Multicentre double-blind randomised placebo-controlled trial evaluating the efficacy of the meningococcal B vaccine, 4CMenB (Bexsero), against Neisseria gonorrhoeae infection in men who have sex with men: the GoGoVax study protocol.

INTRODUCTION: Gonorrhoea, the sexually transmissible infection caused by Neisseria gonorrhoeae, has a substantial impact on sexual and reproductive health globally with an estimated 82 million new infections each year worldwide. N. gonorrhoeae antimicrobial resistance continues to escalate, and disease control is largely reliant on effective therapy as there is no proven effective gonococcal vaccine available. However, there is increasing evidence from observational cohort studies that the serogroup B meningococcal vaccine four-component meningitis B vaccine (4CMenB) (Bexsero), licensed to prevent invasive disease caused by Neisseria meningitidis, may provide cross-protection against the closely related bacterium N. gonorrhoeae. This study will evaluate the efficacy of 4CMenB against N. gonorrhoeae infection in men (cis and trans), transwomen and non-binary people who have sex with men (hereafter referred to as GBM+). METHODS AND ANALYSIS: This is a double-blind, randomised placebo-controlled trial in GBM+, either HIV-negative on pre-exposure prophylaxis against HIV or living with HIV (CD4 count >350 cells/mm3), who have had a diagnosis of gonorrhoea or infectious syphilis in the last 18 months (a key characteristic associated with a high risk of N. gonorrhoeae infection). Participants are randomised 1:1 to receive two doses of 4CMenB or placebo 3 months apart. Participants have 3-monthly visits over 24 months, which include testing for N. gonorrhoeae and other sexually transmissible infections, collection of demographics, sexual behaviour risks and antibiotic use, and collection of research samples for analysis of N. gonorrhoeae-specific systemic and mucosal immune responses. The primary outcome is the incidence of the first episode of N. gonorrhoeae infection, as determined by nucleic acid amplification tests, post month 4. Additional outcomes consider the incidence of symptomatic or asymptomatic N. gonorrhoeae infection at different anatomical sites (ie, urogenital, anorectum or oropharynx), incidence by N. gonorrhoeae genotype and antimicrobial resistance phenotype, and level and functional activity of N. gonorrhoeae-specific antibodies. ETHICS AND DISSEMINATION: Ethical approval was obtained from the St Vincent's Hospital Human Research Ethics Committee, St Vincent's Hospital Sydney, NSW, Australia (ref: 2020/ETH01084). Results will be disseminated in peer-reviewed journals and via presentation at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04415424.

Pilot study to evaluate the safety and effectiveness of etidronate treatment for arterial calcification due to deficiency of CD73 (ACDC).

BACKGROUND: Arterial calcification due to deficiency of CD73 (ACDC; OMIM 211800) is a rare genetic disease resulting in calcium deposits in arteries and small joints causing claudication, resting pain, severe joint pain, and deformities. Currently, there are no standard treatments for ACDC. Our previous work identified etidronate as a potential targeted ACDC treatment, using in vitro and in vivo disease models with patient-derived cells. In this study, we test the safety and effectiveness of etidronate in attenuating the progression of lower-extremity arterial calcification and vascular blood flow based on the computed tomography (CT) calcium score and ankle-brachial index (ABI). METHODS: Seven adult patients with a confirmed genetic diagnosis of ACDC were enrolled in an open-label, nonrandomized, single-arm pilot study for etidronate treatment. They took etidronate daily for 14 days every 3 months and were examined at the NIH Clinical Center bi-annually for 3 years. They received a baseline evaluation as well as yearly follow up after treatment. Study visits included imaging studies, exercise tolerance tests with ABIs, clinical blood and urine testing, and full dental exams. RESULTS: Etidronate treatment appeared to have slowed the progression of further vascular calcification in lower extremities as measured by CT but did not have an effect in reversing vascular and/or periarticular joint calcifications in our small ACDC cohort. CONCLUSIONS: Etidronate was found to be safe and well tolerated by our patients and, despite the small sample size, appeared to show an effect in slowing the progression of calcification in our ACDC patient cohort.(ClinicalTrials.gov Identifier NCT01585402).

Ultra-low dose chest CT with silver filter and deep learning reconstruction significantly reduces radiation dose and retains quantitative information in the investigation and monitoring of lymphangioleiomyomatosis (LAM).

PURPOSE: Frequent CT scans to quantify lung involvement in cystic lung disease increases radiation exposure. Beam shaping energy filters can optimize imaging properties at lower radiation dosages. The aim of this study is to investigate whether use of SilverBeam filter and deep learning reconstruction algorithm allows for reduced radiation dose chest CT scanning in patients with lymphangioleiomyomatosis (LAM). MATERIAL AND METHODS: In a single-center prospective study, 60 consecutive patients with LAM underwent chest CT at standard and ultra-low radiation doses. Standard dose scan was performed with standard copper filter and ultra-low dose scan was performed with SilverBeam filter. Scans were reconstructed using a soft tissue kernel with deep learning reconstruction (AiCE) technique and using a soft tissue kernel with hybrid iterative reconstruction (AIDR3D). Cyst scores were quantified by semi-automated software. Signal-to-noise ratio (SNR) was calculated for each reconstruction. Data were analyzed by linear correlation, paired t-test, and Bland-Altman plots. RESULTS: Patients averaged 49.4 years and 100% were female with mean BMI 26.6 ± 6.1 kg/m2. Cyst score measured by AiCE reconstruction with SilverBeam filter correlated well with that of AIDR3D reconstruction with standard filter, with a 1.5% difference, and allowed for an 85.5% median radiation dosage reduction (0.33 mSv vs. 2.27 mSv, respectively, p < 0.001). Compared to standard filter with AIDR3D, SNR for SilverBeam AiCE images was slightly lower (3.2 vs. 3.1, respectively, p = 0.005). CONCLUSION: SilverBeam filter with deep learning reconstruction reduces radiation dosage of chest CT, while maintaining accuracy of cyst quantification as well as image quality in cystic lung disease. CLINICAL RELEVANCE STATEMENT: Radiation dosage from chest CT can be significantly reduced without sacrificing image quality by using silver filter in combination with a deep learning reconstructive algorithm. KEY POINTS: • Deep learning reconstruction in chest CT had no significant effect on cyst quantification when compared to conventional hybrid iterative reconstruction. • SilverBeam filter reduced radiation dosage by 85.5% compared to standard dose chest CT. • SilverBeam filter in coordination with deep learning reconstruction maintained image quality and diagnostic accuracy for cyst quantification when compared to standard dose CT with hybrid iterative reconstruction.

Quantification of Proteus syndrome-associated lung disease.

BACKGROUND: Proteus syndrome is an ultra-rare mosaic overgrowth disorder. Individuals with Proteus syndrome can develop emphysematous and cystic changes of the lung that may lead to progressive respiratory symptoms and require surgical intervention. This retrospective study seeks to quantify the radiographic features of Proteus syndrome-associated lung disease using computed tomography (CT) of the chest. The first method derives a Cystic Lung Score (CLS) by using a computer-aided diagnostic tool to quantify the fraction of cystic involvement of the lung. The second method yields a Clinician Visual Score (CVS), an observer reported scale of severity based on multiple radiographic features. The aim of this study was to determine if these measurements are associated with clinical symptoms, pulmonary function test (PFT) measurements, and if they may be used to assess progression of pulmonary disease. RESULTS: One hundred and thirteen imaging studies from 44 individuals with Proteus syndrome were included. Dyspnea and oxygen use were each associated with higher CLS (p = 0.001 and < 0.001, respectively) and higher CVS (p < 0.001 and < 0.001). Decreases in percent predicted FVC, FEV1, and DLCO each correlated with increased CLS and CVS. The annual increase of CLS in children, 5.6, was significantly greater than in adults, 1.6. (p = 0.03). The annual increase in CVS in children, 0.4, was similar to adults, 0.2 (p = 0.36). CONCLUSIONS: Proteus syndrome-associated lung disease is progressive. The rate of cystic progression is increased in children. Increased scores in CLS and CVS were associated with clinical symptoms and decreased pulmonary function. Both methods were able to detect change over time and were associated with clinically meaningful outcomes which may enable their use in interventional studies.

Circulating Oxidized mtDNA is Associated Broadly with Cardiovascular Disease in a Longitudinal Cohort Study of Psoriasis.

Psoriasis (PSO) is a chronic and systemic inflammatory autoimmune disease associated with atherosclerosis and myocardial infarction. Given that atherosclerosis is both inflammation and immune driven, we sought to expand on known immune and inflammatory biomarkers in a PSO cohort. In this study, we focus on oxidized mtDNA (ox-mtDNA), a product of cells undergoing pyroptosis, including keratinocytes, which was quantified in patients with PSO and individuals without PSO by ELISA. Patients with PSO had significantly higher ox-mtDNA levels than healthy subjects (mean ± SD = 9246 ± 2518 pg/ml for patients with PSO vs 7382 ± 2506 pg/ml for those without; P = .006). Importantly, ox-mtDNA was positively associated with IL-17a (ß = 0.25; P = .03) and low-density granulocytes (ß = 0.37; P = .005) but negatively associated with high-density lipoprotein-cholesterol (ß = -0.29; P = .006). After adjusting for traditional cardiovascular risk factors, we found that ox-mtDNA was associated with noncalcified coronary burden, which was measured by coronary computed tomography angiography (ß = 0.19; P = .003). Biologic-naïve patients with PSO receiving anti-IL-17a therapy had a 14% decrease in ox-mtDNA (mean ± SD: 10540 ± 614 pg/ml at baseline to 9016 ± 477 pg/ml at 1 year; P = .016) and a 10% reduction in noncalcified coronary artery burden (mean ± SD: 1.06 ± 0.45 at baseline, reducing to 0.95 ± 0.35 at 1 year; P = .0037). In summary, levels of ox-mtDNA in PSO are associated with measures of coronary plaque formation, indicating that this biomarker may be an autoimmune-driven early atherosclerotic feature.

Development of a computed tomography calcium scoring technique for assessing calcinosis distribution, pattern and burden in dermatomyositis.

OBJECTIVES: To utilize whole-body CT imaging and calcium scoring techniques as tools for calcinosis assessment in a prospective cohort of patients with adult and juvenile dermatomyositis (DM and JDM, respectively). METHODS: Thirty-one patients (14 DM and 17 JDM) who fulfilled Bohan and Peter Classification criteria as probable or definite DM, the EULAR-ACR criteria for definite DM, and with calcinosis identified by physical examination or prior imaging studies were included. Non-contrast whole-body CT scans were obtained using low-dose radiation procedures. Scans were read qualitatively and quantitated. We calculated the sensitivity and specificity of calcinosis detection of physician physical exam against CT. We quantified calcinosis burden using the Agatston scoring technique. RESULTS: We identified five distinct calcinosis patterns: Clustered, Disjoint, Interfascial, Confluent and Fluid-filled. Novel locations of calcinosis were observed, including the cardiac tissue, pelvic and shoulder bursa, and the spermatic cord. Quantitative measures using Agatston scoring for calcinosis were used in regional distributions across the body. Physician physical exams had a sensitivity of 59% and a specificity of 90% compared with CT detection. A higher calcium score correlated with higher Physician Global Damage, Calcinosis Severity scores, and disease duration. CONCLUSION: Whole-body CT scans and the Agatston scoring metric define distinct calcinosis patterns and provide novel insights relating to calcinosis in DM and JDM patients. Physicians' physical examinations underrepresented the presence of calcium. Calcium scoring of CT scans correlated with clinical measures, which suggests that this method may be used to assess calcinosis and follow its progression.

Anakinra-Associated Systemic Amyloidosis.

OBJECTIVE: To describe a 41-year-old woman with a history of neonatal onset multisystem inflammatory disease, on treatment with daily subcutaneous injections of 600 mg of recombinant interleukin-1 receptor antagonist (IL-1Ra) protein, anakinra, since the age of 28, who presented with golf-ball size nodules at the anakinra injection sites, early satiety, new onset nephrotic syndrome in the context of normal markers of systemic inflammation. METHODS: Clinical history and histologic evaluation of biopsies of skin, gastric mucosa, and kidney with Congo-red staining and proteomic evaluation of microdissected Congo red-positive amyloid deposits by liquid chromatography-tandem mass spectrometry. RESULTS: The skin, stomach, and kidney biopsies all showed the presence of Congo red-positive amyloid deposits. Mass spectrometry-based proteomics demonstrated that the amyloid deposits in all sites were of AIL1RAP (IL-1Ra protein)-type. These were characterized by high spectral counts of the amyloid signature proteins (apolipoprotein AIV, apolipoprotein E, and serum amyloid P-component) and the amyloidogenic IL-1Ra protein, which were present in Congo red-positive areas and absent in Congo red-negative areas. The amino acid sequence identified by mass spectrometry confirmed that the amyloid precursor protein was recombinant IL-1Ra (anakinra) and not endogenous wild-type IL-1Ra. CONCLUSION: This is the first report of iatrogenic systemic amyloidosis due to an injectable protein drug, which was caused by recombinant IL1Ra (anakinra).

Increased syphilis testing and detection of late latent syphilis among women after switching from risk-based to opt-out testing strategy in an urban Australian sexual health clinic: a retrospective observational study.

Background: The Melbourne Sexual Health Centre (MSHC) implemented an opt-out syphilis test for women in December 2017. We aimed to examine the differences in syphilis testing uptake and confirmed syphilis cases among women after switching from risk-based to opt-out testing strategies. Methods: This was a retrospective study examining all women attending the MSHC for the first time in periods of risk-based testing (2015-2017) and opt-out testing (2018-2020). We calculated the proportion of women who tested for syphilis and the proportion of women with confirmed syphilis in each period. A chi-square test was performed to determine the differences in proportion between the risk-based testing and opt-out periods. Findings: A total of 27,481 women (i.e. 13,059 in the risk-based testing period and 14,422 in the opt-out period) were included in the final analysis, and the mean age was 26.8 years (standard deviation = 6.9). The proportion of women who were tested for syphilis at their first consultation increased from 52.8% (6890/13,059) in the risk-based testing period to 67.4% (9725/14,422) in the opt-out period (p < 0.0001). Syphilis positivity did not differ between the two periods (0.48% [33/6890] vs 0.71% [69/9725], p = 0.061) but late latent causes increased from 36.4% [12/33] to 60.9% [42/69] (p = 0.033). Interpretation: The opt-out testing strategy increased syphilis testing among women with increased detection of asymptomatic late latent syphilis. The opt-out syphilis testing strategy is beneficial in sexual health services. Health education and awareness may be required to improve syphilis testing uptake. Funding: National Health and Medical Research Council.

Cardiovascular Testing in the United States during the COVID-19 Pandemic: Volume Recovery and Worldwide Comparison.

Purpose: To characterize the recovery of diagnostic cardiovascular procedure volumes in U.S. and non-U.S. facilities in the year following the initial COVID-19 outbreak. Materials and Methods: The International Atomic Energy Agency (IAEA) coordinated a worldwide study called the IAEA Noninvasive Cardiology Protocols Study of COVID-19 2 (INCAPS COVID 2), collecting data from 669 facilities in 107 countries, including 93 facilities in 34 U.S. states, to determine the impact of the pandemic on diagnostic cardiovascular procedure volumes. Participants reported volumes for each diagnostic imaging modality used at their facility for March 2019 (baseline), April 2020, and April 2021. This secondary analysis of INCAPS COVID 2 evaluated differences in changes in procedure volume between U.S. and non-U.S. facilities and among U.S. regions. Factors associated with return to prepandemic volumes in the United States were also analyzed in a multivariable regression analysis. Results: Reduction in procedure volumes in April 2020 compared with baseline was similar for U.S. and non-U.S. facilities (-66% vs -71%, P = .27). U.S. facilities reported greater return to baseline in April 2021 than did all non-U.S. facilities (4% vs -6%, P = .008), but there was no evidence of a difference when comparing U.S. facilities with non-U.S. high-income country (NUHIC) facilities (4% vs 0%, P = .18). U.S. regional differences in return to baseline were observed between the Midwest (11%), Northeast (9%), South (1%), and West (-7%, P = .03), but no studied factors were significant predictors of 2021 change from prepandemic baseline. Conclusion: The reductions in cardiac testing during the early pandemic have recovered within a year to prepandemic baselines in the United States and NUHICs, while procedure volumes remain depressed in lower-income countries.Keywords: SPECT, Cardiac, Epidemiology, Angiography, CT Angiography, CT, Echocardiography, SPECT/CT, MR Imaging, Radionuclide Studies, COVID-19, Cardiovascular Imaging, Diagnostic Cardiovascular Procedure, Cardiovascular Disease, Cardiac Testing Supplemental material is available for this article. © RSNA, 2023.

Relationship of Soluble Lectin-Like Low-Density Lipoprotein Receptor-1 (sLOX-1) With Inflammation and Coronary Plaque Progression in Psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory condition associated with coronary artery disease risk. Uptake of oxidized low-density lipoprotein by the lectin-like low-density lipoprotein receptor-1 triggers release of the soluble extracellular domain of the receptor (sLOX-1). We sought to characterize the relationship between sLOX-1, inflammation, and coronary plaque progression in psoriasis. METHODS AND RESULTS: A total of 327 patients with psoriasis had serum sLOX-1 levels measured at baseline by an ELISA-based assay. Stratification by high-sensitivity C-reactive protein ≥4.0 mg/L (quartile 4), identified 81 participants who had coronary plaque phenotyping at baseline and were followed longitudinally by coronary computed tomography angiography. Subjects within high-sensitivity C-reactive protein quartile 4 were middle-aged (51.47±12.62 years), predominantly men (54.3%) with moderate psoriasis disease severity (6.60 [interquartile range, 3.30-13.40]). In the study cohort, participants with sLOX-1 above the median displayed increased vulnerable coronary plaque features. At baseline, sLOX-1 was associated with total burden (rho=0.296; P=0.01), noncalcified burden (rho=0.286; P=0.02), fibro-fatty burden (rho=0.346; P=0.004), and necrotic burden (rho=0.394; P=0.002). A strong relationship between sLOX-1, noncalcified burden (ß=0.19; P=0.03), and fibro-fatty burden (ß=0.29; P=0.003) was found in fully adjusted models at baseline and 1- and 4-year follow-up. Finally, coronary plaque features progressed over 1 year regardless of biologic or systemic treatment in subjects with high sLOX-1. CONCLUSIONS: Patients with psoriasis with both high sLOX-1 and high-sensitivity C-reactive protein levels have increased coronary plaque burden associated with atherosclerotic plaque progression independent of biologic and systemic treatment. Thus, sLOX-1 might be considered as a promising marker in coronary artery disease risk estimation beyond traditional risk factors. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01778569.

Longitudinal association of epicardial and thoracic adipose tissues with coronary and cardiac characteristics in psoriasis.

Background: s: Psoriasis is a disease of systemic inflammation associated with increased cardiometabolic risk. Epicardial adipose tissue (EAT) and thoracic adipose tissue (TAT) are contributing factors for atherosclerosis and cardiac dysfunction. We strove to assess the longitudinal impact of the EAT and TAT on coronary and cardiac characteristics in psoriasis. Methods: The study consisted of 301 patients with baseline coronary computed tomography angiography (CTA), of which 139 had four-year follow up scans. EAT and TAT volumes from non-contrast computed tomography scans were quantified by an automated segmentation framework. Coronary plaque characteristics and left ventricular (LV) mass were quantified by CTA. Results: When stratified by baseline EAT and TAT volume quartiles, a stepwise significant increase in cardiometabolic parameters was observed. EAT and TAT volumes associated with fibro-fatty burden (FFB) (TAT: ρ = 0.394, P < 0.001; EAT: ρ = 0.459, P < 0.001) in adjusted models. Only EAT had a significant four-year time-dependent association with FFB in fully adjusted models (ß = 0.307 P = 0.003), whereas only TAT volume associated with myocardial injury in fully adjusted models (TAT: OR = 1.57 95 % CI = (1.00-2.60); EAT: OR = 1.46 95 % CI = (0.91-2.45). Higher quartiles of EAT and TAT had increased LV mass and developed strong correlation (TAT: ρ = 0.370, P < 0.001; EAT: ρ = 0.512, P < 0.001). Conclusions: Our study is the first to explore how both EAT and TAT volumes associate with increased cardiometabolic risk profile in an inflamed psoriasis cohorts and highlight the need for further studies on its use as a potential prognostic tool for high-risk coronary plaques and cardiac dysfunction.

Treponema pallidum Detection at Asymptomatic Oral, Anal, and Vaginal Sites in Adults Reporting Sexual Contact with Persons with Syphilis.

We investigated Treponema pallidum PCR positivity at mucosal sites (oral, anal, and vaginal sites) among adults who had sexual contact with a person with syphilis (syphilis contacts). All syphilis contacts had oral rinse and swab samples collected for testing. Men who have sex with men had anal swab and women had vaginal swab samples collected for testing, regardless of the presence of lesions. Of 407 persons tested, 42 (10%) had early syphilis diagnosed; of those, 19 (45%) tested positive by PCR from any anatomic site and had a positive serologic test. T. pallidum was positive from vaginal samples in 3 women, anal samples in 3 men, and oral cavity samples in 2 women and 3 men, without symptoms at those sites. Three women had no prior syphilis serologic test. T. pallidum detection at asymptomatic mucosal sites suggests early syphilis infections, particularly in cases that would conventionally be staged as latent syphilis of unknown duration.

Treponema pallidum PCR screening at mucosal sites of asymptomatic men who have sex with men taking HIV pre-exposure prophylaxis.

Early detection and treatment of syphilis will reduce the infectious period and transmission. We aimed to determine whether screening men who have sex with men (MSM) taking HIV pre-exposure prophylaxis (PrEP) for syphilis using Treponema pallidum polymerase chain reaction (PCR) could detect syphilis before the appearance of syphilis antibodies in serology. MSM attending 3-monthly PrEP clinic visits in Melbourne, Australia, were screened with a PCR assay targeting the polA gene of T. pallidum from an anal swab and an oral rinse between November 2019 and March 2020. Participants were serologically screened for syphilis using chemiluminescence immunoassay. A total of 309 asymptomatic participants provided an anal swab and oral rinse sample for T. pallidum PCR screening. Two syphilis cases (0.6%) were detected: one man had a positive serology only; another man had T. pallidum detected by PCR from an anal swab and a positive serology. PCR positivity was 0.3% (n = 1) for anal swabs and 0% (n = 0) for oral rinse. In this study, T. pallidum PCR screening at routine PrEP clinic visits did not identify additional cases of early syphilis over serological screening performed at these visits. IMPORTANCE With the ongoing syphilis epidemic in men who have sex with men (MSM), we investigated the role of using Treponema pallidum polymerase chain reaction (PCR) testing at the oral cavity and anus in MSM taking pre-exposure prophylaxis for the early detection of syphilis. We evaluated whether the PCR tests from these mucosal sites can detect syphilis infection early, before the development of syphilis antibodies in serology. Our study found two syphilis cases among 309 MSM, and only one syphilis case had a positive anal PCR swab, although serology was positive. We conclude that additional PCR testing is likely to be expensive and would not be cost effective for individuals who regularly screen for syphilis. However, future studies with a larger sample size are required.

Consistency of spectral results in cardiac dual-source photon-counting CT.

We evaluate stability of spectral results at different heart rates, acquisition modes, and cardiac phases in first-generation clinical dual-source photon-counting CT (PCCT). A cardiac motion simulator with a coronary stenosis mimicking a 50% eccentric calcium plaque was scanned at five different heart rates (0, 60-100 bpm) with the three available cardiac scan modes (high pitch prospectively ECG-triggered spiral, prospectively ECG-triggered axial, retrospectively ECG-gated spiral). Subsequently, full width half max (FWHM) of the stenosis, Dice score (DSC) for the stenosed region, and eccentricity of the non-stenosed region were calculated for virtual monoenergetic images (VMI) at 50, 70, and 150 keV and iodine density maps at both diastole and systole. FWHM averaged differences of - 0.20, - 0.28, and - 0.15 mm relative to static FWHM at VMI 150 keV across acquisition parameters for high pitch prospectively ECG-triggered spiral, prospectively ECG-triggered axial, and retrospectively ECG-gated spiral scans, respectively. Additionally, there was no effect of heart rate and acquisition mode on FWHM at diastole (p-values < 0.001). DSC demonstrated similarity among parameters with standard deviations of 0.08, 0.09, 0.11, and 0.08 for VMI 50, 70, and 150 keV, and iodine density maps, respectively, with insignificant differences at diastole (p-values < 0.01). Similarly, eccentricity illustrated small differences across heart rate and acquisition mode for each spectral result. Consistency of spectral results at different heart rates and acquisition modes for different cardiac phase demonstrates the added benefit of spectral results from PCCT to dual-source CT to further increase confidence in quantification and advance cardiovascular diagnostics.

Rapid detection of monkeypox virus using a CRISPR-Cas12a mediated assay: a laboratory validation and evaluation study.

BACKGROUND: The 2022 outbreak of mpox (formerly known as monkeypox) led to the spread of monkeypox virus (MPXV) in over 110 countries, demanding effective disease management and surveillance. As current diagnostics rely largely on centralised laboratory testing, our objective was to develop a simple rapid point-of-care assay to detect MPXV in clinical samples using isothermal amplification coupled with CRISPR and CRISPR-associated protein (Cas) technology. METHODS: In this proof-of-concept study, we developed a portable isothermal amplification CRISPR-Cas12a-based assay for the detection of MPXV. We designed a panel of 22 primer-guide RNA sets using pangenome and gene-agnostic approaches, and subsequently shortlisted the three sets producing the strongest signals for evaluation of analytical sensitivity and specificity using a fluorescence-based readout. The set displaying 100% specificity and the lowest limit of detection (LOD) was selected for further assay validation using both a fluorescence-based and lateral-flow readout. Assay specificity was confirmed using a panel of viral and bacterial pathogens. Finally, we did a blind concordance study on genomic DNA extracted from 185 clinical samples, comparing assay results with a gold-standard quantitative PCR (qPCR) assay. We identified the optimal time to detection and analysed the performance of the assay relative to qPCR using receiver operating characteristic (ROC) curves. We also assessed the compatibility with lateral-flow strips, both visually and computationally, where strips were interpreted blinded to the fluorescence results on the basis of the presence or absence of test bands. FINDINGS: With an optimal run duration of approximately 45 min from isothermal amplification to CRISPR-assay readout, the MPXV recombinase polymerase amplification CRISPR-Cas12a-based assay with the selected primer-guide set had an LOD of 1 copy per µL and 100% specificity against tested viral pathogens. Blinded concordance testing of 185 clinical samples resulted in 100% sensitivity (95% CI 89·3-100) and 99·3% specificity (95% CI 95·7-100) using the fluorescence readout. For optimal time to detection by fluorescence readout, we estimated the areas under the ROC curve to be 0·98 at 2 min and 0·99 at 4 min. Lateral-flow strips had 100% sensitivity (89·3-100) and 98·6% specificity (94·7-100) with both visual and computational assessment. Overall, lateral-flow results were highly concordant with fluorescence-based readouts (179 of 185 tests, 96·8% concordant), with discrepancies associated with low viral load samples. INTERPRETATION: Our assay for the diagnosis of mpox displayed good performance characteristics compared with qPCR. Although optimisation of the assay will be required before deployment, its usability and versatility present a potential solution to MPXV detection in low-resource and remote settings, as well as a means of community-based, on-site testing. FUNDING: Victorian Medical Research Accelerator Fund and the Australian Government Department of Health.

Standardized Medical Terminology for Cardiac Computed Tomography 2023 Update: An Expert Consensus Document of the Society of Cardiovascular Computed Tomography (SCCT), American Association of Physicists in Medicine (AAPM), American College of Radiology (ACR), North American Society for Cardiovascular Imaging (NASCI), and Radiological Society of North America (RSNA) with endorsement by the Asian Society of Cardiovascular Imaging (ASCI), the European Association of Cardiovascular Imaging (EACI), and the European Society of Cardiovascular Radiology (ESCR).

Since the emergence of cardiac computed tomography (Cardiac CT) at the turn of the 21st century, there has been an exponential growth in research and clinical development of the technique, with contributions from investigators and clinicians from varied backgrounds: physics and engineering, informatics, cardiology, and radiology. However, terminology for the field is not unified. As a consequence, there are multiple abbreviations for some terms, multiple terms for some concepts, and some concepts that lack clear definitions and/or usage. In an effort to aid the work of all those who seek to contribute to the literature, clinical practice, and investigation of the field, the Society of Cardiovascular Computed Tomography updates a standard set of medical terms commonly used in clinical and research activities related to cardiac CT. Keywords: Cardiac, CT, Medical Terminology Supplemental material is available for this article. This article is published synchronously in Radiology: Cardiothoracic Imaging and Journal of Cardiovascular Computed Tomography. ©2023 Society of Cardiovascular Computed Tomography. Published by RSNA with permission.

Combined Computed Tomography Angiography-Computed Tomography Perfusion in the Identification and Prognostic Assessment of Myocardial Bridging from the CORE320 Study: 5-Year Follow-Up.

Our objective is to use computed tomography angiography (CTA) and computed tomography perfusion (CTP) to identify the ischemic significance of myocardial bridging (MB). We also seek to determine the long-term prognostication of MB in the presence or absence of obstructive coronary artery disease (CAD). The CORE320, a prospective, multicenter study including 381 patients with known or suspected CAD clinically referred for invasive coronary angiography who underwent combined (CTA-CTP) and single-photon emission computed tomography before conventional coronary angiography. The incidence of MB was identified in 135 patients (35.4%) with 93.9% identified in the left anterior descending artery. MB were divided as partially encased versus fully encased. There was no difference in ischemia identified between partially encased MB and fully encased MB (37 [40%] vs 25 [35%], p = 0.54]. Ischemia was identified at similar rates in partially versus fully encased MB by single-photon emission computed tomography at (8 [9%] vs 8 [11%], p = 0.57] and CTP (34 [37%] vs 21 [30%], p = 0.33]. There was no difference in the primary outcome of 5-year outcome of combined incidence of myocardial infarction or death. The restricted mean survival time in patients with CTA with <50% stenosis with or without a MB was 4.906 years (95% confidence interval 4.759 to 5.000) and 4.891 years (95% confidence interval 4.718 to 5.000), respectively (p = 0.824). Cardiac computed tomography perfusion imaging can assess both anatomic and functional significance of myocardial bridging with diagnostic accuracy similar to current standard imaging. Furthermore, 5-year cardiovascular events were not different with the presence of MB in both obstructive and non-obstructive CAD.

Impact of the confluence of cardiac motion and high spatial resolution on performance of ECG-gated imaging with an investigational photon-counting CT system: A phantom study.

PURPOSE: Photon-counting CT (PCCT) has higher spatial resolution that conventional EID CT which improves imaging of stationary coronary plaques and stents.. In this work, we evaluated the relationship between higher spatial resolution and motion acquisition on an investigational PCCT system. METHODS: An investigational photon-counting CT scanner (Siemens CounT) with ECG gating was used to image a coronary tree phantom with models of healthy, stenotic, and stented arteries using a motion simulator. Images were acquired with matched clinical parameters at rest and 60 beats per minute. An additional set of high dose stationary images were averaged to generate a motion-free, reduced noise reference. Scans were completed at standard (0.5 mm2) and high-resolution (0.25 mm2). Motion images were reconstructed at multiple phases. Regions of interest were drawn around vessels and segmented. Percentage difference from the reference standard was evaluated for vessel diameter and circularity. Mutual information between the reference and stationary and motion datasets was used as a measure of volumetric similarity. RESULTS: The stenotic vessel showed the most variation from the reference when compared to healthy or stented vessels. Compared to standard resolution, high-resolution images had lower bias for diameter (-0.012 ± 0.19% vs -0.052 ± 0.14%) and lower variability for circularity (-0.13 ± 0.138% vs -0.12 ± 0.144%). Both differences were found to be statistically significant. High-resolution images had a slightly lower mutual information (1.28) than standard resolution (1.31). CONCLUSION: The higher spatial resolution enabled by photon-counting CT can be harnessed for cardiac imaging as the benefits of high spatial resolution acquisitions remain relevant in the presence of motion.

Association of oxidized ApoB and oxidized ApoA-I with high-risk coronary plaque features in cardiovascular disease.

BACKGROUND: Oxidized apolipoprotein B (oxLDL) and oxidized ApoA-I (oxHDL) are proatherogenic. Their prognostic value for assessing high-risk plaques by coronary computed tomography angiography (CCTA) is missing. METHODS: In a prospective, observational study, 306 participants with cardiovascular disease (CVD) had extensive lipoprotein profiling. Proteomics analysis was performed on isolated oxHDL, and atherosclerotic plaque assessment was accomplished by quantitative CCTA. RESULTS: Patients were predominantly White, overweight men (58.5%) on statin therapy (43.5%). Increase in LDL-C, ApoB, small dense LDL-C (P < 0.001 for all), triglycerides (P = 0.03), and lower HDL function were observed in the high oxLDL group. High oxLDL associated with necrotic burden (NB; ß = 0.20; P < 0.0001) and fibrofatty burden (FFB; ß = 0.15; P = 0.001) after multivariate adjustment. Low oxHDL had a significant reverse association with these plaque characteristics. Plasma oxHDL levels better predicted NB and FFB after adjustment (OR, 2.22; 95% CI, 1.27-3.88, and OR, 2.80; 95% CI, 1.71-4.58) compared with oxLDL and HDL-C. Interestingly, oxHDL associated with fibrous burden (FB) change over 3.3 years (ß = 0.535; P = 0.033) when compared with oxLDL. Combined Met136 mono-oxidation and Trp132 dioxidation of HDL showed evident association with coronary artery calcium score (r = 0.786; P < 0.001) and FB (r = 0.539; P = 0.012) in high oxHDL, whereas Met136 mono-oxidation significantly associated with vulnerable plaque in low oxHDL. CONCLUSION: Our findings suggest that the investigated oxidized lipids are associated with high-risk coronary plaque features and progression over time in patients with CVD. CLINICALTRIALS: gov NCT01621594. FUNDING: National Heart, Lung, and Blood Institute at the NIH Intramural Research Program.