Elevated levels of circulating cobalt ions have been linked with a wide range of systemic complications including neurological, endocrine, and cardiovascular symptoms. Case reports of patients with elevated blood cobalt ions have described significant cardiovascular complications including cardiomyopathy. However, correlation between the actual level of circulating cobalt and extent of cardiovascular injury has not previously been performed. This review examines evidence from the literature for a link between elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties and cardiomyopathy. Correlation between low, moderate, and high blood cobalt with cardiovascular complications has been considered. Elevated blood cobalt at levels over 250 µg/l have been shown to be a risk factor for developing systemic complications and published case reports document cardiomyopathy, cardiac transplantation, and death in patients with severely elevated blood cobalt ions. However, it is not clear that there is a hard cut-off value and cardiac dysfunction may occur at lower levels. Clinical and laboratory research has found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. Further work needs to be done to clarify the link between severely elevated blood cobalt ions and cardiomyopathy. Cite this article: Bone Joint Res 2021;10(6):340–347

Aims. Elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties are a suggested risk factor for developing cardiovascular complications including cardiomyopathy. Clinical studies assessing patients with MoM hips using left ventricular ejection fraction (LVEF) have found conflicting evidence of cobalt-induced cardiomyopathy. Global longitudinal strain (GLS) is an echocardiography measurement known to be more sensitive than LVEF when diagnosing early cardiomyopathies. The extent of cardiovascular injury, as measured by GLS, in patients with elevated blood cobalt levels has not previously been examined. Methods. A total of 16 patients with documented blood cobalt ion levels above 13 µg/l (13 ppb, 221 nmol/l) were identified from a regional arthroplasty database. They were matched with eight patients awaiting hip arthroplasty. All patients underwent echocardiography, including GLS, investigating potential signs of cardiomyopathy. Results. Patients with MoM hip arthroplasties had a mean blood cobalt level of 29 µg/l (495 nmol/l) compared to 0.01 µg/l (0.2 nmol/l) in the control group. GLS readings were available for seven of the MoM cohort, and were significantly lower when compared with controls (-15.5% vs -18% (MoM vs control); p = 0.025)). Pearson correlation demonstrated that GLS significantly correlated with blood cobalt level (r = 0.8521; p < 0.001). However, there were no differences or correlations for other echocardiography measurements, including LVEF (64.3% vs 63.7% (MoM vs control); p = 0.845). Conclusion. This study supports the hypothesis that patients with elevated blood cobalt levels above 13 µg/l in the presence of a MoM hip implant may have impaired cardiac function compared to a control group of patients awaiting hip arthroplasty. It is the first study to use the more sensitive parameter of GLS to assess for any cardiac contractile dysfunction in patients with a MoM hip implant and a normal LVEF. Larger studies should be performed to determine the potential of GLS as a predictor of cardiac complications in patients with MoM arthroplasties. Cite this article: Bone Joint J 2024;106-B(3 Supple A):51–58

Symptomatic cobalt toxicity from a failed total hip replacement is a rare but devastating complication. It has been reported following revision of fractured ceramic components, as well as in patients with failed metal-on-metal articulations. Potential clinical findings include fatigue, weakness, hypothyroidism, cardiomyopathy, polycythaemia, visual and hearing impairment, cognitive dysfunction, and neuropathy. We report a case of an otherwise healthy 46-year-old patient, who developed progressively worsening symptoms of cobalt toxicity beginning approximately six months following synovectomy and revision of a fractured ceramic-on-ceramic total hip replacement to a metal-on-polyethylene bearing. The whole blood cobalt levels peaked at 6521 µg/l. The patient died from cobalt-induced cardiomyopathy. Implant retrieval analysis confirmed a loss of 28.3 g mass of the cobalt–chromium femoral head as a result of severe abrasive wear by ceramic particles embedded in the revision polyethylene liner. Autopsy findings were consistent with heavy metal-induced cardiomyopathy. We recommend using new ceramics at revision to minimise the risk of wear-related cobalt toxicity following breakage of ceramic components. Cite this article: Bone Joint J 2013;95-B:31–7

Revision of fractured ceramic-on-ceramic total hip replacements with a cobalt-chromium (CoCr) alloy-on-polyethylene articulation can facilitate metallosis and require further expensive revision surgery [1–3]. In the present study, a fifty-two year old male patient suffered from fatal cardiomyopathy after undergoing revision total hip arthroplasty. The patient had received a polyethylene-ceramic acetabular liner and a ceramic femoral head as his primary total hip replacement. The polyethylene-ceramic sandwich acetabular liner fractured in vivo after 58 months and the patient underwent his first revision surgery where he received a Vitamin E stabilized acetabular Polyethylene (PE) liner and a CoCr alloy femoral head with documented synovectomy at that time. After 15 months, the patient was admitted to hospital in cardiogenic shock, with retrieval of the bearing components. Before the second revision surgery, peak serum cobalt levels measured 6,521 μg/L, 78-times greater than serum cobalt levels of 83μg/L associated with cobalt poisoning [4]. Serum titanium levels found in the patient measured 17.5 μg/L) normal, healthy range 0–1.4 μg/L). The retrieved CoCr alloy femoral head had lost a total of 28.3g (24% or an estimated amount of 102 × 10. −9. wear particles (∼2 μm diameter) [1]) within 16 months of in vivo service. Despite initiating a cobalt chelating therapy, the patients' cardiac left ventricular ejection fraction remained reduced at 6%. This was followed by multi-organ failure, and ultimately the patient passed away shortly after being taken off life support. Embedded ceramic particles were found on the backside and articular surfaces of the Vitamin E-stabilized PE acetabular liner. Evidence of fretting wear on the titanium (Ti) alloy acetabular shell was present, possibly explaining the increased serum Ti levels. Scanning electron microscopy and energy dispersive X-ray analyses confirmed Ti alloy transfer on the embedded ceramic particles on the backside PE liner surface and CoCr alloy transfer on the embedded ceramic particles on the articular PE liner surface. A fractured ceramic-on-ceramic total hip replacement should not be revised to a CoCr alloy-on-polyethylene articulation irrespective of concurrent synovectomy [5] as it can cause severe, third-body wear to the CoCr alloy femoral head that can lead to metallosis with fatal, systemic consequences

Spondylodiscitis rarely coexists with endocarditis (around 5% of patients with endocarditis). Furthermore, viridans streptococci are not common pathogens of spondylodiscitis and finally the combination of spondylodiscitis and right – sided endocarditis due to viridans streptococci is rare. We present a case of right-sided native valve endocarditis due to Streptococcus mutans presenting as cervical and lumbar spondylodiscitis in a patient with obstructive cardiomyopathy. A 52 year – old man with a history of hypertrophic obstructive cardiomyopathy was admitted with fever and back pain of ten days duration, followed by torticollis. He had undergone dental therapy some weeks before symptom appearance, due to bad oral hygiene, without receiving any chemoprophylaxis. Magnetic resonance imaging revealed L4-L5 and C4-C5 spondylodiscitides. Four blood cultures drawn were all positive for Streptococcus mutans, while fine needle aspiration of the lumbar lesion was unsuccessful. Transesophageal echocardiogram revealed tricuspid and possible pulmonary valve vegetations. The patient was treated with ceftriaxone plus gentamicin for 2 weeks and then ceftriaxone only, for a total of 3 months. He had an uneventful recovery and was referred for cardiosurgical consultation. Physicians managing cases of spondylodiscitides should bear in mind to rule out endocarditis, especially in cases with underlying cardiopathy. The possibility of coexistence is even greater when there is sustained bacteremia and the pathogen isolated from blood cultures is a common pathogen for endocarditis

Elevated blood cobalt secondary to metal-on-metal (MoM) hip arthroplasties has been shown to be a risk factor for developing cardiovascular complications including cardiomyopathy. Published case reports document cardiomyopathy in patients with blood cobalt levels as low as 13µg/l (13ppb, 221nmol/l). Clinical studies have found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. Global longitudinal strain (GLS) is an echocardiography measurement known to be more sensitive than ejection fraction at diagnosing early cardiomyopathies. The extent of cardiovascular injury, as measured by GLS, in patients with elevated blood cobalt levels has not previously been examined. Sixteen patients with documented blood cobalt ion levels above 13µg/l were identified from a regional arthroplasty database. They were matched with eight patients awaiting hip arthroplasty with no history of cobalt implants. All patients underwent electrocardiogram and echocardiogram assessment for signs of cardiomyopathy including GLS. Patients with MoM hip arthroplasties had a mean blood cobalt level of 29µg/l (495nmol/l) compared to 0.01µg/l (0.2nmol/l) in the control group. There was no difference or correlation in ejection fraction (EF), left ventricular (LV) end systolic dimension, LV end diastolic dimension, fractional shortening, ventricular wall thickness or E/e’ ratio. However, GLS was significantly reduced in patients with MoM hip arthroplasties compared to those without (−15.2% v −18%, (MoM v control) p= 0.0125). Pearson correlation demonstrated that GLS is significantly correlated with blood cobalt level (r= 0.8742, p=0.0009). For the first time, this study has demonstrated reduced cardiac function in the presence of normal EF as assessed by GLS in patients with elevated cobalt above 13µg/l. As GLS is a more sensitive measure of systolic function than EF, routine echocardiogram assessment including GLS should be performed in all patients with MoM hip arthroplasties and elevated blood cobalt above 13µg/l. Further work is recommended to assess if these cardiac changes are present in patients with elevated blood cobalt levels below 13µg/l

Elevated blood cobalt secondary to metal-on-metal (MoM) hip arthroplasties has been shown to be a risk factor for developing cardiovascular complications including cardiomyopathy. Published case reports document cardiomyopathy in patients with blood cobalt levels as low as 13µg/l. Clinical studies have found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. The extent of cardiovascular injury, measured by global longitudinal strain (GLS), in patients with elevated blood cobalt levels has not previously been examined. Sixteen patients with prospectively collected blood cobalt ion levels above 13µg/l were identified and matched with eight patients awaiting hip arthroplasty with no history of cobalt implants. Patients underwent echocardiogram assessment including GLS. Patients with MoM hip arthroplasties had a mean blood cobalt level of 29µg/l compared to 0.01µg/l in the control group. There was no difference or correlation in EF, left ventricular (LV) end systolic dimension, LV end diastolic dimension, fractional shortening, ventricular wall thickness or E/e’ ratio. However, GLS was significantly reduced in patients with MoM hip arthroplasties compared to those without (−15.2% v −18%, (MoM v control) p= 0.0125). Pearson correlation demonstrated that GLS is significantly correlated with blood cobalt level (r= 0.8742, p=0.0009). For the first time, this study has demonstrated reduced cardiac function in the presence of normal EF as assessed by GLS in patients with elevated cobalt above 13µg/l. As GLS is a more sensitive measure of systolic function than EF, routine echocardiogram assessment including GLS should be performed in all patients with MoM hip arthroplasties and elevated blood cobalt

Aims. A recent report from France suggested an association between the use of cobalt-chrome (CoCr) femoral heads in total hip arthroplasties (THAs) and an increased risk of dilated cardiomyopathy and heart failure. CoCr is a commonly used material in orthopaedic implants. If the reported association is causal, the consequences would be significant given the millions of joint arthroplasties and other orthopaedic procedures in which CoCr is used annually. We examined whether CoCr-containing THAs were associated with an increased risk of all-cause mortality, heart outcomes, cancer, and neurodegenerative disorders in a large national database. Methods. Data from the National Joint Registry was linked to NHS English hospital inpatient episodes for 374,359 primary THAs with up to 14.5 years' follow-up. We excluded any patients with bilateral THAs, knee arthroplasties, indications other than osteoarthritis, aged under 55 years, and diagnosis of one or more outcome of interest before THA. Implants were grouped as either containing CoCr or not containing CoCr. The association between implant construct and the risk of all-cause mortality and incident heart failure, cancer, and neurodegenerative disorders was examined. Results. There were 158,677 individuals (42.4%) with an implant containing CoCr. There were 47,963 deaths, 27,332 heart outcomes, 35,720 cancers, and 22,025 neurodegenerative disorders. There was no evidence of an association between patients with CoCr implants and higher rates of any of the outcomes. Conclusion. CoCr-containing THAs did not have an increased risk of all-cause mortality, or clinically meaningful heart outcomes, cancer, or neurodegenerative disorders into the second decade post-implantation. Our findings will help reassure clinicians and the increasing number of patients receiving primary THA worldwide that the use of CoCr-containing implants is not associated with significant adverse systemic effects. Cite this article: Bone Joint J 2022;104-B(3):359–367

Ceramic-on-ceramic (CoC) articulations in total hip arthroplasty (THA) have low wear, but the unique risk of fracture. After revision for CoC fracture, ceramic third bodies can lead to runaway wear of cobalt chrome (CoCr) causing extremely elevated blood cobalt. We present five cases of ceramic liner fractures revised to a CoCr head associated with the rapid development of severe cobalt toxicity. We identified 5 cases of fractured CoC THA treated with revision to CoCr on highly cross-linked polyethylene (HXLPE) – three to conventional bearings and two to modular dual mobility bearings (CoCr acetabular liner, CoCr femoral head, and HXLPE). Mean follow up was 2.5 years after CoCr/HXLPE re-revision. Symptoms of cobalt toxicity occurred at average 9.5 months after revision for ceramic fracture (range 6–12). All patients developed vision and hearing loss, balance difficulties, and peripheral neuropathy. Several had cardiomyopathy, endocrinopathy, and local skin discoloration. Two reported hip pain. Re-revision for cobalt toxicity occurred at an average of 22 months (range 10–36) after revision for ceramic fracture. Average serum cobalt level at re-revision was 991 μg/L (range 734–1302, normal <1 μg/L). All CoCr heads exhibited massive wear with asphericity; deep tissues exhibited prominent metallosis. Treatment consisted of debridement and revision to a ceramic head with HXLPE. Serum cobalt improved to an average of 25 μg/L at final follow up. All patients reported partial improvement in vision and hearing; peripheral neuropathy and balance did not recover. Systemic cobalt toxicity is a rare but devastating complication of ceramic fracture in THA treated with cobalt-alloy bearings. Cobalt alloy bearings should be avoided in this setting. The diagnosis of systemic cobalt toxicity requires a high index of suspicion and was typically delayed following systemic symptoms. Debridement and revision to a ceramic-on-HXLPE leads to improvement but not resolution of cobalt toxicity complications

Aims. Many case reports and small studies have suggested that cobalt ions are a potential cause of cardiac complications, specifically cardiomyopathy, after metal-on-metal (MoM) total hip arthroplasty (THA). The impact of metal ions on the incidence of cardiac disease after MoM THA has not been evaluated in large studies. The aim of this study was to compare the rate of onset of new cardiac symptoms in patients who have undergone MoM THA with those who have undergone metal-on-polyethylene (MoP) THA. Patients and Methods. Data were extracted from the Standard Analytics Files database for patients who underwent MoM THA between 2005 and 2012. Bearing surface was selected using International Classification of Diseases ninth revision codes. Patients with a minimum five-year follow-up were selected. An age and gender-matched cohort of patients who underwent MoP THA served as a comparison group. New diagnoses of cardiac disease were collected during the follow-up period. Comorbidities and demographics were identified and routine descriptive statistics were used. Results. We identified 29 483 patients who underwent MoM THA and 24 175 matched patients who underwent MoP THA. Both groups had a mean Charlson comorbidity index score of 4. There were no statistically significant differences in 30 of 31 pre-existing comorbidities. Patients undergoing MoM THA had a slightly lower incidence of cardiac failure compared with those undergoing MoP THA at three years (6.60% versus 7.06%, odds ratio (OR) 0.93, 95% confidence interval (CI) 0.87 to 0.99) and four years (8.73% versus 9.49%, OR 0.91, 95% CI 0.86 to 0.97) postoperatively, with no difference in the incidence of new cardiac failure in between the groups at five years. There was no statistically significant difference in the incidence of arrhythmia, myocardial infarction and cardiomyopathy at any time between the two groups. Conclusion. MoM THA is not associated with cardiac complications. Initial reports may have represented individual instances of cardiac disease in patients with a failing MoM articulation rather than an emerging epidemiological trend. Cite this article: Bone Joint J 2018;100-B:28–32

A recent French report suggested that cobalt metal ions released from total hip replacements (THRs) were associated with an increased risk of dilated cardiomyopathy and heart failure. If the association is causal the consequences would be significant given the millions of Orthopaedic procedures in which cobalt-chrome is used annually. We examined whether cobalt-chrome containing THRs were associated with an increased risk of all-cause mortality, heart failure, cancer, and neurodegenerative disorders. Data from the National Joint Registry was linked to NHS English hospital inpatient episodes for 375,067 primary THRs with up to 14·5 years follow-up. Implants were grouped as either containing cobalt-chrome or not containing cobalt-chrome. The association between implant construct and the risk of all-cause mortality and incident heart failure, cancer, and neurodegenerative disorders was examined. There were 132,119 individuals (35·2%) with an implant containing cobalt-chrome. There were 48,106 deaths, 27,406 heart outcomes, 35,823 cancers, and 22,097 neurodegenerative disorders. There was no evidence of an association that patients with cobalt-chrome implants had higher rates of any of the outcomes. For all-cause mortality there was a very small survival advantage for patients having a cobalt-chrome implant (restricted mean survival time 13·8=days, 95% CI=6·8-20·9). Cobalt-chrome containing THRs did not have an increased risk of all-cause mortality, heart failure, cancer, and neurodegenerative disorders into the second decade post-implantation. Our findings will reassure clinicians and patients that primary THR is not associated with systemic implant effects

Palliative therapy of Malignant Fibrous Histiocytoma (MFH) is mainly based on conventional chemotherapy using anthracyclines and ifosfamide. Intervals between therapies allow abundant recovery of tumour vasculature. An unspecific antiangiogenic effect of chemotherapy can be induced by continuously administering low doses of drug referred to as Metronomic Chemotherapy (MCT). MCT may be combined with specific VEGF targeting drugs in order to increase the antiangiogenic impact on the tumour. We report on a 57 y.o. male patient with heavily pre-treated advanced stage MFH. Previous polychemotherapies consisted of 8 cycles EIA in adjuvant setting in 2002, 4 cycles ICE in recurrent situation in 2003 and 6 cycles of Dacarbacine plus Epirubicine in 2006. In 2005 and 2006 radiation therapy of paravertebral tumour lesions was done. In September 2006 the patient was admitted to our hospital with multilocular metastatic progressive disease. Performance status was WHO1. A moderate asymptomatic anthracycline induced cardiomyopathy was detected. The cumulative dosage threshold for anthracyclines had been exceeded before. We initiated oral MCT with Trofosfamide 150 mg pd plus iv. – antiangiogenic therapy with Bevacizumab 5 mg/kg q 2w. Follow up (FU) was done via F18-PET-CT. First FU after 8 weeks of combined therapy showed metabolic partial remission (PR) (48% decrease in mean Maximum Standard Uptake Valule (SUVmax) of target lesions) and metric stable disease (SD) (5% decrease in sum of diameters according to RECIST criteria). Trofosfamide was tolerated well. Treatment with Bevacizumab had to be stopped after 8 weeks because of symptomatic deterioration of cardiomyopathy (Ejection Fraction now 25%). Trofosfamide was continued as monotherapy. After 8 weeks of Trofosfamide alone PET-CT showed one new lesion indicating progressive disease according to RECIST but persistent metabolic remission of all pre-existing lesions. Bevacizumab then was added again but couldn’t stop further tumour progression (FU in March 2007). In summary disease control was achieved for 4 months. Combined metronomic and antiangiogenic therapy led to disease stabilisation and even metabolic remission measured by F18-PET-CT in a heavily pre-treated patient with soft tissue sarcoma. A pre-existing anthracycline-induced cardiomyopathy deteriorated under treatment with Bevacizumab. Whether response duration could have been prolonged by administering Bevacizumab without interruption remains speculative. The role of PET-CT in early detection of response is still to be determined

We have had experience of an 18-month-old boy with a cardiomyopathy who died a few minutes after removal of his cast with a saw, apparently from a malignant cardiac arrhythmia triggered by anxiety. We therefore examined the anxiety reaction to this method of removal of a plaster cast in 20 healthy children; ten were provided with hearing protectors and ten were not. The level of anxiety was assessed by measuring the heart rate, a known physiological indicator of anxiety, before, during and five minutes after removal of the cast. The noise level was also measured. The results showed a mean increase in heart rate during the procedure of 27.9 beats per minute (bpm) (26.9%) in the children with no hearing protectors and 10.4 bpm (11.1%) in children who used hearing protectors (p < 0.001). Five minutes after the procedure the heart rate had returned to the baseline rate in all patients. We recommend that hearing protectors should be used in children undergoing removal of a plaster cast to decrease the anxiety reaction. If possible, clinicians should avoid the use of a saw for this purpose in children with a cardiomyopathy

Aims

We aimed to develop a gene signature that predicts the occurrence of postmenopausal osteoporosis (PMOP) by studying its genetic mechanism.

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Over the past 15 years metal on metal hip resurfacing (MOMHR) has seen a spectacular resurgence in utilization followed by near abandonment of the procedure. A select group of surgeons still offer the procedure to a select group of patients suggesting that there are benefits of MOMHR over total hip arthroplasty (THA). This is problematic for the following reasons:. 1). MOMHR does not lead to increased survivorship. The Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) and the England and Wales National Joint Registry, from countries with high rates of utilization of MOMHR, both report significantly worse survivorship with MOMHR compared to all types of conventional THA. Risk factors for revision of resurfacing were older patients, females, smaller femoral head size, patients with developmental dysplasia, and certain implant designs. 2). MOMHR is associated with the generation of metal ions that can have devastating effects in some patients. Cobalt and chromium ions generated from MOMHR can result in adverse local tissues reactions around the hip, sometimes with catastrophic consequences, as well as neurological deficits, skin rashes, and cardiomyopathy. It is unclear as to which patients are at risk for the generation of high ion levels and less clear with respect to the host response to these ions. The discriminative and predictive values of ion testing are still being determined. MOMHR subsequently require careful follow-up with limited tools to assess risk and pending problems. 3). MOMHR is not less invasive. In order to deliver the femoral head for safe preparation and to access the acetabulum with the femoral head and neck in situ, significant dissection and retraction are required. The exposure issue is compounded as the procedure is most often performed in younger, larger males. Difficulty with exposure has been associated with an insult to the femoral head's blood supply that may lead to fracture and/or neck narrowing. 4). Preservation of the femoral canal with MOMHR does not improve outcomes of revision. The perceived advantage of preserved femoral head and neck implies that a conversion of a MOMHR to total hip should convey survivorship similar to primary THA. However, this is not the case as confirmed by data from the AOANJRR demonstrating worse survivorship of revised resurfacings when compared to a primary total hip arthroplasty. 5). MOMHR does not result in superior functional outcomes. Advocates for MOMHR often claim that the large femoral head and intact femoral neck in resurfacing results in a better functional outcome and therefore, a better quality of life and satisfaction when compared to a conventional THA. This, however, was not the case when gait speed, postural balance evaluations and functional tests were used in a randomised study of 48 patients, which failed to show an advantage of MOMHR over THA. In conclusion, it is relatively straightforward to oppose and argue against the use of hip resurfacings as they have worse outcomes in all National Joint Registries, produce metal ions with significant clinical consequences, are more invasive, are difficult to revise with subsequent inferior outcomes when compared to a conventional primary THA, and do not provide better function. These adverse features come with a premium price when compared to a conventional THA

Introduction. The use of metal-on-metal (MOM) and modular total hip arthroplasty (THA) is associated with potentially serious complications including elevated serum metal ion levels, pseudotumor, cardiomyopathy and neurologic abnormalities. The primary aim of this analysis was to identify any associations between the presence of pseudotumor, serum metal ion levels, and specific dual modular implant components. Methods. We evaluated prospectively collected data from 49 patients, mean age 58.4 years, who underwent implantation of modular THA from 01/2004-01/2010. The collected data spanned a 5–11 year period from the time of index procedure. Serum metal ion levels, including titanium, cobalt and chromium, were collected in 2012 and 2015. Hip ultrasounds were performed on each patient by a trained musculoskeletal radiologist for evaluation of the presence of soft-tissue pseudotumor. Univariate nonparametric tests were used to compare the two groups: Fisher's exact tests for categorical variables, and Wilcoxon two-group tests for continuous variables. For the purposes of analysis, values that were below the level of detection (LOD) were set to half the LOD. All analyses were performed using SAS 9.4 (SAS Institute Inc, Cary, NC, USA). Statistical significance is set at p<0.05. Results. Eight of 49 patients (16.3%) had pseudotumors on ultrasound examination. The average size measured 35.05 cm3 (7.35 cm3 – 130.81 cm3). In patients without pseudotumor, the serum levels (ng/mL) of titanium, cobalt and chromium were 3.2 ± 2.7, 4.4 ± 5.7 and 3.4 ± 4.9 in 2012 and 3.6 ± 4.9, 11.3 ± 33.7 and 5.3 ± 10.8 in 2015, respectively. Patients with pseudotumor had titanium, cobalt and chromium levels of 3.5 ± 2.3, 8.4 ± 8.7 and 6.2 ± 9.4 in 2012 and 4.1 ± 3.4, 6.0 ± 4.5 and 5.1 ± 6.4 in 2015. The ratio of cobalt to chromium was 1.6 ± 1.3 in 2012 and 1.8 ± 1.2 in 2015 in patients without pseudotumor and 2.1 ± 1.2 and 1.9 ± 1.3 with patients with pseudotumor, respectively. There was no statistical correlation between the presence of pseudotumor and age, component pairings (stem, neck and cup) and any of the serum metal ion levels. Discussion/Conclusion. In this prospective cohort study the incidence of pseudotumor was 16.3% in asymptomatic patients with modular THA. The presence of pseudotumor did not correlate with component pairings, serum metal ion levels or cobalt to chromium ratios

Boys affected by Duchenne Muscular Dystrophy (DMD) often develop significant scoliosis in the second decade of life and require scoliosis surgery. Our aim was to establish whether cardiac MRI (CMR) improves the preoperative risk assessment in DMD patients and evaluate the current risk of surgery. Case records were retrospectively reviewed for 62 consecutive DMD boys who underwent pre-surgical evaluation at a single tertiary neuromuscular centre between 2008–2013. 62 DMD patients aged 7–18 years underwent pre-operative assessment for a total of 70 procedures (45 spinal, 19 foot, 6 gastrostomy). Echocardiography data were available for 68 procedures. Echo revealed a median left ventricular (LV) shortening fraction (SF) of 29% (range: 7–44). 34% of boys (23/68) had abnormal SF <25%, 48% (31/65) showed dyskinesia and 22% (14/64) had LV dilatation. CMR was routinely performed on 35 patients. Of those who underwent CMR, median left ventricular ejection fraction (LVEF) was 52% (range: 27–67%), 71% of boys (25/35) had dyskinesia. Echocardiography shortening fraction (SF) correlated significantly with CMR LVEF (r. s. = 0.67; p<0.001). Increasing severity of dyskinesia on CMR correlated with reduced CMR LVEF (r. s. = −0.64; p<0.001) and reduced echo SF (r. s. = −0.47; p = 0.004). Although functional echocardiography and CMR data tended to correlate in 35 DMD boys who underwent both imaging modalities nine (26%) had discrepant results. Seven (20%) had evidence of dysfunction on CMR (LVEF < 55%) not detected on echocardiography (SF ≥ 27%); in two cases echocardiogram measured worse function than CMR. Based on multi-disciplinary risk assessment, surgery was considered too high risk in 23 out of 67 (34%) cases. In 21 cases (91%) this was due to underlying cardiomyopathy. The highest risk among older boys assessed for spinal surgery; 21 out of 43 (49%). Of 19 boys undergoing spinal surgery, six (32%) experienced complications: two wound infections; three patients required readmission to intensive care; one patient died in the post-operative period with acute heart failure

Aims

Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro.

Childhood cancer survival has increased dramatically over the last 30 years. Childhood Cancer Survivor Study- SG was established to evaluate the outcome and toxicities experienced by long term childhood cancer survivors in Singapore. There were 429 cases of hematological malignancies (HM) and 342 cases of solid tumors (ST) diagnosed and treated at National University Hospital (NUH) Singapore from May 1981 to December 2007. There were seven long term survivors for Osteosarcoma (OS) out of 26 patients seen during the study period. Median age at diagnosis was 13.8 (range, 6.4–15.8 years) and median follow-up was 7.9 (range, 2.6 – 13.2 years). Cumulative doses of chemotherapy received included: cisplatin (240 – 800 mg/m2); doxorubicin 150 – 450 mg/m2); methotrexate (16 – 144 Grams/m2); ifosfamide (27–80 mg/m2); and etoposide (1000 – 3300 mg/ m2). According to the NCI Criteria for Toxicity (CTC version 2.0), three patients experiences grade 2 sensorineural hearing loss; three cases of grade 1 cardiomyopathy; three cases of grade 1 renal tubulopathy; and six cases of post surgical complications (infection-3, length discrepancy-3, poor fitting prosthesis-2). Many of the patients did not have baseline pre-treatment evaluations such as audiograms, renal function, echocardiograms and similar proportion were not adequately followed-up post treatment. This is the first analysis and report in the country on treatment related outcome and toxicity in long-term survivors of childhood cancers such as osteosarcoma and other solid tumors. Authors recommend that future treatment protocols for childhood cancer in Singapore should incorporate pre- and post-treatment evaluations and close follow-up of young survivors with establishment of a multi-disciplinary late effects clinic