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1.
Int Braz J Urol ; 50(5): 616-628, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39106117

RESUMEN

PURPOSE: To compare transperineal (TP) vs transrectal (TR) magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) fusion-guided prostate biopsy (PBx) in a large, ethnically diverse and multiracial cohort. MATERIALS AND METHODS: Consecutive patients who underwent multiparametric (mp) MRI followed by TP or TR TRUS-fusion guided PBx, were identified from a prospective database (IRB #HS-13-00663). All patients underwent mpMRI followed by 12-14 core systematic PBx. A minimum of two additional target-biopsy cores were taken per PIRADS≥3 lesion. The endpoint was the detection of clinically significant prostate cancer (CSPCa; Grade Group, GG≥2). Statistical significance was defined as p<0.05. RESULTS: A total of 1491 patients met inclusion criteria, with 480 undergoing TP and 1011 TR PBx. Overall, 11% of patients were Asians, 5% African Americans, 14% Hispanic, 14% Others, and 56% White, similar between TP and TR (p=0.4). For PIRADS 3-5, the TP PBx CSPCa detection was significantly higher (61% vs 54%, p=0.03) than TR PBx, but not for PIRADS 1-2 (13% vs 13%, p=1.0). After adjusting for confounders on multivariable analysis, Black race, but not the PBx approach (TP vs TR), was an independent predictor of CSPCa detection. The median maximum cancer core length (11 vs 8mm; p<0.001) and percent (80% vs 60%; p<0.001) were greater for TP PBx even after adjusting for confounders. CONCLUSIONS: In a large and diverse cohort, Black race, but not the biopsy approach, was an independent predictor for CSPCa detection. TP and TR PBx yielded similar CSPCa detection rates; however the TP PBx was histologically more informative.


Asunto(s)
Biopsia Guiada por Imagen , Próstata , Neoplasias de la Próstata , Ultrasonografía Intervencional , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Biopsia Guiada por Imagen/métodos , Persona de Mediana Edad , Anciano , Ultrasonografía Intervencional/métodos , Próstata/patología , Próstata/diagnóstico por imagen , Perineo , Imagen por Resonancia Magnética Intervencional/métodos , Clasificación del Tumor , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Reproducibilidad de los Resultados
2.
J Urol ; : 101097JU0000000000004199, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39141845

RESUMEN

PURPOSE: This cross-sectional study assessed a generative-AI platform to automate the creation of accurate, appropriate, and compelling social-media (SoMe) posts from urological journal articles. MATERIALS AND METHODS: One hundred SoMe-posts from the top 3 journals in urology X (Twitter) profiles were collected from Aug-2022 to Oct-2023 A freeware GPT-tool was developed to auto-generate SoMe posts, which included title-summarization, key findings, pertinent emojis, hashtags, and DOI links to the article. Three physicians independently evaluated GPT-generated posts for achieving tetrafecta of accuracy and appropriateness criteria. Fifteen scenarios were created from 5 randomly selected posts from each journal. Each scenario contained both the original and the GPT-generated post for the same article. Five questions were formulated to investigate the posts' likability, shareability, engagement, understandability, and comprehensiveness. The paired posts were then randomized and presented to blinded academic authors and general public through Amazon Mechanical Turk (AMT) responders for preference evaluation. RESULTS: Median (IQR) time for post auto-generation was 10.2 seconds (8.5-12.5). Of the 150 rated GPT-generated posts, 115 (76.6%) met the correctness tetrafecta: 144 (96%) accurately summarized the title, 147 (98%) accurately presented the articles' main findings, 131 (87.3%) appropriately used emojis and hashtags 138 (92%). A total of 258 academic urologists and 493 AMT responders answered the surveys, wherein the GPT-generated posts consistently outperformed the original journals' posts for both academicians and AMT responders (P < .05). CONCLUSIONS: Generative-AI can automate the creation of SoMe posts from urology journal abstracts that are both accurate and preferable by the academic community and general public.

3.
Asian J Urol ; 11(3): 373-376, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39139522

RESUMEN

Objective: Secondary pyeloplasty for recurrent ureteropelvic junction obstructions may be a safe and feasible surgical option for patients. This study aimed to demonstrate outcomes of utilizing a non-transecting buccal mucosa graft ureteroplasty for management of recurrent ureteropelvic junction obstruction after prior failed pyeloplasty. Methods: We performed a retrospective review of our Collaborative of Reconstructive Robotic Ureteral Surgery database for all consecutive patients who underwent buccal mucosa graft ureteroplasty between April 2012 and June 2022 for management of recurrent ureteropelvic junction obstructions after prior failed pyeloplasty. The primary outcome included surgical success which was defined as the absence of flank pain and no obstruction on imaging. Results: Overall, ten patients were included in our analysis. The median stricture length was 2.5 (interquartile range [IQR] 1.8-4.0) cm. The median operative time was 230.5 (IQR 199.5-287.0) min and median estimated blood loss was 50.0 (IQR 28.8-102.5) mL. At a median follow-up of 10.3 (IQR 6.2-14.8) months, 80% of patients were surgically successful and there were no major (Clavien-Dindo Grade>2) complications. Conclusion: Buccal mucosa graft ureteroplasty is a valuable non-transecting surgical option for patients with recurrent ureteropelvic junction obstructions who failed prior pyeloplasty and has comparable outcomes to the literature regarding standard transecting techniques.

4.
Asian J Urol ; 11(3): 366-372, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39139529

RESUMEN

Objective: A vesicourethral anastomotic leak (VUAL) is a known complication following robotic-assisted radical prostatectomy. The natural history of a VUAL has been well described and is frequently managed with prolonged catheterization. With increasing emphasis on patient reported outcomes, catheter duration and VUAL are associated with significant short-term quality of life impairment. We aimed to present a case series of our robotic early post-prostatectomy anastomotic repair technique, defined as revision within 6 weeks from index surgery. Methods: A single institution prospective database identified eleven patients with a VUAL from July 2016 to October 2022 who underwent robotic early post-prostatectomy anastomotic repair by a single surgeon. Patients were diagnosed with a VUAL on pre-operative CT urogram or CT/fluoroscopic cystogram. The primary outcome was resolution of the anastomotic leak, defined as no contrast extravasation on post-operative cystography. Secondary outcomes included post-repair catheter duration and continence on the last follow-up defined as pad(s) per day. Results: The mean time to intervention after robotic-assisted radical prostatectomy was 21 days. Eight of the eleven (72.7%) patients had no evidence of extravasation on post-repair cystogram. The range from intervention to first cystogram was 7-20 days. The median catheter duration for those with successful intervention was 10 days. The median catheter duration for those with the leak on initial post-operative cystogram was 20 days. At a mean follow-up time of 25 months, eight (72.7%) patients reported using no pads per day, and three (27.3%) patients reported one pad per day. Conclusion: Management of a VUAL has traditionally relied on prolonged catheter drainage and the tincture of time. As the role of robotic reconstruction has been shown to be a viable modality for management of bladder neck contracture, it is important to reconsider prior dogmas of urologic care. Our case series suggests that an early repair is safe and has a high success rate. Early robotic intervention gives providers an additional tool in aiding patient recovery.

5.
J Pharmacol Toxicol Methods ; 128: 107530, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38917571

RESUMEN

INTRODUCTION: Cardiac safety assessment, such as lethal arrhythmias and contractility dysfunction, is critical during drug development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been shown to be useful in predicting drug-induced proarrhythmic risk through international validation studies. Although cardiac contractility is another key function, fit-for-purpose hiPSC-CMs in evaluating drug-induced contractile dysfunction remain poorly understood. In this study, we investigated whether alignment of hiPSC-CMs on nanopatterned culture plates can assess drug-induced contractile changes more efficiently than non-aligned monolayer culture. METHODS: Aligned hiPSC-CMs were obtained by culturing on 96-well culture plates with a ridge-groove-ridge nanopattern on the bottom surface, while non-aligned hiPSC-CMs were cultured on regular 96-well plates. Next-generation sequencing and qPCR experiments were performed for gene expression analysis. Contractility of the hiPSC-CMs was assessed using an imaging-based motion analysis system. RESULTS: When cultured on nanopatterned plates, hiPSC-CMs exhibited an aligned morphology and enhanced expression of genes encoding proteins that regulate contractility, including myosin heavy chain, calcium channel, and ryanodine receptor. Compared to cultures on regular plates, the aligned hiPSC-CMs also showed both enhanced contraction and relaxation velocity. In addition, the aligned hiPSC-CMs showed a more physiological response to positive and negative inotropic agents, such as isoproterenol and verapamil. DISCUSSION: Taken together, the aligned hiPSC-CMs exhibited enhanced structural and functional properties, leading to an improved capacity for contractility assessment compared to the non-aligned cells. These findings suggest that the aligned hiPSC-CMs can be used to evaluate drug-induced cardiac contractile changes.


Asunto(s)
Células Madre Pluripotentes Inducidas , Contracción Miocárdica , Miocitos Cardíacos , Humanos , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/citología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/fisiología , Contracción Miocárdica/efectos de los fármacos , Contracción Miocárdica/fisiología , Células Cultivadas , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Técnicas de Cultivo de Célula/métodos , Isoproterenol/farmacología
6.
Am J Infect Control ; 52(9): 1030-1034, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38795903

RESUMEN

BACKGROUND: The coronavirus disease 2019 pandemic has highlighted the need for effective infection control in outpatient health care settings. Germicidal ultraviolet-C (GUV) light, known for inactivating microorganisms by damaging their deoxyribonucleic acid or ribonucleic acid, offers a potential solution. This study examines the efficacy of GUV air disinfection systems in real-world outpatient environments. METHODS: We deployed upper-room and far-UV GUV fixtures in 3 outpatient facilities, assessing their impact on bacterial loads through air and surface sampling and bioindicator tests. Occupancy was also monitored. RESULTS: While manual air and surface sampling did not show a significant difference in bacterial loads between control and Ultraviolet C-treated groups, bioindicator tests demonstrated a high level of spore inactivation (up to 99.7% for upper-room GUV and 96.26% for far-UV). Occupancy levels did not significantly influence these outcomes. DISCUSSION: The discrepancy between bioindicator efficacy and environmental sampling results suggests limitations in the latter's ability to accurately capture environmental bioburden. Bioindicators proved to be reliable for in-situ validation of Ultraviolet C surface disinfection. CONCLUSIONS: Bioindicators are effective for validating GUV surface disinfection efficacy in health care settings, though further research is needed to optimize environmental sampling methods for assessing GUV's impact on real-world bacterial loads.


Asunto(s)
COVID-19 , Desinfección , SARS-CoV-2 , Rayos Ultravioleta , Desinfección/métodos , Humanos , COVID-19/prevención & control , SARS-CoV-2/efectos de la radiación , Instituciones de Atención Ambulatoria , Carga Bacteriana , Microbiología del Aire , Control de Infecciones/métodos
7.
Clin Transl Sci ; 17(4): e13780, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38618722

RESUMEN

Despite a rapid increase in pediatric mortality rate from prescription and illicit opioids, there is limited research on the dose-dependent impact of opioids on respiratory depression in children, the leading cause of opioid-associated death. In this article, we extend a previously developed translational model to cover pediatric populations by incorporating age-dependent pharmacokinetic, pharmacodynamic, and physiological changes compared to adults. Our model reproduced previous perioperative clinical findings that adults and children have similar risk of respiratory depression at the same plasma fentanyl concentration when specific endpoints (minute ventilation, CO2 tension in the blood) were used. However, our model points to a potential caveat that, in a perioperative setting, routine use of mechanical ventilation and supplemental oxygen maintained the blood and tissue oxygen partial pressures in patients and prevented the use of oxygen-related endpoints to evaluate the consequences of respiratory depression. In a community setting when such oxygenation procedures are not immediately available, our model suggests that the higher oxygen demand and reduced cerebrovascular reactivity could make children more susceptible to severe hypoxemia and brain hypoxia, even with the same plasma fentanyl concentration as adults. Our work indicates that when developing intervention strategies to protect children from opioid overdose in a community setting, these pediatric-specific factors may need to be considered.


Asunto(s)
Sobredosis de Opiáceos , Insuficiencia Respiratoria , Adulto , Humanos , Niño , Insuficiencia Respiratoria/inducido químicamente , Oxígeno , Analgésicos Opioides/efectos adversos , Fentanilo/efectos adversos
9.
JAMA Netw Open ; 7(1): e2351839, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38261323

RESUMEN

Importance: Questions have emerged as to whether standard intranasal naloxone dosing recommendations (ie, 1 dose with readministration every 2-3 minutes if needed) are adequate in the era of illicitly manufactured fentanyl and its derivatives (hereinafter, fentanyl). Objective: To compare naloxone plasma concentrations between different intranasal naloxone repeat dosing strategies and to estimate their effect on fentanyl overdose. Design, Setting, and Participants: This unblinded crossover randomized clinical trial was conducted with healthy participants in a clinical pharmacology unit (Spaulding Clinical Research, West Bend, Wisconsin) in March 2021. Inclusion criteria included age 18 to 55 years, nonsmoking status, and negative test results for the presence of alcohol or drugs of abuse. Data analysis was performed from October 2021 to May 2023. Intervention: Naloxone administered as 1 dose (4 mg/0.1 mL) at 0, 2.5, 5, and 7.5 minutes (test), 2 doses at 0 and 2.5 minutes (test), and 1 dose at 0 and 2.5 minutes (reference). Main Outcomes and Measures: The primary outcome was the first prespecified time with higher naloxone plasma concentration. The secondary outcome was estimated brain hypoxia time following simulated fentanyl overdoses using a physiologic pharmacokinetic-pharmacodynamic model. Naloxone concentrations were compared using paired tests at 3 prespecified times across the 3 groups, and simulation results were summarized using descriptive statistics. Results: This study included 21 participants, and 18 (86%) completed the trial. The median participant age was 34 years (IQR, 27-50 years), and slightly more than half of participants were men (11 [52%]). Compared with 1 naloxone dose at 0 and 2.5 minutes, 1 dose at 0, 2.5, 5, and 7.5 minutes significantly increased naloxone plasma concentration at 10 minutes (7.95 vs 4.42 ng/mL; geometric mean ratio, 1.95 [1-sided 97.8% CI, 1.28-∞]), whereas 2 doses at 0 and 2.5 minutes significantly increased the plasma concentration at 4.5 minutes (2.24 vs 1.23 ng/mL; geometric mean ratio, 1.98 [1-sided 97.8% CI, 1.03-∞]). No drug-related serious adverse events were reported. The median brain hypoxia time after a simulated fentanyl 2.97-mg intravenous bolus was 4.5 minutes (IQR, 2.1-∞ minutes) with 1 naloxone dose at 0 and 2.5 minutes, 4.5 minutes (IQR, 2.1-∞ minutes) with 1 naloxone dose at 0, 2.5, 5, and 7.5 minutes, and 3.7 minutes (IQR, 1.5-∞ minutes) with 2 naloxone doses at 0 and 2.5 minutes. Conclusions and Relevance: In this clinical trial with healthy participants, compared with 1 intranasal naloxone dose administered at 0 and 2.5 minutes, 1 dose at 0, 2.5, 5, and 7.5 minutes significantly increased naloxone plasma concentration at 10 minutes, whereas 2 doses at 0 and 2.5 minutes significantly increased naloxone plasma concentration at 4.5 minutes. Additional research is needed to determine optimal naloxone dosing in the community setting. Trial Registration: ClinicalTrials.gov Identifier: NCT04764630.


Asunto(s)
Hipoxia Encefálica , Sobredosis de Opiáceos , Masculino , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Femenino , Etanol , Comercio , Fentanilo , Naloxona/uso terapéutico
10.
BJU Int ; 133(2): 206-213, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37667554

RESUMEN

OBJECTIVE: To determine whether a simple point-of-care measurement system estimating renal parenchymal volume using tools ubiquitously available could be used to replace nuclear medicine renal scintigraphy (NMRS) in current clinical practice to predict estimated glomerular filtration rate (eGFR) after nephrectomy by estimating preoperative split renal function. PATIENTS AND METHODS: We performed a retrospective review of patients who underwent abdominal cross-sectional imaging (computed tomography/magnetic resonance imaging) and mercaptoacetyltriglycine (MAG3) NMRS prior to total nephrectomy at a single institution. We developed the real-time estimation of nephron activity with a linear measurement system (RENAL-MS) method of estimating postoperative renal function via the following technique: renal parenchymal volume of the removed kidney relative to the remaining kidney was estimated as the product of renal length and the average of six renal parenchymal thickness measurements. The utility of this value was compared to the utility of the split renal function measured by MAG3 for prediction of eGFR and new onset Stage 3 chronic kidney disease (CKD) at ≥90 days after nephrectomy using uni- and multivariate linear and logistic regression. RESULTS: A total of 57 patients met the study criteria. The median (interquartile range [IQR]) age was 69 (61-80) years. The median (IQR) pre- and postoperative eGFR was 74 (IQR 58-90) and 46 (35-62) mL/min/1.73 m2 , respectively. [Correction added on 29 December 2023, after first online publication: The data numbers in the preceding sentence have been corrected.] Correlations between actual and predicted postoperative eGFR were similar whether the RENAL-MS or NMRS methods were used, with correlation using RENAL-MS being slightly numerically but not statistically superior (R = 0.82 and 0.76; P = 0.138). Receiver operating characteristic curve analysis using logistic regression estimates incorporating age, sex, and preoperative creatinine to predict postoperative Stage 3 CKD were similar between RENAL-MS and NMRS (area under the curve 0.93 vs. 0.97). [Correction added on 29 December 2023, after first online publication: The data numbers in the preceding sentence have been corrected.] CONCLUSION: A point-of-care tool to estimate renal parenchymal volume (RENAL-MS) performed equally as well as NMRS to predict postoperative eGFR and de novo Stage 3 CKD after nephrectomy in our population, suggesting NMRS may not be necessary in this setting.


Asunto(s)
Neoplasias Renales , Insuficiencia Renal Crónica , Humanos , Anciano , Anciano de 80 o más Años , Tasa de Filtración Glomerular , Neoplasias Renales/cirugía , Riñón/diagnóstico por imagen , Riñón/cirugía , Nefrectomía/métodos , Nefronas/cirugía , Estudios Retrospectivos
11.
NeuroRehabilitation ; 53(4): 595-598, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37899064

RESUMEN

BACKGROUND: Long-term survival after spinal cord injury (SCI) has been extensively studied in the US and UK. OBJECTIVE: To compare SCI epidemiology and survival results between the US and UK for the same time period and patient groups. METHODS: We restricted attention to persons injured at ages 18 and older who had survived at least 2 years post injury and were not ventilator dependent. We performed survival analysis using logistic regression on person-year data with time-dependent covariates. The resulting mortality rates were used to construct life tables in order to obtain life expectancies. RESULTS: The average age at injury, percentage male, and level/grade of injury were rather similar between the two countries. After adjustment for risk factors, UK mortality was 85% of that in the US (95% c.i. 80% to 91%, p < 0.0001). Mortality increased by 0.3% per year over the 1980 to 2012 study period (HR = 1.003); this was not statistically significant (p = 0.44). The US and UK life expectancies are nearly the same percentage of their respective general population values, differing by at most 2%. CONCLUSION: Long-term mortality after SCI in the UK is roughly 15% lower than that in the US. The general population mortality in the UK is also approximately 15% lower, however, and thus the percentages of normal life expectancy in the two countries prove to be strikingly similar.


Asunto(s)
Traumatismos de la Médula Espinal , Humanos , Masculino , Estados Unidos/epidemiología , Modelos Logísticos , Factores de Riesgo , Traumatismos de la Médula Espinal/epidemiología , Esperanza de Vida , Reino Unido/epidemiología
12.
Clin Pharmacol Ther ; 114(6): 1332-1341, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37702218

RESUMEN

Current cardiac safety testing focuses on detecting drug-induced QTC prolongation as a surrogate for risk of Torsade de Pointes. The nonclinical strategy, described in International Conference on Harmonization (ICH) S7B, includes in vitro assessment of hERG block or ventricular repolarization delay and in vivo QT prolongation. Several studies have reported predictive values of ICH S7B results for clinical QTC outcomes for small molecules; none has examined peptides and proteins other than monoclonal antibodies. To address this knowledge gap, information for peptides and proteins submitted to the US Food and Drug Administration (FDA) was collected. Results of hERG assays, ventricular repolarization assays, and in vivo QT assessment were compared with clinical QTC study outcomes. The results show that 14% clinical QTC studies for approved and investigational products failed to exclude 10-ms QTC prolongation. Clinical QTC prolongation for these molecules lacked concentration-dependence which is expected for hERG block-mediated mechanism or QTC prolongation could not be excluded due to characterization in the clinical study. The hERG and ventricular repolarization assays do not identify clinical QTC prolongation potential for peptides and proteins. Lack of alignment between hERG and ventricular repolarization assay results and clinical QTC outcomes suggests that the mechanisms of QTC prolongation by some peptides and proteins are unrelated to direct cardiac ion channel block. Similar to large targeted proteins and monoclonal antibodies, peptides and proteins regardless of size have a low likelihood of direct cardiac ion channel interactions. This characteristic supports waiving the requirement for thorough QT assessment for products comprised of naturally occurring amino acids unless proarrhythmia potential is suggested by nonclinical or clinical data.


Asunto(s)
Síndrome de QT Prolongado , Torsades de Pointes , Humanos , Síndrome de QT Prolongado/inducido químicamente , Corazón , Torsades de Pointes/inducido químicamente , Péptidos/efectos adversos , Canales Iónicos , Anticuerpos Monoclonales/efectos adversos , Electrocardiografía
14.
Front Pharmacol ; 14: 1212092, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37469866

RESUMEN

Introduction: Engineered heart tissues (EHTs) are three-dimensional culture platforms with cardiomyocytes differentiated from human pluripotent stem cells (hPSCs) and were designed for assaying cardiac contractility. For drug development applications, EHTs must have a stable function and provide reproducible results. We investigated these properties with EHTs made with different tissue casting batches and lines of differentiated hPSC-cardiomyocytes and analyzed them at different times after being fabricated. Methods: A video-optical assay was used for measuring EHT contractile outputs, and these results were compared with results from motion traction analysis of beating hPSC-cardiomyocytes cultured as monolayers in two-dimensional cultures. The reproducibility of induced contractile variations was tested using compounds with known mechanistic cardiac effects (isoproterenol, EMD-57033, omecamtiv mecarbil, verapamil, ranolazine, and mavacamten), or known to be clinically cardiotoxic (doxorubicin, sunitinib). These drug-induced variations were characterized at different electrical pacing rates and variations in intracellular calcium transients were also assessed in EHTs. Results: To ensure reproducibility in experiments, we established EHT quality control criteria based on excitation-contraction coupling and contractile sensitivity to extracellular calcium concentration. In summary, a baseline contractile force of 0.2 mN and excitation-contraction coupling of EHTs were used as quality control criteria to select suitable EHTs for analysis. Overall, drug-induced contractile responses were similar between monolayers and EHTs, where a close relationship was observed between contractile output and calcium kinetics. Contractile variations at multiple time points after adding cardiotoxic compounds were also detectable in EHTs. Discussion: Reproducibility of drug-induced effects in EHTs between experiments and relative to published work on these cellular models was generally observed. Future applications for EHTs may require additional mechanistic criteria related to drug effects and cardiac functional outputs to be measured in regard to specific contexts of use.

15.
Anesthesiology ; 139(3): 342-353, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37402248

RESUMEN

Opioids are effective analgesics, but they can have harmful adverse effects, such as addiction and potentially fatal respiratory depression. Naloxone is currently the only available treatment for reversing the negative effects of opioids, including respiratory depression. However, the effectiveness of naloxone, particularly after an opioid overdose, varies depending on the pharmacokinetics and the pharmacodynamics of the opioid that was overdosed. Long-acting opioids, and those with a high affinity at the µ-opioid receptor and/or slow receptor dissociation kinetics, are particularly resistant to the effects of naloxone. In this review, the authors examine the pharmacology of naloxone and its safety and limitations in reversing opioid-induced respiratory depression under different circumstances, including its ability to prevent cardiac arrest.


Asunto(s)
Sobredosis de Droga , Paro Cardíaco , Sobredosis de Opiáceos , Insuficiencia Respiratoria , Humanos , Naloxona/farmacología , Naloxona/uso terapéutico , Analgésicos Opioides/efectos adversos , Antagonistas de Narcóticos/farmacología , Antagonistas de Narcóticos/uso terapéutico , Sobredosis de Opiáceos/tratamiento farmacológico , Insuficiencia Respiratoria/inducido químicamente , Insuficiencia Respiratoria/prevención & control , Insuficiencia Respiratoria/tratamiento farmacológico , Sobredosis de Droga/tratamiento farmacológico , Paro Cardíaco/inducido químicamente , Paro Cardíaco/tratamiento farmacológico , Paro Cardíaco/prevención & control
16.
Urol Case Rep ; 48: 102399, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37193579

RESUMEN

Multimodal immunosuppression is the backbone of modern solid organ transplantation. However, immunosuppression itself is an independent risk factor for post-transplant malignancy. Although skin malignancy is the most common post-transplant malignancy, genitourinary cancers are also described. Dose reduction or cessation of immunosuppression has a beneficial role in the management of transplant patients with concomitant malignancy, but only limited data exist with respect to bladder cancer (BCa). We describe a patient who developed metastatic muscle invasive bladder cancer (MIBC) after diseased donor kidney transplant (DDKT) who was successfully managed with dose reduction and elimination of an immunosuppression regimen.

18.
BJUI Compass ; 4(3): 298-304, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37025480

RESUMEN

Objectives: To describe our multi-institutional experience with robotic ureteral reconstruction (RUR) in patients who failed prior endoscopic and/or surgical management. Materials and Methods: We retrospectively reviewed our Collaborative of Reconstructive Robotic Ureteral Surgery (CORRUS) database for all consecutive patients who underwent RUR between 05/2012 and 01/2020 for a recurrent ureteral stricture after having undergone prior failed endoscopic and/or surgical repair. Post-operatively, patients were assessed for surgical success, defined as the absence of flank pain and obstruction on imaging. Results: Overall, 105 patients met inclusion criteria. Median stricture length was 2 (IQR 1-3) centimetres. Strictures were located at the ureteropelvic junction (UPJ) (41.0%), proximal (14.3%), middle (9.5%) or distal (35.2%) ureter. There were nine (8.6%) radiation-induced strictures. Prior failed management included endoscopic intervention (49.5%), surgical repair (25.7%) or both (24.8%). For repair of UPJ and proximal strictures, ureteroureterostomy (3.4%), ureterocalicostomy (5.2%), pyeloplasty (53.5%) or buccal mucosa graft ureteroplasty (37.9%) was utilized; for repair of middle strictures, ureteroureterostomy (20.0%) or buccal mucosa graft ureteroplasty (80.0%) was utilized; for repair of distal strictures, ureteroureterostomy (8.1%), side-to-side reimplant (18.9%), end-to-end reimplant (70.3%) or appendiceal bypass (2.7%) was utilized. Major (Clavien >2) post-operative complications occurred in two (1.9%) patients. At a median follow-up of 15.1 (IQR 5.0-30.4) months, 94 (89.5%) cases were surgically successful. Conclusions: RUR may be performed with good intermediate-term outcomes for patients with recurrent strictures after prior failed endoscopic and/or surgical management.

19.
J Endourol ; 37(5): 564-567, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36924293

RESUMEN

Background: We compared outcomes of robot-assisted simple prostatectomy (RASP) in patients with and without a history of prior prostate surgery for management of symptomatic benign prostatic hyperplasia (BPH). Methods: We retrospectively reviewed our multi-institutional database for all consecutive patients who underwent RASP between May 2013 and January 2021. Postoperatively, urinary function was assessed using the American Urological Association symptom score (AUASS) and quality of life (QOL) score. Results: Overall, 520 patients met inclusion criteria. Among the 87 (16.7%) patients who underwent prior prostate surgery, 49 (56.3%), 26 (29.9%), 8 (9.2%), 3 (3.4%), and 1 (1.1%) patients underwent transurethral resection of the prostate, photoselective vaporization of the prostate, transurethral microwave therapy, prostatic urethral lift, or water vapor thermal therapy, respectively. There was no difference in mean prostate volume (p = 0.40), estimated blood loss (p = 0.32), robotic console time (p = 0.86), or major 30-day postoperative (Clavien >2) complications (p = 0.80) between both groups. With regard to urinary function, the mean improvement in preoperative and postoperative AUASS (p = 0.31), QOL scores (p = 0.11), and continence rates was similar between both groups. Conclusion: For management of patients with BPH and lower urinary tract symptoms, RASP is associated with an improvement in urinary function outcomes and a low risk of postoperative complications. Perioperative outcomes of RASP are similar in patients who underwent prior prostate surgery vs those that did not undergo prior prostate surgery.


Asunto(s)
Hiperplasia Prostática , Procedimientos Quirúrgicos Robotizados , Robótica , Resección Transuretral de la Próstata , Masculino , Humanos , Hiperplasia Prostática/cirugía , Hiperplasia Prostática/complicaciones , Calidad de Vida , Procedimientos Quirúrgicos Robotizados/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Prostatectomía/efectos adversos
20.
J Pharm Sci ; 112(5): 1315-1323, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36736776

RESUMEN

Control of N-nitrosoamine impurities is important for ensuring the safety of drug products. Findings of nitrosamine impurities in some drug products led FDA to develop new guidance providing recommendations for manufacturers towards prevention and detection of nitrosamine impurities in pharmaceutical products. One of these products, ranitidine, also had a published in vivo study, which has since been retracted by its authors, suggesting a potential for in vivo conversion of ranitidine to the probable human carcinogen, N-nitrosodimethylamine (NDMA). FDA subsequently initiated a randomized, double-blind, placebo-controlled, crossover clinical investigation to assess the potential for in vivo conversion of ranitidine to NDMA with different meals. A bioanalytical method toward characterization of NDMA formation was needed as previously published methods did not address potential NDMA formation after biofluid collection. Therefore, a bioanalytical method was developed and validated as per FDA's Bioanalytical Method Validation guidance. An appropriate surrogate matrix for calibration standards and quality control sample preparation for both liquid matrices (human plasma and urine) was optimized to minimize the artifacts of assay measurements and monitor basal NDMA levels. Interconversion potential of ranitidine to NDMA was monitored during method validation by incorporating the appropriate quality control samples. The validated methods for NDMA were linear from 15.6 pg/mL to 2000 pg/mL. Low sample volumes (2 mL for urine and 1 mL for plasma) made this method suitable for clinical study samples and helped to evaluate the influence of ranitidine administration and meal types on urinary excretion of NDMA in human subjects.


Asunto(s)
Dimetilnitrosamina , Nitrosaminas , Humanos , Dimetilnitrosamina/orina , Ranitidina , Preparaciones Farmacéuticas , Proyectos de Investigación
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