Genito-urinary Reconstruction in Female Children With Congenital Adrenal Hyperplasia: Favorable Surgical Outcomes can be Achieved by Contemporary Techniques and a Dedicated Multidisciplinary Management.

INTRODUCTION: Congenital adrenal hyperplasia (CAH) is the most common cause of genital atypia in females. A dedicated multidisciplinary team (MDT) should be included for an optimal management. Here, we aimed to review our surgical experience and to assess long-term urinary, gynecological and endocrine outcomes after primary genitoplasty in this specific cohort. METHODS: Patients born with CAH and who underwent feminizing genitoplasty in our institution were retrospectively identified (2001-2021). We analyzed patients' characteristics, intraoperative details, and postoperative urinary, gynecological, and endocrine outcomes. RESULTS: Forty patients were included and followed-up for a median (IQR) time of 7 (1-19) years. Thirty-eight (95%) had 21-hydroxylase deficiency. After multidisciplinary decision and written consent from patient and/or family, a single-stage reconstructive surgery was performed at a median age of 10 (3-165) months. Median length of hospital stay was 5 (1-7) days. Procedures were: PUM (N = 35 (87.5%)), TUM (N = 3 (7.5%)), urogenital mobilization was unnecessary in 2 (5%). Reduction clitoroplasty was done in 33 (82.5%) patients. Only 3 (7.5%) experienced significant Clavien-Dindo complications requiring additional surgery during the follow-up period. Recurrent urinary tract infections (UTI) occurred in 6 (15%), one required ureteric reimplantation for symptomatic high-grade vesicoureteric reflux. All patients over 3 years were toilet-trained without incontinence. Severe vaginal stenosis occurred in 1 (2.5%) patient. In patients who achieved puberty, 6/9 had vaginal calibration at a median age of 17.3 (16-21) years without detected stenosis. One (2.5%) had major hypertrophy of the right labia minora requiring labiaplasty. Nine (22.5%) reached puberty. Two (5%) patients developed acne/hirsutism. Short stature was noted in 11 (27.5%) and obesity in 18 (45%). CONCLUSION: Based on our contemporary series, genitourinary reconstructive surgery for female patients born with CAH is technically feasible and safe with a low complication rate. A regular follow-up with a MDT to assess long-term complications is necessary, and it is vital to inform patients and families about the different management options with all the risks and benefits of surgery. TYPE OF THE STUDY: original research, clinical research. LEVEL OF EVIDENCE: Level 3 retrospective study.

Comprehensive bile acid pool analysis during ex-vivo liver perfusion in a porcine model of ischemia-reperfusion injury.

Bile acids (BA) are key for liver regeneration and injury. This study aims at analyzing the changes in the BA pool induced by ischemia-reperfusion (IRI) and investigates the impact of hypothermic oxygenated perfusion (HOPE) on the BA pool compared to static cold storage (SCS). In a porcine model of IRI, liver grafts underwent 30 min of asystolic warm ischemia followed by 6 h of SCS (n = 6) ± 2 h of HOPE (n = 6) and 2 h of ex-situ warm reperfusion. The BA pool in bile samples was analyzed with liquid chromatography coupled with tandem mass spectrometry. We identified 16 BA and observed significant changes in response to ischemia-reperfusion, which were associated with both protective and injury mechanisms. Second, HOPE-treated liver grafts exhibited a more protective BA phenotype, characterized by a more hydrophilic BA pool compared to SCS. Key BA, such as GlycoCholic Acid, were identified and were associated with a decreased transaminase release and improved lactate clearance during reperfusion. Partial Least Square-Discriminant Analysis revealed a distinct injury profile for the HOPE group. In conclusion, the BA pool changes with liver graft IRI, and preservation with HOPE results in a protective BA phenotype compared to SCS.

Kidney and urological involvement in Down syndrome: frequent, underestimated, but associated with impaired quality of life and risk of kidney failure.

Patients with Down syndrome (DS) are at risk of multiorgan dysfunction; kidney and urological impairment are common. This is due to a likely increased risk of congenital kidney and urological malformations (odds ratio of 4.5 compared to the general population in one study), more frequent associated comorbidities at risk of kidney dysfunction (such as prematurity in 9-24% of children, intrauterine growth retardation or low birth weight in 20%, and congenital heart disease in 44%), and more frequent lower urinary tract dysfunction (reported in 27-77% of children with DS). If present, malformations and comorbidities at risk of kidney dysfunction warrant regular kidney monitoring in addition to their treatment. Serum creatinine in children with DS has been shown to be higher than in the general population and asymptomatic hyperuricemia is reported in 12-33% of children or young adults with DS. Moreover cryptorchidism and testicular cancer are also more common and should be detected by clinical examination. Thus, persons with DS at risk of presenting kidney and urological impairment should be identified by prenatal ultrasonography, comorbidities at risk of kidney sequelae considered, and during regular medical follow-up, clinically examined and questioned to diagnose testicular anomalies and lower urinary tract dysfunction. This is of importance as such kidney and urological impairments are associated with impaired quality of life and mental health, and risk of kidney failure.

Hydration and Nephrolithiasis in Pediatric Populations: Specificities and Current Recommendations.

Renal lithiasis is less frequent in children than in adults; in pediatrics, lithiasis may be caused by genetic abnormalities, infections, and complex uropathies, but the association of urological and metabolic abnormalities is not uncommon. The aim of this study is to provide a synthesis of nephrolithiasis in children and to emphasize the role of hydration in its treatment. As an etiology is reported in 50% of cases, with a genetic origin in 10 to 20%, it is proposed to systematically perform a complete metabolic assessment after the first stone in a child. Recent data in the field reported increased incidence of pediatric urolithiasis notably for calcium oxalate stones. These changes in the epidemiology of stone components may be attributable to metabolic and environmental factors, where hydration seems to play a crucial role. In case of pediatric urolithiasis, whatever its cause, it is of utmost importance to increase water intake around 2 to 3 L/m2 per day on average. The objective is to obtain a urine density less than 1010 on a dipstick or below 300 mOsm/L, especially with the first morning urine. Some genetic diseases may even require a more active 24 h over-hydration, e.g., primary hyperoxaluria and cystinuria; in such cases naso-gastric tubes or G-tubes may be proposed. Tap water is adapted for children with urolithiasis, with limited ecological impact and low economical cost. For children with low calcium intake, the use of calcium-rich mineral waters may be discussed in some peculiar cases, even in case of urolithiasis. In contrast, sugar-sweetened beverages are not recommended. In conclusion, even if parents and patients sometimes have the feeling that physicians do not propose "fancy" therapeutic drugs, hydration and nutrition remain cornerstones of the management of pediatric urolithiasis.

Pediatric urolithiasis: what can pediatricians expect from radiologists?

The incidence of urolithiasis in children has increased over the two last decades. Urolithiasis formation results from urine oversaturation following insufficient water intake, urinary obstruction (notably in cases of congenital uropathies), excess production of an insoluble compound, or imbalance between crystallization promoters and inhibitors. Whereas most urolithiases in adults occur secondary to environmental factors, in children, secondary causes are far more frequent, and 15% are related to genetic causes, most often monogenic. This is especially true in recurrent forms, with early and rapid progression and bilateral stones, and in cases of familial history or consanguinity. Because of differing clinical management, one should rule out cystinuria, primary hyperoxaluria and renal tubular acidosis, among other causes of urolithiasis. As such, a complete biochemical evaluation must be performed in all cases of pediatric urolithiasis, even in cases of an underlying uropathy. Ultrasound examination is the first-line modality for imaging pediatric urolithiasis, allowing both diagnosis (urolithiasis and its complications) and follow-up. US examination should also explore clues to an underlying cause of urolithiasis. This review is focused on the role of imaging in the management and etiological assessment of pediatric urolithiasis. Radiologists play an important role in pediatric urolithiasis, facilitating diagnosis, follow-up and surgical management. A trio of clinicians (pediatric nephrologist, pediatric surgeon, pediatric radiologist) is thus necessary in the care of these pediatric patients.

New method for early evaluation of clitoris innervation using clitoro-perineal reflex after feminizing genitoplasty in early childhood: a pilot-study.

A major complication of feminizing genitoplasty in children is the loss of clitoral sensation with serious impact at adult life. We suggest a new method to evaluate the surgical results during childhood based on the bulbocavernosus or clitoro-perineal reflex (CPR). The afferent pathway of CPR implies the intact sensory receptors on the clitoral glans. Girls with congenital adrenal hyperplasia who were followed-up medically without surgery or who underwent feminizing genitoplasty with or without clitoroplasty were included (2002-2018). All clitoroplasties were standardized reduction clitoroplasty with preservation of neurovascular bundles associated with vaginoplasty and vestibuloplasty. Standardized examinations were prospectively performed including the CPR starting at one year postoperatively. The reflex was triggered by gentle touch of the glans by a cotton swab. Contraction of the perineal muscles was considered positive. Thirty-two children were operated at a median age of 8.6 months (5.8-12.1). Median follow-up (FU) was 3.9 years (1.3-6.4). Twenty-four patients had clitoroplasties: 17 were tested for CPR at one-year FU, and all had a positive test. Eight girls had genitoplasty without clitoral surgery, two of them were tested and were positive. Ten patients were managed without surgery, two of them were tested for the CPR and were positive. The reflex was always triggered easily and repeated at least twice during the FU. The clitoro-perineal reflex is a simple, non-invasive and reproducible test in early childhood and may serve as an early evaluation tool of clitoral innervation after feminizing genitoplasty. These results need to be confirmed at long term and completed at adult life.

Management of lower urinary tract fibroepithelial polyps in children.

INTRODUCTION: Fibroepithelial polyps (FEP) of the lower urinary tract are relatively common in adults but rare in children, with fewer than 250 cases reported in the literature to date. OBJECTIVE: The aim of this study was to address the experience of FEP management in children. STUDY DESIGN: A retrospective multicenter review was undertaken in children with defined FEP of the lower urinary tract managed between 2008 and 2018. The data at 18 pediatric surgery centers were collected. Their demographic, radiological, surgical, and pathological information were reviewed. RESULTS: A total of 33 children (26 boys; 7 girls) were treated for FEP of the lower urinary tract at 13 centers. The most common presentation was urinary outflow as hematuria (41%), acute urinary retention (25%), dysuria (19%), or urinary infections (28%). A prenatal diagnosis was made for three patients with hydronephrosis. Almost all of the children (94%) underwent ultrasound imaging of the urinary tract as the first diagnostic examination, 23 (70%) of them also either had an MRI (15%), cystourethrography (25%), computerized tomography (6%), or cystoscopy (45%). Two of these children (6%) had a biopsy prior to the surgery. The median preoperative delay was 7.52 (range: 1-48) months. Most of the patients were treated endoscopically, although four (12.1%) had open surgery and two (6.1%) had an additional incision for specimen extraction. The median hospital stay was 1.5 (range: 1-10) days. There were no recurrences and no complications after a median follow-up of 13 (range: 1-34) months. DISCUSSION: The main limitation of our study is the retrospective design, although it is the largest one for this pathology. CONCLUSION: This series supports sonography as the most suitable diagnosis tool before endoscopy to confirm the diagnosis and to perform the resection for most FEP in children. This report confirms the recognized benign nature in the absence of recurrences. LEVEL OF EVIDENCE: Level V.

Inherited CARD9 deficiency in 2 unrelated patients with invasive Exophiala infection.

BACKGROUND: Exophiala species are mostly responsible for skin infections. Invasive Exophiala dermatitidis disease is a rare and frequently fatal infection, with 42 cases reported. About half of these cases had no known risk factors. Similarly, invasive Exophiala spinifera disease is extremely rare, with only 3 cases reported, all in patients with no known immunodeficiency. Autosomal recessive CARD9 deficiency has recently been reported in otherwise healthy patients with severe fungal diseases caused by Candida species, dermatophytes, or Phialophora verrucosa. METHODS: We investigated an 8-year-old girl from a nonconsanguineous Angolan kindred, who was born in France and developed disseminated E. dermatitidis disease and a 26 year-old woman from an Iranian consaguineous kindred, who was living in Iran and developed disseminated E. spinifera disease. Both patients were otherwise healthy. RESULTS: We sequenced CARD9 and found both patients to be homozygous for loss-of-function mutations (R18W and E323del). The first patient had segmental uniparental disomy of chromosome 9, carrying 2 copies of the maternal CARD9 mutated allele. CONCLUSIONS: These are the first 2 patients with inherited CARD9 deficiency and invasive Exophiala disease to be described. CARD9 deficiency should thus be considered in patients with unexplained invasive Exophiala species disease, even in the absence of other infections.