Time spent with impaired autoregulation is linked with outcome in severe infant/paediatric traumatic brain injury.

BACKGROUND: It could be shown in traumatic brain injury (TBI) in adults that the functional status of cerebrovascular autoregulation (AR), determined by the pressure reactivity index (PRx), correlates to and even predicts outcome. We investigated PRx, cerebral perfusion pressure (CPP) and intracranial pressure (ICP) and their correlation to outcome in severe infant and paediatric TBI. METHODS: Seventeen patients (range, 1 day to 14 years) with severe TBI (median GCS at presentation, 4) underwent long-term computerised ICP and mean arterial pressure (MAP) monitoring using dedicated software to determine CPP and PRx and optimal CPP (CPP level where PRx shows best autoregulation) continuously. Outcome was determined at discharge and at follow-up using the Glasgow Outcome Scale. RESULTS: Favourable outcome was reached in eight patients, unfavourable outcome in seven patients. Two patients died. Nine patients underwent decompressive craniectomy to control ICP during Intensive Care Unit treatment. When dichotomised to outcome, no significant difference was found for overall ICP, CPP and PRx. The time with severely impaired AR (PRx >0.2) was significantly longer for patients with unfavourable outcome (64 h vs 6 h, p = 0.001). Continuously impaired AR of ≥24 h and age <1 year was associated to unfavourable outcome. Children with favourable outcome spent the entire monitoring time at or above the optimal CPP. CONCLUSIONS: Integrity of AR has a similar role for outcome after TBI in the paediatric population as in adults. The amount of time spent with deranged AR seems to be associated with outcome; a factor especially critical for infant patients. The results of this preliminary study need to be validated in the future.

State of Cerebrovascular Autoregulation Correlates with Outcome in Severe Infant/Pediatric Traumatic Brain Injury.

OBJECTIVE: It could be shown in adults with severe traumatic brain injury (TBI) that the functional status of cerebrovascular autoregulation (AR), determined by the pressure reactivity index (PRx), correlates with and even predicts outcome. We investigated PRx and its correlation with outcome in infant and pediatric TBI. Methods Ten patients (median age 2.8 years, range 1 day to 14 years) with severe TBI (Glasgow Coma Scale score <9 at presentation) underwent long-term computerized intracranial pressure (ICP) and mean arterial pressure (MAP) monitoring using dedicated software for continuous determination of cerebral perfusion pressure (CPP) and PRx. Outcome was determined at discharge and at follow-up at 6 months using the Glasgow Outcome Scale (GOS) score. RESULTS: Median monitoring time was 182 h (range 22-355 h). Seven patients underwent decompressive craniectomy to control ICP during treatment in the intensive care unit. Favorable outcome (GOS 4 and 5) was reached in 4 patients, an unfavorable outcome (GOS 1-3) in 6 patients. When dichotomized to outcome, no correlation was found with ICP and CPP, but median PRx correlated well with outcome (r = -0.79, p = 0.006) and tended to be lower for GOS 4 and 5 (-0.04) than for GOS 1-3 (0.32; p = 0.067). CONCLUSION: The integrity of AR seems to play the same fundamental role after TBI in the pediatric population as in adults and should be determined routinely. It carries an important prognostic value. PRx seems to be an ideal candidate parameter to guide treatment in the sense of optimizing CPP, aiming at improvement of cerebrovascular autoregulation (CPPopt concept).

Anti-tumor activity of sorafenib in a model of a pediatric hepatocellular carcinoma.

BACKGROUND: Treatment outcome of children with pediatric hepatocellular carcinoma (pHCC) is poor. Therefore, we evaluated the tyrosine kinase inhibitor sorafenib in a model of pHCC. METHODS: Cell viability after treatment with sorafenib was evaluated in HC-AFW1 cells (pHCC) using MTT assay and compared to an adult HCC (aHCC) and two hepatoblastoma (HB) cell lines. ERK, pERK, E-cadherin, and vimentin expression were investigated using Western Blot. Sorafenib (60 mg/kg) was administered orally to NOD.Cg-Prkdcscid-IL2rgtmWjl/Sz mice bearing subcutaneous HC-AFW1-derived tumors. Tumor progression, viability, and vascularization were monitored by tumor volume, AFP levels, and CD31 immunostaining, respectively. Sensitization to sorafenib was evaluated using the ß-catenin inhibitor ICG001. RESULTS: Sorafenib reduced cell viability in HC-AFW1 (IC50: 8 µM), comparable to HB cells, however less pronounced in aHCC cells (IC50: 23 µM). Sorafenib inhibited ERK signaling in both, HC-AFW1 cells and -xenografts. In vivo, sorafenib treatment only led to a moderate tumor growth inhibition, although significant reduction of vascularization and tumor growth kinetics was observed. Long-term treatment with sorafenib decreased E-cadherin, but showed no induction of vimentin expression. Combining sorafenib with a ß-catenin inhibitor led to an additional reduction of cell viability. CONCLUSION: Sorafenib together with inhibitors of the ß-catenin pathway might be an effective tool in the treatment of pediatric HCC.

Weight-adapted surgical approach for laparoendoscopic single-site surgery in pediatric patients using low-cost reusable instrumentation: a prospective analysis.

OBJECTIVES: Laparoendoscopic single-site surgery (LESS) in pediatric patients has emerged as a viable alternative to standard laparoscopy. The aim of our investigation was to assess different surgical approaches for LESS, stratifying by weight. SUBJECTS AND METHODS: From March 2010 to April 2012 LESS was performed in 42 children. Children weighing below 10 kg underwent LESS through an umbilical incision using two 3-mm trocars and one 5-mm trocar. Patients above 10 kg were operated on using a metal multiuse single-site single port (X-Cone; Karl Storz Endoskope, Tuttlingen, Germany). Conventional straight laparoscopic instruments were used in all cases. RESULTS: Mean age at operation was 100 months (range, 0.25-207 months), and mean weight was 27 kg (range, 3.1-82 kg). Median operating time was 74 minutes (range, 36-300 minutes). Eighteen children underwent LESS using two 3-mm trocars and one 5-mm trocar; 1 case required two 5-mm trocars and one 10-mm trocar. Twenty-three patients were operated on with the multiuse device. All operations were carried out safely in a standard laparoscopic transperitoneal technique with full achievement of the surgical target. In none of the patients was an intraoperative complication noticed. Postoperatively two complications were noted, which resolved spontaneously. CONCLUSIONS: LESS for pediatric patients can be done safely and efficiently with even less trauma than in conventional laparoscopy irrespective of age and weight. However, different surgical approaches have to be considered as disposable single-site ports are not available for infants and small children. To decrease operative expenses, conventional multiuse trocars and a multiuse single-site port were used with conventional laparoscopic instruments.