Alterations of bone geometry, density, microarchitecture, and biomechanical properties in systemic lupus erythematosus on long-term glucocorticoid: a case–control study using HR-pQCT

Summary

Compared to controls, HR-pQCT at distal radius of SLE patients on chronic glucocorticoid (SLE/GC) revealed reduced bone area, vBMD, deteriorated microarchitecture, and unevenly distributed stresses limited to cortical bone. Despite similar trabecular quality, whole bone strength decreased in patients. These alterations may partly explain high fracture rates in SLE/GC.

Introduction

To assess bone geometric, densitometric, microarchitectural, and biomechanical properties in patients with systemic lupus erythematosus (SLE) on long-term glucocorticoid (GC) (SLE/GC) as compared with healthy controls.

Methods

A total of 180 female SLE patients and 180 healthy controls were in this cross-sectional study to assess areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) and microfinite element analysis (μFEA) was performed at distal radius.

Results

In addition to significantly lower aBMD at femoral neck, total hip and lumbar spine, cortical area, average volumetric BMD (vBMD) and cortical vBMD also significantly reduced by 5.3, 5.7, to 1.9 % in SLE patients, respectively. Deteriorations of cortical microarchitecture were pronounced in patients, with 6.3 % reduction in cortical thickness and 13.6 % higher in cortical porosity. Local stresses were more unevenly distributed through cortical bone in patients. SLE/GC patients had decreased whole bone stiffness, estimated failure load, and apparent modulus. Parameters related to trabecular bone density and microarchitecture were comparable between patients and controls.

Conclusion

In SLE/GC patients, despite a reduction in bone area, vBMD and deteriorated microarchitecture and unevenly distributed stresses limited to the cortical compartment, whole bone strength decreased. HR-pQCT and μFEA were promising in elucidating the potential underlying pathophysiology of bone loss and propensity to fracture in SLE/GC and provide us additional information about alterations of bone quality which might better predict fracture risk beyond aBMD in SLE/GC.     

Repair of large midline incisional hernias with polypropylene mesh: Comparison of three operative techniques

Polypropylene mesh is widely used for the reconstruction of incisional hernias that cannot be closed primarily. Several techniques have been advocated to implant the mesh. The objective of this study was to evaluate, retrospectively, early and late results of three different techniques, onlay, inlay, and underlay. The records of 53 consecutive patients with a large midline incisional hernia — 25 women and 28 men, mean age 60.4 (range 28–94) — were reviewed. Polypropylene mesh was implanted using the onlay technique in 13 patients, inlay in 23 patients, and underlay in 17 patients. Either the greater omentum or a polyglactin mesh was interponated between the mesh and the viscera. The records of these 53 patients were reviewed with respect to: size and cause of the hernia, pre- and postoperative mortality and morbidity, with special attention to wound complications. Patients were invited to attend the outpatient clinic at least 12 months after implantation of the mesh for physical examination of the abdominal wall. Postoperative complications occurred in 14 (26.4%) patients. The onlay technique had significantly more complications, as compared to both other techniques. Reherniation occurred in 15 (28.3%) patients. The reherniation rate of the inlay technique was significantly higher than after the underlay technique (44% vs 12%, P=0.03) and tended to be higher than the onlay technique (44% vs 23%, P=0.22). Repair of large midline incisional hernias with the use of a polypropylene mesh carries a high risk of complications and has a high reherniation rate. The underlay technique seems to be the better technique.     

Virchow triad, but not use of an aortic connector device, predicts early graft failure after off-pump coronary bypass

The risk of early thrombosis of coronary artery bypass (CAB) grafts may be increased after off-pump CAB, particularly after the use of an aortic connector device (ACD) to perform the proximal aortosaphenous anastomosis. We have been investigating tools that quantify the risk of early vein graft thrombosis after off-pump CAB on the basis of the Virchow triad of hypercoagulability, endothelial disease, and low conduit flow. These tools were applied in this prospective trial of a heterogeneous group of patients with varying degrees of aortic disease and who received the Symmetry ACD. After controlling for the Virchow risk factor triad, we hypothesized that the ACD does not independently influence graft thrombosis. There was no statistically significant difference in the early thrombosis rates of vein grafts connected with an ACD versus hand-sewn grafts (6.7% versus 6.5%). We found a wide range of graft flow measurements, platelet function, and vein endothelial phenotypes in patients with traditionally hand-sewn vein grafts and with grafts connected with an ACD in patients with a wide range of ascending aortic atherosclerosis. The perioperative combination of platelet hyperreactivity, marginal graft flow, and endothelial disease proved to be highly predictive of early graft failure as seen with postoperative computed tomographic angiography.     

Ultrasound for the detection of vegetative foreign body in hand--a case report.

Foreign bodies in soft tissues are commonly encountered in daily orthopaedic practice. While most of the metals and glass foreign bodies can be detected by plain radiograph, organic substances such as wood and vegetative materials are radiolucent. Unfortunately, these radiolucent foreign bodies are usually more prone to cause an inflammatory reaction and infection. The detection can be even more difficult in cases of multiple foreign bodies and in penetrating injuries with small innocuous skin wounds. Ultrasonography is a sensitive and reliable investigation for detection of foreign bodies in soft tissue. We present a case of penetration injury to thumb with residual radiolucent foreign bodies and demonstrate the proper role of ultrasonography in the management of foreign bodies in soft tissues.     

Ultrastructural localization of human platelet thrombospondin, fibrinogen, fibronectin, and von Willebrand factor in frozen thin section

We have investigated the localization of thrombospondin (TSP), fibrinogen, fibronectin, and von Willebrand factor in human platelets by transmission electron microscopy of antibody-stained ultrathin frozen sections. In negatively stained thin sections, alpha granules were identified on the basis of their smooth, roughly spherical shape, size, single limiting electron-lucent 100 A membrane, and frequent presence of electron-dense nucleoid. In contrast, mitochondria exhibited characteristic double membranes and cristae. Sections were separately stained with affinity-purified polyclonal antibodies to these proteins as well as with three monoclonal anti-TSP antibodies. Antibody specificity was documented in radioimmunoassays, by immunofluorescent cross-blocking, and by staining of bands of appropriate mobility in Western blots of whole platelets. Bound antibody was visualized using a 5-nm colloidal gold-avidin conjugate. In resting cells, staining of virtually all alpha granules was observed for all four proteins. In contrast, consistent staining was absent from other organelles, including plasma membranes, mitochondria, and vacuolar structures that may represent the open canalicular system.     

Results of late programmed electrical stimulation and long-term electrophysiologic effects of amiodarone therapy in patients with refractory ventricular tachycardia

Thirteen patients with refractory, recurrent, life-threatening ventricular tachycardia (VT) underwent electrophysiologic testing before and after long-term amiodarone therapy. Nine patients (69%) had coronary artery disease, 3 (23%) had nonischemic cardiomyopathy and 1 patient (8%) had mitral valve prolapse. At control electrophysiologic study, programmed electrical stimulation (PES) induced VT in all patients: sustained VT in 11 and nonsustained VT in 2 (9 beats and 31 beats). After oral loading with amiodarone, 1200 mg/day for 14 days, followed by maintenance therapy with 408 +/- 20 mg/day (mean +/- standard error of the mean), repeat PES at 6 +/- 1.6 months revealed inducible VT in 12 of 13 patients: sustained VT in 11 and nonsustained VT (32 beats) in 1 patient. Inducible VT was suppressed in only 1 patient. Amiodarone significantly increased sinus cycle length, PR interval, QRS duration and right ventricular effective refractory period. Insignificant increases in AH, HV and QTc intervals were noted. At 24 +/- 2 months, 8 patients (62%) (all with inducible VT at late PES) were free of clinical arrhythmic events (syncope or sudden death), compared with 5 patients (38%) (4 with inducible VT at late PES) with events. There were no significant differences in the induced VT cycle length, VT cycle length change, ease of inducibility or hemodynamic response to induced VT at late PES in patients with and without arrhythmic events.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunophotoelectron microscopy: the electron optical analog of immunofluorescence microscopy.

The electron optical analog of immunofluorescence microscopy combines three developments: (i) photo-electron microscopy to produce a high-resolution image of exposed components of the cell, (ii) site-specific antibodies, and (iii) photoemissive markers coupled to the antibodies to make the distribution of sites visible. This approach, in theory, provides a way to extend the useful immunofluorescence microscopy technique to problems requiring much higher resolution. The resolution limit of fluorescence microscopy is limited to about 200 nm by the wavelength of the light used to form the image, whereas in photoelectron microscopy the image is formed by electrons (current resolution: 10-20 nm; theoretical limit: 5 nm or better depending on the electron optics). As a test system, cytoskeletons of CV-1 epithelial cells were prepared under conditions that preserve microtubules, and the microtubule networks were visualized by both indirect immunofluorescence and immunophotoelectron microscopy using colloidal gold coated with antibodies. Colloidal gold serves as a label for immunophotoelectron microscopy, providing enhanced photoemission from labeled cellular components so that they stand out against the darker background of the remaining unlabeled structures. In samples prepared for both immunofluorescence and immunophotoelectron microscopy, individual microtubules in the same cells were visualized by both techniques. The photoemission of the colloidal gold markers is sufficiently high that the microtubules are easily recognized without reference to the immunofluorescence micrographs, indicating that this approach can be used, in combination with antibodies, to correlate structure and function in cell biological studies.     

Flecainide: electrophysiologic and antiarrhythmic properties in refractory ventricular tachycardia

Twenty-two patients with coronary artery disease and spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) underwent intracardiac electrophysiologic evaluation and, when possible, ambulatory monitoring before and after therapy with flecainide (mean dose 418 +/- 87 mg [mean +/- standard deviation]). An average of 4 antiarrhythmic agents were used and were unsuccessful before therapy with flecainide was begun. During 64 +/- 16 hours of control Holter monitoring in 16 patients, all had 1 or more salvos of VT, as well as ventricular premature complexes (VPCs). Programmed stimulation during the control period induced VT in 17 of 22 patients. After flecainide therapy, Holter monitoring showed elimination of all forms of VT in all but 1 patient, as well as significant reduction of paired VPCs by 95% (p less than 0.03) and single VPCs by 70% (p less than 0.005). Electrophysiologic study during flecainide therapy showed significant increases in AH, HV, PR, QRS and QTc intervals, and the ventricular effective refractory period. Programmed stimulation in 17 patients taking flecainide, with a mean plasma level of 1,075 +/- 521 ng/ml, showed ablation of inducible VT in only 2 patients, a worsening in 5 and continued VT inducibility in 10. Adverse effects that required drug withdrawal were infrequent and encountered in patients who received higher drug levels: 1 patient with congestive heart failure and 1 with severe sinus bradycardia. Thus, although flecainide suppresses complex ventricular arrhythmias on Holter recordings, it rarely alters the response to programmed stimulation. Caution is recommended in its use for recurrent sustained VT or VF and in the interpretation of electrophysiologic studies until the predictive value of programmed stimulation with flecainide therapy is established.     

Short‐term outcome following elective laparoscopic colorectal cancer resection in octogenarians and nonagenarians

Aim The 30‐day outcome after laparoscopic resection for cancer in patients over the age of 80 years was studied. Method An electronic database was used to identify patients over 80 years who underwent laparoscopic bowel resection between December 2000 and October 2009 at three UK laparoscopic colorectal training units. Patients who required abdominoperineal excision of the rectum were excluded. Results In all, 173 patients (80 men) of median age 84 (80–93) years were identified. American Society of Anesthesiologists (ASA) grades were ASA 1, 14; ASA 2, 87; ASA 3, 68; and ASA 4, 4. Median body mass index was 26 (14–45) kg/m². Thirteen (7.5%) patients were converted to open surgery. The major causes for conversion were bleeding and adhesions. Thirty‐three major complications occurred in 21 (12%) patients. Ten (5.8%) required readmission after discharge for complications giving a total of 17.8% of patients with complications. The median hospital stay was 5 (1–37) days. Three (1.7%) patients died within 30 days of surgery. Conclusion This study confirms that laparoscopic large bowel resection is safe and beneficial in a population over 80 years. It has low morbidity and mortality and a shortened hospital stay. Octogenarians should not be denied major laparoscopic bowel surgery based on age alone.     

Bone Density and Microarchitecture: Relationship Between Hand, Peripheral, and Axial Skeletal Sites Assessed by HR-pQCT and DXA in Rheumatoid Arthritis

We assessed the relationship of bone density and microarchitecture between hand, peripheral, and axial skeletal sites using high-resolution peripheral quantitative computed tomography (HR-pQCT) and dual-energy X-ray absorptiometry (DXA) in patients with rheumatoid arthritis (RA) and which factors influence these parameters. This was a cross-sectional study of 100 female patients (53.4?±?9.3?years) with RA. HR-pQCT scans at distal radius and the second metacarpal head were performed to assess cortical and trabecular volumetric bone mineral density (vBMD) and microarchitecture. DXA scans at the hip, lumbar spine, and ultradistal radius were performed to assess areal BMD. There was significant correlation in vBMD and microarchitectural parameters between the second metacarpal head and distal radius (r?=?0.201?0.628). Areal BMD at the axial skeleton was moderately associated with vBMD at the peripheral sites (r?=?0.354–0.558). Factors related to disease severity/chronicity significantly correlated with vBMD and microarchitecture at the distal radius and the second metacarpal head. Factors related to disease activity were more likely to correlate with vBMD and microarchitecture at the second metacarpal head but not those at the distal radius. HR-pQCT is a promising technique that is capable of providing detailed quantitative assessment of disease-associated periarticular bone loss at both cortical and trabecular bone compartments in patients with RA. Future longitudinal studies will be needed to investigate whether assessment by HR-pQCT can be used as a marker of disease activity and a predictor of disease progression in RA.