The Encounter of Two Worlds: Divided Narratives of Decision-Making on Cancer Treatment Between Physicians and Patients.

INTRODUCTION: Divided narratives pose long-standing difficulties in physician and patient communication. In decision-making on cancer treatment, divided narratives between physicians and patients hinder mutual understanding and agreement over the illness and its treatment. For effective decision-making on treatments, it is necessary to investigate the similarities and differences in these divided narratives. METHODS: This study adopted a qualitative research design of narrative inquiry to examine the data, which included interviews with 32 cancer patients and 16 paired physicians in two hospitals in China. Data analysis was conducted using grounded theory to generate findings. RESULTS: Both physicians and patients were concerned about goals and obstacles to their decision-making on cancer treatment. Four common aspects of goal setting were identified from the divided narratives: decision pools, treatment goals, identity practice and preferred identity. Four common obstacles were identified: pains and trust, communication gap, financial issues and complex family. However, the meanings attached to these eight aspects differed between physicians and patients. CONCLUSION: Cancer treatment decision-making is an encounter of the scientific world and lifeworld. A divided narrative approach can identify the similarities and differences in the decision-making on cancer treatment between physicians and patients. Physicians generally adopt a rational decision-making approach, whereas patients generally adopt a relational decision-making approach. Despite the common concerns in their goals and obstacles, physicians and patients differed in their contextualized interpretations, which demonstrates the physicians' and the patients' pursuit of preferred identities in decision-making. The results of this study provide a new perspective to treatment decision-making, emphasizing the importance of narrative integration in reaching mutual agreement. PATIENT AND PUBLIC CONTRIBUTION: The findings were shared with 15 cancer patients and caregivers for feedback and advice in June 2024. This study was also presented at the international conferences of COMET (International and Interdisciplinary Conference on Communication, Medicine, and Ethics) and ICCH (International Conference on Communication in Healthcare) 2023 for continuous feedback and comments.

Prevalence and burden of coronary artery disease on computed tomography coronary angiography and its correlation with high-density lipoprotein in the Northern Territory, Australia.

Indigenous Australians are known to have a higher prevalence of coronary artery disease (CAD) than non-Indigenous counterparts. Atherogenic lipid profiles, characterised by low serum levels of high-density lipoprotein (HDL) and higher serum triglycerides, have been shown to be more prevalent in Indigenous Australians. The use of computed tomography coronary angiography (CTCA) for risk stratification and diagnosis of CAD has been validated in moderate risk populations, but limited data exists in specific high-risk populations such as Indigenous Australians. Through a retrospective study of patient records, we aimed to confirm if an atherogenic lipid profile occurred in Indigenous Australians undergoing CTCA in the Northern Territory of Australia and if so, whether this correlated with the prevalence or burden of CAD. We demonstrate that Indigenous Australians have similar prevalence (52.6% vs. 50.3%, P=0.80) and burden of CAD (Leaman score 6.03±4.66 vs. 6.96±4.82, P=0.44) on CTCA as non-Indigenous patients, but were 8 years younger (41.9±8.9 vs. 50.0±11.9 years, P<0.001) at the time of examination. We confirmed the presence of an atherogenic lipid profile in Indigenous patients and showed low serum-HDL was associated with very premature (patients aged 18-35 years) CAD in comparison to premature (patients aged 36-55 years) and mature-onset (patients aged 56 years and older) CAD (0.71±0.25 vs. 1.09±0.35 vs. 1.18±0.36 mmol/L, P=0.009). Future clinical guidelines should consider the role of CTCA in Indigenous Australians and whether younger patients may benefit. The causes of premature CAD, including atherogenic lipid profiles, require an ongoing focus in order to achieve equitable cardiovascular outcomes for Indigenous and non-Indigenous Australians.

Early therapeutic drug monitoring helps to identify inflammatory bowel disease patients with a high risk to fail thiopurine treatment.

AIMS: Conventional thiopurines (azathioprine and mercaptopurine) remain standard therapy to maintain steroid sparing remission in inflammatory bowel disease (IBD), but are regularly discontinued due to adverse drug reactions (ADRs). Measurement of the metabolites 6-thioguanine nucleotides (6-TGN), 6-methylmercaptopurine ribonucleotides (6-MMPR) and the 6-MMPR/6-TGN ratio, may predict the development of these ADRs. Our aim was to evaluate whether early thiopurine metabolite measurements were associated with clinical outcomes. METHODS: A post-hoc analysis was conducted of a multicentre, prospective, observational study on thiopurine-induced hepatotoxicity. IBD patients who initiated thiopurine therapy were included and thiopurine metabolite concentrations were assessed after 7 days (±1) (T1). Patients were monitored for 12 weeks to document the occurrence of ADRs, early treatment discontinuation and effectiveness. RESULTS: In total, 181 patients were evaluated. At T1, 6-MMPR concentrations and 6-TGN/6-MMPR ratios were independently related to treatment discontinuation within 12 weeks after correction for sex, age and body mass index (BMI) (P = .034 and .002, respectively). The largest effects were observed for 6-MMPR ≥3000 pmol/8 × 108 RBC and 6-TGN/6-MMPR ratio ≥17. Furthermore, 6-MMPR concentrations and 6-TGN/6-MMPR ratios at T1 were independently related to skewed metabolism at steady state (Week 8, 6-MMPR/-6TGN ratio ≥11 and ≥20) (both P < .001). The occurrence of ADRs and effectiveness were not independently related to T1 thiopurine metabolite concentrations. CONCLUSIONS: Thiopurine metabolite concentrations at T1 were related to early treatment discontinuation and skewed metabolism at steady state, but not to effectiveness, helping to identify patients with a high risk of thiopurine treatment failure.

Optical coherence tomography assessment of the impact of colchicine on non-culprit coronary plaque composition after myocardial infarction.

BACKGROUND: Low-dose colchicine reduces the risk of cardiovascular events after myocardial infarction (MI). The purpose of this study was to assess the effect of colchicine post-MI on coronary plaque morphology in non-culprit segments by optical coherence tomography (OCT). METHODS AND RESULTS: COCOMO-ACS was a double-blind, placebo-controlled trial that randomized 64 patients (median age 61.5 years; 9.4% female) with acute non-ST-segment elevation MI to colchicine 0.5 mg daily or placebo for a median of 17.8 months in addition to guideline-recommended therapy. Participants underwent serial OCT imaging within a matched segment of non-culprit coronary artery which contained at least one lipid-rich plaque causing ≥20% stenosis. The primary outcome was the change in minimum fibrous cap thickness (FCT) in non-culprit segments from baseline to final visit. Of those randomized, 57 (29 placebo, 28 colchicine) had evaluable imaging at baseline and follow-up. Overall, colchicine had no effect on relative (placebo +48.0±35.1% vs. colchicine +62.4±38.1%, P=0.18) or absolute changes in minimum FCT (+29.2±20.9 µm vs. +37.2±21.3 µm, P=0.18), or change in maximum lipid arc (-38.8±32.2° vs. -54.8±46.9°, P=0.18) throughout the imaged non-culprit segment. However, in patients assigned colchicine, cap rupture was less frequent (placebo 27.6% vs. colchicine 3.6%, P=0.03). In post-hoc analysis of 43 participants who had been followed for at least 16 months, minimum FCT increased to a greater extent in the colchicine group (placebo +38.7±25.4% vs. colchicine +64.7±34.1%, P=0.005). CONCLUSION: In this study, OCT failed to detect an effect of colchicine on the minimum FCT or maximum lipid arc of plaques in non-culprit segments post-MI. The post-hoc observation that minimum FCT increased to a greater extent with colchicine after more prolonged treatment suggests longer-term studies may be required to detect the effect of anti-inflammatory therapies on plaque morphology by OCT. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier, ACTRN12618000809235, registered on the 11th of May 2018.

Protocol and rationale of the Australian multicentre registry for serial cardiac computed tomography angiography (ARISTOCRAT): a prospective observational study of the natural history of pericoronary adipose tissue attenuation and radiomics.

Background: Vascular inflammation plays a crucial role in the development of atherosclerosis and atherosclerotic plaque rupture resulting in acute coronary syndrome (ACS). Pericoronary adipose tissue (PCAT) attenuation quantified from routine coronary computed tomography angiography (CCTA) has emerged as a promising non-invasive imaging biomarker of coronary inflammation. However, a detailed understanding of the natural history of PCAT attenuation is required before it can be used as a surrogate endpoint in trials of novel therapies targeting coronary inflammation. This article aims to explore the natural history of PCAT attenuation and its association with changes in plaque characteristics. Methods: The Australian natuRal hISTOry of periCoronary adipose tissue attenuation, RAdiomics and plaque by computed Tomographic angiography (ARISTOCRAT) registry is a multi-centre observational registry enrolling patients undergoing clinically indicated serial CCTA in 9 centres across Australia. CCTA scan parameters will be matched across serial scans. Quantitative analysis of plaque and PCAT will be performed using semiautomated software. Discussion: The primary endpoint is to explore temporal changes in patient-level and lesion-level PCAT attenuation by CCTA and their associations with changes in plaque characteristics. Secondary endpoints include evaluating: (I) impact of statin therapy on PCAT attenuation and plaque characteristics; and (II) changes in PCAT attenuation and plaque characteristics in specific subgroups according to sex and risk factors. ARISTOCRAT will further our understanding of the natural history of PCAT attenuation and its association with changes in plaque characteristics. Trial Registration: This study has been prospectively registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12621001018808).

Tandem lesions associate with angiographic progression of coronary artery stenoses.

Background: Although the clinical factors associated with progression of coronary artery disease have been well studied, the angiographic predictors are less defined. Objectives: Our objective was to study the clinical and angiographic factors that associate with progression of coronary artery stenoses. Methods: We conducted a retrospective analysis of consecutive patients undergoing multiple, clinically indicated invasive coronary angiograms with an interval greater than 6 months, between January 2013 and December 2016. Lesion segments were analysed using Quantitative Coronary Angiography (QCA) if a stenosis ≥ 20 % was identified on either angiogram. Stenosis progression was defined as an increase ≥ 10 % in stenosis severity, with progressor groups analysed on both patient and lesion levels. Mixed-effects regression analyses were performed to evaluate factors associated with progression of individual stenoses. Results: 199 patients were included with 881 lesions analysed. 108 (54.3 %) patients and 186 (21.1 %) stenoses were classified as progressors. The median age was 65 years (IQR 56-73) and the median interval between angiograms was 2.1 years (IQR 1.2-3.0). On a patient level, age, number of lesions and presence of multivessel disease at baseline were each associated with progressor status. On a lesion level, presence of a stenosis downstream (OR 3.07, 95 % CI 2.04-4.63, p < 0.001) and circumflex artery stenosis location (OR 1.81, 95 % CI 1.21-2.7, p = 0.004) were associated with progressor status. Other lesion characteristics did not significantly impact progressor status or change in stenosis severity. Conclusion: Coronary lesions which have a downstream stenosis may be at increased risk of stenosis progression. Further research into the mechanistic basis of this finding is required, along with its implications for plaque vulnerability and clinical outcomes.

Performance of Eight Infliximab Population Pharmacokinetic Models in a Cohort of Dutch Children with Inflammatory Bowel Disease.

BACKGROUND AND OBJECTIVE: Efficacy of infliximab in children with inflammatory bowel disease can be enhanced when serum concentrations are measured and further dosing is adjusted to achieve and maintain a target concentration. Use of a population pharmacokinetic model may help to predict an individual's infliximab dose requirement. The aim of this study was to evaluate the predictive performance of available infliximab population pharmacokinetic models in an independent cohort of Dutch children with inflammatory bowel disease. METHODS: In this retrospective study, we used data of 70 children with inflammatory bowel disease (443 infliximab concentrations) to evaluate eight models that focused on infliximab pharmacokinetic models in individuals with inflammatory bowel disease, preferably aged ≤ 18 years. Predictive performance was evaluated with prior predictions (based solely on patient-specific covariates) and posterior predictions (based on covariates and infliximab trough concentrations). Model accuracy and precision were calculated with relative bias and relative root mean square error and we determined the classification accuracy at the trough concentration target of ≥ 5 mg/L. RESULTS: The population pharmacokinetic model by Fasanmade was identified to be most appropriate for the total dataset (relative bias before/after therapeutic drug monitoring: -20.7%/11.2% and relative root mean square error before/after therapeutic drug monitoring: 84.1%/51.6%), although differences between models were small and several were deemed suitable for clinical use. For the Fasanmade model, sensitivity and specificity for maximum posterior predictions for the next infliximab trough concentration to be ≥ 5 mg/L were respectively 83.5% and 80% with an area under the receiver operating characteristic curve of 0.870. CONCLUSIONS: In our paediatric cohort, various models provided acceptable predictive performance, with the Fasanmade model deemed most suitable for clinical use. Model-informed precision dosing can therefore be expected to help to maintain infliximab trough concentrations in the target range.

Early infliximab trough levels in paediatric IBD patients predict sustained remission.

Background: Exposure-response studies have shown that higher infliximab concentrations are associated with better outcomes in inflammatory bowel disease. There is little agreement about the optimal time to measure infliximab levels in children. Objectives: We aimed to evaluate whether trough levels at week 6 or week 14 predict sustained remission. The secondary aim was to define target trough levels at weeks 6 and 14. Design: We used routinely collected electronic healthcare data of 70 anti-tumour necrosis factor naïve children with inflammatory bowel disease treated with a standard infliximab induction- and variable maintenance scheme. Methods: Trough levels and blood and faecal markers for disease activity were measured before every infliximab administration. Sustained remission was defined as the absence of symptoms and low inflammatory markers between weeks 26 and 52 after the start of infliximab therapy. Optimal infliximab levels at weeks 6 and 14 were determined using the receiver operating characteristic curve. Results: The median infliximab level at week 6 was not significantly higher in children who achieved sustained remission compared to those who did not (16.9 mg/L versus 12.0 mg/L; p = 0.058) but the median infliximab level at week 14 was significantly higher in those with sustained remission (7.7 mg/L versus 3.8 mg/L; p = 0.006). The area under the receiver operating characteristics curves at weeks 6 and 14 to predict sustained remission was 0.67 (95% CI 0.51-0.83) and 0.75 (95% CI 0.60-0.90), respectively. Target trough levels at weeks 6 and 14 were ⩾13.2 and ⩾6.9 mg/L, respectively. Conclusion: An infliximab measurement at week 14 with a target through level ⩾6.9 mg/L best predicted sustained remission.

Baked milk and egg diets revisited.

Most children with milk and egg allergy are nonreactive to modified forms of milk and egg in bakery products such as muffins because of conformational changes in proteins. These baked milk (BM) and baked egg (BE) diets have become commonplace in the management of milk and egg allergy, respectively. Current laboratory- and skin test-based diagnostic approaches remain limited in their ability to predict BM/BE tolerance, resulting in various approaches to introduce these foods. One approach to introduce BM/BE is to offer a medically supervised oral food challenge and then advise dietary introduction of baked products for children who have tolerance. Another approach is adapted from a home-based protocol of graded ingestion of BM or BE originally intended for non-IgE mediated allergy, often referred to as a "ladder." The ladder advises home ingestion of increasing amounts of BM or BE. For children who have allergy to BM or BE, the ladder is essentially oral immunotherapy, although not always labeled or recognized as such. Risk assessment and education of patients suitable for home introduction are essential. A home approach that may be called a ladder can also be used to escalate diets after demonstrated tolerance of baked forms by introducing lesser cooked forms of milk or egg after tolerating BM or BE. A randomized controlled trial provided clear evidence that baked diets can hasten the resolution of IgE-mediated milk allergy. Moreover, BM/BE foods have an emerging role in the treatment of non-IgE-mediated allergy. There is tangential evidence for BM and BE diets in the prevention of IgE-mediated allergy.

Pathophysiology of bradykinin and histamine mediated angioedema.

Angioedema is characterized by swelling localized to the subcutaneous and submucosal tissues. This review provides an overview of angioedema, including the different types, triggers, and underlying pathophysiologic mechanisms. Hereditary and acquired angioedema are caused by dysregulation of the complement and kinin pathways. In contrast, drug-induced and allergic angioedema involve the activation of the immune system and release of vasoactive mediators. Recent advances in the understanding of the pathophysiology of angioedema have led to the development of targeted therapies, such as monoclonal antibodies, bradykinin receptor antagonists, and complement inhibitors, which promise to improve clinical outcomes in patients with this challenging condition. To accurately diagnose and manage angioedema, an understanding of this condition's complex and varied pathophysiology is both necessary and critical.

Implications of Tioguanine Dosing in IBD Patients with a TPMT Deficiency.

Tioguanine is metabolised by fewer enzymatic steps compared to azathioprine and mercaptopurine, without generating 6-methylmercaptopurine ribonucleotides. However, thiopurine S-methyl transferase (TPMT) plays a role in early toxicity in all thiopurines. We aimed to describe the hazards and opportunities of tioguanine use in inflammatory bowel disease (IBD) patients with aberrant TPMT metabolism and propose preventative measures to safely prescribe tioguanine in these patients. In this retrospective cohort study, all determined TPMT genotypes (2016-2021) were evaluated for aberrant metabolism (i.e., intermediate and poor TPMT metabolisers). Subsequently, all IBD patients on tioguanine with aberrant TPMT genotypes were evaluated for tioguanine dosages, adverse drug events, lab abnormalities, treatment duration and effectiveness. TPMT genotypes were determined in 485 patients, of whom, 50 (10.3%) and 4 patients (0.8%) were intermediate and poor metabolisers, respectively. Of these patients, 12 intermediate and 4 poor TPMT metabolisers had been prescribed tioguanine in varying doses. In one poor TPMT metaboliser, tioguanine 10 mg/day induced delayed pancytopenia. In general, reduced tioguanine dosages of 5 mg/day for intermediate TPMT metabolisers, and 10 mg two-weekly for poor TPMT metabolisers, resulted in a safe, long-term treatment strategy. Diminished or absent TPMT enzyme activity was related with a pharmacokinetic shift of tioguanine metabolism which is associated with relatively late-occurring myelotoxicity in patients on standard tioguanine dose. However, in strongly reduced dose regimens with strict therapeutic drug and safety monitoring, tioguanine treatment remained a safe and effective option in IBD patients with dysfunctional TPMT.

ZIF-8 Pellets as a Robust Material for Hydrogen Cryo-Adsorption Tanks.

Cryoadsorption on the inner surface of porous materials is a promising solution for safe, fast, and reversible hydrogen storage. Within the class of highly porous metal-organic frameworks, zeolitic imidazolate frameworks (ZIFs) show high thermal, chemical, and mechanical stability. In this study, we selected ZIF-8 synthesized mechanochemically by twin-screw extrusion as powder and pellets. The hydrogen storage capacity at 77 K and up to 100 bar has been analyzed in two laboratories applying three different measurement setups showing a high reproducibility. Pelletizing ZIF-8 increases the packing density close to the corresponding value for a single crystal without loss of porosity, resulting in an improved volumetric hydrogen storage capacity close to the upper limit for a single crystal. The high volumetric uptake combined with a low and constant heat of adsorption provides ca. 31 g of usable hydrogen per liter of pellet assuming a temperature-pressure swing adsorption process between 77 K - 100 bar and 117 K - 5 bar. Cycling experiments do not indicate any degradation in storage capacity. The excellent stability during preparation, handling, and operation of ZIF-8 pellets demonstrates its potential as a robust adsorbent material for technical application in pilot- and full-scale adsorption vessel prototypes.

Pericoronary adipose tissue attenuation on coronary computed tomography angiography associates with male sex and Indigenous Australian status.

To evaluate if Indigenous Australians have higher coronary inflammation demonstrated non-invasively using pericoronary adipose tissue attenuation on coronary computed tomography angiography (CCTA). We retrospectively obtained a cohort 54 Indigenous patients age- and sex-matched to 54 non-Indigenous controls (age: 46.5 ± 13.1 years; male: n = 66) undergoing CCTA at the Royal Darwin Hospital and Monash Medical Centre. Patient groups were defined to investigate the interaction of ethnicity and sex: Indigenous + male, Indigenous + female, control + male, control + female. Semi-automated software was used to assess pericoronary adipose tissue attenuation (PCAT-a) and volume (PCAT-v). Males had significantly higher PCAT-a (- 86.7 ± 7.8 HU vs. - 91.3 ± 7.1 HU, p = 0.003) than females. Indigenous patients had significantly higher PCAT-v (1.5 ± 0.5cm3 vs. 1.3 ± 0.4cm3, p = 0.032), but only numerically higher PCAT-a (p = 0.133) than controls. There was a significant difference in PCAT-a and PCAT-v across groups defined by Indigenous status and sex (p = 0.010 and p = 0.030, respectively). Among patients with matching CCTA contrast density, multivariable linear regression analysis showed an independent association between Indigenous status and PCAT-a. Indigenous men have increased PCAT-a in an age- and sex-matched cohort. Male sex is strongly associated with increased PCAT-a. Coronary inflammation may contribute to adverse cardiovascular outcomes in Indigenous Australians, but larger studies are required to validate these findings.

Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors: JACC State-of-the-Art Review.

Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed.

Profiling novel lateral gene transfer events in the human microbiome.

Lateral gene transfer (LGT) is an important mechanism for genome diversification in microbial populations, including the human microbiome. While prior work has surveyed LGT events in human-associated microbial isolate genomes, the scope and dynamics of novel LGT events arising in personal microbiomes are not well understood, as there are no widely adopted computational methods to detect, quantify, and characterize LGT from complex microbial communities. We addressed this by developing, benchmarking, and experimentally validating a computational method (WAAFLE) to profile novel LGT events from assembled metagenomes. Applying WAAFLE to >2K human metagenomes from diverse body sites, we identified >100K putative high-confidence but previously uncharacterized LGT events (~2 per assembled microbial genome-equivalent). These events were enriched for mobile elements (as expected), as well as restriction-modification and transport functions typically associated with the destruction of foreign DNA. LGT frequency was quantifiably influenced by biogeography, the phylogenetic similarity of the involved taxa, and the ecological abundance of the donor taxon. These forces manifest as LGT networks in which hub species abundant in a community type donate unequally with their close phylogenetic neighbors. Our findings suggest that LGT may be a more ubiquitous process in the human microbiome than previously described. The open-source WAAFLE implementation, documentation, and data from this work are available at http://huttenhower.sph.harvard.edu/waafle.

Scientific document development standards for the society of cardiovascular computed tomography (SCCT): A statement from the SCCT Guidelines Committee.

The Society of Cardiovascular Computed Tomography (SCCT) is an international community of physicians, scientists and technologists advocating for research, education, and clinical excellence in the use of cardiovascular computed tomography (CCT). SCCT members are committed to improving health outcomes through effective use of CCT. The SCCT routinely authors, endorses, and jointly collaborates on scientific documents that reflect the best available evidence and expert consensus supported in practice of CCT. This paper outlines SCCT's methodology for developing scientific documents. It was formulated by members of the SCCT Guidelines Committee and approved by the SCCT Board of Directors.

Inter-software and inter-scan variability in measurement of epicardial adipose tissue: a three-way comparison of a research-specific, a freeware and a coronary application software platform.

OBJECTIVES: Epicardial adipose tissue (EAT) is a proposed marker of cardiovascular risk; however, clinical application may be limited by variability in post-processing software platforms. We assessed inter-vendor agreement of EAT volume (EATv) and attenuation on both contrast-enhanced (CE) and non-contrast CT (NCT) using a standard coronary CT reporting software (Vitrea), an EAT research-specific software (QFAT) and a freeware imaging software (OsiriX). METHODS: Seventy-six consecutive patients undergoing simultaneous CE and NCT had complete volumetric EAT measurement. Between-software, within-software NCT vs. CE, and inter- and intra-observer agreement were evaluated with analysis by ANOVA (with post hoc adjustment), Bland-Altman with 95% levels of agreement (LoA) and intraclass correlation coefficient (ICC). RESULTS: Mean EATv (freeware 53 ± 31 mL vs. research 93 ± 43 mL vs. coronary 157 ± 64 mL) and attenuation (freeware - 72 ± 25 HU vs. research - 75 ± 3 HU vs. coronary - 61 ± 10 HU) were significantly different between all vendors (ANOVA p < 0.001). EATv was consistently higher in NCT vs. CE for all software packages, with most reproducibility found in research software (bias 26 mL, 95% LoA: 2 to 56 mL), compared to freeware (bias 11 mL 95% LoA: - 46 mL to 69 mL) and coronary software (bias 10 mL 95% LoA: - 127 to 147 mL). Research software had more comparable NCT vs. CE attenuation (- 75 vs. - 72 HU) compared to freeware (- 72 vs. - 57 HU) and coronary (- 61 vs. - 39 HU). Excellent inter-observer agreement was seen with research (ICC 0.98) compared to freeware (ICC 0.73) and coronary software (ICC 0.75) with narrow LoA on Bland-Altman analysis. CONCLUSION: There are significant inter-vendor differences in EAT assessment. Our study suggests that research-specific software has better agreement and reproducibility compared to freeware or coronary software platforms. KEY POINTS: • There are significant differences between EAT volume and attenuation values between software platforms, regardless of scan type. • Non-contrast scans routinely have higher mean EAT volume and attenuation; however, this finding is only consistently seen with research-specific software. • Of the three analyzed packages, research-specific software demonstrates the highest reproducibility, agreement, and reliability for both inter-scan and inter-observer agreement.

Reliability of radiologists' first impression when interpreting a screening mammogram.

Previous studies showed that radiologists can detect the gist of an abnormality in a mammogram based on a half-second image presentation through global processing of screening mammograms. This study investigated the intra- and inter-observer reliability of the radiologists' initial impressions about the abnormality (or "gist signal"). It also examined if a subset of radiologists produced more reliable and accurate gist signals. Thirty-nine radiologists provided their initial impressions on two separate occasions, viewing each mammogram for half a second each time. The intra-class correlation (ICC) values showed poor to moderate intra-reader reliability. Only 13 radiologists had an ICC of 0.6 or above, which is considered the minimum standard for reliability, and only three radiologists had an ICC exceeding 0.7. The median value for the weighted Cohen's Kappa was 0.478 (interquartile range = 0.419-0.555). The Mann-Whitney U-test showed that the "Gist Experts", defined as those who outperformed others, had significantly higher ICC values (p = 0.002) and weighted Cohen's Kappa scores (p = 0.026). However, even for these experts, the intra-radiologist agreements were not strong, as an ICC of at least 0.75 indicates good reliability and the signal from none of the readers reached this level of reliability as determined by ICC values. The inter-reader reliability of the gist signal was poor, with an ICC score of 0.31 (CI = 0.26-0.37). The Fleiss Kappa score of 0.106 (CI = 0.105-0.106), indicating only slight inter-reader agreement, confirms the findings from the ICC analysis. The intra- and inter-reader reliability analysis showed that the radiologists' initial impressions are not reliable signals. In particular, the absence of an abnormal gist does not reliably signal a normal case, so radiologists should keep searching. This highlights the importance of "discovery scanning," or coarse screening to detect potential targets before ending the visual search.

Peri-Coronary Adipose Tissue Is a Predictor of Stent Failure in Patients Undergoing Percutaneous Coronary Intervention.

PURPOSE: Coronary inflammation is postulated as a driver of atherosclerosis and dysfunctional arterial healing which may trigger stent failure. Pericoronary adipose tissue (PCAT) attenuation, detected on computer tomography coronary angiography (CTCA), is an emerging non-invasive marker of coronary inflammation. This propensity matched study assessed the utility of both lesion specific (PCATLesion) and standardized PCAT attenuation as assessed in the proximal RCA (PCATRCA) as a predictor of stent failure in patients undergoing elective percutaneous coronary intervention. This is the first study to our knowledge that assesses the association of PCAT with stent failure. METHODS: Patients undergoing CTCA assessment for coronary artery disease with subsequent stent insertion within 60 days and repeat coronary angiography for any clinical reason within 5 years were included in the study. Stent failure was defined as binary restenosis of >50 % on quantitative coronary angiography analysis or stent thrombosis. Both PCATLesion and PCATRCA was assessed utilizing semi-automated proprietary software on baseline CTCA. Patients with stent failure were propensity matched utilizing age, sex, cardiovascular risk factors and procedural characteristics. RESULTS: One hundred and fifty-one patients met inclusion criteria. Of these, 26 (17.2 %) had study-defined failure. A significant difference in PCATLesion attenuation between patients with and without failure was observed (-79.0 ± 12.6 vs. -85.9 ± 10.3HU, p = 0.035). There was no significant difference in PCATRCA attenuation between the two groups (-79.5 ± 10.1 vs -81.0 ± 12.3HU, p = 0.50). Univariate regression analysis showed PCATLesion attenuation was independently associated with stent failure (OR 1.06, 95 % CI 1.01-1.12, P = 0.035). CONCLUSIONS: Patients with stent failure exhibit significantly increased PCATLesion attenuation at baseline. These data suggest that baseline plaque inflammation may be an important driver for coronary stent failure.