Exploring the interplay between kidney function and urinary metabolites in young adults: the African-PREDICT study.

The exposure to modifiable risk factors at young ages have been linked to premature fatal and non-fatal cardiovascular and kidney outcomes. The use of urinary metabolomics has shown strong predictability of kidney function and cardiovascular disease (CVD). We therefore determined the associations between estimated glomerular filtration rate (eGFR) and urinary metabolites in young adults with and without CVD risk factors. Apparently healthy Black and White sexes were included (aged 20-30 years) and categorised by the presence or absence of risk factors, i.e., obesity, physical inactivity, smoking, excessive alcohol intake, masked hypertension, hyperglycemia, dyslipidemia and low socio-economic status, forming the CVD risk group (N = 1036), CVD risk clusters (i.e. presenting with 1 CVD risk factor (N = 344), 2 CVD risk factors (N = 360) and 3 + CVD risk factors (N = 332)) and the control group (N = 166). eGFR was calculated with CKD-EPI equations. A targeted metabolomics approach using liquid chromatography-tandem mass spectrometry was used to measure amino acids and acylcarnitines. Lower cystatin C-based eGFR were indicated in the CVD risk group, 2 and 3 + CVD risk clusters compared to the control group (all P ≤ 0.033). In the CVD risk group, eGFR associated positively with histidine, lysine, asparagine, glycine, serine, glutamine, dimethylglycine, threonine, alanine, creatine, cystine, methionine, tyrosine, pyroglutamic acid, leucine/isoleucine, aspartic acid, tryptophan, glutamic acid, free carnitine, acetylcarnitine, propionylcarnitine, isovalerylcarnitine, octanoylcarnitine and decanoylcarnitine (all P ≤ 0.044), with similar results found in the CVD risk clusters, particularly the 2 CVD risk cluster. eGFR was positively associated with metabolites linked to aromatic amino acid and branched-chain amino acid metabolism, energy metabolism and oxidative stress. These findings may indicate altered reabsorption of these metabolites or altered metabolic regulation to preserve renal health in the setting of CVD risk factors at this young age without established CVD.

Markers of arterial stiffness and urinary metabolomics in young adults with early cardiovascular risk: the African-PREDICT study.

INTRODUCTION: Increased exposure to risk factors in the young and healthy contributes to arterial changes, which may be accompanied by an altered metabolism. OBJECTIVES: To increase our understanding of early metabolic alterations and how they associate with markers of arterial stiffness, we profiled urinary metabolites in young adults with cardiovascular disease (CVD) risk factor(s) and in a control group without CVD risk factors. METHODS: We included healthy black and white women and men (N = 1202), aged 20-30 years with a detailed CVD risk factor profile, reflecting obesity, physical inactivity, smoking, excessive alcohol intake, masked hypertension, hyperglycemia, dyslipidemia and low socio-economic status, forming the CVD risk group (N = 1036) and the control group (N = 166). Markers of arterial stiffness, central systolic blood pressure (BP) and pulse wave velocity were measured. A targeted metabolomics approach was followed by measuring amino acids and acylcarnitines using a liquid chromatography-tandem mass spectrometry method. RESULTS: In the CVD risk group, central systolic BP (adjusted for age, sex, ethnicity) was negatively associated with histidine, arginine, asparagine, serine, glutamine, dimethylglycine, threonine, GABA, proline, methionine, pyroglutamic acid, aspartic acid, glutamic acid, branched chain amino acids (BCAAs) and butyrylcarnitine (all P ≤ 0.048). In the same group, pulse wave velocity (adjusted for age, sex, ethnicity, mean arterial pressure) was negatively associated with histidine, lysine, threonine, 2-aminoadipic acid, BCAAs and aromatic amino acids (AAAs) (all P ≤ 0.044). In the control group, central systolic BP was negatively associated with pyroglutamic acid, glutamic acid and dodecanoylcarnitine (all P ≤ 0.033). CONCLUSION: In a group with increased CVD risk, markers of arterial stiffness were negatively associated with metabolites related to AAA and BCAA as well as energy metabolism and oxidative stress. Our findings may suggest that metabolic adaptations may be at play in response to increased CVD risk to maintain cardiovascular integrity.

Using urinary metabolomics to identify metabolic pathways linked to cardiac structural alterations in young adults: The African-PREDICT study.

BACKGROUND AND AIMS: Risk factor exposure from young ages was shown to contribute to cardiovascular events - cardiac hypertrophy, which may be accompanied by an altered metabolism. To determine how early metabolic alterations associate with myocardial structural changes, we profiled urinary metabolites in young adults with cardiovascular disease (CVD) risk factor(s) and a control group without CVD risk factors. METHODS AND RESULTS: We included healthy adults (N = 1202), aged 20-30 years, stratified based on risk factors, i.e., obesity, physical inactivity, elevated blood pressure (BP), hyperglycemia, dyslipidemia, low socio-economic status, smoking and excessive alcohol use - forming the CVD risk group (N = 1036) and the control group (N = 166). Relative wall thickness (RWT) and left ventricular mass index (LVMi) were measured using echocardiography. Targeted metabolomics data were obtained using a liquid chromatography-tandem mass spectrometry method. Clinic systolic BP, 24 h BP and RWT were higher in the CVD risk group compared to the control group (all P ≤ 0.031). Exclusively in the CVD risk group, RWT associated with creatine and dodecanoylcarnitine; while LVMi associated with glycine, serine, glutamine, threonine, alanine, citrulline, creatine, proline, pyroglutamic acid and glutamic acid (all P ≤ 0.040). Exclusively in the control group, LVMi associated with propionylcarnitine and butyrylcarnitine (all P ≤ 0.009). CONCLUSION: In young adults without CVD, but with CVD risk factors, LVMi and RWT associated with metabolites linked energy metabolism (shifting from solely fatty acid oxidation to glycolysis, with impaired creatine kinase activity) and oxidative stress. Our findings support early onset metabolic changes accompanying cardiac structural alterations due to lifestyle and behavioural risk factors.

The renin-angiotensin-system and left ventricular mass in young adults: the African-PREDICT study.

PURPOSE: Raised blood pressure, with the renin-angiotensin system (RAS) as a central regulatory component, is one of the most important contributors to early development of left ventricular hypertrophy. Factors such as increased age, sex, black ethnicity and a low socio-economic status also contribute to left ventricular remodelling. To better understand early contributors to left ventricular mass, we investigated the relationship between left ventricular mass index (LVMi) and the components of the RAS in young healthy adults while considering ethnicity, sex and socio-economic status. MATERIALS AND METHODS: Black and white women and men (N = 1186) between the ages of 20-30 years were included. By using standard echocardiography, we determined LVMi. Ultra-pressure-liquid chromatography tandem-mass spectrometry (LC-MS/MS) was used to measure the RAS-fingerprint®. RESULTS: Components of the RAS such as plasma renin activity (PRA-S), angiotensin I (Ang I), angiotensin II (Ang II) and aldosterone were suppressed in the black compared to the white group (all p < 0.001). No associations between LVMi and the RAS were evident in the total, black or white groups. With additional grouping according to sex and socio-economic status, inverse associations between LVMi and PRA-S (ß= -0.168;  p = 0.017), Ang I (ß= -0.155; p = 0.028) and Ang II (ß= -0.172; p = 0.015) were found only in low socio-economic black women. CONCLUSION: Despite a suppressed RAS in the black compared to the white group, components of the RAS were not associated with LVMi in this young cohort. The low socio-economic black women of this study population may be vulnerable to future RAS-related increases in left ventricular mass.

Experience with fully covered self-expandable metal stents for anastomotic stricture following esophageal atresia repair.

There is a lack of experience with fully covered self-expandable metal stents (SEMSs) for the treatment of benign esophageal conditions in the pediatric population. This is the evaluation of our institutional experience of placing SEMSs for anastomotic stricture (AS) formation following esophageal atresia (EA) repair. Patients were jointly managed from the Department of Pediatric Surgery and Central Interdisciplinary Endoscopy at our institution. Thirteen children (8 male, 5 female) with a median age of 4 months (range: 1-32 months) who underwent treatment with SEMSs for a postoperative AS following EA repair between February 2006 and April 2016 were recruited into this retrospective study. SEMSs that are originally designed for other organs such as trachea, bronchus, biliary tract, or colon were inserted under general anesthesia via endoscopic guidance. Simultaneous fluoroscopy was not required in any case. In five infants, the stents were inserted primarily without previous therapy. Seven patients underwent stenting following dilatation with or without adjuncts (e.g. Mitomycin C, Triamcinolone). In one case with an AS and a simultaneous persistent tracheoesophageal fistula (TEF), multiple SEMSs were applied after failure to close the fistula with fibrin glue.The median duration of individual stent placement was 30 days (range: 5-91 days). In five children up to four different biliary, bronchial or colonic SEMSs were placed successively over time. There were no problems noted at stent insertion or removal. Eight children (62%) developed complications associated with stenting. At follow-up, in eight patients (62%) AS was resolved, including all of those five cases, who had their stents inserted without previous therapy. Five children (38%), who underwent dilatation prior to stenting did not improve their AS and required further intervention. Overall, the cohort exhibited a slight, but not significant weight gain between stent insertion and (final) stent removal.Insertion of SEMSs for AS following EA repair is safe and often successful with only one single application. It can be used as a primary procedure (without previous therapy) or after failed dilatations.There was one death in this study that was unrelated to stenting and occurred 12 months after stent removal. Because of the absence of manufactured, age-related devices, SEMSs that are originally designed for other organs can be applied. Establishment of a standardized management including stent placement for the treatment of AS following EA repair in the pediatric population is required.

Treatment outcome in 60 children with pathological fractures of the humerus caused by juvenile or aneurysmal bone cysts.

The treatment of pathological fractures of the humerus caused by juvenile or aneurysmal bone cysts (JBC/ABC) should be a single approach with a high success rate and low complication rate. This study evaluates how day by day treatment concepts fulfil these aims. Children below 15 years of age with a pathological fracture of the humerus caused by a JBC or ABC between 01.01.2001 and 31.12.2010, were investigated by chart review in four major paediatric trauma centres. Age, gender, fracture localisation, X-ray findings, treatment and outcome - assessed by the Capanna classification (I to IV), were analysed. 60 children [41male, 19 female; mean age: 9 years (4-14 years)] with 43 JBC and 12 ABC were included as well as five cysts, who could not be classified definitively. First treatment was non-operatively in 33 children. Of these 27 cysts did not improve; likewise the supportive installation of cortisone in six patients did not change the outcome. The first treatment consisted of elastic stable intramedullary in 13 children; up to three nail exchanges included. But only six of these reached (nearly) complete resolution (I/II). Overall the combined mechanical and biological treatment with curettage, elastic stable intramedullary nailing, (artificial) bone substitute and in some cases growth factors was performed as the 1st-line treatment in nine patients and further in 2nd or 3rd-line treatments in 13 humeral cysts. More than half of these reached a complete or nearly complete resolution of the cyst (12x I, 5x II, 1x III, 4x IV). Major complications in all operated patients were six nails not removable and two children with upper extremities length differences. Healing rates are low for non-operative treatment, elastic stable intramedullary nailing alone and by using cortisone for cysts resolution in pathological fractures of the humerus. Data support a combined mechanical and biological treatment with curettage, elastic stable intramedullary nailing, (artificial) bone substitute and the use of growth factors.

[LiLa classification for paediatric long bone fractures. Intraobserver and interobserver reliability]. / LiLa-Klassifikation für Frakturen der langen Röhrenknochen im Wachstumsalter. Intra- und Interobserverreliabilität.

BACKGROUND: There are two child-specific fracture classification systems for long bone fractures: the AO classification of pediatric long-bone fractures (PCCF) and the LiLa classification of pediatric fractures of long bones (LiLa classification). Both are still not widely established in comparison to the adult AO classification for long bone fractures. METHODS: During a period of 12 months all long bone fractures in children were documented and classified according to the LiLa classification by experts and non-experts. Intraobserver and interobserver reliability were calculated according to Cohen (kappa). RESULTS: A total of 408 fractures were classified. The intraobserver reliability for location in the skeletal and bone segment showed an almost perfect agreement (K = 0.91-0.95) and also the morphology (joint/shaft fracture) (K = 0.87-0.93). Due to different judgment of the fracture displacement in the second classification round, the intraobserver reliability of the whole classification revealed moderate agreement (K = 0.53-0.58). Interobserver reliability showed moderate agreement (K = 0.55) often due to the low quality of the X-rays. Further differences occurred due to difficulties in assigning the precise transition from metaphysis to diaphysis. CONCLUSIONS: The LiLa classification is suitable and in most cases user-friendly for classifying long bone fractures in children. Reliability is higher than in established fracture specific classifications and comparable to the AO classification of pediatric long bone fractures. Some mistakes were due to a low quality of the X-rays and some due to difficulties to classify the fractures themselves. Improvements include a more precise definition of the metaphysis and the kind of displacement. Overall the LiLa classification should still be considered as an alternative for classifying pediatric long bone fractures.

Musculoskeletal pain: a new algorithm for differential diagnosis of a cardinal symptom in pediatrics.

Musculoskeletal pain (MSP) is a common childhood complaint associated with multiple differential diagnoses, including cancer. Considering the expanding spectrum of diagnostics, evaluat-ing a young patient with MSP is a challenge today, particularly for non-specialists in a primary care setting. Since childhood cancer is rare and most cardinal symptoms mimic rather non-serious diseases, misdiagnosis is not uncommon, but of significant prognostic relevance. To build the appropriate bridge between primary and secon-dary care for a child presenting with MSP, thereby preventing treatment delay and longterm sequelae, initial evaluation should follow a comprehensive, multidisciplinary, systematic and stepwise approach, which unites the patient's individual anamnestic, psychosocial, and clinical charac-teristics. After a systematic review of the literature, we generated multidisciplinarily quality-assured recommendations for efficient, rational and cost-effective primary care assessment of pediatric MSP. The algorithm promotes the identification and structured interpretation of the patient's individual clinical clues. It should serve the primary care physician to recognize when further intervention, rather than reassurance and follow-up, is needed using the minimum amount of testing to make an appropriate, prompt diagnosis in the clinical situation "child presenting with MSP". A German version of this algorithm has been published in the Guideline-Portal of The Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF) in November 2013.

[Therapy of paediatric pancreatic trauma]. / Therapie traumatischer Pankreasverletzungen im Kindesalter.

BACKGROUND: The goal of this clinical study is to evaluate diagnostics and therapeutical strategies for paediatric pancreatic trauma. It is assumed that conservative treatment is at least as good as operative treatment. PATIENTS / MATERIAL AND METHODS: In a retrospective study 36  children with pancreatic trauma treated between the years 1987 and 2010 in the paediatric surgery department of the University Medical Centre Mannheim were included. Injury grades, diagnostics and treatment were evaluated. RESULTS: In a collective of 36  patients with an average age of seven years the following injuries were found: 26  grade 1, three grade  2, five grade  3 and two grade  4 injuries. Eight patients presented with polytrauma, 20 showed additional injuries. Initial levels of amylase and lipase and screening ultrasound were not always sensitive. 18  patients received conservative treatment. The remaining 18  were operated: either exploratory laparotomy and drainage or pancreas reconstruction with inner stenting or distal pancreatic resection were performed. Pancreatic pseudocysts were drained by transgastric stenting. CONCLUSION: 20 years ago blunt pancreatic trauma was usually treated operatively. Today grade 1 and grade 2 injuries should be treated conservatively. Higher graded pancreatic ductal injuries can be managed operatively with ductal stenting and organ conservation. Pancreatic resections are not always necessary. Endoscopic transgastric drainage of persisting pancreatic pseudocysts is also successful in children.

Bowel Lengthening Procedures in Children with Short Bowel Syndrome: A Systematic Review.

INTRODUCTION: The aims of the study are to systematically assess and critically appraise the evidence concerning two surgical techniques to lengthen the bowel in children with short bowel syndrome (SBS), namely, the longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP), and to identify patient characteristics associated with a favorable outcome. MATERIALS AND METHODS: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception till December 2019. No language restriction was used. RESULTS: In all, 2,390 articles were found, of which 40 were included, discussing 782 patients. The median age of the patients at the primary bowel lengthening procedure was 16 months (range: 1-84 months). Meta-analysis could not be performed due to the incomparability of the groups, due to heterogeneous definitions and outcome reporting. After STEP, 46% of patients weaned off parenteral nutrition (PN) versus 52% after LILT. Mortality was 7% for STEP and 26% for LILT. Patient characteristics predictive for success (weaning or survival) were discussed in nine studies showing differing results. Quality of reporting was considered poor to fair. CONCLUSION: LILT and STEP are both valuable treatment strategies used in the management of pediatric SBS. However, currently it is not possible to advise surgeons on accurate patient selection and to predict the result of either intervention. Homogenous, prospective, outcome reporting is necessary, for which an international network is needed.

Urinary metabolomics profiling by cardiovascular risk factors in young adults: the African Prospective study on Early Detection and Identification of Cardiovascular disease and Hypertension study.

AIM: Risk factors contributes to a dysregulated metabolism and may ultimately increase the predisposition for cardiovascular disease (CVD) development. To increase our understanding of mechanistic pathways associated with CVD risk, we profiled the urinary metabolome according to individual and clusters of CVD risk factors in comparison with a control group without any risk factors. METHODS AND RESULTS: Healthy black and white women and men ( N  = 1202), aged 20-30 years with a detailed CVD risk factor profile were included. CVD risk groups: obese, physical inactive, smoking, excessive alcohol intake, masked hypertensive, hyperglycaemic, dyslipidemic and low socioeconomic status. CVD risk clusters were based on the presence of 1, 2 and 3 or more risk factors. Liquid chromatography-tandem mass spectrometry was used to obtain urinary metabolomics data (amino acids and acylcarnities). Compared with the control group, higher levels of metabolites associated with aromatic and branched chain amino acid metabolism including phenylalanine, tyrosine and leucine/isoleucine were found in the obese, masked hypertensive, hyperglycaemic, low socioeconomic groups (all q  ≤ 0.032) and 3+ CVD risk cluster (all P  ≤ 0.034). Metabolites associated with the y-glutamyl cycle including glycine, histidine, serine, glutamine, methionine, cystine and pyroglutamic acid were found in the hyperglycaemic, low socioeconomic groups (all q  ≤ 0.050), 2 and 3+ CVD risk clusters (all P  ≤ 0.041). Metabolites associated with energetics including acetylcarnitine (lower levels), hexanoylcarnitine and decanoylcarnitine were found in the low socioeconomic group, 1 and 3+ CVD risk clusters ( q / P  ≤ 0.050) ( ß -oxidation). In addition to the above-mentioned amino acids, alanine and threonine were found in the hyperglycaemic, low socioeconomic groups, 2 and 3+ CVD risk clusters (all q / P  ≤ 0.047) (glycolysis). Creatine in the obese, hyperglycaemic groups (all q  ≤ 0.049) and 3+ CVD risk cluster (all P  ≤ 0.041) (creatine pathway). CONCLUSION: Exposure to CVD risk factors is associated with a dysregulated metabolism in the above-mentioned pathways that may precede the development of CVD.

Actual outcome in infants with congenital diaphragmatic hernia: the role of a standardized postnatal treatment protocol.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly with a high rate of mortality and morbidity. OBJECTIVE: Our aim was to determine a possible effect of standardized treatment on outcome in infants with CDH. METHODS: All prenatally diagnosed patients with unilateral CDH born alive between January 2006 and December 2009 at the Erasmus MC or the University Hospital Mannheim were eligible for inclusion. Patients who underwent a fetal tracheal occlusion were excluded. From November 1, 2007, all CDH patients were treated according to a standardized treatment protocol. Patients were divided into two chronological groups according to their date of birth: without standardized treatment (group 1, Jan 2006-Oct 2007) and with standardized treatment (group 2, Nov 2007-Dec 2009). Outcome measures were mortality by day 28, bronchopulmonary dysplasia (BPD), defined as oxygen dependency at day 28, and need for extracorporeal membrane oxygenation (ECMO) therapy. Uni- and multivariate analyses were performed. RESULTS: 167 patients were included. By day 28, 18% of the infants had died. Of the patients who were alive at day 28, 49% had BPD. An ECMO procedure was performed in 31% of the patients. Overall mortality for all included patients was 22%. In group 1, overall mortality was 33% and in group 2 overall mortality was 12% (p = 0.004). A standardized treatment protocol was independently associated with a reduced risk for mortality by day 28 (OR 0.28, 95% CI 0.11-0.68). Higher observed-to-expected lung-to-head ratios were independently associated with a lower risk for mortality by day 28 (OR 0.97, 95% CI 0.95-0.99), BPD (OR 0.97, 95% CI 0.94-0.98) and need for ECMO (OR 0.98, 95% CI 0.96-0.99). An intrathoracic position of the liver was independently associated with an increased risk for BPD (OR 3.12, 95% CI 1.41-6.90) and need for ECMO therapy (OR 3.25, 95% CI 1.54-6.88). CONCLUSION: Survival rates in patients with CDH increased significantly after the implementation of a standardized treatment protocol.

[Do paediatric and adult surgeons follow different approaches to physeal fractures?]. / Haben Kinderchirurgen und Erwachsenenchirurgen unterschiedliche Therapieansätze bei der Behandlung von Wachstumsfugenlösungen?

INTRODUCTION: The treatment of paediatric fractures is the concern of several different surgical specialties. There has been no scientific investigation on the different concepts of paediatric (PS) and adult surgeons (AS). METHODS: 62 paediatric traumatologists were asked concerning their experience with physeal fractures of the leg, including ten cases. RESULTS: Growth disturbances was estimated to be more rare by PS. On evaluation of the examples there were no significant differences in the judgement of degree and direction of the displacement. For displaced fractures, PS rather preferred closed reduction and immobilisation, whereas AS favoured osteosynthesis. DISCUSSION: There were no basic differences between PS and AS in the treatment of lower limb fractures. AS tend to act more invasively. At the same time they are more concerned about growth disturbances.

The relationship of blood pressure with uric acid and bilirubin in young lean and overweight/obese men and women: the African-PREDICT study.

Mounting evidence supports the central role of oxidative stress and inflammation in obesity and the development of hypertension. However, most studies focusing on the non-enzymatic antioxidants, such as uric acid and bilirubin, and their relationship with obesity and hypertension were done in older populations with overt cardiovascular disease. The aim of this study was therefore to compare measures of cardiovascular function (blood pressure and arterial stiffness) and non-enzymatic antioxidants (uric acid and bilirubin) between young healthy lean and overweight/obese men and women and to investigate the link between these variables. We grouped 967 men and women (aged 20-30 years) according to body mass index (BMI) categories (lean BMI < 25 kg/m2; overweight/obese BMI ≥ 25 kg/m2). Cardiovascular measurements included 24 h blood pressure and carotid-femoral pulse wave velocity. Serum samples were used to analyse uric acid and bilirubin. Women and men with a BMI ≥ 25 kg/m2 displayed higher 24 h blood pressure (P < 0.001) and uric acid (P ≤ 0.014) than their lean counterparts; lean women showed higher bilirubin (P < 0.001). In multi-variable adjusted regression analyses we found that 24 h systolic blood pressure was independently associated with uric acid (R2 = 0.10; ß = 0.19; P = 0.017) only in overweight/obese women. In lean women a negative association of 24 h systolic blood pressure with bilirubin (R2 = 0.03; ß = -0.14; P = 0.018) was found. No associations were found in men. In conclusion, we found adverse associations between blood pressure and uric acid in young healthy women with increased adiposity, but not in lean women or men.

Chance fracture--a rare injury in pediatric patients?

We report on a 9-year-old girl who was involved in a car accident. She suffered severe polytrauma with torn abdominal muscles, rupture of the mesenteric arteries, bowel and bladder, hematoma at the right colonic flexure and disruption of the intervertebral ligaments L2/L3, including the intervertebral disc, typical of Chance fracture. The abdominal bleeding was stopped, the bowel resected and the fracture fixed by internal fixation. The patient developed a postoperative enterocutaneous fistula in the right flank and paraplegia. She underwent three laparotomies with ileostomy and closure of the fistula. Two years later, she has normal bowel movement, the wounds are closed, the internal fixation has been removed, she is able to walk with crutches and suffers from a mild bladder dysfunction. Chance fracture is a typical fracture in adults involved in motor vehicle accidents. In the last 10 years, there have only been four case reports describing this fracture in children under the age of 10. All of these individuals were involved in a car accident and had been fixed with a lap belt. With the increasing use of lap belts, this fracture has to be considered even in young children. Mild clinical symptoms can be associated with severe intra-abdominal injuries.

[Bladder augmentation and urinary diversion in children and adolescents]. / Blasenaugmentation und -ersatz bei Kindern und Jugendlichen.

BACKGROUND: In children and adolescents, the indication for continent urinary diversion or bladder augmentation is rare. Today, for most patients with a neurogenic bladder, conservative treatment (clean intermittent catheterization [CIC] and pharmacotherapy) is the method of choice, while for patients with bladder exstrophy-epispadias complex (BEEC), primary reconstruction is recommended. Only after failure of conservative treatment or primary reconstruction should bladder augmentation or urinary diversion be considered. Other rare indications include patients with malignant tumor involving the lower urinary tract (e. g., rhabdomyosarcoma). DISCUSSION: In patients with a hyperreflexive, small capacity, and/or low compliance bladder with a normal upper urinary tract, bladder augmentation (bowel segments/ureter) is an option. For those unable to perform CIC via the urethra, a continent cutaneous stoma should be offered. In patients with irreparable sphincter defects and normal renal function, a continent cutaneous diversion is an option and in those with a competent anal sphincter the rectosigmoid pouch can be offered. CONCLUSION: In this review, surgical options with their advantages and disadvantages are discussed.

Topographic peculiarities of the submucous plexus in the human anorectum--consequences for histopathologic evaluation of rectal biopsies.

Chronic colorectal motility disorders are commonly encountered in the pediatric population. While most cases can be managed successfully by conservative therapy, a subgroup of patients suffers from severe constipation and requires further diagnostic procedures to identify the underlying pathologies, such as aganglionosis, hypoganglionosis or intestinal neuronal dysplasia (IND). The present study provides reference data about the quantitative distribution of nerve cells and ganglia within the submucosal plexus of the human anorectum from healthy subjects. Anorectal specimens (n = 15) obtained postmortem were divided into 6 segments beginning from the dentate line (S1 = 0-2 cm, S 2 = 2-4 cm, S3 = 4-6 cm, S4 = 6-8 cm, S5 = 8-10 cm, S6 = 10-12 cm). From each segment sections (6 microm thickness) were immunostained with a pan-neuronal marker (Protein Gene Product 9.5) to visualize the enteric nervous system. A morphometric analysis was carried out for each segment recording the number of ganglia and nerve cells of the submucous plexus. Neither ganglia nor nerve cells showed a uniform distribution pattern, but decreased continuously towards the anus. However, even the lowest segments (S1, S2) contained nerve cells and were not aganglionic. In the remaining segments ganglia with 7 or more nerve cells could be detected. The findings demonstrate segment-specific quantitative differences of the anorectal submucous plexus which should be taken into consideration for the histopathologic evaluation of rectal biopsies. Moreover, the data support the concept of a physiologic hypoganglionosis of the anal canal.

Early wound closure and early reconstruction. Experience with a dermal substitute in a child with 60 per cent surface area burn.

A dermal substitute was used for wound management and after early scar release on a 4-year-old child with mostly full thickness burns covering 60 per cent of the body surface. The biosynthetic material (INTEGRA Artificial Skin) consists of an upper silicone film and a lower layer of porous cross-linked collagen and chondroitin-6-sulfate as a template for dermal regeneration. Eight sheets each 4 x 10 in. were used to cover the patient's whole trunk after staged tangential necrectomy. In the third and fourth weeks following application the silicone layer was easily removed and the newly formed dermis covered with widely meshed, thin split-thickness autograft. Seven weeks after admission an early neck contracture was released and the skin defect also covered with INTEGRA Artificial Skin. Following the same principle, transplantation of the thin unmeshed autograft was performed successfully 3 weeks later. The good results regarding handling, final take, apparent initial scar reduction, and early recovery may favourably effect initial treatment and reconstruction planning after extensive full-thickness burn injuries.