OnabotulinumtoxinA for the treatment of neurogenic detrusor overactivity in children.

AIMS: This study evaluated whether one (or more) of three doses of onabotulinumtoxinA were safe and effective to treat neurogenic detrusor overactivity (NDO) in children. METHODS: This was a 48-week prospective, multicenter, randomized, double-blind study in children (aged 5-17 years) with NDO and urinary incontinence (UI) receiving one onabotulinumtoxinA treatment (50, 100, or 200 U; not to exceed 6 U/kg). Primary endpoint: change from baseline in daytime UI episodes. Secondary endpoints: change from baseline in urine volume at first morning catheterization, urodynamic measures, and positive response on the treatment benefit scale. Safety was also assessed. RESULTS: There was a similar reduction in urinary incontinence from baseline to Week 6 for all doses (-1.3 episodes/day). Most patients reported positive responses on the treatment benefit scale (75.0%-80.5%). From baseline to Week 6, increases were observed in urine volume at first morning clean intermittent catheterization (50 U, 21.9 ml; 100 U, 34.9 ml; 200 U, 87.5 ml; p = 0.0055, 200 U vs. 50 U) and in maximum cystometric capacity (range 48.6-63.6 ml) and decreases in maximum detrusor pressure during the storage phase (50 U, -12.9; 100 U, -20.1; 200 U, -27.3 cmH2 O; p = 0.0157, 200 U vs. 50 U). The proportion of patients experiencing involuntary detrusor contractions dropped from baseline (50 U, 94.4%; 100 U, 88.1%; 200 U, 92.6%) to Week 6 (50 U, 61.8%; 100 U, 44.7%; 200 U, 46.4%). Safety was similar across doses; urinary tract infection was most frequent. CONCLUSIONS: OnabotulinumtoxinA was well tolerated and effective for the treatment of NDO in children; 200 U showed greater efficacy in reducing bladder pressure and increasing bladder capacity.

Genome-wide association study in patients with posterior urethral valves.

Congenital lower urinary tract obstructions (LUTO) are most often caused by posterior urethral valves (PUV), a male limited anatomical obstruction of the urethra affecting 1 in 4,000 male live births. Little is known about the genetic background of PUV. Here, we report the largest genome-wide association study (GWAS) for PUV in 4 cohorts of patients and controls. The final meta-analysis included 756 patients and 4,823 ethnicity matched controls and comprised 5,754,208 variants that were genotyped or imputed and passed quality control in all 4 cohorts. No genome-wide significant locus was identified, but 33 variants showed suggestive significance (P < 1 × 10-5). When considering only loci with multiple variants residing within < 10 kB of each other showing suggestive significance and with the same effect direction in all 4 cohorts, 3 loci comprising a total of 9 variants remained. These loci resided on chromosomes 13, 16, and 20. The present GWAS and meta-analysis is the largest genetic study on PUV performed to date. The fact that no genome-wide significant locus was identified, can be explained by lack of power or may indicate that common variants do not play a major role in the etiology of PUV. Nevertheless, future studies are warranted to replicate and validate the 3 loci that yielded suggestive associations.

How motor elements at 3 months influence motor performance at the age of 6 months.

ABSTRACT: One of the most important achievements of infancy is mobility, through which the child gradually becomes independent and can discover new places and objects. One form of mobility that occurs in a child's development is rolling over from supine-to-prone.The assumption of the work was to check whether all particular motor elements from the 3rd month had a comparable effect on development in the 6th month of life.The study population included 119 children, 69 born at term, and 50 born preterm. Children were born at week 38 ±â€Š3 (born at term 40  ±â€Š1/preterm 34 ±â€Š3), with a mean body weight of 3100 ±â€Š814 g (born at term 3462 ±â€Š505/ preterm 2282 ±â€Š788). Pre-term children were assessed at the corrected age. The physiotherapeutic qualitative assessment at the age of 3 months was performed in the prone and supine positions, and the qualitative assessment included 15 elements in the prone position and 15 in the supine position. A detailed mathematical analysis was then performed. Values of Cramer's V coefficient with confidence range, Goodman-Kruskal's coefficient, and the values of the probability coefficient p were given.The position of the scapulae and pelvis (3rd month) had the strongest impact on achieving proper support on the upper extremities in the 6th month of life, while the supine position was most significantly affected by the position of the head, spine, and pelvis.

Genome-Wide Survey for Microdeletions or -Duplications in 155 Patients with Lower Urinary Tract Obstructions (LUTO).

Lower urinary tract obstruction (LUTO) is, in most cases, caused by anatomical blockage of the bladder outlet. The most common form are posterior urethral valves (PUVs), a male-limited phenotype. Here, we surveyed the genome of 155 LUTO patients to identify disease-causing CNVs. Raw intensity data were collected for CNVs detected in LUTO patients and 4.392 healthy controls using CNVPartition, QuantiSNP and PennCNV. Overlapping CNVs between patients and controls were discarded. Additional filtering implicated CNV frequency in the database of genomic variants, gene content and final visual inspection detecting 37 ultra-rare CNVs. After, prioritization qPCR analysis confirmed 3 microduplications, all detected in PUV patients. One microduplication (5q23.2) occurred de novo in the two remaining microduplications found on chromosome 1p36.21 and 10q23.31. Parental DNA was not available for segregation analysis. All three duplications comprised 11 coding genes: four human specific lncRNA and one microRNA. Three coding genes (FBLIM1, SLC16A12, SNCAIP) and the microRNA MIR107 have previously been shown to be expressed in the developing urinary tract of mouse embryos. We propose that duplications, rare or de novo, contribute to PUV formation, a male-limited phenotype.

Normal-range albuminuria does not exclude nephropathy in diabetic children.

Clinically detectable diabetic nephropathy (DN) begins with the development of microalbuminuria (MA). However, early renal dysfunction may be overlooked despite using that method. On the other hand, the gold standard in DN detection-that is, renal biopsy-is highly invasive. The aim of this study was to evaluate the level of neutrophil-gelatinase-associated lipocalin (NGAL) and interleukin (IL)-18 and their relations to albumin excretion rate (AER) in children with normal-range albuminuria, e.g. in those considered as not presenting diabetic nephropathy. The study group consisted of 22 children (age 12.7 +/- 3.5 years) with type 1 diabetes mellitus (T1DM). Long-term glycemic control was assessed on hemoglobin A1c (HbA1c) levels (8.52 +/- 1.78%). All patients presented normal estimated glomerular filtration rate (eGFR) (141 +/- 23 ml/min/1.73 m(2)) and normal urinary albumin excretion (13.09 +/- 7.63 mg/24 h). Fourteen healthy children served as a control group. Children with T1DM showed increased NGAL values with respect to controls-interestingly, both in serum (sNGAL) (867.43 +/- 341.98 vs. 655.29 +/- 196.17 ng/ml; p = 0.04) and in urine (uNGAL) (420.04 +/- 374.16 vs. 156.53 +/- 185.18 ng/ml, p = 0.04). IL-18 levels were not different in both groups both in serum (58.52 +/- 20.11 vs. 69.79 +/- 58.76 ng/ml; NS) and in urine (14.53 +/- 12.74 vs. 14.60 +/- 10.92 ng/ml; NS). Despite the relatively small study group, the positive correlation between sNGAL and AER was found [AER (mg/24 h) = 3.1893 + 0.01141 x sNGAL (ng/ml); r = 0.51; p = 0.014] as well as between uNGAL and AER [AER (mg/24 h) = 8.7538 + 0.01032 x uNGAL (ng/ml); r = 0.51; p = 0.016]. No relationship between sNGAL and uNGAL, and GFR and HbA1c were found. Normal-range albuminuria does not exclude diabetic nephropathy defined as increased sNGAL and uNGAL concentration. NGAL measurement can be more sensitive than MA and may become a useful tool for evaluating renal involvement in diabetic children.

[Endoscopic augmentation of neurogenic bladder with botulinum-A toxin in children]. / Ocena skutecznosci endoskopowego powiekszania pojemnosci pecherza neurogennego u dzieci z wykorzystaniem toksyny botulinowej A.

THE AIM: To present our experience with endoscopic intradetrusor injections of botulinum-A toxin. MATERIAL AND METHODS: Endoscopic treatment was proposed for children in which no improvement or side effects were observed. Botulinum-A toxin was injected in 25 children 3 to 7 years old. All children were evaluated with voiding-charts, in all of them urodynamic investigations were also performed in the pre and post-procedure period. RESULTS: Increased bladder volume was found in 18 patients, in 5 children bladder volume decreased. No major side effects were noted post BTX injections. CONCLUSIONS: Botulinum-A toxin in useful in children with neurogenic bladder overactivity.

Pharmacotherapy for Pediatric Neurogenic Bladder.

Neurogenic bladder (NB) is a nonspecific term that may describe conditions ranging from areflectic noncontractile bladder to detrusor overactivity. The most common cause of NB in children is the presence of dysraphic malformations. Urodynamic evaluations make it possible to describe bladder dysfunctions and to plan a therapeutic strategy for each patient. In a child with NB there are two major dangerous functional problems seen in urodynamic investigations: high intravesical pressure in the storage phase and high pressure during urination. The basic goals of urologic treatment for a child with NB are the protection of the urinary tract from complications and improvement of continence. Treatment for a child with NB is usually conservative, and focuses on achieving safe bladder pressures during storage with reliable emptying, via voiding or catheterization. The two most important forms of conservative treatment are clean intermittent catheterization and pharmacological treatment of functional disorders. Some drugs are used in the treatment of functional disorders in children with NB, but none of the drugs are officially approved for small children and babies.

A system for the treatment of nocturnal enuresis in children.

BACKGROUND: This paper presents our findings related to the treatment of children with nocturnal enuresis using our own rehabilitation system. The basic three elements of the therapeutic process include: 1st stage: assessment of the way in which a child urinates; 2nd stage: treatment of bladder dysfunctions; 3rd stage: learning to wake up in order to urinate. METHODS: Medical records of 198 children were used in the study. Group 1: children with monosymptomatic nocturnal enuresis. Group 2: children with polisymptomatic nocturnal enuresis. Group 1 was treated with the use of alarm device (AD). The treatment in group 2 started with the urotherapy and pharamacotherapy of bladder dysfunctions, if the treatment was effective a therapy with the use of alarm device was recommended. RESULTS: A therapy with an AD was carried out in 122 children, 6 started to wake up without episodes of NE that would trigger the alarm, in 31 the ability to wake up in order to urinate developed in the first month of the therapy, 35 were cured after 2 months, in another 5 children the therapy was continued and was successfully completed in the 3rd month of using the AD. In total, 77 children (63.1%) treated using AD were considered as cured. CONCLUSIONS: The system for the treatment based on the functional division is effective both in children with normal bladder function and in patients with symptoms of urinary tract dysfunction. The treatment with AD is more effective in children with monosymptomatic than with polisymptomatic nocturnal enuresis.

Continent catheterizable conduits in pediatric urology: One-center experience.

BACKGROUND: Clean intermittent catheterization (CIC) is a standard treatment for patients who are unable to empty the bladder. In the absence of the urethra or if catheterization through the urethra is problematic, a continent vesicostomy is used as a catheterizable conduit. The Malone procedure is an established treatment option for children with neurogenic constipation and fecal incontinence. OBJECTIVES: The aim of the study was to report the authors' experience with continent catheterizable conduits (CCCs) in children, to review the results and to determine the efficacy of the technique, with an emphasis on continence and the need for revision. MATERIAL AND METHODS: The retrospective study involved children who underwent catheterizable conduit procedures from 2000 to 2015. Two kinds of continent stomas were performed: Mitrofanoff vesicostomies for CIC and Malone antegrade continence enemas (MACEs). The 115 patients treated included 66 girls and 49 boys. A total of 134 operations were performed; 62 were Mitrofanoff vesicostomies and 72 were Malone appendicostomies. In 19 cases, both Mitrofanoff and Malone appendicostomies were formed out of 1 appendix divided into 2 parts. In 5 children vesicocutaneous stomas were constructed using Monti's procedure, and in 1 it was constructed from an intussuscepted ileal loop. In 27 patients Malone procedures were performed laparoscopically. RESULTS: The mean follow-up period was 8.6 years. There was no serious morbidity in relation to the surgery. In 9 children local wound infection was noted, and in 9 others stomal stenosis developed. Out of the 62 children with catheterizable vesicostomies, 59 were continent. The MACE procedure was successful in all 72 patients; problems with constipation and fecal incontinence were resolved in all cases. None of the laparoscopies needed conversion. CONCLUSIONS: Continent catheterizable conduits help patients achieve both fecal and urinary continence. Laparoscopy is effective in performing the Malone procedure. Stoma-related complications could be avoided using end-to-side appendix anastomoses to the skin. Stomal incontinence is rare even when a simplified technique is employed, using the appendix without cecoplication.

[The system of management nocturnal enuresis based on functional classification]. / System leczenia moczenia nocnego oparty na podziale czynnosciowym.

UNLABELLED: The aim of the study was to describe our diagnostic and therapeutic logarithm based on functional classification in children with enuresis, and effects of therapy based on this classification. MATERIALS AND METHODS: we reviewed charts of 123 children managed because of nocturnal enuresis (68 boys, 55 girls, aged 4-18 (mean 7,6) years). Every child had routinely performed ultrasonography, urinalysis, uroflowmetry with estimation of residual urine. Children with urinary tract infections or malformations of the urinary tract were not included in this study. At the first visit all children were instructed to conduct voiding diary. On the base of data from voiding diarys and uroflowmetries children are divided in two groups: Group I (n=21) with monosymptomatic nocturnal enuresis. Group II (n=102) children with bladder dysfunction and enuresis. In the first group rehabilitation program with bladder training, conducting voiding diary and conditioning therapy with alarm device was introduced. In children with bladder dysfunctions therapy started with bladder training and pharmacotherapy of bladder dysfunction. RESULTS: 9 children (6 from Group I and 3 from Group II) started to wake after starting bladder training. 81 children from Group II improved bladder function. 30 children from Group II started to wake up during therapy of bladder dysfunction. In 44 children, who improved bladder function and still had episodes of nocturnal enuresis, therapy with alarm device was introduced. From all 66 children treated with alarm device 5 started to wake up without any one episode of wetting. In 20 children the ability to wake up before alarm started to ring occurred in the first month of therapy. 40 children need to be treated for the second month, in 5 children therapy was prolonged for the third month. 9 children did not learn to wake up for urination. We have 8 drop-outs. In 7 therapy was repeated because of recurrence. CONCLUSION: The system of treatment of nocturnal enuresis is effective both in children with monosymptomatic nocturnal enuresis and in children with enuresis and voiding dysfunction.

[The comparative study on selective alpha1-blocker and behavioural therapy in the treatment of discoordinated voiding in children]. / Porównawcza ocena skutecznosci stosowania selektywnych alfa-blokerów i terapii behawioralnej w leczeniu nieprawidlowej koordynacji wypieraczowo-zwieraczowej.

PURPOSE: To compare the efficiency of selective alpha1-blocker and behavioural therapy in the treatment of detrusor-sphincter discoordination in children. MATERIALS: Prospective, randomized study, approval of Ethics Committee, group of 60 children, age: 5 to 17, detrusor-sphincter discoordination. All children had a history of: recurrent UTI, irregular mictions with or without incontinence in "voiding diary". All have normal upper urinary tract in USG. Dicoordination was diagnosed by pathologic uroflowmetry curve and results with significant postvoiding residual urine in USG. Treatment group 1 (n=30): treatment with selective alpha1-blocker (doxazosin) in age related dosage. Group 2 (n=30): behavioral therapy and rehabilitation with conducting "voiding diary" with timed voiding. All children were also instructed on proper toilet posture, relaxation of the pelvic-floor muscles. After 6 weeks: changes in voiding patterns: No. of micturitions/day, average voided volume were estimated. Uroflowmetry was performed and voided volume, Av. flow rate, shape of the curve (1=normal, 2=flatened, irregular, 3=portions), residual urine (10% of Void.vol.) were calculated. Urinalysis and urin culture were obtained. RESULTS: Of 60 children 57 completed the study: Group 1 (n=30), Group2 (n=27). In Group 1 (alpha1-blocker): improvement in voiding patterns n=21, improvement in UF parameters n=20. In Group 2 (rehabilitation): improvement was estimated in 17 patients. Side effects were noted in 6 children from Group 1 (alpha1-blockers) (headache, hypotonia, vertigo, epistaxis), and non from the Group 2 (rehabilitation). CONCLUSIONS: Both treatment methods seemes to be effective in detrusor-sphincter discoordination. Selective alpha1-blockers alone are more effective than training and rehabilitation exercises.

[New, successful treatment of urinary tract infection caused by Pseudomonas aeruginosa]. / Nowy, skuteczny model leczenia zakazenia ukladu moczowego spowodowanego Pseudomonas aeruginosa.

Urinary tract infection (UTI) is common in pediatric practice and an important cause of morbidity and mortality in children. Escherichia coli remains the predominant uropathogen (80%) isolated in acute community-acquired uncomplicated infections, followed by Staphylococcus saprophyticus (10% to 15%) and Pseudomonas aeruginosa (9%) The pathogens traditionally associated with UTI are changing many of their features, particularly because of antimicrobial resistance. Reinfections and relapses of urinary tract infections caused by PA are very frequent. The aim of the study was to evaluate the efficacy of combined clarithromycine and ceftazidime in terms of eradication of PA infection. We analyzed 20 out of 264 children with UTI where PA infection was confirmed with urine culture. Those children were treated for at least 14 days with the protocol used for PA infection in patients with mucoviscidosis. Short-term eradication was achieved in all patients. Long-term study revealed relapse in 25% of children, all with serious congenital malformations. 75% of children were treated with success. No side effects were observed. Conclusion. We conclude that an empirical combination treatment of clarithromycine and ceftazidime is appropriate and effective in children with UTI caused by PA. This therapy was clinically efficacious, well tolerated, and cost effective, and should prevent unnecessary development of antimicrobial resistance.

Does fibrin sealant applied to the kidney wound of a young rat affect the development of this organ? A comparative study.

OBJECTIVE: The aim of the study was to compare the results of the application of fibrin sealant and absorbable interrupted sutures and to evaluate the impact of the kidney wound closure method on the further development of the organ in young rats. MATERIALS AND METHODS: In 140 rats, a longitudinal bipolar incision of the renal parenchyma was made. In the study group the wound was closed using a fibrin sealant, whereas in the control group single absorbable sutures were applied to the renal parenchyma. Intravenous pyelography, postmortem and histopathological examinations were carried out 4 weeks and 6 months after the surgery. RESULTS: The blood loss was smaller and the time of procedure shorter in the study group than in controls, and the differences were statistically significant. Both 4 weeks and 6 months after the surgery, the differences in the kidney dimensions and kidney weight between the two groups were statistically significant. The differences increased after a longer period of time following the surgery. The histopathological examination revealed that in the case of animals with surgical sutures applied to the wound, the rate of resorptive granulomas and abscess formation was higher, whereas kidneys with fibrin sealant applied to the wound featured a high number of lymphocytic infiltrations of minor severity. CONCLUSIONS: The application of the fibrin sealant simplified the surgical procedure, shortened its duration, and provided hemostasis and permanent closure of the wound. The fibrin sealant facilitates the process of wound healing. The application of a fibrin sealant, compared to surgical sutures, improved the growth of rat kidneys without impairing their functions.

An Evaluation of the Efficacy of Selective Alpha-Blockers in the Treatment of Children with Neurogenic Bladder Dysfunction--Preliminary Findings.

The aim of this study was to assess the usefulness of selective α1-blockers in children with neurogenic urinary tract dysfunctions and increased leak point pressure (LPP). 14 children from age 6 to 16 years with neurogenic urinary tract dysfunctions (neurogenic bladder) and LPP > 40 cm H2O were enrolled in the study. All patients received a selective α1-blocker (doxazosin) for 6-8 weeks with an initial dosage of 0.03 mg/kg. During the observation period the continuation of oral anticholinergics, Clean Intermittent Catheterization (CIC), observation of "urinary dryness" and urinary incontinence periods were recommended. Patients were scheduled for a follow-up visit and urodynamic investigation after 6-8 weeks after the doxazosin therapy was started. In 4 patients, urine leakage occurred at lower pressures; in 9 patients, no significant changes in urine leak point pressures were detected; in 3 patients, there was a significant increase in the bladder capacity; in one patient, deterioration in continence was noted. The differences both in LPP and LPV before and after the treatment were not statistically significant. Our observations are consistent with the conclusions from other studies and showed no evident efficacy of doxazosin in children with neurogenic bladder.

Outcomes of Continuous Renal Replacement Therapy With Regional Citrate Anticoagulation in Small Children After Cardiac Surgery: Experience and Protocol From a Single Center.

Patients after a cardiac surgery in cardiopulmonary bypass often present an acute kidney failure. Continuous renal replacement therapy (CRRT) is often required. The aim of this study was to present effectiveness and safety of CRRT with regional citrate anticoagulation (RCA-CRRT) in small children after cardiac surgery. A retrospective analysis was conducted on 15 patients after cardiac surgery and who had RCA-CRRT performed in 2014. The established protocol was followed. Mean time on the RCA-CRRT was 192 h 40 min with the circuit mean lifetime of 43 h 33 min. Clotting was found to be a cause of shutdown in 29% of circuits. No severe electrolyte and metabolic disorders were observed. The RCA-CRRT is a safe procedure for critically ill children with contraindications to the CRRT with heparin anticoagulation. To avoid adverse effects related to metabolic disorders a proper procedure protocol has to be followed.

[Yersiniosis as a cause of acute tubulointerstitial nephritis and acute renal failure--case report]. / Jersinioza jako rzadka przyczyna ostrego sródmiazszowego zapalenia nerek i niewydolnosci nerek--opis przypadku.

Tubulointerstitial nephritis (TN) is a heterogenous disease, where disturbances of the interstitial tissue and renal tubules are found. Different immunological and nonimmunological mechanisms initiated by infectious and non-infectious factors may lead to TN. A case of 13-years-old girl with primary diagnosis of acute pyelonephritis is presented. The abdominal pain, headache, pain in lumbar region and intermittent fever with loss of appetite were observed in this girl a few weeks before admission. Microcytic anemia, proteinuria and glucosuria, azotemia and elevated markers of inflammatory response were found. In ultrasound examination heterogenous cortex echogenicity of both kidneys and disturbances in parenchymal blood flow were observed. In renal scintigraphy the discriminated catch index was found. Kidney biopsy revealed the edema of the interstitial space with mononuclear and lymphocyte infiltration. The diagnosis of TN was established upon the history, clinical examination, results of laboratory tests, kidney imaging and biopsy. After steroid and doxycycline treatment an improvement and normalization of the results of laboratory tests were observed. It seems to be justified to consider Yersinia infection as a cause of acute tubulointerstitial nephritis.