Alavi-Carlsen Calcification Score (ACCS): A Simple Measure of Global Cardiac Atherosclerosis Burden.

Multislice cardiac CT characterizes late stage macrocalcification in epicardial arteries as opposed to PET/CT, which mirrors early phase arterial wall changes in epicardial and transmural coronary arteries. With regard to tracer, there has been a shift from using mainly 18F-fluorodeoxyglucose (FDG), indicating inflammation, to applying predominantly 18F-sodium fluoride (NaF) due to its high affinity for arterial wall microcalcification and more consistent association with cardiovascular risk factors. To make NaF-PET/CT an indispensable adjunct to clinical assessment of cardiac atherosclerosis, the Alavi-Carlsen Calcification Score (ACCS) has been proposed. It constitutes a global assessment of cardiac atherosclerosis burden in the individual patient, supported by an artificial intelligence (AI)-based approach for fast observer-independent segmentation. Common measures for characterizing epicardial coronary atherosclerosis by NaF-PET/CT as the maximum standardized uptake value (SUV) or target-to-background ratio are more versatile, error prone, and less reproducible than the ACCS, which equals the average cardiac SUV. The AI-based approach ensures a quick and easy delineation of the entire heart in 3D to obtain the ACCS expressing ongoing global cardiac atherosclerosis, even before it gives rise to CT-detectable coronary calcification. The quantification of global cardiac atherosclerotic burden by the ACCS is suited for management triage and monitoring of disease progression with and without intervention.

Assessment of atherosclerosis in multiple myeloma and smoldering myeloma patients using 18F- sodium fluoride PET/CT.

BACKGROUND: To compare the NaF uptake in the thoracic aorta and whole heart, as an early indicator of atherosclerosis, in multiple myeloma (MM) and smoldering multiple myeloma (SMM) patients with a healthy control (HC) group. METHODS: Forty-four untreated myeloma patients (35 MM and nine SMM) and twenty-six age and gender-matched HC subjects were collected. Each individual's NaF uptake in three parts of the aorta (AA: ascending aorta, AR: aortic arch, DA: descending aorta) and the whole heart was segmented. Average global standardized uptake value means were derived by sum of the product of each slice area divided by the sum of those slice areas. Results were reported as target to background ratio (TBR). RESULTS: There was a significant difference between the NaF uptake in the thoracic aorta of myeloma and HC groups [AA (myeloma = 1.82 ± 0.21, HC = 1.24 ± 0.02), AR (myeloma = 1.71 ± 0.19, HC = 1.28 ± 0.03) and DA (myeloma = 1.96 ± 0.28, HC = 1.38 ± 0.03); P-values < 0.001]. The difference in the whole heart NaF uptake between two groups was also significant (P < 0.001). CONCLUSIONS: We observed a higher uptake of NaF in the thoracic aorta and whole heart of myeloma patients in comparison to the matched control group.

Amyloid Hypothesis: The Emperor's New Clothes?

The lengthy debate on the validity of the amyloid hypothesis and the usefulness of amyloid imaging and anti-amyloid therapeutic interventions in dementia continues unabated, even though none of them have been able to convince the medical world of their correctness and clinical value. There are huge financial interests associated with promoting both, but in spite of the large sums of money in their support, no effective anti-amyloid treatments or diagnostic use of amyloid imaging have emerged. There are solid scientific reasons that explain these negative results, and it is time to move forward to other promising options for the benefit of the patients.

A Phase IV, Randomized, Double-Blind, Placebo-Controlled Crossover Study of the Effects of Ustekinumab on Vascular Inflammation in Psoriasis (the VIP-U Trial).

Psoriasis is a T helper type 17 autoimmune disease associated with an increased risk cardiovascular events and mortality. Ustekinumab, an antibody to p40, blocks cytokines IL-12 and IL-23, and is a highly effective and safe treatment for psoriasis. We conducted a randomized double-blinded placebo-controlled trial to determine the effect of ustekinumab on aortic vascular inflammation (AVI) measured by imaging, and key biomarkers of inflammation, lipid, and glucose metabolism in the blood of patients with moderate-to-severe psoriasis. A total of 43 patients were randomized, and at week 12, ustekinumab-treated patients had a -18.65% (95% confidence interval = -29.45% to -7.85%) reduction in AVI, a reduction in inflammatory biomarkers, and an increase in apolipoprotein B lipoproteins compared with placebo. At week 12, placebo patients were crossed over such that all patients received ustekinumab for 52 weeks. At the end of 52 weeks of ustekinumab treatment, there was no change in AVI compared with baseline, inflammatory markers were reduced, and there were increases in selected measures of lipids and leptin. These results show that blockade of IL-12 and/or IL-23 may transiently reduce AVI, with more durable reduction in inflammatory cytokines associated with cardiovascular disease.

Quantifying [¹8F]fluorodeoxyglucose uptake in the arterial wall: the effects of dual time-point imaging and partial volume effect correction.

PURPOSE: The human arterial wall is smaller than the spatial resolution of current positron emission tomographs. Therefore, partial volume effects should be considered when quantifying arterial wall (18)F-FDG uptake. We evaluated the impact of a novel method for partial volume effect (PVE) correction with contrast-enhanced CT (CECT) assistance on quantification of arterial wall (18)F-FDG uptake at different imaging time-points. METHODS: Ten subjects were assessed by CECT imaging and dual time-point PET/CT imaging at approximately 60 and 180 min after (18)F-FDG administration. For both time-points, uptake of (18)F-FDG was determined in the aortic wall by calculating the blood pool-corrected maximum standardized uptake value (cSUVMAX) and cSUVMEAN. The PVE-corrected SUVMEAN (pvcSUVMEAN) was also calculated using (18)F-FDG PET/CT and CECT images. Finally, corresponding target-to-background ratios (TBR) were calculated. RESULTS: At 60 min, pvcSUVMEAN was on average 3.1 times greater than cSUVMAX (P < .0001) and 8.5 times greater than cSUVMEAN (P < .0001). At 180 min, pvcSUVMEAN was on average 2.6 times greater than cSUVMAX (P < .0001) and 6.6 times greater than cSUVMEAN (P < .0001). CONCLUSION: This study demonstrated that CECT-assisted PVE correction significantly influences quantification of arterial wall (18)F-FDG uptake. Therefore, partial volume effects should be considered when quantifying arterial wall (18)F-FDG uptake with PET.

The Appearance Anxiety Inventory: validation of a process measure in the treatment of body dysmorphic disorder.

BACKGROUND: At present there are no measures to identify the cognitive processes and behaviours that might mediate the outcome of treatment in people with Body Dysmorphic Disorder (BDD). AIMS: To develop and validate a process measure that can be used to assess the progress of patients throughout therapy and in research for BDD. METHOD: The psychometric properties of the Appearance Anxiety Inventory (AAI) were explored in a clinical group of participants diagnosed with BDD (Study 1) and in a non-clinical community group with high appearance concerns (Study 2). Item characteristics, reliability, and factor structure were analysed. Convergent validity with measures of related symptoms was assessed. RESULTS: The AAI was found to have good test-retest reliability and convergent validity in the measurement of appearance anxiety. It was also sensitive to change during treatment. The scale was found to have a two-factor structure in the clinical group, with one factor characterized by avoidance, and a second factor comprised of threat monitoring. However, in the community sample it appeared to have a one-factor structure. CONCLUSION: The results suggest that the AAI has the psychometric properties to determine whether changes in cognitive processes and behaviours can mediate the outcome following treatment in patients with BDD. This supports its potential usefulness in clinical and research settings.

Evaluation of diagnostic performance of 18F-FDG-PET compared to CT in detecting potential causes of fever of unknown origin in an academic centre.

Determining the cause of fever of unknown origin (FUO) often proves challenging to attending physicians and the role of conventional imaging in this setting has been uncertain. In this retrospective study, we examined the role of fluorine-18 fluorodesoxyglucose-positron emission tomography ((18)F-FDG-PET) compared to computed tomography (CT) in diagnosing the potential etiology of FUO. To accomplish this task, we identified patients with FUO who underwent (18)F-FDG-PET for detecting the source of fever. Twenty-four patients (16 males and 8 females, age range = 17-80, mean age = 49.5) were examined with (18)F-FDG-PET of which 18 were also assessed with a diagnostic CT (within 3 weeks, mean interval = 7.5 days). The PET and CT findings were reviewed and the presence of focal (18)F-FDG uptake or gross CT lesions was considered a potential site causing FUO. Of patients who underwent PET alone, ⅚ were reported as positive. Of the 18 who had both PET and diagnostic CT, PET was positive in 18 and CT was positive in only 7 cases. Of positive findings on PET, etiologies included infection (11), non-infectious inflammation (8), lymphoma (3), and other cancers (1). Of positive findings on CT, etiologies included infection (3), lymphoma (1), non-infectious inflammation (2) and other cancers (1). Importantly, we found no cases with positive CT and negative PET findings. In conclusion, accordingly to our findings, (18)F-FDG-PET appears to be of great value in assessing patients with FUO, especially when caused by infection or inflammation. Fluorine-18 FDG-PET is more sensitive than diagnostic CT in detecting and localizing diseased sites, and is the optimal imaging modality to evaluate patients with FUO.

Evolving role of FDG PET imaging in assessing joint disorders: a systematic review.

Assessing joint disorders has been a relatively recent and evolving application of 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) imaging. FDG is taken up by inflammatory cells, particularly when they are active as part of an ongoing inflammatory process. Hence FDG PET has been employed to assess a wide array of arthritic disorders. FDG PET imaging has been investigated in various joint diseases for diagnostic purposes, treatment monitoring, and as a prognostic indicator as in other disorders. In some of the diseases the ancillary findings in FDG PET have provided important clues about the underlying pathophysiology and pathogenesis processes. While substantial promise has been demonstrated in a number of studies, it is clear that the potential utility of PET in this clinical realm far outweighs that which has been established to date.

Detection and global quantification of cardiovascular molecular calcification by fluoro18-fluoride positron emission tomography/computed tomography--a novel concept.

The aim of this study was to examine the degree and prevalence of regional (aorta) and global (cardiac) fluorine-18-sodium fluoride ((18)F-NaF) uptake by positron emission tomography (PET)-computed tomography (CT) as evidence for calcification in the atherosclerotic plaques in the aorta and the heart as a function of age. Image data from 51 patients, who had undergone whole-body (18)F-NaF-PET/CT, were evaluated retrospectively. Cardiac and arterial (aorta) radiotracer uptakes were analyzed quantitatively by measuring standard uptake values (SUV). This approach involved examining the entire heart and various aortic segments as identified by CT. By combining CT and PET data, regional and global concentrations of this molecule were calculated and correlated with age over the decades. (18)F-NaF uptake in the heart and aorta increased significantly with advancing age (P<0.01). The Pearson correlation coefficient for the mean (18)F-NaF uptake of cardiac region and 5 age groups was 0.92 (P=0.003) and for aorta and 5 age groups was 0.97 (P=0.004). In conclusion, these preliminary data indicate the feasibility of (18)F-NaF-PET/CT for measurement of regional and global calcification of the heart and major arteries. The (18)F-NaF-PET/CT may provide highly relevant information about the state of calcified plaque before structural calcification is detectable by standard CT techniques. This, therefore, may allow for earlier intervention for risk reduction in cardiovascular diseases. Further studies are needed to validate the role of this promising technique in the management of patients with suspected atherosclerosis.

Clinical utility of FDG-PET and PET/CT in non-malignant thoracic disorders.

There have been several endeavors made to investigate the potential role of 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography (FDG-PET) (and tracers) and PET-computed tomography imaging in various benign disorders, particularly those related to thoracic structures. These various conditions can be broadly categorized into three groups: (a) infectious diseases (mycobacterial, fungal, bacterial infection), (b) active granulomatous disease such as sarcoidosis, and (c) other non-infectious/inflammatory conditions or proliferative disorders (e.g., radiation pneumonitis, post-lung transplant lymphoproliferative disorders, occupational pleuropulmonary complications, and post-surgical conditions), all of which can demonstrate varying degrees of FDG uptake on PET scans based upon the degree of inflammatory activity. This article reviews the current state of this very important application of FDG-PET imaging.

An evidence-based pilot study exploring relationships between psychologic and physiologic factors in post-lung-transplant adolescents with cystic fibrosis.

After using an evidence-based approach to address clinical practice questions, a pilot study was designed to explore the relationships among anxiety and depression self-report data, cyclosporine (CSA) trough values, and biopsy rejection grades within a posttransplant sample of adolescents with cystic fibrosis. Thirteen study participants completed the Revised Children's Manifest Anxiety Scale (RCMAS) and the Children's Depression Inventory (CDI), and had CSA trough levels and biopsy data collected. There was a statistically significant correlation between depression and inflammatory rejection levels. Adolescents with benign rejection scores had lower depression scores than adolescents with higher levels of rejection scores. The data also showed a statistically significant inverse correlation between CSA trough levels and inflammatory rejection levels. Posttransplant success depends on compliance with a strict, antirejection regimen. Adolescence is a turbulent time when many stressors can result in risk-taking behavior such as medication noncompliance and anxiety and depression. Regular psychologic monitoring of posttransplant adolescent patients may be warranted to identify increasing psychologic distress and proactive opportunities for health care intervention. This pilot study is an example of a clinical research question that evolved from a practice situation in which nurses caring for posttransplant adolescents with cystic fibrosis surmised that there were many psychologic issues influencing successful transplant outcomes. Nursing observations suggested a strong connection between poorer medication control, greater risk for rejection, and signs of depression and/or anxiety. The nurse researchers were interested in identifying significant relationships between psychologic factors and physiologic factors, and in discovering objective ways to better assess the psychologic needs of this patient population. A thorough search was conducted of the research literature, and the best clinical practices of other institutions were investigated. There was a lack of transplant research literature on adolescents, and although excellent ideas were generated from inquiries to other institutions, there was a lack of best evidence to answer the clinical questions about this group of patients. The initial clinical question became a research question to determine more about this specific patient population. This article is an example of a clinical research pilot study that resulted from an evidence-based practice process. Pilot studies are springboards for other, more refined research: They help to point the way, or to clarify what the real issues may be. For nurses, they serve as an opportunity to hone critical thinking skills and to contribute to the scientific foundation of our profession.