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Bone & Joint Research
Vol. 10, Issue 6 | Pages 340 - 347
1 Jun 2021
Jenkinson MRJ Meek RMD Tate R MacMillan S Grant MH Currie S

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


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_15 | Pages 20 - 20
1 Mar 2013
Zywiel M Syed K Overgaard CB Cheung AC Turgeon T Brandt J
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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


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_15 | Pages 54 - 54
1 Dec 2015
Mousouli A Stefani D Tsiplakou S Sgouros K Lelekis M
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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


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_11 | Pages 9 - 9
7 Jun 2023
Jenkinson M Meek D MacMillan S Tate R Grant MH Currie S
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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


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_12 | Pages 31 - 31
23 Jun 2023
Meek D Jenkinson M Macmillan S Tate R Grant H Currie S
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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


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_16 | Pages 66 - 66
19 Aug 2024
Terhune EB Sutter EG Balkissoon R Pallante GD Specht L Leikin JB Kwon YM Lewallen DG Gerlinger TL Jacobs JJ
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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


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_10 | Pages 12 - 12
1 Aug 2021
Deere K Matharu G Ben-Shlomo Y Wilkinson J Blom A Sayers A Whitehouse M
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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


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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


Bone & Joint Research
Vol. 11, Issue 8 | Pages 548 - 560
17 Aug 2022
Yuan W Yang M Zhu Y

Aims

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

Methods

Five datasets were obtained from the Gene Expression Omnibus database. Unsupervised consensus cluster analysis was used to determine new PMOP subtypes. To determine the central genes and the core modules related to PMOP, the weighted gene co-expression network analysis (WCGNA) was applied. Gene Ontology enrichment analysis was used to explore the biological processes underlying key genes. Logistic regression univariate analysis was used to screen for statistically significant variables. Two algorithms were used to select important PMOP-related genes. A logistic regression model was used to construct the PMOP-related gene profile. The receiver operating characteristic area under the curve, Harrell’s concordance index, a calibration chart, and decision curve analysis were used to characterize PMOP-related genes. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of the PMOP-related genes in the gene signature.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 321 - 331
3 Jul 2024
Naito T Yamanaka Y Tokuda K Sato N Tajima T Tsukamoto M Suzuki H Kawasaki M Nakamura E Sakai A

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.

Methods

Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_22 | Pages 3 - 3
1 Dec 2016
Dunbar M
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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


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_7 | Pages 141 - 141
1 May 2016
Frisch N Wessell N Van Holsbeeck M Silverton C
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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


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_15 | Pages 2 - 2
1 Oct 2014
Parish E Brunklaus A Muntoni F Scuplak S Tucker S Fenton M Hughes M Manzur A
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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


Bone & Joint Research
Vol. 13, Issue 4 | Pages 157 - 168
4 Apr 2024
Lin M Chen G Yu H Hsu P Lee C Cheng C Wu S Pan B Su B

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.

Methods

MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 457 - 457
1 Jul 2010
Aung L Saw S Khaing T Khyne T Nathan S Yeoh E Quah T Pho R
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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


Bone & Joint Open
Vol. 3, Issue 1 | Pages 85 - 92
27 Jan 2022
Loughenbury PR Tsirikos AI

The development of spinal deformity in children with underlying neurodisability can affect their ability to function and impact on their quality of life, as well as compromise provision of nursing care. Patients with neuromuscular spinal deformity are among the most challenging due to the number and complexity of medical comorbidities that increase the risk for severe intraoperative or postoperative complications. A multidisciplinary approach is mandatory at every stage to ensure that all nonoperative measures have been applied, and that the treatment goals have been clearly defined and agreed with the family. This will involve input from multiple specialities, including allied healthcare professionals, such as physiotherapists and wheelchair services. Surgery should be considered when there is significant impact on the patients’ quality of life, which is usually due to poor sitting balance, back or costo-pelvic pain, respiratory complications, or problems with self-care and feeding. Meticulous preoperative assessment is required, along with careful consideration of the nature of the deformity and the problems that it is causing. Surgery can achieve good curve correction and results in high levels of satisfaction from the patients and their caregivers. Modern modular posterior instrumentation systems allow an effective deformity correction. However, the risks of surgery remain high, and involvement of the family at all stages of decision-making is required in order to balance the risks and anticipated gains of the procedure, and to select those patients who can mostly benefit from spinal correction.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 452 - 452
1 Jul 2010
Longhi A Bacci G Ferrari C Picci P Ferrari S
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Prolonged survival have been reached in the last two decades in patients with Ewing’s sarcoma due to combination of chemotherapy and radiotherapy. We report the analysis of 493 patients treated according to 4 different protocols in 23 years (Jan1983- Dec 2006).Aim of this study was to evaluate the occurrence of late toxicities as Second Malignant Neoplasms (SMN), Cardiomyopathies and sterility. Methods: We reviewed our database to find out all those patients aged from 1 to 40 yrs with localized Ewing’s sarcoma who were treated with chemotherapy according to 4 different protocols from 1983 to December 2006. Data were updated at Dec 2008. Results: 493 patients had adequate follow up and meet the eligibility criteria. Median age was 16 yrs (1–40) female/male: 183/310.Median overall survival 69 ms (4–302).220 patients died and 273 are alive. 44 pts received HDCT + PBSCR.Eleven SMN were found : 2 AMLeukemia, 2 parotid adenocarcinoma, 1 melanoma, 1 thyroid cancer and 5 radioinduced osteosarcoma. The interval between Ewing’s sarcoma diagnosis and leukaemia diagnosis was shorter then interval between Ewing’s sarcoma and RT osteosarcoma. Six patients reported a Cardiomyopathy : in 4 cases it was mild and pts are well compensated,2 patients needed heart transplant,. One of these two pts received also a kidney transplant due to chronic renal failure due to previous chemotherapy. Fertility: 17 women became pregnant after chemotherapy, 20 women experienced postTx amenorrea: 7 pts received RT in pelvic area, 9 did HDCT, 3 pts were over 30 yrs old. 9 male became father. 8 male patients did sperm analysis 3 azospermia, 4 oligospermia and 1 normal sperm count. No congenital abnormalities in offsprings were reported. Conclusions: In this casuistic the Cumulative Risk to have a SMN at 5 yrs is 1.8% and 2.9% at 10 yr. The SMN cumulative incidence in Ewing’s sarcoma seems to be lower then in our previous casistic in osteosarcoma patients (ASCO 2006)


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_II | Pages 117 - 117
1 Feb 2004
Eagle M Mehta JS Bushby KM Gibson MJ
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Objective: To assess the effect of spinal surgery and nocturnal ventilation on lung function and survival in patients with scoliosis secondary to Duchenne Muscular Dystrophy. Study design: Prospective, observational study by a single observer (Research Physiotherapist). Subjects: 80 patients with Duchenne Muscular Dystrophy were treated between 1986 and 2002. During this period 40 patients underwent a spinal fusion at a mean age of 14.05y (95 % CI 13.6 – 14.6). Nocturnal ventilation was commenced when symptoms and signs of respiratory failure were evident. The mean FVC at commencement of nocturnal ventilation was 0.41 litres. The patients were divided into 2 groups based on whether they received nocturnal ventilation. A total of twenty eight patients received nocturnal ventilation and 52 did not. The groups were further sub-divided based on whether they had spinal fusion. There were fourteen patients in each sub-group of the ventilated group and 26 patients in each sub-group of those that were not ventilated. Outcomes: Serial forced vital capacity (FVC) measurements and survival measured by Kaplan Meir survival analysis. Results: The mean vital capacity dropped from 1.41 l (95 % CI 1.21 – 1.61) to 1.13 (95 % CI 0.893 – 1.37), a year post-operatively. This was not associated with the development of respiratory compromise. The vital capacity improved gradually, reaching the pre-operative level before it declined again. The shortest survival was seen in patients who received neither surgery nor ventilation (median survival 19.7y). The patients who received surgery but no ventilatory support were not as good as the patients that were ventilated but did not have surgery (median survival 24.3y). The best results were seen in the patients who had both surgery and ventilation (median survival 26.4y). The worst prognosis is in patients with early onset symptomatic cardiomyopathy (6 patients, with a median survival of 16.3y). Conclusion: Nocturnal ventilation is the most important factor in the improvement in survival of patients with Duchennes muscular dystrophy. Spinal surgery is also beneficial and the best results are in those patients who have both


Bone & Joint Research
Vol. 10, Issue 6 | Pages 348 - 350
1 Jun 2021
Skinner JA Sabah SA Hart AJ


Bone & Joint Open
Vol. 2, Issue 5 | Pages 338 - 343
21 May 2021
Harvey J Varghese BJ Hahn DM

Aims

Displaced distal radius fractures were investigated at a level 1 major trauma centre during the COVID-19 2020 lockdown due to the implementation of temporary changes in practice. The primary aim was to establish if follow-up at one week in place of the 72-hour British Orthopaedic Association Standards for Trauma & Orthopaedics (BOAST) guidance was safe following manipulation under anaesthetic. A parallel adaptation during lockdown was the non-expectation of Bier’s block. The secondary aim was to compare clinical outcomes with respect to block type.

Methods

Overall, 90 patients were assessed in a cross-sectional cohort study using a mixed, retrospective-prospective approach. Consecutive sampling of 30 patients pre-lockdown (P1), 30 during lockdown (P2), and 30 during post-lockdown (P3) was applied. Type of block, operative status, follow-up, and complications were extracted. Primary endpoints were early complications (≤ one week). Secondary endpoints were later complications including malunion, delayed union or osteotomy.