Brain injury exosomal proteins are promising blood biomarker candidates in traumatic brain injury (TBI). A better understanding of their role in the diagnosis, characterization, and management of TBI is essential for upcoming clinical implementation. In the current investigation, we aimed to explore longitudinal trajectories of brain injury exosomal proteins in blood of patients with moderate-to-severe TBI, and to evaluate the relation with the free-circulating counterpart and patient imaging and clinical parameters. Exosomal levels of glial (glial fibrillary acidic protein (GFAP)) and neuronal/axonal (ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light chain (NFL), and total-tau (t-tau)) proteins were measured in serum of 21 patients for up 5 days after injury using single molecule array (Simoa) technology. Group-based trajectory analysis was used to generate distinct temporal exosomal biomarker profiles. We found altered profiles of serum brain injury exosomal proteins following injury. The dynamics and levels of exosomal and related free-circulating markers, although correlated, showed differences. Patients with diffuse injury displayed higher acute exosomal NFL and GFAP concentrations in serum than those with focal lesions. Exosomal UCH-L1 profile characterized by acutely elevated values and a secondary steep rise was associated with early mortality (n = 2) with a sensitivity and specificity of 100%. Serum brain injury exosomal proteins yielded important diagnostic and prognostic information and represent a novel means to unveil underlying pathophysiology in patients with moderate-to-severe TBI. Our findings support their utility as potential tools to improve patient phenotyping in clinical practice and therapeutic trials.

Checkpoint inhibitors are being explored for chronic central nervous system (CNS) infections such as HIV, but safety data in the absence of malignancy are limited. In this phase I, non-randomized study, six virally suppressed individuals with HIV received a single dose of pembrolizumab to assess safety and effects on immune, virologic, and CNS parameters. Over 12 months, 29 adverse events occurred, all grade 1–2, with no serious events. HIV immune responses and viral loads were unchanged, although transient CSF viral increases occurred in two participants. A single dose pembrolizumab appears safe, supporting evaluation of repeated dosing.

Obesity and its related complications continue to be significant challenges for kidney transplant recipients. In previous studies, researchers have reported that brain‐derived neurotrophic factor (BDNF) is closely associated with metabolic imbalance and obesity, but the role of BDNF in weight gain after kidney transplant has not been elucidated. The purpose of this pilot study was to explore the relationship between plasma BDNF levels and weight change. We examined associations between plasma BDNF levels measured at transplantation and 12 months later and measures of weight change during these 12 months in a sample of 55 kidney recipients (mean age of 48 years, 60% male, 56% African American). Of the 55 recipients, 49 had BDNF levels measured at baseline, 33 had BDNF levels measured at 12 months, and 27 had BDNF levels measured at both time points. We found that plasma BDNF levels at baseline (n = 49), but not at 12 months (n = 33), were significantly and positively correlated with the body mass index change (p = 0.037) and percentage weight change (p = 0.036). In addition, average plasma BDNF value at 12 months (307 ± 254 pg/ml) was significantly lower than at baseline (452 ± 345 pg/ml) in the 27 recipients with BDNF levels measured at both time points. Findings from this pilot work suggest that BDNF might serve as a regulator of weight change for kidney transplant related obesity.