Urological Outcome of the Xiao Procedure in Children with Myelomeningocele and Lipomyelomeningocele Undergoing Spinal Cord Detethering.

PURPOSE: Although previous studies have revealed high success rates (70% to 85%) after an intradural somatic-to-autonomic nerve transfer procedure in children with spinal dysraphism, no study has had a control group or blinded observers. We report a rigorously designed study to investigate the effectiveness of the Xiao procedure. MATERIALS AND METHODS: Children with neurogenic bladder dysfunction related to myelomeningocele or lipomyelomeningocele who required spinal cord detethering were randomized to 2 groups at surgery, with half undergoing only spinal cord detethering and half undergoing the Xiao procedure in addition to detethering. Double-blind evaluations were performed at regular intervals during the 3-year followup. RESULTS: A total of 10 patients underwent spinal cord detethering only and 10 underwent detethering plus the Xiao procedure. The Xiao procedure did not result in voluntary voiding or continence in any patient, but patients undergoing spinal cord detethering plus the Xiao procedure were more likely to have greater improvements in total bladder capacity, bladder overactivity and overall quality of life than those who underwent detethering only. By the end of the study no participant or evaluator was able to accurately predict to which group the patients had been assigned. CONCLUSIONS: The results of this randomized controlled trial are in agreement with recently published similarly poor results of the Xiao procedure in patients with spinal cord injury. Improvements in bladder parameters observed in this study may be related to sacral nerve root section, a necessary portion of the Xiao procedure, instead of reinnervation. Confirmatory animal studies are recommended before further clinical trials of the Xiao procedure are performed in humans.

Lack of efficacy of an intradural somatic-to-autonomic nerve anastomosis (Xiao procedure) for bladder control in children with myelomeningocele and lipomyelomeningocele: results of a prospective, randomized, double-blind study.

OBJECTIVE Xiao et al. and other investigators have studied an intradural somatic-to-autonomic (e.g., L-5 to S3-4) nerve transfer as a method to create a reflex arc to allow bladder emptying in response to cutaneous stimulation (the Xiao procedure). In previous clinical studies of patients with spinal dysraphism who underwent the Xiao procedure, high success rates (70%-85%) were reported for the establishment of a "skin-CNS-bladder" reflex arc that allows spontaneous, controlled voiding in children with neurogenic bladder dysfunction. However, many of these studies did not use blinded observers, did not have control groups, and/or featured only limited follow-up durations. METHODS A randomized, prospective, double-blind trial was initiated in March 2009, enrolling children with myelomeningocele (MM), lipomyelomeningocele (LMM), and neurogenic bladder dysfunction who were scheduled for spinal cord detethering (DT) for the usual indications. At the time of DT, patients were randomized between 2 arms of the study: half of the patients underwent a standard spinal cord DT procedure alone (DT group) and half underwent DT as well as the Xiao procedure (DT+X group). Patients, families, and study investigators, all of whom were blinded to the surgical details, analyzed the patients' strength, sensory function, mobility, voiding, and urodynamic bladder function before surgery and at regular intervals during the 3-year follow-up. RESULTS Twenty patients were enrolled in the study: 10 underwent only DT and the other 10 underwent DT+X. The addition of the Xiao procedure to spinal cord DT resulted in longer operative times (p = 0.024) and a greater chance of wound infection (p = 0.03). Patients in both treatment arms could intermittently void or dribble small amounts of urine (< 20% total bladder capacity) in response to scratching in dermatomes T-9 through S-2 using a standardized protocol, but the voiding was not reproducible and the volume voided was not clinically useful in any patient. Voiding in response to scratching was not more frequent in patients who underwent DT+X compared with those who underwent only DT. Bladder contractions in response to scratching occurred in both treatment arms at various intervals after surgery, but they were not more reproducible or more frequent in the patients who underwent the Xiao procedure than in the patients who did not. No patient in either treatment arm was continent of urine before, during, or after the study. CONCLUSIONS Patients with MM and LMM who underwent the Xiao procedure during spinal cord DT were no more likely to be able to void, to control their urination, to achieve continence, or to have a demonstrable urodynamic bladder contraction in response to cutaneous stimulation than patients who underwent only spinal cord DT. This study, in the context of disappointing results reported in other recent studies of the Xiao procedure, raises doubts about the clinical applicability of this procedure in humans until further basic science research is performed.

Neonatal T-cell maturation and homing receptor responses to Toll-like receptor ligands differ from those of adult naive T cells: relationship to prematurity.

INTRODUCTION: Inflammation and infection are associated with premature birth and with activation of the fetal immune system. We hypothesized that exposure to microbial Toll-like receptor (TLR) ligands plays an important role in neonatal T-cell maturation and that early exposure to microbial products may result in early T-cell maturation and a tendency for these matured effector cells to change their homing receptor patterns. RESULTS: Expression of the CD45RO marker was induced in term neonatal T cells after in vitro exposure to TLR ligands for 7 days. Interestingly, naive T cells from adult blood were unaffected by TLR ligand exposure. In addition, neonatal T cells had more cells with decreased expression of the α4ß7 integrins and increased expression of CCR4 after in vitro exposure of TLR ligands-similar to the expression of these molecules in adult naive T cells. DISCUSSION: These findings are relevant for the understanding of neonatal T-cell maturation and may contribute to our understanding of multiorgan inflammatory complications of prematurity. METHODS: Cord blood was obtained from term and preterm infants. Using flow cytometry, we identified a mature (CD45RO(+)) phenotype in preterm infant cord blood (CB) T cells that had decreased expression of the α4ß7 integrins and increased expression of the C-C chemokine receptor 4 (CCR4) as compared with term infant CB.