Gene-environment Interaction on the Risk of Type 2 Diabetes Among Ethnic Minority Populations Living in Europe and North America: A Systematic Review.

BACKGROUND: The body of evidence on gene-environment interaction (GEI) related to type 2 diabetes (T2D) has grown in the recent years. However, most studies on GEI have sought to explain variation within individuals of European ancestry and results among ethnic minority groups are inconclusive. OBJECTIVE: To investigate any interaction between a gene and an environmental factor in relation to T2D among ethnic minority groups living in Europe and North America. METHODS: We systematically searched Medline and EMBASE databases for the published literature in English up to 25th March 2019. The screening, data extraction and quality assessment were performed by reviewers independently. RESULTS: 1068 studies identified through our search, of which nine cohorts of six studies evaluating several different GEIs were included. The mean follow-up time in the included studies ranged from 5 to 25.7 years. Most studies were relatively small scale and few provided replication data. All studies included in the review included ethnic minorities from North America (Native-Americans, African- Americans, and Aboriginal Canadian), none of the studies in Europe assessed GEI in relation to T2D incident in ethnic minorities. The only significant GEI among ethnic minorities was HNF1A rs137853240 and smoking on T2D incident among Native-Canadians (Pinteraction = 0.006). CONCLUSION: There is a need for more studies on GEI among ethnicities, broadening the spectrum of ethnic minority groups being investigated, performing more discovery using genome-wide approaches, larger sample sizes for these studies by collaborating efforts such as the InterConnect approach, and developing a more standardized method of reporting GEI studies are discussed.

Tubal flushing with oil- or water-based contrast medium: can we identify markers that indicate treatment benefit?

STUDY QUESTION: Can we identify patient characteristics that distinguish which ovulatory infertile women undergoing hysterosalpingography (HSG) benefit more or less from flushing with oil-based contrast medium compared to water-based contrast medium? SUMMARY ANSWER: In ovulatory infertile women, HSG with oil-based contrast medium resulted in higher 6-month ongoing pregnancy and live birth rates as compared to HSG with water-based contrast medium and this treatment effect was independent of characteristics of the couple. WHAT IS KNOWN ALREADY: We recently showed that in infertile women undergoing HSG, flushing with oil-based contrast medium resulted in more ongoing pregnancies than flushing with water-based contrast medium. STUDY DESIGN SIZE DURATION: We used data from our randomized clinical trial (RCT) in which 1,119 ovulatory infertile women undergoing HSG during fertility work-up were randomized for use of oil-based (N = 557) or water-based (N = 562) contrast medium. PARTICIPANTS/MATERIALS SETTING METHODS: We built logistic regression models to predict ongoing pregnancy and live birth (secondary outcome) as a function of the specific contrast, the specific marker, and marker-by-contrast-interaction. Markers considered were female age, maternal ethnicity, female smoking, body mass index (BMI), duration of infertility, infertility being primary or secondary, sperm quality, and previous appendectomy. MAIN RESULTS AND THE ROLE OF CHANCE: The 6-month ongoing pregnancy rates in the overall population were 39.7% after use of oil-based contrast versus 29.1% after use of water-based contrast medium [relative risk (RR), 1.37; 95% confidence interval (CI), 1.16-1.61; P < 0.001]. Among the studied baseline characteristics, BMI (P = 0.002) and semen volume (P = 0.02) were statistically significant prognosticators. The treatment effect of oil-based contrast was stronger in women with a BMI ≤30 kg/m2 [RR, 1.54; 95% CI, 1.23-1.92; P = 0.002], and in women whose partner had a semen volume >3 ml [RR, 1.77; 95% CI, 1.28-2.46; P = 0.02]. Also, in women who smoked, the treatment effect of flushing with oil was stronger, but this interaction did not reach statistical significance (P = 0.066). We found no positive effect of oil-based contrast in obese women. We found similar but weaker associations for live birth, which was probably due to lower number of events resulting in less power. LIMITATIONS REASONS FOR CAUTION: The RCT was restricted to infertile ovulatory women younger than 39 years of age without endocrinological disorders and at low risk for tubal pathology. Our results should not be generalized to infertile women who do not share these features. WIDER IMPLICATIONS OF THE FINDINGS: All infertile, ovulatory women younger than 39 years with a low risk for tubal pathology will benefit from an HSG with oil-based contrast; therefore, this should be offered to them after fertility work-up. STUDY FUNDING/COMPETING INTERESTS: The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (AMC and VUmc) of the Amsterdam UMC. The study displayed in this paper was funded by an unconditional research grant from Guerbet. B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548). K.D. reports consultancy for Guerbet, during the conduct of the study, and also reports research grants from Guerbet. C.B.L. reports grants from Guerbet, during the conduct of the study, and grants from Ferring, grants from Merck, and personal fees from Ferring, outside the submitted work. P.H. reports grants from Guerbet, during the conduct of the study, and grants from Ferring and Merck, outside the submitted work. V.M. reports receiving travel and speakers fee as well as research grants from Guerbet. B.W.M. reports consultancy for ObsEva, Merck, Merck KGaA, and Guerbet, and research grants from Guerbet and Merck. The other authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: NTR 3270 www.trialregister.nl. TRIAL REGISTRATION DATE: 1 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 3 February 2012.

The FIGO Stage IVA Versus IVB of Ovarian Cancer: Prognostic Value and Predictive Value for Neoadjuvant Chemotherapy.

OBJECTIVE: The revised version of the International Federation of Gynaecology and Obstetrics (FIGO) staging system (2014) for epithelial ovarian cancer includes a number of changes. One of these is the division of stage IV into 2 subgroups. Data on the prognostic and predictive significance of this classification are scarce. The effect of neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) in relation to the subclassification of FIGO stage IV is also unknown. METHODS: We used data of the EORTC 55971 trial, in which 670 patients with previous stage IIIC or IV epithelial ovarian cancer were randomly assigned to PDS or NACT; 160 patients had previous stage IV. Information on previous FIGO staging and presence of pleural effusion with positive cytology were used to classify tumors as either stage IVA or IVB. We tested the association between stage IVA/IVB and survival to evaluate the prognostic value and interactions between stage, treatment, and survival to evaluate the predictive performance. RESULTS: Among the 160 participants with previous stage IV disease, 103 (64%) were categorized as stage IVA and 57 (36%) as stage IVB tumors. Median overall survival was 24 months in FIGO stage IVA and 31 months in stage IVB patients (P = 0.044). Stage IVB patients treated with NACT had 9 months longer median overall survival compared with IVB patients undergoing PDS (P = 0.025), whereas in IVA patients, no significant difference was observed (24 vs 26 months, P = 0.48). CONCLUSIONS: The reclassification of FIGO stage IV into stage IVA or IVB was not prognostic as expected. Compared with stage IVA patients, stage IVB patients have a better overall survival and may benefit more from NACT.

Which intrauterine growth restricted fetuses at term benefit from early labour induction? A secondary analysis of the DIGITAT randomised trial.

OBJECTIVE: The Disproportionate Intrauterine Growth Intervention Trial at Term (DIGITAT trial) showed that in women with suspected intrauterine growth restriction (IUGR) at term, there were no substantial outcome differences between induction of labour and expectant monitoring. The objective of the present analysis is to evaluate whether maternal or fetal markers could identify IUGR fetuses who would benefit from early labour induction. STUDY DESIGN: The DIGITAT trial was a multicenter, parallel and open-label randomised controlled trial in women who had a singleton pregnancy beyond 36+0 weeks' gestation with suspected IUGR (n=650). Women had been randomly allocated to either labour induction or expectant monitoring. The primary outcome was a composite measure of adverse neonatal outcome, defined as neonatal death before hospital discharge, Apgar score <7, umbilical artery pH <7.05, or admission to neonatal intensive care. Using logistic regression modelling, we investigated associations between outcome and 17 markers, maternal characteristics and fetal sonographic and Doppler velocimetry measurements, all collected at study entry. RESULTS: 17 (5.3%) infants in the induction group had an adverse neonatal outcome compared to 20 (6.1%) in the expectant monitoring group. The only potentially informative marker for inducing labour was maternal pre-pregnancy body mass index (BMI). Otherwise, we observed at best weak associations between a benefit from labour induction and maternal age, ethnicity, smoking, parity, pregnancy-induced hypertension or preeclampsia, Bishop score and gestational age, or fetal sonographic markers (gender, estimated fetal weight, body measurements, oligohydramnios, or umbilical artery pulsatility index and end diastolic flow). CONCLUSION: In late preterm and term pregnancies complicated by suspected intrauterine growth restriction, most of the known prognostic markers seem unlikely to be helpful in identifying women who could benefit from labour induction, except for maternal pre-pregnancy BMI.

Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial.

BACKGROUND: To investigate whether biomarkers consisting of baseline characteristics of advanced stage ovarian cancer patients can help in identifying subgroups of patients who would benefit more from primary surgery or neoadjuvant chemotherapy. METHODS: We used data of the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial in which 670 patients were randomly assigned to primary surgery or neoadjuvant chemotherapy. The primary outcome was overall survival. Ten baseline clinical and pathological characteristics were selected as potential biomarkers. Using Subpopulation Treatment Effect Pattern Plots (STEPP), biomarkers with a statistically significant qualitative additive interaction with treatment were considered as potentially informative for treatment selection. We also combined selected biomarkers to form a multimarker treatment selection rule. FINDINGS: The size of the largest metastatic tumour and clinical stage were significantly associated with the magnitude of the benefit from treatment, in terms of five-year survival (p for interaction: 0.008 and 0.016, respectively). Stage IIIC patients with metastatic tumours ⩽45 mm benefited more from primary surgery while stage IV patients with metastatic tumours >45 mm benefited more from neoadjuvant chemotherapy. In stage IIIC patients with larger metastatic tumours and in stage IV patients with less extensive metastatic tumours both treatments were equally effective. We estimated that by selecting treatments for patients based on largest metastatic tumour and clinical stage, the potential five-year survival rate in the population of treated patients would be 27.3% (95% confidence interval (CI) 21.9-33.0), 7.8% higher than if all were treated with primary surgery, and 5.6% higher if all were treated with neoadjuvant chemotherapy. INTERPRETATION: Although survival was comparable after primary surgery and neoadjuvant chemotherapy in the overall group of patients with ovarian cancer in the EORTC 55971 trial, we found in this exploratory analysis that patients with stage IIIC and less extensive metastatic tumours had higher survival with primary surgery, while patients with stage IV disease and large metastatic tumours had higher survival with neoadjuvant chemotherapy. For patients who did not meet these criteria, both treatment options led to comparable survival rates.

Trial designs for personalizing cancer care: a systematic review and classification.

There is an increasing interest in the evaluation of prognostic and predictive biomarkers for personalizing cancer care. The literature on the trial designs for evaluation of these markers is diverse and there is no consensus in the classification or nomenclature. We set this study to review the literature systematically, to identify the proposed trial designs, and to develop a classification scheme. We searched MEDLINE, EMBASE, Cochrane Methodology Register, and MathSciNet up to January 2013 for articles describing these trial designs. In each eligible article, we identified the trial designs presented and extracted the term used for labeling the design, components of patient flow (marker status of eligible participants, intervention, and comparator), study questions, and analysis plan. Our search strategy resulted in 88 eligible articles, wherein 315 labels had been used by authors in presenting trial designs; 134 of these were unique. By analyzing patient flow components, we could classify the 134 unique design labels into four basic patient flow categories, which we labeled with the most frequently used term: single-arm, enrichment, randomize-all, and biomarker-strategy designs. A fifth category consists of combinations of the other four patient flow categories. Our review showed that a considerable number of labels has been proposed for trial designs evaluating prognostic and predictive biomarkers which, based on patient flow elements, can be classified into five basic categories. The classification system proposed here could help clinicians and researchers in designing and interpreting trials evaluating predictive biomarkers, and could reduce confusion in labeling and reporting.

Antigliadin antibody in sporadic adult ataxia.

BACKGROUND: The most common neurologic manifestation of gluten sensitivity is ataxia, which accounts for up to 40% of idiopathic sporadic ataxia. Timing of diagnosis of gluten ataxia is vital as it is one of the very few treatable causes of sporadic ataxia and causes irreversible loss of Purkinje cells. Antigliadin antibody (AGA) of the IgG type is the best marker for neurological manifestations of gluten sensitivity. This study was conducted to measure the prevalence of gluten ataxia in a group of Iranian patients with idiopathic ataxia. METHODS: For 30 patients with idiopathic cerebellar ataxia, a questionnaire about clinical and demographic data was completed. Serum AGA (IgA and IgG) and antiendomysial antibody (AEA) were assessed. Gluten ataxic patients underwent duodenal biopsy. Magnetic resonance imaging was done for all patients to see if cerebellar atrophy is present. RESULTS: Only 2 patients had a positive IgG AGA (6.7%) who both had a positive AEA while none of them showed changes of celiac disease in their duodenal biopsies. Only presence of gastrointestinal symptoms and pursuit eye movement disorders were higher in patients with gluten ataxia. CONCLUSION: Prevalence of gluten ataxia in Iranian patients with idiopathic ataxia seems to be lower than most of other regions. This could be explained by small sample size, differences in genetics and nutritional habits and also effect of serologic tests in clinical versus research setting. Further researches with larger sample size are recommended.

A randomized trial of ceftriaxone versus trimethoprim-sulfamethoxazole to prevent ventriculoperitoneal shunt infection.

BACKGROUND AND PURPOSE: Shunt infection represents a particularly morbid condition, which can also result in mortality. In order to decrease the high morbidity and mortality rates, prevention is an essential step. The purpose of this study was to compare the prophylactic use of ceftriaxone and trimethoprim-sulfamethoxazole (SXT) for the prevention of ventriculoperitoneal (VP) shunt infection. METHODS: In this prospective, single-institution, randomized clinical trial, 107 children with hydrocephalus and an indication for shunting were randomly assigned to prophylaxis with ceftriaxone (n = 50) or SXT (55), each administered as a single dose during anesthesia and two divided doses postoperatively. Patients were followed up for at least one year. RESULTS: The mean age of patients was 15 months, and 85% were aged 6 months or younger. During the first postoperative year, meningitis occurred in 13.5% of patients receiving ceftriaxone and 14.5% of the SXT group, with no statistically significant difference between the groups. Younger age, presence of cerebrospinal fluid leakage and aqueductal stenosis as a cause of hydrocephalus showed significant correlation with meningitis occurrence on univariate analysis. However, only the latter 2 factors were associated with meningitis on multivariate analysis. The risk of shunt infection did not correlate with the gender of the patient, time of VP shunt surgery, or duration of hospitalization for shunting. CONCLUSION: Ceftriaxone and SXT showed similar efficacy in preventing shunt infection. Cerebrospinal fluid leakage before or after VP shunt placement and aqueductal stenosis were independent risk factors for meningitis after VP shunt.

Serum selenium level and prostate cancer: a case-control study.

Selenium is a potential chemopreventive agent against prostate cancer. This study sought to evaluate and compare the serum selenium level in men with newly diagnosed prostate cancer and noncancerous patients. Between 2005 and 2006, this prospective case-control study was performed on patients referred to Sina and Imam University hospitals, Tehran, Iran; it included 62 men with clinicopathologically confirmed diagnosis of prostate cancer (case group) and 68 men with no detectable prostate cancer [normal digital rectal examination and prostate-specific antigen (PSA) level] or any other malignant disease (control group). The serum selenium level was assessed using Zeeman graphite furnace atomic absorption spectrometer (Varian Company, Australia). The mean serum selenium level in the case and control group was 66.3 +/- 17.7 microg/l and 77.5 +/- 22.5 microg/l, respectively (P = 0.002). Serum selenium was inversely associated with prostate cancer risk. After adjustment for age, body mass index (BMI), and smoking, the odds ratio was 0.16 and 95% confidence intervals were 0.06 to 0.47 (P trendq = 0.001) comparing the highest with the lowest tertile (> or = 89.3 microg/l). No correlation was observed between serum selenium level and age, BMI, or PSA level. In conclusion, serum selenium levels in prostate cancer cases were lower than in controls, which supports the hypothesis that selenium may protect against prostate cancer.

Breastfeeding: a potential protective factor against ventriculoperitoneal shunt infection in young infants.

OBJECT: Previous studies have shown nutritional benefits of breastfeeding for a child's health, especially for protection against infection. Protective factors in human milk locally and systemically prevent infections in the gastrointestinal as well as upper and lower respiratory tracts. It remains unclear whether breastfeeding protects infants against ventriculoperitoneal (VP) shunt infection. METHODS: A cohort study was conducted from December 2003 to December 2006 at Children's Hospital Medical Center in Tehran, Iran. A total of 127 infants with hydrocephalus who were treated using a VP shunt in the first 6 months of life were enrolled. Each infant's breastfeeding method was classified as either exclusively breastfed (EBF), combination feedings of breast milk and formula (CFBF), or exclusively formula-fed (EFF). Infants were followed up to determine the occurrence of shunt infection within 6 months after operation. Statistical analysis was performed using survival methods. RESULTS: Infants ranged in age from 4 to 170 days at the time of shunt insertion (mean 69.6 days), and 57% were males. Regarding the breastfeeding categories, 57.5% were EBF, 25.2% were CFBF, and 17.3% were EFF. During the follow-up, shunt infection occurred in 16 patients, within 15 to 173 days after shunt surgery (median 49 days). The 6-month risk of shunt infection was 8.5% (95% confidence interval [CI] 4-18%) in the EBF group, 16.5% (95% CI 7-35%) in the CFBF group, and 26.0% (95% CI 12-52%) in the EFF group. There was no statistically significant difference between these 3 groups (p=0.11). The trend test showed a significant trend between the extent of breastfeeding and the risk of shunt infection (p=0.035), which persisted even after adjustment for potential confounding variables (hazard ratio=2.01, 95% CI 1.01-4). CONCLUSIONS: This study supports the protective effect of breastfeeding against shunt infection during the first 6 months of life and the presence of a dose-response relationship, such that the higher the proportion of an infant's feeding that comes from human milk, the lower the incidence of shunt infection. Encouraging mothers of infants with VP shunts to breastfeed exclusively in the first 6 months of life is recommended.

Intelligence quotient in children with meningomyeloceles: a case-control study.

OBJECT: Meningomyelocele (MMC) is a common central nervous system birth defect. As one of many problems facing patients with MMC, learning disabilities are often overlooked. The aim of this study was to evaluate IQs in a group of children with MMCs and determine if a correlation exists between intelligence level and the presence of an MMC and/or its complications. METHODS: A case-control study was conducted at the Children's Hospital Medical Center in Tehran, Iran, from December 2004 through December 2005. The patient group included 50 children with MMC from 5 to 12 years of age who were referred to the authors' institution for treatment of complications or for follow up after surgery for MMC closure. The patient group was individually matched for age and sex with a control group of 50 children referred to the hospital for other reasons and who did not have MMC or other neurological abnormalities. The IQs in all children in this study were evaluated using the Ravens Progressive Matrices test. The children in both groups were similar in the socioeconomic status of the family (p = 0.347) and educational status of the father (p = 0.117) and mother (p = 0.439). Patient age at the time of surgery for MMC closure varied from 1 day to 96 months (mean 4.1 months). Only 20% of the patients with MMC could walk with a normal gait. Forty-six percent of the patients had undergone placement of a ventriculoperitoneal shunt, and half of these patients experienced shunt-related complications; 72% of the children in the patient group were completely incontinent for both urine and feces. The IQ results obtained in the patient group ranged from 73 to 134 with a mean (+/- standard deviation) of 96.62 +/- 13.01. In the control group the IQ range was 70 to 128, and the mean was 104.82 +/- 12.30. Compared with the control group there was a statistically significant correlation between having an MMC and having a lower IQ (p < 0.001, paired t-test). CONCLUSIONS: Although the average IQ in the patient group was significantly lower than that in the control group, it is important to note that all children in the patient group had an average or above-average IQ. In contrast with the results reported in other studies, earlier repair of the MMC, the presence of a shunt or shunt-related complications, walking difficulty, and the spinal level of the lesion did not correlate significantly with IQs. Therefore, the lower IQ and reduced cognitive levels noted in these patients result from the disease process itself and not from the associated complications.

Time-dependent neovasculogenesis and regeneration of different bladder wall components in the bladder acellular matrix graft in rats.

OBJECTIVES: To determine the time-dependent regeneration of different cellular components in the bladder acellular matrix graft (BAMG) and the involvement of hematopoietic stem cells in BAMG vascular regeneration. METHODS AND MATERIALS: Thirty-three male Sprague Dawley rats underwent partial cystectomy and the acellular matrices were grafted to the remaining host bladder. At 4, 7, 14, 30, 60, 90, and 180 d after grafting, animals were sacrificed and their bladders were excised and paraffin-embedded. Tissue sections were stained for determination of CD3, CD20, CD34, CD31, CD68, smooth muscle cell (SMC) alpha-actin, and neurofilament protein as well as elastin fibers and collagen typing. Cystometric evaluation of grafted bladders was also performed 3 mo after procedure. RESULTS: In acellular matrices, there was no expression of cellular markers and type-1 collagen fibers were predominant. One month after surgery, all grafted matrices were completely lined with urothelium. Polymorphonuclear cells and lymphocytes densely infiltrated BAMG during the first 2 wk after grafting; however the inflammation resolved by the first post-surgical mo. CD34+ endothelial progenitor cells (EPCs) were found in all grafts 4 d after surgery. The number of CD34+ cells increased continuously and peaked 2 mo after grafting. The increment in number of CD31+ microvessels in grafted matrices followed that of CD34+ cells and reached 144.5% of control values at third post-surgical mo. The mean number of CD34+ and CD31+ cells returned to control ranges by 6 mo after grafting. Expression of SMC alpha-actin was first visualized on day 4 and alpha-actin intensity reached to control values 6 mo after grafting. Neural elements appeared 1 wk after grafting and just 60% of normal intensity was achieved by the sixth post-surgical mo; however complete nerve bundles were found in all grafted matrices after 1 mo. Cystometric studies revealed higher bladder capacity and compliance but lower maximum intravesical pressure in grafted bladders in comparison with controls, 3 mo after surgery. CONCLUSIONS: Our results demonstrate the effective cellular regeneration in BAMG and propose a considerable role for the CD34+ EPCs in the neo-vasculogenesis of the grafts.

Ureteral catheterization in uncomplicated ureterolithotripsy: a randomized, controlled trial.

OBJECTIVE: To evaluate short-term ureteral catheterization in patients undergoing ureteroscopic lithotripsy for ureteral calculi. METHODS: Patients (n = 140) with ureteral calculi who were candidates for ureterolithotripsy were enrolled. Stone size was 5-10mm. The operation was performed with an 8-9.8F semirigid ureteroscope without active dilatation and stones were fragmented with a 1F pneumatic lithotrite. Uncomplicated cases (109 patients) were randomized to catheterized (C) and noncatheterized (NC) groups. In the 54 C group patients, a polyurethane catheter (5F) was passed through the ureter after lithotripsy with the end attached to a Foley placed in urethra, which was removed after 24h. Postoperatively, all patients were evaluated for flank and suprapubic pain, renal colic, irritative urinary symptoms, peritonism, frequency of analgesic usage, urinary tract infection, duration of hospitalization, postdischarge visits (due to renal colic/pain), readmission, and residual stone rates. RESULTS: On the first postoperative day, the percentage of patients experiencing flank pain and renal colic was significantly higher in the NC group (76% and 45%) compared with the C group (20% and 2%); 67% of NC patients required analgesic administration during hospital stay versus 20% of C patients (p<0.001). Suprapubic pain and urethral irritation were reported by 13% and 37% of C patients, respectively, and 5% and 4% of NC patients. However, peritonism was developed more often in NC patients (27% vs. 13%). Hospital stay was 1 d for all patients. Three days postoperatively, 40% of NC patients complained of at least one episode of flank pain compared with 7% of C patients (p<0.001). Incidence of urinary tract infections was 4% in NC and 7% in C group patients. Postdischarge visits were necessary in 20% of NC patients and 5% of C patients. No patient in either group required readmission. No complaints were reported nor residual stones discovered on 2-wk follow-up radiographs in either group. CONCLUSIONS: Short-term ureteral catheterization in uncomplicated ureteroscopy and lithotripsy has a role in reducing early postoperative morbidities. It may also decrease pain and colic after discharge.

Intravesical injection of botulinum toxin type A: management of neuropathic bladder and bowel dysfunction in children with myelomeningocele.

OBJECTIVES: To evaluate the efficacy of botulinum toxin A in the treatment of children with detrusor hyperreflexia caused by myelomeningocele and the effects of this treatment on neuropathic bladder and bowel dysfunction. METHODS: In a prospective study, 26 children with myelomeningocele (20 boys and 6 girls, mean age 6.9 years) were included. All patients had been nonresponders to medical treatment and required clean intermittent catheterization. Under cystoscopic guidance, 10 IU/kg of botulinum toxin A was injected into the detrusor muscle, sparing the trigone and ureteral orifices. In each patient, urinary incontinence grade and improvement in parameters of interest in the evaluation of bowel dysfunction were assessed before and 4 months after injection. Conventional urodynamic studies to determine maximal bladder capacity and maximal detrusor pressure and voiding cystoureterography were also performed. RESULTS: Four months after procedure, 19 patients (73%) had become completely dry between clean intermittent catheterizations, and the total improvement in urine incontinence was 88%. The mean maximal detrusor pressure was decreased to 83.2 +/- 4.6 cm H2O from the baseline of 139.3 +/- 11.2 (P <0.01). The average maximal bladder capacity increased from 102.8 +/- 6.3 mL to 270.2 +/- 9.5 mL (P <0.01). Of the 15 patients who had varying degrees of vesicoureteral reflux before the procedure, 11 (73%) had decrease in the vesicoureteral reflux grade. Also, bowel dysfunction improved in 10 (66%) of the 15 patients. CONCLUSIONS: Botulinum toxin A appears to be a safe, minimally invasive procedure for the management of neuropathic bladder and bowel dysfunction in children with myelomeningocele.

Bladder exstrophy and epispadias complex in sibling: case report and review of literature.

The bladder exstrophy and classic epispadias represent a spectrum of congenital anomalies with different degrees of anterior midline defect. Although the anomaly usually occurs sporadically there are some cases indicative of a strong genetic component. We present the clinical data of two siblings with bladder exstrophy and epispadias complex (BEEC), who were the product of consanguineous union. All previous reports of familial BEEC in the literature have been reviewed.

The prenatal ultrasonographic detection of myelomeningocele in patients referred to Children's Hospital Medical Center: a cross sectional study.

BACKGROUND: To find out about the prenatal diagnosis rate of myelomeningocele (MMC) by ultrasound scan in patients referred to the Children's Hospital Medical Center in Tehran, Iran from July 2004 to July 2005. METHODS: We included 140 children born with MMC and who were referred for management, surgery and treatment of complications associated with it. The ultrasound reports were examined. Data on sex, age, location of MMC, time of prenatal ultrasound and the trimester in which the diagnosis was made along with the results of the diagnosis (MMC, hydrocephalus, or both), were collected. RESULTS: Among the studied patients, 136 (97.1%) cases had prenatal ultrasound, amongst those, 58 (42.6%) sonographic evaluations were diagnostic for hydrocephalus and/or MMC. The prenatal ultrasound was positive for MMC in 16 (11.8%), hydrocephalus in 25 (18.4%) and both MMC and hydrocephalus in 17 (12.5%) cases. Among all cases with prenatal diagnosis of MMC, 3.4% were detected in the first, 31% in the second and 65.5% in the third trimester. Thoracic/thoracolumbar lesions were found prenatally in 40% of cases, which is significantly higher than the detection rate of other locations including cervical/cervicothoracic and lumbar/lumbosacral/sacral regions diagnosed only in 0% and 21% of cases respectively. CONCLUSION: There is a large difference between the detection rate of our population (24.3%) compared to others (68%). Pregnant women should have an ultrasound at 20-22 week for detection of congenital anomalies including MMC.

Cervical myelomeningocele.

OBJECTIVE: Cervical myelomeningocele (cMMC) is a rare disease. Only a few series have been published regarding cMMC. Different issues regarding the etiology, classification, clinical, surgical, and pathological aspects of cMMC are still a matter of conflict. METHODS: Sixteen children operated on for cMMC between July 2000 and 2003 were followed by the neurosurgical service at Children's Hospital Medical Center in Tehran. The patients were followed up for 2 to 5 years (median, 3 yr). RESULTS: The studied patients were nine boys and seven girls, ages 1 day to 4 months. Neurological examination was normal in all but two patients. All children had a normal anal fold, could void spontaneously, and showed no evidence of gross orthopedic deformity. We found eight patients with hydrocephalus, four patients with Chiari II malformation, two patients with syringomyelia, one patient with diastematomyelia at the level of cervical hemimyelomeningocele, and one patient with associated sacral myeloschisis. A thorough urological evaluation was planned for 13 patients, which confirmed bladder dysfunction in 10 (71%) patients. All infants had midline lesions, which consisted of a protruding sac from the back of neck, covered with purplish rudimentary or dysplastic skin at the dome. All patients underwent surgical resection of the sac and intradural exploration to release any adhesion and to exclude other associated anomalies. CONCLUSION: Cervical myelomeningocele differs structurally and clinically from myelomeningocele in distal areas and has a more favorable outcome. We think that some trivial neurological deficits in cMMC are caused by the late and limited neurulation abnormality during its development. We advise thorough preoperative evaluation of the brain, spinal column, and urinary system. Intradural exploration to release any potential adhesion bands as well as correcting associated anomalies is recommended in all cMMC operations.

Endoscopic subureteral urocol injection for the treatment of vesicoureteral reflux.

PURPOSE: We evaluated the effect of Urocol injection for the endoscopic treatment of VUR in children. MATERIALS AND METHODS: A total of 208 children (62 boys and 146 girls, mean age 4.78 years) with 346 refluxing ureters underwent subureteral injection of Urocol between January 2000 and February 2002. VCUG was performed at 6 months, and ultrasound was performed at 1 week and 3 months postoperatively. RESULTS: Followup VCUG showed no evidence of reflux in 240 ureters (69%), significant decrease in reflux grade in 62 (18%) and no change in 44 (13%). Ultrasound revealed no obstruction or hydronephrosis. CONCLUSIONS: The results of this study demonstrate that subureteral injection of Urocol was effective for the treatment of VUR. We conclude that Urocol represents a new, safe, simple, less expensive and repeatable technique in treating VUR.