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1.
Neurourol Urodyn ; 43(1): 258-266, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37961019

RESUMEN

PURPOSE: The etiology of ureteral dilation in primary nonrefluxing, nonobstructing megaureters is still not well understood. Impaired ureteral peristalsis has been theorized as one of the contributing factors. However, ureteral peristalsis and its "normal" function is not well defined. In this study, using mathematical modeling techniques, we aim to better understand how ureteral peristalsis works. This is the first model to consider clinically observed, back-and-forth, cyclic wall longitudinal motion during peristalsis. We hypothesize that dysfunctional ureteral peristalsis, caused by insufficient peristaltic amplitudes (e.g., circular muscle dysfunction) and/or lack of ureteral wall longitudinal motion (e.g., longitudinal muscle dysfunction), promotes peristaltic reflux (i.e., retrograde flow of urine during an episode of peristalsis) and may result in urinary stasis, urine accumulation, and consequent dilation. METHODS: Based on lubrication theory in fluid mechanics, we developed a two-dimensional (planar) model of ureteral peristalsis. In doing so, we treated ureteral peristalsis as an infinite train of sinusoidal waves. We then analyzed antegrade and retrograde flows in the ureter under different bladder-kidney differential pressure and peristalsis conditions. RESULTS: There is a minimum peristaltic amplitude required to prevent peristaltic reflux. Ureteral wall longitudinal motion decreases this minimum required amplitude, increasing the nonrefluxing range of peristaltic amplitudes. As an example, for a normal bladder-kidney differential pressure of 5 cmH2 O, ureteral wall longitudinal motion increases nonrefluxing range of peristaltic amplitude by 65%. Additionally, ureteral wall longitudinal motion decreases refluxing volumetric flow rates. For a similar normal bladder pressure example of 5 cmH2 O, refluxing volumetric flow rate decreases by a factor of 18. Finally, elevated bladder pressure, not only increases the required peristaltic amplitude for reflux prevention but it increases maximum refluxing volumetric flow rates. For the case without wall longitudinal motion, as bladder-kidney differential pressure increases from 5 to 40 cmH2 O, minimum required peristaltic amplitude to prevent reflux increases by 40% while the maximum refluxing volumetric flow rate increases by approximately 100%. CONCLUSION: The results presented in this study show how abnormal ureteral peristalsis, caused by the absence of wall longitudinal motion and/or lack of sufficient peristaltic amplitudes, facilitates peristaltic reflux and retrograde flow. We theorize that this retrograde flow can lead to urinary stasis and urine accumulation in the ureters, resulting in ureteral dilation seen on imaging studies and elevated infection risk. Our results also show how chronically elevated bladder pressures are more susceptible to such refluxing conditions that could lead to ureteral dilation.


Asunto(s)
Uréter , Obstrucción Ureteral , Humanos , Peristaltismo/fisiología , Dilatación , Uréter/fisiología , Vejiga Urinaria
2.
Neurourol Urodyn ; 40(1): 85-94, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33017072

RESUMEN

AIMS: Paquin asserts that in order for ureterovesical junctions (UVJs) to prevent reflux, the ureteral tunnel length-to-diameter ratio needs to be 5:1. We hypothesize that the surgical implementation of this observation results in an overestimation of the needed length-to-diameter ratio to prevent vesicoureteral reflux. METHODS: With finite elements, we model the urine storage phase of the bladder under nonlinear conditions. In the reference state, the bladder is assumed to be a sphere with an oblique straight elliptical hole as the UVJ. Broad parametric studies on different length-to-diameter ratios are performed as the bladder volume increases from 10% to 110% capacity. RESULTS: The capability of the UVJ to prevent reflux during storage depends on its length-to-diameter ratio. UVJs with larger length-to-diameter ratios lengthen and narrow as the bladder volume increases, causing the closure of the UVJ and rise in its flow resistance. Our model shows that the UVJ length-to-diameter ratio decreases as the bladder volume increases. The 5:1 ratio implemented at 80% capacity-approximate volume or bladder wall stretch during ureteroneocystostomy (UNC)-corresponds to 7:1 at the reference state-used by Paquin. The 5:1 ratio implemented at the reference state corresponds to 3:1 at 80% capacity. CONCLUSIONS: Our modeling results are consistent with Paquin's original observation on the significance of the UVJ length-to-diameter ratio in preventing reflux. They, however, indicate that the surgical implementation of this rule during UNC results in an overestimation of the requisite tunnel length-to-diameter ratio to prevent reflux. They also suggest that the UVJ closure is due to the bladder wall deformation rather than the pressure.


Asunto(s)
Reimplantación/métodos , Uréter/cirugía , Preescolar , Femenino , Humanos , Masculino , Estudios Retrospectivos
4.
J Surg Res ; 229: 192-199, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29936989

RESUMEN

BACKGROUND: Preclinical validation of scaffold-based technologies in animal models of urethral disease is desired to assess wound healing efficacy in scenarios that mimic the target patient population. This study investigates the feasibility of bilayer silk fibroin (BLSF) scaffolds for the repair of previously damaged urethras in a rabbit model of onlay urethroplasty. MATERIALS AND METHODS: A focal, partial thickness urethral injury was created in adult male rabbits (n = 12) via electrocoagulation and then onlay urethroplasty with 50 mm2 BLSF grafts was carried out 2 wk after injury. Animals were randomly divided into three experimental groups and harvested at 2 wk after electrocoagulation (n = 3), and 1 (n = 3) or 3 (n = 6) months after scaffold implantation. Outcome analyses were performed preoperatively and at 2 wk after injury in all groups as well as at 1 or 3 mo after scaffold grafting and included urethroscopy, retrograde urethrography (RUG), and histological and immunohistochemical analyses. RESULTS: At 2 wk after electrocoagulation, urethroscopic and RUG evaluations confirmed urethral stricture formation in 92% (n = 11/12) of rabbits. Gross tissue assessments at 1 (n = 3) and 3 (n = 6) mo after onlay urethroplasty revealed host tissue ingrowth covering the entire implant site. At 3 mo post-op, RUG analyses of repaired urethral segments demonstrated a 39% reduction in urethral stenosis detected following electrocoagulation injury. Histological and immunohistochemical analyses revealed the formation of innervated, vascularized neotissues with α-smooth muscle actin+ and SM22α+ smooth muscle bundles and pan-cytokeratin + epithelium at graft sites. CONCLUSIONS: These results demonstrate the feasibility of BLSF matrices to support the repair of previously damaged urethral tissues.


Asunto(s)
Procedimientos de Cirugía Plástica/instrumentación , Andamios del Tejido , Uretra/lesiones , Enfermedades Uretrales/cirugía , Procedimientos Quirúrgicos Urológicos Masculinos/instrumentación , Animales , Materiales Biocompatibles/uso terapéutico , Modelos Animales de Enfermedad , Fibroínas/uso terapéutico , Humanos , Masculino , Conejos , Procedimientos de Cirugía Plástica/métodos , Regeneración , Resultado del Tratamiento , Uretra/fisiología , Uretra/cirugía , Procedimientos Quirúrgicos Urológicos Masculinos/métodos
5.
Neurourol Urodyn ; 37(5): 1583-1593, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29427331

RESUMEN

AIMS: Mounting evidence indicates that a variety of factors released from the urothelium or suburothelium can modulate smooth muscle activity. Although the relationship between the mucosa and smooth muscle has been investigated, little is known about the pathophysiologic changes in detrusor-mucosa interactions in neurogenic bladders. The goal of the study was to determine the impact of the mucosa on evoked responses in spinal cord injured (SCI) bladders. METHODS: Urinary bladders were obtained from 6wk SCI rats or age-matched uninjured controls. Ex vivo isometric tension studies were performed and muscarinic receptor expression was measured in bladder tissue with and without mucosa. RESULTS: The magnitude and area of nerve evoked responses in SCI tissue with mucosa was higher than without mucosa. The duration and decay time of nerve-evoked responses were longer in SCI than control tissue irrespective of the mucosa. The level of the muscarinic M2 receptor was decreased in the mucosa of SCI bladders. CONCLUSIONS: Detrusor-mucosa interactions are substantially altered in the neurogenic bladder. After spinal cord injury, an excitatory modulation of smooth muscle contraction by the mucosa emerges, and could be targeted via intravesical treatment in the context of neurogenic bladder dysfunction.


Asunto(s)
Potenciales Evocados , Membrana Mucosa/fisiopatología , Traumatismos de la Médula Espinal/fisiopatología , Vejiga Urinaria/fisiopatología , Animales , Contracción Isométrica , Masculino , Contracción Muscular , Músculo Liso/fisiopatología , Unión Neuromuscular , Ratas , Ratas Sprague-Dawley , Receptores Muscarínicos/biosíntesis , Vejiga Urinaria Neurogénica/etiología , Vejiga Urinaria Neurogénica/fisiopatología
6.
Neurourol Urodyn ; 36(4): 1104-1107, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27283922

RESUMEN

AIMS: To determine if minimizing the number of onabotulinumtoxinA (BTX) injection sites to one to three locations provides similar clinical efficacy and duration of effect compared to the established technique in treating patients with neurogenic (NDO) or idiopathic detrusor overactivity (IDO). METHODS: Prospective data were collected on BTX naïve patients with NDO or IDO who were intolerant or refractory to oral medications. Patients were treated with 100-300 U of BTX via one to three injection sites. Patients completed the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) prior to and after treatment. The primary endpoint was defined as ICIQ-SF score improvement of >5 points. Secondary endpoints included subjective success, complete continence, quality of life score, post void residual (PVR), duration of effect and adverse events. RESULTS: Fourty-five patients (22 IDO, 23 NDO) were included. ICIQ-SF score improvement of >5 points was achieved in 73% (IDO 55%, NDO 91%) and the subjective success rate was 69% (50% IDO, 87% NDO). 52% of NDO patients attained complete continence. PVR increased by a mean of 32 and 156 ml in the IDO and NDO groups. Hematuria occurred in 6.7% and symptomatic urinary tract infection occurred in 11.1%. No systemic BTX adverse events occurred. Mean duration of effect was 31 weeks. CONCLUSIONS: Our technique for administering BTX via one to three intradetrusor injection sites has similar clinical efficacy and rates of adverse events compared to the established technique for treating patients with IDO and NDO. Neurourol. Urodynam. 36:1104-1107, 2017. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Toxinas Botulínicas Tipo A/administración & dosificación , Fármacos Neuromusculares/administración & dosificación , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Proyectos Piloto , Adulto Joven
7.
Curr Urol Rep ; 18(5): 38, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28315171

RESUMEN

The primary indication for varicocele repair in adults, that of failed paternity, must be substituted in the adolescent population with surrogate parameters of testicular size differential and semen analysis. Making recommendations based on these two parameters is incredibly difficult because studies often have contradictory findings, different patient populations, and lack of long-term follow up of the key endpoint, paternity. Therefore, it is not a surprise that recommendations for adolescent varicocele repair are general (with some exceptions) and necessarily so because of limitations in quality of evidence. Apart from pain, all indications for varicocele repair in adolescence remain controversial. This highlights the most important task for future studies: to prevent pediatric urologists from allowing a potentially damaging process to go untreated, while at the same time avoiding unnecessary intervention on a highly prevalent condition.


Asunto(s)
Varicocele/cirugía , Adolescente , Fertilidad , Humanos , Masculino , Varicocele/epidemiología , Varicocele/etiología
8.
Curr Urol Rep ; 17(2): 16, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26801192

RESUMEN

Urologic tissue engineering efforts have been largely focused on bladder and urethral defect repair. The current surgical gold standard for treatment of poorly compliant pathological bladders and severe urethral stricture disease is enterocystoplasty and onlay urethroplasty with autologous tissue, respectively. The complications associated with autologous tissue use and harvesting have led to efforts to develop tissue-engineered alternatives. Natural and synthetic materials have been used with varying degrees of success, but none has proved consistently reliable for urologic tissue defect repair in humans. Silk fibroin (SF) scaffolds have been tested in bladder and urethral repair because of their favorable biomechanical properties including structural strength, elasticity, biodegradability, and biocompatibility. SF scaffolds have been used in multiple animal models and have demonstrated robust regeneration of smooth muscle and urothelium. The pre-clinical data involving SF scaffolds in urologic defect repair are encouraging and suggest that they hold potential for future clinical use.


Asunto(s)
Fibroínas/metabolismo , Seda/metabolismo , Ingeniería de Tejidos , Uretra , Vejiga Urinaria , Animales , Fibroínas/química , Humanos , Seda/química , Andamios del Tejido , Uretra/metabolismo , Uretra/cirugía , Vejiga Urinaria/metabolismo , Vejiga Urinaria/cirugía
9.
WMJ ; 115(2): 70-3, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27197339

RESUMEN

INTRODUCTION: We investigated the outcomes and quality of life measures in men who underwent cystectomy and urinary diversion for devastating lower urinary tract toxicity after prostatic radiotherapy and/or cryotherapy for the treatment of prostate cancer. METHODS: Records of patients who underwent cystectomy and urinary diversion for the management of a devastated lower urinary tract following prostatic radiotherapy or cryotherapy were reviewed retrospectively. A postoperative, retrospective quality of life (QOL) survey was designed specific to this patient subset and obtained by telephone interview. RESULTS: Extirpative surgery with urinary diversion for management of a devastated lower urinary tract was performed on 15 patients with a mean age of 72 years (range 63-82). Toxicities leading to bladder removal included bladder neck contractures, prostatic necrosis, incontinence, osteomyelitis, bladder calculi, fistulae, urethral strictures, abscesses, necrotizing fasciitis, and radiation/hemorrhagic cystitis. The mean number of failed conservative, minimally invasive interventions per patients prior to cystectomy was 3.7 (range 1-12). The average time period from major complication following radiotherapy/cryotherapy to cystectomy was 29.1 months (range 5-65). The QOL survey showed all of the patients who completed the survey (n = 13) would undergo the procedure again and 11 (85%) would have undergone the procedure an average of 13.2 months sooner (range 5-36). CONCLUSION: Toxicities secondary to prostatic radiotherapy or cryotherapy may be debilitating. Our results demonstrate that cystectomy with urinary diversion can improve QOL in patients with a devastated lower urinary tract.


Asunto(s)
Crioterapia/efectos adversos , Cistectomía/métodos , Neoplasias de la Próstata/terapia , Radioterapia/efectos adversos , Vejiga Urinaria/lesiones , Vejiga Urinaria/cirugía , Derivación Urinaria/métodos , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/radioterapia , Calidad de Vida , Traumatismos por Radiación/cirugía , Resultado del Tratamiento , Vejiga Urinaria/efectos de la radiación
10.
Ultrasound Med Biol ; 50(10): 1494-1505, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39054243

RESUMEN

OBJECTIVE: The goal of this study was to evaluate the performance of different commercial ultrasound contrast microbubbles (MBs) when measuring bladder phantom pressure with sub-harmonic-aided pressure estimation (SHAPE) methodology. We hypothesized that SHAPE performance is dependent on MB formulation. This study aimed to advance the SHAPE application for bladder pressure measurements in humans. METHODS: Using a previously designed and built bladder phantom, we tested four different commercial agents: Definity, Lumason, Sonazoid and Optison. A standard clinical cystometrogram (CMG) system was used to infuse a MB-saline mixture into the bladder phantom to measure pressure. Ultrasound imaging was performed using the GE Healthcare LOGIQ E10 scanner. RESULTS: All agents showed a predicted inverse linear relationship between change in pressure and SHAPE signal. However, they differ from each other in terms of stability, linear correlation, sensitivity to pressure and error. Generally, Definity and Lumason showed the highest performance during the SHAPE-based bladder phantom pressure assessments. CONCLUSION: Our results show that the SHAPE signal decreases as bladder phantom pressures increases, regardless of the agent or CMG phase, suggesting the possibility of using SHAPE for measuring bladder pressure without a catheter. However, the efficacy of SHAPE in measuring pressure varies by MB formulation. These observations support using Lumason and Definity in a human subject feasibility study as we advance toward a catheter-free solution for measuring voiding bladder pressure via SHAPE.


Asunto(s)
Medios de Contraste , Fluorocarburos , Microburbujas , Fantasmas de Imagen , Presión , Ultrasonografía , Vejiga Urinaria , Vejiga Urinaria/diagnóstico por imagen , Ultrasonografía/métodos , Humanos , Hierro , Compuestos Férricos , Óxidos , Reproducibilidad de los Resultados , Albúminas
11.
Acad Med ; 99(8): 868-873, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38166317

RESUMEN

PURPOSE: Left-handed medical students contend with unique educational barriers within surgery, such as lack of educational resources, lack of left-handed-specific training, and widespread stigmatization of surgical left-handedness. This study aimed to highlight the surgical experiences of left-handed medical students so educators may be empowered to act with greater care and appreciation of these students' circumstances. METHOD: In this qualitative study, the authors conducted semistructured interviews on surgical experiences during medical school between January 31, 2021, and June 20, 2021, on 31 current surgical residents and fellows from 15 U.S. institutions and 6 surgical specialties. Left-handed trainees were included regardless of their surgical hand dominance. RESULTS: The authors identified 3 themes related to left-handed medical students' surgical experience: (1) disorienting advice from faculty or residents, (2) discouraging right-handed pressures and left-handed stigmatization, and (3) educational wishes of left-handed medical students. Trainees describe dialogues during medical school in which their handedness was directly addressed by residents and faculty with disorienting and nonbeneficial advice. Often trainees were explicitly told which hand to use, neglecting any preferences of the left-handed student. Participants also described possible changes in future surgical clerkships, including normalization of left-handedness, tangible mentorship, or granular and meaningful instruction. CONCLUSIONS: Left-handed medical students encounter unique challenges during their surgical education. These students report being disoriented by the variability of advice provided by mentors, discouraged by how pressured they feel to operate right-handed, and burdened by the need to figure things out by themselves in the absence of adequate left-handed educational resources. Surgical education leadership should detail the unique problems left-handed learners face, impartially elicit the learner's current operative hand preference, take responsibility for their left-handed students, promote acceptance and accommodation strategies of left-handed surgical trainees, and endeavor to improve the breadth of left-handed surgical resources.


Asunto(s)
Investigación Cualitativa , Estudiantes de Medicina , Humanos , Estudiantes de Medicina/psicología , Estudiantes de Medicina/estadística & datos numéricos , Femenino , Masculino , Lateralidad Funcional , Internado y Residencia , Estados Unidos , Adulto , Cirugía General/educación , Entrevistas como Asunto , Educación de Pregrado en Medicina/métodos
12.
Ultrasound Med Biol ; 49(1): 136-151, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36244919

RESUMEN

The goal of this study was to evaluate ultrasound contrast microbubbles (MB) stability during a typical cystometrogram (CMG) for bladder pressure measurement application using the subharmonic-aided pressure estimation technique. A detailed study of MB stability was required given two unique characteristics of this application: first, bulk infusion of MBs into the bladder through the CMG infusion system, and second, duration of a typical CMG which may last up to 30 min. To do so, a series of size measurement and contrast-enhanced ultrasound imaging studies under different conditions were performed and the effects of variables that we hypothesized have an effect on MB stability, namely, i) IV bag air headspace, ii) MB dilution factor, and iii) CMG infusion system were investigated. The results verified that air volume in intravenous (IV) bag headspace was not enough to have a significant effect on MB stability during a CMG. We also showed that higher MB dosage results in a more stable condition. Finally, the results indicated that the CMG infusion system adversely affects MB stability. In summary, to ensure MB stability during the entire duration of a CMG, lower filling rates (limited by estimated bladder capacity in clinical applications) and/or higher MB dosage (limited by FDA regulations and shadowing artifact) and/or the consideration of alternative catheter design may be needed.


Asunto(s)
Microburbujas , Vejiga Urinaria , Vejiga Urinaria/diagnóstico por imagen , Ultrasonografía , Medios de Contraste , Pelvis
13.
Invest Radiol ; 58(3): 181-189, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36070543

RESUMEN

OBJECTIVES: The long-term goal of this study is to investigate the efficacy of a novel, ultrasound-based technique called subharmonic-aided pressure estimation (SHAPE) to measure bladder pressure as a part of a cystometrogram (CMG) in a urodynamic test (ie, pressure-flow study). SHAPE is based on the principle that subharmonic emissions from ultrasound contrast microbubbles (MBs) decrease linearly with an increase in ambient pressure. We hypothesize that, using the SHAPE technique, we can measure voiding bladder pressure catheter-free. This is of importance because the CMG catheter, due to its space-occupying property and non-physiological effects, can undermine the reliability of the test during voiding and cause misdiagnosis. In this study, we tested this hypothesis and optimized the protocol in a controlled benchtop environment. MATERIALS AND METHODS: A bladder phantom was designed and built, capable of simulating clinically relevant bladder pressures. Laboratory-made lipid-shelled MBs (similar in composition to the commercial agent, DEFINITY) was diluted in 0.9% normal saline and infused into the bladder phantom using the CMG infusion system. A typical simulated CMG consists of 1 filling and 4 post-filling events. During CMG events, the bladder phantom is pressurized multiple times at different clinically relevant levels (small, medium, and large) to simulate bladder pressures. Simultaneous with pressurization, MB subharmonic signal was acquired. For each event, the change in MB subharmonic amplitude was correlated linearly with the change in bladder phantom pressure, and the SHAPE conversion factor (slope of the linear fit) was determined. In doing so, a specific signal processing technique (based on a small temporal window) was used to account for time-decay of MB subharmonic signal during a simulated CMG. RESULTS: A strong inverse linear relationship was found to exist between SHAPE and bladder phantom pressures for each of the CMG filling and post-filling events ( r2> 0.9, root mean square error < 0.3 dB, standard error <0.01 dB, and P < 0.001). SHAPE showed a transient behavior in measuring bladder phantom pressure. The SHAPE conversion factor (in dB/cm H 2 O) varied between filling and post-filling events, as well as by post-filling time. The magnitude of the SHAPE conversion factor tended to increase immediately after filling and then decreases with time. CONCLUSIONS: Microbubble subharmonic emission is an excellent indicator of bladder phantom pressure variation. The strong correlation between SHAPE signal and bladder phantom pressure is indicative of the applicability of this method in measuring bladder pressure during a CMG. Our results suggest that different SHAPE conversion factors may be needed for different events during a CMG (ie, at different time points of a CMG). These findings will help us better protocolize this method for introduction into human subjects and allow us to take the next step toward developing a catheter-free voiding CMG using SHAPE.


Asunto(s)
Medios de Contraste , Vejiga Urinaria , Humanos , Vejiga Urinaria/diagnóstico por imagen , Reproducibilidad de los Resultados , Ultrasonografía/métodos , Fantasmas de Imagen , Microburbujas
14.
bioRxiv ; 2023 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-38106029

RESUMEN

Spinal cord injury (SCI) evokes profound bladder dysfunction. Current treatments are limited by a lack of molecular data to inform novel therapeutic avenues. Previously, we showed systemic inosine treatment improved bladder function following SCI in rats. Here, we applied multi-omics analysis to explore molecular alterations in the bladder and their sensitivity to inosine following SCI. Canonical pathways regulated by SCI included those associated with protein synthesis, neuroplasticity, wound healing, and neurotransmitter degradation. Upstream regulator analysis identified MYC as a key regulator, whereas causal network analysis predicted multiple regulators of DNA damage response signaling following injury, including PARP-1. Staining for both DNA damage (γH2AX) and PARP activity (poly-ADP-ribose) markers in the bladder was increased following SCI, and attenuated in inosine-treated tissues. Proteomics analysis suggested that SCI induced changes in protein synthesis-, neuroplasticity-, and oxidative stress-associated pathways, a subset of which were shown in transcriptomics data to be inosine-sensitive. These findings provide novel insights into the molecular landscape of the bladder following SCI, and highlight a potential role for PARP inhibition to treat neurogenic bladder dysfunction.

15.
Adv Chronic Kidney Dis ; 29(3): 308-317, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-36084977

RESUMEN

Common causes of pediatric ESRD are distinct from those seen in the adult population. In the pediatric population, the most common are congenital anomalies of the kidney and urinary tract (CAKUT), affecting approximately 30% of children with CKD. These structural anomalies often require coordinated care with the pediatric urology team to address voiding issues, bladder involvement, and the potential need for surgical intervention. For pediatric nephrologists and urologists, common CAKUT that are encountered include antenatal hydronephrosis, obstructive uropathies (eg, posterior urethral valves), and vesicoureteral reflux. As more pediatric patients with CAKUT, CKD, and ESRD transition to adult care, it is important for receiving adult nephrologists to understand the clinical presentation, natural history, and prognosis for these diagnoses. This review outlines the diagnosis and potential interventions for these conditions, including strategies to address bladder dysfunction that is often seen in children with CAKUT. A discussion of these management decisions (including surgical intervention) for CAKUT, which are quite common to pediatric nephrology and urology practices, may provide unique learning opportunities for adult nephrologists who lack familiarity with these pediatric conditions.


Asunto(s)
Fallo Renal Crónico , Insuficiencia Renal Crónica , Urología , Reflujo Vesicoureteral , Adulto , Niño , Femenino , Humanos , Fallo Renal Crónico/cirugía , Embarazo , Insuficiencia Renal Crónica/terapia , Anomalías Urogenitales , Reflujo Vesicoureteral/complicaciones , Reflujo Vesicoureteral/diagnóstico , Reflujo Vesicoureteral/terapia
16.
J Pediatr Adolesc Gynecol ; 35(4): 496-500, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35124215

RESUMEN

BACKGROUND: Cloacal anomalies occur when a fetus's rectum, vagina, and urethra fail to separate and result in 1 common channel at birth. They are commonly managed by complex reconstruction in the first year of life. This manuscript presents an alternative approach to management in patients with absent or nondilated Mullerian structures. CASE: Image-guided, combined endoscopic and laparoscopic surgery (CELS) was used to perform an anorectal pull-through at 5 months of age on a patient with persistent cloaca and no definite vaginal or uterine structures seen on MRI and endoscopy. Urogenital reconstruction is delayed until adolescence. SUMMARY AND CONCLUSION: We hypothesize that performing a minimally invasive anorectoplasty on patients with complicated anatomy and low risk for hydrocolpos could potentially result in improved urologic function and better psychosocial outcomes. Delaying vaginoplasty will enable determination of the function of remnant Mullerian structures and allow the patient to direct the augmentation approach.


Asunto(s)
Hidrocolpos , Laparoscopía , Adolescente , Animales , Cloaca/anomalías , Cloaca/cirugía , Femenino , Procedimientos Quirúrgicos Ginecológicos , Humanos , Hidrocolpos/cirugía , Recién Nacido , Recto/cirugía , Uretra , Vagina/anomalías , Vagina/cirugía
17.
J Clin Med ; 11(15)2022 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-35956025

RESUMEN

People with cloacal malformation and 46,XX cloacal exstrophy are at risk of developing Müllerian outflow tract obstruction (OTO). Management of OTO requires expertise of many medical and surgical specialties. The primary presenting symptom associated with OTO is cyclical and later continuous pain and can be initially quelled with hormonal suppression as a temporizing measure to allow for patient maturation. The decision for timing and method of definitive treatment to establish a patent outflow tract that can also be used for penetrative sexual activity and potential fertility is a complicated one and incredibly variable based on patient age alone. To understand the management approach to OTO, we put forth five phases with associated recommendations: (1) caregiver and patient education and evaluation before obstruction; (2) presentation, diagnosis, and symptom temporization; (3) readiness assessment; (4) peri-procedural management; (5) long-term surveillance. This review will emphasize the importance of interdisciplinary team management of the complex shared medical, surgical, and psychological decision making required to successfully guide developing patients with outflow obstruction secondary to cloacal malformations and cloacal exstrophy through adolescence.

18.
J Pediatr Urol ; 17(6): 795.e1-795.e6, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34544632

RESUMEN

INTRODUCTION: Flexible ureteroscopes are not tailored for pediatric ureteral size and may not pass at first attempt into the pediatric ureter. Administration of tamsulosin preoperatively in adults has been shown to facilitate ureteral access sheath placement. Several studies have shown tamsulosin to be safe and effective when utilized for medical expulsive therapy in pediatric patients, but its utility for preoperative ureteral dilation has not been studied to date. OBJECTIVE: We hypothesized that preoperative tamsulosin reduces failed ureteroscopic access in children. MATERIALS AND METHODS: We conducted a retrospective review of patients aged 0-18 years undergoing flexible ureteroscopy (URS) from 2014 to 2019 at a single institution. Patients were divided into those taking 0.4 mg of tamsulosin daily for at least 1 week prior to surgery and those not taking tamsulosin. The primary outcome was failure to pass a 7.95 Fr flexible ureteroscope on initial attempt, requiring stent placement and staged management. Patients undergoing URS or stent placement within the prior year, requiring semi-rigid URS, or with genitourinary anomalies were excluded. RESULTS AND DISCUSSION: A total of 49 patients met inclusion criteria. The tamsulosin group (n = 13) and non-tamsulosin group (n = 36) were similar with respect to demographic data. The percentage of prepubertal patients was 53% vs 33% (p = 0.19). The tamsulosin group had lower failed URS (38% vs 61%, p = 0.20). When stratified by age, both prepubertal and postpubertal patients in the tamsulosin group had lower failed URS (43% vs 67%, p = 0.67 and 33% vs 58%, p = 0.38). These clinically significant results suggest initial passage of a flexible ureteroscope is more successful in pediatric patients on preoperative tamsulosin. This study was largely limited by its low power and flaws inherent to its retrospective design. CONCLUSION: Our results have implications for prescribing tamsulosin preoperatively to reduce multiple procedures and anesthetics in children. Adequately powered prospective trials are warranted to confirm preoperative tamsulosin reduces failed first-attempt flexible URS in children.


Asunto(s)
Cálculos Ureterales , Ureteroscopía , Adulto , Niño , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Instituciones Académicas , Stents , Tamsulosina , Resultado del Tratamiento
19.
J Biomech ; 113: 110123, 2020 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-33242822

RESUMEN

The motivation behind this study is to understand how ureterovesical junction (UVJ) deformation during urine storage in the bladder affects vesicoureteral reflux (VUR), when urine flows backward from the bladder toward the kidneys. Using nonlinear, large deformation finite element simulations, the deformation of the bladder wall during urine storage is modeled in this study. The bladder wall is assumed to be a homogeneous, isotropic, hyperelastic spherical shell with a finite thickness. The UVJ is defined as a straight elliptical cylindrical hole through the bladder wall at the reference configuration before inflation. Broad parametric studies on different UVJ configurations are performed as the bladder inner surface stretches by a factor of 2.2 from an initial radius corresponding to bladder volumes of 10% to slightly over physiologic capacity. For each considered UVJ configuration, a simple fluid analysis of the tunnel flow resistance compares different bladder inner surface stretch ratios. Our model shows that the deformation of the UVJ depends on its orientation with respect to the bladder wall radial and circumferential directions. We show that as the UVJ insertion angle increases, the UVJ cross section decreases and its tunnel length increases during urine storage causing the closure of the UVJ and a rise in its flow resistance. The modeling results indicate that UVJ closure could be explained by bladder wall deformation rather than the local differential pressure. Our findings are consistent with the accepted primary anti-reflux mechanism of the UVJ being dependent on the tunnel length-to-diameter ratio and consequently the UVJ insertion angle.


Asunto(s)
Líquidos Corporales , Uréter , Reflujo Vesicoureteral , Humanos
20.
J Pediatr Urol ; 16(4): 435.e1-435.e6, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32616376

RESUMEN

PURPOSE: The Multi-Institutional Bladder Exstrophy Consortium (MIBEC) was established in 2013 to refine technical aspects of the complete primary repair of bladder exstrophy (CPRE), to decrease complications, and to improve outcomes. In order to place outcomes from the consortium into context of historic outcomes, we evaluated continence and dry intervals in children who were repaired prior to the beginning of the consortium at these institutions. We hypothesized that continence (voiding with dryness) is rarely achieved after primary CPRE and surgery following CPRE improves dryness but may hinder voiding per urethra. MATERIALS AND METHODS: We reviewed prospectively maintained IRB approved databases of children who underwent CPRE for classic bladder exstrophy (BE) between 5/1993 and 1/2013 at 3 institutions. Exclusion criteria included: lack of continence documentation, and lack of follow up subsequent to January 2014. We recorded age at closure, method of bladder emptying, bladder capacity and surgical history. We used a 3 part dryness scale for both patients who void volitionally and those on CIC. Children were considered dry if they could hold urine for over 3 h. An intermediate group was defined as having a dry interval of 2-3 h, with minimal dampness in between voids. If dry intervals were <2 h with frequent leakage, children were considered wet. RESULTS: A total of 54 of 73 (38 M) children met inclusion criteria. 35 of 54 (64.8%) children void per urethra, while 18 (33.3%) perform clean intermittent catheterization (CIC) and 1 underwent a vesicostomy due to incomplete emptying and UTI's. 25/35 (71.4%) of those voiding per urethra underwent CPRE only, while the remaining 10 underwent secondary continence procedures. In total, 26 of 54 (48.1%) are dry, that is either continent or not wet for > 3 h, while only 11/54 (20.4%) are truly continent, i.e., voiding per urethra. Only 9/54 (16.7%) are continent after a single surgery (CPRE). 14/54 children who are dry (25.9%) underwent a bladder neck procedure with or without augmentation and empty with CIC. DISCUSSION AND CONCLUSION: Granular detail about the specifics of emptying, surgical history, and dry intervals is crucial to understand the true outcomes from the repair of BE. Children with BE undergoing CPRE prior to the institution of MIBEC experienced variable results, with only 17% achieving continence while spontaneously voiding per urethra without additional reconstruction. We are now engaged in MIBEC to identify factors that contribute to continence and to attempt to render such findings reproducible.


Asunto(s)
Extrofia de la Vejiga , Extrofia de la Vejiga/cirugía , Niño , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Micción , Procedimientos Quirúrgicos Urológicos
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