PURPOSE The HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy. PATIENTS AND METHODS From 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia. RESULTS Five years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012). CONCLUSION Systemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma.

The prevalence of DSA was 33% for group 1 and 68% for group 2. Antibodies were predominantly HLA class II. Values of mean fluorescence intensity were comparable in both groups. Only one of the DSA+ ve patients from group 1 exhibited preformed antibodies. In conclusion, pediatric patients with chronic rejection revealed a higher rate of de novo DSA, especially of HLA-class II DSA. Further studies are necessary to confirm these data with a larger pediatric cohort.

IntroductionElectrical velocimetry (EV) is a type of impedance cardiography, and is a non-invasive and continuously applicable method of cardiac output monitoring. Transthoracic echocardiography (TTE) is non-invasive but discontinuous.MethodsWe compared EV with TTE in pediatric intensive care patients in a prospective single-center observational study. Simultaneous, coupled, left ventricular stroke volume measurements were performed by EV using an Aesculon® monitor and TTE (either via trans-aortic valve flow velocity time integral [EVVTI], or via M-mode [EVMM]). H0: bias was less than 10% and the mean percentage error (MPE) was less than 30% in Bland–Altman analysis between EV and TTE. If appropriate, data were logarithmically transformed prior to Bland–Altman analysis.ResultsA total of 72 patients (age: 2 days to 17 years; weight: 0.8 to 86 kg) were analyzed. Patients were divided into subgroups: organ transplantation (OTX, n =28), sepsis or organ failure (SEPSIS, n =16), neurological patients (NEURO, n =9), and preterm infants (PREM, n =26); Bias/MPE for EVVTI was 7.81%/26.16%. In the EVVTI subgroup analysis for OTX, NEURO, and SEPSIS, bias and MPE were within the limits of H0, whereas the PREM subgroup had a bias/MPE of 39.00%/46.27%. Bias/MPE for EVMM was 8.07%/37.26% where the OTX and NEURO subgroups were within the range of H0, but the PREM and SEPSIS subgroups were outside the range. Mechanical ventilation, non-invasive continuous positive airway pressure ventilation, body weight, and secondary abdominal closure were factors that significantly affected comparison of the methods.ConclusionsThis study shows that EV is comparable with aortic flow-based TTE for pediatric patients.