Background: Rodent cancer models have limitations in predicting efficacy, tolerability and accompanying biomarkers of ICIs in humans. Companion dogs suffering from neoplastic diseases have gained attention as a highly relevant translational disease model. Despite successful reports of PD-1/PD-L1 blockade in dogs, no compounds are available for veterinary medicine. Methods: Here, we assessed suitability of seven FDA-approved human ICIs to target CTLA-4 or PD-1/PD-L1 in dogs. Cross-reactivity and blocking potential was assessed using ELISA and flow cytometry. Functional responses were assessed on peripheral blood mononuclear cells (PBMCs) derived from healthy donors (n = 12) and cancer patient dogs (n = 27) as cytokine production after stimulation. Immune composition and target expression of healthy donors and cancer patients was assessed via flow cytometry. Results: Four candidates showed cross-reactivity and two blocked the interaction of canine PD-1 and PD-L1. Of those, only atezolizumab significantly increased cytokine production of healthy and patient derived PBMCs in vitro. Especially lymphoma patient PBMCs responded with increased cytokine production. In other types of cancer, response to atezolizumab appeared to correlate with a lower frequency of CD8 T cells. Conclusions: Cross-functionality of atezolizumab encourages reverse translational efforts using (combination) immunotherapies in companion dog tumor patients to benefit both veterinary and human medicine.

Companion dogs are increasingly recognized as large-animal models of diseases such as cancer, infectious-, inflammatory-, or autoimmune diseases. At the same time, compared to human clinics, veterinarians have only a fraction of the treatment options available. To study the immunological aspects of canine diseases and ultimately develop or adapt human treatments for the dog, the methodology also needs to be in place. Such tools include robust and reliable flow cytometric panels. The purpose of the panel described here is to assess the immune cell composition and their functionality in the peripheral blood mononuclear cells (PBMCs) of dogs. Moreover, its "plug and play" composition allows for an in-depth analysis of T-cell responses in ex vivo assays (Table 1). Initially, this panel has been designed for the analysis of cryopreserved PBMCs to allow batched analysis and to reduce interexperimental variation. Withers and colleagues published a comparable and-to our knowledge-currently the most extensive canine panel to date (1). While their study focused on the aging and activation status of T cells in dogs, our panel is designed to look at a broader range of cells with a higher number of markers. This allows a more in-depth analysis of functional extracellular and intracellular markers. In addition, all antibodies in our proposed panel are directly labeled. In combination with suitable lymphocyte isolation protocols, this panel could potentially also be adapted to analyze tissue biopsies from various different organs.

Anaesthetic drugs are commonly used during the evaluation of laryngeal function in dogs. The aim of this review was to systematically analyse the literature describing the effects of anaesthetic drugs and doxapram on laryngeal motion in dogs and to determine which drug regime provides the best conditions for laryngeal examination. PubMed, Google Scholar, and EMBASE databases were used for the literature search up to November 2019. Relevant search terms included laryngeal motion, anaesthetic drugs and dogs. Studies were scored based on their level of evidence (LoE), according to the Oxford Centre for Evidence-based Medicine, and the quality was assessed using the risk-of-bias tool and SIGN-checklist. In healthy dogs, premedication before laryngeal examination provided better examination conditions and maintained overall adequate laryngeal motion in 83% of the studies. No difference in laryngeal motion between induction drugs was found in 73% of the studies but the effects in dogs with laryngeal paralysis remain largely unknown. Doxapram increased laryngeal motion in healthy dogs without serious side effects, but intubation was necessary for some dogs with laryngeal paralysis. Methodological characteristics varied considerably between studies, including the technique and timing of evaluation, number of assessors, study design, drug dose, combinations, route and speed of administration.

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A 17-year-old, 550-kg, neutered male Oldenburger horse was referred for an exploratory coeliotomy after acute collapse, profuse sweating and abdominal pain refractory to conventional analgesics. Clinical evaluation was only possible under sedation and revealed pale mucous membranes, tachypnoea, tachycardia with irregular heart rhythm and distended small intestines with decreased motility. Preoperative blood testing revealed severe hyperlactataemia and hyperglycaemia, whereas an abdominocentesis showed evidence of haemoperitoneum. Under general anaesthesia, polymorphic tachyarrhythmias, hypotension, peripheral oedema, persistent hyperlactataemia, electrolyte imbalances and haemorrhage complicated the anaesthetic management of this case. Despite cardiovascular support, including administration of fluid therapy, inotropes, 3.5 litres of fresh whole blood and 5 litres of fresh frozen plasma, the horse did not recover from general anaesthesia. A pheochromocytoma of the left adrenal gland with parenchymal rupture and haemorrhage was diagnosed postmortem. The present report describes the anaesthetic challenges of an undiagnosed pheochromocytoma in a horse with colic.