Osteosarcoma patient survival has remained stagnant for 30 years. Novel therapeutic approaches are needed to improve outcomes. We examined the expression of Programmed Death Ligand 1 (PD-L1) and defined the tumor immune microenvironment to assess the prognostic utility in osteosarcoma. PD-L1 expression in osteosarcoma was examined in two patient cohorts using immunohistochemistry (IHC) (n = 48, n = 59) and expression was validated using quantitative real time PCR (n = 21) and western blotting (n = 9). IHC was used to determine the presence of tumor infiltrating lymphocytes and antigen-presenting cells (APCs) in the tumor. Expression of PD-L1 was correlated with immune cell infiltration and event-free-survival (EFS). The 25% of primary osteosarcoma tumors that express PD-L1 were more likely to contain cells that express PD-1 than PD-L1 negative tumors (91.7% vs 47.2%, p = 0.002). Expression of PD-L1 was significantly associated with the presence of T cells, dendritic cells, and natural killer cells. Although all immune cell types examined were present in osteosarcoma samples, only infiltration by dendritic cells (28.3% vs. 83.9%, p = 0.001) and macrophages (45.5% vs. 84.4%, p = 0.031) were associated with worse five-year-EFS. PD-L1 expression was significantly associated with poorer five-year-EFS (25.0%. vs. 69.4%, p = 0.014). Further studies in osteosarcoma are needed to determine if targeting the PD-L1:PD-1 axis improves survival.

Background We sought to assess the impact and predictors of Coronavirus Disease 2019 (COVID‐19) infection and severity in a cohort of congenital heart disease (CHD) patients at a large CHD center in New York City. Methods and Results We performed a retrospective review of all individuals with CHD followed at Columbia University Irving Medical Center who were diagnosed with COVID‐19 between 3/1/2020 and 7/1/2020. The primary endpoint was moderate/severe response to COVID‐19 infection defined as a) death during COVID‐19 infection; or 2) need for hospitalization and/or respiratory support secondary to COVID‐19 infection. Among 53 COVID‐19 positive patients with CHD, 10 (19%) were <18 years old (median age 34 years). 31 (58%) had complex congenital anatomy including 10 (19%) with a Fontan repair. Eight (15%) had a genetic syndrome, six (11%) had pulmonary hypertension (PH), and nine (17%) were obese. Among adults, 18 (41%) were physiologic class C or D. For the entire cohort, nine (17%) had a moderate/severe infection, including three deaths (6%). After correcting for multiple comparisons, the presence of a genetic syndrome (OR=35.82: p=0.0002), and in adults, physiological Stage C or D (OR=19.38: p=0.002) were significantly associated with moderate/severe infection. Conclusions At our CHD center, the number of symptomatic COVID‐19 patients was relatively low. CHD patients with a genetic syndrome and adults at advanced physiological stage were at highest risk for moderate/severe infection.

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) has spread through the pediatric population during the coronavirus disease 2019 pandemic. Our objective for the study was to report the prevalence of conduction anomalies in MIS-C and identify predictive factors for the conduction abnormalities. METHODS: We performed a single-center retrospective cohort study of pediatric patients &lt;21 years of age presenting with MIS-C over a 1-month period. We collected clinical outcomes, laboratory findings, and diagnostic studies, including serial electrocardiograms, in all patients with MIS-C to identify those with first-degree atrioventricular block (AVB) during the acute phase and assess for predictive factors. RESULTS: Thirty-two patients met inclusion criteria. Median age at admission was 9 years. Six of 32 patients (19%) were found to have first-degree AVB, with a median longest PR interval of 225 milliseconds (interquartile range 200–302), compared with 140 milliseconds (interquartile range 80–178) in patients without first-degree AVB. The onset of AVB occurred at a median of 8 days after the initial symptoms and returned to normal 3 days thereafter. No patients developed advanced AVB, although 1 patient developed a PR interval &gt;300 milliseconds. Another patient developed new-onset right bundle branch block, which resolved during hospitalization. Cardiac enzymes, inflammatory markers, and cardiac function were not associated with AVB development. CONCLUSIONS: In our population, there is a 19% prevalence of first-degree AVB in patients with MIS-C. All patients with a prolonged PR interval recovered without progression to high-degree AVB. Patients admitted with MIS-C require close electrocardiogram monitoring during the acute phase.

Identification and quantification of somatic alterations in plasma-derived, circulating tumor DNA (ctDNA) is gaining traction as a non-invasive and cost effective method of disease monitoring in cancer patients, particularly to evaluate response to treatment and monitor for disease recurrence. To our knowledge, genetic analysis of ctDNA in osteosarcoma has not yet been studied. To determine whether somatic alterations can be detected in ctDNA and perhaps applied to patient management in this disease, we collected germline, tumor, and serial plasma samples from pediatric, adolescent, and young adult patients with osteosarcoma and used targeted Next Generation Sequencing (NGS) to identify somatic single nucleotide variants (SNV), insertions and deletions (INDELS), and structural variants (SV) in 7 genes commonly mutated in osteosarcoma. We demonstrate that patient-specific somatic alterations identified through comparison of tumor-germline pairs can be detected and quantified in cell-free DNA of osteosarcoma patients.