Use of Cardiac Troponin for the Diagnosis of Cardiac Pathology in Postmortem Samples Taken at Autopsy

The diagnosis of acute cardiac pathology is a clinical challenge in both the living and in the postmortem setting. Cardiac troponin (cTn) T and cardiac troponin I released from the contractile apparatus of cardiomyocytes into the circulation can be detected by sensitive and specific immunoassays and are the gold standard biochemical test for diagnosis of acute coronary syndromes (ACS). Recently with the advent of more sensitive detection methods, elevation in non-ACS has become apparent causing clinical confusion. In most cases, these elevations are related to subclinical cardiac damage and often confer poor prognosis in cTn-positive patients. Biomarkers of cardiomyocyte damage may be of value in routine hospital and medico-legal autopsy. A significant body of evidence has emerged since the late 1990s, assessing the clinical utility of cardiac troponin in biological fluids or in immunohistochemical staining of cardiac tissue to aid in the diagnosis of acute cardiac pathology when standard microscopic evidence is inconclusive. This chapter reviews the extensive literature on the subject and details the disparity between pericardial fluid and serum for the use of cTn in the postmortem setting

Coronavirus Disease: Epidemiology, Aetiology, Pathophysiology and Involvement of the Cardiovascular System

Since the emergence in China of coronavirus disease (COVID-19) in December 2019; the virus causing the pandemic has infected the human population in almost every country and territory on the globe. At the time of writing there are over 84 million confirmed cases of infection and over 1.8 million deaths globally. Rates of infection differ as does the number of severe cases and subsequent deaths between countries and continents. This is due in part to lockdown measures, social distancing and wearing of face coverings. It is also reflected by how healthcare systems record coronavirus deaths along with access to testing as well as tracking and tracing of infected individuals. Symptoms of COVID-19 include a novel persistent cough, fever and anosmia (loss of smell). In most cases, such symptoms are mild. A small proportion of those who become infected however, have a severe reaction to the disease affecting multiple organ systems and often require respiratory support in the intensive care setting. One such physiological system affected is the cardiovascular system. This is likely due to the increased number of ACE2 receptors in co-morbid cardiac pathologies. ACE2 receptors serve as the entry port for the coronavirus into human cells. Those individuals with underlying cardiovascular risk factors are therefore disproportionately at risk of COVID-19 infection. This chapter reviews the aetiology and epidemiology of the coronavirus infection; potential pathophysiological mechanisms of disease involving the cardiovascular system including the clinical utility of biomarkers, electrocardiography and echocardiography as well as autopsy cardiac pathology and histopathology

Identifying Surrogates for Heart and Ipsilateral Lung Dose to Guide Field Placement and Treatment Modality Selection during Virtual Simulation of Breast Radiotherapy

AIMS: Virtual simulation (VSim) of tangential photon fields is a common method of field localisation for breast radiotherapy. Heart and ipsilateral lung dose is unknown until the dosimetric plan is produced. If heart and ipsilateral lung tolerance doses are exceeded, this can prolong the pre-treatment pathway, particularly if a change of technique is required. The aim of this study was to identify predictive surrogates for heart and ipsilateral lung dose during VSim to aid optimum field placement and treatment modality selection. MATERIALS AND METHODS: Computed tomography data from 50 patients referred for left breast/chest wall radiotherapy were retrospectively analysed (model-building cohort). The prescribed dose was 40.05 Gy in 15 fractions using a tangential photon technique. The heart and ipsilateral lung contours were duplicated, cropped to within the field borders and labelled heart-in-field (HIF) and ipsilateral lung-in-field (ILF). The percentage of HIF (%HIF) and ILF (%ILF) was calculated and correlated with mean heart dose (MHD) and volume of the ipsilateral lung receiving 18 Gy (V18Gy). Linear regression models were calculated. A validation cohort of 10 left- and 10 right-sided cases with an anterior supraclavicular fossa (SCF) field, and 10 left- and 10 right-sided cases including the internal mammary nodes using a wide tangential technique and anterior SCF field, tested the predictive model. Threshold values for %HIF and %ILF were calculated for clinically relevant MHD and ipsilateral lung V18Gy tolerance doses. RESULTS: For the model-building cohort, the median %HIF and MHD were 2.6 (0.4-16.7) and 2.3 (1.2-8) Gy. The median %ILF and ipsilateral lung V18Gy were 12.1 (2.8-33.6) and 12.6 (3.3-35) %. There was a statistically significant strong positive correlation of %HIF with MHD (r2 = 0.97, P < 0.0001) and of %ILF with ipsilateral lung V18Gy (r2 = 0.99, P < 0.0001). For the validation cohort, the median %HIF and MHD were 3.9 (0.6-8) and 2.5 (1.4-4.7) Gy. The median %ILF and ipsilateral lung V18Gy were 20.1 (12.4-32.0) and 20.9 (12.4-34.4) %. The validation cohort confirmed that %HIF and %ILF continue to be predictive surrogates for heart and ipsilateral lung dose during VSim of left- and right-sided cases when including the SCF ± internal mammary nodes with a three-field photon technique. DISCUSSION: The ability to VSim breast radiotherapy (±nodal targets) and accurately predict the heart and ipsilateral lung doses on the dosimetric plan will ensure that tolerance doses are not exceeded, and identify early in the pre-treatment pathway those cases where alternative techniques or modalities should be considered

Is it safe to go back into the water? A systematic review and meta-analysis of the risk of acquiring infections from recreational exposure to seawater

Background: Numerous illnesses are associated with bathing in natural waters, although it is assumed that the risk of illness among bathers exposed to relatively clean waters found in high-income countries is negligible. A systematic review was carried out to quantify the increased risk of experiencing a range of adverse health outcomes among bathers exposed to coastal water compared with non-bathers. Methods: In all 6919 potentially relevant titles and abstracts were screened, and from these 40 studies were eligible for inclusion in the review. Odds ratios (OR) were extracted from 19 of these reports and combined in random-effect meta-analyses for the following adverse health outcomes: incident cases of any illness, ear infections, gastrointestinal illness and infections caused by specific microorganisms. Results: There is an increased risk of experiencing symptoms of any illness [OR = 1.86, 95% confidence interval (CI): 1.31 to 2.64, P = 0.001] and ear ailments (OR = 2.05, 95% CI: 1.49 to 2.82, P < 0.001) in bathers compared with non-bathers. There is also an increased risk of experiencing gastrointestinal ailments (OR = 1.29, 95% CI: 1.12 to 1.49, P < 0.001). Conclusions: This is the first systematic review to evaluate evidence on the increased risk of acquiring illnesses from bathing in seawater compared with non-bathers. Our results support the notion that infections are acquired from bathing in coastal waters, and that bathers have a greater risk of experiencing a variety of illnesses compared with non-bathers

Radiomics-Based Texture Analysis of Ga-68-DOTATATE Positron Emission Tomography and Computed Tomography Images as a Prognostic Biomarker in Adults With Neuroendocrine Cancers Treated With Lu-177-DOTATATE

Purpose: Neuroendocrine tumors (NET) are rare cancers with variable behavior. A better understanding of prognosis would aid individualized management. The aim of this hypothesis-generating pilot study was to investigate the prognostic potential of tumor heterogeneity and tracer avidity in NET using texture analysis (TA) of 68Ga-DOTATATE positron emission tomography (PET) and non-enhanced computed tomography (CT) performed at baseline in patients treated with 177Lu-DOTATATE. It aims to justify a larger-scale study to evaluate its clinical value. Methods: The pretherapy 68Ga-DOTATATE PET-CT scans of 44 patients with metastatic NET (carcinoid, pancreatic, thyroid, head and neck, catecholamine-secreting, and unknown primary NET) treated with 177Lu-DOTATATE were analyzed retrospectively using commercially available texture analysis research software. Image filtration extracted and enhanced objects of different sizes (fine, medium, coarse), then quantified heterogeneity by statistical and histogram-based parameters (mean intensity, standard deviation, entropy, mean of positive pixels, skewness, and kurtosis). Regions of interest were manually drawn around up to five of the most 68Ga-DOTATATE avid lesions for each patient. 68Gallium uptake on PET was quantified as SUVmax and SUVmean. Associations between imaging and clinical markers with progression-free (PFS) and overall survival (OS) were assessed using univariate Kaplan-Meier analysis. Independence of the significant univariate markers of survival was tested using multivariate Cox regression analysis. Results: Measures of heterogeneity (higher kurtosis, higher entropy, and lower skewness) on coarse-texture scale CT and unfiltered PET images predicted shorter PFS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness: p=0.03) and shorter OS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness p=0.02). Conventional PET parameters such as SUVmax and SUVmean showed trends towards predicting outcome but were not statistically significant. Multivariate analysis identified that CT-TA (coarse kurtosis: HR=2.57, 95% CI=1.22–5.38, p=0.013) independently predicted PFS, and PET-TA (unfiltered skewness: HR=9.05, 95% CI=1.19–68.91, p=0.033) independently predicted OS. Conclusion: These preliminary data generate a hypothesis that radiomic analysis of neuroendocrine cancer on 68Ga-DOTATATE PET-CT may be of prognostic value and a valuable addition to the assessment of patients

Trace levels of sewage effluent are sufficient to increase class 1 integron prevalence in freshwater biofilms without changing the core community

Most river systems are impacted by sewage effluent. It remains unclear if there is a lower threshold to the concentration of sewage effluent that can significantly change the structure of the microbial community and its mobile genetic elements in a natural river biofilm. We used novel in situ mesocosms to conduct replicated experiments to study how the addition of low-level concentrations of sewage effluent (nominally 2.5 ppm) affects river biofilms in two contrasting Chalk river systems, the Rivers Kennet and Lambourn (high/low sewage impact, respectively). 16S sequencing and qPCR showed that community composition was not significantly changed by the sewage effluent addition, but class 1 integron prevalence (Lambourn control 0.07% (SE ± 0.01), Lambourn sewage effluent 0.11% (SE ± 0.006), Kennet control 0.56% (SE ± 0.01), Kennet sewage effluent 1.28% (SE ± 0.16)) was significantly greater in the communities exposed to sewage effluent than in the control flumes (ANOVA, F = 5.11, p = 0.045) in both rivers. Furthermore, the difference in integron prevalence between the Kennet control (no sewage effluent addition) and Kennet sewage-treated samples was proportionally greater than the difference in prevalence between the Lambourn control and sewage-treated samples (ANOVA (interaction between treatment and river), F = 6.42, p = 0.028). Mechanisms that lead to such differences could include macronutrient/biofilm or phage/bacteria interactions. Our findings highlight the role that low-level exposure to complex polluting mixtures such as sewage effluent can play in the spread of antibiotic resistance genes. The results also highlight that certain conditions, such as macronutrient load, might accelerate spread of antibiotic resistance genes

Assessment of the impact of CT calibration procedures for proton therapy planning on paediatric treatments

PURPOSE: Relative stopping powers (RSP) for proton therapy are estimated using single-energy CT (SECT), calibrated with standardised tissues of the adult male. It is assumed that those tissues are representative of tissues of all age and sex. Female, male and paediatric tissues differ from one another in density and composition. In this study, we use tabulated paediatric tissues and computational phantoms to investigate the impact of this assumption on paediatric proton therapy. The potential of dual-energy CT (DECT) to improve the accuracy of these calculations is explored. METHODS: We study 51 human body tissues, categorised into male/female for the age groups newborn, 1-, 5-, 10-, 15-year old and adult, with given compositions and densities. CT numbers are simulated and RSPs are estimated using SECT and DECT methods. Estimated tissue RSPs from each method are compared to theoretical RSP. The dose and range errors of each approach is evaluated on 3 computational phantoms (Ewing's sarcoma, salivary sarcoma, glioma) derived from paediatric proton therapy patients. RESULTS: With SECT, soft tissues have mean estimation errors and standard deviation up to (1.96 ± 4.18)% observed in newborns, compared to (0.20 ± 1.15)% in adult males. Mean estimation errors for bones are up to (-3.35 ± 4.76)% in paediatrics as opposed to (0.10 ± 0.66)% in adult males. With DECT, mean errors reduce to (0.17 ± 0.13)% and (0.23 ± 0.22)% in newborns (soft tissues/bones). With SECT, dose errors in a Ewing's sarcoma phantom are exceeding 5 Gy (10% of prescribed dose) at the distal end of the treatment field, with volumes of dose errors >5 Gy of Vdiff> 5 = 4630.7mm3 . Similar observations are made in the head and neck phantoms, with overdoses to healthy tissue exceeding 2 Gy (4%). A systematic Bragg peak shift resulting in either over- or underdosage of healthy tissues and target volumes depending on the crossed tissues RSP prediction errors is observed. Water equivalent range errors of single beams are between -1.53mm and 5.50mm (min, max) (Ewing's sarcoma phantom), -0.78mm and 3.62mm (salivary sarcoma phantom), and -0.43mm and 1.41mm (glioma phantom). DECT can reduce dose errors to <1 Gy and range errors to <1 mm. CONCLUSION: SECT estimates RSPs for paediatric tissues with systematic shifts. DECT improves the accuracy of RSPs and dose distributions in paediatric tissues compared to the SECT calibration curve based on adult males tissues

Atlas construction and spatial normalisation to facilitate radiation-induced late effects research in childhood cancer

Reducing radiation-induced side effects is one of the most important challenges in paediatric cancer treatment. Recently, there has been growing interest in using spatial normalisation to enable voxel-based analysis of radiation-induced toxicities in a variety of patient groups. The need to consider three-dimensional distribution of doses, rather than dose-volume histograms, is desirable but not yet explored in paediatric populations. In this paper, we investigate the feasibility of atlas construction and spatial normalisation in paediatric radiotherapy. We used planning computed tomography (CT) scans from twenty paediatric patients historically treated with craniospinal irradiation to generate a template CT that is suitable for spatial normalisation. This childhood cancer population representative template was constructed using groupwise image registration. An independent set of 53 subjects from a variety of childhood malignancies was then used to assess the quality of the propagation of new subjects to this common reference space using deformable image registration (i.e., spatial normalisation). The method was evaluated in terms of overall image similarity metrics, contour similarity and preservation of dose-volume properties. After spatial normalisation, we report a dice similarity coefficient of 0.95±0.05, 0.85±0.04, 0.96±0.01, 0.91±0.03, 0.83±0.06 and 0.65±0.16 for brain and spinal canal, ocular globes, lungs, liver, kidneys and bladder. We then demonstrated the potential advantages of an atlas-based approach to study the risk of second malignant neoplasms after radiotherapy. Our findings indicate satisfactory mapping between a heterogeneous group of patients and the template CT. The poorest performance was for organs in the abdominal and pelvic region, likely due to respiratory and physiological motion and to the highly deformable nature of abdominal organs. More specialised algorithms should be explored in the future to improve mapping in these regions. This study is the first step toward voxel-based analysis in radiation-induced toxicities following paediatric radiotherapy

Survey to explore understanding of the principles of aseptic technique: Qualitative content analysis with descriptive analysis of confidence and training

BACKGROUND: In many countries, aseptic procedures are undertaken by nurses in the general ward setting, but variation in practice has been reported, and evidence indicates that the principles underpinning aseptic technique are not well understood. METHODS: A survey was conducted, employing a brief, purpose-designed, self-reported questionnaire. RESULTS: The response rate was 72%. Of those responding, 65% of nurses described aseptic technique in terms of the procedure used to undertake it, and 46% understood the principles of asepsis. The related concepts of cleanliness and sterilization were frequently confused with one another. Additionally, 72% reported that they not had received training for at least 5 years; 92% were confident of their ability to apply aseptic technique; and 90% reported that they had not been reassessed since their initial training. Qualitative analysis confirmed a lack of clarity about the meaning of aseptic technique. CONCLUSION: Nurses' understanding of aseptic technique and the concepts of sterility and cleanliness is inadequate, a finding in line with results of previous studies. This knowledge gap potentially places patients at risk. Nurses' understanding of the principles of asepsis could be improved. Further studies should establish the generalizability of the study findings. Possible improvements include renewed emphasis during initial nurse education, greater opportunity for updating knowledge and skills post-qualification, and audit of practice