Azura Mansor

Synovial chondrosarcoma: Report of two cases and literature review

Synovial chondrosarcoma is a rare soft tissue tumor that can arise from a previous synovial chondromatosis or as de novo tumor. The clinical and radiological findings of this malignancy are very similar to those of aggressive synovial chondromatosis. Confusion with other joint pathologies makes the diagnosis of synovial chondrosarcoma difficult in most of the cases. We present one recently diagnosed and treated case of synovial chondrosarcoma. The review of our hospital database revealed one more similar case. In both cases the malignancy arose from a pre-existing synovial chondromatosis. We also present a literature review emphasizing the clinical and histological findings of this rare entity.

Acute haematogenous community-acquired methicillin-resistant Staphylococcus aureus osteomyelitis in an adult: Case report and review of literature

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) has of late emerged as a cause of community-acquired infections among immunocompetent adults without risk factors. Skin and soft tissue infections represent the majority of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clinical presentations, whilst invasive and life-threatening illness like necrotizing pneumonia, necrotizing fasciitis, pyomyositis, osteomyelitis and sepsis syndrome are less common. Although more widely described in the pediatric age group, the occurrence of CA-MRSA osteomyelitis in adults is an uncommonly reported entity.Case presentationWe describe an invasive CA-MRSA infection in a 28 year-old previously healthy male, manifesting with bacteraemia, osteomyelitis of femur, pyomyositis and septic arthritis of the knee. Initially a preliminary diagnosis of osteosarcoma was suggested by imaging studies and patient underwent a bone biopsy. MRSA was subsequently isolated from blood cultures taken on day of admission, bone, tissue and pus cultures. Incision and drainage of abscess was performed and patient was treated with vancomycin, with fusidic acid added later. It took 6 months for the inflammatory markers to normalize, warranting 6-months of anti-MRSA therapy. Patient was a fervent deer hunter and we speculate that he acquired this infection from extensive direct contact with deer.Molecular characterization of this isolate showed that it belonged to multilocus sequence type (MLST) ST30 and exhibited the staphylococcal chromosome cassette mec (SCCmec) type IV, staphylococcus protein A (spa) type t019, accessory gene regulator (agr) type III and dru type dt10m. This strain harbored Panton-Valentine leukocidin (pvl) genes together with 3 other virulent genes; sei (enterotoxin), hlg (hemolysin) and fnbA (fibronectin binding protein).ConclusionThis case study alerts physicians that beyond the most commonly encountered skin and soft tissue infections, pvl positive CA-MRSA can lead to invasive life-threatening disease especially in an immunocompetent adult. Heightened alertness is needed for osteomyelitis of long bones in adults, as it is not uncommon for this disease to mimic primary bone malignancy. Cure is achievable with early appropriate antibiotics guided by inflammatory markers.

Prospects of implant with locking plate in fixation of subtrochanteric fracture: experimental demonstration of its potential benefits on synthetic femur model with supportive hierarchical nonlinear hyperelastic finite element analysis

BackgroundEffective fixation of fracture requires careful selection of a suitable implant to provide stability and durability. Implant with a feature of locking plate (LP) has been used widely for treating distal fractures in femur because of its favourable clinical outcome, but its potential in fixing proximal fractures in the subtrochancteric region has yet to be explored. Therefore, this comparative study was undertaken to demonstrate the merits of the LP implant in treating the subtrochancteric fracture by comparing its performance limits against those obtained with the more traditional implants; angle blade plate (ABP) and dynamic condylar screw plate (DCSP).Materials and MethodsNine standard composite femurs were acquired, divided into three groups and fixed with LP (n = 3), ABP (n = 3) and DCSP (n = 3). The fracture was modeled by a 20 mm gap created at the subtrochanteric region to experimentally study the biomechanical response of each implant under both static and dynamic axial loading paradigms. To confirm the experimental findings and to understand the critical interactions at the boundaries, the synthetic femur/implant systems were numerically analyzed by constructing hierarchical finite element models with nonlinear hyperelastic properties. The predictions from the analyses were then compared against the experimental measurements to demonstrate the validity of each numeric model, and to characterize the internal load distribution in the femur and load bearing properties of each implant.ResultsThe average measurements indicated that the constructs with ABP, DCPS and LP respectively had overall stiffness values of 70.9, 110.2 and 131.4 N/mm, and exhibited reversible deformations of 12.4, 4.9 and 4.1 mm when the applied dynamic load was 400 N and plastic deformations of 11.3, 2.4 and 1.4 mm when the load was 1000 N. The corresponding peak cyclic loads to failure were 1100, 1167 and 1600 N. The errors between the displacements measured experimentally or predicted by the nonlinear hierarchical hyperelastic model were less than 18 %. In the implanted femur heads, the principal stresses were spatially heterogeneous for ABP and DCSP but more homogenous for LP, meaning LP had lower stress concentrations.ConclusionWhen fixed with the LP implant, the synthetic femur model of the subtrochancteric fracture consistently exceeds in the key biomechanical measures of stability and durability. These capabilities suggest increased resistance to fatigue and failure, which are highly desirable features expected of functional implants and hence make the LP implant potentially a viable alternative to the conventional ABP or DCSP in the treatment of subtrochancteric femur fractures for the betterment of clinical outcome.

Differential Protein Expression between Chondrogenic Differentiated MSCs, Undifferentiated MSCs and Adult Chondroctyes Derived from Oryctolagus cuniculus in vitro

Objective: This preliminary study aims to determine the differentially expressed proteins from chondrogenic differentiated multipotent stromal cells (cMSCs) in comparison to undifferentiated multipotent stromal cells (MSCs) and adult chondrocytes (ACs). Methods: ACs and bone marrow-derived MSCs were harvested from New Zealand White rabbits (n = 3). ACs and cMSCs were embedded in alginate and were cultured using a defined chondrogenic medium containing transforming growth factor-beta 3 (TGF-β3). Chondrogenic expression was determined using type-II collagen, Safranin-O staining and glycosaminoglycan analyses. Two-dimensional gel electrophoresis (2-DE) was used to isolate proteins from MSCs, cMSCs and ACs before being identified using liquid chromatography-mass spectrometry (LC-MS). The differentially expressed proteins were then analyzed using image analysis software. Results: Both cMSCs and ACs were positively stained with type-II collagen and safranin-O. The expression of glycosaminoglycan in cMSCs was comparable to AC at which the highest level was observed at day-21 (p>0.05). Six protein spots were found to be most differentially expressed between MSCs, cMSCs and ACs. The protein spots cofilin-1 (CFL1) and glycealdehyde-3-phosphate dehydrogenase (GAPD) from cMSCs had expression levels similar to that of ACs whereas the others (ie. MYL6B, ALDOA, TAGLN2, EF1-alpha), did not match the expression level of ACs. Conclusion: Despite having similar phenotypic expressions to ACs, cMSCs expressed proteins which were not typically expected. This may explain the reason for the unexplained lack of improvement in cartilage repair outcomes reported in previous studies.

Students’ performance in the different clinical skills assessed in OSCE: what does it reveal?

Introduction The purpose of this study was to compare students’ performance in the different clinical skills (CSs) assessed in the objective structured clinical examination. Methods Data for this study were obtained from final year medical students’ exit examination (n=185). Retrospective analysis of data was conducted using SPSS. Means for the six CSs assessed across the 16 stations were computed and compared. Results Means for history taking, physical examination, communication skills, clinical reasoning skills (CRSs), procedural skills (PSs), and professionalism were 6.25±1.29, 6.39±1.36, 6.34±0.98, 5.86±0.99, 6.59±1.08, and 6.28±1.02, respectively. Repeated measures ANOVA showed there was a significant difference in the means of the six CSs assessed [F(2.980, 548.332)=20.253, p<0.001]. Pairwise multiple comparisons revealed significant differences between the means of the eight pairs of CSs assessed, at p<0.05. Conclusions CRSs appeared to be the weakest while PSs were the strongest, among the six CSs assessed. Students’ unsatisfactory performance in CRS needs to be addressed as CRS is one of the core competencies in medical education and a critical skill to be acquired by medical students before entering the workplace. Despite its challenges, students must learn the skills of clinical reasoning, while clinical teachers should facilitate the clinical reasoning process and guide students’ clinical reasoning development.

Replantation and revascularization of amputated upper limb appendages outcome and predicting the factors influencing the success rates of these procedures in a tertiary hospital: An 8-year retrospective, cross-sectional study

Purpose: Worldwide advances in microsurgery have made salvaging of amputated hand via replantation and revascularization common procedures. The present study examines the outcome of these procedures in a tertiary hospital in Malaysia. Methods: Patients with hand amputation who underwent replantation or revascularization from 2005 to 2012 were identified and reviewed for patient characteristics, amputation characteristics and survival rates. Successfully treated patients were interviewed to assess the functional outcome using Quick Disability of the Arm, Shoulder and Hand (Quick-DASH) questionnaire and Michigan Hand Outcome Questionnaire (MHQ). Statistical analysis was performed to evaluate outcome and elicit predictive factors. Results: Fifty-five patients were enrolled: 37 (67.3%) underwent replantation and 18 (32.7%) underwent revascularization. The overall success rate of 78% (n = 43) was within the range of previously reported data (61.6% to 96.0%). Ischaemic time <6 h provided significantly better survival rates (p < 0.05). Functional outcomes were successfully assessed in 34 patients (79%), at a mean follow-up of 40 months (range 11–93 months). The overall Quick-DASH and MHQ scores were 42.82 ± 23.69 and 60.94 ± 12.82, respectively. No previous reports of functional outcome were available for comparison. Both Quick-DASH (p = 0.001) and MHQ scores (p < 0.001) were significantly higher for finger injuries, followed by thumb, wrist and palm injuries. Conclusion: Ischaemic time and level of injury are important predictors of success rate of replantation and revascularization of amputated upper limb appendages.

Performance of cooling materials and their composites in maintaining freezing temperature during irradiation and transportation of bone allografts

Purpose: Bone allografts supplied by University Malaya Medical Centre Bone Bank are sterilized by gamma radiation at 25 kGy in dry ice (DI) to minimize radiation effects. Use of cheaper and easily available cooling materials, gel ice (GI) and ice pack (IP), was explored. Composites of DI and GI were also studied for the use in routine transportations and radiation process. Methods: (a) Five dummy bones were packed with DI, GI, or IP in a polystyrene box. The bone temperatures were monitored while the boxes were placed at room temperature over 96 h. Durations for each cooling material maintaining freezing temperatures below −40°C, −20°C, and 0°C were obtained from the bone temperature over time profiles. (b) Composites of DI (20, 15, 10, 5, and 0 kg) and GI were used to pack five dummy bones in a polystyrene box. The durations maintaining varying levels of freezing temperature were compared. Results: DI (20 kg) maintained temperature below −40°C for 76.4 h as compared to 6.3 h in GI (20 bags) and 4.0 h in IP (15 packs). Composites of 15DI (15 kg DI and 9 GI bags) and 10DI (10 kg DI and 17 GI bags) maintained the temperature below −40°C for 61 and 35.5 h, respectively. Conclusion: Composites of DI and GI can be used to maintain bones in deep frozen state during irradiation, thus avoiding radiation effects on biomechanical properties. Sterile frozen bone allograft with preserved functional properties is required in clinical applications.

Avoiding diagnostic pitfalls in mimics of neoplasia: the importance of a comprehensive diagnostic approach

Any medical diagnosis should take a multimodal approach, especially those involving tumour-like conditions, as entities that mimic neoplasms have overlapping features and may present detrimental outcomes if they are underdiagnosed. These case reports present diagnostic pitfalls resulting from overdependence on a single diagnostic parameter for three musculoskeletal neoplasm mimics: brown tumour (BT) that was mistaken for giant cell tumour (GCT), methicillin-resistant Staphylococcus aureus osteomyelitis mistaken for osteosarcoma and a pseudoaneurysm mistaken for a soft tissue sarcoma. Literature reviews revealed five reports of BT simulating GCT, four reports of osteomyelitis mimicking osteosarcoma and five reports of a pseudoaneurysm imitating a soft tissue sarcoma. Our findings highlight the therapeutic dilemmas that arise with musculoskeletal mimics, as well as the importance of thorough investigation to distinguish mimickers from true neoplasms.

Proteome Comparisons between Pre-Chemotherapy and Post-Chemotherapy Serum of Metastatic Osteosarcoma Patients Reveals Potential Novel Biomarker

This study is the first to show on differential protein profiles between serum isolated from healthy individual and metastatic osteosarcoma patients at different stages (Pre- and post-chemotherapy). The analyses have identified significant number of proteins that involved in the progression of the osteosarcoma metastasis. This data could provide a new insight in the osteosarcoma biological processes and use as a potential biomarker for better OS prognosis. Osteosarcoma (OS), a malignant bone tumour, is commonly occurs in children and young adults between the ages of 10 to 30. Although the standard treatment for OS is advancing and significantly improved the survival rate in recent years, its poor prognosis continues to remain the major problem in managing the disease. In this study, we have conducted a series of systematic analysis to identify novel proteins associated with the metastatic progression of human OS using a 4-plex iTRAQ analysis. Pooled serum samples were collected from patients who were diagnosed with metastatic osteosarcoma. The serum was collected at two stages; pre-chemotherapy and post-chemotherapy. iTRAQ analysis identified 217 proteins with 104214 spectra from the patients’ plasma. The proteins identified were analysed using bioinformatics software and categorized according to their role in biological processes. Most of the proteins fall under cellular component organization or biogenesis (39.4%), cellular process (35.4%), biological regulation (20.0%) and immune system process (29.3%). In addition, these proteins have also shown to be significantly altered in their expression when compare between preand post-chemotherapy patients samples such as C-reactive proteins, vascular adhesion molecule-1 and gelsolin. To date, this is the first differential protein expression study to use metastatic osteosarcoma patients’ serum at different stages for the protein profiling. We have successfully generated a comprehensive data on the differentially expressed protein and the comparative study has revealed a significant amount of proteins expression has been altered. This data could provide a new insight in the OS biological processes and use as a potential biomarker for better OS prognosis.

Response to the letter by Dr Klein

Thank you for giving us the opportunity to answer Dr. Klein’s questions. Our article was a good example of imaging and pathology cooperation. While reviewing the 199 surface osteosarcomas at the Rizzoli Institute, we noticed one histological report of parosteal osteosarcoma dedifferentiated into a telangiectatic osteosarcoma. A very characteristic radiological pattern was noted in this case (Fig. 1 of the original article). As we found only one comparable case in the literature, we started to review our database. Four additional cases were detected, with fluid-filled cavities, combined with a typical image of parosteal osteosarcoma. The cases were all reviewed by a pathologist, who confirmed the diagnosis in two cases (the ones in Figs. 2 and 3, with multiple small cavities, shown radiologically) and rejected the two with only one cavity, which was considered to represent a hematoma in the dedifferentiated part. Therefore, we had two components in each case.We admit that not all informationmay be represented in published images. The authors, being too familiar with the cases and knowing the selection history, might not have been sufficiently aware of the needs of a reader not familiar with the tumors presented. Therefore, we have provided some additional histological images (Figs. 1 and 2) relating to Figs. 2 and 3 of the original paper, hopefully clarifying the situation.