Cedars-Sinai Medical Center

We describe the repair of a symptomatic anomalous origin of the circumflex coronary artery from the left pulmonary artery (ACXPA) in a child with a modified Cabrol technique as a bail-out option as direct aortic implantation or a left pulmonary artery (LPA)-based tubularized flap aortic implantation was not feasible to establish circumflex coronary artery (CX) to aortic continuity.

Dennis M. Tang is a consultant for Aerin Medical, Acclarent, 3D Matrix, SoundHealth, and Regeneron. He is a speaker for Regeneron and Paratek. He receives research support from Acclarent. The data that support the findings of this study are available from the corresponding author upon reasonable request.

The study goal was to evaluate the outcomes associated with albumin use in children with sepsis and shock compared with those without shock, using causal inference analysis in a multicenter cohort. This was a secondary analysis of electronic health record data collected from 13 U.S. PICUs between 2012 and 2018, consisting of children younger than 18 years who met Phoenix sepsis criteria within the first 24 hours of PICU admission. Covariate-balancing propensity score weighting was applied to adjust for indication bias in the albumin use. Patients receiving at least 0.5 g/kg albumin within 24 hours of PICU admission were assigned to the albumin group; others to the control. Only 24-hour survivors were included to address immortal time bias. Overall, 17,307 children with sepsis survived at least 24 hours. Of these, 1,344 patients (7.8%) who received albumin within the first 24 hours, and 9,678 (55.9%) met the criteria for septic shock. A significant interaction between albumin use and shock status was observed (interaction: -0.353, p = 0.007), with albumin administration in pediatric septic shock patients associated with lower in-hospital mortality: odds ratio equals to 0.698 (95% CI, 0.629-0.774), risk ratio equals to 0.746 (95% CI, 0.625-0.891), and hazard ratio equals to 0.688 (95% CI, 0.558-0.848). In contrast, there was no difference in outcomes between the albumin and control groups in the non-shock group. Early albumin administration was associated with improved outcomes in children with septic shock, but not in those without shock. These results highlight the importance of considering clinical heterogeneity, such as the presence of shock, in identifying treatment-responsive subgroups and enabling more targeted interventions in pediatric sepsis. Further prospective validation is warranted.

Amivantamab is an EGFR-MET bispecific antibody approved as an intravenous formulation for EGFR-mutated advanced non-small cell lung cancer (NSCLC). Intravenous delivery is frequently associated with infusion-related reaction (IRRs), which require adopting slow infusion rates and splitting the first dose over 2 days. The PALOMA study assessed the safety and feasibility of subcutaneous amivantamab administration and identified the formulation and recommended phase II doses (RP2Ds) for multiple dosing schedules. PALOMA is a phase Ib dose-escalation study in 158 participants with advanced solid malignancies. Primary objectives included pharmacokinetics, safety, and determining RP2Ds for every-2-week (Q2W), every-3-week (Q3W), and every-4-week (Q4W) administration. The safety profile of subcutaneous amivantamab was largely consistent with intravenous monotherapy; most common toxicities reflected on-target EGFR/MET inhibition. Subcutaneous amivantamab resulted in meaningfully shorter administration time (≤ 10 minutes vs. 2.3 hours for intravenous beyond cycle 3) and lower incidence and severity of IRRs versus historical intravenous data, which eliminates the need for split-dose administration. Pharmacokinetic analyses and population pharmacokinetic modeling/simulation were used to estimate subcutaneous amivantamab RP2Ds of 1600 mg (2240 mg, ≥ 80 kg), 2400 mg (3360 mg, ≥ 80 kg), and 3520 mg (4640 mg, ≥ 80 kg) for Q2W, Q3W, and Q4W schedules, respectively. The observed efficacy was consistent with intravenous amivantamab monotherapy. Subcutaneous amivantamab administration substantially reduced IRRs, obviating the need for prolonged infusions and 2-day split-dosing at first administration. The identified RP2Ds for subcutaneous amivantamab are implemented in ongoing studies evaluating amivantamab regimens in NSCLC, colorectal cancer, and head and neck squamous cell carcinoma.