ImportanceAcute necrotizing encephalopathy (ANE) is a rare disease with high mortality. Plasma exchange (PLEX) has recently been reported to treat ANE of childhood (ANEC), but its efficacy is uncertain.ObjectiveThis study aimed to investigate the effectiveness of PLEX on ANEC.MethodsA retrospective study was conducted in four pediatric intensive care units from December 2014 to December 2020. All patients who were diagnosed with ANEC were included; however, these patients were excluded if their length of stay was less than 24 h. Participants were classified into PLEX and non‐PLEX groups.ResultsTwenty‐nine patients with ANEC were identified, 10 in the PLEX group and 19 in the non‐PLEX group. In the PLEX group, C‐reactive protein, procalcitonin, alanine aminotransferase, and aspartate aminotransaminase levels were significantly lower after 3 days of treatment than before treatment (13.1 vs. 8.0, P = 0.043; 9.8 vs. 1.5, P = 0.028; 133.4 vs. 31.9, P = 0.028; 282.4 vs. 50.5, P = 0.046, respectively). Nine patients (31.0%, 9/29) died at discharge, and a significantly difference was found between the PLEX group and non‐PLEX group [0 vs. 47.4% (9/19), P = 0.011]. The median follow‐up period was 27 months, and three patients were lost to follow‐up. Thirteen patients (50.0%, 13/26) died at the last follow‐up, comprising three (33.3%, 3/9) in the PLEX group and ten (58.8%, 10/17) in the non‐PLEX group, but there was no significant difference between the two groups (P = 0.411). Three patients (10.3%, 3/29) fully recovered.InterpretationPLEX may reduce serum C‐reactive protein and procalcitonin levels and improve liver function in the short term. PLEX may improve the prognosis of ANEC, and further studies are needed.

Background We explored the differences in baseline characteristics, pathogens, complications, outcomes, and risk factors between children with hospital-acquired septic shock (HASS) and community-acquired septic shock (CASS) in the pediatric intensive care unit (PICU). Methods This retrospective study enrolled children with septic shock at the PICU of Beijing Children’s Hospital from January 1, 2016, to December 31, 2019. The patients were followed up until 28 days after shock or death and were divided into the HASS and CASS group. Logistic regression analysis was used to identify risk factors for mortality. Results A total of 298 children were enrolled. Among them, 65.9% (n = 91) of HASS patients had hematologic/oncologic diseases, mainly with Gram-negative bacterial bloodstream infections (47.3%). Additionally, 67.7% (n = 207) of CASS patients had no obvious underlying disease, and most experienced Gram-positive bacterial infections (30.9%) of the respiratory or central nervous system. The 28-day mortality was 62.6% and 32.7% in the HASS and CASS groups, respectively (P < 0.001). Platelet [odds ratio (OR) = 0.996, 95% confidence interval (CI) = 0.992–1.000, P = 0.028], positive pathogen detection (OR = 3.557, 95% CI = 1.307–9.684, P = 0.013), and multiple organ dysfunction syndrome (OR = 10.953, 95% CI = 1.974–60.775, P = 0.006) were risk factors for 28-day mortality in HASS patients. Lactate (OR = 1.104, 95% CI = 1.022–1.192, P = 0.012) and mechanical ventilation (OR = 8.114, 95% CI = 1.806–36.465, P = 0.006) were risk factors for 28-day mortality in patients with CASS. Conclusions The underlying diseases, pathogens, complications, prognosis, and mortality rates varied widely between the HASS and CASS groups. The predictors of 28-day mortality were different between HASS and CASS pediatric patients with septic shock.

Background Thiamine metabolism dysfunction syndrome 4 (THMD4, OMIM #613710) is an autosomal recessive inherited disease caused by the deficiency of SLC25A19 that encodes the mitochondrial thiamine pyrophosphate (TPP) transporter. This disorder is characterized by bilateral striatal degradation and progressive polyneuropathy with the onset of fever of unknown origin. The limited number of reported cases and lack of functional annotation of related gene variants continue to limit diagnosis. Results We report three cases of encephalopathy from two unrelated pedigrees with basal ganglia signal changes after fever of unknown origin. To distinguish this from other types of encephalopathy, such as acute necrotizing encephalopathy, exome sequencing was performed, and four novel heterozygous variations, namely, c.169G>A (p.Ala57Thr), c.383C>T (p.Ala128Val), c.76G>A (p.Gly26Arg), and c.745T>A (p.Phe249Ile), were identified in SLC25A19. All variants were confirmed using Sanger sequencing. To determine the pathogenicity of these variants, functional studies were performed. We found that mitochondrial TPP levels were significantly decreased in the presence of SLC25A19 variants, indicating that TPP transport activities of mutated SLC25A19 proteins were impaired. Thus, combining clinical phenotype, genetic analysis, and functional studies, these variants were deemed as likely pathogenic. Conclusions Exome sequencing analysis enables molecular diagnosis as well as provides potential etiology. Further studies will enable the elucidation of SLC25A19 protein function. Our investigation supplied key molecular evidence for the precise diagnosis of and clinical decision-making for a rare disease.