Multipeptide vaccines for melanoma in the adjuvant setting: long-term survival outcomes and post-hoc analysis of a randomized phase II trial.

The critical roles of CD4+ T cells have been understudied for cancer vaccines. Here we report long-term clinical outcomes of a randomized multicenter phase II clinical trial (NCT00118274), where patients with high-risk melanoma received a multipeptide vaccine targeting CD8+ T cells (12MP) and were randomized to receive either of two vaccines for CD4+ (helper) T cells: 6MHP (6 melanoma-specific helper peptides), or tet (a nonspecific helper peptide from tetanus toxoid). Cyclophosphamide (Cy) pre-treatment was also assessed. Primary outcomes for T cell responses to 12MP, 6MHP, and tet were previously reported, suggesting immunogenicity of both vaccines but that CD8 T cell responses to 12MP were lower when tet was replaced with 6MHP. Here, in post-hoc analyses, we report durable prolongation of overall survival by adding 6MHP instead of tet. That benefit was experienced only by male patients. A favorable interaction of 6MHP and Cy is also suggested. Multivariable Cox regression analysis of the intent-to-treat population identify vaccine arm (12MP + 6MHP+Cy) and patient sex (male) as the two significant predictors of enhanced survival. These findings support the value of adding cognate T cell help to cancer vaccines and also suggest a need to assess the impact of patient sex on immune therapy outcomes.

Risk Factors for Sepsis-Associated Acute Kidney Injury in the PICU: A Retrospective Cohort Study.

OBJECTIVES: Acute kidney injury (AKI), particularly of greater severity and longer duration, is associated with increased morbidity and mortality in the pediatric population. AKI frequently occurs during sepsis, yet the knowledge of risk factors for sepsis-associated AKI in the PICU is limited. We aimed to identify risk factors for AKI that develops or persists after 72 hours from sepsis recognition in pediatric patients with severe sepsis. DESIGN: Retrospective cohort study. SETTING: PICU at an academic, tertiary-care center. PATIENTS: Children greater than 1 month and less than or equal to 18 years with severe sepsis in the combined cardiac and medical/surgical PICU between December 1, 2013, and December 31, 2020, at the University of Virginia Children's Hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort included 124 patients with severe sepsis with 33 patients (27%) who were postcardiac surgery with cardiopulmonary bypass. AKI was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The primary outcome was severe AKI, defined as KDIGO stage 2 or 3 AKI present at any point between days 3 and 7 after sepsis recognition. Severe AKI was present in 25 patients (20%). Factors independently associated with severe AKI were maximum vasoactive-inotropic score (VIS) within 48 hours after sepsis recognition and fluid overload. The presence of severe AKI was associated with increased inhospital mortality. CONCLUSIONS: In children with severe sepsis, the degree of hemodynamic support as measured by the VIS and the presence of fluid overload may identify patients at increased risk of developing severe AKI.

Adenoviral Respiratory Infection-Associated Mortality in Children: A Retrospective Case Series.

Viral respiratory infections are a leading cause of illness and hospitalization in young children worldwide. Case fatality rates in pediatric patients with adenoviral lower respiratory tract infection requiring intensive care unit (ICU) admission have been reported between 7 and 22%. We investigated the demographics and clinical characteristics in pediatric mortalities associated with adenoviral respiratory infection at 12 academic children's hospitals in the United States. There were 107 mortality cases included in our study, 73% of which had a chronic medical condition. The most common chronic medical condition was immunocompromised state in 37 cases (35%). The incidences of pediatric acute respiratory distress syndrome (78%) and multiple organ dysfunction syndrome (94%) were profound. Immunocompetent cases were more likely to receive mechanical ventilation within the first hour of ICU admission (60 vs. 14%, p < 0.001) and extracorporeal membrane oxygenation (27 vs. 5%, p = 0.009), and less likely to receive continuous renal replacement therapy (20 vs. 49%, p = 0.002) or have renal dysfunction (54 vs. 78%, p = 0.014) as compared with immunocompromised cases. Immunocompromised cases were more likely to have bacteremia (57 vs. 16%, p < 0.001) and adenoviremia (51 vs. 17%, p < 0.001) and be treated with antiviral medications (81 vs. 26%, p < 0.001). We observed a high burden of nonrespiratory organ system dysfunction in a cohort of pediatric case fatalities with adenoviral respiratory infection. The majority of cases had a chronic medical condition associated with an increased risk of complications from viral respiratory illness, most notably immunocompromised state. Important treatment differences were noted between immunocompromised and immunocompetent cases.