Barbara N. Weissman

Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years

IntroductionAnkylosing spondylitis (AS) is a chronic rheumatic disease associated with spinal inflammation that subsequently leads to progression of structural damage and loss of function. The fully human anti-tumor necrosis factor (anti-TNF) antibody adalimumab reduces the signs and symptoms and improves overall quality of life in patients with active AS; these benefits have been maintained through 2 years of treatment. Our objective was to compare the progression of structural damage in the spine in patients with AS treated with adalimumab for up to 2 years versus patients who had not received TNF antagonist therapy.MethodsRadiographs from patients with AS who received adalimumab 40 mg every other week subcutaneously were pooled from the Adalimumab Trial Evaluating Long-Term Efficacy and Safety for Ankylosing Spondylitis (ATLAS) study and a Canadian AS study (M03-606). Radiographic progression from baseline to 2 years in the spine of adalimumab-treated patients from these two studies (adalimumab cohort, n = 307) was compared with an historic anti-TNF-naïve cohort (Outcome in AS International Study [OASIS], n = 169) using the modified Stoke AS Spine Score (mSASSS) method.ResultsmSASSS results were not significantly different between the adalimumab cohort and the OASIS cohort, based on baseline and 2-year radiographs. Mean changes in mSASSS from baseline to 2 years were 0.9 for the OASIS cohort and 0.8 for the adalimumab cohort (P = 0.771), indicating similar radiographic progression in both groups. When results for patients in the OASIS cohort who met the baseline disease activity criteria for the ATLAS and Canadian studies (OASIS-Eligible cohort) were analyzed, there was no significant difference in mean change in mSASSS from baseline to 2 years between OASIS-Eligible patients and adalimumab-treated patients; the mean changes in mSASSS were 0.9 for the OASIS-Eligible cohort and 0.8 for the adalimumab cohort (P = 0.744).ConclusionsTwo years of treatment with adalimumab did not slow radiographic progression in patients with AS, as assessed by the mSASSS scoring system, when compared with radiographic data from patients naïve to TNF antagonist therapy.Trial registrationCanadian study (M03-606) ClinicalTrials.gov identifier: NCT00195819; ATLAS study (M03-607) ClinicalTrials.gov identifier: NCT00085644.

The Clinical and Genetic Spectrum of the Holt-Oram Syndrome (Heart-Hand Syndrome)

BACKGROUND The Holt-Oram syndrome is an autosomal dominant condition characterized by skeletal abnormalities that are frequently accompanied by congenital cardiac defects. The cause of these disparate clinical features is unknown. To identify the chromosomal location of the Holt-Oram syndrome gene, we performed clinical and genetic studies. METHODS Two large families with the Holt-Oram syndrome were evaluated by radiography of the hands, electrocardiography, and transthoracic echocardiography. Genetic-linkage analyses were performed with polymorphic DNA loci dispersed throughout the genome to identify a locus that was inherited with the Holt-Oram syndrome in family members. RESULTS A total of 19 members of Family A had Holt-Oram syndrome with mild-to-moderate skeletal deformities, including triphalangeal thumbs and carpal-bone dysmorphism. All affected members of Family A had moderate-to-severe congenital cardiac abnormalities, such as ventricular or atrial septal defects or atrioventricular-canal defects. Eighteen members of a second kindred (Family B) had Holt-Oram syndrome with moderate-to-severe skeletal deformities, including phocomelia. Twelve of the affected members had no cardiac defects; six had only atrial septal defects. Genetic analyses demonstrated linkage of the disease in each family to polymorphic loci on the long arm of chromosome 12 (combined multipoint lod score, 16.8). These data suggest odds greater than 10(16):1 that the genetic defect for Holt-Oram syndrome is present on the long arm of chromosome 12 (12q2). CONCLUSIONS Mutations in a gene on chromosome 12q2 can produce a wide range of disease phenotypes characteristic of the Holt-Oram syndrome. This gene has an important role in both skeletal and cardiac development.

Genetic Heterogeneity of Heart-Hand Syndromes

BACKGROUND Heart-hand syndromes compose a class of combined congenital cardiac and limb deformities. The proto-typical heart-hand disorder is Holt-Oram syndrome, which is characterized by cardiac septation defects and radial ray limb deformity. We have recently mapped the Holt-Oram syndrome gene defect to the long arm of human chromosome 12 in two families. The role of this disease locus in the pathogenesis of related conditions such as heart-hand syndrome type III (cardiac conduction disease accompanied by skeletal malformations) or familial atrial septal defects is unknown. METHODS AND RESULTS Clinical evaluations and genetic linkage analyses were performed in five additional kindreds with Holt-Oram syndrome and also in one kindred with heart-hand syndrome type III and one kindred with familial atrial septal defect and conduction disease. Holt-Oram syndrome in all five kindreds mapped to chromosome 12q2. These studies and previous data provide odds of greater than 10(25):1 that the Holt-Oram syndrome disease gene is at chromosome 12q2. In contrast, neither the phenotypically similar disorder heart-hand syndrome type III nor the locus responsible for a familial atrial septal defect with atrioventricular block maps to chromosome 12q2. CONCLUSIONS We demonstrate that heart-hand syndromes are genetically heterogeneous. Conditions that clinically appear to be partial phenocopies of Holt-Oram syndrome arise from distinct disease genes.

The fate of acetabular allografts after bipolar revision arthroplasty of the hip. A radiographic review.

We reviewed the radiographs of thirty-one patients (thirty-two hips) who had had revision of the acetabular component of a total hip arthroplasty with a bipolar socket supplemented by allograft and were followed for twenty-four to forty-eight months. The grafts were categorized according to their consistency (solid or crushed bone), the location of the acetabular defect (peripheral [rim] or central), and the extent of the acetabular defect (contained--the medial part of the acetabular wall was intact, or non-contained--it was deficient). We recorded the time to incorporation of the graft, the amount of migration of the socket in the superior and medial axes, and the percentage of graft remaining at the time of the most recent follow-up. The time to healing was similar for all categories of grafts. The central, contained, solid grafts had less resorption than did the central, contained, crushed-bone grafts, as evidenced by less migration of the socket during follow-up. The non-contained grafts, in both peripheral and central locations, were associated with high rates of migration and of instability of the socket.

Radiographic Findings in the Hands in Patients with Systemic Lupus Erythematosus

Hand radiographs of 59 patients with systemic lupus erythematosus (SLE) were examined. Thirty-four revealed radiographic abnormalities, most commonly periarticular soft-tissue swelling or demineralization. Alignment abnormalities, acral sclerosis, avascular necrosis, soft-tissue calcification and terminal tuft resorption were also seen. All patients with periarticular calcification or terminal tuft resorption had Raynauds phenomenon. Clinical indicators of disease activity (including low serum complement levels) did not correlate with the presence or severity of radiographic abnormalities. Patients with abnormal radiographs generally were older at the time of diagnosis than those with normal studies.

Arthrosonography--technique, sonographic anatomy, and pathology.

Ultrasound scanning of the hips, shoulders, and elbows was investigated as a noninvasive technique for the diagnosis of joint disorders. Sixteen patients with known intra-articular fluid collections, loose bodies, or periarticular abnormalities were studied. Ultrasound images clearly demonstrated the contours of bony surfaces, normal muscles, and other soft-tissue structures around joints. Intra-articular fluid collections were seen as sonolucent halos around the femoral neck and humeral head and as an oval, sonolucent area anterior to the distal humerus. Collections of fluid as small as 10 ml in the hip and 16 ml in the shoulder were visualized. Intra-articular loose bodies and para-articular fluid collections were also demonstrated. It is concluded that gray-scale ultrasound can demonstrate some of the basic pathologic processes in joint disorders. Further evaluation of its scope and applicability is indicated.

Radiographic evaluation of osteoarthritis

Osteoarthritis is the most widespread form of arthritis in the United States. Classically, osteoarthritis has been grouped into primary and secondary types. Primary or idiopathic osteoarthritis is believed to be a sequela of altered biomechanical stresses across joints in susceptible individuals. Secondary osteoarthritis is a consequence of underlying cartilage damage, such as from preceding inflammatory arthritis, metabolic abnormality, or injury. The radiographic hallmark of osteoarthritis is asymmetric loss of cartilage space. Osteophytosis bony eburnation, subchondral cysts, and eventual subluxation follow. Osteoporosis and erosions are not usual features of this disease.

Radiographic detection of metal-induced synovitis as a complication of arthroplasty of the knee.

Radiographs of eighteen patients who had had a diagnosis of metal-induced synovitis subsequent to a knee-replacement arthroplasty were retrospectively reviewed. The presence of a dense line outlining a portion of the capsule or articular surface of the knee joint (the so-called metal-line sign) was noted in association with wear in eleven patients. In the nine patients who had a positive sign and also had specimens available for histological examination, there was dense deposition of metal particles, whereas in the six patients who did not have a metal-line sign and had specimens available for histological examination, five had only a slight amount of metal in the synovial tissue and one, a moderate amount. The presence of the metal-line sign was associated with metal-induced synovitis in eleven of the eighteen patients. The sign should be useful in helping to make this diagnosis preoperatively in many patients.

Distal loss of femoral bone following total knee arthroplasty. Measurement with visual and computer-processing of roentgenograms and dual-energy x-ray absorptiometry.

The changes in bone-mineral content in the distal aspect of a cadaveric femur that had been prepared for insertion of the femoral component of a total condylar knee prosthesis were evaluated with visual inspection and computer-processing of roentgenograms and with dual-energy x-ray absorptiometry. Seventeen small slices of bone, each three millimeters wide, were removed so that, finally, 89 per cent of the bone was lost from the distal femoral metaphysis. Standardized lateral roentgenograms of the specimen were made with use of a reference step-wedge of hydroxyapatite, and dual-energy x-ray absorptiometry studies were performed with the x-ray beam tangential to the interface. The roentgenograms were digitized and the bone mineral was measured with use of computer analysis. Dual-energy x-ray absorptiometry was performed with and without the femoral prosthesis in place, in order to determine the effect of the metallic prosthesis on the accuracy of the measurement. A bone loss of 25 per cent or more was identified visually by all five of the readers 100 per cent of the time; losses of 20 to 24 per cent, 15 to 19 per cent, 10 to 14 per cent, and 3 to 9 per cent were correctly identified 92, 75, 66, and 59 per cent of the time, respectively. The measurements of bone-mineral content that were obtained from the digitized roentgenograms were linearly correlated with the actual bone-mineral content (the ash content) (r = 0.97, p < 0.001) and were three times more accurate than the visual readings. The determinations of bone-mineral content with dual-energy x-ray absorptiometry correlated highly with the ash content (r = 1.00, p < 0.001) and were seven times more accurate than the visual readings. There was only a 4 per cent difference between the measurements with dual-energy x-ray absorptiometry made with the prosthesis in place and those made without it in place (p < 0.01). Dual-energy x-ray absorptiometry was the most accurate of the three methods and could detect the smallest experimentally created loss; computer-processing and visual-processing of roentgenograms detected losses of 8 per cent or more and 25 per cent or more, respectively. Dual-energy x-ray absorptiometry and computer-processing of the roentgenograms quantified the bone loss, while visual-processing could detect only the presence or absence of bone loss.(ABSTRACT TRUNCATED AT 400 WORDS)

ACR Appropriateness Criteria® on Suspected Osteomyelitis in Patients With Diabetes Mellitus

Imaging of the diabetic foot is among the most challenging areas of radiology. The authors present a consensus of the suggested tests in several clinical scenarios, such as early neuropathy, soft-tissue swelling, skin ulcer, and suspected osteomyelitis. In most of these situations, magnetic resonance imaging (MRI) with or without contrast is the examination of choice. Most other imaging tests have complementary roles. For soft-tissue swelling or an ulcer, radiography and MRI with or without contrast are suggested. Bone scintigraphy with white blood cell scanning is used when MRI is contraindicated. In patients with diabetes without ulcers, radiography and MRI with or without contrast are suggested; bone scanning may be used when MRI is contraindicated.