Frolicking is greater than colicking: epiploic foramen entrapment in a Warmblood gelding

A 7 year old Warmblood gelding presented to the Cornell Equine Hospital in November of 2012 for acute onset of colic of several hours' duration. At admission, the patient was quiet but appeared painful, tachypneic, and tachycardic with pale mucous membranes. The pain was refractory to alpha-2 agonists and butorphanol. Physical examination revealed absence of gut sounds in all four quadrants. Ultrasound and rectal examination showed multiple dilated and amotile loops of small intestine. The patient was brought to surgery for an exploratory celiotomy. At surgery, approximately 40 feet of small intestine were incarcerated through the epiploic foramen. After careful extraction, a 22-foot-long segment of the incarcerated portion appeared devitalized and was subsequently resected. Since the patient's large colon was impacted with a significant amount of fecal material, an enterotomy was performed and the colonic lumen was evacuated. The patient remained in the hospital for 11 days after his surgery, during which time he was treated with antibiotics, anti-endotoxic agents, plasma, gastroprotectants, and prokinetic medications. He steadily improved and was discharged. He re-presented to Cornell 5 days later with signs of colic, and was discharged after six days of medical management. This report will discuss the progression of this particular case as well as general strategies for managing colic resulting in epiploic foramen entrapmetn of small intestine

Establishing a model system for evaluating CAR T cell therapy using dogs with spontaneous diffuse large B cell lymphoma

Multiple rodent and primate preclinical studies have advanced CAR T cells into the clinic. However, no single model accurately reflects the challenges of effective CAR T therapy in human cancer patients. To evaluate the effectiveness of next-generation CAR T cells that aim to overcome barriers to durable tumor elimination, we developed a system to evaluate CAR T cells in pet dogs with spontaneous cancer. Here we report on this system and the results of a pilot trial using CAR T cells to treat canine diffuse large B cell lymphoma (DLBCL). We designed and manufactured CD20-targeting, second-generation canine CAR T cells for functional evaluation in vitro and in vivo using lentivectors to parallel human CAR T cell manufacturing. A first-in-species trial of five dogs with DLBCL treated with CAR T was undertaken. Canine CAR T cells functioned in an antigen-specific manner and killed CD20+ targets. Circulating CAR T cells were detectable post-infusion, however, induction of canine anti-mouse antibodies (CAMA) was associated with CAR T cell loss. Specific selection pressure on CD20+ tumors was observed following CAR T cell therapy, culminating in antigen escape and emergence of CD20-disease. Patient survival times correlated with ex vivo product expansion. Altering product manufacturing improved transduction efficiency and skewed toward a memory-like phenotype of canine CAR T cells. Manufacturing of functional canine CAR T cells using a lentivector is feasible. Comparable challenges to effective CAR T cell therapy exist, indicating their relevance in informing future human clinical trial design