Towards a flexible and personalised development of veterinarians and veterinary nurses working in a companion animal referral care setting.

In the Netherlands, the demand for veterinarians and veterinary nurses (VNs) working within referral care is rapidly growing and currently exceeds the amount of available board-certified specialists. Simultaneously, a transparent structure to guide training and development and to assess quality of non-specialist veterinarians and VNs working in a referral setting is lacking. In response, we developed learning pathways guided by an entrustable professional activity (EPA) framework and programmatic assessment to support personalised development and competence of veterinarians and VNs working in referral settings. Between 4 and 35 EPAs varying per discipline (n = 11) were developed. To date, 20 trainees across five disciplines have been entrusted. Trainees from these learning pathways have proceeded to acquire new EPAs in addition to their already entrusted set of EPAs or progressed to specialist training during (n = 3) or after successfully completing (n = 1) the learning pathway. Due to their outcome-based approach, the learning pathways support flexible ways of development.

Vertebral Osteosarcoma in Two Cats-Diagnosis, Treatment, and Outcome.

In this case report, we describe the diagnosis, treatment, and outcome of two feline cases of vertebral osteosarcoma. Case 1: A 6-year-old female neutered domestic longhaired cat was presented with progressive paraparesis, ataxia, and spinal hyperesthesia. MRI of the thoracolumbar spinal cord and vertebral column revealed a strongly contrast-enhancing mass lesion originating from the dorsal lamina and spinous process of T13. The lesion caused extradural compression of the spinal cord. Surgical debulking was performed, and the histopathological evaluation of surgical biopsies was consistent with vertebral osteosarcoma. The cat was paraplegic with intact nociception post-surgery. Subsequently, the cat recovered ambulation while remaining mildly ataxic and paraparetic at long-term follow-up. Post-operative chemotherapy was started with doxorubicin. CT scans at 2, 4, 9, 13, and 20 months post-surgery showed no signs of local recurrence or metastasis. Case 2: A 15.5-year-old male neutered domestic shorthaired cat was presented with progressive paraparesis, tail paresis, and spinal hyperesthesia. Radiographs and CT scan of the lumbar vertebral column showed a large mass originating from the dorsal lamina and spinous process of L6, suggestive of neoplasia, with severe compression of the spinal cord. Surgical debulking was performed, and the histopathological evaluation was consistent with vertebral osteosarcoma. Post-operative chemotherapy was started with doxorubicin. Seven months post-surgery, the patient was neurologically normal with no signs of metastatic disease. This case report highlights the possibility of good outcomes after the surgical treatment of feline vertebral osteosarcoma supplemented with post-surgical chemotherapy.

Vaccination against Extracellular Vimentin for Treatment of Urothelial Cancer of the Bladder in Client-Owned Dogs.

It was recently shown that targeting extracellular vimentin (eVim) is safe and effective in preclinical models. Here, we report the safety and efficacy in client-owned dogs with spontaneous bladder cancer of CVx1, an iBoost technology-based vaccine targeting eVim in combination with COX-2 inhibition. This was a single-arm prospective phase 1/2 study with CVx1 in 20 client-owned dogs with spontaneous UC which involved four subcutaneous vaccinations with CVx1 at 2-week intervals for induction of antibody titers, followed by maintenance vaccinations at 2-month intervals. Additionally, daily cyclooxygenase (COX)-2 inhibition with meloxicam was given. The response was assessed by antibody titers, physical condition, abdominal ultrasound and thorax X-ray. The primary endpoints were the development of antibody titers, as well as overall survival compared to a historical control group receiving carboplatin and COX-2 inhibition with piroxicam. Kaplan-Meier survival analysis was performed. All dogs developed antibodies against eVim. Titers were adequately maintained for the duration of this study. A median overall survival of 374 days was observed, which was 196 days for the historical control group (p < 0.01). Short-term grade 1-2 toxicity at the injection site and some related systemic symptoms peri-vaccination were observed. No toxicity was observed related to the induced antibody response. A limitation of this study is the single-arm prospective setting. CVx1 plus meloxicam consistently induced efficient antibody titers, was well tolerated and showed prolonged survival. The results obtained merit further development for human clinical care.

Extracellular vimentin mimics VEGF and is a target for anti-angiogenic immunotherapy.

Anti-angiogenic cancer therapies possess immune-stimulatory properties by counteracting pro-angiogenic molecular mechanisms. We report that tumor endothelial cells ubiquitously overexpress and secrete the intermediate filament protein vimentin through type III unconventional secretion mechanisms. Extracellular vimentin is pro-angiogenic and functionally mimics VEGF action, while concomitantly acting as inhibitor of leukocyte-endothelial interactions. Antibody targeting of extracellular vimentin shows inhibition of angiogenesis in vitro and in vivo. Effective and safe inhibition of angiogenesis and tumor growth in several preclinical and clinical studies is demonstrated using a vaccination strategy against extracellular vimentin. Targeting vimentin induces a pro-inflammatory condition in the tumor, exemplified by induction of the endothelial adhesion molecule ICAM1, suppression of PD-L1, and altered immune cell profiles. Our findings show that extracellular vimentin contributes to immune suppression and functions as a vascular immune checkpoint molecule. Targeting of extracellular vimentin presents therefore an anti-angiogenic immunotherapy strategy against cancer.