The impact of a significant weight loss on inflammation assessed on DCE-MRI and static MRI in knee osteoarthritis: a prospective cohort study.

OBJECTIVE: To study the impact of weight loss on inflammation in individuals with overweight and knee osteoarthritis (OA) using both static- and dynamic contrast-enhanced (DCE)-MRI and assess the association of these changes to pain. DESIGN: Individuals with overweight (BMI > 27) and knee OA were examined before and after a >5% weight loss over 8 weeks (ClinicalTrials.gov NCT02905864). Using 3-T MRI, inflammation was quantified from non-contrast enhanced static-MRI according to MOAKS and contrast enhanced static MRI according to BLOKS and 11-point whole-knee synovitis score. DCE-MRI was used to assess the inflammation in the infra patellar fat pad (IPFP). Pain was assessed using KOOS. RESULTS: Complete data were available in 117 participants with a mean age of 60 years, BMI of 35 kg/m2 and KOOS pain score of 64. Mean weight loss was 12 kg and KOOS pain was improved by 13 points at follow-up. Change in inflammation was not associated with weight loss in static MRI. None of the MRI variables correlated with the change in KOOS pain. CONCLUSION: Weight loss did not induce a significant change in inflammation in individuals with overweight and OA. The significant clinical beneficial effect of weight loss on knee pain in individuals with overweight and knee OA seems uncoupled to changes in imaging markers of synovitis.

Transanal total mesorectal excision for rectal cancer has been suspended in Norway.

BACKGROUND: Transanal total mesorectal excision (TaTME) for rectal cancer has emerged as an alternative to the traditional abdominal approach. However, concerns have been raised about local recurrence. The aim of this study was to evaluate local recurrence after TaTME. Secondary aims included postoperative mortality, anastomotic leak and stoma rates. METHODS: Data on all patients who underwent TaTME were recorded and compared with those from national cohorts in the Norwegian Colorectal Cancer Registry (NCCR) and the Norwegian Registry for Gastrointestinal Surgery (NoRGast). Kaplan-Meier estimates were used to compare local recurrence. RESULTS: In Norway, 157 patients underwent TaTME for rectal cancer between October 2014 and October 2018. Three of seven hospitals abandoned TaTME after a total of five procedures. The local recurrence rate was 12 of 157 (7·6 per cent); eight local recurrences were multifocal or extensive. The estimated local recurrence rate at 2·4 years was 11·6 (95 per cent c.i. 6·6 to 19·9) per cent after TaTME compared with 2·4 (1·4 to 4·3) per cent in the NCCR (P < 0·001). The adjusted hazard ratio was 6·71 (95 per cent c.i. 2·94 to 15·32). Anastomotic leaks resulting in reoperation occurred in 8·4 per cent of patients in the TaTME cohort compared with 4·5 per cent in NoRGast (P = 0·047). Fifty-six patients (35·7 per cent) had a stoma at latest follow-up; 39 (24·8 per cent) were permanent. CONCLUSION: Anastomotic leak rates after TaTME were higher than national rates; local recurrence rates and growth patterns were unfavourable.

ANTECEDENTES: La resección total del mesorrecto transanal (transanal total mesorectal excision, TaTME) para el cáncer de recto se ha propuesto como una alternativa al abordaje abdominal tradicional. Sin embargo, la recidiva local (local recurrence, LR) después de este procedimiento es motivo de preocupación. El objetivo de este estudio fue evaluar la LR en pacientes operados mediante TaTME. Los objetivos secundarios incluyeron la mortalidad postoperatoria, las fugas anastomóticas y el porcentaje de estomas. MÉTODOS: Se registraron los datos de todos los pacientes operados mediante TaTME y se compararon con las cohortes nacionales del Registro Noruego de Cáncer Colorrectal (Norwegian Colorectal Cancer Registry, NCCR) y del Registro Noruego de Cirugía Gastrointestinal (Norwegian Registry for Gastrointestinal Surgery, NoRGast) utilizando estimaciones de Kaplan-Meier y la prueba de log-rank para comparar curvas de LR. RESULTADOS: En Noruega, 157 pacientes se sometieron a TaTME por cáncer de recto entre octubre de 2014 y octubre de 2018. Tres de siete hospitales abandonaron el TaTME después de un total de cinco procedimientos. La LR observada fue 12/157 (7,6%), siendo ocho de ellas multifocales o extensas. La tasa estimada de LR a 2,4 años fue de 11,6 % (i.c. del 95% 6,6 a 19,9) versus 2,4 % (1,4 a 4,3) en el NCCR (log rank P < 0,001). El cociente de riesgos instantáneos (hazard ratio, HR) ajustado fue 6,7 (i.c. del 95% 2,9 a 15,3). Las fugas anastomóticas que precisaron una reintervención después de TaTME ocurrieron en un 8,4% versus 4,5% en el registro NoRGast (P = 0,047). Cincuenta y seis pacientes (35,7%) tenían un estoma en el último seguimiento; 39 (24,8%) eran permanentes. CONCLUSIÓN: Las tasas de fuga anastomótica tras una TaTME fueron más altas que los datos nacionales con tasas de LR y patrones de crecimiento desfavorables.

Osteoarthritis year in review 2016: imaging.

PURPOSE: The current narrative review covers original research related to imaging in osteoarthritis (OA) in humans published in English between April 1st 2015 and March 31st 2016, in peer reviewed journals available in Medline via PubMed (http://www.ncbi.nlm.nih.gov/pubmed/). METHODS: Relevant studies in humans, subjectively decided by the authors, contributing significantly to the OA imaging field, were selected from an extensive Medline search using the terms "Osteoarthritis" in combination with "MRI", "Imaging", "Radiography", "X-rays", "Ultrasound", "Computed tomography", "Nuclear medicine", "PET-CT", "PET-MRI", "Scintigraphy", "SPECT". Publications were sorted according to relevance for the OA imaging research community with an emphasis on high impact special interest journals using the software for systematic reviews www.covidence.org. RESULTS: An overview of newly published studies compared to studies reported previous years is presented, followed by a review of selected imaging studies of primarily knee, hip and hand OA focussing on (1) results for detection of OA and OA-related pathology (2) studies dealing with treatments and (3) studies focussing on prognosis of disease progression or joint replacement. A record high number of 1420 articles were published, among others, of new technologies and tools for improved morphological and pathophysiological understanding of OA-related changes in joints. Also, imaging data were presented of monitoring treatment effect and prognosis of OA progression, primarily using established radiographic, magnetic resonance imaging (MRI), and ultrasound (US) methods. CONCLUSION: Imaging continues to play an important role in OA research, where several exciting new technologies and computer aided analysis methods are emerging to complement the conventional imaging approaches.

The effects of intra-articular glucocorticoids and exercise on pain and synovitis assessed on static and dynamic magnetic resonance imaging in knee osteoarthritis: exploratory outcomes from a randomized controlled trial.

OBJECTIVE: The aims of the present knee osteoarthritis (KOA)-study were to: (1) describe and compare the changes in magnetic resonance imaging (MRI)-measures of synovitis following an exercise program preceded by an intra-articular injection of either corticosteroid or isotonic saline and (2) investigate if any of the changes in patient reported outcome measures (PROMs) were associated with changes in MRI-measures of synovitis. DESIGN: We performed a randomized, double-blinded, placebo-controlled clinical trial evaluating the effects of intra-articular corticosteroid vs placebo injections given before exercise therapy in KOA-patients. PROMs were assessed using the KOOS (knee injury and osteoarthritis outcome score). Synovitis was assessed on conventional non-contrast-enhanced, conventional contrast-enhanced (CE) and dynamic contrast-enhanced (DCE) MRI. PROMs and MRIs were obtained prior to the intra-articular injection, after termination of the exercise program (week 14-primary time point) and week 26. RESULTS: Of 100 randomized participants (50 in each allocation group), 91 had complete MRI-data at baseline (63% female, mean age: 62 years, median Kellgren-Lawrence-grade: 3). There were no statistically significant differences between the two interventions in regards of changes in MRI-measures of synovitis at any time-point. At week 14, we found no statistical significant MRI-explanatory variables of either of the PROMs. CONCLUSIONS: The present study does not justify the use of intra-articular corticosteroids over intra-articular saline when combined with an exercise program for reduction of synovitis in KOA. The improvement in pain and function following the intervention with intra-articular corticosteroids/saline and exercise could not be explained by a decrease in synovitis on MRI indicating other pain causing/relieving mechanisms in KOA.

The association between histological, macroscopic and magnetic resonance imaging assessed synovitis in end-stage knee osteoarthritis: a cross-sectional study.

OBJECTIVES: To investigate the association between magnetic resonance imaging (MRI), macroscopic and histological assessments of synovitis in end-stage knee osteoarthritis (KOA). METHODS: Synovitis of end-stage osteoarthritic knees was assessed using non-contrast-enhanced (CE), contrast-enhanced magnetic resonance imaging (CE-MRI) and dynamic contrast-enhanced (DCE)-MRI prior to (TKR) and correlated with microscopic and macroscopic assessments of synovitis obtained intraoperatively. Multiple bivariate correlations were used with a pre-specified threshold of 0.70 for significance. Also, multiple regression analyses with different subsets of MRI-variables as explanatory variables and the histology score as outcome variable were performed with the intention to find MRI-variables that best explain the variance in histological synovitis (i.e., highest R2). A stepped approach was taken starting with basic characteristics and non-CE MRI-variables (model 1), after which CE-MRI-variables were added (model 2) with the final model also including DCE-MRI-variables (model 3). RESULTS: 39 patients (56.4% women, mean age 68 years, Kellgren-Lawrence (KL) grade 4) had complete MRI and histological data. Only the DCE-MRI variable MExNvoxel (surrogate of the volume and degree of synovitis) and the macroscopic score showed correlations above the pre-specified threshold for acceptance with histological inflammation. The maximum R2-value obtained in Model 1 was R2 = 0.39. In Model 2, where the CE-MRI-variables were added, the highest R2 = 0.52. In Model 3, a four-variable model consisting of the gender, one CE-MRI and two DCE-MRI-variables yielded a R2 = 0.71. CONCLUSION: DCE-MRI is correlated with histological synovitis in end-stage KOA and the combination of CE and DCE-MRI may be a useful, non-invasive tool in characterising synovitis in KOA.

Associations between muscle perfusion and symptoms in knee osteoarthritis: a cross sectional study.

OBJECTIVE: To investigate the association between muscle perfusion in the peri-articular knee muscles assessed by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and symptoms in patients with knee osteoarthritis (KOA). DESIGN: In a cross-sectional setting, muscle perfusion was quantified by DCE-MRI in KOA. Regions of interest (ROI) were drawn around the peri-articular muscles, summed and averaged into one single "Total Muscle Volume" volume of interest (VOI). Symptoms were assessed via the Knee injury and Osteoarthritis Outcome Score (KOOS) (0: worst; 100: best). RESULTS: DCE-MRI and clinical data were analyzed in 94 patients. The typical participant was a woman with a mean age of 65 years, and a body mass index (BMI) of 32 kg/m(2). Reduced multiple regression models analyzing the association between KOOS and DCE-MRI perfusion variables of Total Muscle Volume showed a statistically significant association between Nvoxel% and KOOS pain (0.41 (SE 0.14); P = 0.0048). Nvoxel% was defined as the proportion of highly perfused voxels; i.e., the voxels that show an early and rapid increase on the signal intensity vs time curves, reach a plateau state (plateau pattern) and then showing a relatively rapid decline (washout pattern) relative to the total number of voxels within the muscle VOI. CONCLUSIONS: More widespread perfusion in the peri-articular knee muscles was associated with less pain in patients with KOA. These results give rise to investigations of the effects of exercise on muscle perfusion and its possible mediating role in the causal pathway between exercise and pain improvements in the conservative management of KOA.

Knee pain and inflammation in the infrapatellar fat pad estimated by conventional and dynamic contrast-enhanced magnetic resonance imaging in obese patients with osteoarthritis: a cross-sectional study.

OBJECTIVE: To investigate the association between knee pain and signs of inflammation in the infrapatellar fat pad (IPFP) in obese patients with knee osteoarthritis (KOA). DESIGN: In a cross-sectional setting, 3-T conventional contrast-enhanced (CE) magnetic resonance imaging (MRI) and dynamic contrast-enhanced (DCE)-MRI of KOA were analysed to quantify the extent of inflammation in the IPFP, and correlated (Spearman's rank correlation) to pain and other symptoms assessed via the Knee injury and Osteoarthritis Outcome Score (KOOS) (100 = no pain, 0 = extreme pain). The extent of inflammation in the IPFP was assessed according to the MRI Osteoarthritis Knee Score (MOAKS) using CE-MRI and by DCE-MRI perfusion variables. The perfusion variable, "Inflammation", was chosen as primary perfusion variable in the analysis. Intraclass correlation coefficients for the perfusion variables ranged from 0.81 to 0.99. RESULTS: MRI and clinical data were obtained in 95 patients. The typical patient was a woman (82%) with an average age of 65 years (SD 6.5) and a body mass index (BMI) of 32 kg/m(2) (SD 3.7). The bivariate association between KOOS pain and the DCE-MRI perfusion variable "Inflammation" showed a statistically significant correlation (r = -0.42, P < 0.0001). A statistically significant correlation was also found between KOOS pain and MOAKS Hoffa-synovitis (r = -0.21, P = 0.046). CONCLUSIONS: Perfusion variables on DCE-MRI reflecting the severity of inflammation in the IPFP and MOAKS Hoffa-synovitis were associated with the severity of pain in KOA. These results suggest that severe inflammation in the IPFP is associated with severe pain in KOA and that DCE-MRI is a promising method to study the impact of inflammation in KOA.

Inflammatory myofibroblastic tumors in two dogs.

Two soft tissue masses from different locations in 2 dogs were submitted for histopathologic examination. Each was well demarcated and consisted of interweaving streams of bland spindle cells among which numerous plasma cells and lymphocytes were scattered. All the spindle cells reacted strongly to antibodies against vimentin and calponin, whereas a subset of the spindle cells expressed smooth muscle actin and desmin. Immunohistochemistry results were consistent with a myofibroblastic derivation for the spindle-cell population and the diagnosis of inflammatory myofibroblastic tumor (IMT) was made. This is the second report of IMT in the veterinary literature.

Comparative immunolocalization of the plasma membrane calcium pump and calbindin D28K in chicken retina during embryonic development.

The immunolocalization of the plasma membrane calcium pump (PMCA) was studied in 4-week-old chick retina in comparison with calbindin D28K (CaBP) immunostaining. We have demonstrated that the monoclonal anti-PMCA antibody SF10 from human erythrocyte plasma membrane cross-reacts with a Ca2+ pump epitope of the cells from the neural retina. The immunolocalization of both proteins was also studied during the embryonic development of the chicken retina. At age 4.5 days, the cells of the retina were faintly immunoreactive to PMCA and CaBP antibodies, but the lack of cellular aggregation and differentiation did not allow discrimination between the two proteins. A clear difference in the localization was seen from the tenth day of development through post-hatching with slight variation. PMCA localized mainly in the outer and inner plexiform layers, in some cells in the ganglion layer, in the nerve fiber layer and slightly in the photoreceptor cells. CaBP was intensely stained in cones, cone pedicles and some amacrine cells. The number of CaBP positive amacrine cells declined after hatching. A few ganglion cells and several nerve fibers were CaBP immunoreactive. The role of these proteins in the early stages of retinal development is unknown, but the results suggest that Ca2+ homeostasis in the retina is well regulated, probably to avoid excessive accumulation of Ca2+, which often leads to neurodegeneration.

Ocular manifestations of equine motor neuron disease.

The characteristics of the ocular manifestations of equine motor neuron disease (EMND) are described. Forty-two horses with histories, clinical signs and necropsies compatible with EMND were the subjects of this study. Ophthalmoscopic lesions that varied in severity were found in 40 of 42 horses and appeared as a distinct pigmented reticulated pattern at the tapetal-nontapetal junction or throughout the fundus, depending upon severity. The pattern colours ranged from yellow brown to black. Areas of hyperreflectivity formed mosaic patterns in the tapetal fundus. ERG B-wave amplitudes were usually at least 50% reduced and many animals showed extinguished amplitudes. None of the horses had apparent visual impairment. Histopathologically, all 42 horses had retinal pigment epithelial (RPE) congestion with ceroid-lipofuscin. Retinal degeneration was variable even within the eyes. Thin layer chromatography (TLC) analysis of the RPE and neural retina identified both green and orange emitting fluorescent compounds not found in normal horses. All unsupplemented horses had plasma vitamin E levels <1.0 microg/ml. The potential significance of this report is the pathognomonic role the ocular manifestations exhibit in helping to diagnose equine motor neuron disease.

Tetracycline and niacinamide for the treatment of sterile pyogranuloma/granuloma syndrome in a dog.

A sterile pyogranuloma/granuloma syndrome in a dog is described. Diagnosis was based on cytological examinations of the skin and lymph nodes and histopathological examinations of the skin and nictitans. Although the condition initially was responsive to large doses of glucocorticoids, it subsequently was treated successfully with tetracycline and niacinamide. The excellent responses of this dog suggest that this drug combination may be a viable therapeutic option for dogs in which glucocorticoids cannot be used.

Retinoblastoma in a dog.

OBJECTIVE: To describe and classify a retinal tumor found in a dog that histologically resembles human retinoblastoma and to discuss the molecular mechanisms of retinal oncogenesis. METHODS: A dog eye with a retinal tumor was examined histologically. Studies including immunocytochemical analysis for retinal S-antigen and glial fibrillary acidic protein, enzyme histochemical analysis for carbonic anhydrase, and nick-end DNA labeling were used to characterize the tumor. Normal retina from another dog and other tumors from dogs, including 2 ciliary body medulloepitheliomas and a brain medulloepithelioma, were examined as controls. RESULTS: The retinal tumor disclosed characteristics typical of human retinoblastoma, including Flexner-Wintersteiner rosettes. It showed strong immunoreactivity with S-antigen and glial fibrillary acidic protein. Carbonic anhydrase activity also could be shown in the tumor. Apoptosis was found to be the predominant method of cell death as shown by nick-end DNA labeling. In contrast to the other tumors examined, this tumor contained areas with retinal photoreceptor and glial differentiation. CONCLUSIONS: The histopathologic findings and differential staining characteristics in this retinal tumor are compatible with retinoblastoma, making this, to our knowledge, the first documented case of spontaneous retinoblastoma in an animal.

Intraocular bacterial contamination during cataract surgery in dogs.

Prevalence of intraoperative contamination of the eyelids, conjunctival sac, and aqueous humor of 50 canine eyes that underwent elective cataract surgery was determined, and the short-term outcomes for contaminated and noncontaminated eyes were compared by scoring media clarity, pupil size and shape, and behavioral evidence of vision during the initial 30-day postoperative period. Results of bacteriologic culture of anterior chamber samples were positive for 12 of the 50 (24%) eyes, but anterior chamber contamination was unrelated to results of bacteriologic culture of eyelids or conjunctival sac swab samples. Eyes undergoing phacoemulsification were less likely to be contaminated than were eyes undergoing intra- or extracapsular extraction. Eyes undergoing intra- or extracapsular extraction and eyes with anterior chamber contamination had a greater likelihood of developing glaucoma postoperatively. We did not detect an association between intraocular contamination and the surgeon performing the operation, the need for postoperative administration of tissue plasminogen activator, or the presence or absence of diabetes mellitus. Also, we did not detect any differences in outcome between eyes with and without intraocular contamination. Despite intraoperative bacterial contamination of the anterior chamber, bacterial endophthalmitis did not develop in any of the eyes.

Ocular manifestation of systemic histiocytosis in a dog.

A 3-year-old sexually intact female Bernese Mountain Dog was referred for treatment of a descemetocele of the left eye. Physical examination revealed bilateral exophthalmos and scleral thickening, multiple cutaneous nodules, and mandibular paralysis in addition to ulcerative keratitis associated with a Pseudomonas infection. One year prior to examination, a biopsy specimen of the episcleral tissue from the right eye had been interpreted as nodular granulomatous episclerokeratitis (fibrous histiocytoma). Immunosuppressive treatment prior to referral had not resulted in remission of the ocular lesions. When we examined the biopsy specimen, we interpreted the lesions to represent episcleral involvement of systemic histiocytosis. Because of the poor prognosis, the dog was euthanatized.

Ocular-chondrodysplasia in labrador retriever dogs: a morphometric and electron microscopical analysis.

Ocular-chondrodysplasia in Labrador Retriever dogs is characterized by short-limbed dwarfism and ocular abnormalities. The purposes of the present study were to develop morphological criteria to define the matrix and/or chondrocytic abnormalities associated with this chondrodysplasia, and to test the hypothesis that ineffective matrix-directed cellular swelling was associated with the decreased longitudinal bone growth in these animals. The proximal and distal radial growth plates were collected from four affected animals of the same litter. Stereological techniques were used to analyze both cellular shapes and cellular volume changes in the hypertrophic zone. The pathological changes seen in these growth plates varied between animals and included disorganization of cellular columns with abnormal extent of calcification. Chondrocytes of all zones contained two types of abnormal cellular inclusions classified as light and dark, based on the intensity of eosinophilic staining. Both types of inclusions contained material that resembled the surrounding extracellular matrix, varying only in the apparent hydration of the contents. It could be demonstrated that light inclusions were located in the peripheral cytoplasm and connected to the extracellular matrix through narrow channels. By contrast, dark inclusions were membrane bound and perinuclear. Chondrocytes with multiple, large inclusions appeared to be undergoing degenerative changes. Although the final volume achieved by hypertrophic chondrocytes was consistent with that of normal growth plates, there was a high level of variability of chondrocytic shape and evidence of premature cellular condensation in the maturation zone. The severity of the dwarfism correlated both with the extent of chondrocytic changes and the severity of the ocular lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Tibetan terrier model of canine ceroid lipofuscinosis.

Over a 10-year period, we have studied the Tibetan terrier's visual electrophysiology, light and electron microscopic (EM) retinal characteristics of a slowly evolving inherited ceroid lipofuscinosis (CL). The retinal degeneration with CL inclusions (rdi) in the inner nuclear layer (bipolar cells) and nerve fiber layer (ganglion cells) has been called "rdi" to differentiate the visual abnormality from typical early retinal degeneration (erd) reported also in the Tibetan terrier. The unique "rdi" electroretinogram (ERG) gives a predominant P III wave at age 7 weeks but becomes more characteristically depressed in all phases over several years. Nyctalopia is the only functional abnormality for the first 5 to 6 year of life. Signs are remarkably few considering the pathology. Microscopic studies of the retina show accumulations, increasing with age, of autofluorescent dense inclusion particles which stain intensely by Luxol fast blue, PAS, and acid-fast procedures. Ultrastructural studies of the retina show the dense particles to be lamellar membranes repeating every 2 to 4 nm, consistent with ceroid lipofuscin. The inner retinal layers were always the target layer to be affected first and most severely. The ganglion cells were most frequently involved. The photoreceptors eventually degenerated but relatively few particles were found in this layer. The cytosomes in the cerebral cortex and brainstem neurons resemble lipofuscin, containing granular, lamellar, and globular components. Different pigment bodies were present in the cerebellar Purkinje cells. Neuronal loss which was moderate in the cerebellum and mild in the cerebrum was accompanied by astrogliosis and a striking presence of macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of a persistent corneal erosion in a boxer dog.

A dog was presented to the New York State College of Veterinary Medicine with a one-month history of corneal ulceration. The corneal lesion was diagnosed as a persistent corneal erosion (PCE) and treated initially with debridement and supported with a contact lens. One week later, the corneal erosion remained unepithelialized. Following debridement, multiple anterior stromal punctures were performed. Within 10 days, the erosion was healed as evidenced by coverage of the cornea with adherent, uninterrupted epithelium. The proposed etiology and management of PCE in dogs is discussed.