KMT2A-rearranged infant ALL (KMT2A-r ALL) has a poor prognosis. Adding blinatumomab, a bispecific T-cell engager targeting CD19, to standard chemotherapy for infants with KMT2A-r ALL improved short-term outcomes. Here, we present long-term results, toxicity, and pharmacokinetics of blinatumomab from this study. Thirty infants received Interfant-06 protocol chemotherapy with one additional postinduction blinatumomab course. Disease-free survival (DFS) and overall survival (OS) were compared with a historical Interfant-06-selected cohort without blinatumomab. Infection and administration of intravenous immunoglobulin (IVIg) and granulocyte-colony stimulating factor (G-CSF) were documented. Blinatumomab's steady-state concentration (Css) and clearance (CL) were analyzed. The median follow-up was 4.2 years (range, 3.2-6.0). Blinatumomab significantly improved outcomes compared with controls, with a 4-year DFS of 83.3% versus 44.0% and a 4-year OS of 93.3% versus 60.2%. No infection-related fatality occurred postinduction, in contrast to 4% in Interfant-06. IVIg was administered in 19 (63%) patients, and G-CSF in five (17%). The mean Css of blinatumomab was 706 ± 194 pg/mL/d, and the median CL was 0.89 L/h/m2 (range, 0.57-2.66). Adding blinatumomab to standard treatment for infants with KMT2A-r ALL resulted in sustained improvement in outcome. Pharmacokinetics were comparable across pediatric age groups. The benefit of blinatumomab in frontline therapy remains promising and awaits further confirmation in ongoing trials.
BACKGROUND:Children's Hospital 2 in Ho Chi Minh City is the only public pediatric center performing pediatric liver transplantation (PLT) in Southern Vietnam. Before the COVID-19 pandemic, our PLT program was implemented and operated in collaboration with Belgian surgical teams who supported both graft procurement and implantation. The program enabled capacity-building and protocol development. METHODS:Travel restrictions necessitated a transition to a hybrid local model. Building on the Pre-COVID groundwork, the team successfully performed 12 living-donor PLTs between 10/2021 and 9/2022. Standardized protocols- developed through earlier international collaboration- were consistently applied. Procurement surgery was carried out by an experienced adult hepatobiliary surgeon from a local hospital, while the implantation was conducted by the pediatric surgical team. RESULTS:Donors had a mean age of 32 ± 6.1 years. Procurement surgery lasted 422 ± 78.1 min. Mean blood loss was 237.5 ± 122.7 mL, and two donors required transfusion. All donor complications were Clavien-Dindo grade I. Recipients had a median age of 28 months and a weight of 10.4 kg. Biliary atresia accounted for 91.7% of indications. Grafts included seven left lateral segments and five full-left lobes. Recipient surgeries lasted 650 ± 91.5 min; mean transfusion volume was 231.2 ± 164.3 mL; cold ischemia time was 83.2 ± 24.9 min. Complications included chylous ascites (n = 2), portal vein stenosis (n = 1), and acute rejection (n = 2). One patient died from a hospital-acquired infection. CONCLUSION:This crisis-driven transition to local autonomization demonstrated that prior supportive preparation and implementation enabled safe and effective PLT during a global health emergency.
EEG functional connectivity analysis is increasingly used to study neurological disorders. However, the lack of standardization in connectivity estimation limits its clinical translation. This work addresses the need for more guidance in connectivity pipeline design by evaluating numerous techniques in two seizure-related disorders to identify optimal approaches. Retrospective EEG data were analyzed from two cohorts: acutely ill adults stratified by seizure occurrence (140 patients; 70 with seizures), and children with self-limited focal epilepsy with centro-temporal spikes (SeLECTS) stratified by cognitive regression (32 patients; 16 with regression). In each cohort, 960 connectivity pipelines were evaluated for their ability to discriminate between sub-groups using statistical testing and logistic regression. Pipelines were constructed by systematically varying re-referencing schemes, frequency bands, association measures, and network features. Significant connectivity differences were observed between sub-groups in both cohorts. Pipelines using corrected association measures (e.g., corrected correlation, weighted phase lag index) and network features capturing integration and segregation (e.g., characteristic path length, clustering coefficient) consistently showed superior performance. Pipeline rankings differed substantially across disorders, underscoring the importance of clinical context on the choice of parameters for connectivity analysis. These findings demonstrate the potential of EEG functional connectivity as a biomarker in seizure-related conditions, while emphasizing the critical impact of methodological choices. This study provides quantitative guidelines for informed pipeline design and supports the development of automated EEG connectivity analyses in clinical practice.
AIM:The European Pediatric Surgeons' Association (EUPSA) recently established a Global Surgery Committee to promote equitable access to pediatric surgical care through international collaboration and capacity building. This study aimed to explore and prioritize pediatric surgeons' expectations regarding the role and activities of the EUPSA Global Surgery Committee across different World Bank income groups, with particular attention to perspectives from low- and middle-income settings. METHODS:A two-round modified Delphi study was conducted using online surveys distributed via EUPSA networks, pediatric surgical societies, and professional social media. In Round 1, participants provided up to five free-text expectations; responses underwent inductive thematic analysis. In Round 2, participants ranked six themes, rated 20 subthemes on a 1-10 Likert scale and selected three top priorities. Countries were classified using the 2025 World Bank income groups, and descriptive statistics were used for analysis. RESULTS:A total of 230 participants from 68 countries completed Round 1; 113 (49%) practiced in low- or lower-middle-income settings, 165 (72%) were consultant pediatric surgeons, and 196 (85%) worked in urban environments. Thematic analysis of 218 valid free-text responses identified six themes spanning guidelines, training, research, advocacy, infrastructure, and cross-cutting support. In Round 2, 65 complete responses were analyzed. Training-related support ranked highest across all income groups, followed by guidelines and knowledge resources and by infrastructure and service delivery. Fellowships or observerships and structured mentorship were consistently among the highest-rated subthemes. High-income respondents more often prioritized guidelines and registry or multicenter research support, whereas low- and lower-middle-income respondents placed greater emphasis on equipment, infrastructure, and advocacy. CONCLUSIONS:Pediatric surgeons across income settings perceive EUPSA's global surgery role as multidimensional, with a consistent prioritization of capacity building through training, mentorship, guidelines, and systems-oriented support.
OBJECTIVES:Complex stimuli such as two-tone stimuli (f 1 and f 2 ) elicit frequency-following responses that reflect phase-locking to the stimulus envelope (f 2 - f 1 ) and temporal fine structure at multiple stages of the auditory pathway, from the cochlea to the cortex. The relative contribution of these structures to the scalp-recorded envelope-following response (EFR) remains a matter of debate. Although subcortical sources have been proposed as the main contributors, near-field recordings close to the cochlea contain pre-neural components and have recently been reported in auditory steady-state responses (ASSRs), a version of the EFR used to measure thresholds at the four frequencies (0.5, 1, 2, 4 kHz) most relevant for objective audiogram estimations. The present study evaluated the EFR in 26 auditory neuropathy spectrum disorder (ANSD) cases and 79 children with normal electrophysiological thresholds and distortion product otoacoustic emissions (controls). In addition, this study presents data from a battery of auditory neurophysiological objective tests applied to the 26 ANSD cases. DESIGN:EFRs were recorded using horizontal (EFR-H) and vertical (EFR-V) channels and the generalized primary tone phase variation method, allowing isolation of the EFR waveforms in the time domain to obtain direct latency and phase-locking value (PLV) measurements. EFRs detected in ANSD cases were compared with those of the controls. The standard audiological objective tests included tympanograms, distortion product otoacoustic emissions, click-evoked auditory brainstem responses (ABRs), and ASSRs. RESULTS:EFR-H was detected in five ANSD cases, showing shorter onset latencies, shorter response durations, and lower PLVs than controls. Lower PLVs were also observed in the EFR-H from the contralateral ears of unilateral ANSD cases. The EFR-V was undetected in all ANSD patients except for two, who showed milder neural desynchronization in their click-evoked ABRs and exhibited the lowest ABR thresholds within the ANSD cases. In 15 ANSD cases, with totally absent neural click-evoked ABRs, ASSRs were detected for at least one tested frequency, indicating a discrepancy between ABR and ASSR-estimated thresholds. CONCLUSIONS:The EFR-H observations suggested a pre-neural origin, with the asymmetrical mechanoelectrical transduction process at the sensory hair cells as the main contributor. These findings provide further evidence of a pre-neural potential explaining the discrepancy between ABR and ASSR threshold estimations in ANSD. In addition, the results from the contralateral ears of unilateral ANSD cases may reveal subtle deficits typically undetected by standard audiological techniques. Overall, the study of noninvasive EFR recordings in ANSD may contribute to refining their diagnosis, ultimately improving their treatment.
