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1.
J Urol ; 208(6): 1314-1322, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36215077

RESUMO

PURPOSE: Vesicoureteral reflux grading from voiding cystourethrograms is highly subjective with low reliability. We aimed to demonstrate improved reliability for vesicoureteral reflux grading with simple and machine learning approaches using ureteral tortuosity and dilatation on voiding cystourethrograms. MATERIALS AND METHODS: Voiding cystourethrograms were collected from our institution for training and 5 external data sets for validation. Each voiding cystourethrogram was graded by 5-7 raters to determine a consensus vesicoureteral reflux grade label and inter- and intra-rater reliability was assessed. Each voiding cystourethrogram was assessed for 4 features: ureteral tortuosity, proximal, distal, and maximum ureteral dilatation. The labels were then assigned to the combination of the 4 features. A machine learning-based model, qVUR, was trained to predict vesicoureteral reflux grade from these features and model performance was assessed by AUROC (area under the receiver-operator-characteristic). RESULTS: A total of 1,492 kidneys and ureters were collected from voiding cystourethrograms resulting in a total of 8,230 independent gradings. The internal inter-rater reliability for vesicoureteral reflux grading was 0.44 with a median percent agreement of 0.71 and low intra-rater reliability. Higher values for each feature were associated with higher vesicoureteral reflux grade. qVUR performed with an accuracy of 0.62 (AUROC=0.84) with stable performance across all external data sets. The model improved vesicoureteral reflux grade reliability by 3.6-fold compared to traditional grading (P < .001). CONCLUSIONS: In a large pediatric population from multiple institutions, we show that machine learning-based assessment for vesicoureteral reflux improves reliability compared to current grading methods. qVUR is generalizable and robust with similar accuracy to clinicians but the added prognostic value of quantitative measures warrants further study.


Assuntos
Ureter , Refluxo Vesicoureteral , Criança , Humanos , Refluxo Vesicoureteral/diagnóstico por imagem , Reprodutibilidade dos Testes , Cistografia/métodos , Aprendizado de Máquina , Estudos Retrospectivos
2.
urol. colomb. (Bogotá. En línea) ; 30(3): 199-203, 15/09/2021. tab, ilus
Artigo em Inglês | LILACS, COLNAL | ID: biblio-1369431

RESUMO

Introduction and objective Standardization of surgical interventions reduces complications and costs and positively impacts intra and postoperative outcomes. Implementation of the lean concept, initially proposed in the auto industry, now becomes an interesting approach in the surgical setting. We want to present the results of how percutaneous nephrolithotripsy (PCNL) in a high-level center can be positively impacted by implementing the lean concept. Methods We evaluated a total of 140 PCNL procedures. Group 1 included all cases operated prior to implementing the lean concept and group 2 was composed of those operated after implementing the lean concept. We looked for all seven sources of waste to identify and modify our practice to improve efficiency and safety. We then collected intraoperative times and compared the ones prior to those after the implementation. Results After implementing the lean concept, with an average of six PCNL cases per day, a comparison was made to an equivalent number of cases prior to the lean implementation (group 1). The average total operative time for PCNL preintervention was 138 (confidence interval [CI]: 79 to 170) minutes and postlean intervention was 71.1 (CI: 43 to 157) minutes. Surgical time (cystoscopy to skin closure) was 36.1 (CI: 25 to 50) minutes prelean and 50 minutes postlean (CI: 23 to 154). For this last one, bilateral procedures were performed. Operative room turnover time was 27.8 (CI: 21 to 38) minutes prelean and 5.67 (CI: 3.5 to 12) minutes postlean. Induction time was 16.5 (CI: 5 to 55) minutes prelean and 5.4 (CI: 3.5 to 7.5) minutes postlean. Conclusion Implementation of the lean concept enables optimization of the surgical procedure, allowing hospitals to reduce costs and standardization.


Introducción y objetivo La estandarización de los procedimientos quirúrgicos reduce complicaciones, costos, y mejora resultados intra y postoperatorios. El concepto lean fue utilizado por primera vez en la industria automotriz. El presente trabajo busca implementar el concepto lean para optimizar el procedimiento de nefrolitotomía percutánea (NLP) en nuestro medio. Métodos Se realizaron 140 procedimientos de nefrolitotomía percutánea, los cuales se dividieron en 2 grupos: uno en el cual se registraron los tiempos intraoperatorios, y el segundo en que se registraron los tiempos luego de la implementación del concepto lean. Resultados Durante el período estudiado, se realizaron 70 procedimientos luego de la implementación del concepto lean, y se logró realizar un promedio de 6 procedimientos por día. Se compararon los tiempos operatorios, y se encontró un tiempo operatorio total promedio de 138 (intervalo de confianza [IC]: 79 a 170) minutos pre-lean, y de 71,1 (IC: 43 a 157) minutos post-lean. El tiempo quirúrgico (cistoscopia a cierre de piel) pre-lean fue de 36,1 (IC: 25 a 50) minutos, y el post-lean fue de 50 (IC: 23 a 154) minutos. Para este último, se trató de procedimientos bilaterales. El cambio de sala fue de 27,8 (IC: 21a 38) minutos pre-lean, y de 5,67 (IC: 3.5 a 12) minutos post-lean. El tiempo de inducción fue de 16.5 (IC: 5 a 55) minutos pre-lean, y de 5.4 (IC: 3.5 a 7.5) minutos post-lean. Conclusiones La implementación del concepto lean permite optimizar el procedimiento, con reducción de costos y estandarización del modelo de atención para cualquier centro asistencial. La movilización de los especialistas en nuestro modelo de atención permite un mayor cubrimiento poblacional de alta calidad.


Assuntos
Humanos , Procedimentos Cirúrgicos Operatórios , Gestão da Qualidade Total , Cistoscopia , Nefrolitotomia Percutânea , Organização e Administração , Otimização de Processos , Duração da Cirurgia
3.
Urology ; 156: 256-259, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33689765

RESUMO

Bladder agenesis is a rare congenital anomaly infrequently reported in the literature, with an incidence of 1/600,000 patients.1 Commonly associated with other fatal malformations, the condition is often incompatible with life.2 Prior reports estimate that over 90% of living children born with this malformation are female, owing to renal preservation resulting from low pressure drainage of urine into the vagina, uterus, and vestibule.3,4 Herein we report a rare case of an infant male born with penoscrotal transposition and end stage renal disease secondary to bilateral cystic renal dysplasia found to have concurrent bladder agenesis and bilateral ureteral ectopia.


Assuntos
Anus Imperfurado/complicações , Pênis/anormalidades , Rim Policístico Autossômico Recessivo/complicações , Escroto/anormalidades , Ureter/anormalidades , Doenças Uretrais/complicações , Bexiga Urinária/anormalidades , Anormalidades Múltiplas/diagnóstico por imagem , Humanos , Recém-Nascido , Falência Renal Crônica/etiologia , Masculino , Pênis/diagnóstico por imagem , Rim Policístico Autossômico Recessivo/diagnóstico por imagem , Escroto/diagnóstico por imagem , Doenças Uretrais/diagnóstico por imagem
4.
World J Urol ; 39(9): 3677-3684, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33660089

RESUMO

OBJECTIVE: To describe the evolution of practice patterns for pediatric pyeloplasty and determine how these changes have impacted length of stay (LOS), reoperation rates and return emergency department (ER) visits. METHODS: We reviewed our pyeloplasty database from 2008 to 2020 at a quaternary pediatric referral center and we included children 0-18 years undergoing pyeloplasty. Variables captured included: age, sex, baseline and follow-up anteroposterior diameter (APD) and differential renal function (DRF). We also collected data on the use of drains, catheters and/or stents, nausea and vomiting prophylaxis, opioids, regional anesthesia, and non-opioid analgesia. Outcomes were LOS, reoperation rates and ER visits. RESULTS: A total of 554 patients (565 kidneys) were included. Reoperation rate was 7%, redo rate 4% and ER visits 17%. There was a trend towards less opioids, indwelling catheters and internal stents and increasing non-opioid analgesia, externalized stents, and regional anesthesia during the study period. Same-day discharge (SDD) was possible for 88 (16%) children with no differences in reoperation or readmission rates between SDD and admitted (ADM). There was a difference in ER visits (21 [24%] vs. 26 [6%]; p = 0.04) for SDD vs. ADM, respectively. On multivariate analysis, the only predictor of ER visits was younger age. Patients < 7 months were more likely to present to ER (15/41; 37% vs. 6/47, 13%; p = 0.009). Multivariate analysis determined indwelling catheters and opioids were associated with ADM while dexamethasone and ketorolac with SDD. CONCLUSION: Progressive changes in care have contributed to a shorter LOS and increasing rates of SDD for pyeloplasty patients. SDD appears to be feasible and does not result in higher complication rates. These data support the development of a pediatric pyeloplasty ERAS protocol to maximize quicker recovery and foster SDD as a goal.


Assuntos
Procedimentos Cirúrgicos Ambulatórios , Pelve Renal/cirurgia , Assistência Perioperatória/tendências , Padrões de Prática Médica/tendências , Obstrução Ureteral/cirurgia , Urologia , Feminino , Humanos , Lactente , Masculino , Fatores de Tempo , Procedimentos Cirúrgicos Urológicos/métodos
5.
Pediatr Transplant ; 24(8): e13814, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32840044

RESUMO

BACKGROUND: There are two main techniques for arterial reconstruction in RT: TA using a stab longitudinal incision which creates an elliptical opening and AP which fashions a circular defect. We hypothesized that AP creates a natural anastomosis lumen, similar to the donor renal artery, which optimizes RT perfusion. METHODS: A retrospective review of a single-institution database was performed between 2000 and 2018. Twenty patients who underwent AP arteriotomy were compared to 40 TA-matched controls. Data were collected on creatinine (preoperative, nadir, and time to nadir), and DUS RI and PSV at 1 week, 3 months, and 6-12 months post-RT. RESULTS: ttNC was shorter in the AP group (5 ± 4 vs 12 ± 13 days; P = .03). PSV at 1 week was lower in the AP group (186 ± 65 cm/s vs 232 ± 89 cm/s; P = .04). There was no difference in nadir creatinine value (P = .26), preoperative creatinine (P = .66), and initial postoperative creatinine (P = .80). RI at week 1 were not different between groups (P = .37). Follow-up DUS showed the difference in PSV between groups became non-significant (1 month P = .50 and 6-12 months P = .53). CONCLUSIONS: AP arteriotomy in RT improves early perfusion and function parameters (ttNC and initial PSV) as compared to TA. AP arteriotomy optimizes early allograft reperfusion, which may have important long-term implications and deserves further evaluation.


Assuntos
Transplante de Rim/métodos , Rim/irrigação sanguínea , Artéria Renal/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Aloenxertos , Criança , Feminino , Humanos , Masculino , Complicações Pós-Operatórias , Estudos Retrospectivos
6.
Pediatr Transplant ; 24(4): e13715, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32324334

RESUMO

This case report describes an 8-year-old girl who underwent a segmental LT for a primary diagnosis of citrullinemia at the age of 12 months. She presented with cholangitis secondary to stenosis of the biliary-enteric anastomosis. MRI revealed dilatation of intrahepatic bile ducts associated with multiple stones. An endoscopic approach failed to decompress the bile ducts and remove the stones. A percutaneous approach was then undertaken. After placement of a temporary external biliary drain for 12 days, a 26 French sheath was placed to access the bile ducts. Using a 14Fr flexible cystoscope, 80%-90% of the biliary stones were removed. This was followed by antegrade balloon dilatation of the biliary-enteric anastomosis. Two months later, the procedure was repeated, resulting in complete clearance of the biliary stones. An internal-external biliary drain was maintained in placed for 10 months. The patient has been asymptomatic, with no evidence of stone recurrence for 13 months after drain removal. Percutaneous biliary stone removal is commonly performed in adults with non-transplanted livers, especially in complex cases, and has also been shown to be successful in the pediatric population. However, it is rarely reported in transplanted livers in adults, and to the best of our knowledge, no pediatric cases have been reported. This case illustrates that this technique can be successfully utilized in pediatric LT patients.


Assuntos
Ductos Biliares Intra-Hepáticos , Cálculos Biliares/cirurgia , Transplante de Fígado , Complicações Pós-Operatórias/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Criança , Feminino , Humanos
7.
Urology ; 139: 141-150, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32068110

RESUMO

OBJECTIVE: To review the literature of 5 pediatric urology topics and conduct gender based and forecasting analyses of first and corresponding authors. METHODS: A PubMed search was performed for hypospadias, hydronephrosis, vesicoureteral reflux, bladder and bowel dysfunction, and cryptorchidism over 3 decades from 1990 to 2019. The 50 most relevant "best match" papers from each decade were extracted by topic. Author gender, specialty, and advanced degrees, along with journal and publication variables were collected. Forecasting analyses were conducted through the Holt-Winters method. RESULTS: Among 750 papers analyzed, 78% of corresponding and 70% of first authors were male. A significant upward trend was observed for female-authored publications in both first and corresponding positions over time (P <.01). Forecasting analyses predicted a continuing upward trend for female corresponding (55%) and first authors (83%) by 2049. Most studies originated from pediatric urology (59%), followed by pediatric surgery (9%) and endocrinology/genetics (5%). Papers focused in The Journal of Urology (30%) with the majority originating from the United States (38%). Most were retrospective (44%) and discussed medical (54%) versus surgical management (20%). CONCLUSION: The majority of pediatric urology literature has been generated by male authors. A persistent, rising trend in female authorship across all examined pediatric urology topics was noted. These encouraging findings are projected to continue to increase in the future, suggesting a movement toward equal and fair gender representation in authorship in pediatric urology.


Assuntos
Autoria , Bibliometria , Pediatria , Médicas , Editoração , Urologia , Humanos , Pediatria/métodos , Pediatria/organização & administração , Pediatria/tendências , Médicas/estatística & dados numéricos , Médicas/tendências , Editoração/ética , Editoração/organização & administração , Editoração/tendências , Sexismo/prevenção & controle , Sexismo/tendências , Estados Unidos , Urologia/métodos , Urologia/organização & administração , Urologia/tendências
10.
Urology ; 134: 203-208, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31560913

RESUMO

OBJECTIVE: To review our single institution experience, exploring the role of testis-sparing surgical resection in a cohort of children with Testicular Leydig cell tumors (LCTs). MATERIALS AND METHODS: We reviewed all consecutive children presenting with testicular tumors between 2003 and 2017 (n = 66), excluding patients with alternative pathologies (n = 57). Subsequently data were collected on age at surgery, laterality, type of surgery, operative time, presenting symptoms, serum markers, imaging findings, frozen section, final pathology, and follow-up. RESULTS: During the study period, a total of 9 (9/66; 14%) children were treated for LCT of the testis. Age at surgery was 8.4 ± 1.7 years and the majority (7/9; 77%) had unilateral disease. Most presented with a testicular mass, and 3 (33%) complained of testicular pain. None of the patients had elevated tumor markers. The primary method of management was ultrasound-guided testis-sparing surgery, with an operative time of 98.5 ± 58.7 minutes. Mean tumor size was 15 ± 10.8 mm (range 5-40 mm). In 2 of 6 patients with positive margins radical orchidectomy was performed without residual disease encountered. At a mean follow-up of 31.8 ± 26.3 months (range 2-87) none of the patients demonstrated disease recurrence. CONCLUSION: Our data suggest that LCT in children is associated with a good prognosis, and that TSS is a reasonable surgical approach without detrimental perioperative morbidity or negative long-term outcomes. Moreover, positive margins should not prompt a reflex decision for completion of orchidectomy.


Assuntos
Tumor de Células de Leydig/cirurgia , Tratamentos com Preservação do Órgão , Neoplasias Testiculares/cirurgia , Testículo , Criança , Pré-Escolar , Estudos de Coortes , Seguimentos , Humanos , Tumor de Células de Leydig/diagnóstico por imagem , Tumor de Células de Leydig/patologia , Masculino , Margens de Excisão , Duração da Cirurgia , Orquiectomia/estatística & dados numéricos , Estudos Retrospectivos , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/patologia , Ultrassonografia de Intervenção
11.
Pediatr Transplant ; 23(5): e13455, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31081212

RESUMO

INTRODUCTION: Pediatric renal transplantation has been heavily published since the 1950s. Herein, we describe the bibliometrics and impact of the 200 most-cited pediatric renal transplantation manuscripts. METHODS: We identified pediatric renal transplantation publications from 1900 onwards. Year, citations, h-index, geographic origin, impact factor, topic, and design of the 200 top-cited papers were extracted. Impact index was calculated, adjusting for citation volume and time since publication. RESULTS: Of the top 200 papers, mean citation count was 80 ± 40, impact factor 3.9 ± 3.7, h-index 35 ± 20, and impact index 25 ± 13. Studies were mostly retrospective (31%) or observational (32%). Most papers originated from the United States (58%), Germany (9%), and Italy (6%), which did not correlate with citation counts. Transplantation (18%), Pediatric Nephrology (16%), and American Journal of Transplantation (11%) had the highest publication volume, which did not correlate with citation count. The main topics were medical renal disease, drug monitoring, compliance, and viruses. Most of the top-cited papers (179; 90%) were published after 1991. The difference in the number of times cited between papers published before and after 1991 was insignificant (75 ± 24 vs 80 ± 42; P = 0.59). There was a difference in impact index for the same period (48 ± 15 vs 22 ± 10; P < 0.01). CONCLUSIONS: The most-cited papers were concentrated in three journals, but the top three cited papers were published elsewhere. Recent publications were more cited with a higher impact than older papers. Despite the importance of surgery in transplantation, there is a paucity of high-impact papers on this topic.


Assuntos
Bibliometria , Transplante de Rim , Nefrologia , Editoração/tendências , Criança , Humanos
12.
Urology ; 128: 78-83, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30885542

RESUMO

OBJECTIVE: To examine the implications of varicoceles and nutcracker phenomenon (NcP) in a large cohort of adolescent patients. Varicoceles are common in adolescent males, generating concerns regarding etiology and management. At our institution, Doppler ultrasound (US) of the renal vessels is routinely obtained with the goal of assessing for an associated nutcracker phenomenon. METHODS: Between 1/2000 and 3/2017, 182 patients with clinical varicoceles were evaluated with US. Retrospective assessment provided complete data in 137, including maximum varicose vein diameter, testicular measurements, left renal vein velocities at the hilum and impingement point by the superior mesenteric artery, and procedural interventions. RESULTS: NcP was detected in 77 patients (56.2%), who experienced higher venous velocity ratios (8.33 vs 2.87; P < 0.001) than those without. Overall, 39 patients (28.5%) had a testicular volume discrepancy >20%, without a significant difference based on the presence or absence of NcP (27.3 vs 30.0%, respectively; P = 0.36). Both groups had similar ages at diagnosis, bilateral volume parameters, volume difference, maximum varicose vein sizes, and follow-up duration (P ≥ 0.05 for all). Intervention was more likely in patients with volume difference >20% (P = 0.014). Having NcP was not associated with a higher incidence of initial (P = 0.59) or reoperative surgery (P = 0.73). CONCLUSION: NcP is common in adolescent patients with a varicocele, but it is not associated with differences in testicular parameters or an increased frequency of initial or reoperative surgery. As such, NcP may have few clinical ramifications as an isolated finding in this patient population, calling into question routine assessment for its presence.


Assuntos
Testículo/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Varicocele/diagnóstico , Adolescente , Criança , Seguimentos , Humanos , Masculino , Ontário/epidemiologia , Prevalência , Estudos Retrospectivos , Varicocele/epidemiologia
13.
Urology ; 126: 200-203, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30615895

RESUMO

Herein we present the first case report of laparoscopic exploration, endovascular valvulotomy, and open side-to-side bypass of a gonadal vein into the ipsilateral external iliac vein for Nutcracker syndrome in an adolescent patient with solitary kidney without pelvic congestion. Though prior management has included various large open surgeries or endovascular or extravascular approaches with the use of stents and shields, this case offers an expanded novel approach to weigh the unique challenges of the patient's age and solitary renal status. If reproducible, this technique may gain value in the management of patients with this rare, incapacitating condition.


Assuntos
Síndrome do Quebra-Nozes/cirurgia , Adolescente , Anastomose Cirúrgica/métodos , Feminino , Humanos , Veia Ilíaca/cirurgia , Ovário/irrigação sanguínea , Síndrome do Quebra-Nozes/complicações , Rim Único/complicações , Procedimentos Cirúrgicos Vasculares/métodos , Veias/cirurgia
14.
Urology ; 112: 151-154, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29031839

RESUMO

OBJECTIVE: To determine the effect of the postpenile surgery illustrated healing atlas on caregivers' anxiety levels pre- and postoperatively, the frequency of family's postoperative communication with the urology care team, and the number of unplanned emergency room (ER) return for wound checks. METHODS: A prospective cohort enrolled children who underwent penile surgeries (distal hypospadias repair and phalloplasty) with no concomitant procedures from December 2016 to June 2017. A 6-item short-form Spielberger State-Trait Anxiety Inventory (STAI) was used to determine baseline and postoperative anxiety levels of the caregivers. Two groups were created: caregivers who did not view the illustrated atlas vs caregivers who were shown the atlas. Baseline characteristics and demographics were compared, along with caregiver's pre- to postoperative anxiety level difference, frequency of postoperative communication, and number of unplanned ER return for wound checks. RESULTS: Fifty-four patients were enrolled with 27 families in each group. Baseline characteristics and demographics were comparable with no significant differences. The assessment of the pre- to postoperative anxiety levels in both groups showed no significant differences (median difference -5 [interquartile range -8 to -5] vs -5 [interquartile range -8 to -4], P = .94). Although no differences were noted for ER-return rates between the groups (18% vs 11.1%, P = .704), significantly less postoperative calls and e-mails were noted among families who received or viewed the postpenile surgery illustrated healing atlas (51.9% vs 11.1%, P = .003). CONCLUSION: The utilization of a postpenile surgery illustrated healing atlas as part of the postoperative support provided to families was able to decrease postoperative calls and e-mails.


Assuntos
Ansiedade/prevenção & controle , Cuidadores/psicologia , Saúde da Família , Hipospadia/cirurgia , Pênis/cirurgia , Ferida Cirúrgica , Cicatrização , Adolescente , Adulto , Atlas como Assunto , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Adulto Jovem
15.
Curr Urol ; 11(1): 9-15, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29463971

RESUMO

BACKGROUND/AIMS: The morbidity of radical cystectomy remains high. A multidisciplinary approach utilizing hospitalist comanagement may improve outcomes. It is unclear what factors should be considered to determine which patients might benefit from this approach. We sought to determine if there are differences between the perceived need for co-management between urologists and hospitalists. Preoperative variables were analyzed to determine which factors might be associated with need for comanagement. METHODS: A case-based survey was emailed to urologists and hospitalists at 3 academic institutions to investigate perceptions regarding need for inpatient medical comanagement of fictitious patients following cystectomy. Decisions were rated based on patient comorbidities, age, race, sex, cancer stage, neoadjuvant therapy, alcohol intake, performance status, and English literacy. A Wilcoxon rank sum test assessed each question for differences. A Mantel-Haenszel chi-square test was used to assess whether the proportion of respondents who advocated for comanagement increased as Charlson comorbidity score increased. RESULTS: The most significant determinant of need for postoperative comanagement was patients' comorbidities. Urologists and hospitalists did not differ significantly in beliefs regarding need for comanagement. CONCLUSION: The most important determining factor for comanagement was presence of comorbidities. Further studies are needed to evaluate the impact of this multidisciplinary approach.

16.
PLoS One ; 10(9): e0138643, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26398705

RESUMO

Recent studies have demonstrated that mesenchymal stem cells (MSCs) combined with CD34+ hematopoietic/stem progenitor cells (HSPCs) can function as surrogate urinary bladder cells to synergistically promote multi-faceted bladder tissue regeneration. However, the molecular pathways governing these events are unknown. The pleiotropic effects of Wnt5a and Cyr61 are known to affect aspects of hematopoiesis, angiogenesis, and muscle and nerve regeneration. Within this study, the effects of Cyr61 and Wnt5a on bladder tissue regeneration were evaluated by grafting scaffolds containing modified human bone marrow derived MSCs. These cell lines were engineered to independently over-express Wnt5a or Cyr61, or to exhibit reduced expression of Cyr61 within the context of a nude rat bladder augmentation model. At 4 weeks post-surgery, data demonstrated increased vessel number (~250 vs ~109 vessels/mm2) and bladder smooth muscle content (~42% vs ~36%) in Cyr61OX (over-expressing) vs Cyr61KD (knock-down) groups. Muscle content decreased to ~25% at 10 weeks in Cyr61KD groups. Wnt5aOX resulted in high numbers of vessels and muscle content (~206 vessels/mm2 and ~51%, respectively) at 4 weeks. Over-expressing cell constructs resulted in peripheral nerve regeneration while Cyr61KD animals were devoid of peripheral nerve regeneration at 4 weeks. At 10 weeks post-grafting, peripheral nerve regeneration was at a minimal level for both Cyr61OX and Wnt5aOX cell lines. Blood vessel and bladder functionality were evident at both time-points in all animals. Results from this study indicate that MSC-based Cyr61OX and Wnt5aOX cell lines play pivotal roles with regards to increasing the levels of functional vasculature, influencing muscle regeneration, and the regeneration of peripheral nerves in a model of bladder augmentation. Wnt5aOX constructs closely approximated the outcomes previously observed with the co-transplantation of MSCs with CD34+ HSPCs and may be specifically targeted as an alternate means to achieve functional bladder regeneration.


Assuntos
Regeneração/fisiologia , Bexiga Urinária/fisiologia , Animais , Antígenos CD34/metabolismo , Vasos Sanguíneos/metabolismo , Células da Medula Óssea/citologia , Linhagem Celular , Proteína Rica em Cisteína 61/antagonistas & inibidores , Proteína Rica em Cisteína 61/genética , Proteína Rica em Cisteína 61/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Regeneração Nervosa , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Ratos , Ratos Nus , Engenharia Tecidual , Urodinâmica , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Proteína Wnt-5a
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