Publications by authors named "Abdol-Mohammad Kajbafzadeh"

243 Publications

A Novel Technique for Management of Simultaneous Fibro-Epithelial Polyp and Blind-Ending Branch in a Duplicated Ureter: A Case Report With 23-year Follow-Up.

Urology 2020 Dec 15. Epub 2020 Dec 15.

Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Ureteral duplication with a blind-ending branch (BEB) is rare anomaly. The presence of fibro-epithelial polyps in duplicated ureters is also infrequent. Despite the noticeability of endoscopic polypectomy, further recurrence of polyps and persistence of pain increase the probability of further ureteral resection with surgical procedures. In such cases, BEB of duplicated ureter is an excellent reservoir to save the function of the kidney. This is the first case with concomitant presence of fibro-epithelial polyps and BEB in duplicated ureter managed with novel surgical technique of uretero-pelvic junction and BEB branch anastomosis. We followed-up the patient for 23 years.
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http://dx.doi.org/10.1016/j.urology.2020.12.004DOI Listing
December 2020

Management of urinary and bowel dysfunction in rabbit model of spinal cord injury using Schwann cells and muscle progenitors: functional study and evidence for novel mechanism of action.

Int Urol Nephrol 2020 Nov 27. Epub 2020 Nov 27.

Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, No. 62, Dr. Gharib's Street, Keshavarz Boulevard, Tehran, Iran.

Purpose: We tried to investigate the role of Schwann and satellite cells in the treatment of neurogenic bladder and bowel dysfunction; following spinal cord injury in the rabbit model.

Methods: Twelve male New Zealand rabbits underwent induction of neurogenic bladder by spinal cord injury. Rabbits underwent the fiber tractography analysis to confirm the induction of spinal cord injury. Then, animals were randomly divided into two groups. In group I (n = 4), Schwann cells were obtained from autologous peroneal nerve. In group II (n = 4), the co-culture of nerve-muscle cells was obtained from autologous peroneal nerve and quadriceps muscle. Animals in the control group (n = 4) did not undergo any rehabilitation therapy. One and 4 months after injection of cells into the external anal sphincter, electromyography, urethral pressure profiles, urodynamic studies, voiding cystourethrogram, and manometry was performed to confirm the efficacy of treatment in short- (1 month) and long-term (4 months) follow-ups.

Results: The investigations validated that no statistically significant difference was detected between the two experimental groups in a short-term follow-up (p-value > 0.05). However, the functional features were improved in group II in long-term follow-up. In both groups, the external anal sphincter contracted in response to electrical signals delivered to the muscle. However, more signals were detected in group II in electromyography evaluation. The immunohistochemical staining demonstrated that the histological features of the bladder and spinal cord were more satisfactory in group II in all follow-ups compared to group I, in terms of less edema, inflammation, presence of progenitor cells, and expression of muscle and nerve markes.

Conclusion: Our results suggested that the injection of nerve-muscle co-culture cells into the external anal sphincter may be a helpful tactic for ameliorating the urological complications; following spinal cord injury induction in the rabbit model.
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http://dx.doi.org/10.1007/s11255-020-02722-5DOI Listing
November 2020

Local tissue reaction and histopathological characteristics of three different bulking agents: a rabbit model.

Int Braz J Urol 2021 Mar-Apr;47(2):322-332

Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran (IRI).

Purpose: We assessed the efficacy and safety of a single injection of three bulking agents over the short- and long-term follow-ups in rabbits. Dermal and preputial matrices were compared with Deflux (DxHA) injection.

Material And Methods: Twenty-four rabbits were divided into three groups. Group I (n=8) underwent the injection of a lyophilized dermal matrix (LDM) beneath the seromuscular layer of the bladder wall. Rabbits in group II (n=8) were injected with lyophilized preputial matrix (LPM). Rabbits of group III (n=8) were injected with DxHA as the control group. They were followed up for 1 and 6 months after the injection. Subcutaneous injection of all bulking agents was also performed in nude mice. Biopsies were stained with LCA (leukocyte common antibody), CD68, CD31, and CD34. Scanning electron microscopy (SEM) and MTT assay were also performed.

Results: Immunohistochemistry staining with CD68 and LCA revealed higher inflammation grade in LDM as compared with LPM and DxHA. Fibrosis grade was also higher in LDM both in short- and long-term follow-ups. However, no significant difference was detected in CD31 and CD34 staining between control and experimental groups. SEM analysis showed that the particle size of LPM was more similar to DxHA. MTT assay revealed that cell proliferation was similar in DxHA, LDM, and LPM. In-vivo assay in nude mice model showed more promising results in LPM as compared with LDM.

Conclusion: The long-term results demonstrated that LPM was more similar to Deflux with the least local tissue reaction, inflammation, and fibrosis grade.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2020.0171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857764PMC
March 2020

Recellularization of testicular feminization testis in C57bl6 as a natural bioreactor for creation of cellularized seminiferous tubules: an experimental study.

Cell Tissue Bank 2020 Nov 4. Epub 2020 Nov 4.

Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, No. 62, Dr. Gharib's Street, Keshavarz Boulevard, Tehran, 1419433151, Iran.

We determined histological aspects of implanted human decellularized testicular matrix (DTM) in C57BL6 as a primitive step for further testis tissue engineering. A total of 4 immature human testicles were obtained after bilateral orchiectomy from patients with testicular feminization syndrome. The optimal decellularization protocol was determined and the efficacy of decellularization was evaluated in two of the testicles. The remaining scaffolds were cut in 3 × 3 mm pieces and implanted between the tight muscles in 32 C57BL6. Biopsies were taken at 2, 4, 8, and 24 weeks postoperatively and stained with PLZF, protamine, and tekt1 markers. Histological examination of DTMs confirmed complete absence of nuclear remnants and preservation of the extracellular matrix. Successful cell seeding was observed in all follow-ups confirmed by H&E and IHC staining that increased continuously during the whole study. Interestingly, spermatogonial stem-like cells were observed on decellularized implants that were well differentiated during the follow-ups. Natural bioreactors may provide a good cell source for testes tissue regeneration. This technique may provide testis bioscaffold as a three-dimensional platform and further successful cell seeding to produce a functional testis. This novel technique may be beneficial for patients who require testicular supplementation.
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http://dx.doi.org/10.1007/s10561-020-09877-6DOI Listing
November 2020

Authors' Reply.

Urology 2020 Dec 21;146:299-300. Epub 2020 Oct 21.

Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

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http://dx.doi.org/10.1016/j.urology.2020.10.011DOI Listing
December 2020

Application of adipose-derived, muscle-derived, and co-cultured stem cells for the treatment of stress urinary incontinence in rat models.

Low Urin Tract Symptoms 2020 Oct 23. Epub 2020 Oct 23.

Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Objectives: Based on the recent advancements in cell therapy techniques, we aimed to evaluate the efficacy of transurethral injection of autologous adipose-derived stem cells, muscle-derived stem cells, and co-cultured cells for the rehabilitation of stress urinary incontinence rat models. We hypothesized that the utilization of co-cultured stem cells could result in enhanced therapeutic outcomes attributed to their more comprehensive environment of paracrine factors and cytokines.

Methods: We performed bilateral pudendal nerve transection surgeries to simulate urinary incontinence in 25 female Wistar rats and employed urodynamic evaluations to confirm the injury. We autologously isolated and cultured adipose-derived mesenchymal stem cells, muscle-derived stem cells, and a mixed culture of the two types, which we subsequently injected into the urethral lumen of the damaged animals. Three weeks after the injection, urodynamic assays, histological staining, and immunohistochemical evaluations were performed to determine the efficacy of the implanted cell cultures in sphincter function improvements or structural modifications.

Results: Histological evaluations suggested a regenerative process in the muscular layer of the external sphincter 3 weeks after the injection. Also, immunohistochemical analysis revealed a thickened periurethral striated muscle layer in the co-cultured group. Postinjection urodynamic analysis indicated that the urethral pressure profile significantly increased in the co-cultured group compared with other groups.

Conclusions: The outcomes of this investigation indicated that the application of co-cultured adipose-derived and muscle-derived stem cells could be associated with higher therapeutic value in stress urinary incontinence patients compared with singular-cell treatments.
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http://dx.doi.org/10.1111/luts.12360DOI Listing
October 2020

Intrarectal Electromotive Botulinum Toxin Type A Administration in Children With Intractable Constipation: A Randomized Clinical Trial.

Am J Gastroenterol 2020 12;115(12):2060-2067

Pediatric Gastroenterology and Hepatology Research Center, Department of Pediatrics, Pediatric Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran (IRI).

Introduction: Children with refractory constipation might not respond to conventional medical treatments. In this study, we assessed the effectiveness of intrarectal botulinum toxin type A/electromotive drug administration (BoNTA/EMDA) on constipation in these children and compared its efficacy with routine intrasphincteric BoNTA injection.

Methods: From 2017 to 2019, 60 children aged 5-13 years who fulfilled Rome III criteria for intractable constipation were enrolled and randomly assigned into 2 treatment groups. EMDA group (n = 30) underwent BoNTA/EMDA, whereas the control group (n = 30) received injection of BoNTA into the internal anal sphincter. A complete bowel habit diary (with data on the frequency of defecation per week, stool form, and the number of fecal soiling episodes), a constipation score questionnaire, and a visual pain score were recorded before treatment and at 1 month and 6 months after treatment. In addition, children in both groups were assessed with a constipation-related quality of life questionnaire.

Results: After 1-month follow-up, treatment reduced the number of patients fulfilling the diagnostic criteria in both EMDA (24/30, 80%) and injection (25/30, 83.3%) groups (P < 0.001). The stool form was normalized in 73.3% (22/30) in EMDA group and 80% (24/30) in injection group after treatment. The median of constipation score and pain score decreased significantly in both groups after treatment (P < 0.001 and P < 0.001, respectively).

Discussion: BoNTA/EMDA seems to be as effective as intrasphincteric BoNTA injection for treatment of intractable constipation. In addition, this technique is associated with less comorbidity, is less costly, and can be performed in an office-based setting without general anesthesia.
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http://dx.doi.org/10.14309/ajg.0000000000000940DOI Listing
December 2020

Single-staged male bladder exstrophy-epispadias complex reconstruction with pubic bone adaptation without osteotomy: 15-year single-center experience.

Int Urol Nephrol 2021 Feb 26;53(2):191-198. Epub 2020 Sep 26.

Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: To represent the 15 years' experience of an academic referral center for the reconstruction of bladder exstrophy-epispadias complex with a modified single-stage approach. Single-staged reconstruction techniques are commonly used for classic bladder exstrophy. However, combined bladder closure and epispadias repair have been taken into great consideration in patients with initially failed reconstruction or delayed primary closure.

Methods: A total of 49 boys underwent 1-stage bladder and epispadias repair with pubic bone adaptation and without the application of pelvic osteotomy. The mean ± SD age at surgery was 5.23 ± 2.04 months. Continence and social dryness were assessed in the follow-ups with 3 months intervals for the first year and biannually thereafter.

Results: The mean ± SD of follow-up was 127.25 ± 71.32 months. Urethrocutaneous fistula, stricture, wound infection, and hemiglans were developed in six distinct patients. However, no other major complications were noted. Three patients (6.1%) remained incontinent; while 32 (65.3%) children were socially continent and 14 (28.6%) children were waiting for toilet training. All the patients without previous failed closure were socially continent, while all incontinent patients had two failed closures in their history. No patient was rendered hypospadiac.

Conclusion: Based on the experience of this institution, the application of single-stage reconstructive techniques can lead to continence, cosmetically pleasing appearance with promising outcomes, and reduction of overall operations, hospital stay and costs in the majority of cases as compared to multiple surgical procedures.
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http://dx.doi.org/10.1007/s11255-020-02648-yDOI Listing
February 2021

Comparing predictive values of carbohydrate antigen 19-9, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 in 161 patients with ureteropelvic junction obstruction.

Pediatr Nephrol 2021 Mar 16;36(3):631-638. Epub 2020 Sep 16.

Section of Tissue Engineering and Stem Cell Therapy, Pediatric Urology and Regenerative Medicine Research Center, Children's Hospital Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, No. 62, Dr.Gharib's Street, Keshavarz Boulevard, Tehran, 1419733151, Iran.

Background: To evaluate and compare the efficacy of urinary carbohydrate antigen 19-9 (CA19-9), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) biomarkers as predictive factors to determine the surgery requirement in patients with ureteropelvic junction obstruction.

Methods: We obtained urine samples from 161 patients at diagnosis and evaluated their levels of the three biomarkers. The patients were under observation for 2 years; subsequently, they were divided into two groups based on their requirement of pyeloplasty. We determined the correlation between the urinary concentration of the biomarkers and surgical interventions, as well as the kidney function deterioration and sonography outcomes.

Results: The non-surgery group included 60 male and 22 female patients with mean age of 21 months. The surgery group comprised 58 boys and 21 girls with mean age of 26.9 months with no significant difference of age and gender between the two groups. The outcomes were indicative of higher efficacy of CA19-9 level with a sensitivity and specificity of 84.2% and 73.2% at the cutoff point of 59.09 U/ml. Also, a significant negative correlation was detected between the kidney function and the concentrations of CA19-9 and NGAL.

Conclusions: Our evaluations demonstrate the higher efficacy of CA19-9 to predict the requirement of surgical intervention in comparison with the other biomarkers, as well as a significant correlation between kidney function deterioration and urinary CA19-9 and NGAL. The outcomes of this investigation could pave the way for more extensive clinical application of these urinary biomarkers, besides future research determining the association between markers and kidney fibrosis.
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http://dx.doi.org/10.1007/s00467-020-04750-wDOI Listing
March 2021

Evaluation of different sterilization methods for decellularized kidney tissue.

Tissue Cell 2020 Oct 2;66:101396. Epub 2020 Jun 2.

Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

The main goal of this study was to assess the effect of different sterilization treatment for sterilization of decellularized kidney tissue. Rabbit kidneys were decellularized by the perfusion-based method using sodium dodecyl sulfate (SDS) and Triton X-100. Then, decellularized kidney slices were prepared and sterilized by an antibiotic cocktail, PAA (0.5 %, 1% and 1.5 %), 5KG γ-irradiation and 320-480 nm UV-irradiation. Histological evaluations, DNA quantification assay, MTT assay, scanning electron microscopy (SEM), mechanical test and bacterial and fungal culture tests were performed to determine the quality of decellularization and sterilization processes. The kidney slices were seeded by adipose-derived mesenchymal stem cells (ASCs) to assess the cell adhesion capability after treatment. The results of the current study indicated that PAA 0.5 % was the most efficient method to completely decontaminate rabbit decellularized kidney tissue while preserving the mechanical properties and main components of the matrix which are necessary for cell-matrix interaction and cell adhesion. The 5KG γ-irradiation was determined to be the most destructive sterilization method, with reduced the mechanical strengths as well as altered microstructure of the kidney matrix and no cell adhesion. In addition, UV-irradiation is not able to sterile the decellularized tissues. Therefore PAA 0.5 % sterilization method can be a powerful means for sterilization of biological scaffolds.
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http://dx.doi.org/10.1016/j.tice.2020.101396DOI Listing
October 2020

A Step-by-Step Guide to Double-Puncture Technique for Endoscopic Management of Ureterocele.

Urol J 2020 Sep 13. Epub 2020 Sep 13.

Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

To date, the optimal surgical technique for treatment of ureterocele remains unclear and the available options are variable. The endoscopic techniques that are gaining popularity mostly share major drawbacks including low success rate, high probability of mandatory secondary surgery and de novo vesicoureteral reflux to the ureterocele moiety. The Double-Puncture technique is shown to have promising outcomes in terms of long-term success and low rate of complications. In this video, a step-by-step guide to this technique is presented.
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http://dx.doi.org/10.22037/uj.v16i7.6028DOI Listing
September 2020

Management of Bladder Bowel Dysfunction in Children by Pelvic Floor Interferential Electrical Stimulation and Muscle Exercises: A Randomized Clinical Trial.

Urology 2020 Oct 25;144:182-187. Epub 2020 Jul 25.

Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran (IRI). Electronic address:

Objective: To assess efficacy of combined pelvic floor interferential (IF) electrical stimulation and muscle exercises on bladder bowel dysfunction (BBD) in children.

Materials And Methods: A total of 34 children with BBD (6 boys, 28 girls; mean age 7.4 ± 2.2) were included in this study. Children were evaluated with kidney and bladder ultrasounds, uroflowmetry + electromyography (EMG), and a complete voiding and bowel habit diary before treatment. Exclusion criteria were neuropathic disease, anatomical defects, and mental retardation. Participants were randomly allocated into 2 treatment groups including group A (n = 17) who underwent IF electrical stimulation in addition to pelvic floor muscle (PFM) exercises and group B (n = 17) who received PFM exercises alone. All children were re-evaluated by kidney and bladder ultrasounds, uroflowmetry + EMG and a voiding and bowel habit diary at the end of treatment sessions and 6 months later.

Results: Constipation improved in 14 of 17(82%) and 8 of 17(47%) children in group A and B respectively at the end of treatment sessions (P = .03). Daytime incontinence improved in all children in group A and 2 of 8(25%) children in group B after the treatment (P = .007). Urinary tract infection improved in 8 of 10(80%) and 5 of 13(38.4%) children in group A and B respectively, 6 months after the treatment (P = .02). No significant difference was observed in uroflowmetry measures between 2 groups after the treatment.

Conclusion: Combination of IF electrical stimulation and PFM exercises is an effective and safe modality for treatment of BBD in children.
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http://dx.doi.org/10.1016/j.urology.2020.07.015DOI Listing
October 2020

In vivo application of decellularized rat colon and evaluation of the engineered scaffolds following 9 months of follow-up.

Cell Biol Int 2020 Nov 8;44(11):2253-2262. Epub 2020 Aug 8.

Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

The aim of this study was to investigate the rat small intestine mesentery and colon as natural bio-reactors for rat colon-derived scaffolds. We decellularized eight whole rat colons by a perfusion-based protocol using 0.1% sodium dodecyl sulfate for 24 hr. The provided bio-scaffolds were examined by histological staining, scanning electron microscopy, and collagen and sulfated glycosaminoglycan quantification. Subsequently, we implanted 4 cm segments of the provided bio-scaffolds into two groups of animal models comprising tissue grafting into the mesenteric tissue (n: 10) and end-to-end anastomosis (n: 10) to the colon of host rats. Following 9 months of follow-up, we harvested the grafts and performed histological and immunohistochemical studies as well as real-time PCR evaluation for telomerase activity of the samples. Histological staining, scanning electron microscopy and protein content evaluation of the acellular tissues confirmed the complete removal of the cellular components and preservation of the extracellular matrix. Histopathological assessment of the implanted scaffolds was suggestive of a regenerative process in both groups. Moreover, immunohistochemical analysis of the samples confirmed the presence of smooth muscle cells, endothelial progenitor cells, and neural elements in both groups of grafted scaffolds. Our data confirmed the recellularization of the acellular colon grafts in both groups after 9 months of follow up. Also, the implanted tissues demonstrated different characteristics based on their implantation location. The outcomes of this investigation illustrate the capability of acellular tissues for in vivo application and regeneration.
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http://dx.doi.org/10.1002/cbin.11433DOI Listing
November 2020

Resolution of Hydronephrosis in Children with Dysfunctional Voiding After Biofeedback Therapy: A Randomized Clinical Trial.

Appl Psychophysiol Biofeedback 2020 12;45(4):259-266

Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, No. 62, Dr. Qarib St, Keshavarz Blvd, 4194 33151, Tehran, Iran.

We assessed efficacy of biofeedback therapy and home pelvic floor muscle exercises in children with dysfunctional voiding (DV) associated with mild to moderate hydronephrosis. This prospective study comprised fifty seven children (21 boys, 36 girls; mean age 8.9 ± 2.6) with DV and mild to moderate hydronephrosis. Children were randomly allocated into two treatment groups including control group who underwent standard urotherapy and case group who received biofeedback therapy in addition to standard urotherapy. A 99mTc diethylenetriamine pentaacetic acid (99mDTPA) scan, voiding cystoureterography, kidney and bladder ultrasounds, voiding diary and uroflowmetry with electromyography (EMG) were performed in all study participants at the baseline. Children with evidence of complete obstruction in DTPA scan and vesicoureteral reflux were excluded from enrollment. A complete voiding diary, kidney and bladder ultrasounds and uroflowmetry/EMG were also performed 6 months and 1 year after completion of the treatment. We noted a more significant decline in anteroposterior pelvic diameter in case group compared to control group (P < 0.05). The mean maximal urine flow rate prior to treatment was 16.5 ± 2.6 and 16.1 ± 3 ml/s in case and control groups, respectively. This finding increased significantly 1 year after the treatment in case group compared to controls (25 ± 7.2 ml/s vs. 18.4 ± 5.9 ml/s, respectively; P < 0.001). Improvement of various parameters in voiding diary was also more significant in the case group. Biofeedback therapy can effectively resolve non-refluxing and non-obstructive hydronephrosis in children with DV.
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http://dx.doi.org/10.1007/s10484-020-09474-zDOI Listing
December 2020

Botulinum Toxin Type A Therapy: Intravesical Injection or Electromotive Drug Administration.

Urology 2020 Aug 11;142:190-194. Epub 2020 May 11.

Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Pediatric Center Excellence, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Objectives: To compare the outcomes of intravesical injection of botulinum toxin A (BoNTA) with intravesical electromotive drug administration (EMDA) of BoNTA on urinary incontinence secondary to neuropathic detrusor overactivity (NDO) in children with myelomeningocele (MMC).

Materials And Methods: A total of 26 children with MMC (11 boys, 15 girls) who had urinary incontinence secondary to NDO were retrospectively enrolled in the study. Patients in EMDA group (n = 14), using an electrode-catheter, 10 IU/kg of BoNTA were inserted into the bladder for EMDA without anesthesia and on an outpatient basis. The EMDA equipment was connected to the electrode of indwelling catheter and 2 dispersive electrodes, a pulsed current generator delivered 10-20 mA for 20 minutes. Patients in injection group (n = 12) were received interavesical injection of 10 IU/kg of BoNTA via rigid cystoscope on an inpatient basis. All patients had been evaluated by a voiding diary, urodynamic study, renal, and bladder ultrasounds before, 6 months and 1 year after the treatment.

Results: Six months after the treatment, 12 of 14 (85.7 %) and 8 of 12 (66.6%) patients in EMDA and injection groups respectively became completely dry between 2 consecutive clean intermittent catheterizations, which maintained in 11 of 14 (78.5%) of patients in EMDA group compared to 6 of 12 (50%) of patients in injection group, 1 year after the treatment.

Conclusion: Patients in both groups improved after the treatment; however improvement in EMDA group was more prominent with better sustained effects. BoNTA/EMDA is a feasible, reproducible, cost benefit, and pain free method as an outpatient basis and no need for anesthesia.
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http://dx.doi.org/10.1016/j.urology.2020.04.104DOI Listing
August 2020

Correction to: Clinical and genetic analysis of two wolfram syndrome families with high occurrence of wolfram syndrome and diabetes type II: a case report.

BMC Med Genet 2020 03 20;21(1):58. Epub 2020 Mar 20.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Following publication of the original article [1], the authors flagged that the name of 'Asal Hojjat' was misspelled; the name had been spelled as 'Asal Hojat'.
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http://dx.doi.org/10.1186/s12881-020-0980-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082902PMC
March 2020

Urinary carbohydrate antigen 19-9 level as a biomarker in children with acute pyelonephritis.

Eur J Pediatr 2020 Sep 7;179(9):1389-1394. Epub 2020 Mar 7.

Pediatric Nephrology Department, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Early and prompt diagnosis of pyelonephritis is of great importance in children. The aim of this study is to evaluate the diagnostic accuracy of urinary carbohydrate antigen 19-9 (CA19-9) levels for predicting acute pyelonephritis (APN) in children with urinary tract infection (UTI). Patients were allocated into two groups of APN and acute cystitis according to their diagnosis. Urine samples of all patients were collected. Also, complete history was taken, and physical examination, kidney and bladder ultrasonography, Tc-dimercaptosuccinic acid renal cortical scintigraphy, and urine analysis and culture were performed. Urinary CA19-9 was measured by an electrochemiluminescence enzyme immunometric kit. In addition, CA19-9 levels were measured in the APN group 2 weeks and 3 months later. A total of 100 children were included in this study (mean age 46 ± 31 months, 16 males and 84 females). CA19-9 levels were significantly greater in the APN group than acute cystitis group (510 ± 328 vs. 18.7 ± 18.6 U/ml, P < 0.001). During follow-up periods of the APN group, CA19-9 levels decreased to 180 ± 124 U/ml after 2 weeks (P < 0.001) and 30 ± 23 U/ml after 3 months (P < 0.001). Urinary CA-19-9 had 95.3% sensitivity and 80% specificity for the diagnosis of APN. The area under the curve value of CA19-9 was 0.904 (95% CI 0.831-0.977).Conclusion: Urinary CA19-9 level can be used as a reliable biomarker for early detection of APN prior to urine culture confirmation in children with UTI. What is known: • Early and prompt diagnosis of pyelonephritis is necessary in children to prevent renal damage. • Acute pyelonephritis can present with vague and nonspecific symptoms in infants and children. What is new: • Urinary carbohydrate antigen 19-9 is a reliable biomarker for early detection of acute pyelonephritis prior to urine culture confirmation. • Urinary carbohydrate antigen 19-9 has 95.3% sensitivity and 80% specificity for diagnosis of acute pyelonephritis.
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http://dx.doi.org/10.1007/s00431-020-03626-3DOI Listing
September 2020

Correspondence: Efficacy of electromotive drug administration in delivering botulinum toxin A in children with neuropathic detrusor overactivity - outcomes of a pilot study.

J Pediatr Urol 2020 04 30;16(2):265-266. Epub 2020 Jan 30.

Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

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http://dx.doi.org/10.1016/j.jpurol.2020.01.010DOI Listing
April 2020

Bladder Herniation as an Auto-Augmentation Technique in Bladder Exstrophy: Initial Experience in Patients with Small Bladder Plate.

Urology 2020 May 24;139:151-155. Epub 2020 Feb 24.

Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran (IRI). Electronic address:

Objective: To present our long-term experience of bladder plate herniation technique in patients with bladder exstrophy epispadias complex (BEEC) and inadequate bladder plate.

Methods: Ten BEEC patients with inadequate bladder plates were referred. The bladder underlying fascia was opened and the exstrophic bladder was fixed above the peritoneal cavity to herniate the peritoneal contents beneath the bladder plate so that the abdominal pressure would be directly transferred to the posterior bladder wall; causing gradual bladder expansion and auto-augmentation. In 5 patients, the inguinal hernia was fixed to increase the pressure transferred to the exstrophic bladder. The bladder capacity was measured while the patient was crying and when the bladder was enlarged. Cystometry and voiding cystourethrogram were performed before the application of this technique and during the next 6 to 8 months, to determine the bladder capacity for further primary bladder closure.

Results: The bladder was enlarged during straining/crying without any complications. The average bladder capacity was increased about 2.5 to 3 times after 8 months of follow-up so that it was suitable for undergoing primary closure. None of the children needed bladder augmentation following the single-stage total BEEC reconstruction.

Conclusion: This technique seems to be safe, effective, and feasible in patients with small-sized bladder and may be performed before the primary closure to increase the success rate. This technique may be effective in increasing the bladder capacity for staged bladder closure and bladder neck reconstruction without further need for bladder augmentation.
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http://dx.doi.org/10.1016/j.urology.2020.02.013DOI Listing
May 2020

In-vivo regeneration of bladder muscular wall with whole decellularized bladder matrix: A novel hourglass technique for duplication of bladder volume in rabbit model.

J Pediatr Surg 2020 Oct 27;55(10):2226-2232. Epub 2019 Dec 27.

Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran (IRI). Electronic address:

Objective: To determine histological aspects of decellularized bladder graft to achieve a double-sized bladder by novel hourglass technique; using rabbit models.

Methods: Sixteen rabbit bladders were decellularized and underwent laboratory investigations. After making a laparotomy incision and exposure of bladders in another 16 rabbits (partial detrusor myomectomy), they were separated into two groups. The fundus of the decellularized scaffold was anastomosed to the fundus of the native bladder via the serosal layer, and the omentum and a double-J stent were placed in the decellularized bladder by no direct contact with the urine (Group A, n=8). In group B (n=8), the bladder was augmented applying the decellularized bladder that was in contact with the urine. After 6 months, the omentum was brought out of the neck of the engineered bladder and the anastomosis was opened. Biopsies were taken at 1, 3, and 9 months postoperatively.

Results: Cell removal with preservation of extracellular matrix structure was confirmed in decellularized bladders. Histological examination after 1 month demonstrated few cells at the border of the grafts. After 3 months, the region of the graft was indistinguishable from the natural bladder with continuity of transitional epithelium of natural bladder on the decellularized grafted scaffolds. The organization of muscle layers was similar to native bladder muscle layers after 9 months. IHC staining markers were highly expressed after 9 months. Interestingly, bladders had a high fibrosis grade in group B compared with hourglass technique.

Conclusion: We confirmed that decellularized bladder may be a reliable scaffold and viable material for bladder augmentation.
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http://dx.doi.org/10.1016/j.jpedsurg.2019.11.020DOI Listing
October 2020

Clinical and genetic analysis of two wolfram syndrome families with high occurrence of wolfram syndrome and diabetes type II: a case report.

BMC Med Genet 2020 01 14;21(1):13. Epub 2020 Jan 14.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Mutations of the WFS1 gene are responsible for most cases of Wolfram syndrome (WS), a rare, recessively inherited neurodegenerative disorder characterized by juvenile-onset non-autoimmune diabetes mellitus and optic atrophy. Variants of WFS1 are also associated with non-syndromic hearing loss and type-2 diabetes mellitus (T2DM). Our study adds to literature significant associations between WS and T2DM.

Case Presentation: In this study, we analyzed the clinical and genetic data of two families with high prevalence of WS and T2DM. Genetic linkage analysis and DNA sequencing were exploited to identify pathogenic variants. One novel pathogenic variant (c.2243-2244insC) and one known pathogenic (c.1232_1233delCT) (frameshift) variant were identified in exon eight of WFS1 gene.

Conclusions: The mutational and phenotypic spectrum of WS is broadened by our report of novel WFS1 mutation. Our results reveal the value of molecular analysis of WFS1 in the improvement of clinical diagnostics for WS. This study also confirms the role of WFS1 in T2DM.
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http://dx.doi.org/10.1186/s12881-020-0950-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961406PMC
January 2020

Correction to: Development of an efficient perfusion-based protocol for whole-organ decellularization of the ovine uterus as a human-sized model and in vivo application of the bioscaffolds.

J Assist Reprod Genet 2020 Feb;37(2):491

Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

This article was unintentionally published twice in this journal, by the same authors. Following should be considered the version of record and used for citation purposes.
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http://dx.doi.org/10.1007/s10815-019-01668-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056750PMC
February 2020

Impact of transcutaneous interferential electrical stimulation for management of primary bladder neck dysfunction in children.

J Pediatr Urol 2020 Feb 18;16(1):36.e1-36.e6. Epub 2019 Oct 18.

Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Introduction: Several studies have revealed that electrical stimulation is an effective modality for treatment of lower urinary tract (LUT) dysfunction via raising the capacity or compliance of the bladder or maybe by pelvic floor relaxation and reducing detrusor pressure as well.

Objective: This study aimed to assess the efficacy of transcutaneous interferential (IF) electrical stimulation on LUT symptoms as well as urine flow parameters in children with primary bladder neck dysfunction (PBND).

Study Design: We reviewed the charts of all children with persistent LUT symptoms who underwent IF electrical stimulation between 2010 and 2017. Twenty-three neurologically and anatomically normal children (mean age: 7.7 years, range: 5-13) with LUT symptoms were included in this study. Children had different LUT symptoms such as hesitancy, straining, urinary incontinence and constipation with no sufficient response to medical treatment (α -blocker) for at least 6 months. IF electrical stimulation was performed for 15 sessions, two times per week. All children were symptomatic and had abnormal urine flow pattern with an electromyographic (EMG) lag time of more than 6 s on uroflowmetry with EMG. A voiding chart, uroflowmetry with EMG and kidney and bladder ultrasounds were performed before and after the treatment for all children. Maximum and average urine flow rates, EMG lag time and postvoid residual volume were analyzed. In addition, alpha blocker therapy was continued during IF therapy.

Results: Mean maximum and average urine flow rates improved from 14.1 to 7.6-19.7 ml/s and 9.5 ml/s, respectively, while mean EMG lag time decreased from 11.7 to 5.2 s after the treatment (all P < 0.05). Also postvoid residual volume decreased significantly from 35.6 to 7.6 ml at the end of treatment courses.

Discussion: Pelvic floor EMG lag time, a documented parameter on uroflowmetry with EMG, defined as the time from the start of pelvic floor relaxation during a volitional voiding effort (the first stage of normal voiding) to the start of urine flow. Results showed that IF therapy decreased pelvic floor EMG lag time in children with PBND. In addition, increase in mean maximum and average urine flow rates in our patients indicated that pelvic IF therapy and behavioral modification improved voiding dysfunction in most of the patients and probably decreased bladder neck activity during voiding. Future studies with larger sample size are needed to support this finding.

Conclusion: IF therapy appears safe, effective and reproducible in improvement of PBND in children.
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http://dx.doi.org/10.1016/j.jpurol.2019.10.004DOI Listing
February 2020

Preparation and characterization of human size whole heart for organ engineering: scaffold microangiographic imaging.

Regen Med 2019 10 8;14(10):939-954. Epub 2019 Oct 8.

Pediatric Urology & Regenerative Medicine Research Center, Section of Tissue Engineering & Stem Cells Therapy, Children's Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.

Definitive treatment for end-stage heart failure is heart transplantation, however, this is associated with several limitations. We decellularized and assessed ovine hearts through coronary perfusion. To evaluate recellularization, a decellular graft was transplanted hetrotopically into the omental wrap. Cell removal was confirmed by DNA count (11.68 ± 3.42 ng/mg dry weight). Elastic, reticular and collagen fiber were well preserved. There was a slight change in both glycosaminoglycan (7.01 ± 1.36 to 8.37 ± 0.32 μg/mg) and collagen (32.37 ± 2.3 to 36.31 ± 2.1) μg/mg (p > 0.05). Angiography and blood circulation revealed an intact vascular network. Implantation led to proper vascularization. Image J indicated CD31: 23.98 ± 12.3; CD34: 48.67 ± 19.5 and αSMA: 78.33 ± 27.8 inch/cm. Bio-scaffold of human size heart is achievable for future steps employing this technique.
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http://dx.doi.org/10.2217/rme-2018-0111DOI Listing
October 2019

Prenatal Diagnosis of Concomitant Accessory Scrotum and Diphallia in the Accessory Tissues: Case Report.

Urology 2019 Dec 19;134:217-220. Epub 2019 Sep 19.

Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

A case of accessory scrotum with duplicated penis (diphallia) in a male fetus is reported because of its rarity. This case is presented with proved negative androgen receptors in the accessory genitalia. The results of excisional surgery as well as immunostaining for androgen receptors in the resected specimens are presented as well. The outcomes of prenatal ultrasonography, clinical examination of the infant, and pathologic findings of the resected accessory genitalia are also discussed.
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http://dx.doi.org/10.1016/j.urology.2019.09.005DOI Listing
December 2019

Correction to: Development of an efficient perfusion-based protocol for whole-organ decellularization of the ovine uterus as a human-sized model and in vivo application of the bioscaffolds.

J Assist Reprod Genet 2019 10;36(10):2191

Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

The original version of this article unfortunately contained a mistake. The affiliation of Fariba Ghorbani should be Tracheal Diseases Research Center (TDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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http://dx.doi.org/10.1007/s10815-019-01578-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823407PMC
October 2019

Increased risk of atopic diseases in boys with meatal stenosis: a possible pathophysiological relation.

J Pediatr Surg 2020 Mar 22;55(3):490-492. Epub 2019 Jul 22.

Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Purpose: To evaluate the role of atopy (i.e. atopic dermatitis, allergic rhinitis, asthma, and food allergies) and its consequences on developing meatal stenosis in boys.

Methods: After obtaining ethics approval from institutional review board, a retrospective chart review was conducted to gather records of patients with meatal stenosis (Group A) presented to our pediatric urology center between August 2012 and May 2016. History of any allergic reactions including allergic rhinitis, asthma, skin, food and drug allergies was considered as positive history of atopy. A control group of children referring to our center due to other etiologies were considered as control group (Group B). Data were analyzed using student t-test and Chi-square test.

Results: During the study period, a total of 206 boys (mean age 41.01 months) were assigned to group A and 221 (mean age 35.56 months) to group B. 126 (61.16%) boys had history of allergic reactions in group A compared to 29 (13.12%) in the control arm (group B). Patients with meatal stenosis have a significantly higher (P-value <0.001) likelihood of suffering from allergic reactions.

Conclusions: The pathophysiology of meatal stenosis remains not fully understood yet. This study reveals a significant relation between hypersensitivity reactions and meatal stenosis in boys. Persistent inflammation in meatal area could potentially lead to scarring and stenosis. However, more investigation is required to elucidate this pathophysiology.

Type Of Study: Case-control study.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1016/j.jpedsurg.2019.07.011DOI Listing
March 2020

Clinical and molecular assessment of 13 Iranian families with Wolfram syndrome.

Endocrine 2019 11 16;66(2):185-191. Epub 2019 Jul 16.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Poursina Ave, 16 Azar St. Keshavarz BLVD, Tehran, 1417613151, Iran.

Purpose: Wolfram syndrome (WS) is a rare genetic disorder described by a pattern of clinical manifestations such as diabetes mellitus, diabetes insipidus, optic nerve atrophy, sensorineural hearing loss, urinary tract abnormalities, and psychiatric disorders. WFS1 and WFS2 loci are the main genetic loci associated with this disorder.

Methods: In the current study, we investigated associations between these loci and WS via STR markers and homozygosity mapping in 13 Iranian families with WS. All families were linked to WFS1 locus.

Results: Mutation analysis revealed four novel mutations (Q215X, E89X, S168Del, and E391Sfs*51) in the assessed families. Bioinformatics tools confirmed the pathogenicity of the novel mutations. Other identified mutations were previously reported in other populations for their pathogenicity.

Conclusions: The current study adds to the mutation repository of WS and shows a panel of mutations in Iranian population. Such panel would facilitate genetic counseling and prenatal diagnosis in families with WS cases.
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http://dx.doi.org/10.1007/s12020-019-02004-wDOI Listing
November 2019

Homozygosity mapping and direct sequencing identify a novel pathogenic variant in the CISD2 gene in an Iranian Wolfram syndrome family.

Acta Diabetol 2020 Jan 15;57(1):81-87. Epub 2019 Jul 15.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran.

Aims: Wolfram syndrome (WS) is a rare recessive neurodegenerative disorder characterized by diabetes mellitus and optic atrophy. Mortality and morbidity rate of the disease is high in adulthood due to neurological and respiratory defects. So far, two WS genes, WFS1 (more than 90% of cases) and CISD2, have been identified. In the present study, we aimed to determine the role of WFS2 in a group of Iranian WS families.

Methods: We recruited 27 families with the clinical diagnosis of WS. Homozygosity mapping was implemented using short tandem repeat polymorphic markers and bi-directional sequencing of the CISD2 gene in families negative for WFS1 mutations. The candidate variant was checked among family members. In silico analysis and protein modeling were applied to assess the pathogenic effect of the variant. Tetra-primers ARMS PCR was set up for checking the variant in 50 ethnic-matched controls.

Results: One family showed homozygosity by descent at WFS2. A novel missense variant, c.310T > C (p.S104P), was found in exon 2 of the CISD2 gene. Computational predictions revealed its pathogenic effect on protein structure, function, and stability. Parents and his healthy brother were heterozygous for the variant. The variant was not observed in the control group.

Conclusions: This is the first study that elucidates the role of the CISD2 gene among Iranian WS families with a novel disease-causing missense variant. Next-generation sequencing could unravel disease-causing genes in remained families to expand genetic heterogeneity of WS.
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http://dx.doi.org/10.1007/s00592-019-01381-yDOI Listing
January 2020

Intravesical Electromotive Botulinum Toxin Type A (Dysport) Administration in Children With Myelomeningocele.

Urology 2019 Oct 9;132:210-211. Epub 2019 Jul 9.

Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Objective: Electromotive drug administration (EMDA) presents a minimally invasive method of intravesical instillation of therapeutic agents without the need for general anesthesia. It employs a combination of iontophoresis, electrophoresis, and electroporation to deliver drugs into deep tissue layers using an electrical current created between 2 electrodes. This video shows feasibility of botulinum toxin type A (BoNTA) EMDA in myelomeningocele children with urinary incontinence secondary to neuropathic detrusor overactivity.

Methods: In this technique (Video 1), catheterization was performed with a 10-Fr (CE-DAS, UROGENICS/Ag 9900 (pediatric), Mirandola, Italy) catheter electrode, after providing a local transurethral anesthesia with 2% lidocaine gel. The cuff of the catheter was filled by 2 cc saline solution. The bladder was then drained and irrigated with 0.9% saline solution until the catheter outflow became clear. The bladder was subsequently filled with sterile water to its maximal capacity. BoNTA (Dysport) at a dose of 10 IU/kg was added to the intravesical solution. Negative electrode as 2 dispersive electrodes was placed on the abdomen. Positive electrode was connected to the intravesical catheter. A pulsed current generator (Physionizer 30, Physion srl, Mirandola, Italy), delivered a current with frequency of 2,800 Hz, interval of 50 µs and amplitude of 10-20 mA for 20 minutes. At the end of the procedure, the bladder was emptied.

Results: For the first time, BoNTA/EMDA was performed on myelomeningocele patients with urinary incontinence in our center. According to our prior reports, urinary incontinence improved in 75% of the patients between 2 consecutive clean intermittent catheterizations at 1-year follow-up. Mean maximal cystometric capacity significantly increased from 148 ± 62 mL at baseline to 239 ± 73 mL 1 year after the treatment. CONCLUSION: This technique is a feasible, safe, reproducible, cost effective, long lasting, and pain free method, on an outpatient basis with long-term duration of effects and without anesthesia or cystoscopy procedure.
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http://dx.doi.org/10.1016/j.urology.2019.06.033DOI Listing
October 2019