Objective: To evaluate the impact of early disseminated intravascular coagulation (DIC) on illness severity in children using a database of ED encounters for children with suspected sepsis, in view of similar associations in adults.Study design: Laboratory and clinical data were extracted from a registry of Emergency Department (ED) encounters of children with suspected sepsis between April 01, 2012 and June 26, 2017. International Society of Thrombosis and Hemostasis DIC scores were calculated from laboratory values obtained within 24 hours of ED admission. Univariate logistic regression, multivariable logistic regression, and Cox regression were used to assess the influence of DIC scores on vasopressor use (primary outcome), mortality, ventilator requirement, pediatric intensive care unit admission, and hospital duration (secondary outcomes). The optimal DIC score cutoff for outcome prediction was determined.Results: Of 1,653 eligible patients, 284 had DIC scores within 24 hours, including 92 who required vasopressors and 23 who died within one year. An initial DIC score≥3 was the most sensitive and specific DIC score for predicting adverse outcomes. Those with a DIC score ≥3 vs.

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IntroductionDetermining which febrile pediatric hematology/oncology (PHO) patients will decompensate from severe infection is a significant challenge. Serum lactate is a well-established marker of illness severity in general adult and pediatric populations, however its utility in PHO patients is unclear given that chemotherapy, organ dysfunction, and cancer itself can alter lactate metabolism. In this retrospective analysis, we studied the association of initial serum lactate in febrile immunosuppressed PHO patients with illness severity, defined by the incidence of clinical deterioration events (CDE) and invasive bacterial infection (IBI) within 48 hours.MethodsReceiver operating characteristic (ROC) curves were reported using initial lactate within two hours of arrival as the sole predictor for CDE and IBI within 48 hours. Using a generalized estimating equations (GEE) approach, the association of lactate with CDE and IBI within 48 hours was tested in univariate and multivariable analyses including covariates based on Quasi-likelihood under Independence Model Criterion (QIC). Additionally, the association of lactate with secondary outcomes (i.e., hospital length of stay (LOS), intensive care unit (PICU) admission, PICU LOS, non-invasive infection) was assessed.ResultsAmong 897 encounters, 48 encounters had ≥1 CDE (5%), and 96 had ≥1 IBI (11%) within 48 hours. Elevated lactate was associated with increased CDE in univariate (OR 1.77, 95%CI: 1.48-2.12, p<0.001) and multivariable (OR 1.82, 95%CI: 1.43-2.32, p<0.001) analyses, longer hospitalization (OR 1.15, 95%CI: 1.07-1.24, p<0.001), increased PICU admission (OR 1.68, 95%CI: 1.41-2.0, p<0.001), and longer PICU LOS (OR 1.21, 95%CI: 1.04-1.4, p=0.01). Elevated lactate was associated with increased IBI in univariate (OR 1.40, 95%CI: 1.16-1.69, p<0.001) and multivariable (OR 1.49, 95%CI: 1.23-1.79, p<0.001) analyses. Lactate level was not significantly associated with increased odds of non-invasive infection (p=0.09). The QIC of the model was superior with lactate included for both CDE (305 vs. 325) and IBI (563 vs. 579).ConclusionsThese data demonstrated an independent association of elevated initial lactate level and increased illness severity in febrile PHO patients, suggesting that serum lactate could be incorporated into future risk stratification strategies for this population.

The additional sex combs like (ASXL) gene family, comprised of the ASXL1, ASXL2, and ASXL3 genes, encodes proteins involved in epigenetic regulation, embryogenesis, and carcinogenesis. [1][2][3] Despite the implication of somatic ASXL mutations in a variety of malignancies, germline ASXL mutations do not appear to have an association with increased malignancy risk. Bainbridge-Ropers syndrome (BRPS) is a rare autosomal dominant genetic disorder with an estimated 89 known cases 4 that results from de novo ASXL3 gene mutations, 5 characterized by poor growth, hypotonia, intellectual disability, language delay, and dysmorphic facial features. 6 Many affected patients have autism disorder, and approximately one-third of patients have epilepsy. 7,8 The few published reports of cancer in patients with germline ASXL mutations are limited to patients with ASXL1 mutations, implicated in Bohring-Opitz syndrome (BOS), a phenotypically similar neurodevelopmental syndrome to BRPS. These include two patients with bilateral Wilms tumor, 9 and a father and son with identical germline ASXL1 mutations with acute myeloid leukemia. 10 Unlike BOS, there are no reported cases of malignancy in patients with BRPS. Here, we report the clinical course of a 3-year-old male with BRPS found to have precursor B-cell acute lymphoblastic leukemia (ALL).At age 10 months, the patient underwent neurologic evaluation due to developmental delay, feeding difficulties, and growth failure. He was hypotonic and had subtle dysmorphic features, including arched eyebrows and anteverted nares. A trio-based Autism/ID Xpanded Panel (GeneDx, LLC 2019) sent with samples from biological parents demonstrated a de novo pathogenic variant (c.4678C>T; p.R2560X) in the ASXL3 gene (RefSeq transcript NM_030632.1, human genome build GRCH37/UCSC hg19), consistent with BRPS.At age 3 years, he presented with feeding intolerance, fatigue, and abdominal pain. Laboratory analysis showed white blood cells (WBCs) 12.7/mm 3 with 27% peripheral blasts, hemoglobin 8.3 g/dl, and platelet count 69,000/mm 3 . Peripheral flow cytometry identified an immature lymphoid population, consistent with precursor B-cell ALL (Table 1).Bone marrow analysis revealed no detectable clonal abnormalities on standard cytogenetics, and fluorescence in situ hybridization (FISH)