Kong Chiu Wong

Cardiovascular risk profile of patients with psoriatic arthritis compared to controls—the role of inflammation

OBJECTIVE To examine the distribution of traditional and novel risk factors of cardiovascular disease (CVD) in patients with PsA compared with healthy controls. METHODS We compared risk factors for CVD between 102 consecutive PsA patients and 82 controls, adjusting for BMI. We also assessed the role of inflammation on the CVD risk factor by using a BMI and high-sensitivity CRP (hsCRP)-adjusted model. RESULTS The BMI of PsA patients were significantly higher than healthy controls. After adjusting for the BMI, PsA patients still have a higher prevalence of diabetes mellitus (DM) [odds ratio (OR) 9.27, 95% CI 2.09, 41.09) and hypertension (OR 3.37, 95% CI 1.68, 6.72), but a lower prevalence of low high density lipoprotein (HDL) cholesterol (OR 0.16, 95% CI 0.07, 0.41). PsA patients have significantly increased systolic and diastolic blood pressures, insulin resistance and inflammatory markers (hsCRP and white cell count) compared to controls. PsA patients have higher HDL cholesterol and apolipoprotein (Apo) A1 levels; and lower total cholesterol (TC) and low density lipoprotein cholesterol levels; and a lower TC/HDL ratio. However, the Apo B level (P < 0.05), and the Apo B/Apo A1 ratio (P = 0.07) were higher in PsA patients. Further adjustment for hsCRP level rendered the differences in the prevalence of hypertension and DM; the TC, and sugar levels; and white cell count non-significant between the two groups; while the differences in other parameters remained significant. CONCLUSION These data support the hypothesis that PsA may be associated with obesity, hypertension, dyslipidaemia and insulin resistance because of the shared inflammatory pathway.

Is combination rituximab with cyclophosphamide better than rituximab alone in the treatment of lupus nephritis

OBJECTIVE To assess if combination rituximab and cyclophosphamide is more effective than rituximab monotherapy as an induction therapy for proliferative lupus nephritis. METHODS A randomized open-label pilot study in which 9 patients received rituximab alone and 10 patients received two doses rituximab + intravenous cyclophosphamide. The clinical, laboratory and renal histological changes were assessed after 48 weeks of treatment. RESULTS At week 48, four patients had a complete response, 11 patients achieved partial response, 2 patients remained the same or stable and 2 worsened. There were no statistical differences in the proportion of patients with complete or partial response between the two groups. None of the variables was an independent predictor of response at week 48. Nine patients had significant improvement in activity indices in renal biopsies, but there were no significant differences between the two groups. Overall, 18 out of 19 patients were found to have effective B-cell depletion. The median duration of complete B-cell depletion in all patients was 22 weeks. There were no statistically significant differences in the proportion of patients with complete depletion at weeks 4, 8, 24 and 48 between the two groups except at week 2. CONCLUSIONS Rituximab monotherapy appears to be effective as induction therapy in lupus nephritis. The addition of cyclophosphamide offers no additional improvement in clinical, laboratory and renal histological assessment or the duration of B-cell depletion at 48 weeks. Large-scale studies with longer duration are needed to confirm these findings.

High prevalence of asymptomatic vertebral fractures in Chinese women with systemic lupus erythematosus.

Objective. To investigate the prevalence of vertebral fractures and to identify risk factors associated with vertebral fractures in Chinese women with systemic lupus erythematosus (SLE). Methods. One hundred fifty-two consecutive patients with SLE were recruited in this cross-sectional study. Bone mineral density (BMD) measurements of the hip and spine were performed using the same dual energy X-ray absorptiometry (DEXA). Lateral radiographs of the spine (T5–L4) were assessed for vertebral fractures using a method described by Genant. Inflammatory and biochemical markers included C-reactive protein, receptor activator of nuclear factor-κB ligand, serum ß-CrossLaps assay for C-terminal telopeptides of type 1 collagen, and osteoprotegerin (OPG). Results. Asymptomatic vertebral fractures occurred in 20.4% of patients with SLE. Univariate analyses of variables associated with fractures were older age, higher body mass index (BMI), lower BMD spine, lower BMD hips, higher serum C3 and C4, longer estrogen exposure, higher levels of OPG, and the use of sunscreen. Multivariate analysis showed older age (p = 0.017), higher BMI (p < 0.036), and lower BMD of the spine were significantly associated with vertebral fractures in the thoracic and/or lumbar spine (odds ratio 1.068, 1.166, 0.005; p = 0.018, p = 0.025, p = 0.003, respectively). Conclusion. Asymptomatic vertebral fractures occur in 20.4% of patients with SLE and 30% of these patients have normal BMD. The current method using DEXA to predict the presence of vertebral fracture has limited value and there is a need for assessment of bone quality. Vertebral morphometry in patients with SLE is recommended and early therapeutic intervention is necessary to prevent vertebral fractures in patients with SLE.

Bone Microarchitecture Assessment by High-Resolution Peripheral Quantitative Computed Tomography in Patients with Systemic Lupus Erythematosus Taking Corticosteroids

Objective. We assessed the relationship between vertebral fracture and bone microarchitecture in patients with systemic lupus erythematosus (SLE) on chronic corticosteroid therapy using high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods. Fifty-nine Chinese women with SLE taking corticosteroid were selected to participate in a cross-sectional study. Vertebral fracture was confirmed semiquantitatively by lateral radiographs of the thoracic and lumbar spine. Density and microarchitecture at the distal radius were measured with HR-pQCT. Areal bone mineral density (aBMD) at hip and lumbar spine was measured by dual-energy x-ray absorptiometry (DEXA). Results. Twelve patients had vertebral fractures. The aBMD of spine or hip did not differ between those with and without vertebral fractures. Measures by HR-pQCT revealed that patients with vertebral fractures had significantly lower level of average bone density (p = 0.007), cortical bone density (p = 0.029), trabecular bone density (p = 0.024), trabecular bone volume to tissue volume (p = 0.023), and trabecular thickness (p = 0.011) than those without vertebral fractures. Independent explanatory variables associated with higher risk of vertebral fractures were older age (p = 0.013) and lower average cortical bone density (p = 0.029). Conclusion. Vertebral fracture in patients with SLE on chronic corticosteroid treatment was associated with alterations of bone density and microarchitectures measured by HR-pQCT and DEXA. However, alterations were more pronounced in measurements by HR-pQCT. Low cortical bone density and old age were significant predictors of vertebral fracture risk.

IMAGE FUSION FOR COMPUTER ASSISTED TUMOUR SURGERY (CATS)

CT and MRI scans are complementary preoperative imaging investigations for planning complex musculoskeletal bone tumours resection and reconstruction. Conventionally, tumour surgeons analyse two-dimensional (2-D) imaging information, mentally integrate and formulate a three-dimensional (3-D) surgical plan. Difficulties are anticipated with increase in case complexity and distorted surgical anatomy. Incorporating computer technology to aid in this surgical planning and executing the intended resection may improve precision. Although computer-assisted surgery has been widely used in cranial biopsies and tumour resection, only small case series using CT-based navigation are recently reported in the field of musculoskeletal tumor surgery. We investigated the results of CT/MRI image fusion for Computer Assisted Tumor Surgery (CATS) with the help of a navigation system. We studied 21 patients with 22 musculoskeletal tumours who underwent CATS from March 2006 to July 2009. A commercially available CT-based spine navigation system (Stryker Navigation; CT spine) was used. Of the 22 patients, 10 were males, 11 were females, and the mean age was 32 years at the time of surgery (range, 6–80 years). Five tumours were located in the pelvis, seven sacrum, eight femurs, and two tibia. The primary diagnosis was primary bone tumours in 16 (3 benign, 13 sarcoma) and metastatic carcinoma in four. The minimum follow-up was 17 months (average, 35.5 months; range, 17–52 months). Preoperative CT and MRI scan of each patient were performed. Axial CT slices of 0.0625mm or 1.25mm thickness and various sequences of MR images in Digital Imaging and Communications in Medicine (DICOM) format were obtained. CT and MR images for 22 cases were fused using the navigation software. All the reconstructed 2-D and 3-D images were used for preoperative surgical planning. The plane of tumour resection was defined and marked using multiple virtual screws sited along the margin of the planned resection. We also integrated the computer-aided design (CAD) data of custom-made prostheses in the final navigation resection planning for eight cases. All tumour resections could be carried out as planned under navigation guidance. Navigation software enabled surgeons to examine all fused image datasets (CT/MRI scans) together in two spatial and three spatial dimensions. It allowed easier understanding of the exact anatomical tumor location and relationship with surrounding structures. Intraoperatively, image guidance with the help of fusion images, provided precise visual orientation, easy identification of tumor extent, neural structures and intended resection planes in all cases. The mean time for preoperative navigation planning was 1.85 hours (1 to 3.8). The mean time for intraoperative navigation procedures was 29.6 minutes (13 to 60). The time increased with case complexity but lessened with practice. The mean registration error was 0.47mm (0.31 to 0.8). The virtual preoperative images matched well with the patients9 operative anatomy. A postoperative superficial wound infection developed in one patient with sacral chordoma that resolved with antibiotic whereas a wound infection in another with sacral osteosarcoma required surgical debridement and antibiotic. After a mean follow-up of 35.5 months (17–52 months), five patients died of distant metastases. Three out of four patients with local recurrence had tumors at sacral region. Three of them were soft tissue tumour recurrence. The mean functional MSTS score in patients with limb salvage surgery was 28.3 (23 to 30). All patients (except one) with limb sparing surgery and prosthetic reconstruction could walk without aids. Multimodal image fusion yields hybrid images that combine the key characteristics of each image technique. Back conversion of custom prosthesis in CAD to DICOM format allowed fusion with navigation resection planning and prosthesis reconstruction in musculoskeletal tumours. CATS with image fusion offers advanced preoperative 3-D surgical planning and supports surgeons with precise intraoperative visualisation and identification of intended resection for pelvic, sacral tumors. It enables surgeons to reliably perform joint sparing intercalated tumor resection and accurately fit CAD custom-made prostheses for the resulting skeletal defect.

Specific biochemical markers of bone metabolism and cytokine study confirm the diagnosis of malignant infantile osteopetrosis at birth using cord blood sample.

AIMS To investigate the serum creatine kinase isoenzyme pattern, specific biochemical markers of bone metabolism, and cytokines in a Chinese family with osteopetrosis, and correlate abnormalities with the pathophysiology of this condition. METHODS A Chinese female baby was diagnosed with malignant infantile osteopetrosis at the age of 3 weeks by clinical history and biochemical investigations. We studied the laboratory and radiological manifestations of this index case and her family members. RESULTS Serum CK-BB fraction of our index patient was elevated to 18.0% (normal 1.6-7.6%). Her biochemical markers of bone resorption including serum C-terminal telopeptide concentration and urine N-terminal telopeptide to creatinine ratio were decreased to 0.54 microg/L (normal 0.72-1.56 microg/L) and 159 x 10(-6) (normal 372-900 x 10(-6)), respectively. Serum cytokines including soluble receptor activator of nuclear factor kappa-B ligand (sRANKL) concentration was suppressed to 0.11 pmol/L (normal 0.23-0.82 pmol/L) and osteoprotegerin (OPG) concentration was 4.9 pmol/L (normal 2.8-4.9 pmol/L), resulting in an elevated OPG to sRANKL ratio of 44.5 (normal 3.8-19.4) in favour of bone formation. CONCLUSIONS If left untreated, this condition is usually fatal within the first year of life. With early diagnosis, management including bone marrow transplantation can be planned ahead and will result in a better survival.

Aggressive surgical palliation for advanced girdle tumours

Background: The surgical management of advanced, incurable, malignant disease presents particular ethical and technical challenges. The clear goal is palliation and the surgical futility must be avoided. This case series presents some particular challenges in end-of-life surgery. Materials and Methods: Fifteen patients referred with advanced malignant disease involving a limb girdle were reviewed. Results: In one case, a patient pleaded for surgery after initially requesting a delay to seek treatment from a Chinese Traditional Herbalist. The increase in tumour bulk led to problems with surgery and the patient died in a hospital a few weeks later. This case illustrates ‘futility’ not recognized and encountered. The remaining 14 patients exhibited positive palliation with improved quality of dying and appreciation expressed by patients, relatives and staff. Conclusion: In selected cases, with a skilled and experienced surgical team, patients with advanced malignant disease can still benefit from aggressive surgical palliation. The margin of error is small between palliation being attempted and futility being achieved. This considerably adds to the challenge of end-of-life surgery.