Diagnostic accuracy of computed tomography coronary angiography in patients with high heart rates: a systematic review

Introduction: An understanding of the diagnostic accuracy of computed tomography coronary angiography (CTCA) is critical for clinicians and guideline developers to determine the appropriate use and position of the scan in the diagnostic pathway. Current imaging guidelines, which are based on evidence from non-contemporary CT technology, only recommend the routine use of CTCA in patients with low heart rates (HR). The aim of this systematic review was to investigate the diagnostic accuracy of CT coronary angiography using state-of-the-art scanner technology, in comparison with invasive coronary angiography, for patients with high HRs. Methods: Methods for the systematic review were determined a priori, based on a previously published protocol. A systematic search of PubMed, CINAHL, Embase and Scopus was performed as well as a search of unpublished sources and reference lists. Titles and abstracts were screened by two independent reviewers. Full-text screening was then performed on all studies that met the criteria for inclusion in the systematic review at the title and abstract level. Studies were included that described diagnostic accuracy metrics in patients with high HR. Studies that did not compare CTCA to invasive coronary angiography were excluded. Only current generation scanners with greater than 128 detectors were included. Included studies underwent critical appraisal using the QUADAS-2 tool. All critically appraised studies were then included in the final review regardless of methodological quality. Data extraction was then undertaken and the results were collated and analysed through narrative synthesis and a diagnostic test accuracy meta-analysis. Results: Twelve studies were included in the systematic review; 11 of these studies were also included in a diagnostic test accuracy meta-analysis. Meta-analysis indicated high level pooled sensitivity 99% (95% CI: 97%,100%) in CTCA at high HR. Pooled specificity was lower at 79% (95% CI: 72%, 85%). Diagnostic accuracy performed better at artery level (pooled sensitivity 96% (95% CI: 93%, 97%) and pooled specificity 93% (95% CI: 90%, 96%)); and segment level (pooled sensitivity 91% (95% CI: 88%, 93%) and pooled specificity 96% (95% CI 95%, 98%)). The prevalence of clinically significant coronary artery disease was high in each of the included studies. There were insufficient data to effectively evaluate the accuracy of CTCA at individual HRs. No significant difference was evident between different CT makes and models included in the review in terms of diagnostic accuracy. Conclusion: Diagnostic sensitivity of CTCA is high at elevated HRs. Consequently, CTCA can still be performed when standard HR control is contraindicated or ineffective as it is an effective test to rule out coronary artery disease. However, the modest results for sensitivity indicate a positive result should be assessed with caution. Implications for Practice: CT scanning is still appropriate in patients with high HRs when contraindications to HR lowering medications exist or are ineffective and when the CTCA is performed in order to rule out rather than quantify coronary artery stenosis. Implications for Future Research Further research is required to better understand the effect high HRs have on important patient outcomes, such as over-testing and anxiety related to false negative results.Thesis (MClinSc) -- University of Adelaide, The Joanna Briggs Institute, 201

Tumor-Associated Macrophages (TAMs) Form an Interconnected Cellular Supportive Network in Anaplastic Thyroid Carcinoma

BACKGROUND: A relationship between the increased density of tumor-associated macrophages (TAMs) and decreased survival was recently reported in thyroid cancer patients. Among these tumors, anaplastic thyroid cancer (ATC) is one of the most aggressive solid tumors in humans. TAMs (type M2) have been recognized as promoting tumor growth. The purpose of our study was to analyze with immunohistochemistry the presence of TAMs in a series of 27 ATC. METHODOLOGY/PRINCIPAL FINDINGS: Several macrophages markers such as NADPH oxidase complex NOX2-p22phox, CD163 and CD 68 were used. Immunostainings showed that TAMs represent more than 50% of nucleated cells in all ATCs. Moreover, these markers allowed the identification of elongated thin ramified cytoplasmic extensions, bestowing a "microglia-like" appearance on these cells which we termed "Ramified TAMs" (RTAMs). In contrast, cancer cells were totally negative. Cellular stroma was highly simplified since apart from cancer cells and blood vessels, RTAMs were the only other cellular component. RTAMs were evenly distributed and intermingled with cancer cells, and were in direct contact with other RTAMs via their ramifications. Moreover, RTAMs displayed strong immunostaining for connexin Cx43. Long chains of interconnected RTAMs arose from perivascular clusters and were dispersed within the tumor parenchyma. When expressed, the glucose transporter Glut1 was found in RTAMs and blood vessels, but rarely in cancer cells. CONCLUSION: ATCs display a very dense network of interconnected RTAMs in direct contact with intermingled cancer cells. To our knowledge this is the first time that such a network is described in a malignant tumor. This network was found in all our studied cases and appeared specific to ATC, since it was not found in differentiated thyroid cancers specimens. Taken together, these results suggest that RTAMs network is directly related to the aggressiveness of the disease via metabolic and trophic functions which remain to be determined

Mathematical models for immunology:current state of the art and future research directions

The advances in genetics and biochemistry that have taken place over the last 10 years led to significant advances in experimental and clinical immunology. In turn, this has led to the development of new mathematical models to investigate qualitatively and quantitatively various open questions in immunology. In this study we present a review of some research areas in mathematical immunology that evolved over the last 10 years. To this end, we take a step-by-step approach in discussing a range of models derived to study the dynamics of both the innate and immune responses at the molecular, cellular and tissue scales. To emphasise the use of mathematics in modelling in this area, we also review some of the mathematical tools used to investigate these models. Finally, we discuss some future trends in both experimental immunology and mathematical immunology for the upcoming years

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Imaging of the Thorax

Since the advent of helical scanning in the late 1980s, computed tomography (CT) scanning of the chest has become a core part of CT practice. This has been largely due to the relative non-invasive nature of the procedure, coupled with the capability of CT of the chest to assess multiple differentials concurrently and at high sensitivity. CT of the thorax (CT of the chest) can be performed as a routine investigation such as when investigating trauma or staging of oncological condition. However, dedicated examinations investigating suspected or known pathology are also common. Often the investigation follows detection of an anomaly on a chest X-ray. CT provides visualisation of the airways and lungs; mediastinum and vascular structures; soft tissues of the thoracic region; and the bony thorax

Imaging of the Neck

This chapter provides an overview of protocols and approaches for CT acquisition for the neck. For this respective anatomical system, common clinical indications and the implications for the imaging protocol are discussed. The intention of this section is to provide an overview of the contemporary approaches for CT Imaging procedures to provide quality image acquisition with a patient centred perspective

Imaging of Paediatric Patients

This chapter provides an overview of protocols and approaches for computed tomography (CT) acquisition during paediatric imaging. For this respective anatomical system, common clinical indications and the implications for the imaging protocol are discussed. The intention of this section is to provide an overview of the contemporary approaches for CT Imaging procedures to provide quality image acquisition with a patient centred perspective