A 6-Year-Old With Episodes of Hand-Waving and Loss of Attention.

A 6-year-old girl was referred to pediatric neurology because of concerns about her behavior. Her mother had noticed episodes in which the girl would wave her hand in front of her face and lose awareness of her surroundings several times per day. These episodes usually occurred when she was outdoors and had caused the child to walk into objects and stop in traffic. The patient otherwise had no neurological deficits or cognitive impairment, and there was no family history of neuropsychiatric disorders. Although the patient was aware of her behavior, she could not explain why she performed these hand-waving motions. A neurological workup revealed that these behaviors were not complex stereotypies but rather a rare and unusual disorder. This case highlights the role of neurology in assessing complex motor behaviors and offers insight into when a practicing pediatrician should consider a neurological workup for complex stereotypies. [Pediatr Ann. 2023;52(8):e309-e312.].

Lactate induces PD-L1 in HRASG12V-positive oropharyngeal squamous cell carcinoma.

Intratumoral lactate production negatively correlates with survival and tumor clearance in the setting of human papillomavirus positive oropharyngeal squamous cell carcinoma (HPV-positive OPSCC). Robust anti-tumor immune activity is required for tumor clearance in human patients and animal models of this disease, and intratumoral lactate interferes with this process. While lactate is known to directly inhibit T cell activity, recent evidence has demonstrated that lactate can affect gene expression in multiple cell types. We therefore sought to determine if lactate in the tumor microenvironment could aid immune evasion by inducing the expression of immune checkpoint co-inhibitors. Using a mouse cell line transformed with HPV16 E6, E7, and HRASG12V, we determined that OPSCC cells carrying the HRASG12V mutant showed significantly increased expression of PD-L1 in the presence of extracellular lactate. Furthermore, we demonstrate here that lactate activates the MEK/ERK pathway in Ras-mutated cells.