Assessing the quality of life in infants with deformational plagiocephaly.

This was a parent-reported outcome study on the impact of helmet therapy on the quality of life of infants with deformational plagiocephaly and their caregivers. Using survey-based analysis, we compared the quality of life in infants with deformational plagiocephaly with a cohort of their healthy peers. In addition, we compared infant quality of life before and after helmet therapy to evaluate the impact of this mainstay therapy for deformational plagiocephaly. Our results demonstrated that infants with plagiocephaly and their caregivers had a significantly decreased quality of life compared with healthy controls. This reframes our understanding of deformational plagiocephaly and emphasizes the need for therapeutic intervention in these individuals. A common therapeutic option - helmet remolding therapy - was shown to have no negative impact on quality of life, underscoring this as an appropriate therapeutic option. These data will allow us to counsel our future parents more effectively regarding the impact of deformational plagiocephaly and helmet therapy.

Nanotopography-based lymphatic delivery for improved anti-tumor responses to checkpoint blockade immunotherapy.

Rationale: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a co-inhibitory checkpoint receptor that is expressed by naïve T-cells in lymph nodes (LNs) to inhibit activation against "self" antigens (Ags). In cancer, anti-CTLA-4 blocks inhibitory action, enabling robust activation of T-cells against tumor Ags presented in tumor draining LNs (TDLNs). However, anti-CTLA-4 is administered intravenously with limited exposure within TDLNs and immune related adverse events (irAEs) are associated with over-stimulation of the immune system. Methods: Herein, we first deliver anti-CTLA-4 in an orthotopic mammary carcinoma murine model using a nanotopographical microneedle-array device to compare its anti-tumor response to that from systemic administration. Additionally, to demonstrate the feasibility of lymphatic delivery in humans using the device, we use near-infrared fluorescence imaging to image delivery of ICG to LNs. Results: Our data show that lymphatic infusion results in more effective tumor growth inhibition, arrest of metastases, increased tumor infiltrating lymphocytes and complete responses when compared to conventional systemic administration. In clinical studies, we demonstrate for the first time that nanotopographic infusion can deliver ICG through the lymphatics directly to the axilla and inguinal LNs of healthy human volunteers. Conclusion: Taken together, these results suggest that regional delivery using a nanotopography-based microneedle array could revolutionize checkpoint blockade immunotherapy by reducing systemic drug exposure and maximizing drug delivery to TDLNs where tumor Ags present. Future work is needed to determine whether lymphatic delivery of anti-CTLA-4 can alleviate irAEs that occur with systemic dosing.