How early can myocardial iron overload occur in Beta thalassemia major?

BACKGROUND: Myocardial siderosis is the most common cause of death in patients with beta thalassemia major(TM). This study aimed at investigating the occurrence, prevalence and severity of cardiac iron overload in a young Chinese population with beta TM. METHODS AND RESULTS: We analyzed T2* cardiac magnetic resonance (CMR), left ventricular ejection fraction (LVEF) and serum ferritin (SF) in 201 beta TM patients. The median age was 9 years old. Patients received an average of 13 units of blood per year. The median SF level was 4536 ng/ml and 165 patients (82.1%) had SF>2500 ng/ml. Myocardial iron overload was detected in 68 patients (33.8%) and severe myocardial iron overload was detected in 26 patients (12.6%). Twenty-two patients ≤10 years old had myocardial iron overload, three of whom were only 6 years old. No myocardial iron overload was detected under the age of 6 years. Median LVEF was 64% (measured by CMR in 175 patients). Five of 6 patients with a LVEF<56% and 8 of 10 patients with cardiac disease had myocardial iron overload. CONCLUSIONS: The TM patients under follow-up at this regional centre in China patients are younger than other reported cohorts, more poorly-chelated, and have a high burden of iron overload. Myocardial siderosis occurred in patients younger than previously reported, and was strongly associated with impaired LVEF and cardiac disease. For such poorly-chelated TM patients, our data shows that the first assessment of cardiac T2* should be performed as early as 6 years old

Quantitative and qualitative differences in subcutaneous adipose tissue stores across lipodystrophy types shown by magnetic resonance imaging

BACKGROUND: Lipodystrophies are characterized by redistributed subcutaneous fat stores. We previously quantified subcutaneous fat by magnetic resonance imaging (MRI) in the legs of two patients with familial partial lipodystrophy subtypes 2 and 3 (FPLD2 and FPLD3, respectively). We now extend the MRI analysis across the whole body of patients with different forms of lipodystrophy. METHODS: We studied five subcutaneous fat stores (supraclavicular, abdominal, gluteal, thigh and calf) and the abdominal visceral fat stores in 10, 2, 1, 1 and 2 female subjects with, respectively, FPLD2, FPLD3, HIV-related partial lipodystrophy (HIVPL), acquired partial lipodystrophy (APL), congenital generalized lipodystrophy (CGL) and in six normal control subjects. RESULTS: Compared with normal controls, FPLD2 subjects had significantly increased supraclavicular fat, with decreased abdominal, gluteal, thigh and calf subcutaneous fat. FPLD3 subjects had increased supraclavicular and abdominal subcutaneous fat, with less severe reductions in gluteal, thigh and calf fat compared to FPLD2 subjects. The repartitioning of fat in the HIVPL subject closely resembled that of FPLD3 subjects. APL and CGL subjects had reduced upper body, gluteal and thigh subcutaneous fat; the APL subject had increased, while CGL subjects had decreased subcutaneous calf fat. Visceral fat was markedly increased in FPLD2 and APL subjects. CONCLUSION: Semi-automated MRI-based adipose tissue quantification indicates differences between various lipodystrophy types in these studied clinical cases and is a potentially useful tool for extended quantitative phenomic analysis of genetic metabolic disorders. Further studies with a larger sample size are essential for confirming these preliminary findings

Lithium suppression of tau induces brain iron accumulation and neurodegeneration

Lithium is a first-line therapy for bipolar affective disorder. However, various adverse effects, including a Parkinson-like hand tremor, often limit its use. The understanding of the neurobiological basis of these side effects is still very limited. Nigral iron elevation is also a feature of Parkinsonian degeneration that may be related to soluble tau reduction. We found that magnetic resonance imaging T2 relaxation time changes in subjects commenced on lithium therapy were consistent with iron elevation. In mice, lithium treatment lowers brain tau levels and increases nigral and cortical iron elevation that is closely associated with neurodegeneration, cognitive loss and parkinsonian features. In neuronal cultures lithium attenuates iron efflux by lowering tau protein that traffics amyloid precursor protein to facilitate iron efflux. Thus, tau- and amyloid protein precursor-knockout mice were protected against lithium-induced iron elevation and neurotoxicity. These findings challenge the appropriateness of lithium as a potential treatment for disorders where brain iron is elevated (for example, Alzheimer’s disease), and may explain lithium-associated motor symptoms in susceptible patients

Reducing pain in children with cancer: Methodology for the development of a clinical practice guideline

Abstract Although pain is one of the most prevalent and bothersome symptoms children with cancer experience, evidence-based guidance regarding assessment and management is lacking. With 44 international, multidisciplinary healthcare professionals and nine patient representatives, we aimed to develop a clinical practice guideline (following GRADE methodology), addressing assessment and pharmacological, psychological, and physical management of tumor-, treatment-, and procedure-related pain in children with cancer. In this paper, we present our thorough methodology for this development, including the challenges we faced and how we approached these. This lays the foundation for our clinical practice guideline, for which there is a high clinical demand

Ultrasound diagnosis and evaluation of plantar heel pain

BACKGROUND: One of the most common causes of heel pain is plantar fasciitis; however, there are other pathologic disorders that can mimic the symptoms and clinical presentation of this disorder. The purpose of this study was to retrospectively review the prevalence of various pathologic disorders on ultrasound in patients with proximal plantar heel pain. METHODS: The medical records and diagnostic ultrasound reports of patients presenting with plantar heel pain between March 1, 2006, and March 31, 2007, were reviewed retrospectively, and the prevalence of various etiologies was collected. The inclusion criteria were based on their clinical presentation of plantar fasciitis or previous diagnosis of plantar fasciitis from an unknown source. Ultrasound evaluation was then performed to confirm the clinical diagnosis. RESULTS: We examined 175 feet of 143 patients (62 males and 81 females; age range, 16-79 years). Plantar fibromas were present in 90 feet (51%). Plantar fasciitis was diagnosed in 128 feet (73%). Coexistent plantar fibroma and plantar fascial thickening was found in 63 feet (36%). Of the 47 feet that were negative for plantar fasciitis on ultrasound, 27 (57%) revealed the presence of plantar fibroma. CONCLUSIONS: Diagnostic ultrasound can effectively and safely identify the prevalence of various etiologies of heel pain. The high prevalence of plantar fibromas and plantar fascial tears cannot be determined by clinical examination alone, and, therefore, ultrasound evaluation should be performed for confirmation of diagnosis

An image-based and RBF mesh morphing CFD simulation for aTAA hemodynamic

It is well known that haemodynamic parameters, such as blood flow velocity, blood pressure and wall shear stress (WSS), are closely related with the pathophysiology of aortic diseases. However, the data regarding the formation and the progression of the bulge are still difficult to be obtained in a clinical setting. In this study, 3D surface models defined from healthy subjects and patients with ascending thoracic aorta aneurysms (aTAA), selected for surgical repair, have been generated. A representative shape model for both healthy and pathological groups has been identified. A morphing technique based on radial basis functions (RBF) has been applied to mould the shape relative to healthy patient into the representative shape of aTAA dataset so as to enable the parametric simulation of the aTAA formation. CFD simulations were performed by means of a finite volume solver using the mean boundary conditions obtained from three-dimensional (PC-MRI) acquisition

Computational Fluid Dynamic Study for aTAA Hemodynamics: An Integrated Image-Based and Radial Basis Functions Mesh Morphing Approach

We present a novel framework for the fluid dynamics analysis of healthy subjects and patients affected by ascending thoracic aorta aneurysm (aTAA). Our aim is to obtain indications about the effect of a bulge on the hemodynamic environment at different enlargements. 3D surface models defined from healthy subjects and patients with aTAA, selected for surgical repair, were generated. A representative shape model for both healthy and pathological groups has been identified. A morphing technique based on radial basis functions (RBF) was applied to mould the shape relative to healthy patient into the representative shape of aTAA dataset to enable the parametric simulation of the aTAA formation. CFD simulations were performed by means of a finite volume solver using the mean boundary conditions obtained from three-dimensional (PC-MRI) acquisition. Blood flow helicity and flow descriptors were assessed for all the investigated models. The feasibility of the proposed integrated approach of RBF morphing technique and CFD simulation for aTAA was demonstrated. Significant hemodynamic changes appear at the 60% of the bulge progression. An impingement of the flow toward the bulge was observed by analyzing the normalized flow eccentricity index