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Integrated Assessment Models (IAMs) were initially developed to inform decision processes relating to climate change and then extended to other natural resource management decisions, including issues around integrated water resources management. Despite their intention to support long-term planning decisions, model uptake has generally been limited, partly due to their unfulfilled capability to manage deep uncertainty issues and consider multiple perspectives and trade-offs involved when solving problems of interest. In recent years, more emphasis has been put on the need for existing models to evolve to be used for exploratory modeling and analysis to capture and manage deep uncertainty. Building new models is a solution but may face challenges in terms of feasibility and the conservation of knowledge assets. Integration and augmentation of existing models is another solution, but little guidance exists on how to realize model augmentation that addresses deep uncertainty and how to use such models for exploratory modeling purposes. To provide guidance on how to augment existing models to support decisions under deep uncertainty we present an approach for identifying minimum information requirements (MIRs) that consists of three steps: (1) invoking a decision support framework [here, Dynamic Adaptive Policy Pathways (DAPP)] to synthesize information requirements, (2) characterizing misalignment with an existing integrated model, (3) designing adjustable solutions that align model output with immediate information needs. We employ the Basin Futures model to set up the approach and illustrate outcomes in terms of its effectiveness to augment models for exploratory purposes, as well as its potential for supporting the design of adaptative pathways. The results are illustrated in the context of the Brahmani River Basin (BRB) system and discussed in terms of generalization and transferability of the approach to identifying MIRs. Future work directions include the refinement and evaluation of the approach in a planning context and testing of the approach with other models.

IntroductionHemibiotrophic Phytophthora are a group of agriculturally and ecologically important pathogenic oomycetes causing severe decline in plant growth and fitness. The lifestyle of these pathogens consists of an initial biotrophic phase followed by a switch to a necrotrophic phase in the latter stages of infection. Between these two phases is the biotrophic to necrotrophic switch (BNS) phase, the timing and controls of which are not well understood particularly in Phytophthora spp. where host resistance has a purely quantitative genetic basis.MethodsTo investigate this we sequenced and annotated the genome of Phytophthora medicaginis, causal agent of root rot and substantial yield losses to Fabaceae hosts. We analyzed the transcriptome of P. medicaginis across three phases of colonization of a susceptible chickpea host (Cicer arietinum) and performed co-regulatory analysis to identify putative small secreted protein (SSP) effectors that influence timing of the BNS in a quantitative pathosystem.ResultsThe genome of P. medicaginis is ~78 Mb, comparable to P. fragariae and P. rubi which also cause root rot. Despite this, it encodes the second smallest number of RxLR (arginine-any amino acid-leucine-arginine) containing proteins of currently sequenced Phytophthora species. Only quantitative resistance is known in chickpea to P. medicaginis, however, we found that many RxLR, Crinkler (CRN), and Nep1-like protein (NLP) proteins and carbohydrate active enzymes (CAZymes) were regulated during infection. Characterization of one of these, Phytmed_10271, which encodes an RxLR effector demonstrates that it plays a role in the timing of the BNS phase and root cell death.DiscussionThese findings provide an important framework and resource for understanding the role of pathogenicity factors in purely quantitative Phytophthora pathosystems and their implications to the timing of the BNS phase.

The increasing use of endovascular aneurysm repair to treat abdominal aortic aneurysms has mandated solutions to the limitations of this operation, including the requirement for additional procedures. A 64-year-old man had presented with symptomatic thrombosis of the left iliac limb after endovascular aneurysm repair. We have reported the use of an innovative endovascular repair for our patient.

Objectives Informing research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.Design In the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.Setting UK stroke services.Participants 3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.Results Of those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.Conclusion It is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration number ISRCTN83290762; Post-results.

Introduction: The Structured Observational Test of Function (SOTOF; Laver and Powell, 1995) is a standardised occupational therapy assessment used to observe older people's performance of activities of daily living and identify underlying neurological deficits. The 2nd edition (Laver-Fawcett and Marrison, 2016) added a formalised dynamic assessment component that applies a graduated mediation protocol. Purpose: To explore the SOTOF's clinical utility from the perspective of occupational therapists working with older adults. Methods: A mixed methods survey design was utilised. A volunteer, convenience sample was obtained from an email circulated to the College of Occupational Therapists' specialist section for older people members and to therapists who had previously requested a copy of the SOTOF. Participants were emailed the SOTOF materials and following review completed an online survey comprising both closed and open questions. Ethical approval was obtained from York St John University. Results: Seven participants completed the survey (17% response rate); they worked in hospital (n=2), community (n=4) and care home (n=1) settings. Views on the ease of understanding, administration and time required were varied. The graduated mediation protocol was deemed useful and the SOTOF was considered as useful to inform intervention plans, clinical reasoning and decision making. Comments included: 'I found it very comprehensive and occupational focused' and 'in depth and ... easy to understand and administer'. Conclusion: The SOTOF (2nd edition) appears to be longer and more complex to administer than the original version. A training video and/or workshop would be beneficial for therapists learning to administer the assessment. [ABSTRACT FROM AUTHOR]

ABSTRACT A long-standing biological question is how evolution has shaped the genomic architecture of dikaryotic fungi. To answer this, high-quality genomic resources that enable haplotype comparisons are essential. Short-read genome assemblies for dikaryotic fungi are highly fragmented and lack haplotype-specific information due to the high heterozygosity and repeat content of these genomes. Here, we present a diploid-aware assembly of the wheat stripe rust fungus Puccinia striiformis f. sp. tritici based on long reads using the FALCON-Unzip assembler. Transcriptome sequencing data sets were used to infer high-quality gene models and identify virulence genes involved in plant infection referred to as effectors. This represents the most complete Puccinia striiformis f. sp. tritici genome assembly to date (83 Mb, 156 contigs, N50 of 1.5 Mb) and provides phased haplotype information for over 92% of the genome. Comparisons of the phase blocks revealed high interhaplotype diversity of over 6%. More than 25% of all genes lack a clear allelic counterpart. When we investigated genome features that potentially promote the rapid evolution of virulence, we found that candidate effector genes are spatially associated with conserved genes commonly found in basidiomycetes. Yet, candidate effectors that lack an allelic counterpart are more distant from conserved genes than allelic candidate effectors and are less likely to be evolutionarily conserved within the P. striiformis species complex and Pucciniales. In summary, this haplotype-phased assembly enabled us to discover novel genome features of a dikaryotic plant-pathogenic fungus previously hidden in collapsed and fragmented genome assemblies. IMPORTANCE Current representations of eukaryotic microbial genomes are haploid, hiding the genomic diversity intrinsic to diploid and polyploid life forms. This hidden diversity contributes to the organism’s evolutionary potential and ability to adapt to stress conditions. Yet, it is challenging to provide haplotype-specific information at a whole-genome level. Here, we take advantage of long-read DNA sequencing technology and a tailored-assembly algorithm to disentangle the two haploid genomes of a dikaryotic pathogenic wheat rust fungus. The two genomes display high levels of nucleotide and structural variations, which lead to allelic variation and the presence of genes lacking allelic counterparts. Nonallelic candidate effector genes, which likely encode important pathogenicity factors, display distinct genome localization patterns and are less likely to be evolutionary conserved than those which are present as allelic pairs. This genomic diversity may promote rapid host adaptation and/or be related to the age of the sequenced isolate since last meiosis.

The nitrogen-fixing cyanobacterium Nostoc is a commonly occurring terrestrial and aquatic cyanobacterium often found in symbiosis with a wide range of plant, algal, and fungal species. We investigated the diversity of cyanobacterial species occurring within the coralloid roots of different Macrozamia cycad species at diverse locations throughout Australia. In all, 74 coralloid root samples were processed and 56 endosymbiotic cyanobacteria were cultured. DNA was isolated from unialgal cultures and a segment of the 16S rRNA gene was amplified and sequenced. Microscopic analysis was performed on representative isolates. Twenty-two cyanobacterial species were identified, comprising mostly Nostoc spp. and a Calothrix sp. No correlation was observed between a cycad species and its resident cyanobiont species. The predominant cyanobacterium isolated from 18 root samples occurred over a diverse range of environmental conditions and within 14 different Macrozamia spp. Phylogenetic analysis indicated that endosymbionts were not restricted to previously described terrestrial species. An isolate clustering with Nostoc PCC7120, an aquatic strain, was identified. This is the first comprehensive study to identify the endosymbionts within a cycad genus using samples obtained from their natural habitats. These results indicate that there is negligible host specialization of cyanobacterial endosymbionts within the cycad genus Macrozamia in the wild.

Transthyretin cardiac amyloidosis (ATTR-CA) predominantly affects older adults with multiple chronic conditions, leading to significant physical, cognitive, and emotional challenges. New disease-modifying drugs are effective in early stages, prompting a shift toward comprehensive assessments, including functional capacity and quality of life. However, these assessments may not fully capture the complexity of older ATTR-CA patients, especially regarding frailty and mood disorders, which can influence symptom reporting. Thus, integrating comprehensive geriatric assessment tools into routine clinical practice may be crucial to detect early signs of frailty or functional impairment that could impact outcomes and mitigate futility and ageism in the decision-making process. This review highlights the importance of evaluating multimorbidity, disability, and frailty in older patients with ATTR-CA to optimize management strategies., Competing Interests: Dr Maurer is supported by grant from 10.13039/100000002NIH R01HL139671 and R01AG081582-01; grants and personal fees from Alnylam, Pfizer, Eidos, Prothena, and Ionis; and personal fees from AstraZeneca, Akcea, Intellia, and Novo Nordisk. Dr Fontana is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/18/21/33447). Dr Gillmore has received consultancy fees from Alnylam, AstraZeneca, ATTRalus, Bridgebio, Ionis, Intellia, Lycia, and Pfizer. Dr Goyal is supported by 10.13039/100000049National Institute on Aging grants K76AG064428, R21AG077092, R01AG085420, and R24AG064025; and has received consulting fees from Agepha Pharma, Akros Pharma, Axon therapies, and Sensorum Health. Dr Fine has received research support and consulting honoraria from Pfizer, Alnylam, Ionis, AstraZeneca, Novo Nordisk, Sanofi/Genzyme, and Eidos/BridgeBio. Dr Grogan has received research support and or advisory board/consulting fees from Alnylam, BridgeBio/Eidos, Janssen, Pfizer, AstraZeneca, Novo, and Nordisk (all funds paid to employer, no personal compensation). Dr Marfella is supported by Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale (Scientific research programs of high national interest) # 2020LM8WNW. Dr Limongelli has received research support and or advisory board/consulting fees from Alnylam, Pfizer, and AstraZeneca. Dr Longhi is supported by the Italian Ministry of Health, RC-2022-2773270 project. Dr Cuddy is supported by grant support from 10.13039/100000002NIH 1K23HL166686-01 and 10.13039/100000967AHA 23CDA857664; and has received personal fees from Pfizer, Bridgebio, Ionis, AstraZeneca, and Novo Nordisk. Dr Masri is supported by Research Grants from 10.13039/100004319Pfizer, Ionis, Attralus, and 10.13039/100014941Cytokinetics; and has received fees from Cytokinetics, BMS, Eidos, Pfizer, Ionis, Lexicon, Attralus, Haya, BioMarin, Alexion, and Tenaya. Dr Olivotto is supported by grants for “Respect,” “StratifyHF,” and “SmashHCM” and has received grants from 10.13039/100015340Bayer, 10.13039/100016619MyoKardia, Inc, which is a wholly owned subsidiary of Bristol Myers Squibb, Sanofi Genzyme, and Shire, which is now part of Takeda; personal fees from Bayer, Sanofi Genzyme, and Shire/Takeda; and payments as a consultant from MyoKardia, Inc. Dr Perfetto has received honoraria for advisory board participation from Pfizer, Alnylam, and Akcea. Dr Ungar is supported by Piano Nazionale di Ripresa e Resilienza grants. Dr Cappelli has received consultant fees from Pfizer, Alnylam, AstraZeneca, BridgeBio, Daiichi Sankyo, and Novo Nordisk. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Abstract: This review summarizes the evaluation for underlying rheumatic conditions in patients presenting with acute pericarditis, treatment considerations for specific rheumatic conditions, and the role of imaging in diagnosis and monitoring. Pericarditis may be one of the initial presentations of a rheumatic disease or identified in a patient with known rheumatic disease. There is also growing evidence for using anti-inflammatory and immunosuppressive agents for treating recurrent pericarditis, which can overlap with the treatment of rheumatic diseases., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Herpes simplex virus-1 (HSV-1) establishes a latent infection in peripheral neurons and periodically reactivates to permit transmission, which can result in clinical manifestations. Viral transactivators required for lytic infection are largely absent during latent infection, and therefore, HSV-1 relies on the co-option of neuronal host signaling pathways to initiate its gene expression. The activation of the neuronal c-Jun N-terminal kinase (JNK) cell stress pathway is central to initiating biphasic reactivation in response to multiple stimuli. However, how host factors work with JNK to stimulate the initial wave of gene expression (known as Phase I) or the progression to full Phase II reactivation remains unclear. Here, we found that c-Jun, the primary target downstream of neuronal JNK cell stress signaling, functions during reactivation but not during the JNK-mediated initiation of Phase I gene expression. Instead, c-Jun was required to transition from Phase I to full HSV-1 reactivation and was detected in viral replication compartments of reactivating neurons. Interestingly, we also identified a role for both c-Jun and enhanced neuronal stress during initial neuronal infection in promoting a more reactivation-competent form of HSV-1 latency. Therefore, c-Jun functions at multiple stages during the HSV latent infection of neurons to promote reactivation but not during the initial JNK-dependent Phase I. Importantly, by demonstrating that initial infection conditions can contribute to later reactivation abilities, this study highlights the potential for latently infected neurons to maintain a molecular scar of previous exposure to neuronal stressors.IMPORTANCEThe molecular mechanisms that regulate the reactivation of herpes simplex virus-1 (HSV-1) from latent infection are unknown. The host transcription and pioneer factor c-Jun is the main target of the JNK cell stress pathway that is known to be important in exit of HSV from latency. Surprisingly, we found that c-Jun does not act with JNK during exit from latency but instead promotes the transition to full reactivation. Moreover, c-Jun and enhanced neuronal stress during initial neuronal infection promoted a more reactivation-competent form of HSV-1 latency. c-Jun, therefore, functions at multiple stages during HSV-1 latent infection of neurons to promote reactivation. Importantly, this study contributes to a growing body of evidence that de novo HSV-1 infection conditions can modulate latent infection and impact future reactivation events, raising important questions on the clinical impact of stress during initial HSV-1 acquisition on future reactivation events and consequences., Competing Interests: The authors declare no conflict of interest.

Aim: The purpose of this study was to determine the inter- and intra-observer variability in 99m technetium-pyrophosphate ( 99m Tc-PYP) scan interpretation for diagnosis of transthyretin cardiac amyloidosis (ATTR)., Methods and Results: Our study cohort comprised 100 consecutive subjects referred for  99m Tc-PYP imaging based on clinical suspicion of ATTR cardiac amyloidosis. Myocardial  99m Tc-PYP uptake was assessed by both visual (comparison of myocardial to rib uptake) and semi-quantitative (heart-to-contralateral lung uptake ratio, H:CL) methods. Twenty scans were analyzed twice, at least 48 hours apart, by each of two independent observers. Patients with visual scores of ≥ 2 on planar imaging as well as myocardial uptake on SPECT/CT were classified as ATTR positive. Diagnosis of ATTR by visual  99m Tc-PYP grade was perfectly reproducible [concordance: positive and negative scans 100% (53/53 and 47/47, respectively). Both inter- and intra-observer correlations for H:CL ratio (r 2  = 0.90, 0.99 (Observer 1) and 0.98 (Observer 2), respectively) and repeatability values on Bland-Altman plots were excellent. The coefficient of variation (%) for Observers 1 and 2 was 3.21 (2.14 to 4.29) and 7.49 (4.95 to 10.09), respectively. In addition, there was 100% concordance in positive and negative scan interpretation by visual grading between novice CV imagers (< 3 years' experience) and an experienced CV imager (10 years' experience)., Conclusions: This study showed excellent inter-observer reproducibility and intra-observer repeatability of  99m Tc-PYP visual scan interpretation and H:CL ratio for diagnosis of cardiac ATTR amyloidosis. Cardiac ATTR amyloidosis can be diagnosed reliably using 99m Tc-PYP SPECT/CT by novice and experienced CV imagers., (© 2020. American Society of Nuclear Cardiology.)

Background: An upcoming national mandate will require consultation of appropriate use criteria (AUC) through a clinical decision support mechanism (CDSM) for advanced imaging. We aimed to evaluate our current ability to ascertain test appropriateness., Methods: We prospectively collected data on 288 consecutive stress tests and coronary computed tomography angiography studies for medical inpatients. Study appropriateness was determined independently by two physicians using the 2013 Multimodality AUC., Results: The median age of the study population was 66 years [interquartile range (IQR) 56, 75], 40.8% were female, and 52.8% had a history of coronary artery disease. Review of the electronic health record (EHR) alone was sufficient to deem appropriateness for 87.2% of cases. The most common reason it was insufficient was inability to determine if the patient could exercise (59.5%). After reviewing the EHR and pilot CDSM data together, appropriateness could be determined for 95.8% of the cases. The most common reason appropriateness could not be determined was that the exam indication was not addressed by an AUC criterion (83.3%)., Conclusion: In preparing for the mandate, it will be important for future CDSM to obtain information on the patient's ability to exercise and for future AUC to include additional indications that are not currently addressed., (© 2019. American Society of Nuclear Cardiology.)

Wetland water level fluctuations often influence benthic macroinvertebrate communities through changes in water quality, substrate, and macrophytes and, hence, affect the structure and function of aquatic ecosystems. However, there is lack of understanding on how water level fluctuations affect the structure and composition of benthic macroinvertebrates in subtropical shallow wetlands in Nepal. Here, we assessed the changes in benthic macroinvertebrate community composition in response to water level fluctuations and identified indicator taxa sensitive to such fluctuations. A study was conducted over 4 seasons covering one annual cycle of water level fluctuation in 4 wetlands of Koshi Tappu Wildlife Reserve, Nepal. The study revealed that benthic macroinvertebrate composition significantly differed across water levels. Dissimilarities in macroinvertebrate community composition were mainly attributed by families Atyidae, Dytiscidae, Baetidae, Planorbidae, Chironomidae, Bithyniidae, Sphaeriidae, and Thiaridae. Taxon specific richness, densities, and biomass varied across the water levels while no difference was documented for overall family richness, density, and biomass. Ephemeroptera and Trichoptera richness decreased when water levels were low while Coleoptera and Diptera richness increased. Medium water level supported high benthic macroinvertebrate diversity. Indicator taxa analysis identified Coleoptera: Hydrophilidae and Dytiscidae, Hemiptera: Pleidae, Diptera: Muscidae and Mollusca: Sphaeriidae, Viviparidae, and Thiaridae, as indicators of low water level. Similarly, Coleoptera: Scirtidae, Hemiptera: Micronectidae and Oligochaeta: Tubificidae as indicators of medium water level, and Trichoptera: Polycentropodidae and Ephemeroptera: Caenidae as indicators of high water level. Redundancy analysis identified water level as one of the most influencing factors in benthic macroinvertebrate community variation. Considering the significant response of benthic macroinvertebrates to water level fluctuations, they are important as ecological indicators in research aimed at developing environmental flow frameworks. Indicator species are likely to be a vital tool in environmental impact assessment and monitoring in relation to hydrological development. The outcomes of this research have important implications to conservation and management of wetlands to preserve the valuable ecosystem functions provided by wetlands., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The primary aims of this study were to determine the correlation between absolute quantitative 99m Tc-pyrophosphate metrics and traditional measures of cardiac amyloid burden and to measure the intraobserver repeatability of the quantitative metrics. Methods: We studied 72 patients who underwent 99m Tc-pyrophosphate SPECT/CT using a novel general-purpose cadmium-zinc-telluride-based SPECT/CT system. The clinical standard for these studies is visual grading (with grades of 0, 1, 2, and 3 indicating myocardial uptake absent, less than rib uptake, equal to rib uptake, or more than rib uptake, respectively). A visual grade of 2 or more was considered positive. For 72 patients, SUV max , SUV mean , cardiac amyloid activity (CAA; i.e., SUV mean × left ventricular [LV] volume), and percentage injected dose (%ID) were calculated, and visual grading was performed. The correlation was determined between the 4 quantitative metrics or visual grades and the LV mass index (LVMI) (indexed to body surface area on echocardiography, 67 patients). For a subset of 11 patients, the correlation was determined between the visual or quantitative metrics and the extracellular volume (ECV) on cardiac MRI. Normal linear regression was used to compare the standardized association of each of the 4 quantitative metrics with LVMI, as a surrogate for amyloid burden. Receiver-operating-characteristic curve analysis was used to determine the diagnostic accuracy of quantitative metrics, using visual grading as the reference standard. The intraobserver repeatability of generating quantitative metrics was also determined. Results: All 4 quantitative metrics were highly accurate, with an area under the receiver-operating-characteristic curve of more than 0.96 for diagnosis of transthyretin cardiac amyloidosis. SUV max , SUV mean , CAA, %ID, and visual grade were moderately positively correlated with LVMI ( r = 0.485 for %ID) and strongly positively correlated, albeit in a small cohort, with ECV ( r = 0.873, SUV max ). Intraobserver repeatability was excellent, with less than a 2% coefficient of variation for SUV max , %ID, and CAA and 3.8% for SUV mean All 4 quantitative metrics had a standardized effect of more than 0.324 on LVMI; the largest standardized effect was 0.485, for %ID. Conclusion: In this first (to our knowledge) study of 99m Tc-pyrophosphate cardiac imaging using a novel cadmium-zinc-telluride SPECT/CT scanner, SUV max , SUV mean , CAA, and %ID measured by absolute quantitation of 99m Tc-pyrophosphate were moderately correlated with LVMI and strongly correlated, albeit in a small cohort, with ECV. The intraobserver repeatability of generating the quantitative metrics was excellent., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Systemic amyloidosis is a heterogeneous group of disorders where misfolded proteins deposit in the various organs as nonbranching fibrils with a β-pleated-sheet structure called amyloid. Extensive extracellular deposition of these amyloid fibrils eventually leads to organ dysfunction. Involvement of the heart, termed as cardiac amyloidosis, leads to heart failure if left untreated and carries high morbidity and mortality. Current interest in cardiac amyloidosis is growing rapidly thanks to the recent development of effective targeted treatment options, driving the need for better and earlier detection of the condition, which is largely underdiagnosed and far commoner than recognized. Timely diagnosis of cardiac amyloidosis is challenging, but is poised to improve with emergence of newer noninvasive imaging techniques, potentially obviating the need for endomyocardial biopsy in some patients and providing prognostic information. With recent advances in the therapeutic options for cardiac amyloidosis, an area of immense interest is the adoption of imaging as biomarkers for longitudinal assessment of disease progression and treatment response. In this article, we provide an overview of cardiac amyloidosis, discuss the role of imaging modalities in cardiac amyloidosis, and explore future directions for imaging in cardiac amyloidosis., Competing Interests: Conflicts of Interest RHF has received consulting fees from Ionis Pharmaceuticals and Alnylam Pharmaceuticals and research funding from GlaxoSmithKline. SD has received consulting fees from Pfizer, GE Health Care, and AAA. YMK and SC report no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The clinical diagnosis of pulmonary involvement in individuals with systemic AL amyloidosis remains challenging. [ 18 F]florbetapir imaging has previously identified AL amyloid deposits in the heart and extra-cardiac organs. The aim of this study is to determine quantitative [ 18 F]florbetapir pulmonary kinetics to identify pulmonary involvement in individuals with systemic AL amyloidosis., Methods: We prospectively enrolled 58 subjects with biopsy-proven AL amyloidosis and 9 control subjects (5 without amyloidosis and 4 with ATTR cardiac amyloidosis). Pulmonary [ 18 F]florbetapir uptake was evaluated visually and quantified as distribution volume of specific binding (Vs) derived from compartmental analysis and simpler semiquantitative metrics of maximum standardized uptake values (SUVmax), retention index (RI), and target-to-blood ratio (TBR)., Results: On visual analysis, pulmonary tracer uptake was absent in most AL subjects (40/58, 69%); 12% (7/58) of AL subjects demonstrated intense bilateral homogeneous tracer uptake. In this group, compared to the control group, Vs (median Vs 30-fold higher, 9.79 vs. 0.26, p < 0.001), TBR (median TBR 12.0 vs. 1.71, p < 0.001), and RI (median RI 0.310 vs. 0.033, p < 0.001) were substantially higher. Notably, the AL group without visually apparent pulmonary [ 18 F]florbetapir uptake also demonstrated a > 3-fold higher Vs compared to the control group (median 0.99 vs. 0.26, p < 0.001). Vs was independently related to left ventricular SUVmax, a marker of cardiac AL deposition, but not to ejection fraction, a marker of cardiac dysfunction. Also, intense [ 18 F]florbetapir lung uptake was not related to [ 11 C]acetate lung uptake, suggesting that intense [ 18 F]florbetapir lung uptake represents AL amyloidosis rather than heart failure., Conclusions: [ 18 F]florbetapir PET/CT offers the potential to noninvasively identify pulmonary AL amyloidosis, and its clinical relevance warrants further study.

Cardiac amyloidosis (CA) is one of the most rapidly progressive forms of heart disease, with a median survival from diagnosis, if untreated, ranging from <6 months for light chain amyloidosis to 3 to 5 years for transthyretin amyloidosis. Early diagnosis and accurate typing of CA are necessary for optimal management of these patients. Emerging novel disease modifying therapies increase the urgency to diagnose CA at an early stage and identify patients who may benefit from these life-saving therapies. The goal of this review is to provide a practical approach to echocardiography, cardiac magnetic resonance, and radionuclide imaging in patients with known or suspected CA., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Diagnosing myocarditis is challenged by nonspecific clinical signs and symptoms and low accuracy of endomyocardial biopsy. Cardiac magnetic resonance imaging (CMR) provides both cardiac anatomy and tissue characterization in this setting, but the prognostic value of this method as a primary assessment tool in patients with suspected myocarditis remains limited., Objectives: This study sought to determine cardiac event-free survival of a consecutive cohort with suspected myocarditis with regard to CMR findings., Methods: Six hundred seventy patients with suspected myocarditis underwent CMR including late gadolinium enhancement (LGE) parameters between 2002 and 2015 and were included and followed. We performed multivariable model for major adverse cardiovascular events (MACE) and determined the continuous net reclassification improvement by LGE markers., Results: At a median follow-up of 4.7 years (interquartile range [IQR]: 2.3 to 7.3 years), 98 patients experienced a MACE. Two hundred ninety-four (44%) patients showed LGE presence, which was associated with a more than doubling risk of MACE (hazard ratio [HR]: 2.22; 95% confidence interval [CI]: 1.47 to 3.35; p < 0.001). Annualized MACE rates were 4.8% and 2.1% corresponding to LGE presence and absence, respectively (p < 0.001). In the multivariable model, LGE presence maintained significant association with MACE (HR: 1.72; 95% CI: 1.08 to 2.76; p = 0.023). The computed continuous net reclassification improvement was 0.39 (95% CI: 0.10 to 0.67) when LGE presence was added to the multivariable model for MACE. Regarding location and pattern, septal and midwall LGE showed strongest associations with MACE (HR: 2.55; 95% CI: 1.77 to 3.83 and HR: 2.39; 95% CI: 1.54 to 3.69, respectively; both p < 0.001). A patchy distribution portended to a near 3-fold increased hazard to MACE (HR: 2.93; 95% CI: 1.79 to 4.80; p < 0.001). LGE extent (per 10% increase) corresponded to a 79% increase in risk of MACE (HR: 1.79; 95% CI: 1.25 to 2.57; p = 0.002). A normal CMR study corresponded to low annual MACE and death rates of 0.8% and 0.3%, respectively., Conclusions: CMR tissue characterization provides effective risk stratification in patients with suspected myocarditis., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)