Acetabular margin changes in feline hip joints-Implications for radiologic diagnosis and development of osteoarthritis

The development and early morphological features of feline hip osteoarthritis (OA) are largely unknown. Tears in the acetabular labrum and at the chondrolabral transition zone are suggested to be important in the pathogenesis of human hip OA, but in cats such lesions have not been described. We investigated associations between computed tomography (CT)-detected joint changes and microscopic articular cartilage lesions, the distribution of detected changes, and histologically evaluated the acetabular margin (AM) in hip joints from 20 cats. Histologic evaluation was undertaken on at least one joint from each cat. CT-detected joint changes and articular cartilage lesions were graded and the histological appearance of CT-detected osteophytes evaluated. The majority of CTdetected lesions and cartilage lesions were mild. Whole-joint CT scores and AM osteophyte CT scores showed moderate to strong correlation with cartilage scores. The odds were higher for presence of CT-detected osteophytes in craniodorsal, cranial, cranioventral, ventral and dorsal AM regions. Peripheral acetabular regions showed higher cartilage lesion grades than central regions. Tears, seen as fissures/clefts, in labral and perilabral tissues were common. CT-detected AM osteophytes morphologically presented as pointed sclerotic bone, spurshaped bone or rounded chondro-osteophytes. The results suggest that CT is a valuable tool for diagnosing early feline hip OA. CT-detected osteophytes showed variable histologic morphologies, which may implicate different disease mechanisms and/or disease stages. Tears in the AM could represent an early event in feline hip OA and this warrants further investigation

Falciform fat:femur length ratio provides a novel method for objective postmortem estimation of total body fat in overweight and obese cats

Determination of the nutritional condition, including estimation of amounts of total body fat (tBF), at routine postmortem examination of cats is typically based on subjective visual assessment. Subjective assessment may result in uncertainties regarding degree of overweight, and objective methods that provide a numerical value reflecting the tBF could be valuable to accurately judge excess body fat. We investigated if the falciform fat pad weight (FFPW) was correlated to tBF and could be used to detect overweight and obesity in cats. The FFPW and the femur length (FL) were recorded at postmortem examination in 54 cats and the FFPW:FL ratio (FFR) calculated. Each cat was additionally assigned to a fat category (FC) according to subjective assessment. Computed tomography was used to determine tBF as the body fat percentage (%BF), the body fat volume (BFV), and BFV normalized to animal size (nBFV) in 39 cats. There was strong correlation between the FFPW and the BFV (r = 0.888) and between the FFR and the nBFV (r = 0.897). The correlation between the nBFV and %BF was very strong (r = 0.974). Using a lower FFR cutoff value of 3.5 for obesity and 1.6 for overweight, there was a discrepancy in FC between using the FFR and subjective assessment in 6 of 54 cats (11%). We conclude that the FFPW increases proportionally with tBF and that the FFR provides a method for objective tBF estimation. We suggest introducing the FFR to feline postmortem examination protocols as an objective estimate of tBF

Navicular bone location in radiographs and solar scintigrams

The anatomical location of the navicular bone region in the solar projection scintigram has not been clearly established and it is often not possible to define the navicular bone in solar projection bone phase scintigrams. This is due to the relatively poor anatomical detail of scintigrams. In contrast, skeletal radiology has high spatial and contrast resolutions and skeletal structures can be well defined, however radiology does not provide the functional information that scintigraphy does. Techniques using quantitative analysis of scintigrams, particularly the navicular bone region in the solar scintigram, seem to be becoming more popular. For these techniques to be reliable, correct positioning of regions of interest or profiles is essential, and this requires accurate location of anatomical structures. Superimposition of the proximal interphalangeal joint region on the navicular bone region in the solar projection scintigram is a recognised problem when evaluating the palmar regions of the foot for abnormal areas of radiopharmaceutical uptake, and this superimposition could result in incorrect interpretation of the radiopharmaceutical uptake in a navicular bone region of interest. It was hypothesised that landmarks in the solar projection scintigram could be used to locate the navicular bone region and that there would be the least superimposition of the proximal interphalangeal joint region on the navicular bone region when the interphalangeal joints were flexed. Measurements were taken from radiographs of specimen horse legs to determine if the navicular bone moved relative to the distal phalanx when the leg position was changed. Using both specimen horse legs and live horses radiographs were examined to investigate the navicular bone position relative to landmarks on the distal phalanx. Radiographs of specimen horse legs were taken with the legs positioned in maximum interphalangeal joint flexion, maximum interphalangeal joint extension and a fixed angle (50º), and the degree of overlap of the proximal interphalangeal joint region and the navicular bone region was measured. Leg positioning did not change the position of the navicular bone relative to the distal phalanx in a dorsal to palmar plane. Very little variation existed between individuals in: the ratio of the distance from the dorsodistal margin of the distal phalanx to the dorsal margin of the navicular bone (P3-Navicular) compared to the dorsopalmar length of the navicular bone (Navicular length), the ratio between the maximum lateral width (P3 width) of the distal phalanx and P3-Navicular, and the ratio between P3 width and the maximum lateral width of the navicular bone (Navicular width). In contrast, large variation existed in the ratio of the distance from the palmar aspect of the palmar processes to the palmar aspect of the navicular bone (Navicular-PP), compared to Navicular length. Positioning the pastern in maximum flexion resulted in the least overlap of the proximal interphalangeal joint and navicular regions. It is recommended that the phalanges are flexed and the sole is placed flat on a raised horizontal gamma camera when the solar projection is acquired. The measurement ratios of the distal phalanx and the navicular bone were applied to a solar projection scintigram to predict navicular bone position and position a navicular bone region of interest using anatomical landmarks that could be distinctly identified in the scintigram

Imaging of early distal tarsal osteoarthritis in Icelandic horses

The early stages of osteoarthritis (OA) are characterised by focal morphological changes that may slowly progress if joint repair fails. Validated, non-invasive and affordable methods to diagnose the early stage of OA in horses are lacking. The objectives of this thesis were to investigate and validate OA detection methods, and describe the morphological OA changes in the distal tarsal region of a group of young Icelandic horses. Radiography, computed tomography (CT) and magnetic resonance imaging (MRI), light microscopy histology, backscattered electron scanning electron microscopy, and confocal scanning light microscopy were used to investigate osteochondral changes in the joints of the distal tarsal region in 38 two-and-a-half year old Icelandic horses. Radiographs were taken of live horses standing, all other examinations were performed 2-3 months later on non-weight bearing cadaver specimens from the same horses. The results showed that a novel CT and MRI guidance method for osteochondral tissue sample collection improved detection of early OA changes in centrodistal (distal intertarsal) joints compared to standardised sample collection from predetermined locations. Diagnostic imaging and microscopy showed that early OA morphological changes primarily occur in the articular hyaline and calcified cartilage rather than the subchondral bone. The lesions articular mineralisation front defect, central osteophytes and hyperdense mineralisation front protrusions were described in detail in the joints of the distal tarsal region using combined microscopic imaging of embedded block specimens. A comparison of clinical diagnostic imaging methods found that radiography was equal or better than low-field MRI for the detection of early OA in centrodistal joints. Articular mineralisation front defects were identified as a highly specific imaging feature in radiographs for early OA. This thesis provides a detailed morphological description of the osteochondral changes occurring in the early stages of OA in the centrodistal joint of Icelandic horses and proposes a validated, non-invasive, cost-effective radiography method for proceeding with future longitudinal studies of early OA in Icelandic horses

Osteochondral lesions in distal tarsal joints of Icelandic horses reveal strong associations between hyaline and calcified cartilage abnormalities

Osteochondral lesions in the joints of the distal tarsal region of young Icelandic horses provide a natural model for the early stages of osteoarthritis (OA) in low-motion joints. We describe and characterise mineralised and non-mineralised osteochondral lesions in left distal tarsal region joint specimens from twenty-two 30 ±1 month-old Icelandic horses. Combinations of confocal scanning light microscopy, backscattered electron scanning electron microscopy (including, importantly, iodine staining) and three-dimensional microcomputed tomography were used on specimens obtained with guidance from clinical imaging. Lesion-types were described and classified into groups according to morphological features. Their locations in the hyaline articular cartilage (HAC), articular calcified cartilage (ACC), subchondral bone (SCB) and the joint margin tissues were identified and their frequency in the joints recorded. Associations and correlations between lesion-types were investigated for centrodistal joints only. In centrodistal joints the lesion-types HAC chondrocyte loss, HAC fibrillation, HAC central chondrocyte clusters, ACC arrest and ACC advance had significant associations and strong correlations. These lesion-types had moderate to high frequency in centrodistal joints but low frequencies in tarsometatarsal and talocalcaneal-centroquartal joints. Joint margin lesion-types had no significant associations with other lesion-types in the centrodistal joints but high frequency in both the centrodistal and tarsometatarsal joints. The frequency of SCB lesion-types in all joints was low. Hypermineralised infill phase lesion-types were detected. Our results emphasise close associations between HAC and ACC lesions in equine centrodistal joints and the importance of ACC lesions in the development of OA in low-motion compression-loaded equine joints

Osteochondrosis in the central and third tarsal bones of young horses

Recently, the central and third tarsal bones of 23 equine fetuses and foals were examined using micro-computed tomography. Radiological changes, including incomplete ossification and focal ossification defects interpreted as osteochondrosis, were detected in 16 of 23 cases. The geometry of the osteochondrosis defects suggested they were the result of vascular failure, but this requires histological confirmation. The study aim was to examine central and third tarsal bones from the 16 cases and to describe the tissues present, cartilage canals, and lesions, including suspected osteochondrosis lesions. Cases included 9 males and 7 females from 0 to 150 days of age, comprising 11 Icelandic horses, 2 standardbred horses, 2 warmblood riding horses, and 1 coldblooded trotting horse. Until 4 days of age, all aspects of the bones were covered by growth cartilage, but from 105 days, the dorsal and plantar aspects were covered by fibrous tissue undergoing intramembranous ossification. Cartilage canal vessels gradually decreased but were present in most cases up to 122 days and were absent in the next available case at 150 days. Radiological osteochondrosis defects were confirmed in histological sections from 3 cases and consisted of necrotic vessels surrounded by ischemic chondronecrosis (articular osteochondrosis) and areas of retained, morphologically viable hypertrophic chondrocytes (physeal osteochondrosis). The central and third tarsal bones formed by both endochondral and intramembranous ossification. The blood supply to the growth cartilage of the central and third tarsal bones regressed between 122 and 150 days of age. Radiological osteochondrosis defects represented vascular failure, with chondrocyte necrosis and retention, or a combination of articular and physeal osteochondrosis

Enterorhabdus caecimuris sp. nov., a member of the family Coriobacteriaceae isolated from a mouse model of spontaneous colitis, and emended description of the genus Enterorhabdus Clavel et al. 2009

The C3H/HeJBir mouse model of intestinal inflammation was used for isolation of a Gram-positive, rod-shaped, non-spore-forming bacterium (B7T) from caecal suspensions. On the basis of partial 16S rRNA gene sequence analysis, strain B7T was a member of the class Actinobacteria, family Coriobacteriaceae, and was related closely to Enterorhabdus mucosicola Mt1B8T (97.6 %). The major fatty acid of strain B7T was C16 : 0 (19.1 %) and the respiratory quinones were mono- and dimethylated. Cells were aerotolerant, but grew only under anoxic conditions. Strain B7T did not convert the isoflavone daidzein and was resistant to cefotaxime. The results of DNA–DNA hybridization experiments and additional physiological and biochemical tests allowed the genotypic and phenotypic differentiation of strain B7T from the type strain of E. mucosicola. Therefore, strain B7T represents a novel species, for which the name Enterorhabdus caecimuris sp. nov. is proposed. The type strain is B7T (=DSM 21839T =CCUG 56815T)

Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma

Head and neck cell squamous-cell carcinomas (HNSCC) are a group of common cancers typically associated with tobacco use and human papilloma virus infection. Up to half of all cases will suffer a recurrence after primary treatment. As such, new therapies are needed, including therapies which promote the anti-tumor immune response. Prior work has characterized changes in the mutation burden between primary and recurrent tumors; however, little work has characterized the changes in neoantigen evolution. We characterized genomic and neoantigen changes between 23 paired primary and recurrent HNSCC tumors. Twenty-three biopsies from patients originally diagnosed with locally advanced disease were identified from the Washington University tumor bank. Whole exosome sequencing, RNA-seq, and immunohistochemistry was performed on the primary and recurrent tumors. Within these tumors, we identified 6 genes which have predicted neoantigens in 4 or more patients. Interestingly, patients with neoantigens in these shared genes had increased CD3+ CD8+ T cell infiltration and duration of survival with disease. Within HNSCC tumors examined here, there are neoantigens in shared genes by a subset of patients. The presence of neoantigens in these shared genes may promote an anti-tumor immune response which controls tumor progression

Osteochondrosis, Synovial Fossae, and Articular Indentations in the Talus and Distal Tibia of Growing Domestic Pigs and Wild Boars

Articular osteochondrosis (OC) often develops in typical locations within joints, and the characterization of OC distribution in the pig tarsus is incomplete. Prevalence of OC is high in domestic pigs but is presumed to be low in wild boars. Postmortem and computed tomography (CT) examinations of the talus and distal tibia from 40 domestic pigs and 39 wild boars were evaluated for the locations and frequencies of OC, synovial fossae, and other articular indentations, and frequency distribution maps were made. All domestic pigs but only 5 wild boars (13%) had OC on the talus. In domestic pigs, OC consistently affected the axial aspect of the medial trochlea tali in 11 (28%) joints and the distomedial talus in 26 (65%) joints. In wild boars, all OC lesions consistently affected the distomedial talus. On the articular surface of the distal tibia, all domestic pigs and 34 wild boars (87%) had synovial fossae and 7 domestic pigs (18%) had superficial cartilage fibrillation opposite an OC lesion (kissing lesion). Other articular indentations occurred in the intertrochlear groove of the talus in all domestic pigs and 13 wild boars (33%) and were less common on the trochlea tali. The prevalence of tarsal OC in wild boars is low. In domestic pigs and wild boars, OC is typically localized to the distomedial talus and in domestic pigs also to the medial trochlea tali. Further investigations into the reasons for the low OC prevalence in wild boars may help in developing strategies to reduce OC incidence in domestic pigs