Introduction to radiomics for a clinical audience.

Radiomics is a rapidly developing field of research focused on the extraction of quantitative features from medical images, thus converting these digital images into minable, high-dimensional data, which offer unique biological information that can enhance our understanding of disease processes and provide clinical decision support. To date, most radiomics research has been focused on oncological applications; however, it is increasingly being used in a raft of other diseases. This review gives an overview of radiomics for a clinical audience, including the radiomics pipeline and the common pitfalls associated with each stage. Key studies in oncology are presented with a focus on both those that use radiomics analysis alone and those that integrate its use with other multimodal data streams. Importantly, clinical applications outside oncology are also presented. Finally, we conclude by offering a vision for radiomics research in the future, including how it might impact our practice as radiologists.

Surgical outcomes for chronic exertional compartment syndrome following improved diagnostic criteria.

INTRODUCTION: Chronic exertional compartment syndrome (CECS) presents with pain during exercise, most commonly within the anterior compartment of the lower limb. A diagnosis is classically made from a typical history and the measurement of intramuscular compartmental pressure (IMCP) testing. Improved, more specific diagnostic criteria for IMCP testing allow clinicians to now be more certain of a diagnosis of CECS. Outcomes following surgical treatment in patients diagnosed using these more robust criteria are unknown. METHODS: All patients undergoing fasciectomy for anterior compartment CECS at a single rehabilitation unit were identified between 2014 and 2017. Wilcoxen signed-rank test was used to compare military fitness grading and paired t-test was used to compare Foot and Ankle Ability Measure, FAAM Sport Specific and Exercise-Induced LimbPain-G outcome measures, presurgery and postsurgery. RESULTS: There was a significant difference in fitness grading between presurgical and postsurgical intervention (Z = -2.68, p < 0.01) with 46 % of patients improving their occupational medical grading. All secondary measures of outcome, looking at clinical symptoms, also improved. CONCLUSION: Almost half of the patients undergoing fasciectomy, following diagnosis using more specific criteria, will have an improvement in occupational medical grading. These outcomes represent the lower end of those reported in civilian populations. This is likely a result of a combination of factors, most notably the different diagnostic criteria followed and the more stringent criteria applied to military occupational grading, compared with civilian practice. Further work is now required to evaluate the impact of differing rehabilitation regimes on postoperative patients identified through this more specific diagnostic testing.

Barefoot plantar pressure measurement in Chronic Exertional Compartment Syndrome.

BACKGROUND: Patients with Chronic Exertional Compartment Syndrome (CECS) have exercise-limiting pain that subsides at rest. Diagnosis is confirmed by intramuscular compartment pressure (IMCP) measurement. Accompanying CECS, subjective changes to gait (foot slap) are frequently reported by patients. This has not previously been investigated. The aim of this study was to investigate differences in barefoot plantar pressure (BFPP) between CECS cases and asymptomatic controls prior to the onset of painful symptoms. METHODS: 40 male military volunteers, 20 with symptoms of CECS and 20 asymptomatic controls were studied. Alternative diagnoses were excluded with rigorous inclusion criteria, magnetic resonance imaging and dynamic IMCP measurement. BFPP was measured during walking and marching. Data were analysed for: Stance Time (ST); foot progression angle (FPA); centre of force; plantarflexion rate after heel strike (IFFC-time); the distribution of pressure under the heel; and, the ratio between inner and outer metatarsal loading. Correlation coefficients of each variable with speed and leg length were calculated followed by ANCOVA or t-test. Receiver operating characteristic (ROC) curves were constructed for IFFC-time. RESULTS: Caseshad shorter ST and IFFC-times than controls. FPA was inversely related to walking speed (WS) in controls only. The area under the ROC curve for IFFC-time ranged from 0.746 (95%CI: 0.636-0.87) to 0.773 (95%CI: 0.671-0.875) representing 'fair predictive validity'. CONCLUSION: Patients with CECS have an increased speed of ankle plantarflexion after heel strike that precedes the onset of painful symptoms likely resulting from a mechanical disadvantage of Tibialis Anterior. These findings provide further insight into the pathophysiology of CECS and support further investigation of this non-invasive diagnostic. The predictive value of IFFC-time in the diagnosis of CECS is comparable to post-exercise IMCP but falls short of dynamic IMCP measured during painful symptoms.

Effects of anterior compartment fasciotomy on intramuscular compartment pressure in patients with chronic exertional compartment syndrome.

BACKGROUND: Patients with chronic exertional compartment syndrome (CECS) have pain during exercise that usually subsides at rest. Diagnosis is usually confirmed by measurement of intramuscular compartment pressure (IMCP) following exclusion of other possible causes. Management usually requires fasciotomy but reported outcomes vary widely. There is little evidence of the effectiveness of fasciotomy on IMCP. Testing is rarely repeated postoperatively and reported follow-up is poor. Improved diagnostic criteria based on preselection and IMCP levels during dynamic exercise testing have recently been reported. OBJECTIVES: (1) To compare IMCP in three groups, one with classical symptoms and no treatment and the other with symptoms of CECS who have been treated with fasciotomy and an asymptomatic control group. (2) Establish if differences in IMCP in these groups as a result of fasciotomy relate to functional and symptomatic improvement. METHODS: Twenty subjects with symptoms of CECS of the anterior compartment, 20 asymptomatic controls and 20 patients who had undergone fasciotomy for CECS were compared. All other possible diagnoses were excluded using rigorous inclusion criteria and MRI. Dynamic IMCP was measured using an electronic catheter wire before, during and after participants exercised on a treadmill during a standardised 15 min exercise challenge. Statistical analysis included t-tests and analysis of variance. RESULTS: Fasciotomy results in reduced IMCP at all time points during a standardised exercise protocol compared with preoperative cases. In subjects responding to fasciotomy, there is a significant reduction in IMCP below that of preoperative groups (P<0.001). Postoperative responders to fasciotomy have no significant differences in IMCP from asymptomatic controls (P=0.182). CONCLUSION: Fasciotomy reduces IMCP in all patients. Larger studies are required to confirm that the reduction in IMCP accounts for differences in functional outcomes and pain reductions seen in postoperative patients with CECS.

Extra-articular stabilization of the cranial cruciate deficient stifle with anchor systems.

Complete or partial rupture of the cranial cruciate ligament (CCL) is a common injury of the canine stifle. Most practicing veterinarians would agree that optimal outcome is best achieved with surgical intervention. A popular method of stabilization is an extra-articular suture stabilization. The objective of this manuscript is to describe suture placement in a more isometric position as compared to traditional suture placement. A second objective is to introduce the veterinary surgeon to novel anchor products used for stabilization.

Minimally invasive application of a radial plate following placement of an ulnar rod in treating antebrachial fractures. Technique and case series.

OBJECTIVE: To describe a surgical technique for placement of a minimally invasive radial plate following application of an ulnar rod (MIPR) for treatment of antebrachial fractures. METHODS: Medical records (November 2005-June 2009) were searched to identify dogs with diaphyseal radius and ulna fractures stabilised by MIPR. Data retrieved included signalment, weight, limb affected, cause of injury, open versus closed fracture, number of fragments, implant size, number of screws used and cortices engaged, number of open screw holes, operative time, rod removal, complications and time to radiographic healing. To be included, dogs had to have evidence of radiographic healing during follow-up. RESULTS: Eight dogs with diaphyseal radius and ulna fractures treated with MIPR were included in the case series. All fractures were due to trauma and two fractures were open (grade 1). Rod loosening and osteomyelitis of the ulna occurred in one case which subsequently resolved with rod removal. Healing occurred in all cases with no implant failures. Median time to radiographic union was 10.5 weeks (mean ± SD = 17 ± 15 weeks; range 4-52 weeks). CLINICAL RELEVANCE: Use of MIPR constructs on diaphyseal fractures of the radius and ulna is an effective technique for managing these fractures using principles of biological osteosynthesis. An intramedullary rod in the ulna assists with fracture reduction and stabilisation and rod removal is recommended once fracture healing has occurred.

Determination of isometric points for placement of a lateral suture in treatment of the cranial cruciate ligament deficient stifle.

Complete or partial rupture of the cranial cruciate ligament (CCL) is a common injury of the canine stifle. While numerous techniques have been developed for surgical treatment, extra-articular methods with placement of a lateral suture remain a popular treatment method. The purpose of this study was to determine the potential isometry of the six suture-paired sites; two on the femur and three on the tibia. In six femoro-tibial specimens with intact passive joint restraints, femoral sites adjacent to the proximal (F1) and distal (F2) poles of the fabella, and tibial sites adjacent to the patella insertion (T1), immediately cranial to (T2) and caudal to (T3) the long digital extensor tendon, were identified. A suture from one femoral site to one tibial site was placed under 0 or 5 N of preload, and tension was measured at joint angles of 150 degrees , 130 degrees , 90 degrees and 50 degrees . The F2-T3 combination was found to be most isometric. Isometry was re-assessed in the same specimens with the suture in the F2-T3 position, and under 5 N, 10 N and 15 N of preload, and after transection of the CCL. The suture pair retained its isometric pattern in the CCL transected specimens. There was no effect of preload on isometry patterns.

Relationship of the biceps-brachialis complex to the medial coronoid process of the canine ulna.

OBJECTIVE: To describe the anatomic relationship of the biceps brachii-brachialis muscle complex and the medial compartment of the canine elbow. STUDY DESIGN: Anatomical cadaveric study. METHODS: Cadaveric forelimbs, and radius and ulna bones were examined to study the anatomy of the biceps brachii-brachialis complex and its relationship to the medial compartment of the elbow. RESULTS: The biceps brachii and brachialis muscles comprise a large muscular complex. The biceps brachii is a pennate fibred muscle which plays a major role in stabilising the elbow joint during the stance phase and facilitating limb acceleration during the swing phase. Additionally, the insertion of the muscular complex onto the ulnar tuberosity is such that a moment is generated which the authors hypothesise rotates the medial coronoid process against the radial head. The result is a compressive force which generates internal shear stress oblique to the long axis of the medial coronoid process. The authors further hypothesise that this may result in the microdamage or fragmentation of the medial coronoid process. CONCLUSION: The authors' conclude that contraction of the biceps brachii and brachialis complex may explain an aetiopathogenesis for fragmented medial coronoid process not associated with elbow dysplasia.

A review of osteoarthritis and obesity: current understanding of the relationship and benefit of obesity treatment and prevention in the dog.

Obesity is an increasingly important health problem for both man and dog. Osteoarthritis (OA) is a significant cause of pain and disability in both species. A link between obesity and OA has been established in man, though the exact mechanism of the relationship remains to be fully elucidated - current research supports both biomechanical and biochemical theories. There is good evidence (class I*) to support weight loss as an effective treatment for human knee OA. In the dog, the relationship is just beginning to be investigated. The results of one study in dogs (class IV evidence*) suggest that preventing the development of overweightness and obesity reduces the prevalence of hip dysplasia and OA of the hip and other joints. Three other studies (class III and IV evidence*) support weight loss as an effective treatment for OA in affected overweight and obese dogs. Further research could yield greater understanding of the pathophysiology of this relationship, perhaps identifying novel therapeutic targets. Confirmation and better understanding of the positive effect of treating and preventing obesity on symptoms and prevalence of OA is likely to be valuable in the campaign against canine obesity.

Meniscal injury following initial cranial cruciate ligament stabilization surgery in 26 dogs (29 stifles).

OBJECTIVE: To describe clinical signs, arthroscopic findings, and outcome in a group of dogs undergoing second look arthroscopy for the treatment of meniscal tears following original surgery to correct a CCL deficient stifle joint. METHODS: The medical records of 26 dogs from the Veterinary Teaching Hospital at Texas A&M University and the Veterinary Orthopedic Center (Round Rock, Texas) that had second look arthroscopy for lameness following an original surgical procedure were reviewed. Pre-operative clinical findings, 2nd look arthroscopic findings and owner assessed outcome were documented. RESULTS: Postliminary bucket handle tears of the medial meniscus were detected in 22 (75.9%) cases. Other postliminary meniscal injuries included frayed caudal horn tears of the medial meniscus 6 (20.7%), and longitudinal tears of the lateral meniscus 1 (3.4%). An audible or palpable click was present in 27.6% of cases. An improvement or resolution of lameness was reported in 96.5% of cases reported. In conclusion, tears of the medial meniscus are a significant cause of lameness in dogs subsequent to surgery for cranial crucial ligament ruptures. Increased lameness or acute onset of lameness after surgery for cranial crucial rupture is a consistent finding. In rare cases, a palpable or audible click will be appreciated. Arthroscopic evaluation and partial meniscectomy improve or resolve lameness in the majority of cases. CLINICAL SIGNIFICANCE: Sudden or increased lameness in dogs with historical CCL stabilization surgery should be evaluated and treated arthroscopically for postliminary meniscal injury if another cause for lameness can not be determined.

Comparison of dynamic ultrasound and stress radiology for assessment of inferior glenohumeral laxity in asymptomatic shoulders.

OBJECTIVE: To determine the level of agreement between dynamic ultrasound imaging and stress radiography used for the measurement of inferior glenohumeral laxity in asymptomatic shoulders, and to determine the repeatability of the dynamic ultrasound technique. MATERIALS AND METHODS: Using a custom-made stress device to apply an inferior displacement force of 90 N, we assessed 20 asymptomatic male subjects for inferior glenohumeral laxity, using stress radiography and dynamic ultrasound. Paired differences between the two methods were evaluated by the 95% limits of agreement method. At a separate session, 19 subjects had inferior glenohumeral laxity assessed by two observers, using dynamic ultrasound. Inter- and intra-observer repeatability was determined for the ultrasound technique. RESULTS: The mean [(+/-standard deviation (SD)] inferior translation was 4.7+/-4.1 mm by stress radiography and 4.4+/-2.3 mm by dynamic ultrasound. The 95% limits of agreement showed good agreement between the two methods. The paired difference between the two measurement methods varied with the magnitude of the measurement (P<0.001). Intra-observer repeatability of dynamic ultrasound was determined by the use of intra-class correlation coefficients and was 0.94 and 0.89 for the two investigators. Inter-observer repeatability was 0.85. The standard error of the measurement was 0.60 mm and 0.66 mm, for repeated measurements by the two investigators, and 0.85 mm between investigators. Repeatability coefficients demonstrated excellent consistency of measurement between sessions and good consistency between observers. CONCLUSION: Dynamic ultrasound is a valid and reproducible method for the assessment and quantification of inferior glenohumeral laxity.

Cranial cruciate ligament rupture in large and giant dogs. A retrospective evaluation of a modified lateral extracapsular stabilization.

Forty-two dogs weighing between 30 and 87 kg (mean body weight of 49 kg) with cranial cruciate ligament ruptures (CCLR) were treated with a modified lateral extra-capsular stabilization using braided polyester prosthetic ligament-suture anchor technique. Clinical and radiographic outcomes of 48 stifles were retrospectively evaluated with a mean follow-up of 18 months. Ten dogs had pulled out their bone anchors with no clinical relevance. Draining tracts did not appear. Despite mild radiographic progression of osteoarthritis, all of the dogs regained acceptable function of the operated limb.

Arthroscopic treatment of osteochondritis dissecans of the shoulder in 126 dogs.

Osteochondritis dissecans of the shoulder joint was treated by arthroscopy in 126 dogs. Twenty-four dogs had bilateral surgery, making a total of 150 joints treated. The OCD flaps were removed in small pieces through the cannula or in a single piece through a stab incision. The lameness resolved completely within seven-60 days following arthroscopy in 137 out of 150 affected limbs. Within a subset of 47 dogs with unilateral OCD, it was found that lesions located on the caudo-medial region of the humeral head had a better functional outcome than those lesions located in the caudo-central region of the humeral head.

Microbial adaptation and change: avian influenza.

The evolution of influenza is a continuing process involving viral and host factors. The increasing frequency of emergence of the highly pathogenic H5N1, H7N3 and H7N7 influenza viruses and the panzootic spread of H9N2 influenza virus, all of which can be potentially transmitted to humans, are of great concern to both veterinary and human public health officials. The question is how soon the next pandemic will emerge. A convergence of factors, including the population densities of poultry, pigs and humans, are likely factors affecting the evolution of the virus. Highly concentrated poultry and pig farming, in conjunction with traditional live animal or 'wet' markets, provide optimal conditions for increased mutation, reassortment and recombination of influenza viruses. Strategies to reduce the evolution of influenza and the emergence of pandemics include the separation of species, increased biosecurity, the development of new vaccine strategies and better basic knowledge of the virus. More effective co-operation between scientists and veterinary and public health officials is required to achieve these goals.

Fate of plasmid DNA encoding infectious bursal disease virus VP2 capsid protein gene after injection into the pectoralis muscle of the chicken.

The objective of this study was to determine whether recombinant plasmid DNA injected intramuscularly into chickens expressed the gene of interest in vivo and could be subsequently detected in primary and secondary lymphoid tissues with polymerase chain reaction (PCR). The VP2 capsid protein gene of the standard challenge strain (STC) of infectious bursal disease virus (IBDV) was cloned into a eukaryotic plasmid, and purified DNA was prepared. Fourteen 2-wk-old chickens were injected in the pectoral musculature with 500 microg of plasmid DNA dissolved in sterile PBS. Seven chickens were similarly injected with PBS alone. Pectoral muscle, thymus, spleen, bursa of Fabricius, and cecal tonsils were collected at 12, 24, 36, 48, 72, 96, and 168 h postinjection for detection of protein expression (in muscle) and to extract total DNA for PCR amplification of the VP2 capsid gene. Expression of VP2 was demonstrated in muscle tissue at 12 and 24 h postinjection by using an indirect immunofluorescence assay. PCR amplification with primers specific for the VP2 gene showed that the DNA was present in the thymus, spleen, and bursa of Fabricius but not in cecal tonsils. These results demonstrate that plasmid DNA injected directly into the pectoral muscle of chickens is transcribed and translated at the injection site and promptly distributed to primary and secondary lymphoid tissues.

Concentrations of chondroitin sulfate epitopes 3B3 and 7D4 in synovial fluid after intra-articular and extracapsular reconstruction of the cranial cruciate ligament in dogs.

OBJECTIVE: To evaluate effects of intra-articular and extracapsular reconstruction of the cranial cruciate ligament (CCL) on metabolism of articular cartilage as reflected by concentrations of chondroitin sulfate epitopes 3B3 and 7D4 in synovial fluid. ANIMALS: 13 adult dogs. PROCEDURE: Each dog underwent unilateral CCL transection (CCLT). One month after CCLT, sham CCL reconstruction (3 dogs), intra-articular CCL reconstruction (5), or extracapsular CCL reconstruction (5) was performed. Synovial fluid was collected by direct arthrocentesis from CCLT and contralateral stifle joints immediately before (time 0) and 1, 3, and 5 months after CCLT. Fluid was examined for concentrations of 3B3 and 7D4 epitopes and total sulfated glycosaminoglycan (GAG) content. RESULTS: Concentrations of 3B3, 7D4, and GAG, 3B3:GAG, or 7D4:GAG in CCLT joints did not differ significantly among treatment groups nor in the ratios of these variables in CCLT joints to contralateral joints at 3 months. In a longitudinal analysis, concentrations of 3B3 and 7D4, 3B3:GAG, and 7D4:GAG in CCLT joints in all groups changed significantly with time, but we did not detect time X group interactions. CONCLUSIONS AND CLINICAL RELEVANCE: Transection of CCL resulted in significant perturbation in articular cartilage metabolism as reflected by alterations in concentrations of 3B3 and 7D4 in synovial fluid. These changes over time were not significantly influenced by method of CCL reconstruction. We did not find evidence that surgical stabilization of CCL-deficient joints by intra-articular or extracapsular techniques had any effect on preventing alterations in composition of synovial fluid that have been associated with secondary osteoarthritis.

Effects of an orally administered mixture of chondroitin sulfate, glucosamine hydrochloride and manganese ascorbate on synovial fluid chondroitin sulfate 3B3 and 7D4 epitope in a canine cruciate ligament transection model of osteoarthritis.

OBJECTIVE: To evaluate effects of an orally administered mixture of chondroitin sulfate, glucosamine hydrochloride and manganese ascorbate (CS-G-M) on articular cartilage metabolism in dogs with cranial cruciate ligament (CCL) deficient and reconstructed knees, as reflected by concentrations of synovial fluid 3B3, 7D4 and total sulfated glycosaminoglycan (GAG). METHODS: Sixteen adult dogs that underwent unilateral CCL transection were randomized into four groups. Thereafter, group I (N=3) had a sham CCL reconstruction, group II (N=3) had CS-G-M and sham CCL reconstruction, group III (N=5) had CCL reconstruction, and group IV (N=5) had CS-G-M and CCL reconstruction. Synovial fluid collected at 0, 1, 3 and 5 months was examined by ELISA for 3B3 and 7D4 epitope, and by DMMB assay for total GAG. RESULTS: Synovial fluid from CCL transected knees of CS-G-M treated dogs contained significantly elevated concentrations of 3B3 (P=0.029), 7D4 (P=0.036) and 7D4/GAG (P=0.007) in comparison to controls, in a cross-sectional analysis at 3 months. Furthermore, 7D4 and 7D4/GAG concentrations remained significantly elevated (P=0.012) in CCL transected knees of CS-G-M treated dogs over the 5 month period. However, when epitope concentrations were expressed as a ratio of CCL-transected to contralateral non-operated knee, treatment effect of CS-G-M was no longer significant. Reconstruction of the CCL had no significant effect on synovial fluid epitope. CONCLUSIONS: Administration of CS-G-M was associated with altered concentrations of 3B3 and 7D4 epitope in synovial fluid, suggesting that these compounds may act to modulate articular cartilage matrix metabolism in vivo.

Treatment methods for pain in the osteoarthritic patient.

Osteoarthritis is one of the most common clinical problems for which pet owners seek veterinary consultation. Proper management of osteoarthritis is rewarding to the patient, client, and veterinarian alike. The foundation for treatment of osteoarthritis is weight control, exercise moderation, and administration of anti-inflammatory agents. This section of the text addresses clinically important mechanisms of osteoarthritis and the use of anti-inflammatory agents targeted to reduce pain and inflammation associated with the disease.

Reduction in plate strain by addition of an intramedullary pin.

OBJECTIVE: The purpose of this study was to determine the strain sparing effect of a bone plate and rod system compared with a bone plate alone. STUDY DESIGN: Mathematical analysis and in vitro modeling of implant-bone constructs. Implants were instrumented with uniaxial strain gauges. ANIMALS OR SAMPLE PREPARATION: Five pairs of canine femurs. METHODS: Bone plates were instrumented with two 350-ohm strain gauges. The bone plates were used to bridge a simulated fracture gap in five pairs of canine femurs. In one femur of each pair, a bone plate alone was used to bridge the gap; in the opposite femur, a bone plate and intramedullary rod combination was used. Each specimen was mounted on a custom jig and loaded in an axial servohydraulic testing machine. A constantly increasing compressive load was applied at the rate of 0.7 cm/sec. Strains at 400.5 N were recorded and analyzed using Wilcoxon's signed rank test. Mathematical modeling was done using parallel beam theory. RESULTS: Stress reduction in the plate and rod system was twofold compared with the plate alone (P = .059). As important, based on stress reduction in the plate, the fatigue life of the plate/rod system increased 10-fold over the plate system alone and was greater than 10-fold at higher absolute stress values. Mathematical analysis of the plate/rod system was similar to that seen with the in vitro analysis. CONCLUSIONS: The combination of a bone plate and intramedullary pin was superior in reducing plate stress when compared with the plate alone and functioned as two beams acting in concert. CLINICAL RELEVANCE: Stabilization of comminuted fractures by bridging the zone of fragmentation with a bone plate without anatomic reduction of each fragment is a useful method of managing this type of injury. Addition of an intramedullary pin reduces the stress applied to the plate and thereby extends the fatigue life of the bone plate.

Gracilis or semitendinosus myopathy in 18 dogs.

The clinical findings in 18 dogs with gracilis (n = 17) or semitendinosus (n = 1) myopathy are described. Each dog had a similar hind-limb gait abnormality characterized by a shortened stride with a rapid, elastic medial rotation of the paw, internal rotation of the hock and external rotation of the calcaneus [corrected] and internal rotation of the stifle during the mid-to-late swing phase of the stride. Medical management prior to or in lieu of surgery was attempted (n = 8) with no apparent response. Fifteen dogs had one or multiple surgical procedures. Although transection, partial excision, or complete resection of the affected muscle resulted in resolution of lameness following surgery, lameness recurred six weeks to five months (mean, 2.5 months; median, two months) following surgery. Adjunctive medical treatment did not prevent recurrence. Variable replacement of the affected muscle with fibrous connective tissue (predominantly along the caudolateral border of the muscle) was evident grossly, and replacement of myofibers with fibrous connective tissue was confirmed histologically. A definitive etiology could not be established.