Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma.

Few patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) achieve prolonged disease-free survival. Blinatumomab, a bispecific T-cell engaging antibody construct, transiently links CD3-positive T cells to CD19-positive B cells. This phase 2 study evaluated stepwise (9-28-112 µg/d with weekly dose increases; n = 23) or flat (112 µg/d; n = 2) dosing of blinatumomab by continuous infusion, with dexamethasone prophylaxis, in patients with relapsed/refractory DLBCL. Patients received a median of 3 prior lines of therapy. Median time since last regimen was 1.5 months. Seventeen patients ended treatment in cycle 1 (induction), 7 in cycle 2 (consolidation), and 1 in retreatment. Among 21 evaluable patients, the overall response rate after 1 blinatumomab cycle was 43%, including complete responses (CRs) in 19%. Three patients had late CR in follow-up without other treatment. The most common adverse events with stepwise dosing were tremor (48%), pyrexia (44%), fatigue (26%), and edema (26%). Grade 3 neurologic events with stepwise dosing were encephalopathy and aphasia (each 9%) and tremor, speech disorder, dizziness, somnolence, and disorientation (each 4%). Of 5 (22%) patients who discontinued stepwise dosing because of adverse events, 4 (17%) had neurologic events. Most neurologic events resolved. The flat-dose cohort was stopped because of grade 3 neurologic events in both patients. Blinatumomab monotherapy appears effective in patients with relapsed/refractory DLBCL, a heavily pretreated patient population with a high unmet medical need. Further studies need to define the optimal approach to achieve the target dose without early dropout. The study was registered at www.clinicaltrials.gov as #NCT01741792.

Detection of acute pulmonary embolism: feasibility of diagnostic accuracy of MRI using a stepwise protocol.

Multidetector computed tomography (MDCT) has become the imaging method of choice in patients suspected of having pulmonary embolism (PE) but has the inherent limitation of radiation dose and the side effects of contrast agents. The purpose of the study was to assess the feasibility of a stepwise MRI protocol in the clinical setting of acute PE. The stepwise approach should make it possible to diagnose acute PE in critically ill patients using fast MR sequences and included the option to add comprehensive sequences when patients were stable. Forty-five patients with acute PE (26 men, 19 women; 41 ± 16 years) were included in this prospective study. The diagnosis was initially confirmed by MDCT as gold standard. MRI at 1.5 T was subsequently performed without any delay in medical treatment. The MRI protocol proceeded stepwise from robust to detailed imaging techniques (i.e., from TrueFISP and single shot HASTE sequence to MR perfusion and 3D-MR angiography) if the patient was able to tolerate additional imaging time. Diagnostic accuracy was evaluated on the central (lobar) and peripheral (segmental) levels. The complete MR protocol was applied in 40 of the 45 patients (88 %). In the remaining five patients with severe dyspnea the diagnosis of acute PE was established by using fast TrueFISP sequences that were insensitive to respiratory movement. All five patients suffered from a major central PE. Highest sensitivity was achieved by MR perfusion (lobar, 98 %; segmental, 95 %). Real-time TrueFISP and MR angiography showed the highest specificity (lobar, 90-100 %; segmental, 95-97 %). The combination of all MR sequences matched closely the results of MDCT (lobar: sensitivity 98 %, specificity 100 %; segmental: sensitivity 95 %, specificity 97 %). MRI using a stepwise protocol is a promising approach for diagnosing acute PE. The protocol can be tailored for dyspneic patients with central PE using real-time MRI sequences. The diagnostic accuracy for peripheral PE can be improved by using combined MR techniques, achieving comparable results to MDCT.

Dynamic contrast-enhanced MRI for monitoring bisphosphonate therapy in Paget's disease of bone.

PURPOSE: The purpose of this study was to evaluate changes in regional bone perfusion in Paget's disease (PD) following bisphosphonate therapy. We used dynamic contrast-enhanced MRI (DCE-MRI) for assessment of bone perfusion and compared MRI findings with alkaline phosphatase (AP) as a serum marker of bone turnover. MATERIALS AND METHODS: We examined 20 patients (8 women, 12 men, 66 ± 11 years) with symptomatic PD of the axial skeleton. Patients were selected for infusion therapy with the bisphosphonate pamidronate. The most affected bone of lumbar spine or pelvis was examined by DCE-MRI prior to therapy and after a 6-month follow-up. The contrast uptake was evaluated using a two-compartment model with the parameters amplitude A and exchange rate constant K(ep). Color-coded parametric images were generated to visualize bone vascularization. RESULTS: After a 6-month follow-up there was a significant decrease in alkaline phosphatase and in DCE-MRI parameters A and K(ep) (p < 0.0001). Patients without previous bisphosphonate treatment showed a significantly greater decrease in alkaline phosphatase and K(ep) (p < 0.001). CONCLUSION: DCE-MRI shows a significant reduction in regional bone perfusion in PD following parenteral bisphosphonate treatment. Reduction in bone perfusion is greater in bisphosphonate-naïve patients than in those who had been previously treated.

Detection and size of pulmonary lesions: how accurate is MRI? A prospective comparison of CT and MRI.

BACKGROUND: Although CT is the modality of choice for morphological lung imaging, an increasing proportion of chest imaging is performed by MRI due to the utilization of whole-body MRI. Therefore, the diagnostic performance of MRI in reliably detecting pulmonary lesions should be established. PURPOSE: To investigate the detection rate of pulmonary lesions by MRI that can be expected in a clinical setting and to assess the accuracy of lesion measurement by MRI compared to CT. MATERIAL AND METHODS: Twenty-eight patients (median age 66 years) with indication for CT imaging due to suspected thoracic malignancy were prospectively included. Chest MRI performed on the same day as CT, comprised unenhanced TrueFisp, ecg-gated T2-weighted HASTE, T1-weighted VIBE, and contrast-enhanced T1-weighted, fat-saturated VIBE sequences. MR sequences were evaluated for lesion detection by two readers independently and measurement of lesion size was performed. MR findings were correlated with CT. RESULTS: One hundred and eight pulmonary lesions (20 thoracic malignancies, 88 lung nodules) were detected by CT in 26 patients. Lesions were ruled out in two patients. All thoracic malignancies were identified by MRI with strong correlation (r = 0.97-0.99; P < 0.01) in lesion size measurement compared to CT. Unenhanced, T1-weighted VIBE correctly classified 94% of thoracic malignancies into T-stages. Contrast-enhanced, T1-weighted VIBE performed best in identifying 36% of lung nodules, 40% were detected combining unenhanced and contrast-enhanced T1-weighted VIBE. Detection rate increased to 65% for the combined sequences regarding lesions ≥5 mm. Lesion size measurement by all MR sequences strongly correlated with CT (r = 0.96-0.97; P = 0.01). CONCLUSION: MRI is as accurate as CT in detection and size measurement of primary thoracic malignancies >1 cm in diameter. If a lung lesion is detected by MRI, it is a reliable finding and its measurement is accurate. CT remains superior in detecting small lung nodules (<6 mm). Detection rate of MRI for small lesions is improved using a multi-sequence protocol including contrast administration.

Three-year outcomes after kyphoplasty in patients with osteoporosis with painful vertebral fractures.

PURPOSE: Kyphoplasty immediately improves pain and mobility in patients with painful osteoporotic vertebral fractures, but long-term clinical outcomes are still unclear. This controlled trial evaluates pain, mobility and fracture incidence 3 years after kyphoplasty. MATERIALS AND METHODS: Kyphoplasty was performed in 40 patients with painful osteoporotic vertebral fractures; 20 patients who were selected for kyphoplasty but chose not to undergo the procedure served as controls. All patients received pharmacologic antiosteoporosis treatment, pain medication, and physiotherapy. Pain (visual analog scale of 0-100), mobility (European Vertebral Osteoporosis Study questionnaire score of 0-100), and incident vertebral fractures were assessed at baseline, postprocedurally, and after 12 and 36 months. RESULTS: Pain score improved after kyphoplasty from 73.8 to 55.9 (immediately after kyphoplasty), 55.6 (12 months), and 54.0 (36 months; P < .001). Pain score in the control group changed from 66.4 to 65.7 at 12 months and 64.0 at 36 months (P = .521). The pain score of the kyphoplasty group was significantly improved versus controls after 36 months (P = .023). Mobility score improved after kyphoplasty from 43.8 to 54.2 (immediately after kyphoplasty), 54.5 (12 months), and 54.8 (36 months; P = .0008) and remained increased (P = .308) compared with controls (39.8 immediately after kyphoplasty, 44.3 at 12 months, and 43.6 at 36 months). The incidence of new vertebral fractures after kyphoplasty was significantly reduced versus controls after 3 years (P = .0341). CONCLUSIONS: Kyphoplasty reduces pain and improves mobility as long as 3 years after the procedure. The long-term risk of new vertebral fractures after kyphoplasty of chronically painful vertebral fractures is reduced versus controls.

MR-relaxometry of myocardial tissue: significant elevation of T1 and T2 relaxation times in cardiac amyloidosis.

OBJECTIVE: This study evaluates if MR-relaxometry of myocardial tissue reveals significant differences in cardiac amyloidosis (CA) compared with patients with systemic amyloidosis but without cardiac involvement (NCA) and a healthy control group. Therefore, we measured T1 and T2 relaxation times (RT) of the left ventricular myocardium with magnetic resonance imaging at 1.5 T. MATERIAL AND METHODS: Nineteen consecutive patients (14 males, 5 females; mean age, 59 +/- 6.1 years) with histologically proven CA were evaluated. T1-RT and T2-RT were measured by using a saturation-recovery TurboFLASH sequence and a HASTE sequence, respectively. Additionally, morphologic and functional data were acquired. Results were compared with patients with systemic amyloidosis but without cardiac involvement (NCA; 5 males, 4 females, 48.9 +/- 15.4 years) and 10 healthy, age-matched control subjects (5 males, 5 females, 60.4 +/- 6.4 years). RESULTS: MR-relaxometry revealed a significant elevation of T1-RT of the left ventricular myocardium in CA-patients compared with that in NCA-patients and the age-matched control group [mean +/- SD (95% CI) 1340 +/- 81 (1303-1376) msec, 1213 +/- 79 (1160-1266) msec, 1146 +/- 71 (1096-1196) msec, respectively; CA vs. control, P < 0.0001; CA vs. NCA:, P < 0.0003; NCA vs. control, P = 0.07]. T2-RT showed a marginal but significant increase in CA-patients compared with NCA-patients and the control group [mean +/- SD (95% CI) 81 +/- 12 (76-86) msec, 71 +/- 11 (64-79) msec, 72 +/- 9 (65-79) msec, respectively; CA vs. control, P = 0.04; CA vs. NCA, P = 0.04; NCA vs. control, P = 0.91]. T1-RT was best suited to discriminate between the groups as shown by logistic regression. A cut-off value of >or=1273 milliseconds for T1-RT was defined using receiver-operator characteristics-analysis to establish the diagnosis of CA with a high sensitivity (84%) and specificity (>89%). CONCLUSIONS: Measurement of T1 and T2 RT is a novel approach for noninvasive evaluation of CA. MR-relaxometry might improve diagnostic reliability of magnetic resonance imaging for evaluation of cardiac involvement in systemic amyloidosis.

Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma: Final Results From a Phase I Study.

PURPOSE: Blinatumomab is a CD19/CD3 BiTE (bispecific T-cell engager) antibody construct for the treatment of Philadelphia chromosome-negative acute B-lymphoblastic leukemia. We evaluated blinatumomab in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: This 3 + 3 design, phase I dose-escalation study determined adverse events and the maximum tolerated dose (MTD) of continuous intravenous infusion blinatumomab in patients with relapsed/refractory NHL. Blinatumomab was administered over 4 or 8 weeks at seven different dose levels (0.5 to 90 µg/m(2)/day). End points were incidence of adverse events, pharmacokinetics, pharmacodynamics, and overall response rate. RESULTS: Between 2004 and 2011, 76 heavily pretreated patients with relapsed/refractory NHL, who included 14 with diffuse large B-cell lymphoma, were enrolled; 42 received treatment in the formal dose-escalation phase. Neurologic events were dose limiting, and 60 µg/m(2)/day was established as the MTD. Thirty-four additional patients were recruited to evaluate antilymphoma activity and strategies for mitigating neurologic events at a prespecified MTD. Stepwise dosing (5 to 60 µg/m(2)/day) plus pentosan polysulfate SP54 (n = 3) resulted in no treatment discontinuations; single-step (n = 5) and double-step (n = 24) dosing entailed two and seven treatment discontinuations due to neurologic events, respectively. Grade 3 neurologic events occurred in 22% of patients (no grade 4/5). Among patients treated at 60 µg/m(2)/day (target dose; n = 35), the overall response rate was 69% across NHL subtypes and 55% for diffuse large B-cell lymphoma (n = 11); median response duration was 404 days (95% CI, 207 to 1,129 days). CONCLUSION: In this phase I study of relapsed/refractory NHL, continuous infusion with CD19-targeted immunotherapy blinatumomab at various doses and schedules was feasible, with an MTD of 60 µg/m(2)/day. Single-agent blinatumomab showed antilymphoma activity.

Treatment of painful vertebral fractures by kyphoplasty in patients with primary osteoporosis: a prospective nonrandomized controlled study.

UNLABELLED: This study investigates the effects of kyphoplasty on pain and mobility in patients with osteoporosis and painful vertebral fractures compared with conventional medical management. INTRODUCTION: Pharmacological treatment of patients with primary osteoporosis does not prevent pain and impaired activity of patients with painful vertebral fractures. Therefore, we evaluated the clinical outcome after kyphoplasty in patients with vertebral fractures and associated chronic pain for >12 months. MATERIALS AND METHODS: Sixty patients with primary osteoporosis and painful vertebral fractures presenting for >12 months were included in this prospective, nonrandomized controlled study. Twenty-four hours before performing kyphoplasty, the patients self-determined their inclusion into the kyphoplasty or control group so that 40 patients were treated with kyphoplasty, whereas 20 served as controls. This study assessed changes in radiomorphology, pain visual analog scale (VAS) score, daily activities (European Vertebral Osteoporosis Study [EVOS] score), number of new vertebral fractures, and health care use. Outcomes were assessed before treatment and at 3 and 6 months of follow-up. All patients received standard medical treatment (1g calcium, 1000 IE vitamin D(3), standard dose of oral aminobisphosphonate, pain medication, physical therapy). RESULTS: Kyphoplasty increased midline vertebral height of the treated vertebral bodies by 12.1%, whereas in the control group, vertebral height decreased by 8.2% (p = 0.001). Augmentation and internal stabilization by kyphoplasty resulted in a reduction of back pain. VAS pain scores improved in the kyphoplasty group from 26.2 +/- 2 to 44.2 +/- 3.3 (SD; p = 0.007) and in the control group from 33.6 +/- 4.1 to 35.6 +/- 4.1 (not significant), whereas the EVOS score increased in the kyphoplasty group from 43.8 +/- 2.4 to 54.5 +/- 2.7 (p = 0.031) and in the control group from 39.8 +/- 4.5 to 43.8 +/- 4.6 (not significant). The number of back pain-related doctor visits within the 6-month follow-up period decreased significantly after kyphoplasty compared with controls: mean of 3.3 visits/patient in the kyphoplasty group and a mean of 8.6 visits/patient in the control group (p = 0.0147). CONCLUSIONS: The results of this study show significantly increased vertebral height, reduced pain, and improved mobility in patients after kyphoplasty. Kyphoplasty performed in appropriately selected osteoporotic patients with painful vertebral fractures is a promising addition to current medical treatment.

Gastrointestinal stromal tumours and their response to treatment with the tyrosine kinase inhibitor imatinib.

Gastrointestinal stromal tumours (GISTs), the most common mesenchymal tumours of the digestive tract, are largely resistant to chemo- and radiotherapy. They are currently defined by their overexpression of the KIT receptor tyrosine kinase (CD117), a member of the family of receptor tyrosine kinases (RTKs), and exhibit KIT mutations in more than 85% of cases. Additionally, in more than one-third of KIT wild-type GISTs, mutations of platelet-derived growth factor receptor alpha (PDGF-R alpha), which also belongs to the family of RTKs, were recently found. Since these data indicate that uncontrolled RTK signalling may be implicated in the pathogenesis of GISTs, RTKs and the activated downstream signalling cascades are attractive targets in the therapy of these tumours. Imatinib is a small-molecule inhibitor that selectively blocks the activity of the PDGF-R, ABL and KIT receptor tyrosine kinases by competitive binding to the adenosine triphosphate binding site of their catalytic domains. We herein review the molecular pathological, preclinical and clinical data that identify imatinib as a valuable new agent in the treatment of GISTs.

Occlusion of the internal iliac artery prior EVAR: comparison of coils and plugs.

PURPOSE: We compared occlusion of the internal iliac artery (IIA) using coils or the Amplatzer vascular plug (AVP) II prior to endovascular aortic aneurysm repair. MATERIALS AND METHODS: Occlusion of the IIA was performed in 32 patients (aged 74 ± 8 years) using coils (N = 17) or the AVP II (N = 15). We retrospectively compared procedural data, initial success, and clinical outcome in a 12-month follow-up. RESULTS: Occlusion was successful in all patients without detection of an endoleak after 12 months. Procedure time and fluoroscopy time for coils versus plugs were 77 ± 35 versus 43 ± 13 minutes and 36 ± 19 versus 18 ± 8 minutes, respectively (P < .003). Incidence of initial buttock claudication (BC) for coils versus plugs was 47% versus 27% and was significantly more severe after coil occlusion (P = .03). After a 12-month follow-up, 2 patients of each group reported of mild BC. CONCLUSION: Occlusion of the IIA is safe and effective using coils or plugs. Initial BC is significantly more severe when coils are used, but after a 12-month follow-up, there is no significant difference. Using a plug is associated with a significant reduction of procedure time and radiation exposure.

Occlusion of arteriovenous fistulas of in-situ saphenous vein bypass grafts using the amplatzer vascular plug 4: initial experience.

We examined the safety and efficacy of vessel occlusion of the Amplatzer Vascular Plug 4 (AVP-4) in patients with arteriovenous fistulas after in-situ saphenous vein bypass grafts. We treated 18 fistulas of seven patients (four women, mean±standard deviation age 76±7 years, range 63-88 years). All fistulas were detected within 14 days after surgery. Initial diagnosis and follow-up was established by sonography. We measured the diameter of the feeding vessel and the time of vessel occlusion after plug deployment. Additionally, we recorded procedure time and the dose area product. Additional interventional procedures were necessary in three patients. We successfully used 19 AVP-4 for occlusion of all fistulas without thromboembolic complications. There was no need for recapturing the device, and we did not observe dislocation. Mean occlusion time was 9.6 min (range 5-22 min). Mean diameter of the feeding vessels was 3.5 mm (range 2.6-5.1 mm). Plug sizes ranged from 4-8 mm (mean 5.5 mm) resulting in an oversizing of 33-88%. Mean procedure time for patients with and without additional intervention was 91±38 min and 35±18 min, respectively. Mean dose area product was 11,790 cGy/cm2 (range 1,850-23,500 cGy/cm2). Permanent occlusion of the fistulas was confirmed by ultrasound after a mean follow-up of 4 months (1-6 months). Occlusion of arteriovenous fistulas with an AVP-4 seems to be effective and safe in patients with in-situ saphenous vein bypass grafts. The AVP-4 is well suited for this purpose because of the appropriate diameter of the feeding vessels.

CIRSE vascular closure device registry.

PURPOSE: Vascular closure devices are routinely used after many vascular interventional radiology procedures. However, there have been no major multicenter studies to assess the safety and effectiveness of the routine use of closure devices in interventional radiology. METHODS: The CIRSE registry of closure devices with an anchor and a plug started in January 2009 and ended in August 2009. A total of 1,107 patients were included in the registry. RESULTS: Deployment success was 97.2%. Deployment failure specified to access type was 8.8% [95% confidence interval (95% CI) 5.0-14.5] for antegrade access and 1.8% (95% CI 1.1-2.9) for retrograde access (P = 0.001). There was no difference in deployment failure related to local PVD at the access site. Calcification was a reason for deployment failure in only <0.5% of patients. Postdeployment bleeding occurred in 6.4%, and most these (51.5%) could be managed with light manual compression. During follow-up, other device-related complications were reported in 1.3%: seven false aneurysms, three hematoma >5.9 cm, and two vessel occlusions. CONCLUSION: The conclusion of this registry of closure devices with an anchor and a plug is that the use of this device in interventional radiology procedures is safe, with a low incidence of serious access site complications. There seems to be no difference in complications between antegrade and retrograde access and other parameters.

Late enhancement in cardiac amyloidosis: correlation of MRI enhancement pattern with histopathological findings.

Late enhancement (LE) in cardiac magnetic resonance imaging (MRI) is a characteristic finding in patients with cardiac amyloidosis (CA) but the histomorphological explanation has not been clarified yet. Five patients with CA were evaluated by MRI prior to heart transplantation. This consisted of morphological, volumetric, and functional data, including LE analysis. For LE analysis, left ventricular (LV) short-axis sections from basal, midventricular, and apical positions were divided into 12 segments resulting in a 36-segment model. Each segment was differentiated by subendocardial, midmural, and subepicardial localization. Histological amyloid and collagenous fiber deposition was correlated with LE in corresponding MRI slides. LE was visualized in 103/180 (57.2%) predominantly subendocardial segments. Histological analysis of amyloid deposition was (peri-)vascular (n = 5), diffuse interstitial (n = 3) and/or nodular (n = 4). Extent of fibrosis was moderate to severe. Cytoplasmatic vacuolization and decline of myofibrils was seen in all patients. Fibrosis was significantly associated with LE in subendocardial and midmural localizations (p<0.05), whereas the extent of amyloid deposition was not associated with LE findings in any region. LE seems to be associated with fibrosis due to ischemia of cardiomyocytes by small vessel amyloid deposition rather than with amyloid deposition in CA, suggesting that amyloid deposition might be present prior to LE detection.

Calcium-phosphate and polymethylmethacrylate cement in long-term outcome after kyphoplasty of painful osteoporotic vertebral fractures.

STUDY DESIGN: A comparative prospective trial evaluating 3-year outcome. OBJECTIVE: To compare clinical and morphologic outcomes as well as follow-up fractures after kyphoplasty of painful osteoporotic vertebral fractures with calcium-phosphate (CaP) cement (group 1) and with polymethylmethacrylate (PMMA)-cement (group 2). SUMMARY OF BACKGROUND DATA: CaP cements seem to be an alternative material for usage in kyphoplasty of vertebral fractures. CaP cements are biodegradable and replaceable by newly formed bone after implantation. Concerns have been raised with regard to the stability of resorbable CaP-cements after implantation into vertebrae post kyphoplasty. Calcibon is a possible CaP cement, which exhibited adequate stability in short-term observations. MATERIALS AND METHODS: Kyphoplasty was performed in 40 consecutive patients with primary osteoporosis and painful vertebral fractures, 20 received CaP-cement, 20 were treated with PMMA-cement. All patients received a pharmacological antiosteoporosis treatment (1000 mg calcium, 1000 IU vitamin D3, and oral aminobisphosphonate), pain medication, and physiotherapy. Pain (visual analog scale [VAS]; range, 0-100), mobility (EVOS-score; range, 0-100) and radiomorphologic measurements were assessed at baseline and after 6, 12, and 36 months. RESULTS: There were no statistically significant differences between the CaP and PMMA-cement group regarding VAS-scores, EVOS-scores, or height-restoration at any time point. Furthermore, there was no significant difference in the occurrence of vertebral follow-up fractures between both groups during the 3-year follow-up period. CONCLUSION: CaP cement, e.g., Calcibon, is as effective and safe as conventional PMMA-cement with regard to immediate and sustained pain reduction and improvement of mobility after kyphoplasty of patients with painful osteoporotic vertebral fractures. CaP cement has the potential of being resorbed and replaced by newly formed bone tissue; thus, it seems to be a promising alternative for PMMA also in younger patients with painful vertebral fractures.

Familial early onset sarcoidosis with bone cysts and erosions.

Early onset sarcoidosis is a granulomatous disease which is characterized by synovitis, polyarthritis, skin and eye involvement. We report the skeletal features of one patient with a family history and clinical symptoms suggestive of early onset sarcoidosis (EOS) which was confirmed by skin biopsy. Radiographs reveal postarthritic deformities of the MCP joints, contractures, a coarsened trabecular pattern at the PIP joints and small bone cysts resembling osteitis cystoides multiplex. Similar lesions were described in radiographs of the older sister and an uncle of our patient. This is the first report demonstrating bone cysts and erosions which could be a diagnostic feature in this rare disease and may help to differentiate other rheumatoid disorders.

The intravertebral vacuum phenomen as specific sign of osteonecrosis in vertebral compression fractures: results from a radiological and histological study.

This study investigated the prevalence of the intravertebral vacuum phenomenon (IVP) and osteonecroses in vertebral compression fractures (VCFs). We therefore performed an histological analysis of biopsies obtained from VCFs prior to balloon kyphoplasty. Computed tomography (CT) scans were reviewed regarding the presence of an IVP (i.e. cleft sign, Kümmell disease). We reviewed the data of 266 consecutive patients treated by balloon kyphoplasty in 501 procedures from 2002 to 2004. From 180 patients (68%) we obtained adequate bone tissue for histological evaluation. Biopsy specimens were analysed regarding the presence of osteoporosis, infection, malignancy and osteonecrosis. CT scans of all 180 patients were reviewed for presence of an IVP. Histological examination revealed 135 (75%) osteoporoses, 20 (11%) neoplasms, 12 (7%) trauma cases and 13 (7%) osteonecroses. An IVP was present in 12 (7%) patients. There was a significant association of osteonecrosis and IVP (P < 0.0001). Eleven of 12 patients with a vacuum phenomenon showed an osteonecrosis on histology, whereas 11 of 13 patients with osteonecrosis showed an IVP on CT. The IVP is a specific sign of osteonecrosis in vertebral compression fractures (sensitivity 85%, specificity 99%, positive predictive value 91%). Our findings strongly support the thesis that an IVP indicates local bone ischemia associated with a non-healing vertebral collapse and pseudarthrosis.

Interventional therapy of vascular complications following renal transplantation.

Renal transplantation is accepted as the preferred treatment for most cases of end-stage renal disease. Postoperative vascular complications include stenosis or thrombosis of the transplant renal artery or arteriovenous fistulas after biopsy. Impaired arterial perfusion of the transplant may be the leading cause for graft dysfunction or refractory hypertension. Therefore, non-invasive imaging modalities are required to detect and locate vascular complications with high accuracy. Doppler ultrasound is suited as a screening method for the detection of impaired graft perfusion. Magnetic resonance imaging (MRI) is used for an accurate diagnosis of vascular complications and to support decision for appropriate surgical or interventional treatment. Minimal invasive techniques like percutaneous transluminal angioplasty and stent placement have evolved as safe procedures with a high technical success rate reducing substantial morbidity. They can be considered as an alternative to surgical treatment of transplant renal artery stenosis (TRAS). Embolization of severe arteriovenous fistulas is the method of choice if the feeding artery can be occluded through a microcatheter. In selected cases, even catheter-guided fibrinolytic treatment of arterial thrombosis might be considered, if instantaneous surgery is considered a high-risk procedure. This article reviews the imaging features of common vascular complications after renal transplantation with focus on MRI. In addition, interventional radiological techniques are described for the treatment of TRAS, acute thrombotic occlusion, and arteriovenous fistulas.

Early changes in experimental osteoarthritis using the Pond-Nuki dog model: technical procedure and initial results of in vivo MR imaging.

The purpose of this study was to prove the feasibility of combining in vivo MR imaging with the Pond-Nuki animal model for the evaluation of osteoarthritis. In an experimental study, 24 beagle dogs underwent transection of the anterior cruciate ligament of the left leg (modified Pond-Nuki model). The dogs were randomly assigned into four groups and examined by MRI after 6, 12, 24 and 48 weeks. MR imaging of both knees was performed under general anesthesia with the contralateral joint serving as control. In group 1 (6 weeks postoperatively), the first sign detected on MRI was subchondral bone marrow edema in the posteromedial tibia. After 12 weeks, erosion of the posteromedial tibial cartilage could be observed, followed by meniscus degeneration and osteophytosis after 24 and 48 weeks. The contralateral knee joint showed transient joint effusion, but no significant signs of internal derangement (P<0.001). By combining in vivo MR imaging with the Pond-Nuki model, it is possible to detect early signs of osteoarthritis. The first sign was posteromedial subchondral bone marrow edema in the tibia followed by progressive cartilage degeneration and joint derangement. The in vivo model therefore seems to be suitable for longitudinal studies or monitoring the therapeutic effects of osteoarthritis.

Reduction of pain and fracture incidence after kyphoplasty: 1-year outcomes of a prospective controlled trial of patients with primary osteoporosis.

Previously, we reported significantly reduced pain and improved mobility persisting for 6 months after kyphoplasty of chronically painful osteoporotic vertebral fractures in the first prospective controlled trial. Since improvement of spinal biomechanics by restoration of vertebral morphology may affect the incidence of fracture, long-term clinical benefit and thereby cost-effectiveness, here we extend our previous work to assess occurrence of new vertebral fractures and clinical parameters 1 year after kyphoplasty compared with a conservatively treated control group. Sixty patients with osteoporotic vertebral fractures due to primary osteoporosis were included: 40 patients were treated with kyphoplasty, 20 served as controls. All patients received standard medical treatment. Morphological characteristics, new vertebral fractures, pain (visual analog scale), physical function [European Vertebral Osteoporosis Study (EVOS) score] (range 0-100 each) and back-pain-related doctors' visits were re-assessed 12 months after kyphoplasty. There were significantly fewer patients with new vertebral fractures of the thoracic and lumbar spine, after 12-months, in the kyphoplasty group than in the control group (P=0.0084). Pain scores improved from 26.2 to 44.4 in the kyphoplasty group and changed from 33.6 to 34.3 in the control group (P=0.008). Kyphoplasty treated patients required a mean of 5.3 back-pain-related doctors' visits per patient compared with 11.6 in the control group during 12 months follow-up (P=0.006). Kyphoplasty as an addition to medical treatment and when performed in appropriately selected patients by an interdisciplinary team persistently improves pain and reduces occurrence of new vertebral fractures and healthcare utilization for at least 12 months in individuals with primary osteoporosis.