Laminitis in equids is a clinical syndrome usually associated with systemic disease. Endocrinopathies recently have been recognized as the most common cause of laminitis, with hyperinsulinemia ...playing a key role. Descriptions of laminitis-associated lesions have been confusing due to the wide range of experimental models used, failure of adequate clinical documentation for naturally occurring cases, lack of separate analysis of inflammatory and endocrinopathic laminitis, and uncertainty regarding normal morphological variation of lamellae. In this study, lamellar morphology and pathology were described in 14 laminitic horses and ponies that had hyperinsulinemia (>20 mIU/l), with reference to 25 age- and breed-matched controls. The type and severity of lesions noted had no correlation with reported clinical duration and in at least some cases must have preceded it. Lesions were largely localized abaxially within the lamellar tissue and included apoptotic cell death, as well as lamellar fusion, hyperplasia, and partial replacement with aberrant keratin containing nucleated debris and proteinaceous lakes. The lesions resulted in irregular margins between the inner horn and the lamellar tissue. Acute separation originated from the abaxial region, with minimal associated inflammation. Axially, epidermal lamellar tapering was the most frequent morphological observation. The lesions in these chronic cases of laminitis were similar to those described in some inflammatory laminitis models and contained features seen in developmental phases of hyperinsulinemic models. These findings support the theory that repeated episodes of subclinical laminitis occur prior to clinical presentation. In addition, the pathology does not include extensive basement membrane failure seen in some inflammatory models.
Saccular intracranial aneurysm is a common disease that may cause devastating intracranial hemorrhage. Hemodynamics, wall remodeling, and wall inflammation have been associated with saccular ...intracranial aneurysm rupture. We investigated how saccular intracranial aneurysm hemodynamics is associated with wall remodeling and inflammation of the saccular intracranial aneurysm wall.
Tissue samples resected during a saccular intracranial aneurysm operation (11 unruptured, 9 ruptured) were studied with histology and immunohistochemistry. Patient-specific computational models of hemodynamics were created from preoperative CT angiographies.
More stable and less complex flows were associated with thick, hyperplastic saccular intracranial aneurysm walls, while slower flows with more diffuse inflow were associated with degenerated and decellularized saccular intracranial aneurysm walls. Wall degeneration (P = .041) and rupture were associated with increased inflammation (CD45+, P = .031). High wall shear stress (P = .018), higher vorticity (P = .046), higher viscous dissipation (P = .046), and high shear rate (P = .046) were associated with increased inflammation. Inflammation was also associated with lack of an intact endothelium (P = .034) and the presence of organized luminal thrombosis (P = .018), though overall organized thrombosis was associated with low minimum wall shear stress (P = .034) and not with the flow conditions associated with inflammation.
Flow conditions in the saccular intracranial aneurysm are associated with wall remodeling. Inflammation, which is associated with degenerative wall remodeling and rupture, is related to high flow activity, including elevated wall shear stress. Endothelial injury may be a mechanism by which flow induces inflammation in the saccular intracranial aneurysm wall. Hemodynamic simulations might prove useful in identifying saccular intracranial aneurysms at risk of developing inflammation, a potential biomarker for rupture.
Aneurysm hemodynamics has been associated with wall histology and inflammation. We investigated associations between local hemodynamics and focal wall changes visible intraoperatively.
Computational ...fluid dynamics models were constructed from 3D images of 65 aneurysms treated surgically. Aneurysm regions with different visual appearances were identified in intraoperative videos: 1) "atherosclerotic" (yellow), 2) "hyperplastic" (white), 3) "thin" (red), 4) rupture site, and 5) "normal" (similar to parent artery), They were marked on 3D reconstructions. Regional hemodynamics was characterized by the following: wall shear stress, oscillatory shear index, relative residence time, wall shear stress gradient and divergence, gradient oscillatory number, and dynamic pressure; these were compared using the Mann-Whitney test.
Hyperplastic regions had lower average wall shear stress (
= .005) and pressure (
= .009) than normal regions. Flow conditions in atherosclerotic and hyperplastic regions were similar but had higher average relative residence time (
= .03) and oscillatory shear index (
= .04) than thin regions. Hyperplastic regions also had a higher average gradient oscillatory number (
= .002) than thin regions. Thin regions had lower average relative residence time (
< .001), oscillatory shear index (
= .006), and gradient oscillatory number (
< .001) than normal regions, and higher average wall shear stress (
= .006) and pressure (
= .009) than hyperplastic regions. Thin regions tended to be aligned with the flow stream, while atherosclerotic and hyperplastic regions tended to be aligned with recirculation zones.
Local hemodynamics is associated with visible focal wall changes. Slow swirling flow with low and oscillatory wall shear stress was associated with atherosclerotic and hyperplastic changes. High flow conditions prevalent in regions near the flow impingement site characterized by higher and less oscillatory wall shear stress were associated with local "thinning" of the wall.
Summary
Background
Arthroscopic optical coherence tomography (OCT) is a promising tool for the detailed evaluation of articular cartilage injuries. However, OCT‐based articular cartilage scoring ...still relies on the operator's visual estimation.
Objectives
To test the hypothesis that semi‐automated International Cartilage Repair Society (ICRS) scoring of chondral lesions seen in OCT images could enhance intra‐ and interobserver agreement of scoring and its accuracy.
Study design
Validation study using equine cadaver tissue.
Methods
Osteochondral samples (n = 99) were prepared from 18 equine metacarpophalangeal joints and imaged using OCT. Custom‐made software was developed for semi‐automated ICRS scoring of cartilage lesions on OCT images. Scoring was performed visually and semi‐automatically by five observers, and levels of inter‐ and intraobserver agreement were calculated. Subsequently, OCT‐based scores were compared with ICRS scores based on light microscopy images of the histological sections of matching locations (n = 82).
Results
When semi‐automated scoring of the OCT images was performed by multiple observers, mean levels of intraobserver and interobserver agreement were higher than those achieved with visual OCT scoring (83% vs. 77% and 74% vs. 33%, respectively). Histology‐based scores from matching regions of interest agreed better with visual OCT‐based scoring than with semi‐automated OCT scoring; however, the accuracy of the software was improved by optimising the threshold combinations used to determine the ICRS score.
Main limitations
Images were obtained from cadavers.
Conclusions
Semi‐automated scoring software improved the reproducibility of ICRS scoring of chondral lesions in OCT images and made scoring less observer‐dependent. The image analysis and segmentation techniques adopted in this study warrant further optimisation to achieve better accuracy with semi‐automated ICRS scoring. In addition, studies on in vivo applications are required.
Background
Clinical and imaging surveillance practices following endovascular aneurysm repair (EVAR) for intact abdominal aortic aneurysm (AAA) vary considerably and compliance with recommended ...lifelong surveillance is poor. The aim of this study was to develop a dynamic prognostic model to enable stratification of patients at risk of future secondary aortic rupture or the need for intervention to prevent rupture (rupture‐preventing reintervention) to enable the development of personalized surveillance intervals.
Methods
Baseline data and repeat measurements of postoperative aneurysm sac diameter from the EVAR‐1 and EVAR‐2 trials were used to develop the model, with external validation in a cohort from a single‐centre vascular database. Longitudinal mixed‐effects models were fitted to trajectories of sac diameter, and model‐predicted sac diameter and rate of growth were used in prognostic Cox proportional hazards models.
Results
Some 785 patients from the EVAR trials were included, of whom 155 (19·7 per cent) experienced at least one rupture or required a rupture‐preventing reintervention during follow‐up. An increased risk was associated with preoperative AAA size, rate of sac growth and the number of previously detected complications. A prognostic model using predicted sac growth alone had good discrimination at 2 years (C‐index 0·68), 3 years (C‐index 0·72) and 5 years (C‐index 0·75) after operation and had excellent external validation (C‐index 0·76–0·79). More than 5 years after operation, growth rates above 1 mm/year had a sensitivity of over 80 per cent and specificity over 50 per cent in identifying events occurring within 2 years.
Conclusion
Secondary sac growth is an important predictor of rupture or rupture‐preventing reintervention to enable the development of personalized surveillance intervals. A dynamic prognostic model has the potential to tailor surveillance by identifying a large proportion of patients who may require less intensive follow‐up.
Potential to tailor surveillance
An 11-yr-old Dressage mare had abnormal gait, and an abscess of the left hoof was suspected but not observed. Radiographic and computerized tomographic evaluations showed a large cystic lesion near ...the apex of the pedal bone, and a smaller, similar lesion at the lateral wing. Sagittal sections through the affected member revealed two intraosseous cysts at the third phalanx. Histologic and histochemical results characterized the lesions as intraosseous epidermoid cysts of the third phalanx.
Summary
Despite the importance of noninfectious joint diseases in equine medicine, little is known about the acute phase response which may be elicited if the local inflammatory process of ...noninfectious arthritis is sufficiently strong, Therefore the aim of this study was to monitor the systemic inflammatory response during experimentally‐induced noninfectious arthritis by studying the dynamics in serum of the acute phase proteins serum amyloid A (SAA), haptoglobin, fibrinogen and α2‐globulins. Twenty‐four Standardbred horses, age 3–7 years, found healthy on thorough clinical, radiological, haematological and serum biochemical examination, were injected aseptically into the right midcarpal joint with amphotericin B. Blood samples were drawn before induction of arthritis (0 h), and at 8, 16, 24, 36 and 48 h postinduction and then on Days 3, 4, 5 and 15 postinduction. All horses developed lameness with joint effusion and joint heat as well as increased respiratory rate, heart rate and body temperature. The lameness started to decline after 24–36 h and, in most animals, systemic signs disappeared on Day 2 postinjection. The concentration of the acute phase proteins increased following induction of arthritis. The SAA concentrations were higher than baseline concentrations from 16 h postinduction and were maximal at 36–48 h (227 times baseline concentration). The haptoglobin concentrations were higher than baseline concentrations from 24 h and were maximal at 48–96 h (1.14 times baseline concentration). The maximal concentrations of fibrinogen were seen between 36–72 h postinjection and increased on average 0.87 times from baseline concentrations. The fibrinogen concentrations were higher than baseline concentrations from 24 h postinjection. α2‐globulins concentrations showed a minor in crease and increased 0.55 times from baseline concentrations. The markers had returned to baseline concentrations by Day 15.
Our results demonstrate that amphotericin B‐induced arthritis in a single joint gives rise to a systemic acute phase response measurable as increased concentrations in serum SAA, haptoglobin, fibrinogen and α2‐globulins during the first 2 weeks of the condition and, thereby, that such an increase need not be indicative of infectious arthritis. Further research should be aimed at determining whether chronic noninfectious arthritis in the horse gives rise to increased acute phase protein concentrations in serum.
Summary
The objective here was to evaluate the acute effects of induced arthritis on synovial fluid (SF) levels of matrix metalloproteinases (MMP) ‐2, ‐8 and ‐9 in horses. To evaluate MMP‐2 and ‐9 ...activities and the effect of non‐steroidal anti‐inflammatory drug (NSAID) bufexamac during remission from acute arthritis. Aseptic arthritis was induced in 24 Standardbred horses using 20 mg of amphotericin B as a single intra‐articular (IA) injection in the right intercarpal joint. After 1 week and 2 weeks, horses were treated intra‐articularly with 10, 20, or 40 mg of bufexamac suspension or with sterile saline solution as control. SF was sampled prior to induction and at weekly intervals for 5 weeks. Fluids were evaluated for MMP‐2 and MMP‐9 activity by gelatin zymography or for MMP‐8 immunoreactivity by Western Blotting. IA injection of amphotericin B consistently resulted in significant increase in the immunoreactivity of MMP‐8 and activity of both the latent and the active forms of MMP‐2 and ‐9, among which the active form of MMP‐2 increased the most. MMP‐9 levels declined to pre‐induction levels within 2 weeks, whereas levels of MMP‐2 remained still high after 5 weeks. Treatment with bufexamac did not significantly affect levels of gelatinolytic MMP. Results suggest that after acute arthritis of horses, elevated MMP activity is present in the joint, for several weeks, to a degree that could promote cartilage degradation, and treatment with the NSAID bufexamac is not likely to affect that. Furthermore, analysing levels of MMP‐9 activity and especially levels of active forms of MMP‐2 activity may be valuable to predict the time of occurrence of arthritis in horses.
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