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Background Abusive head trauma (AHT), previously known as the shaken baby syndrome, is a severe and potentially fatal form of traumatic brain injury in infant children who have been shaken, and sometimes also sustained an additional head impact. The clinical and autopsy findings in AHT are not pathognomonic and, due to frequent obfuscation by perpetrators, the circumstances surrounding the alleged abuse are often unclear. The concept has evolved that the finding of the combination of subdural hemorrhage, brain injury, and retinal hemorrhages (“the triad”) is the result of shaking of an infant (“shaken baby syndrome”) and has led to the ongoing controversy whether shaking alone is able to generate sufficient force to produce these lesions. Objective In an attempt to investigate whether shaking can engender this lesion triad, animal models have been developed in laboratory rodents and domestic animal species. This review assesses the utility of these animal models to reliably reproduce human AHT pathology and evaluate the effects of shaking on the immature brain. Results Due largely to irreconcilable anatomic species differences between these animal brains and human infants, and a lack of resemblance of the experimental head shaking induced by mechanical devices to real-world human neurotrauma, no animal model has been able to reliably reproduce the full range of neuropathologic AHT changes. Conclusion Some animal models can simulate specific brain and ophthalmic lesions found in human AHT cases and provide useful information on their pathogenesis. Moreover, one animal model demonstrated that shaking of a freely mobile head, without an additional head impact, could be lethal, and produce significant brain pathology.

Refereed/Peer-reviewed Immune agonist antibodies (IAAs) are promising immunotherapies that target co-stimulatory receptors toinduce potent anti-tumor immune responses, particularly when combined with checkpoint inhibitors. Unfor-tunately, their clinical translation is hampered by serious dose-limiting, immune-mediated toxicities,including high-grade and sometimes fatal liver damage, cytokine release syndrome (CRS), and colitis. Weshow that the immunotoxicity, induced by the IAAs anti-CD40 and anti-CD137, is dependent on the gut micro-biota. Germ-free or antibiotic-treated mice have significantly reduced colitis, CRS, and liver damagefollowing IAA treatment compared with conventional mice or germ-free mice recolonized via fecal microbiotatransplant. MyD88 signaling is required for IAA-induced CRS and for anti-CD137-induced, but not anti-CD40-induced, liver damage. Importantly, antibiotic treatment does not impair IAA anti-tumor efficacy, alone or incombination with anti-PD1. Our results suggest that microbiota-targeted therapies could overcome thetoxicity induced by IAAs without impairing their anti-tumor activity.