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1.
Am J Physiol Renal Physiol ; 326(2): F241-F248, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37916288

RESUMO

Neurogenic bladder poses a major morbidity in children with spina bifida (SB), and videourodynamic studies (VUDS) are used to stratify this risk. This small-scale pilot study utilized current mass-spectrometry-based proteomic approaches to identify peptides or proteins in urine that may differentiate children at high risk of developing renal complications from a neurogenic bladder. Twenty-two urine samples of which nine had high bladder pressure storage that put the upper urinary tract at risk, while 13 with a lower risk for renal compromise were analyzed. More than 1,900 peptides across all 22 samples were quantified, and 115 peptides differed significantly (P < 0.05) between the two groups. Using machine learning approaches five peptides that showed the greatest differences between these two clinical categories were used to build a classifier. We tested this classifier by blind analysis of an additional six urine samples and showed that it correctly assigned the unknown samples in their proper risk category. These promising results indicate that a urinary screening test based on peptides could be performed on a regular basis to stratify the neurogenic bladder into low or high-risk categories. Expanding this work to larger cohorts as well as across a broad spectrum of urodynamics outcomes may provide a useful diagnostic test for neurogenic bladder.NEW & NOTEWORTHY This approach could help risk stratify the neurogenic bladder in patients with spina bifida and could allow us to safely defer on up to 1/3 of urodynamic studies. These pilot data justify a larger trial before this approach becomes a clinical tool.


Assuntos
Disrafismo Espinal , Bexiga Urinaria Neurogênica , Criança , Humanos , Bexiga Urinaria Neurogênica/diagnóstico , Bexiga Urinaria Neurogênica/etiologia , Projetos Piloto , Proteômica , Bexiga Urinária , Disrafismo Espinal/complicações , Disrafismo Espinal/diagnóstico , Urodinâmica , Peptídeos
2.
J Pediatr Urol ; 19(5): 542.e1-542.e7, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37537092

RESUMO

INTRODUCTION: Non-neurogenic lower urinary tract dysfunction (LUTD) is one of the most common reasons for presentation to a pediatric urologist, affecting up to 20% of children. Predicting who will benefit from RBUS as part of their work-up is challenging as the majority will have normal imaging. OBJECTIVE: Our objective was to assess the utility of using the Dysfunctional Voiding and Incontinence Scoring System (DVISS) and urinary tract infection (UTI) history to predict which LUTD patients were most likely to have an abnormal RBUS as well as determine a DVISS cutoff to aid in making this prediction. We hypothesized that higher DVISS scores and a positive urinary tract infection (UTI) history would be associated with increased likelihood of RBUS abnormality. STUDY DESIGN: We retrospectively reviewed outpatients seen for LUTD from 5/2014-1/2016 who received an RBUS. Association between prior UTI, DVISS score, gender, and race and RBUS abnormality were evaluated using logistic regression analysis. Receiver operating characteristic (ROC) curves were created to evaluate the predictive model and a Youden index calculated to determine the optimal cutoff for DVISS score to predict abnormal RBUS. RESULTS: 15 of 333 patients (4.5%) had a clinically significant RBUS abnormality. Significantly more patients with abnormal RBUS had a positive UTI history and median DVISS was higher. UTI history and DVISS score were associated with RBUS abnormality whereas neither gender nor race were. A DVISS score cutoff of 12 was determined to be ideal for predicting abnormal imaging. Using DVISS≥12 and positive UTI history, patients with both risk factors were significantly more likely to have an abnormal RBUS than those with zero or one risk factor (Figure). DISCUSSION: To the best of our knowledge this is the first study to try to identify risk factors associated with RBUS abnormality in pediatric LUTD patients and create an evidence-based approach to imaging these patients. We found both DVISS cutoff ≥12 and positive UTI history to be useful to risk stratify LUTD patients' likelihood of abnormal RBUS. Limitations include the study's retrospective nature as well as the fact the population was drawn from a tertiary care pediatric hospital with a large referral population and the fact that the decision to order an RBUS was based on individual clinician preference and decision making. CONCLUSIONS: We found that DVISS score≥12 and UTI history are useful in guiding the decision to obtain RBUS in pediatric LUTD patients.


Assuntos
Infecções Urinárias , Criança , Humanos , Estudos Retrospectivos , Infecções Urinárias/epidemiologia , Bexiga Urinária/diagnóstico por imagem , Ultrassonografia , Fatores de Risco
3.
J Pediatr Urol ; 19(5): 566.e1-566.e8, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37286464

RESUMO

INTRODUCTION: Grading of hydronephrosis severity on postnatal renal ultrasound guides management decisions in antenatal hydronephrosis (ANH). Multiple systems exist to help standardize hydronephrosis grading, yet poor inter-observer reliability persists. Machine learning methods may provide tools to improve the efficiency and accuracy of hydronephrosis grading. OBJECTIVE: To develop an automated convolutional neural network (CNN) model to classify hydronephrosis on renal ultrasound imaging according to the Society of Fetal Urology (SFU) system as potential clinical adjunct. STUDY DESIGN: A cross-sectional, single-institution cohort of postnatal renal ultrasounds with radiologist SFU grading from pediatric patients with and without hydronephrosis of stable severity was obtained. Imaging labels were used to automatedly select sagittal and transverse grey-scale renal images from all available studies from each patient. A VGG16 pre-trained ImageNet CNN model analyzed these preprocessed images. Three-fold stratified cross-validation was used to build and evaluate the model that was used to classify renal ultrasounds on a per patient basis into five classes based on the SFU system (normal, SFU I, SFU II, SFU III, or SFU IV). These predictions were compared to radiologist grading. Confusion matrices evaluated model performance. Gradient class activation mapping demonstrated imaging features driving model predictions. RESULTS: We identified 710 patients with 4659 postnatal renal ultrasound series. Per radiologist grading, 183 were normal, 157 were SFU I, 132 were SFU II, 100 were SFU III, and 138 were SFU IV. The machine learning model predicted hydronephrosis grade with 82.0% (95% CI: 75-83%) overall accuracy and classified 97.6% (95% CI: 95-98%) of the patients correctly or within one grade of the radiologist grade. The model classified 92.3% (95% CI: 86-95%) normal, 73.2% (95% CI: 69-76%) SFU I, 73.5% (95% CI: 67-75%) SFU II, 79.0% (95% CI: 73-82%) SFU III, and 88.4% (95% CI: 85-92%) SFU IV patients accurately. Gradient class activation mapping demonstrated that the ultrasound appearance of the renal collecting system drove the model's predictions. DISCUSSION: The CNN-based model classified hydronephrosis on renal ultrasounds automatically and accurately based on the expected imaging features in the SFU system. Compared to prior studies, the model functioned more automatically with greater accuracy. Limitations include the retrospective, relatively small cohort, and averaging across multiple imaging studies per patient. CONCLUSIONS: An automated CNN-based system classified hydronephrosis on renal ultrasounds according to the SFU system with promising accuracy based on appropriate imaging features. These findings suggest a possible adjunctive role for machine learning systems in the grading of ANH.


Assuntos
Hidronefrose , Urologia , Humanos , Criança , Feminino , Gravidez , Urologia/educação , Estudos Retrospectivos , Reprodutibilidade dos Testes , Estudos Transversais , Hidronefrose/diagnóstico por imagem , Ultrassonografia
4.
J Urol ; 210(2): 352-359, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37195856

RESUMO

PURPOSE: Testosterone administration prior to hypospadias repair is common practice among pediatric urologists; however, its impact on surgical outcomes remains controversial. We hypothesize that testosterone administration prior to distal hypospadias repair with urethroplasty significantly decreases postoperative complications. MATERIALS AND METHODS: We queried our hypospadias database for primary distal hypospadias repairs with urethroplasty from 2015 to 2021. Patients undergoing repair without urethroplasty were excluded. We collected information on patient age, procedure type, testosterone administration status, initial visit and intraoperative glans width, urethroplasty length, and postoperative complications. To determine the role of testosterone administration on incidence of complications, a logistic regression adjusting for initial visit glans width, urethroplasty length, and age was performed. RESULTS: A total of 368 patients underwent distal hypospadias repair with urethroplasty. One hundred thirty-three patients received testosterone and 235 did not. Initial visit glans width was significantly larger in the no-testosterone vs testosterone group (14.5 mm vs 13.1 mm, P = .001). Testosterone patients had significantly larger glans width at the time of surgery (17.1 mm vs 14.6 mm [no-testosterone group], P = .001). On multivariable logistic regression analysis after controlling for age at surgery, preoperative glans width, testosterone status, and urethroplasty length, testosterone administration did show significant association with reduced odds of postoperative complications (OR 0.4, P = .039). CONCLUSIONS: This retrospective review of patients shows that on multivariable analysis there is significant association between testosterone administration and decreased incidence of complications in patients undergoing distal hypospadias repair with urethroplasty. Future studies on testosterone administration should focus on specific cohorts of patients with hypospadias as benefits of testosterone may be more evident in some subgroups than others.


Assuntos
Hipospadia , Procedimentos de Cirurgia Plástica , Masculino , Humanos , Criança , Lactente , Hipospadia/cirurgia , Hipospadia/complicações , Testosterona , Uretra/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos , Procedimentos Cirúrgicos Urológicos Masculinos/métodos
7.
Urology ; 178: 137, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37230865
9.
J Urol ; 209(5): 994-1003, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36787376

RESUMO

PURPOSE: Urologists rely heavily on videourodynamics to identify patients with neurogenic bladders who are at risk of upper tract injury, but their interpretation has high interobserver variability. Our objective was to develop deep learning models of videourodynamics studies to categorize severity of bladder dysfunction. MATERIALS AND METHODS: We performed a cross-sectional study of patients aged 2 months to 28 years with spina bifida who underwent videourodynamics at a single institution between 2019 and 2021. The outcome was degree of bladder dysfunction, defined as none/mild, moderate, and severe, defined by a panel of 5 expert reviewers. Reviewers considered factors that increase the risk of upper tract injury, such as poor compliance, elevated detrusor leak point pressure, and detrusor sphincter dyssynergia, in determining bladder dysfunction severity. We built 4 models to predict severity of bladder dysfunction: (1) a random forest clinical model using prospectively collected clinical data from videourodynamics studies, (2) a deep learning convolutional neural network of raw data from the volume-pressure recordings, (3) a deep learning imaging model of fluoroscopic images, (4) an ensemble model averaging the risk probabilities of the volume-pressure and fluoroscopic models. RESULTS: Among 306 videourodynamics studies, the accuracy and weighted kappa of the ensemble model classification of bladder dysfunction when at least 75% expected bladder capacity was reached were 70% (95% CI 66%,76%) and 0.54 (moderate agreement), respectively. The performance of the clinical model built from data extracted by pediatric urologists was the poorest with an accuracy of 61% (55%, 66%) and a weighted kappa of 0.37. CONCLUSIONS: Our models built from urodynamic pressure-volume tracings and fluoroscopic images were able to automatically classify bladder dysfunction with moderately high accuracy.


Assuntos
Aprendizado Profundo , Disrafismo Espinal , Bexiga Urinaria Neurogênica , Criança , Humanos , Bexiga Urinária/diagnóstico por imagem , Estudos Transversais , Bexiga Urinaria Neurogênica/diagnóstico , Bexiga Urinaria Neurogênica/etiologia , Disrafismo Espinal/complicações , Urodinâmica
10.
J Racial Ethn Health Disparities ; 10(4): 1735-1744, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-35960437

RESUMO

BACKGROUND AND OBJECTIVES: The Dysfunctional Voiding and Incontinence Scoring System (DVISS) is a validated tool to evaluate lower urinary tract dysfunction (LUTD) severity in children. DVISS provides a quantitative score (0-35) including a quality-of-life measure, with higher values indicating more/worse symptoms. Clinically, variability exists in symptom severity when patients present to pediatric urology with LUTD. We hypothesized that symptom severity at consultation varied based on race, gender, and/or socioeconomic status. METHODS: All urology encounters at a single institution with completed modified DVISS scores 6/2015-3/2018 were reviewed. Initial visits for patients 5-21 years old with non-neurogenic LUTD were included. Patients with neurologic disorders or genitourinary tract anomalies were excluded. Wilcoxon rank sum tests compared scores between White and Black patients and between male and female patients. Multiple regression models examined relationships among race, gender, estimated median household income, and insurance payor type. All statistics were performed using Stata 15. RESULTS: In total, 4086 initial patient visits for non-neurogenic LUTD were identified. Median DVISS scores were higher in Black (10) versus White (8) patients (p < 0.001). Symptom severity was higher in females (9) versus males (8) (p < 0.001). When estimated median income and insurance payer types were introduced into a multiple regression model, race, gender, and insurance payer type were significantly associated with symptom severity at presentation. CONCLUSIONS: Race, gender, and socioeconomic status significantly impact LUTS severity at the time of urologic consultation. Future studies are needed to clarify the etiologies of these disparities and to determine their clinical significance.


Assuntos
Sintomas do Trato Urinário Inferior , Qualidade de Vida , Encaminhamento e Consulta , Determinantes Sociais da Saúde , Transtornos Urinários , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Adulto Jovem , População Negra , Classe Social , Transtornos Urinários/diagnóstico , Sintomas do Trato Urinário Inferior/diagnóstico , Fatores Sexuais , Fatores Raciais , Negro ou Afro-Americano , Brancos , Índice de Gravidade de Doença , Fatores Socioeconômicos
11.
J Ultrasound Med ; 42(1): 17-26, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35460290

RESUMO

PURPOSE: This retrospective study was designed to evaluate which lower urinary tract ultrasound parameter(s) could predict the results of invasive urodynamic testing which are the current reference standard in the evaluation of bladder dysfunction in children with spina bifida. MATERIALS AND METHODS: Fifty eight children with spina bifida undergoing video urodynamic evaluation and a renal bladder ultrasound as their standard of care were evaluated. Quantitative and qualitative ultrasound parameters were then correlated with the videourodynamic study results which served as the reference standard. RESULTS: For bladders with ending storage pressures above 15 cm H2 O, there were increases in these ultrasound measured parameters: 1) bladder mass (P = .00019), 2) bladder/body mass ratio (P = .0059), and 3) wall thickness (P = .01). We defined the storage cost as the final storage pressure divided by the percentage of expected bladder capacity attained. These data were analyzed to compute receiver operating curves with assuming end storage pressures cutoff points of 15, 20, 30, and 40 cm H2 O. The optimal area under the curve was found for a bladder weight of 65 g and a pressure cutoff of 30 cm H2 O with a sensitivity of 75% with a specificity of 84%. CONCLUSION: Bladder weight is independent of luminal volume, can be normalized to body weight, and may serve as a clinically valuable tool for noninvasive screening to define a subset of patients with neurogenic bladder with a higher likelihood of having abnormal videourodynamic results.


Assuntos
Disrafismo Espinal , Bexiga Urinaria Neurogênica , Criança , Humanos , Bexiga Urinária , Bexiga Urinaria Neurogênica/diagnóstico , Estudos Retrospectivos , Fluoroscopia , Urodinâmica
12.
J Pediatr Urol ; 18(4): 501.e1-501.e7, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35803865

RESUMO

INTRODUCTION AND OBJECTIVE: Opioid stewardship is recognized as a critical clinical priority. We previously reported marked reductions in narcotic administration after implementation of an opioid reduction protocol for pediatric ambulatory urologic surgery. We hypothesize that a decrease in post-operative and discharge opioid administration will not increase short-term adverse events. STUDY DESIGN: All pediatric patients undergoing open or robot-assisted laparoscopic pyeloplasty or ureteral reimplantation between 2015 and 2019 were included. Patients' demographics, opioid and NSAID administration, urology or pain-related emergency department (ED) visits, readmissions, and reoperations within 30 days of surgery, were aggregated. RESULTS: 438 patients, with a median age of 3.5 years (IQR 1.5-8.3) at the time of surgery, met the inclusion criteria. Annual rates of inpatient opioid administration and prescriptions decreased significantly over the study period, while rates of intra-operative, inpatient, and prescribed NSAIDs significantly increased. There was no significant difference in the occurrence of ED visits, readmissions, or reoperations within 30 days of surgery between patients who received an opioid prescription and those who did not. Multivariate regression showed that patients who did not receive an opioid prescription at discharge were found to be at a lower risk for unplanned encounters including ED visits, readmissions, or reoperations (OR:0.5, 95%CI: 0.2-0.9, p = 0.04). DISCUSSION: The present study shows the decreasing trend in inpatient opioid administration and opioid prescription after discharge, when accompanied by an increase NSAID administration, does not result in a significant change in rates of unplanned encounters and complications, similar to results from previous studies on non-urological and ambulatory urological surgeries. CONCLUSIONS: Non-opioid pain control after major pediatric urologic reconstruction is safe and effective. We found that a reduction in opioid administration can be associated with a reduced risk of unplanned ED visits, readmissions, or reoperations. Further investigations are required to corroborate this finding.


Assuntos
Analgésicos Opioides , Ureter , Humanos , Criança , Lactente , Pré-Escolar , Analgésicos Opioides/uso terapêutico , Ureter/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor , Estudos Retrospectivos
13.
Urology ; 166: 223-226, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35461916

RESUMO

OBJECTIVE: To report on our experience performing office-based pediatric urologic procedures. We hypothesize that office-based interventions are safe and effective for children, avoiding unnecessary risk and cost associated with general anesthesia. METHODS: We retrospectively identified patients undergoing office-based interventions from 2014 to 2019, including lysis of penile or labial adhesions, division of skin bridges, meatotomy and excision of benign lesion. Success was defined as a completed attempt in the office. Failure includes any unsuccessful office attempts. Complications include 30-day ED visits/readmissions and recurrent skin bridge post division of skin bridge. RESULTS: We identified 1326 interventions: 491 lyses of penile adhesions (37%), 320 division of skin bridges (24%), 128 lyses of labial adhesions (10%), 348 meatotomies (26%), and 39 excisions of benign lesions (3%) [Table 1]. There was a >95% success rate reported in every procedure with an overall complication rate of 0.6%. Excision of benign lesion had 100% success rate. ED visits within 30 days are rare (0.2%), and no patients required admission after their procedure [Table 2]. The rate of recurrence was highest following lysis of labial adhesions (13.3%). Of the 54 patients who underwent retreatment, very few required general anesthesia (n = 6). CONCLUSION: Office-based urologic interventions in children are well tolerated with excellent safety and efficacy. Complications and recurrence are universally low. Ultimately, 99.5% of this cohort was managed under local anesthetics, thereby avoiding the risks of anesthesia use in the pediatric population.


Assuntos
Procedimentos Cirúrgicos Ambulatórios , Anestésicos Locais , Procedimentos Cirúrgicos Ambulatórios/métodos , Anestesia Geral , Criança , Estudos de Coortes , Humanos , Estudos Retrospectivos
14.
J Pediatr Urol ; 18(3): 326.e1-326.e8, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35400575

RESUMO

BACKGROUND: Patients with neurogenic bladders are monitored with renal bladder ultrasounds and video urodynamics studies (VUDS) to assess upper urinary tract injury. Ultrasound shear wave elastography (US-SWE) can assess tissue stiffness. If bladder compliance is affected by bladder wall fibrosis and stiffening, then high-pressure bladders may be detectable by US-SWE therefore reducing the need for VUDS in some patients. OBJECTIVE: To determine if US-SWE can differentiate between low- and high-pressure bladders and hence be used for noninvasive assessment of neurogenic bladder in children. STUDY DESIGN: Prospective study of patients with neurogenic bladder undergoing clinically indicated VUDS between February and July of 2017. During VUDS, bladder wall US-SWE was measured at different filling percentages of estimated bladder capacity (EBC). The bladders were divided into cohorts according to the detrusor muscle pressure (Pdet) reached at the maximum bladder capacity: normal (1 to <15 cmH2O) and abnormal (≥15 cmH2O) pressure. T-test was used to compare elastography values at different bladder volumes and Pdet; (statistical significance set at p < 0.05). RESULTS: 30/31 enrolled children completed the protocol. With an empty bladder, as well as at all other bladder volumes, no relationship was observed between Pdet and mean SWE of the anterior or posterior bladder wall. At maximum bladder capacity, there was no difference between mean SWE values of the anterior or posterior bladder walls in those with normal pressure, 2.97 m/s (SD ± 0.82) and 1.96 m/s (SD ± 0.75), compared to those with abnormal pressures 3.08 m/s (SD ± 0.84) and 2.39 m/s (SD ± 0.96), p = 0.75 and p = 0.2, respectively. DISCUSSION: We found no difference between SWE values of either the anterior or posterior bladder wall in neurogenic bladders with normal and abnormal filling pressures measured during VUDS. Our study differs from previously reported studies with more positive results in that our cut-off for abnormal bladder pressure was (Pdet ≥15 cmH2O). This is lower than the more commonly used leak point pressure of 40 cmH2O because our practice is to intervene earlier. Moreover, SWE would be most useful if it can identify changes before the bladder has reached such severe conditions, to allow for early intervention. Additional differences between ours and other studies include US manufacturer and younger age of the participating children. CONCLUSIONS: US-SWE, while feasible, was not able to discriminate between low- and high-pressure bladders. Moreover, US-SWE did not show significant correlation with the current gold standard, VUDS.


Assuntos
Técnicas de Imagem por Elasticidade , Doenças da Bexiga Urinária , Bexiga Urinaria Neurogênica , Criança , Humanos , Técnicas de Imagem por Elasticidade/métodos , Estudos Prospectivos , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinaria Neurogênica/diagnóstico por imagem
15.
Front Synaptic Neurosci ; 13: 754786, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675794

RESUMO

The pontine nuclei comprising the locus coeruleus (LC) and Barrington's nucleus (BRN) amongst others form the neural circuitry(s) that coordinates arousal and voiding behaviors. However, little is known about the synaptic connectivity of neurons within or across these nuclei. These include corticotropin-releasing factor (CRF+) expressing neurons in the BRN that control bladder contraction and somatostatin expressing (SST+) neurons whose role in this region has not been discerned. To determine the synaptic connectivity of these neurons, we employed optogenetic stimulation with recordings from BRN and LC neurons in brain stem slices of channelrhodopsin-2 expressing SST or CRF neurons. Optogenetic stimulation of CRF+ BRN neurons of Crf Cre ;chr2-yfp mice had little effect on either CRF+ BRN neurons, CRF- BRN neurons, or LC neurons. In contrast, in Sst Cre ;chr2-yfp mice light-activated inhibitory postsynaptic currents (IPSCs) were reliably observed in a majority of LC but not BRN neurons. The GABAA receptor antagonist, bicuculline, completely abolished the light-induced IPSCs. To ascertain if these neurons were part of the neural circuitry that controls the bladder, the trans-synaptic tracer, pseudorabies virus (PRV) was injected into the bladder wall of Crf Cre ;tdTomato or Sst Cre ;tdTomato mice. At 68-72 h post-viral infection, PRV labeled neurons were present only in the BRN, being preponderant in CRF+ neurons with few SST+ BRN neurons labeled from the bladder. At 76 and 96 h post-virus injection, increased labeling was observed in both BRN and LC neurons. Our results suggest SST+ neurons rather than CRF+ neurons in BRN can regulate the activity of LC neurons.

16.
J Neurosci ; 41(34): 7314-7325, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34193553

RESUMO

Lower urinary tract or voiding disorders are prevalent across all ages and affect >40% of adults over 40 years old, leading to decreased quality of life and high health care costs. The pontine micturition center (PMC; i.e., Barrington's nucleus) contains a large population of neurons that localize the stress-related neuropeptide, corticotropin-releasing hormone (CRH) and project to neurons in the spinal cord to regulate micturition. How the PMC and CRH-expressing neurons in the PMC control volitional micturition is of critical importance for human voiding disorders. To investigate the specific role of CRH in the PMC, neurons in the PMC-expressing CRH were optogenetically activated during in vivo cystometry in unanesthetized mice of either sex. Optogenetic activation of CRH-PMC neurons led to increased intermicturition interval and voided volume, similar to the altered voiding phenotype produced by social stress. Female mice showed a significantly more pronounced phenotype change compared with male mice. These effects were eliminated by CRH-receptor 1 antagonist pretreatment. Optogenetic inhibition of CRH-PMC neurons led to an altered voiding phenotype characterized by more frequent voids and smaller voided volumes. Last, in a cyclophosphamide cystitis model of bladder overactivity, optogenetic activation of CRH-PMC neurons returned the voiding pattern to normal. Collectively, our findings demonstrate that CRH from PMC spinal-projecting neurons has an inhibitory function on micturition and is a potential therapeutic target for human disease states, such as voiding postponement, urinary retention, and underactive or overactive bladder.SIGNIFICANCE STATEMENT The pontine micturition center (PMC), which is a major regulator of volitional micturition, is neurochemically heterogeneous, and excitatory neurotransmission derived from PMC neurons is thought to mediate the micturition reflex. In the present study, using optogenetic manipulation of CRH-containing neurons in double-transgenic mice, we demonstrate that CRH, which is prominent in PMC-spinal projections, has an inhibitory function on volitional micturition. Moreover, engaging this inhibitory function of CRH can ameliorate bladder hyperexcitability induced by cyclophosphamide in a model of cystitis. The data underscore CRH as a novel target for the treatment of voiding dysfunctions, which are highly prevalent disease processes in children and adults.


Assuntos
Núcleo de Barrington/fisiologia , Hormônio Liberador da Corticotropina/metabolismo , Micção/fisiologia , Vias Aferentes/fisiologia , Animais , Proteínas Arqueais/genética , Núcleo de Barrington/citologia , Channelrhodopsins/genética , Hormônio Liberador da Corticotropina/genética , Ciclofosfamida/toxicidade , Cistite/induzido quimicamente , Cistite/tratamento farmacológico , Cistite/fisiopatologia , Feminino , Genes Reporter/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/fisiologia , Optogenética , Fotoquímica , Proteínas Recombinantes/genética , Medula Espinal/fisiologia , Urodinâmica , Volição
17.
J Pediatr Urol ; 17(4): 480.e1-480.e7, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34078574

RESUMO

INTRODUCTION: Widespread utilization of telemedicine in our practice to date has been limited to the evaluation of certain post-surgical patients. The COVID-19 pandemic acutely stressed our established system and required us to enhance our utilization of telemedicine. We hypothesized that expansion of telemedicine to new and follow up patient visits for pediatric urology could be done effectively in a way that satisfied patient and parental expectations. MATERIALS AND METHODS: Using a pre-COVID-19 established telemedicine program based in our electronic medical record (EMR), patients and providers transitioned to primarily virtual visits when clinically appropriate. Guidelines were formulated to direct patient scheduling, provider and staff education was provided, including a process map designed for multiple providers to complete video visits (VV), and the EMR was redesigned to incorporate telehealth terminology. The number of VV per provider was recorded using the electronic medical record, and patient reported outcomes (PRO) were measured using a standardized questionnaire. RESULTS: A total of 631 VV met inclusion criteria during the period of May 2018-April 2020. This included 334 follow up, 172 new, and 125 postoperative visits. The median age of patients at time of visit was 7 years (IQR 2-12 years), median visit time was 20 min (IQR 15-30 min), and the median travel distance saved by performing a VV was 12.2 miles (IQR 6.3-26.8 miles). Diagnoses were varied and included the entire breadth of a standard pediatric urology practice. The PRO questionnaire was completed for 325 of those patient visits. Families reported a high overall satisfaction with the video visits (median score of 10 out of 10) and felt that the visit met their child's medical needs. 90% stated that they would strongly recommend a telehealth visit to other families. Patients and parents reported benefits of VV including decreased travel costs and less time taken off from work and school. CONCLUSION: The EMR enabled nimble redirection of clinical care in the setting of a global pandemic. The enhanced use of telemedicine has proved to be an alternative method to provide care for pediatric urology patients. Families indicate a high degree of satisfaction with this technology in addition to significant time and cost savings. Telemedicine should remain a key aspect of medical care and expanded from post-operative visits to new patient and follow up visits, even as we return to our normal practices as the pandemic restrictions soften.


Assuntos
COVID-19 , Telemedicina , Urologia , Criança , Pré-Escolar , Redução de Custos , Humanos , Pacientes Ambulatoriais , Pandemias , Satisfação do Paciente , SARS-CoV-2
18.
J Urol ; 205(5): 1465, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33656358
19.
J Urol ; 205(3): 888-894, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33026928

RESUMO

PURPOSE: The risk factors for future infertility in adolescents with varicocele are controversial, and little is known about the association between hormone levels and semen parameters. Semen analysis is likely the closest marker of fertility but may be difficult to obtain in some boys secondary to personal, familial or religious reasons. Identifying other clinical surrogates for abnormal semen parameters may offer an alternative for assessing varicocele severity in these boys. We hypothesized that hormone levels and total testicular volume are predictive of abnormal total motile sperm count. MATERIALS AND METHODS: We retrospectively reviewed Tanner 5 boys with palpable left varicoceles who underwent a semen analysis and had serum hormone levels tested (luteinizing hormone, follicle-stimulating hormone, inhibin B, anti-müllerian hormone and/or total testosterone) within a 6-month period. Total testicular volume was also calculated. Abnormal total motile sperm count was defined as <9 million sperm per ejaculate. RESULTS: A total of 78 boys (median age 17.2 years, IQR 16.5-18.0) were included. Luteinizing hormone, anti-müllerian hormone and total testosterone were not correlated with any semen analysis parameter. There was a negative correlation between follicle-stimulating hormone and total motile sperm count (ρ -0.35, p=0.004) and positive correlation between inhibin B and total motile sperm count (ρ 0.50, p <0.001). Total testicular volume was significantly positively correlated with total motile sperm count (ρ 0.35, p=0.01). ROC analyses revealed an optimal follicle-stimulating hormone cutoff of 2.9, an optimal inhibin B cutoff of 204 and an optimal total testicular volume cutoff of 34.4 cc to predict abnormal total motile sperm count. CONCLUSIONS: Total motile sperm count is inversely associated with follicle-stimulating hormone levels, and directly associated with inhibin B levels and total testicular volume. Optimized cutoffs for serum follicle-stimulating hormone, inhibin B and total testicular volume may prove to be reasonable surrogates for total motile sperm count in boys who defer semen analysis for personal or religious/cultural reasons.


Assuntos
Contagem de Espermatozoides , Motilidade dos Espermatozoides , Testículo/anatomia & histologia , Varicocele/complicações , Adolescente , Hormônio Antimülleriano/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Inibinas/sangue , Hormônio Luteinizante/sangue , Masculino , Estudos Retrospectivos , Testosterona/sangue
20.
Urology ; 148: 264-266, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32707269

RESUMO

Ureteral triplication is a rare anomaly with about 100 total cases reported in the literature. In this case presentation, we present a case of ureteral triplication in a young female with a history of neurogenic bladder secondary to L5 lipomeningocele who presented with recurrent febrile urinary tract infections (UTIs) and vesicoureteral reflux despite antibiotic prophylaxis. Given her high grade reflux, she underwent ureteral reimplantation which ultimately led to resolution of her UTIs and reflux. Later in her clinical course, toilet training unmasked additional bladder dysfunction and she was successfully managed with clean intermittent catheterization and anticholinergics. To the best of our knowledge, this is the first case report to describe ureteral triplication, recurrent febrile UTIs and vesicoureteral reflux in the setting of a concomitant neurogenic bladder with a successful outcome.


Assuntos
Ureter/anormalidades , Ureter/cirurgia , Bexiga Urinaria Neurogênica/complicações , Infecções Urinárias/complicações , Refluxo Vesicoureteral/complicações , Anormalidades Múltiplas/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Reimplante , Ureter/diagnóstico por imagem , Infecções Urinárias/tratamento farmacológico , Refluxo Vesicoureteral/diagnóstico por imagem , Refluxo Vesicoureteral/cirurgia
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