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HDAC6 has been reported as a deacetylase of p53 at multiple lysine residues, associated with the canonical functions of p53, such as apoptosis and tumor suppression. We have previously reported that p53 acetylation at the lysine 320 site accumulates due to the genetic ablation of HDAC6 in mice liver. However, the biological processes affected by K320 acetylation of p53 are yet to be elucidated. In this study, we demonstrate that K320 acetylation of p53 is regulated by HDAC6 deacetylase activity. HDAC6 knockout mouse brains exhibit a significant accumulation of K320 acetylated p53 compared to other tissues. The level of K320 acetylation of p53 inversely correlates with the level of BNIP3, a direct target of p53 and essential for mitophagy. Notably, overexpressing the deacetylation mimic K320R mutant p53 restored BNIP3 expression in HDAC6 knockout MEFs. Furthermore, we observed that neurons are particularly susceptible to the genetic ablation of HDAC6, impacting BNIP3 expression, which inversely correlates with the accumulation of abnormal mitochondria characterized by swollen cristae. Our findings suggest that HDAC6 plays a crucial role in maintaining BNIP3 expression by deacetylating p53 at the K320 site, which is linked to the structural integrity of mitochondria.
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Lisina , Proteína p53 Supresora de Tumor , Ratones , Animales , Lisina/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Procesamiento Proteico-Postraduccional , Neuronas/metabolismo , Mitocondrias/metabolismo , Ratones NoqueadosRESUMEN
PURPOSE: To analyze cardiovascular and cerebrovascular adverse events (ADRs) after intravitreal anti-vascular endothelial growth factor (VEGF; aflibercept, bevacizumab, brolucizumab, and ranibizumab) treatment. SUBJECTS: VigiBase, a World Health Organization (WHO) global safety report database DESIGN: Pharmacovigilance study METHODS: The individual-case-safety reports (ICSR) of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment were compared with those reported in the full database. From 2004 to 2023, 23,129 ADRs after intravitreal anti-VEGF therapy and 25,015,132 ADRs associated with any drug (full database). MAIN OUTCOME MEASURES: The reporting odds ratio (ROR) and information components (IC) were calculated, and the 95% lower credibility interval endpoint of the information component (IC025) was used for disproportionate Bayesian reporting. Inter-drug comparisons were performed using the ratio of odd ratio (rOR). RESULTS: Compared with the full database, anti-VEGFs were associated with an increased reporting of myocardial infarction (IC025 0.75; ROR: 1.78 [95% CI 1.70-1.86]), angina pectoris (IC025 0.53; ROR: 1.61 [95% CI 1.47-1.77]), arrythemias including atrial fibrillation, atrial flutter, ventricular fibrillation, supraventricular tachycardia (all IC025 >0, ROR>1), hypertension (IC025 2.22; ROR: 4.91 [95% CI 4.82-5.01]), and hypertensive crisis (IC025 1.97; ROR: 4.49 [95% CI 4.07-4.97]). Moreover, anti-VEGFs were associated with a higher reporting of cerebrovascular ADRs such as cerebral infarction (IC025 4.34; ROR: 23.19 [95% CI 22.10-24.34]), carotid artery stenosis (IC025 1.85; ROR: 5.24 [95% CI 3.98-6.89]), cerebral hemorrhage (IC025 2.29; ROR: 5.38 [95% CI 5.03-5.76]), and subarachnoid hemorrhage (IC025 1.98; ROR: 4.81 [95% CI 4.14-5.6]). Inter-drug comparison indicated that compared to ranibizumab, patients with aflibercept showed overall under-reporting of cardiovascular and cerebrovascular ADRs such as myocardial infarction (rOR 0.55 [95% CI 0.49-0.52]), atrial fibrillation (rOR 0.28 [95% CI 0.23-0.35]), cerebrovascular accident (rOR, 0.15 [95% CI 0.14-0.17]), and cerebral hemorrhage (rOR, 0.51 [95% CI 0.40-0.65]). CONCLUSIONS: In this pharmacovigilance case-noncase study, significantly increased reporting of cardiovascular and cerebrovascular ADRs were identified after intravitreal anti-VEGF treatment. While ranibizumab may exhibit superior systemic safety regarding its biological characteristics, it is crucial not to overlook the occurrence of cardiovascular and cerebrovascular ADRs considering its higher reporting rate than bevacizumab or aflibercept.
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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.
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Dexametasona , Implantes de Medicamentos , Cirugía Filtrante , Glaucoma , Glucocorticoides , Presión Intraocular , Inyecciones Intravítreas , Humanos , Dexametasona/administración & dosificación , Presión Intraocular/fisiología , Presión Intraocular/efectos de los fármacos , Estudios Retrospectivos , Glucocorticoides/administración & dosificación , Femenino , Masculino , Anciano , Cirugía Filtrante/métodos , Glaucoma/cirugía , Glaucoma/fisiopatología , Estudios de Seguimiento , Persona de Mediana Edad , Tonometría Ocular , Agudeza VisualRESUMEN
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.
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Nefrostomía Percutánea , Stents , Infecciones Urinarias , Urolitiasis , Humanos , Tiempo de Internación/estadística & datos numéricos , Nefrostomía Percutánea/métodos , Stents/efectos adversos , Resultado del Tratamiento , Urolitiasis/complicaciones , Urolitiasis/cirugíaRESUMEN
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.
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Cálculos Renales , Trasplante de Riñón , Urolitiasis , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pueblo Asiatico , Riñón , Trasplante de Riñón/efectos adversos , Urolitiasis/etiología , República de CoreaRESUMEN
Klebsiella pneumoniae bacteremia is known to present a virulent clinical course, including multiple metastatic infections, which is not uncommon in Asia. However, there are limited data on the incidence and risk factors for ocular involvement in K. pneumoniae bacteremia. We retrospectively reviewed the medical records of all patients with K. pneumoniae bacteremia who underwent ophthalmologic examination in a tertiary center in Seoul, Korea, from February 2012 to December 2020. Two retinal specialists reviewed the findings of the ophthalmologic examinations and classified them as endophthalmitis, chorioretinitis, and no ocular involvement. Of 689 patients, 56 [8.1%; 95% confidence interval (CI) 6.2-10.4] had ocular involvement, and 9 (1.3%; 95% CI 0.6-2.5) were diagnosed with endophthalmitis. Of 47 patients with chorioretinitis, 45 (95.7%) improved with systemic antibiotic therapy alone. Community-onset bacteremia (100% vs 62.1% vs 57.4%, P = 0.04), cryptogenic liver abscess (55.6% vs 11.8% vs 8.5%, P = 0.003), and metastatic infection (66.7% vs 5.8% vs 10.6%, P < 0.001) were more common in endophthalmitis than in no ocular involvement or chorioretinitis. In the multivariable analysis, cryptogenic liver abscess [adjusted odds ratio (aOR), 6.63; 95% CI 1.44-35.20] and metastatic infection (aOR, 17.52; 95% CI 3.69-96.93) were independent risk factors for endophthalmitis. Endophthalmitis was not associated with 30-day mortality. Endophthalmitis is rare in Asian patients with K. pneumoniae bacteremia. Targeted ophthalmologic examination in those with cryptogenic liver abscess, metastatic infection, or ocular symptoms may be more appropriate than routine examination of all patients.
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Bacteriemia , Coriorretinitis , Endoftalmitis , Infecciones por Klebsiella , Absceso Hepático , Humanos , Klebsiella pneumoniae , Incidencia , Estudios Retrospectivos , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/epidemiología , Antibacterianos/uso terapéutico , Absceso Hepático/tratamiento farmacológico , Endoftalmitis/tratamiento farmacológico , Endoftalmitis/epidemiología , Coriorretinitis/complicaciones , Coriorretinitis/tratamiento farmacológico , Bacteriemia/epidemiología , Factores de RiesgoRESUMEN
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.
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Antineoplásicos , Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Sunitinib/uso terapéutico , Axitinib/uso terapéutico , República de Corea/epidemiología , Antineoplásicos/uso terapéuticoRESUMEN
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.
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Hidronefrosis , Neoplasias Renales , Pólipos , Uréter , Neoplasias Ureterales , Humanos , Ureteroscopía , Constricción Patológica , Neoplasias Ureterales/cirugía , Uréter/diagnóstico por imagen , Uréter/cirugía , Pólipos/cirugía , Hidronefrosis/etiología , Hidronefrosis/cirugíaRESUMEN
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.
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Diabetes Mellitus , Retinopatía Diabética , Microaneurisma , Humanos , Bevacizumab/uso terapéutico , Retinopatía Diabética/cirugía , Retinopatía Diabética/tratamiento farmacológico , Inhibidores de la Angiogénesis/uso terapéutico , Estudios Retrospectivos , Coagulación con Láser , Angiografía con Fluoresceína , Inyecciones Intravítreas , Tomografía de Coherencia ÓpticaRESUMEN
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.
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Degeneración Macular , Vasculitis Retiniana , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Inflamación , RetinaRESUMEN
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.
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Glaucoma , Presión Intraocular , Humanos , Ratones , Animales , Células Ganglionares de la Retina/metabolismo , Fibronectinas/metabolismo , Tiorredoxinas/metabolismo , Células HeLa , Transferasas/metabolismo , Glaucoma/genética , Glaucoma/terapia , Glaucoma/metabolismo , Modelos Animales de EnfermedadRESUMEN
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.
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Cálculos Urinarios , Urolitiasis , Humanos , Ureteroscopios , Ureteroscopía , Inteligencia Artificial , Estudios Retrospectivos , Urolitiasis/cirugía , Cálculos Urinarios/cirugía , Redes Neurales de la ComputaciónRESUMEN
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.
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Cálculos Renales , Nefrolitotomía Percutánea , Nefrostomía Percutánea , Uréter , Adulto , Humanos , Ureteroscopía , Nefrostomía Percutánea/métodos , Cálculos Renales/cirugía , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
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.
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Hidronefrosis , Cálculos Renales , Uréter , Urolitiasis , Humanos , Uréter/cirugía , Estudios Retrospectivos , Urolitiasis/cirugía , Ureteroscopía , Cálculos Renales/cirugía , Hidronefrosis/cirugía , Stents , Resultado del TratamientoRESUMEN
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.
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Cálculos , Urolitiasis , Humanos , Oxalato de Calcio , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
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.
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Carcinoma Hepatocelular , Histona Desacetilasa 6 , Neoplasias Hepáticas , Regeneración Hepática , Acetilación , Animales , Carcinogénesis/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Histona Desacetilasa 6/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Ratones , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
PURPOSE: The study aimed to evaluate the macular microvasculature of X-linked retinoschisis (XLRS) and identify correlations between vascular changes, structural changes, and functional outcome. METHODS: Genetically confirmed XLRS patients and heathy control subjects underwent complete ophthalmic examination, dilated funduscopic examination, optical coherence tomography, and optical coherence tomography angiography. Schisis distribution, outer plexiform layer discontinuation, photoreceptor layer thickness, and photoreceptor outer segment length were reviewed using optical coherence tomography. Vascular flow density and foveal thickness at foveal and parafoveal area were measured using optical coherence tomography angiography. RESULTS: A total of 17 eyes of 9 XLRS patients and 22 eyes of 11 control subjects were examined from July 2018 to August 2020. Flow density in the deep capillary plexus at foveal and parafoveal area decreased in XLRS patients compared with control subjects (P = 0.014 and 0.001, respectively), whereas foveal avascular zone area and perimeter remarkably increased (P = 0.015 and 0.001, respectively). Although outer and total retinal layers were significantly thicker in XLRS, inner retinal layer was thinner with reduced photoreceptor layer thickness and shortened photoreceptor outer segment length (P < 0.001 and P < 0.001, respectively). Foveal flow loss in deep capillary plexus, foveal avascular zone enlargement, thinner inner retina and photoreceptor layer thickness, and shortened photoreceptor outer segment length correlated with best-corrected visual acuity. CONCLUSION: X-linked retinoschisis eyes exhibit decreased flow density in the deep capillary plexus and variable foveal avascular zone with enlarged perimeter. Structural deterioration of the photoreceptor best reflects the degenerative changes, whereas microvascular alteration shows considerable correlation with functional outcome in XLRS.
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Retinosquisis , Angiografía con Fluoresceína/métodos , Fóvea Central , Humanos , Microvasos , Vasos Retinianos/diagnóstico por imagen , Retinosquisis/diagnóstico por imagen , Retinosquisis/genética , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Agudeza VisualRESUMEN
PURPOSE: To demonstrate the effects of epiretinal membrane (ERM) and epiretinal proliferation on surgical outcomes for full-thickness macular hole. METHODS: Nested case-control study with propensity score matching. Patients operated on for full-thickness macular hole between January 2011 and March 2020 were enrolled. The primary outcome was failure of the macular hole closure, and the secondary outcome was unfavorable hole closure (V or λ type closure) at 6 months after the surgery. RESULTS: Five hundred and thirty-four eyes of 534 patients met the inclusion criteria. After 1:1 propensity score matching (127 pairs), patients demonstrating ERM were more likely to have a failure of hole closure (adjusted odds ratio, 2.71; 95% confidence interval, 1.19-6.14) and unfavorable hole closure (adjusted odds ratio, 2.07; 95% confidence interval, 1.16-3.71). Epiretinal membrane spanning the hole margin (hole marginal ERM) greatly increased the likelihood of unfavorable hole closure (adjusted odds ratio, 2.13; 95% confidence interval, 1.12-4.07). Patients with hole marginal-ERM + epiretinal proliferation were more likely to have a failure of hole closure (38.4%) compared with those with no ERM (11.8%). CONCLUSION: Patients with ERM had a higher risk for adverse surgical outcomes for full-thickness macular hole closure. The location of the ERM relative to the macular hole and the presence of epiretinal proliferation might affect the surgical outcomes for full-thickness macular hole closure.
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Membrana Epirretinal/etiología , Mácula Lútea/diagnóstico por imagen , Complicaciones Posoperatorias , Perforaciones de la Retina/complicaciones , Tomografía de Coherencia Óptica/métodos , Vitrectomía/efectos adversos , Anciano , Membrana Epirretinal/diagnóstico , Membrana Epirretinal/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , República de Corea/epidemiología , Perforaciones de la Retina/diagnóstico , Perforaciones de la Retina/cirugía , Estudios Retrospectivos , Factores de TiempoRESUMEN
As a central feature of neuroinflammation, microglial dysfunction has been increasingly considered a causative factor of neurodegeneration implicating an intertwined pathology with amyloidogenic proteins. Herein, we report the smallest synthetic molecule (N,N'-diacetyl-p-phenylenediamine [DAPPD]), simply composed of a benzene ring with 2 acetamide groups at the para position, known to date as a chemical reagent that is able to promote the phagocytic aptitude of microglia and subsequently ameliorate cognitive defects. Based on our mechanistic investigations in vitro and in vivo, 1) the capability of DAPPD to restore microglial phagocytosis is responsible for diminishing the accumulation of amyloid-ß (Aß) species and significantly improving cognitive function in the brains of 2 types of Alzheimer's disease (AD) transgenic mice, and 2) the rectification of microglial function by DAPPD is a result of its ability to suppress the expression of NLRP3 inflammasome-associated proteins through its impact on the NF-κB pathway. Overall, our in vitro and in vivo investigations on efficacies and molecular-level mechanisms demonstrate the ability of DAPPD to regulate microglial function, suppress neuroinflammation, foster cerebral Aß clearance, and attenuate cognitive deficits in AD transgenic mouse models. Discovery of such antineuroinflammatory compounds signifies the potential in discovering effective therapeutic molecules against AD-associated neurodegeneration.
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Enfermedad de Alzheimer/tratamiento farmacológico , Antiinflamatorios/farmacología , Cognición/efectos de los fármacos , Microglía/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Fagocitosis/efectos de los fármacos , Fenilendiaminas/farmacología , Enfermedad de Alzheimer/psicología , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animales , Antiinflamatorios/uso terapéutico , Evaluación Preclínica de Medicamentos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inflamasomas/efectos de los fármacos , Inflamasomas/genética , Aprendizaje por Laberinto , Ratones , Ratones Transgénicos , Microglía/fisiología , Estructura Molecular , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Fármacos Neuroprotectores/uso terapéutico , Fragmentos de Péptidos/genética , Fenilendiaminas/química , Fenilendiaminas/uso terapéutico , Presenilina-1/genética , Memoria Espacial/efectos de los fármacosRESUMEN
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.