Gastric and enteric phytobezoars caused by ingestion of persimmon in equids

Abstract Case Description—13 equids (10 horses, 2 donkeys, and 1 pony) were examined for signs of colic (n = 7), weight loss (6), anorexia (3), and diarrhea (2). Ten equids were evaluated in the fall (September to November). Seven equids had a history of persimmon ingestion. Clinical Findings—A diagnosis of phytobezoar caused by persimmon ingestion was made for all equids. Eight equids had gastric persimmon phytobezoars; 5 had enteric persimmon phytobezoars. Gastroscopy or gastroduodenoscopy revealed evidence of persimmon ingestion in 8 of 10 equids in which these procedures were performed. Treatment and Outcome—2 of 13 equids were euthanatized prior to treatment. Supportive care was instituted in 11 of 13 equids, including IV administration of fluids (n = 8) and treatment with antimicrobials (5), NSAIDs (5), and gastric acid suppressants (4). Persimmon phytobezoar–specific treatments included dietary modification to a pelleted feed (n = 8); oral or nasogastric administration of cola or diet cola (4), cellulase (2), or mineral oil (2); surgery (4); and intrapersimmon phytobezoar injections with acetylcysteine (1). Medical treatment in 5 of 7 equids resulted in resolution of gastric persimmon phytobezoars. Seven of 8 equids with gastric persimmon phytobezoars and 1 of 5 equids with enteric persimmon phytobezoars survived &gt; 1 year after hospital discharge. Clinical Relevance—Historical knowledge of persimmon ingestion in equids with gastrointestinal disease warrants gastroduodenoscopy for evaluation of the presence of persimmon phytobezoars. In equids with gastric persimmon phytobezoars, medical management (including administration of cola or diet cola and dietary modification to a pelleted feed) may allow for persimmon phytobezoar dissolution.</jats:p

A two-part, phase II, multi-center study of the ERK inhibitor ulixertinib (BVD-523) for patients with advanced malignancies harboring MEK or atypical BRAF alterations (BVD-523-ABC).

TPS3172 Background: Ulixertinib (BVD-523) is a small molecule inhibitor of extracellular signal-regulated kinases 1/2 (ERK1/2) in development as a novel anti-cancer drug. Early clinical data demonstrated anti-tumor activity, especially for patients with tumors harboring atypical BRAF or MEK1/2 alterations (Sullivan et al., Cancer Discov. 2018;8(2):184-195). Atypical BRAF (non-V600) alterations can be categorized according to characteristics of molecular signaling (Class II or III), are seen in approximately 3% of all human cancers, and there are currently no approved therapies for this indication. Similar to atypical BRAF alterations, the incidence of MEK1/2 alterations are rare in human tumors (&lt; 1 %). Preclinical data have demonstrated activity of ulixertinib in MEK mutant models. Ulixertinib has FDA fast-track designation for patients with solid tumors, other than CRC, with specific BRAF mutations (G469A, L485W, or L597Q). Designed with intent to register, the BVD-523-ABC clinical trial will continue evaluation of ulixertinib in patients with tumors harboring any atypical BRAF or MEK1/2 alteration (NCT04488003). Methods: This multi-center, phase II study, will be conducted in two parts and assess the clinical benefit, safety, pharmacokinetics, and pharmacodynamics of ulixertinib in patients with advanced malignancies. Ulixertinib will be administered at the RP2D of 600 mg BID for 28-day treatment cycles. Eligible patients will have locally advanced or metastatic cancer which progressed following standard systemic therapies, or for which the patient is not a candidate or refused systemic therapy. Planned correlative analyses include reverse phase protein array and transcriptomics of tumor tissue. Part A is open-label and tumor agnostic, except for group 4 and 6 (CRC patients only). Patients will enroll into one of six groups based on BRAF (groups 1-4) or MEK1/2 (groups 5-6) tumor alteration (38 patients per group). Overall response rate (ORR) is the primary endpoint for Part A, with secondary endpoints including duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Part B is tumor histology specific. Patients will be randomized to receive either ulixertinib or physician's choice of treatment in a 2:1 ratio. Up to three specified tumor histologies will be defined, guided by available Part A data (n = 80-100 per histology). The primary endpoint of Part B is PFS, and secondary endpoints include OS, ORR, and DOR. This study has enrolled 43 patients of the planned 228 in Part A at the time of abstract submission. Clinical trial information: NCT04488003. </jats:p