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ABSTRACTThe development of bispecific antibodies that bind at least two different targets relies on bringing together multiple binding domains with different binding properties and biophysical characteristics to produce a drug-like therapeutic. These building blocks play an important role in the overall quality of the molecule and can influence many important aspects from potency and specificity to stability and half-life. Single-domain antibodies, particularly camelid-derived variable heavy domain of heavy chain (VHH) antibodies, are becoming an increasingly popular choice for bispecific construction due to their single-domain modularity, favorable biophysical properties, and potential to work in multiple antibody formats. Here, we review the use of VHH domains as building blocks in the construction of multispecific antibodies and the challenges in creating optimized molecules. In addition to exploring traditional approaches to VHH development, we review the integration of machine learning techniques at various stages of the process. Specifically, the utilization of machine learning for structural prediction, lead identification, lead optimization, and humanization of VHH antibodies.

Background Foreign body (FB) ingestions cause lead toxicity in pediatric patients. These ingestions result in continued lead absorption until passage or removal from the gastrointestinal (GI) tract. Whole-bowel irrigation (WBI) is frequently recommended to aid in the removal of FBs, however effectiveness of this practice is not clear.Methods We performed a retrospective chart review of pediatric patients (

AbstractClonidine and guanfacine are centrally acting sympatholytics (CAS). Poisoning with these agents is common in children, and management of this poisoning is controversial. We sought to characterize our experience with pediatric CAS poisonings. We used an internal database to identify patients with CAS poisoning seen by the medical toxicology service at our children’s hospital from January 2001 through November 2019. We performed a retrospective chart review. We identified 56 patients with clonidine poisoning and 19 patients with guanfacine poisoning. Sixty-six percent of patients with clonidine poisoning underwent any medical intervention, as did 32% of patients with guanfacine poisoning. The most common interventions were fluids and naloxone. Endotracheal intubation was uncommon. The median hospital length of stay was one day and the median ICU length of stay was one day. Two patients died; one co-ingested a large amount of bupropion and one aspirated charcoal, leading to pneumonitis and anoxic brain injury. No patient with isolated CAS poisoning died. In this retrospective single-center review, pediatric patients tolerated CAS poisoning well. CAS poisoning did not directly result in death. Most pediatric patients with CAS poisoning had short hospital lengths of stay and did not undergo critical care interventions.