Predictive Models for the Management of Vesicoureteral Reflux from the View of Statisticians

Abstract: The management of vesicoureteral reflux (VUR) is one of the most challenging issues not only for pediatric urologists but also for pediatric nephrologists and all other related subspecialties. Urinary tract infections (UTI), pyelonephritis and renal scarring which may lead to deterioration in renal function are the common complications in a child presenting with VUR. Due to the patient heterogeneity and varying management options, patient selection for each treatment modality remains as a controversial issue. The different bio-statistical models have been used in order to disclose the factors affecting success of different management modalities and represent the incidence of possible complications. Bio-statistical models are useful to define variables which may help predict the outcome of disease during the different managements. Artificial neural networks (ANN) and regression models are popular methods employed to predict the outcome of urological abnormalities. Statistical models and ANNs provide an estimation of the probability of outcome that is of utmost importance in clinical decision. This study addresses both bio-statistical methods and ANNs employed to predict the outcome of VUR management and their clinical applications. To reach the best fit model that predicts the VUR outcome in a child, widespread knowledge regarding available bio-statistical methods is needed

A Rare case of Aphallia

.Aphallia (total absence of penis) is an extremely rare abnormality that can be part of the urorectal septum malformation sequence.We are reporting a 40-day-old boy who was referred to our nephrology clinic due to the absence of the penis and urinating through the rectum. He was born to a 17-year-old mother and a 24-year-old father, and was delivered term via normal vaginal delivery.The pregnancy was uncomplicated with no maternal toxin or medication exposure. Both parents were healthy and there was no family history of congenital abnormality. The parents were also unrelated.  Physical examination revealed agenesis of the penis, a normal scrotum, and bilateral normally positioned testises. Moreover, the heart, lungs, abdomen, head and neck, and spinal column were all normal on examination. The karyotype was 46XY and the gender was male. Initial ultrasonography one week after birth revealed moderate bilateral hydronephrosis but the last ultrasonography 45 days later revealed only mild fullness of both kidneys.Keywords: Aphallia; Gender; penile agenesis

Dystrophic Epidermolysis Bullosa: COL7A1 Mutation Landscape in a Multi-Ethnic Cohort of 152 Extended Families with High Degree of Customary Consanguineous Marriages

Dystrophic epidermolysis bullosa is a heritable skin disease manifesting with sub-lamina densa blistering, erosions, and chronic ulcers. COL7A1, encoding type VII collagen, has been identified as the candidate gene for dystrophic epidermolysis bullosa. In this study, we have identified COL7A1 mutations in a large multi-ethnic cohort of 152 extended Iranian families with high degree of consanguinity. The patients were diagnosed by clinical manifestations, histopathology, and immunoepitope mapping. Mutation detection consisted of a combination of single nucleotide polymorphism-based whole-genome homozygosity mapping, Sanger sequencing, and gene-targeted next-generation sequencing. A total of 104 distinct mutations in COL7A1 were identified in 149 of 152 families (98%), 56 (53%) of them being previously unreported. Ninety percent of these mutations were homozygous recessive, reflecting consanguinity in these families. Three recurrent mutations were identified in five or more families, and haplotype analysis suggested a founder effect in two of them. In conclusion, COL7A1 harbored mutations in the overwhelming majority of patients with dystrophic epi-dermolysis bullosa, and most of them in this Iranian cohort were consistent with autosomal recessive inheri-tance. The mutation profile attests to the impact of consanguinity in these families

Uroflowmetry nomogram in Iranian children aged 7 to 14 years

BACKGROUND: As the voiding habits of Iranian children differs from other children because of some cultural and religious considerations, we aimed to establish normal reference values of urinary flow rates in Iranian children between 7 to 14 years of age. METHODS: Eight hundred and two uroflowmetry studies were performed on children with no history of a renal, urological, psychological or neurological disorder, between the ages 7 and 14. Five hundred twenty five studies from 192 girls and 335 boys were considered in this study excluding the staccato/interrupted voiding pattern or voided volume less than 20 ml. The voiding volume, the maximum and average urinary flow rates were extensively analyzed. RESULTS: The maximal and average urine flow rate nomograms were plotted for both girls and boys. Mean maximum urine flow rate was 19.9 (ml/sec) for boys and 23.5 (ml/sec) for girls with a mean voided volume of 142 (ml) for boys and 147 (ml) for girls. Flow rates showed a close association with voiding volume in both sexes. The maximum and average flow rates were higher in girls than in boys, and they showed a significant increase in flow rates with increasing age, where boys did not. The mean maximum urine flow rates (19.9 ml/sec for boys and 23.5 ml/sec for girls) were found to be higher in this study than other studies. CONCLUSION: Nomograms of maximal and average flow rates of girls and boys are presented in centile form, which can help the physician to evaluate the response to medical or surgical treatment and be useful for the screening of lower urinary tract disturbances in children, for a wide range of voided volumes

Comparison of the Incidence of Postoperative Hyponatremia after Infusion of Hypotonic Versus Isotonic Intravenous Solutions in Children

Introduction: Hyponatremia is the most common electrolyte disorder in patients following surgical interventions (19-50%). Hospital acquired hyponatremia is often due to using hypotonic solution s and can be lethal.Materials and Methods:Between January and December 2014, 190 children (1 month to 12 years) who were admitted in the urology department of Children’s Hospital Medical Center for elective surgical procedures were enrolled in the study. The patients were randomly divided into two groups: group I received 50 mEq/L sodium and 20 mEq/L potassium in D/W 5% and group II received 154 mEq/l sodium and 20 mEq/L potassium in D/W 5% at the maintenance dose for a period of 6 hours following the operation. The patients did not have any oral fluid intake 6 hours postoperatively. The incidence of hyponatremia before and after maintenance IV fluid therapy was analyzed. Other characteristics of the patients such as age, gender, duration of hospitalization, other concomitant electrolyte disturbances, and symptoms of hypervolemia were also evaluated. The incidence of fluid-IV therapy-induced hyponatremia was investigated and analyzed in different categories of patients.  Results: One hundred and ninety patients were enrolled. The mean age was 3.75 years (ranging from 1 month to 12years).  One hundred and thirty-three patients (70%) were boys. The incidence of hyponatremia before and after maintenance IV fluid therapy was 9.5% and 36%, respectively. After the therapy, the incidence of hyponatremia was 54% and 17% in hypotonic and isotonic groups, respectively. Final multivariate logistic analysis showed that hyponatremia was common in patients that received hypotonic solution after surgery.Conclusions: Hyponatremia was markedly induced in patients receiving hypotonic solution after surgery. It seems isotonic fluid therapy after surgery protects the patients from hyponatremia.Keywords: Hyponatremia; Isotonic solutions; Hypotonic solutions; Child

Recessive mutation in tetraspanin CD151 causes Kindler syndrome-like epidermolysis bullosa with multi-systemic manifestations including nephropathy

Epidermolysis bullosa (EB) is caused by mutations in as many as 19 distinct genes. We have developed a next-generation sequencing (NGS) panel targeting genes known to be mutated in skin fragility disorders, including tetraspanin CD151 expressed in keratinocytes at the dermal-epidermal junction. The NGS panel was applied to a cohort of 92 consanguineous families of unknown subtype of EB. In one family, a homozygous donor splice site mutation in CD151 (NM_139029; c.351 + 2T > C) at the exon 5/intron 5 border was identified, and RT-PCR and whole transcriptome analysis by RNA-seq confirmed deletion of the entire exon 5 encoding 25 amino acids. Immunofluorescence of proband's skin and Western blot of skin proteins with a monoclonal antibody revealed complete absence of CD151. Transmission electron microscopy showed intracellular disruption and cell-cell dysadhesion of keratinocytes in the lower epidermis. Clinical examination of the 33-year old proband, initially diagnosed as Kindler syndrome, revealed widespread blistering, particularly on pretibial areas, poikiloderma, nail dystrophy, loss of teeth, early onset alopecia, and esophageal webbing and strictures. The patient also had history of nephropathy with proteinuria. Collectively, the results suggest that biallelic loss-of-function mutations in CD151 underlie an autosomal recessive mechano-bullous disease with systemic features. Thus, CD151 should be considered as the 20th causative, EB-associated gene

Is D-penicillamine Safe in Management of Little Children with Kidney Cystine Stones? A Case Series

Nephrolithiasis is quite common in children. It sometimes has a genetic basis and can lead to serious complications like urinary obstruction, multiple surgical interventions, or even renal insufficiency if left treated. Cystinic stones and cystinuria account for approximately 8% of the cases of nephrolithiasis in children. We studied seven pediatric patients, 1 to 3 years old (mean age: 20.5 months), with cystinic urinary stones receiving D-penicillamine plus other drugs to dissolve the stone. All of them tolerated the treatment very well and did not show any serious complication. All of our cases were managed with D-penicillamine that was initiated at a low dose and then increased progressively. We used low dose D-penicillamine, maximim15 mg/kg/day, which was beneficial without any specific side effects. D-penicillamine can be used safely in little children. Gradual induction and close observation with CBC, urine analysis, BUN, creatinine, and liver function tests may be required. D-penicillamine can prevent new stone formation and resolve the present cystinic calculi. Low dose D-penicillamine may be sufficient in treating cystinic calculi in children. We suggest more evaluations on the advantage of low dose D-penicillamine in cystinuria.Keywords: D-Penicillamine; Cystinuria; Nephrolithiasis; Complications 

In vitro evaluation of human endometrial stem cell-derived osteoblast-like cells’ behavior on gelatin/collagen/bioglass nanofibers’ scaffolds

New biomimetic nanocomposite scaffold was prepared by the combination of nanofibrilar bioglass containing copper ion as the inorganic phase and gelatin/collagen as the organic phase of bone tissue. In this study for fabrication of the scaffold, freeze drying and electrospinning methods were used, and genipin was used as the cross-linking agent for increasing the mechanical properties of the scaffold. The growth and viability of human endometrial stem cell-derived osteoblast-like cells were investigated on this biomimetic scaffold. Cellular biocompatibility assays illustrated that this scaffold has more viabilities and osteoblast growths in comparison with two-dimensional culture. Copper ion increased growth of the osteoblasts on nanocomposite scaffold containing nanofibrous bioglass. Thus, the results obtained from this study indicate that the prepared scaffold is suitable for osteoblast growth and attachment; thus, potentially, this nanocomposite scaffold is an appropriate scaffold for bone tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2210–2219, 2016

Low Frequency Mechanical Actuation Accelerates Reperfusion In-Vitro

Background Rapid restoration of vessel patency after acute myocardial infarction is key to reducing myocardial muscle death and increases survival rates. Standard therapies include thrombolysis and direct PTCA. Alternative or adjunctive emergency therapies that could be initiated by minimally trained personnel in the field are of potential clinical benefit. This paper evaluates a method of accelerating reperfusion through application of low frequency mechanical stimulus to the blood carrying vessels. Materials and method We consider a stenosed, heparinized flow system with aortic-like pressure variations subject to direct vessel vibration at the occlusion site or vessel deformation proximal and distal to the occlusion site, versus a reference system lacking any form of mechanical stimulus on the vessels. Results The experimental results show limited effectiveness of the direct mechanical vibration method and a drastic increase in the patency rate when vessel deformation is induced. For vessel deformation at occlusion site 95% of clots perfused within 11 minutes of application of mechanical stimulus, for vessel deformation 60 centimeters from the occlusion site 95% percent of clots perfused within 16 minutes of stimulus application, while only 2.3% of clots perfused within 20 minutes in the reference system. Conclusion The presented in-vitro results suggest that low frequency mechanical actuation applied during the pre-hospitalization phase in patients with acute myocardial infarction have potential of being a simple and efficient adjunct therapy

Endoscopic treatment of vesicoureteral reflux using calcium hydroxyl apatite in dogs

<p>Abstract</p> <p>Background</p> <p>Injection of biomaterial to suburetral region, using minimally invasive procedure, has become an interesting topic for urologists to treat vesicoureteral reflux. The objective of this study was to evaluate the feasibility of injecting newly introduced calcium hydroxyl apatite to suburetral region, for treating an experimentally induced vesicoureteral reflux in dogs.</p> <p>Findings</p> <p>Bilateral vesicoureteral refluxed (VUR) mixed breed dogs (n = 12; 10-15 kg live weight, 3-6 months of age) were selected for this study. The presence and grade of the reflux were determined using cystography. Accordingly, 6 dogs displayed grade 1 & 2 and the other 6 showed grade 3 & 4 bilateral VUR. Every single dog, with bilateral VUR, underwent endoscopic treatment and received an injection of calcium hydroxyl apatite (an Iranian made product) into the left (treated side) and an injection of the similar volume of normal saline in to the right (control side) subureteric space. One week, 3 and 6 months after treatment, cystography was performed. On each occasion, 4 dogs were euthanized by gas inhalation and biopsy samples were collected for histopathological study from ureter, bladder, kidney, lung and spleen in order to investigate the biomaterial migration into different organs. Data were analyzed using Chi-squared test. In control sides, radiographs confirmed the same grade of VUR, found at the initiation of the study. VUR was resolved in 100% (6/6) of Grade 1 & 2 and 83.33% (5/6) of Grade 3 & 4 in treated side. Therefore, the total success rate of this study was 91.67% (11/12). Macroscopic examination of the vesicouretral region of the treated side revealed a firm and consistent biomaterial mass at the site of injection. Histological findings confirmed inflammation at treated side. In contrast, there was no tissue reaction on control side. There was no evidence for biomaterial migration in macroscopic and microscopic observations in this study.</p> <p>Conclusion</p> <p>In the present study, a new biocompatible material produced a firm, consist and sustainable biomaterial mass in the suburetral region for treating vesicouretral reflux without any evidence of biomaterial migration.</p