Inflammation-induced haemostatic response in layer chickens infected with Streptococcus equi subsp. zooepidemicus as evaluated by fibrinogen, prothrombin time and thromboelastography.

Streptococcus zooepidemicus has recently been shown to be a severe pathogen in layer chickens, where it is able to cause serious lesions in the vascular system. To evaluate the haemostatic response, 10 layer chickens were inoculated intravenously with S. zooepidemicus. Four hypotheses were tested: that the infection-induced inflammation would increase the plasma fibrinogen (Fbg) concentration, would prolong the prothrombin time (PT) and would prompt hypercoagulability or hypocoagulability as assessed by whole-blood thromboelastography (TEG), and that a possible correlation would exist between one of the TEG values and Fbg/PT. Each parameter was measured at days 1, 3 and 6 post inoculation (p.i.), and compared with the values at day 0 from each individual bird and with values obtained from non-infected control chickens (n = 10). In the infected chickens, the mean (± standard error) of Fbg was higher at day 3 p.i. (9.4 ± 1.4 g/l) and day 6 p.i. (8.0 ± 0.7 g/l) and the PT was prolonged at day 6 p.i. (168.1 ± 21.0 sec) compared with the day 0 standards (2.6 ± 0.2 g/l and 104.6 ± 2.0 sec, respectively) (P < 0.05). The majority of infected chickens demonstrated a hypercoagulable TEG result with increased mean values of the clot formation rate (α-angle) and maximal amplitude (MA) of TEG tracing at day 3 p.i. (83.1 ± 0.7°, 83.8 ± 1.4 mm) and day 6 p.i. (84.0 ± 0.4°, 89.8 ± 1.0 mm) compared with the day 0 values (75.8 ± 2.2° and 66.9 ± 1.4 mm, respectively) (P < 0.05). In control birds, the means of Fbg (1.5 ± 0.1 g/l), PT (79.4 ± 6.4 sec), TEG-α (76.7 ± 1.5°) and TEG-MA (64.0 ± 2.3 mm) were lower at day 6 compared with values observed for the infected chickens (P < 0.05). A negative correlation coefficient (-0.71) was found between the clot formation time (TEG-K) and Fbg at day 1 in the control group (P = 0.02). In conclusion, infection with S. zooepidemicus following intravenous injection in layer chickens induced haemostatic alterations including hyperfibrinogenaemia, prolonged PT, and hypercoagulability as measured by increased TEG-α and TEG-MA.

Danish dog owners' use and the perceived effect of unlicensed cannabis products in dogs.

The interest in the use of medical cannabis has increased in recent years in both human and veterinary fields. In Denmark, there are no veterinary-licensed medical cannabis or cannabinoid supplements, and it is illegal to prescribe or sell cannabinoids intended for the treatment of veterinary patients. This study aimed to explore the unlicensed cannabinoid use in Danish dogs, by questioning dog owners about usage, indication for use, way of purchase, and their perceived effect of the cannabinoid treatment. An anonymous online survey was distributed via social media. The total number of respondents were 2,002, of which 38% indicated using or having administered cannabinoids to their dog. The majority of the respondents confirming the use of cannabinoids (93%) had used cannabidiol drops/oil and only few (4%) reported using Δ9-tetrahydrocannabinol-based products. Most owners (67%) purchased the products online. The three most common indications for use were pain alleviation, behavioural issues, and allergy. When asked about the respondent-perceived effect the majority reported a good or very good effect. The indication with the highest percentage of owner-perceived positive effect (77%) was pain alleviation. This study shows that, despite no licensed veterinary cannabinoid products being available in Denmark, dog owners do supplement their dogs with cannabinoids and the majority of these perceive that the treatment had a positive effect. This supports the need for more evidence-based knowledge in veterinary cannabinoid therapy.

Noninvasive Molecular Imaging of the Enhanced Permeability and Retention Effect by 64Cu-Liposomes: In vivo Correlations with 68Ga-RGD, Fluid Pressure, Diffusivity and 18F-FDG.

BACKGROUND: The accumulation of liposome encapsulated chemotherapy in solid cancers is dependent on the presence of the enhanced permeability and retention (EPR) effect. Positron emission tomography (PET) imaging with a liposome encapsulated radioisotope, such as liposome encapsulated Cu-64 (64Cu-liposome) may help to identify tumors with high liposome accumulation, and thereby stratify patients based on expected benefit from liposomal chemotherapy. However, intravenous administration of liposomes without a cytotoxic content is complicated by the accelerated blood clearance (ABC) phenomenon for succeeding therapeutic liposome dosing. Alternative markers for assessing the tumor's EPR level are therefore warranted. MATERIALS AND METHODS: To increase our understanding of EPR variations and to ultimately identify an alternative marker for the EPR effect, we investigated the correlation between 64Cu-liposome PET/CT (EPR effect) and 68Ga-RGD PET/CT (neoangiogenesis), 18F-FDG PET/CT (glycolysis), diffusion-weighted MRI (diffusivity) and interstitial fluid pressure in two experimental cancer models (CT26 and COLO 205). RESULTS: 64Cu-liposome and 68Ga-RGD SUVmax displayed a significant moderate correlation, however, none of the other parameters evaluated displayed significant correlations. These results indicate that differences in neoangiogenesis may explain some EPR variability, however, as correlations were only moderate and not observed for SUVmean, 68Ga-RGD is probably insufficient to serve as a stand-alone surrogate marker for quantifying the EPR effect and stratifying patients.

Thromboelastography-guided transfusion in dogs with hypocoagulable disorders: a case series.

BACKGROUND: Thromboelastography (TEG) is a global whole blood hemostasis assay which includes plasma as well as cellular components of hemostasis in the analysis and follows the quality and dynamics of clot development, stabilization, and lysis. In human medicine TEG is also a valuable asset in the therapeutic setting, allowing evaluation of the effect of transfusion therapy in vitro. This case series describes the use of TEG as a guiding tool for transfusion therapy in four dogs with hypocoagulable hemostatic disorders. CASE PRESENTATION: Four dogs presented with hypocoagulable disorders of hemostasis, diagnosed as rodenticide intoxication, angiostrongylosis, disseminated intravascular coagulation following severe systemic inflammation, and immune-mediated thrombocytopenia, respectively. TEG was used as a diagnostic tool as well as a guiding tool in the decision of whether or not, and in what dose, fresh frozen plasma would be of benefit in the treatment protocol for each dog. CONCLUSIONS: TEG may be applied in the therapeutic setting as a means to tailor individual patient transfusion therapy in critically ill dogs with hypocoagulable states.

D-Dimer Concentrations and Thromboelastography in Five Dogs With Ischemic Stroke.

Ischemic stroke is a condition increasingly recognized in dogs; however, the number of publications on dogs with ischemic stroke is still limited and hemostatic parameters are infrequently reported. D-dimer levels have been shown to be elevated in people with acute ischemic stroke compared to a healthy control population and it has been proposed that a normal D-dimer can be used to exclude thromboembolism in dogs. In this case series, we report hemostatic parameters, including D-dimer and thromboelastography (TEG) along with clinical and imaging findings for five dogs diagnosed with ischemic stroke. All dogs had a normal D-dimer concentration on presentation. A hypercoagulable state was identified in two dogs based on the results of the TEG, and was suspected in the remaining three cases based on a shortened TEG clot reaction time. Based on the findings in the present cases, a D-dimer within the normal reference range does not seem an appropriate negative predictor for canine ischemic stroke. The demonstration of a possible hypercoagulable state, as identified by the TEG, is an interesting finding which should be explored further to help reveal predisposing hypercoagulable conditions in dogs with ischemic stroke.

Veterinarians' role in clients' decision-making regarding seriously ill companion animal patients.

BACKGROUND: When companion animals become seriously ill clients may have doubts about treatment choices, if any, and turn to veterinarians for help. But how should veterinarians reply? Influence on clients' decision-making may or may not be acceptable-depending on one's attitude to principles such as 'paternalism', 'respect for autonomy' and 'shared decision-making'. This study takes as a starting point a situation where the animal is chronically ill, or aged, with potentially reduced animal welfare and client quality of life, and thus where clients need to consider treatment options or euthanasia. It is assumed throughout that both veterinarians and clients have the animals' best interest at heart. The purpose of the study was to explore the challenges these situations hold and to investigate how clients experience veterinary influence. A second aim was to reflect on the ethical implications of the role of veterinarians in these situations. Qualitative interviews were conducted with 12 dog owners considering treatment or euthanasia of their chronically ill or aged dogs. RESULTS: Challenges relating to the dog and to the client were identified. Some situations left the interviewees hesitant, e.g. if lacking a clear cut-off point, the dog appeared normal, the interviewee felt uncertain about treatments or animal welfare, or experienced conflicting concerns. Some interviewees found that veterinarians could influence their decisions. Such influence was received in different ways by the interviewees. Some interviewees wanted active involvement of the veterinarian in the decision-making process, and this may challenge a veterinarian's wish to respect client autonomy. CONCLUSIONS: Different preferences are likely to exist amongst both veterinarians and clients about veterinary involvement in clients' decision-making, and such preferences may vary according to the situation. It is suggested, that one way to handle this challenge is to include respect for client preference on veterinary involvement under a wider understanding of respect for autonomy, and to apply models of shared decision-making to veterinary practice. In any case there is a need to further explore the challenges these situations raise, and for the veterinary profession to engage in more formal and structured deliberation over the role of veterinarians in relation to clients' decision-making.

[Canine cancer patients are included in translational research]. / Hunde med spontan cancer indgår i translationel forskning

Cancer bearing dogs represent a unique clinical cancer model with a direct potential for accelerating translation into human patients. A research collaboration between the veterinary and human medical facilities at Copenhagen University and Rigshospitalet has taken offset in this. Canine cancer patients are implemented for development of new strategies in molecular imaging and radiotherapy. The obtained results will be used to guide human clinical trials.

Dose painting based on tumor uptake of Cu-ATSM and FDG: a comparative study.

BACKGROUND: Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The purpose of this study was to investigate differences in radiotherapy (RT) dose painting based on the uptake of 2-deoxy-2-[(18) F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer, copper(II)diacetyl-bis(N(4))-methylsemithiocarbazone (Cu-ATSM) using spontaneous clinical canine tumor models. METHODS: Positron emission tomography/computed tomography scans of five spontaneous canine sarcomas and carcinomas were obtained; FDG on day 1 and (64)Cu-ATSM on day 2 and 3 (approx. 3 and 24 hours pi.). Sub-volumes for dose escalation were defined by a threshold-based method for both tracers and five dose escalation levels were formed in each sub-volume. Volumetric modulated arc therapy plans were optimized based on the dose escalation regions for each scan for a total of three dose plans for each dog. The prescription dose for the GTV was 45 Gy (100%) and it was linearly escalated to a maximum of 150%. The correlations between dose painting plans were analyzed with construction of dose distribution density maps and quality volume histograms (QVH). Correlation between high-dose regions was investigated with Dice correlation coefficients. RESULTS: Comparison of dose plans revealed varying degree of correlation between cases. Some cases displayed a separation of high-dose regions in the comparison of FDG vs. (64)Cu-ATSM dose plans at both time points. Among the Dice correlation coefficients, the high dose regions showed the lowest degree of agreement, indicating potential benefit of using multiple tracers for dose painting. QVH analysis revealed that FDG-based dose painting plans adequately covered approximately 50% of the hypoxic regions. CONCLUSION: Radiotherapy plans optimized with the current approach for cut-off values and dose region definitions based on FDG, (64)Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that (64)Cu-ATSM at two different time-points and FDG provide different biological information that has to be taken into account when using the dose painting strategy in radiotherapy treatment planning.