Effects of denosumab on bone histomorphometry: The FREEDOM and STAND studies

Denosumab, a human monoclonal antibody against RANKL, reversibly inhibits osteoclast‐mediated bone resorption and has been developed for use in osteoporosis. Its effects on bone histomorphometry have not been described previously. Iliac crest bone biopsies were collected at 24 and/or 36 months from osteoporotic postmenopausal women in the FREEDOM study (45 women receiving placebo and 47 denosumab) and at 12 months from postmenopausal women previously treated with alendronate in the STAND study (21 continuing alendronate and 15 changed to denosumab at trial entry). Qualitative histologic evaluation of biopsies was unremarkable. In the FREEDOM study, median eroded surface was reduced by more than 80% and osteoclasts were absent from more than 50% of biopsies in the denosumab group. Double labeling in trabecular bone was observed in 94% of placebo bones and in 19% of those treated with denosumab. Median bone‐formation rate was reduced by 97%. Among denosumab‐treated subjects, those with double labels and those with absent labels had similar levels of biochemical markers of bone turnover. In the STAND trial, indices of bone turnover tended to be lower in the denosumab group than in the alendronate group. Double labeling in trabecular bone was seen in 20% of the denosumab biopsies and in 90% of the alendronate samples. Denosumab markedly reduces bone turnover and also reduces fracture numbers. Longer follow‐up is necessary to determine how long such low turnover is safe. © 2010 American Society for Bone and Mineral Research.     

Osteosarcoma of the spine: experience in 26 patients treated at the Massachusetts General Hospital

Background contextBecause of the low incidence, treatment recommendations for spinal osteosarcoma are guided by the results of small series and case reports. Many include patients who presented for treatment over the course of three to four decades.PurposeThe goal of this investigation was to report the treatments, results, and overall survivorship of 26 patients treated for osteosarcoma of the spine at a single institution.Study designRetrospective prognostic series (Level III evidence).Patient sampleTwenty-six patients treated at a single center for osteosarcoma of the spine over a 26-year period.Outcome measuresEstimation of patient survival, local recurrence, and the presence of metastatic disease.MethodsWe performed a retrospective review of cases of osteosarcoma involving the spine treated at our institution between 1982 and 2008. Medical charts, radiology reports, pathology reports, and operative notes were reviewed for all patients. Available imaging studies were also reviewed. The log-rank test was used to compare baseline differences between groups. Survivorship analysis was performed using Kaplan–Meier methodology. The effect of Paget osteosarcoma, type of resection, presence of local recurrence, tumor size, surgical margins, and metastases on overall survival were also investigated using the log-rank test.ResultsTwenty-six patients were included for review in this study. Twenty individuals were treated surgically, and 24 were treated with radiation with a mean dose of 62.2 Gy (range 20–84.7 Gy). Twenty-five patients received chemotherapy. Of those treated surgically, seven received en bloc resection. The median overall survival for all patients in our series was 29.5 months (standard error 14.7, 95% confidence interval 0.6–58). Local recurrence developed in 7 patients (27%), and metastasis occurred in 16 individuals (62%). Patients with Paget osteosarcoma had worse overall survival (p<.001).ConclusionsResults presented here confirm a poor prognosis for patients with spinal osteosarcoma. Although combination therapies, including surgery, chemotherapy, and high-dose radiation, achieve adequate short-term survival, the 5-year mortality rate remains high.     

Hippocampal blood flow in normal aging measured with arterial spin labeling at 3T

Due to methodological difficulties related to the small size, variable distribution of hippocampal arteries, and the location of the hippocampus in the proximity of middle cranial fossa, little is known about hippocampal blood flow (HBF). We have tested the utility of a pulsed arterial spin labeling sequence based on multi‐shot true fast imaging in steady precession to measure HBF in 34 normal volunteers (17 women, 17 men, 26–92 years old). Flow sensitivity to a mild hypercapnic challenge was also examined. Coregistered 3D MPRAGE sequence was used to eliminate from hippocampal and cortical regions of interest all voxel with <75% of gray matter. Large blood vessels were also excluded. HBF in normal volunteers averaged 61.2 ± 9.0 mL/(100 g min). There was no statistically significant age or gender effect. Under a mild hypercapnia challenge (end tidal CO₂ pressure increase of 6.8 ± 1.9 mmHg over the baseline), HBF response was 14.1 ± 10.8 mL/(100 g min), whereas cortical gray matter flow increased by 18.0 ± 12.2 mL/(100 g min). Flow response among women was significantly larger than in the men. The average absolute difference between two successive HBF measures was 3.6 mL/(100 g min) or 5.4%. The 3T true fast imaging in steady precession arterial spin labeling method offers a HBF measurement strategy that combines good spatial resolution, sensitivity, and minimal image distortions. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Dissection of the Abdominal Aorta in Blunt Trauma: Management by Percutaneous Stent Placement

We implanted stents in three patients who had traumatic abdominal aortic dissections, complicated by right limb ischemia in one case. The circulating false channel extended to the left iliac artery in one case and to both iliac arteries in the last case. Diagnosis and radiological follow-up included ultrasound, computed tomography, and arteriography. Two patients were treated with Wallstents, one with a Palmaz stent. The occlusion of the false channel was obtained in all patients without any significant residual stenosis. No early or late complication was noted in any of the patients. The longest follow-up was 2 years. We conclude that stent placement is an efficient method for the treatment of noniatrogenic inframesenteric aortic dissections. Received: 0/00/00/Accepted: 0/00/00     

Computed tomography of Paget disease of the skull versus fibrous dysplasia

Objective. Radiologists are often challenged to review CT examinations of the skull without pertinent clinical information or plain radiographs. Skull lesions of fibrous dysplasia (FD) may often be confused with Paget disease (PD). The purpose of this article is to evaluate radiographic similarities and to find the signs that can differentiate PD from FD of the skull on head CT and to describe the CT imaging features of PD and FD. Design and patients. CT scans of the skull in eight cases of PD, 18 cases of FD (13 cases of skull and facial bones, five cases of only facial bones) and 10 normals were studied retrospectively. Results. Ten features were found to be similar in PD and FD and 10 other features were found to be dissimilar. The frequency of the 10 differentiating features was evaluated to determine their reliability in distinguishing one disorder from the other. The differentiating features in order of significance include: (1) “groundglass” appearance, (2) symmetry, (3) involvement of the paranasal sinuses, (4) thickness of the cranial cortices, (5) involvement of the sphenoid bone, (6) orbital involvement, (7) nasal cavity involvement, (8) presence of a soft tissue mass, (9) maxillary involvement, and (10) the presence of cyst-like changes. Conclusion. These 10 signs improve the radiologist’s skill in differentiating FD and PD.     

Increased incidence of gastrointestinal surgical complications in renal transplant recipients with polycystic kidney disease

BACKGROUND: We had the impression that, although our renal transplant recipients with polycystic kidney disease (PKD) had excellent long-term renal graft function, they had an increased incidence of postoperative gastrointestinal (GI) complications. METHODS: Over a 10-year period (1987 through 1996), 1467 renal transplants were performed in 1417 patients; 145 of these transplants involved PKD recipients. In the PKD group, 18 patients (12.4%) developed a posttransplant complication necessitating GI surgery (PKD-GI), an incidence twice that in the non-PKD recipients (73 patients or 6.2%, non-PKD-GI). RESULTS: PKD and non-PKD recipients displayed no significant difference in mortality. The PKD patients had better long-term renal graft survival than the non-PKD patients (P=0.08). There was no difference in mortality (P>0.6) or renal graft survival (P>0.6) between the PKD-GI and PKD-non-GI groups. The PKD-GI group had no increased mortality over the non-PKD-GI patients (P>0.6), despite a higher incidence of GI surgical complications in the PKD group versus the non-PKD group (overall: 12.4 vs. 6.2%, P<0.01; within 90 days of transplant: 7.6 vs. 3.3%, P<0.02) and a greater propensity for small and large bowel complications (overall: 9.0 vs. 2.6%; P< 0.001; less than 90 days: 6.9 vs. 2.0%, P<0.002). The PKD-GI recipients tended toward less long-term graft loss than their non-PKD-GI counterparts (11.1 vs. 27.4%; P=.22). The PKD-GI recipients suffered no acute rejection episodes within 90 days after their GI operation versus 11 of 73 non-PKD-GI recipients (O vs. 15.1%; P=0.075). CONCLUSIONS: PKD recipients of renal grafts should be watched closely early after transplant because of their increased risk of GI complications. These complications resulted in no increase in mortality or graft loss compared to non-PKD recipients with GI complications despite the PKD group's higher incidence of bowel perforation and increased age at time of transplant.     

Total hip prosthesis CT with single-energy projection-based metallic artifact reduction: impact on the visualization of specific periprosthetic soft tissue structures

Objectives

To compare the image quality of CT with iterative reconstruction alone and in association with projection-based single-energy metal artifact reduction (SEMAR) for the visualization of specific periarticular soft tissue structures in patients with hip prostheses.

Methods

CT studies from 48 consecutive patients with a hip prosthesis (24 unilateral and 24 bilateral) were retrospectively reconstructed using two different methods: iterative reconstruction (IR) alone and IR associated with SEMAR. The influence of metallic artifacts on the identification of various periarticular structures was evaluated subjectively by two readers. The image quality was compared in patients with unilateral and bilateral prostheses.

Results

Visualization of periprosthetic soft tissue was significantly improved by the SEMAR algorithm (p?<?0.0001). When SEMAR was associated with IR, the gluteus minimus and medius tendons, obturator internus muscle, prostate/uterus and bladder could be seen with medium or high confidence. There were no significant differences in image quality between patients with unilateral or bilateral prosthesis when SEMAR was used (p?>?0.2). This algorithm increased the detection of periarticular masses by 30 %.

Conclusion

SEMAR significantly improves the image quality of periarticular soft-tissue structures in patients with hip prostheses.     

Effect of Ascorbic Acid on Infarct Size in Experimental Focal Cerebral Ischaemia and Reperfusion in a Primate Model

Summary  Temporary occlusion of major cerebral blood vessels occasionally becomes necessary during surgical procedures. Ascorbic acid (Vitamin C) is an important non-enzymatic scavenger of free radicals and its protective effect on the brain in permanent focal cerebral ischaemia has been proven in a primate model of focal cerebral ischaemia [16]. Additional damage caused by reperfusion of the infarcted area has been shown in the rat model [22].  This study was undertaken to study the efficacy of ascorbic acid in decreasing infarct size in ischaemic reperfused brain.  Maccaca radiata monkeys in the treated group were given two grams of ascorbic acid, parentally immediately before clipping the middle cerebral artery and the control group was given placebo. Reperfusion was done after four hours. Mean infarct size in all the three brain slices in the ascorbic acid pretreated group was 7.3%±2.7 and in the placebo group 22.1±6.7 under similar conditions. The mean infarct size in the ascorbic acid pretreated group of monkeys was significantly lower when compared with the placebo group (p=0.0003).     

Adenocarcinoma of the duodenum: factors influencing long-term survival

This single-institution retrospective analysis reviews the management and outcome of patients with surgically treated adenocarcinoma of the duodenum. Between February 1984 and August 1996, fifty-five patients with adenocarcinoma of the duodenum underwent surgery at The Johns Hopkins Hospital. Univariate analysis was performed to identify possible prognostic indicators. Curative resection was performed in 48 patients (87%): 35 of these patients (73%) underwent a pancreaticoduodenectomy (PD), whereas 27% (n = 13) underwent a pancreas-sparing duodenectomy (PSD). Patients undergoing PD were comparable to those undergoing PSD with respect to demographic factors, presenting symptoms, and tumor pathology. The remaining 13% of patients (n = 7) were deemed unresectable at the time of surgery and underwent biopsy and/or palliative bypass. PD was associated with an increase in postoperative complications when compared to PSD (57% vs. 30%), but this difference was not statistically significant. One perioperative death occurred following PD (mortality 2.9%), The overall 5-year survival rate for the 48 patients undergoing potentially curative resection was 53 %. Negative resection margins (P <0.001), PD (P <0.005), and tumors in the first and second portions of the duodenum (P <0.05) were favorable predictors of long-term survival by univariate analysis. Nodal status, tumor diameter, degree of differentiation, and the use of adjuvant chemoradiation therapy did not influence survival. These data support an aggressive role for resection in patients with adenocarcinoma of the duodenum Presented at the Thirty-Eighth Annual Meeting of The Society for Surgery of the Alimentary Tract, Washington, D.C., May 11–14, 1997.