This study aimed to review currently reported methods of assessing the effects of chemotherapy on the quality of life (QoL) of canine and feline patients and to explore novel ways to assess QoL in such patients in the light of the experience to date in human pediatric oncology. A qualitative comparative analysis of published papers on the effects of chemotherapy on QoL in dogs and cats were conducted. This was supplemented with a comparison of the parameters and domains used in veterinary QoL-assessments with those used in the Pediatric Quality of Life Inventory (PedsQL ) questionnaire designed to assess QoL in toddlers. Each of the identified publications including QoL-assessment in dogs and cats receiving chemotherapy applied a different method of QoL-assessment. In addition, the veterinary QoL-assessments were mainly focused on physical clinical parameters, whereas the emotional (6/11), social (4/11) and role (4/11) domains were less represented. QoL-assessment of cats and dogs receiving chemotherapy is in its infancy. The most commonly reported method to assess QoL was questionnaire based and mostly included physical and clinical parameters. Standardizing and including a complete range of potentially relevant parameters in future QoL assessments may benefit owner decision making.

Fast, extensive and simultaneous cartilage and bone degeneration developed shortly after haemarthrosis, as shown by the detailed mapping of the early pathogenesis of HA. The almost immediate loss of cartilage and the pathological bone turnover suggest a direct influence of blood on these processes and are unlikely to be attributed simply to an indirect effect of inflammation.

Background Haemophilic arthropathy is the main morbidity of haemophilia. The individual pathological response to the same number of clinically evident joint bleeds is highly variable; thus, it remains unknown if certain joint bleeding characteristics are critical for the development of arthropathy. Aim To study the relation between bleed volume and subsequent development of arthropathy, we aimed to develop quantitative in vivo imaging of active joint bleeds in a mouse model of haemophilia. Methods Haemophilia A (F8‐KO) and wild‐type (WT) mice were IV‐dosed with a micro‐CT blood pool contrast agent prior to an induced knee haemarthrosis or sham procedure. The mice were micro‐CT scanned five times the following 2 days to characterise and quantify the induced haemarthrosis in vivo. On Day 14, the mice were euthanized and pathological changes evaluated by histology and micro‐CT. Additionally, bleeding characteristics in vehicle‐treated F8‐KO mice were compared with those of recombinant FVIII (rFVIII)‐treated F8‐KO mice. Results F8‐KO mice had a significantly larger bleed volume than WT mice at all scan time points. The bleed volume 12 hours after induction of haemarthrosis correlated with the subsequent degree of arthropathy. Presence of µCT‐detectable bone pathology was associated with a significantly increased bleed volume among F8‐KO mice. rFVIII treatment significantly reduced bleed volume in F8‐KO mice. Conclusion Quantitative in vivo contrast‐enhanced micro‐CT imaging can be used to characterize and quantify joint bleeds in a mouse model of haemophilic arthropathy. The bleed volume correlates with the subsequent degree of arthropathy.

Introduction:Haemophilic animal models are used to study blood-induced cartilage damage, but quantitative and sensitive outcome measures are needed. Aim:To develop a novel quantitative method for detecting early cartilage degeneration in a haemophilic rat model of blood-induced joint damage. Methods: The 35 Sulphate incorporation ( 35 SO 4 2− assay) was applied to tibial and patellar cartilage of wild-type rats to quantify baseline proteoglycan synthesis and to evaluate the effect of 4-day blood exposure in vitro. Next, haemarthrosis was induced in 39 FVIII-deficient rats and characterized by changes in knee joint diameter and development of bone pathology (using micro-CT). Four-and 16-day posthaemarthrosis proteoglycan synthesis rate (PSR) was assessed using the 35 SO 4 2− assay, with the contralateral knee as control.Results: In vitro, a decrease in PSR in tibial and patellar cartilage was demonstrated following blood exposure. In vivo, joint diameter and development of bone pathology confirmed successful induction of haemarthrosis. In the blood-exposed knee, tibial and patellar PSR was inhibited 4 and 16 days after induced haemarthrosis.Interestingly, at day 16 the proteoglycan synthesis in the contralateral knee was also inhibited to an extent correlating with that of the blood-exposed knee. Conclusion: For the first time, early changes in cartilage matrix synthesis upon blood exposure were quantified with the 35 SO 4 2− assay in a haemophilic rat model, establishing this assay as a novel method to study blood-induced cartilage damage. K E Y W O R D S arthropathies, cartilage, experimental animal models, haemarthrosis, haemophilia | e89 PULLES Et aL.

Background: Haemophilic arthropathy is a chronic and debilitating joint disease caused by recurrent spontaneous joint bleeds in patients with haemophilia. Understanding how characteristics of individual joint bleeds relate to the subsequent development of arthropathy could improve management and prevention of this joint disease. Here, we aimed to explore relations between joint bleed characteristics and development of bone pathology in a mouse model of haemophilic arthropathy by using novel in vivo imaging methodology. Methods: We characterised induced knee bleeds in a murine model of haemophilic arthropathy by quantitative in vivo fluorescence molecular tomography (FMT) and by measurements of changes in the diameter of the injured knee. Wild-type mice and non-injured haemophilic mice acted as controls. Development of arthropathy was characterised by post mortem evaluation of bone pathology by micro-CT 14 days after bleed-induction. In an in vitro study, we assessed the effect of blood on the quantification of fluorescent signal with FMT. Results: In most injured haemophilic mice, we observed significant loss of trabecular bone, and half of the mice developed pathological bone remodelling. Development of pathological bone remodelling was associated with significantly increased fluorescent signal and diameter of the injured knee just 1 day after induction of the bleed. Further, a correlation between the fluorescent signal 1 day after induction of the bleed and loss of trabecular bone reached borderline significance. In the in vitro study, we found that high concentrations of blood significantly decreased the fluorescent signal. Conclusion: Our results add novel insights on the pathogenesis of haemophilic arthropathy and underline the importance of the acute phase of joint bleeds for the subsequent development of arthropathy.

BackgroundHemophilic arthropathy is a debilitating morbidity of hemophilia caused by recurrent joint bleeds. We investigated if the joint bleed volume, before initiation of treatment, was linked to the subsequent degree of histopathological changes and the development of bone pathology in a mouse model of hemophilic arthropathy.MethodsFVIII knock‐out (F8‐KO) mice were dosed with a micro‐CT blood pool agent prior to induction of hemarthrosis. Eight hours after induction, the bleed volume was quantified with micro computed tomography (micro‐CT) and recombinant FVIII treatment initiated. On Day 8, inflammation in the knees was characterized by fluorescence molecular tomography. On Day 14, knee pathology was characterized by micro‐CT and histopathology. In a second study, contrast agent was injected into the knee of wild‐type (WT) mice, followed by histopathological evaluation on Day 14.ResultsThe average joint bleed volume before treatment was 3.9 mm3. The inflammation‐related fluorescent intensities in the injured knees were significantly increased on Day 8. The injured knees had significantly increased synovitis scores, vessel counts, and areas of hemosiderin compared to un‐injured knees. However, no cartilage‐ or bone pathology was observed. The bleed volume before initiation of treatment correlated with the degree of synovitis and was associated with high fluorescent intensity on Day 8. In F8‐KO and WT mice, persistence of contrast agent in the joint elicited morphological changes.ConclusionWhen applying a delayed on‐demand treatment regimen to hemophilic mice subjected to an induced knee hemarthrosis, the degree of histopathological changes on Day 14 reflected the bleed volume prior to initiation of treatment.