Eficacia y seguridad de la ureteroscopia y la cirugía retrógrada intrarrenal sin fluoroscopia para el tratamiento de la urolitiasis: estudio comparativo / Efficacy and safety of fluoroless ureteroscopy and retrograde intrarenal surgery for the treatment of urolithiasis: A comparative study

Introducción Las técnicas convencionales de ureteroscopia (URS) y cirugía retrógrada intrarrenal (CRIR) requieren el uso de guía fluoroscópica, pero los riesgos derivados de la exposición a radiaciones ionizantes constituyen un motivo de preocupación entre pacientes y urólogos. El objetivo de este estudio fue evaluar la eficacia y la seguridad de la URS y la CRIR sin fluoroscopia y compararlas con los procedimientos convencionales guiados por fluoroscopia para el tratamiento de litiasis ureterales y renales. Material y métodos Los pacientes tratados con URS o CRIR para litiasis urinaria entre agosto de 2018 y diciembre de 2019 fueron evaluados retrospectivamente y agrupados según el uso de o la ausencia de fluoroscopia. Los datos se recopilaron de las historias individuales de los pacientes. Los criterios de valoración principales fueron la tasa libre de cálculos (TLC) y las complicaciones, comparadas entre los grupos con fluoroscopia y sin fluoroscopia. Se realizó un análisis de subgrupos por tipo de procedimiento (URS y CRIR) y un análisis multivariante para identificar los factores predictivos de litiasis residual. Resultados Un total de 231 pacientes cumplieron los criterios de inclusión: 120 (51,9%) en el grupo tratado con fluoroscopia convencional y 111 (48,1%) en el grupo tratado sin fluoroscopia. No se hallaron diferencias significativas entre los grupos en cuanto a la TLC (82,5% vs. 90,1%; p=0,127) o de complicaciones postoperatorias (35,0% vs. 31,5%; p=0,675). No se hallaron diferencias significativas entre estas variables en el análisis de subgrupos, independientemente del procedimiento considerado (AU)

Introduction Ureteroscopy (URS) and retrograde intrarenal surgery (RIRS) are traditionally guided by fluoroscopy, but the risks of exposure to ionizing radiation may present a matter of concern for patients and urologists. The aim of this study was to evaluate the efficacy and safety of fluoroless URS and RIRS compared with conventional fluoroscopy-guided procedures for the treatment of ureteral and renal stones. Material and methods Patients treated with URS or RIRS for urolithiasis between August 2018 and December 2019 were retrospectively evaluated and grouped according to the use of fluoroscopy. Data was collected from individual patient records. The main outcomes were stone-free rate (SFR) and complications, compared between the fluoroscopy and fluoroless groups. A subgroup analysis by type of procedure (URS and RIRS) and a multivariate analysis to identify predictors of residual stones were conducted. Results A total of 231 patients met the inclusion criteria: 120 (51.9%) in the conventional fluoroscopy group and 111 (48.1%) in the fluoroless group. No significant differences were found between groups regarding SFR (82.5% vs 90.1%; P=.127) or postoperative complication rate (35.0% vs 31.5%; P=.675). In the subgroup analysis these variables did not present significant differences, regardless of the procedure considered. In the multivariate analysis the fluoroless technique was not an independent predictor of residual lithiasis (OR: 0.991; 95%IC: 0.407-2.411; P=.983), when adjusted for procedure type, stone size and stone number. Conclusion URS and RIRS can be done without fluoroscopic guidance in selected cases, without affecting the efficacy or safety of the procedure (AU)

Efficacy and safety of fluoroless ureteroscopy and retrograde intrarenal surgery for the treatment of urolithiasis: A comparative study.

INTRODUCTION: Ureteroscopy (URS) and retrograde intrarenal surgery (RIRS) are traditionally guided by fluoroscopy, but the risks of exposure to ionizing radiation may present a matter of concern for patients and urologists. The aim of this study was to evaluate the efficacy and safety of fluoroless URS and RIRS compared with conventional fluoroscopy-guided procedures for the treatment of ureteral and renal stones. MATERIAL AND METHODS: Patients treated with URS or RIRS for urolithiasis between August 2018 and December 2019 were retrospectively evaluated and grouped according to the use of fluoroscopy. Data was collected from individual patient records. The main outcomes were stone-free rate (SFR) and complications, compared between the fluoroscopy and fluoroless groups. A subgroup analysis by type of procedure (URS and RIRS) and a multivariate analysis to identify predictors of residual stones were conducted. RESULTS: A total of 231 patients met the inclusion criteria: 120 (51.9%) in the conventional fluoroscopy group and 111 (48.1%) in the fluoroless group. No significant differences were found between groups regarding SFR (82.5% vs 90.1%, p=.127) or postoperative complication rate (35.0% vs 31.5%, p=.675). In the subgroup analysis these variables did not present significant differences, regardless of the procedure considered. In the multivariate analysis the fluoroless technique was not an independent predictor of residual lithiasis (OR 0.991; 95% IC 0.407-2.411; p=.983), when adjusted for procedure type, stone size and stone number. CONCLUSION: URS and RIRS can be done without fluoroscopic guidance in selected cases, without affecting the efficacy or safety of the procedure.

Selenium-Derivative Compounds: A Review of New Perspectives in the Treatment of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is one of the most prevalent types of dementia, affecting millions of older people worldwide. AD is stimulating efforts to develop novel molecules targeting its main features associated with a decrease in acetylcholine levels, an increase in oxidative stress and depositions of amyloid-ß (Aß) and tau protein. In this regard, selenium-containing compounds have been demonstrated as potential multi-targeted compounds in the treatment of AD. These compounds are known for their antioxidant and anticholinesterase properties, causing a decrease in Aß aggregation. OBJECTIVE: In this review, we approach structure-activity relationships of each compound, associating the decrease of ROS activity, an increase of tau-like activity and inhibition of AChE with a decrease in the self-aggregation of Aß. METHODS: We also verify that the molecular descriptors apol, nHBAcc and MlogP may be related to optimized pharmacokinetic properties for anti-AD drugs. RESULTS: In our analysis, few selenium-derived compounds presented similar molecular features to FDA-approved drugs. CONCLUSION: We suggest that unknown selenium-derived molecules with apol, nHBAcc and MlogP like FDA-approved drugs may be better successes with optimized pharmacokinetic properties in future studies in AD.

Antioxidant Activity, Molecular Docking, Quantum Studies and In Vivo Antinociceptive Activity of Sulfonamides Derived From Carvacrol.

The synthesis and antioxidant, antinociceptive and antiedematogenic activities of sulfonamides derived from carvacrol-a druglike natural product-are reported. The compounds showed promising antioxidant activity, and sulfonamide derived from morpholine (S1) demonstrated excellent antinociceptive and antiedematogenic activities, with no sedation or motor impairment. The mechanism that underlies the carvacrol and derived sulfonamides' relieving effects on pain has not yet been fully elucidated, however, this study shows that the antinociceptive activity can be partially mediated by the antagonism of glutamatergic signaling. Compound S1 presented promising efficacy and was predicted to have an appropriate medicinal chemistry profile. Thus, derivative S1 is an interesting starting point for the design of new leads for the treatment of pain and associated inflammation and prooxidative conditions.

Quantitative Structure-Activity Relationships for Structurally Diverse Chemotypes Having Anti-Trypanosoma cruzi Activity.

Small-molecule compounds that have promising activity against macromolecular targets from Trypanosoma cruzi occasionally fail when tested in whole-cell phenotypic assays. This outcome can be attributed to many factors, including inadequate physicochemical and pharmacokinetic properties. Unsuitable physicochemical profiles usually result in molecules with a poor ability to cross cell membranes. Quantitative structure-activity relationship (QSAR) analysis is a valuable approach to the investigation of how physicochemical characteristics affect biological activity. In this study, artificial neural networks (ANNs) and kernel-based partial least squares regression (KPLS) were developed using anti-T. cruzi activity data for broadly diverse chemotypes. The models exhibited a good predictive ability for the test set compounds, yielding q2 values of 0.81 and 0.84 for the ANN and KPLS models, respectively. The results of this investigation highlighted privileged molecular scaffolds and the optimum physicochemical space associated with high anti-T. cruzi activity, which provided important guidelines for the design of novel trypanocidal agents having drug-like properties.

Development of a pharmacophore for cruzain using oxadiazoles as virtual molecular probes: quantitative structure-activity relationship studies.

Chagas's is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. According to the World Health Organization, 7 million people are infected worldwide leading to 7000 deaths per year. Drugs available, nifurtimox and benzimidazole, are limited due to low efficacy and high toxicity. As a validated target, cruzain represents a major front in drug discovery attempts for Chagas disease. Herein, we describe the development of 2D QSAR ([Formula: see text] = 0.81) and a 3D-QSAR-based pharmacophore ([Formula: see text] = 0.82) from a series of non-covalent cruzain inhibitors represented mostly by oxadiazoles (lead compound, IC50 = 200 nM). Both models allowed us to map key intermolecular interactions in S1', S2 and S3 cruzain sub-sites (including halogen bond and C‒H/π). To probe the predictive capacity of obtained models, inhibitors available in the literature from different classes displaying a range of scaffolds were evaluate achieving mean absolute deviation of 0.33 and 0.51 for 2D and 3D models, respectively. CoMFA revealed an unexplored region where addition of bulky substituents to produce new compounds in the series could be beneficial to improve biological activity.