neoadjuvant chemotherapy (NAC) should be avoided for patients with T2-3N0M0 MIBC. This meta-analysis aims to evaluate the efficacy of NAC compared with radical cystectomy (RC) alone in improving the overall survival (OS) of patients with T2-4aN0M0 MIBC. Materials and methods: A systematic review was performed according to the PRISMA guidelines. The PubMed/Medline, EMBASE, and Cochrane Library databases were searched. The primary outcome was OS of patients with T2-4aN0M0 MIBC, and the secondary outcome was OS of patients with only T2N0M0 MIBC. Results: Eight studies were included in this meta-analysis. Overall, the quality of all studies was relatively high, and little publication bias was demonstrated. The OS was significantly better in the NAC with RC group than in RC alone (HR, 0.79; 95% CI, 0.68–0.92; p = 0.002). A subgroup analysis was performed on only patients with T2N0M0 MIBC, and five studies were included. There was no difference in the OS between the NAC with RC and the RC alone groups (HR, 0.83; 95% CI, 0.69–1.01 p = 0.06). Conclusions: As recommended by the EAU guidelines Rapid Reaction Group, patients with T2N0M0 MIBC should strongly consider omitting NAC until the end of the COVID-19 pandemic. Whether to omit NAC in T3-4aN0M0 MIBC needs further discussion, and studies targeting only T2-3N0M0 MIBC are expected to proceed further. [ABSTRACT FROM AUTHOR]

Introduction: A single dose of preventive antibiotics is known to be sufficient to reduce the rate of infection-related complications in percutaneous nephrolithotomy (PCNL). However, some studies reported that the extended dose showed lower complications for high-risk groups. Therefore, we performed a systematic review and meta-analysis comparing single- and extended-dose antibiotic prophylaxis for PCNL. Materials and methods: Relevant studies that compared single- and extended-dose antibiotic prophylactic therapies were identified. Articles were selected from PubMed, EMBASE, KoreaMed, and Google Scholar up to September 2021. Fever and systemic inflammatory response syndrome (SIRS) were compared by meta-analysis. A subgroup analysis was performed according to the degree of risk to the patient. Results: A total of 10 articles were included in this study. There were no significant differences between single dose and extended dose in the rate of fever [p = 0.93, OR = 0.96, 95% confidence interval (CI) 0.44–2.13, I2 = 64%]. Extended dose showed lower rate of SIRS compared to single dose (p = 0.0005, OR = 1.81, 95% CI 1.30–2.53, I2 = 53%); in the subgroup analysis, extended dose also showed lower rates of SIRS compared to single dose in high-risk patients (p <0.0001, OR = 3.53, 95% CI 1.91–6.54, I2 = 36%). Conclusions: The results of our meta-analysis showed that single-dose antibiotic prophylaxis can be effective for PCNL, but extended-dose antibiotics can be required in high-risk patients to reduce post-PCNL infection-related complications. [ABSTRACT FROM AUTHOR]

Miniaturized percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) for renal stones have been developed to overcome the invasive disadvantages of PCNL. We aimed to compare the therapeutic effect and safety of ultra-mini percutaneous nephrolithotomy (UMPCNL) and RIRS for renal stones using an updated systematic review and meta-analysis. We searched clinical trials comparing UMPCNL and RIRS for renal stones using the PubMed, EMBASE, Cochrane Library, and Google Scholar databases up to October 2021. Seven studies were included in the current study. The renal stone size was 10–20 mm in three studies, 10–25 mm in one study, 10–35 mm in two studies, and not specified in one study. The stone-free rate of UMPCNL was higher than that of RIRS (p = 0.02; odds ratio (OR) = 2.01; 95% confidence interval (CI) = 1.12, 3.61). The complication rate showed no significant difference between UMPCNL and RIRS (p = 0.48; OR = 1.20; 95% CI = 0.73, 1.98). Regarding the operative time, UMPCNL was shorter than RIRS (p = 0.005; weighted mean difference (WMD) = −15.63; 95% CI = −26.60, −4.67). The hospital stay of UMPCNL was longer than that of RIRS (p = 0.0004; WMD = 1.48; 95% CI = 0.66, 2.31). UMPCNL showed higher efficacy than RIRS and similar safety to RIRS. UMPCNL may be a useful therapeutic option for moderate-sized renal stones. [ABSTRACT FROM AUTHOR]

Expanding on previous demonstrations of the therapeutic effects of adeno‐associated virus (AAV) carrying small‐hairpin RNA (shRNA) in downregulating the mechanistic target of rapamycin (mTOR) in in vivo retinal vascular disorders, vascular endothelial growth factor (VEGF)‐stimulated endothelial cells were treated with AAV2‐shmTOR to examine the role of mTOR inhibition in retinal angiogenesis. AAV2‐shmTOR exposure significantly reduced mTOR expression in human umbilical vein endothelial cells (HUVECs) and decreased downstream signaling cascades of mTOR complex 1 (mTORC1) and mTORC2 under VEGF treatment. Moreover, the angiogenic potential of VEGF was significantly inhibited by AAV2‐shmTOR, which preserved endothelial integrity by maintaining tight junctions between HUVECs. These data thus support previous in vivo studies and provide evidence that AAV2‐shmTOR induces therapeutic effects by inhibiting the neovascularization of endothelial cells. [ABSTRACT FROM AUTHOR]

Gas hydrate exploration was conducted using logging-while-drilling (LWD) and wireline logging (WLL) at two sites (UBGH2-6 and UBGH2-10) in the Ulleung Basin, East Sea (Sea of Japan). Coring for gas hydrate sampling was also conducted. Seismic profiles revealed that the upper layers at the logged sites (∼180 m at UBGH2-6 and ∼150 m at UBGH2-10) are dominated by turbidite/hemipelagic sediments, whereas the lower-lying sediments are characterised by thick mass transport deposits. Except in the gas hydrate-bearing interval (140–160 metres below the seafloor) of UBGH2-6, the WLL velocity and resistivity data are a little higher (∼100 m/s and ∼0.4 ohm-m, respectively) than those indicated by LWD. Conversely, the density and porosity do not show a consistent pattern for the two methods. Discrepancies between LWD and WLL can be caused by the methodology, borehole condition, and gas hydrate occurrence type. The high resistivity values (∼100 ohm-m) in the gas hydrate-bearing zone of UBGH2-6 are typical of inclined fracture-filling gas hydrate. In this case, the LWD resistivity may be overestimated as a result of the data acquisition principle. The relationships between the physical properties are significantly controlled by the presence of gas hydrate. Therefore, in fracture-filling gas hydrate-bearing sediments, the WLL resistivity data are more reasonable than the LWD resistivity data. Both methods have advantages and disadvantages in terms of data quality, efficiency, and resolution. Therefore, it is necessary to compare and interpret data measured using both methods to identify the physical properties of gas hydrate-bearing sediments. [ABSTRACT FROM AUTHOR]

Purpose. Retinitis pigmentosa (RP) shows great diversity between genotypes and phenotypes, and it is important to identify the causative genes. This study aimed to analyze the molecular profiles, associated ocular characteristics, and progression of RP in Korean patients. Methods. All the genetic variants in patients with RP, identified using targeted next-generation sequencing (NGS) with a panel of 88 RP-related genes between November 2018 and November 2019, were retrospectively reviewed. All the patients underwent comprehensive ophthalmological evaluations, and their clinical and family histories were recorded. The best-corrected visual acuity (BCVA) deterioration and photoreceptor disruption progression rates were determined based on the major causative mutational genes using nonlinear mixed models, and the differences among them were investigated using the interaction effect. Results. Among the 144 probands, 82 variants in 24 causative genes were identified in 77 families (53.5%). Most of the RP cases were associated with autosomal recessive variants (N = 64 (44.4%)), followed by autosomal dominant (N = 10 (6.9%)) and X-linked variants (N = 3 (2.1%)). The four most frequently affected genes were EYS (N = 15 (10.4%)), USH2A (N = 12 (8.3%)), PDE6B (N = 9 (6.3%)), and RP1 (N = 8 (5.6%)). Epiretinal membranes and cystoid macular edema were frequently noted in the patients with USH2A (75.0%) and PDE6B (50.0%) variants, respectively. During the follow-up period, the BCVA and photoreceptor disruption changes were significantly different among the patients carrying the four common causative genes (P = 0.014 and 0.034, resp.). Patients with PDE6B variants showed faster BCVA changes (0.2 LogMAR/10 years), and those with USH2A variants showed the fastest ellipsoid zone disruptions (−170.4 µm/year). Conclusion. In conclusion, our genetic analysis using targeted NGS provides information about the prevalence of RP-associated mutations in Korean patients. Delineating clinical characteristics according to genetic variations may help clinicians identify subtype features and predict the clinical course of RP. [ABSTRACT FROM AUTHOR]

The depressurization method is known as the most productive and effective method for successful methane recovery from hydrate deposits. However, this method can cause considerable subsidence because of the increased effective stress. Maintenance of geomechanical stability is necessary for sustainable production of gas from gas hydrate deposits. In this study, the cyclic depressurization method, which uses changing the bottomhole pressure and production time during primary and secondary depressurization stage, was utilized in order to increase stability in the Ulleung Basin of the Korea East Sea. Various case studies were conducted with alternating bottomhole pressure and production time of the primary and secondary depressurization stages over 400 days. Geomechanical stability was significantly enhanced, while cumulative gas production was relatively less reduced or nearly maintained. Specially, the cumulative gas production of the 6 MPa case was more than three times higher than that of the 9 MPa case, while vertical displacement was similar between them. Therefore, it was found that the cyclic depressurization method should be applied for the sake of geomechanical stability. [ABSTRACT FROM AUTHOR]

To evaluate the long-term outcomes of ranibizumab (RBZ) vs. aflibercept (AFL) in treatment-naïve eyes with typical neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). This multicenter, retrospective, matched-cohort analysis was conducted on data up to 4 years of follow-ups. The primary outcome was the visual acuity (VA) change from baseline. The secondary outcomes included the number of injections, proportion of eyes without a yearly injection, and the number of eyes with treatment switching. Subgroup analyses were performed for typical nAMD and PCV. Typical nAMD was defined as nAMD other than PCV. We included VA-matched 215 eyes of 209 patients (131 and 84 eyes with RBZ and AFL, respectively). The crude mean VA changes from baseline were + 6.7 vs. + 2.6, + 2.1 vs. − 0.4, − 1.3 vs. − 1.8, and − 2.2 vs. − 5.0 letters in the RBZ and AFL groups, at 1, 2, 3, and 4 years, respectively (p > 0.05). The adjusted predicted VA by linear mixed model, proportion of eyes stratified by VA, and the survival curve for significant vision loss were comparable during the 4-year follow-up (p > 0.05). The mean number of injections were similar between the RBZ and AFL groups (2.9 vs. 3.0, respectively, p = 0.692). The subgroup analysis for typical nAMD and PCV showed similar results between the groups. The visual outcomes did not differ between RBZ and AFL during 4 years with comparable numbers of injections. Our study reflects the long-term, real-world clinical practice and treatment pattern of two treatments for typical nAMD and PCV. [ABSTRACT FROM AUTHOR]

Purpose: To compare the functional and anatomical outcomes of central retinal vein occlusion (CRVO) according to the presence of glaucoma before the onset of CRVO, and to assess whether pre‐existing glaucoma affects the prognosis of CRVO in terms of development and conversion to ischaemic CRVO. Methods: In this retrospective cohort study, patients with treatment‐naïve CRVO were enrolled between December 2009 and February 2019. The patients were classified into two groups according to the presence of pre‐existing primary open‐angle glaucoma at CRVO diagnosis. We reviewed medical records regarding basic demographics, ocular characteristics and treatments. The effects of pre‐existing glaucoma on the occurrence of ischaemic CRVO were also investigated using Cox proportional hazard models. Results: Of 166 eyes from 166 patients, 26 (15.7%) had pre‐existing glaucoma. The pre‐existing glaucoma group revealed significantly older (69.4 ± 13.3 versus 56.5 ± 15.9) and lower BCVA at baseline (1.06 ± 0.75 versus 0.64 ± 0.58, logMAR) and final visits (1.56 ± 1.35 versus 0.64 ± 0.48, logMAR) (all p < 0.05) than non‐glaucomatous group. In terms of perfusion status of CRVO, the glaucoma group showed higher incidence of ischaemic CRVO (30.8% versus 5.3%, p = 0.052) at initial and last visits as well as more disorganization of retinal inner layers (DRIL) at 3 months (76.0% versus 49.6%, p = 0.015). Pre‐existing glaucoma (hazard ratio (HR) = 2.141, p = 0.014), lower vision at baseline (HR = 2.071, p = 0.001) and DRIL at 3 months (HR = 2.905, p = 0.011) were significant risk factors for the occurrence of ischaemic CRVO. Conclusion: In patients with CRVO, pre‐existing glaucoma was associated with poorer visual and anatomical outcomes, and played as a significant risk factor for the development and conversion to ischaemic CRVO with lower vision and presence of DRIL at early phase of CRVO. [ABSTRACT FROM AUTHOR]

Purpose: To investigate and compare the clinical features of cytomegalovirus (CMV) retinitis after solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) and to determine the poor prognostic factors. Methods: Patients consulted to the ophthalmology department for CMV viremia after transplantation between March 2008 and February 2018 and followed for more than 6 months were analyzed. Medical records regarding demographic, serologic, and ocular characteristics were compared between the SOT and HSCT groups. Factors associated with poor visual outcomes were determined with logistic regression. Results: CMV retinitis developed in 11.3% of patients with CMV viremia following transplantation. In the SOT group (25 eyes/18 patients) and the HSCT group (33 eyes/21 patients), CMV retinitis occurred at 5.8 months and 3.7 months post-transplantation, respectively. Mortality was significantly higher in the HSCT group (52.4% vs. 5.6%, P < 0.001). During the mean 11.7 months of follow-up, visual acuity tended to be aggravated (P = 0.087) despite antiviral treatment, which was especially notable in the SOT group (P = 0.028). Six eyes (10.3%) underwent vitrectomy due to retinal detachment, most of which (5 eyes) were in the SOT group. Multivariate logistic regression analysis showed that the presence of concurrent CMV disease (OR = 14.11, P = 0.009) and foveal involvement (OR = 114.85, P = 0.001) were poor prognostic factors. Conclusion: Clinical manifestations of CMV retinitis differed between the HSCT and SOT group. Concurrent CMV diseases and foveal involvement were associated with poor visual outcomes in CMV retinitis following transplantation. [ABSTRACT FROM AUTHOR]