PE MIMICS: a structured approach for the emergency radiologist in the evaluation of chest pain.

Chest pain is a common reason for presentation to the emergency department. In many cases, a CTPA or CT thoracic aorta is performed during work up to assess for pulmonary embolism and aortic pathology, critical diagnoses that can be difficult to out rule clinically. However, the causes of chest pain are myriad. It is therefore crucial for the interpreting radiologist to be cognizant of other potential etiologies when interpreting these studies. The purpose of this pictorial essay is to highlight the causes of non-PE or aortic-related chest pain and provide radiologists with a structured approach to interpreting these studies, ensuring a comprehensive search strategy so that important pathologies are not missed.

Creation of a protective space between the rectum and prostate prior to prostate radiotherapy using a hydrogel spacer.

The placement of a polyethylene glycol (PEG) hydrogel spacer is a recently developed technique employed to reduce the radiation dose administered to the rectum during prostate radiotherapy. This procedure has been adopted by urologists and radiation oncologists involved in transperineal prostate biopsy and brachytherapy, and more recently by radiologists with experience in transperineal prostate procedures. Radiologists should be familiar with the product, which may be encountered on computed tomography (CT) or magnetic resonance imaging (MRI). Radiologists may wish to become involved in the delivery of this increasingly utilised procedure. This review familiarises radiologists with the technique and risks and benefits of the use of transperineal delivery of hydrogel spacers with imaging examples.

A systematic review of cannabidiol dosing in clinical populations.

AIMS: Cannabidiol (CBD) is a cannabis-derived medicinal product with potential application in a wide-variety of contexts; however, its effective dose in different disease states remains unclear. This review aimed to investigate what doses have been applied in clinical populations, in order to understand the active range of CBD in a variety of medical contexts. METHODS: Publications involving administration of CBD alone were collected by searching PubMed, EMBASE and ClinicalTrials.gov. RESULTS: A total of 1038 articles were retrieved, of which 35 studies met inclusion criteria covering 13 medical contexts. Twenty-three studies reported a significant improvement in primary outcomes (e.g. psychotic symptoms, anxiety, seizures), with doses ranging between <1 and 50 mg/kg/d. Plasma concentrations were not provided in any publication. CBD was reported as well tolerated and epilepsy was the most frequently studied medical condition, with all 11 studies demonstrating positive effects of CBD on reducing seizure frequency or severity (average 15 mg/kg/d within randomised controlled trials). There was no signal of positive activity of CBD in small randomised controlled trials (range n = 6-62) assessing diabetes, Crohn's disease, ocular hypertension, fatty liver disease or chronic pain. However, low doses (average 2.4 mg/kg/d) were used in these studies. CONCLUSION: This review highlights that CBD has a potential wide range of activity in several pathologies. Pharmacokinetic studies as well as conclusive phase III trials to elucidate effective plasma concentrations within medical contexts are severely lacking and highly encouraged.

Age-Dependent Association Between Pre-transplant Blood Transfusion and Outcomes of Pediatric Heart Transplantation.

Avoidance of red blood cell (RBC) transfusions in patients awaiting heart transplantation (HTx) has been suggested to minimize the risk of allosensitization. Although recent studies have suggested that an immature immune system in younger HTx recipients may reduce risks associated with RBC transfusion, the role of age in moderating the influence of transfusion on HTx outcomes remains unclear. We used available data from a national transplant registry to explore whether the association between pre-transplant transfusions and outcomes of pediatric HTx varies by patient age. De-identified data were obtained from the United Network for Organ Sharing registry, including first-time recipients of isolated HTx performed at age 0-17 years in 1995-2015. The primary exposure was receiving blood transfusions within 2 weeks prior to HTx. Patient survival after HTx was evaluated using multivariable Cox proportional hazards, where age at transplant was interacted with exposure to pre-transplant transfusion. Age-specific hazard ratios (HRs) of pre-transplant transfusion were plotted across ages at transplant. There were 4883 patients meeting inclusion criteria, of whom 1258 died during follow-up (mean follow-up duration 6 ± 5 years). Patients receiving pre-transplant transfusions were distinguished by younger age, higher prevalence of prior cardiac surgery, greater likelihood of being in the intensive care unit, and greater use of left ventricular assist device bridge to transplant. In multivariable analysis, pre-transplant transfusions were associated with increased mortality hazard among infants < 1 year of age (HR = 1.46; 95% CI 1.23, 1.74; p < 0.001). For each additional year of age, the excess hazard associated with pre-transplant transfusions decreased by 3% (interaction HR = 0.97; 95% CI 0.98, 0.99; p = 0.003). By age 8, the association between pre-transplant transfusions and post-transplant mortality was no longer statistically significant (HR = 1.15; 95% CI 0.99, 1.32; p = 0.060). Pre-transplant transfusions were associated with increased mortality hazard only among younger children (age < 8 years) undergoing HTx. These data support the current practices of transfusion avoidance prior to HTx, particularly in younger patients.

2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty

OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). METHODS: A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. RESULTS: The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence. CONCLUSION: This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.

2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty

OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). METHODS: A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. RESULTS: The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence. CONCLUSION: This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.

Implementing Intensity-modulated Radiotherapy with Simultaneous Integrated Boost for Anal Cancer: 3 Year Outcomes at Two Sydney Institutions.

AIMS: Modern chemoradiotherapy used for the treatment of anal cancer has significant acute toxicity. Intensity-modulated radiotherapy (IMRT) may reduce these side-effects. We report our experience implementing IMRT with simultaneous boost at the Sydney Cancer Centre and Royal North Shore Hospital. MATERIALS AND METHODS: We retrospectively collected acute toxicity data on all consecutive patients treated definitively with IMRT between January 2008 and December 2011. Patients received concurrent 5-fluorouracil and mitomycin-C. The radiotherapy dose varied by stage in accordance with the Radiation Therapy Oncology Group (RTOG) 0529 protocol. The first 30 plans were evaluated for adherence to RTOG 0529 dose specifications. Locoregional control and survival outcomes were analysed in July 2014. RESULTS: We included 42 patients (stage I 12%; II 41%; III 45%) with a median follow-up time of 43 months. At 3 years the locoregional control was 94% (95% confidence interval: 78-99), overall survival was 92% (95% confidence interval: 78-97), disease-free survival was 89% (95% confidence interval: 73-96), metastasis-free survival was 89% (95% confidence interval: 73-96) and colostomy-free survival was 89% (95% confidence interval: 72-96). There was no acute grade 4 toxicity. Acute grade 3 toxicity rates were: dermatological (33%), gastrointestinal (14%) and haematological (19%). Twenty-six per cent of patients were hospitalised for treatment-related toxicity. Only 12% required a treatment break greater than 3 days. All patients achieved RTOG 0529 planning target volume dose specifications. Most critical organ dose constraints were either met or met with minor deviation. The exception was 76% major deviation in small bowel constraints. Despite this no increase in gastrointestinal toxicity was observed. CONCLUSIONS: IMRT with simultaneous integrated boost is safe and well tolerated in an unselected population. Most dose specifications are achievable. Excellent locoregional control and survival outcomes are achievable outside of a clinical trial setting.

The EPIICAL project: an emerging global collaboration to investigate immunotherapeutic strategies in HIV-infected children.

The EPIICAL (Early-treated Perinatally HIV-infected Individuals: Improving Children's Actual Life with Novel Immunotherapeutic Strategies) project arises from the firm belief that perinatally infected children treated with suppressive antiretroviral therapy (ART) from early infancy represent the optimal population model in which to study novel immunotherapeutic strategies aimed at achieving ART-free remission. This is because HIV-infected infants treated within 2-3 months of life have a much reduced viral reservoir size, and rarely show HIV-specific immunity but preserve normal immune development. The goal of EPIICAL is the establishment of an international collaboration to develop a predictive platform using this model to select promising HIV therapeutic vaccine candidates, leading to prioritisation or deprioritisation of novel immunotherapeutic strategies. To establish this platform, the EPIICAL Consortium aims to: develop predictive models of virological and immunological dynamics associated with response to early ART and to treatment interruption using available data from existing cohorts/studies of early-treated perinatally HIV-infected children; optimise methodologies to better characterise immunological, virological and genomic correlates/profiles associated with viral control; test novel immunotherapeutic strategies using in vivo proof-of-concept (PoC) studies with the aim of inducing virological, immunological and transcriptomic correlates/profiles equivalent to those defined by the predictive model. This approach will strengthen the capacity for discovery, development and initial testing of new therapeutic vaccine strategies through the integrated efforts of leading international scientific groups, with the aim of improving the health of HIV-infected individuals.

Polychlorinated biphenyl (PCB) and dioxin concentrations in residential dust of pregnant women.

Polychlorinated biphenyls (PCBs) and dioxins are well known for their persistence in the environment. PCBs can be found in the residential environment long after the use of these chemicals in domestic products and industrial processes has ceased. Dioxins have been assessed in Australia as being of very low concentrations. Despite concerns about residential dust as a source of human exposure to persistent chemicals, there has been limited testing of PCBs and dioxins in dust in Australia. As part of an assessment of maternal exposure to a variety of persistent toxic substances, we analysed 30 residential dust samples from a variety of geographical settings for their dioxin and PCB concentrations. PCBs were found in most samples, the median and range concentrations (pg g(-1)) of dominant congeners of PCB were as follows: PCB118 (315; <35.0-29 000), PCB105 (130; 14.0-16 000) and PCB156 (440; <5.00-2800). Dioxin concentrations were generally low with median concentrations for the total sum of dioxin-like polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) of 3.75 pg g(-1) each. There was a very high percentage of non-detects. Concentrations of both PCBs and dioxins were low compared with most studies reporting residential dust concentrations internationally. Age of dwelling was the only factor observed to influence both PCB congener concentrations and dioxin isomers in multivariate regression analyses. No other housing or sociodemographic variables, including proximity to industry, were important predictors in multivariate linear regression models.

Stability study of full-length antibody (anti-TNF alpha) loaded PLGA microspheres.

Antibodies (Abs) require the development of stable formulations and specific delivery strategies given their susceptibility to a variety of physical and chemical degradation pathways. In this study, the encapsulation of an antibody into polylactide-co-glycolide (PLGA) based microspheres was explored to obtain a controlled-release of the incorporated drug. In order to avoid stability issues, a solid-in-oil-in-water (s/o/w) method was preferred. The solid phase was made of anti-TNF alpha monoclonal antibody (MAb) spray-dried microparticles, and the PLGA microspheres were produced using two different polymers (i.e., Resomer(®) RG505 and Resomer(®) RG755S). The stability of the MAb incorporated into the microspheres was investigated under three conditions (5 ± 3°C, 25 ± 2°C/60% RH and 40 ± 2°C/75% RH) for 12 weeks. During this stability study, it was demonstrated that the MAb loaded PLGA microspheres were stable when stored at 5 ± 3°C and that the Resomer(®) RG755S, composed of 75%(w/w) lactic acid as PLGA, was preferred to preserve the stability of the system. Storage at temperatures higher than 5°C led to antibody stability issues such as aggregation, fragmentation and loss of activity. The release profiles were also altered. Physical ageing of the system associated with changes in the glass transition temperature and enthalpy of relaxation was noticed during the storage of the MAb loaded PLGA microspheres.

Imaging pancreas transplants.

Pancreas transplants are performed in multiple centres across the UK with good graft survival rates. This places an increasing demand on radiology services, particularly as the complication rates are not insignificant. The imaging appearances of pancreas transplants and their complications can be difficult to interpret. This review provides an illustrative journey through the anatomical appearances of a graft and the imaging appearances of complications, as a reference tool for radiologists.

Quantitation of fetomaternal haemorrhage and F cells in unusual maternal blood samples by flow cytometry using anti-D and anti-HbF.

BACKGROUND: Fetomaternal haemorrhage (FMH) assessment by the Kleihauer-Betke test (KBT) is rapid but semi-quantitative and liable to false positive results. OBJECTIVES: To compare FMH estimated by KBT with flow cytometry (FC) quantitation for 37 patients with massive FMH, obstetric risk factors or technical problems. METHODS: Maternal blood was sent for analysis by FC after KBT. A variety of reagents including anti-haemoglobin F (HbF), anti-D and combined anti-HbF/anti-carbonic anhydrase (CA) were used. RESULTS: Eight cases of massive FMH (>100 mL fetal cells) causing fetal death or severe neonatal anaemia in late gestation were confirmed by FC. Anti-HbF FC identified maternal F cells and fetal cells. In some cases these red cell populations merged but they could be differentiated by anti-CA, labelling F cells only. Using KBT, false positive FMH results were obtained for 12 patients, who had strongly stained cells that were then shown by FC to be maternal F cells. All these patients had increased F cells (>5% of total red cells) whereas only 16% of patients with FMH and 22% of donors had elevated F cells. In contrast, anti-D FC was simple and rapid, quantitating D-positive FMH in all 15 D-negative patients except one with massive FMH of weak D fetal cells. Leucocytes in four samples bound anti-D, variably, giving erroneously high FMH, but they could be eliminated from FC analysis using combined anti-D/anti-CD45. CONCLUSION: FMH quantitation using anti-D by FC is suitable for the majority of maternal samples and could enable accurate targeted dosing of anti-D prophylaxis.

Formation of artefacts while sampling emissions of PCDD/PCDF from open burning of biomass.

Emission factors for PCDD/PCDF determined from open combustion are used to estimate national emission budgets; therefore, it is important to have confidence in their accuracy. It has been suspected that artefacts may form due to the presence of hot metal surfaces of sampling equipment, thus skewing emission factors. In this study, emissions of PCDD/PCDF from open burning of forest biomass over a brick hearth were sampled. Five experiments were carried out using a portable sampler. Experiments were designed where the key variable, sample hood and inlet temperatures were manipulated. Other variables such as fuel origin, type and density were consistent. The measured concentration of PCDD/PCDF in the smoke samples ranged from 0.01 µg TEQ (t fuel)(-1) at the lowest maximum hood temperature (185°C) to 15 µg TEQ (t fuel)(-1) at the highest maximum hood temperature (598°C). when hood inlet temperatures exceeded 400°C emission factors were significantly elevated and this is attributed to the formation of artefacts that can cause the over estimation of emission factors. The increase in hood temperature also resulted in a change in the PCDD/PCDF congener and homologue profile of the emissions. For example at the lowest temperature (Fire 1) the PCDD/PCDF ratio measured was 50:1, whereas at the highest temperature (Fire 5) this ratio was about 0.53:1. When the sampler hood and inlet temperatures were kept in the normal operating range of <200°C, emission factors were comparable to those observed in many previous studies in Australia with emissions dominated by PCDD.

An analysis of the metabolic syndrome phenotype in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is associated with an increased risk of coronary heart disease (CHD) not fully explained by classic risk factors. Metabolic syndrome (MetS) is associated with an increased risk of CHD in the general population and whilst its prevalence is increased in SLE, its phenotypic expression may differ. We studied 200 women with SLE and 100 controls and compared the prevalence of MetS and its individual components. We examined whether any SLE features were associated with MetS and whether MetS in SLE patients was associated with carotid plaque. Patients with SLE were more likely to meet the MetS criteria (age-adjusted OR 2.1 (1.1-3.8)). However, this was not due to increased central obesity (median waist circumference 84 cm vs. 82 cm, p = 0.65) but rather increased prevalence of hypertension (p <0.01) and low HDL-cholesterol (p = 0.01). In a multivariable analysis, age, disease duration, low complement C3 and corticosteroid use ever, were associated with the presence of MetS in SLE. Overall MetS was not associated with the presence of carotid plaque in either SLE or controls. We have shown that MetS is more prevalent in SLE, but the lupus-MetS phenotype reflects risk factor changes driven by disease activity and steroid exposure, rather than obesity. Reliance on clinical measures of central obesity to consider MetS in SLE is not reliable and continued attention to individual CHD risk factors is recommended.

Anti-Mullerian hormone-tailored stimulation protocols improve outcomes whilst reducing adverse effects and costs of IVF.

BACKGROUND: Anti-Müllerian hormone (AMH) is increasingly used to quantify ovarian reserve, but it has not yet realized its full clinical potential in assisted reproduction technology. We investigated the possible benefits of using novel, stratified ovarian hyperstimulation protocols, tailored to individual AMH levels, compared with conventional stimulation. METHODS: Retrospective data were collected from 769 women (first cycle of IVF, using fresh embryos), in a UK tertiary care unit: 346 women using conventional stimulation protocols; 423 women treated under new AMH-tailored protocols. RESULTS: Embryo transfer rates increased significantly (79-87%: P= 0.002) after the introduction of AMH-tailored stimulation protocols. Pregnancy rate per cycle started and live birth rate also increased significantly compared with conventionally treated women (17.9-27.7%, P= 0.002 and 15.9-23.9%, P = 0.007, respectively). Moreover, in the AMH group, the incidence of the ovarian hyperstimulation syndrome (OHSS) fell significantly (6.9-2.3%, P = 0.002) and failed fertilization fell from 7.8 to 4.5%. The cost of fertility drug treatment fell by 29% per patient and the overall cost of clinical management of OHSS fell by 43% in the AMH group. GnRH antagonist protocols, introduced as part of AMH-tailored treatment, may have contributed to the observed improvements: however, within the AMH-tailored group, the live birth rate was not significantly different between agonist and antagonist-treated groups. CONCLUSIONS: Although large, prospective, multicentre studies are indicated, we have clearly demonstrated that individualized, AMH-guided, controlled ovarian hyperstimulation protocols significantly improved positive clinical outcomes, reduced the incidence of complications and reduced the financial burden associated with assisted reproduction.

Emergency head injury imaging: implementing NICE 2007 in a tertiary neurosciences centre and a busy district general hospital.

BACKGROUND: Head injuries are a common emergency department (ED) presentation. The National Institute for Health and Clinical Excellence (NICE) updated its guidance in September 2007 regarding imaging required for patients with head injuries. METHODS: A two-centre observational ED study was carried out, examining imaging practice in adults and children with head injuries attending pre-guideline and post-guideline implementation. Guideline implementation occurred through a formal implementation programme at the teaching hospital, and informally at the district general hospital (DGH). Retrospective extraction took place of prospectively recorded data case records and radiology department imaging registers. Pre-implementation data were collected from Salford Royal Foundation NHS Trust (SRFT) from January and February 2008 and post-implementation data in May 2008. Post-implementation data was collated from Royal Bolton Hospital Foundation NHS Trust (RBFT) from September to November 2007. Compliance with NICE 2007 was the primary outcome assessed. RESULTS: With the implementation of NICE 2007 guidelines at SRFT, a significant increase in compliance from 94.2% (92.9-95.5) to 98.8% (98.2-99.3) was observed for adults requiring head CTs, with an overall trend to improved clinical practice in the adult patient populations. However, a significant number of children (SRFT 68.7% and RBFT 77.1%) did not receive the indicated head CT scan following a head injury, after implementation of the guidelines. CONCLUSIONS: The SRFT implementation strategy employed was successful for adults, with the overall trend to increased clinical compliance post-guideline introduction. Evidence of a reluctance to adhere to the NICE recommendations for children indicated for CT head scan after a head injury was observed.