Mesenchymal tumours of the mediastinum—part II

This is the second part of a two-part review on soft tissue tumours which may be encountered in the mediastinum. This review is based on the 2013 WHO classification of soft tissue tumours and the 2015 WHO classification of tumours of the lung, pleura, thymus and heart and provides an updated overview of mesenchymal tumours that have been reported in the mediastinum

Diseases of the Chest, Breast, Heart and Vessels 2019-2022

This open access book focuses on diagnostic and interventional imaging of the chest, breast, heart, and vessels. It consists of a remarkable collection of contributions authored by internationally respected experts, featuring the most recent diagnostic developments and technological advances with a highly didactical approach. The chapters are disease-oriented and cover all the relevant imaging modalities, including standard radiography, CT, nuclear medicine with PET, ultrasound and magnetic resonance imaging, as well as imaging-guided interventions. As such, it presents a comprehensive review of current knowledge on imaging of the heart and chest, as well as thoracic interventions and a selection of "hot topics". The book is intended for radiologists, however, it is also of interest to clinicians in oncology, cardiology, and pulmonology

Diseases of the Chest, Breast, Heart and Vessels 2019-2022

This open access book focuses on diagnostic and interventional imaging of the chest, breast, heart, and vessels. It consists of a remarkable collection of contributions authored by internationally respected experts, featuring the most recent diagnostic developments and technological advances with a highly didactical approach. The chapters are disease-oriented and cover all the relevant imaging modalities, including standard radiography, CT, nuclear medicine with PET, ultrasound and magnetic resonance imaging, as well as imaging-guided interventions. As such, it presents a comprehensive review of current knowledge on imaging of the heart and chest, as well as thoracic interventions and a selection of "hot topics". The book is intended for radiologists, however, it is also of interest to clinicians in oncology, cardiology, and pulmonology

Comparative effect of metformin versus sulfonylureas with dementia and Parkinson’s disease risk in US patients over 50 with type 2 diabetes mellitus

Introduction Type 2 diabetes is a risk factor for dementia and Parkinson’s disease (PD). Drug treatments for diabetes, such as metformin, could be used as novel treatments for these neurological conditions. Using electronic health records from the USA (OPTUM EHR) we aimed to assess the association of metformin with all-cause dementia, dementia subtypes and PD compared with sulfonylureas. Research design and methods A new user comparator study design was conducted in patients ≥50 years old with diabetes who were new users of metformin or sulfonylureas between 2006 and 2018. Primary outcomes were all-cause dementia and PD. Secondary outcomes were Alzheimer’s disease (AD), vascular dementia (VD) and mild cognitive impairment (MCI). Cox proportional hazards models with inverse probability of treatment weighting (IPTW) were used to estimate the HRs. Subanalyses included stratification by age, race, renal function, and glycemic control. Results We identified 96 140 and 16 451 new users of metformin and sulfonylureas, respectively. Mean age was 66.4±8.2 years (48% male, 83% Caucasian). Over the 5-year follow-up, 3207 patients developed all-cause dementia (2256 (2.3%) metformin, 951 (5.8%) sulfonylurea users) and 760 patients developed PD (625 (0.7%) metformin, 135 (0.8%) sulfonylurea users). After IPTW, HRs for all-cause dementia and PD were 0.80 (95% CI 0.73 to 0.88) and 1.00 (95% CI 0.79 to 1.28). HRs for AD, VD and MCI were 0.81 (0.70–0.94), 0.79 (0.63–1.00) and 0.91 (0.79–1.04). Stronger associations were observed in patients who were younger (<75 years old), Caucasian, and with moderate renal function. Conclusions Metformin users compared with sulfonylurea users were associated with a lower risk of all-cause dementia, AD and VD but not with PD or MCI. Age and renal function modified risk reduction. Our findings support the hypothesis that metformin provides more neuroprotection for dementia than sulfonylureas but not for PD, but further work is required to assess causality

Multiple morbidity across the lifespan in people with Down syndrome or intellectual disabilities: a population-based cohort study using electronic health records.

BACKGROUND: The Down syndrome phenotype is well established, but our understanding of its morbidity patterns is limited. We comprehensively estimated the risk of multiple morbidity across the lifespan in people with Down syndrome compared with the general population and controls with other forms of intellectual disability. METHODS: In this matched population-based cohort-study design, we used electronic health-record data from the UK Clinical Practice Research Datalink (CRPD) from Jan 1, 1990, to June 29, 2020. We aimed to explore the pattern of morbidities throughout the lifespan of people with Down syndrome compared with people with other intellectual disabilities and the general population, to identify syndrome-specific health conditions and their age-related incidence. We estimated incidence rates per 1000 person-years and incidence rate ratios (IRRs) for 32 common morbidities. Hierarchical clustering was used to identify groups of associated conditions using prevalence data. FINDINGS: Between Jan 1, 1990, and June 29, 2020, a total of 10 204 people with Down syndrome, 39 814 controls, and 69 150 people with intellectual disabilities were included. Compared with controls, people with Down syndrome had increased risk of dementia (IRR 94·7, 95% CI 69·9-128·4), hypothyroidism (IRR 10·6, 9·6-11·8), epilepsy (IRR 9·7, 8·5-10·9), and haematological malignancy (IRR 4·7, 3·4-6·3), whereas asthma (IRR 0·88, 0·79-0·98), cancer (solid tumour IRR 0·75, 0·62-0·89), ischaemic heart disease (IRR 0·65, 0·51-0·85), and particularly hypertension (IRR 0·26, 0·22-0·32) were less frequent in people with Down syndrome than in controls. Compared to people with intellectual disabilities, risk of dementia (IRR 16·60, 14·23-19·37), hypothyroidism (IRR 7·22, 6·62-7·88), obstructive sleep apnoea (IRR 4·45, 3·72-5·31), and haematological malignancy (IRR 3·44, 2·58-4·59) were higher in people with Down syndrome, with reduced rates for a third of conditions, including new onset of dental inflammation (IRR 0·88, 0·78-0·99), asthma (IRR 0·82, 0·73-0·91), cancer (solid tumour IRR 0·78, 0·65-0·93), sleep disorder (IRR 0·74, 0·68-0·80), hypercholesterolaemia (IRR 0·69, 0·60-0·80), diabetes (IRR 0·59, 0·52-0·66), mood disorder (IRR 0·55, 0·50-0·60), glaucoma (IRR 0·47, 0·29-0·78), and anxiety disorder (IRR 0·43, 0·38-0·48). Morbidities in Down syndrome could be categorised on age-related incidence trajectories, and their prevalence clustered into typical syndromic conditions, cardiovascular diseases, autoimmune disorders, and mental health conditions. INTERPRETATION: Multiple morbidity in Down syndrome shows distinct patterns of age-related incidence trajectories and clustering that differ from those found in the general population and in people with other intellectual disabilities, with implications for provision and timing of health-care screening, prevention, and treatment for people with Down syndrome. FUNDING: The European Union's Horizon 2020 Research and Innovation Programme, the Jérôme Lejeune Foundation, the Alzheimer's Society, the Medical Research Council, the Academy of Medical Sciences, the Wellcome Trust, and William Harvey Research Limited

Exploiting Radiosensitivity in the Modern Management of Neuroblastoma

Neuroblastoma is a biologically diverse and clinically challenging tumour. At one end of the clinical spectrum, children with localised, low risk disease, can survive with little or no therapy. Spontaneous resolution of this tumour has been seen and children have survived despite residual macroscopic tumour remaining at the end of therapy. In contrast, the majority of children present with widespread metastatic disease and are rarely curable. Paradoxically this is an aggressive form of disease despite appearing sensitive to both chemotherapy and radiotherapy. The majority of these patients relapse and only 20% survive 2 years. This thesis is concerned only with the management of stage 4 patients and concentrates on 3 main areas. Firstly, the role of control of the primary tumour was considered, in this essentially systemic disease. It was shown that complete surgical resection of the primary reduces local relapse and improves survival. Prognostic factors for stage 4 patients were examined during this analysis and the identification of prognostic subgroups was possible. Secondly a retrospective analysis of all stage 4 patients treated within this centre was completed, to determine the usefulness of external beam radiotherapy in the palliation of advanced disease. The final part of this thesis is experimentally based. Factors that may improve the clinical effectiveness of 131I-meta-iodobenzylguanidine (131I-mIBG) were investigated. This molecule is a targeting agent, which, when administered systemically, is selectively accumulated by tumours of neural crest origin. In clinical practice the individual tumour uptake can be variable and the optimum timing of administration is still undetermined. Initially a new formulation of 131I-mIBG was investigated. This 'no carrier added' (nca) formulation meant that smaller quantities of drug could be administered and tumour specific accumulation increased. Before clinical studies could be contemplated, laboratory investigations had to be completed, to determine if this new preparation behaved similarly to the traditional formulation. The work documented in this thesis confirms this is the case. Another aim of this thesis was to examine biological factors that may modulate specific tumour accumulation of this agent. The effect of pre-dosing neuroblastoma cells in culture, with chemotherapy agents, resulted in a 2-5 fold increase in specific type 1 tumour accumulation. This may be a very significant finding for the future administration of 131I-mIBG in combination therapy regimens. Unfortunately the combination of elevated temperature and 131I-mIBG exposure resulted in decreased tumour accumulation of 131I-mIBG

Medical-Data-Models.org:A collection of freely available forms (September 2016)

MDM-Portal (Medical Data-Models) is a meta-data repository for creating, analysing, sharing and reusing medical forms, developed by the Institute of Medical Informatics, University of Muenster in Germany. Electronic forms for documentation of patient data are an integral part within the workflow of physicians. A huge amount of data is collected either through routine documentation forms (EHRs) for electronic health records or as case report forms (CRFs) for clinical trials. This raises major scientific challenges for health care, since different health information systems are not necessarily compatible with each other and thus information exchange of structured data is hampered. Software vendors provide a variety of individual documentation forms according to their standard contracts, which function as isolated applications. Furthermore, free availability of those forms is rarely the case. Currently less than 5 % of medical forms are freely accessible. Based on this lack of transparency harmonization of data models in health care is extremely cumbersome, thus work and know-how of completed clinical trials and routine documentation in hospitals are hard to be re-used. The MDM-Portal serves as an infrastructure for academic (non-commercial) medical research to contribute a solution to this problem. It already contains more than 4,000 system-independent forms (CDISC ODM Format, www.cdisc.org, Operational Data Model) with more than 380,000 dataelements. This enables researchers to view, discuss, download and export forms in most common technical formats such as PDF, CSV, Excel, SQL, SPSS, R, etc. A growing user community will lead to a growing database of medical forms. In this matter, we would like to encourage all medical researchers to register and add forms and discuss existing forms

Impact of decentring patients for abdominal CT scan

Purpose: To evaluate the effect on skin dose and image quality when decentering in the y- and x-direction for abdominal CT scans.Methods: Patient centering data in CT were collected retrospectively from dose management software (DoseWatch, GE Healthcare) from a single university hospital (n=4 scanners) in 2017. Deviations from the isocentre were categorized for both vertical (±1.5cm, ±3.0cm, ±4.5cm) and horizontal (±1.5cm, ±3cm) planes on 498 patients. An anthropomorphic phantom (PBU-60) was subsequently scanned using each deviation on two scanners (Toshiba Prime, GE HD750) to allow dose and image quality (noise and visual grading assessment) comparisons. Results: Significant skin dose increases (4.3mSv/50%) were detected anteriorly for both scanners when centered above the isocenter and reductions (2.0mSv, 24%) when below the isocenter. For the HD750, dose decreased up to 8.3mSv in four locations at the -4.5 position with increases (2.0mSv) noted on the right side with horizontal deviation. With upward vertical deviation noise increased from 13HU (isocenter) to 15HU. No change in standard deviation (SD) was detected with the phantom below isocenter. With left horizontal deviation SD increased by 12HU while SD decreased by 12HU dextro-laterally. VGA-score was lowest at the largest vertical ISO-center deviation. Conclusion: Positioning above ISO-center may increase noise and skin dose. Similarly, horizontal deviation may increase dose. Subjective image quality is negatively affected by extreme vertical ISO-center deviation. <br/