Reduction in Fracture Rate and Back Pain and Increased Quality of Life in Postmenopausal Women Treated with Teriparatide: 18-Month Data from the European Forsteo Observational Study (EFOS)

The European Forsteo Observational Study was designed to examine the effectiveness of teriparatide in postmenopausal women with osteoporosis treated for up to 18 months in normal clinical practice in eight European countries. The incidence of clinical vertebral and nonvertebral fragility fractures, back pain, and health-related quality of life (HRQoL, EQ-5D) were assessed. Spontaneous reports of adverse events were collected. All 1,648 enrolled women were teriparatide treatment-naive, 91.0% of them had previously received other anti-osteoporosis drugs, and 72.8% completed the 18-month study. A total of 168 incident clinical fractures were sustained by 138 (8.8%) women (821 fractures/10,000 patient-years). A 47% decrease in the odds of fracture in the last 6-month period compared to the first 6-month period was observed (P < 0.005). Mean back pain VAS was reduced by 25.8 mm at end point (P < 0.001). Mean change from baseline in EQ-VAS was 13 mm by 18 months. The largest improvements were reported in the EQ-5D subdomains of usual activities and pain/discomfort. There were 365 adverse events spontaneously reported, of which 48.0% were considered related to teriparatide; adverse events were the reason for discontinuation for 79 (5.8%) patients. In conclusion, postmenopausal women with severe osteoporosis who were prescribed teriparatide in standard clinical practice had a significant reduction in the incidence of fragility fractures and a reduction in back pain over an 18-month treatment period. This was associated with a clinically significant improvement in HRQoL. Safety was consistent with current prescribing information. These results should be interpreted in the context of the open-label, noncontrolled design of the study.     

DC‐gated high resolution three‐dimensional lung imaging during free‐breathing

Purpose:

To use the acquisition of the k‐space center signal (DC signal) implemented into a Cartesian three‐dimensional (3D) FLASH sequence for retrospective respiratory self‐gating and, thus, for the examination of the whole human lung in high spatial resolution during free breathing.

Materials and Methods:

Volunteer as well as patient measurements were performed under free breathing conditions. The DC signal is acquired after the actual image data acquisition within each excitation of a 3D FLASH sequence. The DC signal is then used to track respiratory motion for retrospective respiratory gating.

Results:

It is shown that the acquisition of the DC signal after the imaging module can be used in a 3D FLASH sequence to extract respiratory motion information for retrospective respiratory self‐gating and allows for shorter echo times (TE) and therefore increased lung parenchyma SNR.

Conclusion:

The acquisition of the DC signal after image signal acquisition allows successful retrospective gating, enabling the reconstruction of high resolution images of the whole human lung under free breathing conditions. J. Magn. Reson. Imaging 2013;37:727–732. © 2012 Wiley Periodicals, Inc.     

Reconstruction of undersampled non-Cartesian data sets using pseudo-Cartesian GRAPPA in conjunction with GROG.

Most k-space-based parallel imaging reconstruction techniques, such as Generalized Autocalibrating Partially Parallel Acquisitions (GRAPPA), necessitate the acquisition of regularly sampled Cartesian k-space data to reconstruct a nonaliased image efficiently. However, non-Cartesian sampling schemes offer some inherent advantages to the user due to their better coverage of the center of k-space and faster acquisition times. On the other hand, these sampling schemes have the disadvantage that the points acquired generally do not lie on a grid and have complex k-space sampling patterns. Thus, the extension of Cartesian GRAPPA to non-Cartesian sequences is nontrivial. This study introduces a simple, novel method for performing Cartesian GRAPPA reconstructions on undersampled non-Cartesian k-space data gridded using GROG (GRAPPA Operator Gridding) to arrive at a nonaliased image. Because the undersampled non-Cartesian data cannot be reconstructed using a single GRAPPA kernel, several Cartesian patterns are selected for the reconstruction. This flexibility in terms of both the appearance and number of patterns allows this pseudo-Cartesian GRAPPA to be used with undersampled data sets acquired with any non-Cartesian trajectory. The successful implementation of the reconstruction algorithm using several different trajectories, including radial, rosette, spiral, one-dimensional non-Cartesian, and zig-zag trajectories, is demonstrated.     

Potential of magnetization transfer MRI for target volume definition in patients with non‐small‐cell lung cancer

Purpose

To develop a magnetization transfer (MT) module in conjunction with a single‐shot MRI readout technique and to investigate the MT phenomenon in non‐small‐cell lung cancer (NSCLC) as an adjunct for radiation therapy planning.

Materials and Methods

A total of 10 patients with inoperable NSCLC were investigated using a 1.5T MR scanner. MT ratio (MTR) maps of several slices throughout the tumor were assessed. Each MTR‐map was acquired within a short breathhold. Fluorodeoxyglucose positron emission tomography (FDG‐PET) investigations were performed in addition to the MRI protocol. A total of 60 structures appearing conspicuous in FDG‐PET were compared with structures appearing conspicuous in corresponding MTR maps. Quantification of similarity between both modalities was performed using similarity index calculation.

Results

MTR‐maps showed different contrast than FDG‐PET images. However, structures that appeared conspicuous in FDG‐PET images, either by a marked signal enhancement or signal decrease, were found to be similarly present in MTR maps. A mean similarity index of 0.65 was calculated. MTR values of suspected atelectasis were on average lower than MTR values of tumor tissue.

Conclusion

The proposed MT‐MRI technique provides a high MT efficiency, while being robust and fast enough for breathhold acquisition. The results obtained encourage for further exploration of MT‐MRI as an adjunct for radiotherapy planning in NSCLC. J. Magn. Reson. Imaging 2008;28:1417–1424. © 2008 Wiley‐Liss, Inc.     

MRI thermometry: Fast mapping of RF‐induced heating along conductive wires

Conductive implants are in most cases a strict contraindication for MRI examinations, as RF pulses applied during the MRI measurement can lead to severe heating of the surrounding tissue. Understanding and mapping of these heating effects is therefore crucial for determining the circumstances under which patient examinations are safe. The use of fluoroptic probes is the standard procedure for monitoring these heating effects. However, the observed temperature increase is highly dependent on the positioning of such a probe, as it can only determine the temperature locally. Temperature mapping with MRI after RF heating can be used, but cooling effects during imaging lead to a significant underestimation of the heating effect. In this work, an MRI thermometry method was combined with an MRI heating sequence, allowing for temperature mapping during RF heating. This technique may provide new opportunities for implant safety investigations. Magn Reson Med, 2008. © 2008 Wiley‐Liss, Inc.     

Postoperative Cognitive Dysfunction in Middle-aged Patients

Background: Postoperative cognitive dysfunction (POCD) after noncardiac surgery is strongly associated with increasing age in elderly patients; middle-aged patients (aged 40-60 yr) may be expected to have a lower incidence, although subjective complaints are frequent.

Methods: The authors compared the changes in neuropsychological test results at 1 week and 3 months in patients aged 40-60 yr, using a battery of neuropsychological tests, with those of age-matched control subjects using Z-score analysis. They assessed risk factors and associations of POCD with measures of subjective cognitive function, depression, and activities of daily living.

Results: At 7 days, cognitive dysfunction as defined was present in 19.2% (confidence interval [CI], 15.7-23.1) of the patients and in 4.0% (CI, 1.6-8.0) of control subjects (P < 0.001). After 3 months, the incidence was 6.2% (CI, 4.1-8.9) in patients and 4.1% (CI, 1.7-8.4) in control subjects (not significant). POCD at 7 days was associated with supplementary epidural analgesia and reported avoidance of alcohol consumption. At 3 months, 29% of patients had subjective symptoms of POCD, and this finding was associated with depression. Early POCD was associated with reports of lower activity scores at 3 months.     

Endoluminal stent graft repair for acute and chronic type B aortic dissection and atherosclerotic aneurysm of the thoracic aorta: an interdisciplinary task

Objective: Endoluminal thoracic aortic stenting is a new therapeutic tool in reducing the operative trauma of the patient. However, the inherent risks of aortic stent grafting are perivascular leakage, stent dislocation, blunt rupture of the aorta, side branch occlusion and neurological sequelae. To reduce these risks, in our institution all stent implantations were performed in close collaboration with our fellow cardiologists under biplane X-ray control supported by simultaneous intravascular and transoesophageal ultrasound imaging. Methods: Between August 1999 and August 2001, endovascular stent graft repair was performed in 34 patients (27 male, seven female) with a mean age of 68.6±7 years (range 58–84). Indication for treatment was an acute Type B aortic dissection in six patients (18%), a symptomatic chronic Type B dissection in 12 patients (35%), a true aneurysm of the descending aorta in seven patients (21%) and an atherosclerotic contained rupture of the descending aorta in nine (26%) patients. Out of six acute type B dissections three patients (8.8%) and one patient (2.9%) out of the chronic dissection group were in severe haemorrhagic shock, ventilated and required high-dose adrenergic support. The others (30 patients, 88.3%) remained symptomatic despite maximum medical treatment. In a special case a combined surgical and endoluminal stent graft repair was performed. Individually manufactured Talent, Medtronic AVE (33), and Gore (1) stents were used. Follow-up examination was performed 1 week after implantation and repeated every 3 months (mean follow-up 8 months, range 1–24). Results: In all patients the aneurysm or the entry of the dissection could be excluded. The observed hospital mortality was 2.9% (one patient). No perivascular leakage, no stent dislocation, no neurological deficit or perfusion impairment was observed. All patients except four were extubated immediately after the procedure and discharged from hospital on postoperative day 2–3. The late procedure-related mortality was 5.8% (two patients) resulting in an overall mortality of 8.8% (three patients). Conclusion: Stent graft repair is a safe and feasible treatment option for selected patients, especially in emergency situations, if the aortic lesions can be clearly identified and localized. The use of biplane X-ray control combined with simultaneous intravascular and transoesophageal ultrasound imaging in an interdisciplinary approach enables a more precise targeting of the stent landing zone, resulting in low morbidity and mortality rates.     

Design considerations in implant-related randomized trials

Implant-related research is particularly prone to produce biased results. Despite a common commitment to evidence-based principles (EBM) principles in current literature, a gap remains between the existing available evidence and its actual implementation in orthopaedic clinical practice. Knowledge of basic principles of implant related trial design is a prerequisite for critical appraisal of the value of scientific evidence and thereby the degree of uncertainty. This article discusses how the quality of implant-related randomized controlled trials (RCT) can be affected by the level of expertise, the choice of outcome measures, the allocation procedure, and the method of blinding. Taking these issues into consideration in the design of an implant-related study improves the value of the study, thereby achieving an unbiased assessment of the safety and efficacy of an innovative implant prior to its widespread implementation in daily health care.     

Central mesenteric lymph node BER-Ep4+ cells in colorectal cancer: challenge to sentinel node concept?

BACKGROUND: The role of sentinel lymph nodes in colorectal cancer remains unclear. METHODS: Cryosections from central para-aortic mesenterial lymph nodes were stained using mAb BER-Ep4. Overall survival and distant recurrence were calculated using Kaplan-Meier plots. RESULTS: All patients (n = 48) were free of distant metastases and curatively resected (R0). 23 pN0, 13 pN1 and 12 pN2 stages were found. 21/48 patients (44%) showed BER-Ep4+ cells in their central lymph nodes (7/23 pN0, 8/13 pN1, 6/12 pN2). In 6/23 pN0 patients, BER-Ep4+ cells were also found in locoregional nodes (p = 0.03, Fisher's exact test). pN status predicted overall survival (p = 0.006, Kaplan-Meier curve, log-rank test). An impact was exerted by central mesenteric BER-Ep4+ cells on overall survival (p = 0.009 in pN0 patients, p = 0.07 for all pN) and distant recurrence-free survival (p = 0.001 in pN0 patients, p = 0.007 for all pN). Multivariate analysis showed an independent prognostic effect on overall survival in pN0 patients (p = 0.022). CONCLUSION: Central lymph nodes are sentinels of disease not amenable to extended lymphadenectomy and might identify patients at risk of distant organ recurrence.     

A virtual environment for surgical image guidance in intraoperative MRI.

Intraoperative MRI has recently entered the operating room as a new imaging modality. Customized visualization systems might further facilitate the use of this imaging technology. A visualization system for use in the interventional MRI has been developed, providing a virtual environment for surgical navigation using real-time images and for controlling the scanner. The visualization system has customized features for certain clinical applications. A training and testing facility has also been established. The introduction of the visualization system in the interventional MRI overcame several ambiguities and inconsistencies that were previously present, and resulted in a more transparent man-machine interface approach. A pilot study using the software to place cryoprobes in an animal liver showed promising results. Augmentation of real-time MR images with 3D rendering and customized navigation features opens new possibilities in intraoperative MRI. The described system can also be extended to other intraoperative imaging modalities.