Background: While rare in children, chylothorax is a significant cause of respiratory morbidity and can lead to malnutrition and immunodeficiency. Historically, the traditional pharmacological treatment has been octreotide. There are several treatments that have been utilized in the past few years including sirolimus, however data regarding their efficacy and outcomes is limited. Furthermore, sirolimus has proven efficacy in complex vascular malformations, and hence, its utility/efficacy in pediatric chylous effusions warrants further investigation. Methods: In this retrospective study at Texas Children’s Hospital, data were extracted for all patients with chylothorax who were treated with sirolimus between 2009 and 2020. Details regarding underlying diagnosis, co-morbidities and number of days from sirolimus initiation to resolution of effusion were collected. Descriptive statistics were used to analyze the study cohort. Results: Initially a total of twelve infants were identified. Among them, seven patients had complete data and were included in the study. The mean duration of sirolimus treatment needed for chest tube removal was 16 days, with a median of 19 days and range of 7- 22 days. Chest tube output corresponded with sirolimus serum trough levels and trended down prior to chest tube removal. Conclusion: With close monitoring, sirolimus is a safe and effective therapy for pediatric lymphatic effusions even in critically-ill infants. The study also demonstrates shorter duration of chest tube requirement after initiation of sirolimus compared to previous studies. Our conclusion is based on a small case series due to the rare incidence of the condition.

Background: Children with hematologic malignancies, especially those who receive intensive chemotherapy, are at high risk for invasive mold infections (IMI) that confer substantial mortality. Randomized controlled trials support the use of anti-fungal prophylaxis with anti-mold activity as an optimal strategy for risk reduction in this population, but studies outlining the practical application of evidence-based recommendations are lacking. Procedure: We conducted a 15-year, single-institution retrospective review of children with hematologic malignancies treated with chemotherapy to determine the incidence of proven or probable IMI diagnosed between 2006 and 2020 and to identify the host and disease factors associated with IMI risk. We then compared the incidence and type of IMI and related factors before and after 2016 implementation of an evidence-based, risk-adapted anti-fungal prophylaxis algorithm that broadened coverage to include molds in patients at highest risk for IMI. Multivariable linear regression was used to determine factors related to IMI risk. Results: We identified 61 cases of proven or probable IMI in 1,456 patients diagnosed with hematologic malignancies during the study period (4.2%). Implementation of an anti-fungal prophylaxis algorithm reduced the IMI incidence in this population from 4.8% to 2.9%. After multivariable analysis, both Hispanic ethnicity and cancer diagnosis prior to 2016 were significantly associated with risk for IMI. Conclusion: An evidence-based, risk-adapted approach to anti-fungal prophylaxis for children with hematologic malignancies is an effective strategy to reduce incidence of IMI.

Background: Pediatric papillary thyroid carcinoma (PTC) is clinically and biologically distinct from adult PTC. We sequenced a cohort of clinically-annotated pediatric PTC cases enriched for high-risk tumors to identify genetic alterations of relevance for diagnosis and therapy. Methods: Tumor DNA and RNA were extracted from FFPE tissue and subjected to next generation sequencing (NGS) library preparation using a custom 124 gene hybridization capture panel and the 75 gene Archer Oncology Research Panel, respectively. NGS libraries were sequenced on an Illumina MiSeq. Results: Thirty-six pediatric PTC cases were analyzed. Metastases were frequently observed to cervical lymph nodes (29/36, 81%), with pulmonary metastases less commonly found (10/36, 28%). Relapsed or refractory disease occurred in 18 patients (18/36, 50%). DNA sequencing revealed targetable mutations in 8 of 31 tumors tested (26%), most commonly BRAF p.V600E (n=6). RNA sequencing identified targetable fusions in 13 of 25 tumors tested (52%): RET (n=8), NTRK3 (n=4), and BRAF. Mutually-exclusive targetable alterations were discovered in 15 of the 20 tumors (75%) with both DNA and RNA analyzed. Fusion positive PTC was associated with multifocal disease, higher tumor staging, and higher American Thyroid Association (ATA) risk levels. Both BRAF V600E mutations and gene fusions were correlated with the presence of cervical metastases. Conclusions: Targetable alterations were identified in 75% of pediatric PTC cases with both DNA and RNA evaluated. Inclusion of RNA sequencing for detection of fusion genes is critical for evaluation of these tumors. Patients with fusion positive tumors were more likely to have features of high-risk disease.