Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation (4Is)-related cardiovascular diseases: a joint collaboration of the EACVI and the EANM

With this document, we provide a standard for PET/(diagnostic) CT imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is). This standard should be applied in clinical practice and integrated in clinical (multicenter) trials for optimal procedural standardization. A major focus is put on procedures using [18F]FDG, but 4Is PET radiopharmaceuticals beyond [18F]FDG are also described in this document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicenter trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Finally, PET/MR applications in 4Is cardiovascular diseases are also briefly described. Diagnosis and management of 4Is-related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/MR, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications

Performance of advanced imaging modalities at diagnosis and treatment response evaluation of patients with post-transplant lymphoproliferative disorder:A systematic review and meta-analysis

Introduction and aim: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ and hematopoietic stem cell transplantation, associated with significant morbidity and mortality. In this systematic review we evaluated the clinical performance of advanced imaging modalities at diagnosis and treatment response evaluation of PTLD patients after solid organ and hematopoietic stem cell transplantation. Methods: We have carried out a literature search until December 15, 2017 using PubMed/Medline, Embase, "Web of Science" and Cochrane Library databases concerning the performance of computed tomography (CT), magnetic resonance imaging (MRI) and F-18-flurodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) at diagnosis or treatment response evaluation of PTLD patients. Results: A total of 11 studies were included comprising 368 patients, from which FDG-PET(/CT) was the primary imaging modality investigated. The methodological quality according to QUADAS-2 of the reviewed studies was moderate-poor. Subgroup analysis of imaging results for detection and staging in patients with PTLD indicated that FDG-PET/(CT) identified additional lesions not detected by CT and/or MRI in 27.8%, (95% confidence interval [95%CI]) 17.0%-42.0% (I-2 = 51.1%), from which extra-nodal sites in 23.6% (95%CI: 7.9%-52.4%) (I-2 = 76.6%). False negative results occurred in 11.5% (95%CI: 4.9%-24.5%) (I-2 = 73.4%), predominantly in physiological high background activity regions and in early PTLD lesions. False positive results occurred in 4.8% (95%CI: 2.6%-8.6%) (I-2 = 0%) predominantly due to inflammatory conditions. Subgroup analysis of imaging results at treatment response evaluation indicated that FDG-PET(/CT) findings altered or guided treatment in 29.0% (95%CI: 14.0%-50.5%) (I-2 = 40.1%). False positive results during treatment response evaluation were reported in 20.0% (95%CI: 10.7%-34.2%) (I-2 = 0%), predominantly due to inflammatory conditions. Conclusion: FDG-PET(/CT) is currently the most frequently investigated imaging modality in PTLD patients. Available studies report promising results in detection, staging and therapy evaluation but suffer from methodological shortcomings. Concerns remain with regard to occurrence of false negatives due to physiological high background activity and early PTLD lesions as well as false positives due to inflammatory conditions

Non-Invasive Imaging of Cysteine Cathepsin Activity in Solid Tumors Using a 64Cu-Labeled Activity-Based Probe

The papain family of cysteine cathepsins are actively involved in multiple stages of tumorigenesis. Because elevated cathepsin activity can be found in many types of human cancers, they are promising biomarkers that can be used to target radiological contrast agents for tumor detection. However, currently there are no radiological imaging agents available for these important molecular targets. We report here the development of positron emission tomography (PET) radionuclide-labeled probes that target the cysteine cathepsins by formation of an enzyme activity-dependent bond with the active site cysteine. These probes contain an acyloxymethyl ketone (AOMK) functional group that irreversibly labels the active site cysteine of papain family proteases attached to a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) tag for labeling with 64Cu for PET imaging studies. We performed biodistribution and microPET imaging studies in nude mice bearing subcutaneous tumors expressing various levels of cysteine cathepsin activity and found that the extent of probe uptake by tumors correlated with overall protease activity as measured by biochemical methods. Furthermore, probe signals could be reduced by pre-treatment with a general cathepsin inhibitor. We also found that inclusion of a Cy5 tag on the probe increased tumor uptake relative to probes lacking this fluorogenic dye. Overall, these results demonstrate that small molecule activity-based probes carrying radio-tracers can be used to image protease activity in living subjects

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

Small molecules in silks

Whereas most silk research is focused on silk proteins, the focus of this thesis is on small molecules present in silk and why they are so important for anyone working in this field with silk. Silks are known to perform a range of different functions in nature, whereas for people, silk can be used in a wide variety of applications. A major disadvantage of using silk in these applications however, is its large variation in properties. In this thesis, the importance of small molecules will be discussed in light of this variation. I present for the first time that calcium oxalate monohydrate is present in the cocoons of Wild Silkmoths resulting in the inability of reeling these cocoons. Furthermore, a method was developed for removing this mineral coating resulting in that these cocoons could be reeled for the very first time, what has vast commercial implications. Additionally, I found that the cocoon spinning between B. mori and G. postica was significantly different resulting in a mineral-free cocoon for B. mori. Further, an unknown polyphenol in dragline and egg sac silk was identified responsible for the yellow coloration of these silks. An enzymatic method for the synthesis of this molecule was found in vitro and was believed to happen similarly in vivo. Whereas the function of this molecule is still unknown, the extended hydrogen bonding capabilities suggest it will bind to the silk peptide. Finally we highlight the importance of small molecules in silk and point at the significance of the food of silkmoths and spiders as the origin of these small molecules, which has never been controlled for in any research or application. </p

Een 53-jarige vrouw met ernstige nierinsufficiëntie

A 53-year-old patient with acute kidney injury A 53-year-old patient was admitted with acute kidney injury and hypercalcemia. Further investigation with PET-CT revealed a strong FDG-uptake in the spleen and minor uptake in some mediastinal lymph nodes. EBUS-FNA of a mediastinal lymph node was unrevealing. Other examinations could not differentiate reliably between lymphoma and sarcoidosis. A diagnostic splenectomy was necessary to make a definitive diagnosis.status: publishe

Silk inverse opals from template-directed ϐ-sheet transformation of regenerated silk fibroin

We describe a novel and facile method for the fabrication of reconstituted silk monoliths with ordered interconnected air spheres based on intercalation and in situ β-sheet transformation of regenerated silk fibroin solutions within the interstitial spaces of a sacrificial colloidal crystal template. The silk inverse opals are elastic and can withstand and recover from compressive loads of up to 112 MPa by reversible pore deformation. They also exhibit super-hydrophobicity with water droplet contact angles of up to 140° due to periodic nanoscale protrusions associated with the surface texture of the inverse opal architecture. These properties indicate that silk inverse opals could have potential applications as biocompatible elastic scaffolds, storage–release, barrier and self-cleaning materials, and in the design of load-responsive microfluidic devices

Weaving our way towards a new generation of fibre-optic chemical sensors based on spider silk

From the spider's perspective, silk is not only a building material but also a safety net, a weapon and a sensory organ to detect the presence of preys on its web. Indeed, this primeval material has been shaped over hundreds of millions of years by spiders to create a myriad of silk fibre types with different level of toughness, elasticity, stickiness depending on its attributed function in the web. From a human perspective, scientists are currently working on harnessing all the extraordinary properties of this material for applications spiders would never thought of, from biocompatible tissue engineering (enhancement of skin regeneration and nerve guides) to biodegradable electronics and development of specialised textile and composites. However, the potential of using spider silk fibre for chemical sensing has been overlooked. In this communication, we will explore the potential of using spider silk as a new type of fibre optic chemical sensor in a fully bio-inspired approach

Multimodality imaging for diagnosis, risk stratification, and treatment monitoring of cardiac sarcoidosis

Cardiac sarcoidosis (CS), with either extracardiac involvement or in isolation, is increasingly recognized. Complications from cardiac involvement are the leading cause of death in patients with sarcoidosis, rendering early detection extremely important given the significant therapeutic and prognostic implications. However, the diagnosis of CS remains challenging due to the lack of a reliable gold standard, largely due to the low sensitivity of traditional endomyocardial biopsy and patchy myocardial involvement. Recent advances in cardiac imaging with [18F] fluorodeoxyglucose positron emission tomography–computed tomography ([18F]FDG PET/CT) and cardiac magnetic resonance (CMR) have provided unprecedented information on the prevalence of CS and have revolutionized the diagnosis and management of CS patients. Abnormal PET/CMR findings are now major criteria in societal guidelines to establish a probabilistic diagnosis of CS. This review provides a brief introduction to CS and a summary of current diagnostic criteria, followed by a review on the current use and strengths of PET/CT and CMR for diagnosis, risk stratification, and treatment response evaluation. CMR is the most robust technique to assess left ventricular function, to detect myocardial fibrosis, and differentiate CS from other cardiomyopathies and has an excellent negative predictive value. On the other hand, [18F]FDG PET/CT is the modality of choice to assess active myocardial inflammation which may be amenable to immunosuppressive treatment as well as to detect extracardiac involvement, to identify potential biopsy sites, and to monitor treatment efficacy. Understanding the complementary value of both techniques is crucial to the optimal utilization of advanced imaging in patients with CS. Lastly, some gaps are identified for future research. © 2023, The Author(s), under exclusive licence to Italian Association of Nuclear Medicine and Molecular Imaging