Are trait-associated genes clustered together in a gene network?

Genome-wide association studies (GWAS) have provided an abundance of information about the genetic variants and their loci that are associated to complex traits and diseases. However, due to linkage disequilibrium (LD) and noncoding regions of loci, it remains a challenge to pinpoint the causal genes. Gene network-based approaches, paired with network diffusion methods, have been proposed to prioritize causal genes and to boost statistical power in GWAS based on the assumption that trait-associated genes are clustered in a gene network. Due to the difficulty in mapping trait-associated variants to genes in GWAS, this assumption has never been directly or rigorously tested empirically. On the other hand, whole exome sequencing (WES) data focuses on the protein-coding regions, directly identifying trait-associated genes. In this study, we tested the assumption by leveraging the recently available exome-based association statistics from the UK Biobank WES data along with two types of networks. We found that almost all trait-associated genes were significantly more proximal to each other than randomly selected genes within both networks. These results support the assumption that trait-associated genes are clustered in gene networks, which can be further leveraged to boost the power of GWAS such as by introducing less stringent p value thresholds.

Low- or standard-dose edoxaban versus antiplatelet therapy for leaflet thrombus and cerebral thromboembolism after TAVR: A prespecified analysis of randomized ADAPT-TAVR trial.

BACKGROUND: The risks of leaflet thrombosis and the associated cerebral thromboembolism are unknown according to different anticoagulation dosing after transcatheter aortic valve replacement (TAVR). The aim was to evaluate the incidence of leaflet thrombosis and cerebral thromboembolism between low-dose (30 mg) or standard-dose (60 mg) edoxaban and dual antiplatelet therapy (DAPT) after TAVR. METHODS: In this prespecified subgroup analysis of the ADAPT-TAVR trial, the primary endpoint was the incidence of leaflet thrombosis on 4-dimensional computed tomography at 6-months. Key secondary endpoints were new cerebral lesions on brain magnetic resonance imaging and neurological and neurocognitive dysfunction. RESULTS: Of 229 patients enrolled in this study, 118 patients were DAPT group and 111 were edoxaban group (43 [39.1%] 60 mg vs 68 [61.3%] 30 mg). There was a significantly lower incidence of leaflet thrombosis in the standard-dose edoxaban group than in the DAPT group (2.4% vs 18.3%; odds ratio [OR] 0.11; 95% confidence interval [CI], 0.01-0.55; P = .03). However, no significant difference was observed between low-dose edoxaban and DAPT (15.0% vs 18.3%; OR 0.79; 95% CI, 0.32-1.81; P = .58). Irrespective of different antithrombotic regiments, the percentages of patients with new cerebral lesions on brain MRI and worsening neurological or neurocognitive function were not significantly different. CONCLUSIONS: In patients without an indication for anticoagulation after TAVR, the incidence of leaflet thrombosis was significantly lower with standard-dose edoxaban but not with low-dose edoxaban, as compared with DAPT. However, this differential effect of edoxaban on leaflet thrombosis was not associated with a reduction of new cerebral thromboembolism and neurological dysfunction.

Imaging Very Late Antigen-4 on MOLT4 Leukemia Tumors with Cysteine Site-Specific 89Zr-Labeled Natalizumab Immuno-Positron Emission Tomography.

Very late antigen-4 (VLA4; CD49d) is a promising immune therapy target in treatment-resistant leukemia and multiple myeloma, and there is growing interest in repurposing the humanized monoclonal antibody (Ab), natalizumab, for this purpose. Positron emission tomography with radiolabeled Abs (immuno-PET) could facilitate this effort by providing information on natalizumab's in vivo pharmacokinetic and target delivery properties. In this study, we labeled natalizumab with 89Zr specifically on sulfhydryl moieties via maleimide-deferoxamine conjugation. High VLA4-expressing MOLT4 human T cell acute lymphoblastic leukemia cells showed specific 89Zr-natalizumab binding that was markedly blocked by excess Ab. In nude mice bearing MOLT4 tumors, 89Zr-natalizumab PET showed high-contrast tumor uptake at 7 days postinjection. Biodistribution studies confirmed that uptake was the highest in MOLT4 tumors (2.22 ± 0.41%ID/g) and the liver (2.33 ± 0.76%ID/g), followed by the spleen (1.51 ± 0.42%ID/g), while blood activity was lower at 1.12 ± 0.21%ID/g. VLA4-specific targeting in vivo was confirmed by a 58.1% suppression of tumor uptake (0.93 ± 0.15%ID/g) when excess Ab was injected 1 h earlier. In cultured MOLT4 cells, short-term 3 day exposure to the proteasome inhibitor bortezomib (BTZ) did not affect the α4 integrin level, but BTZ-resistant cells that survived the treatment showed increased α4 integrin expression. When the effects of BTZ treatment were tested in mice, there was no change of the α4 integrin level or 89Zr-natalizumab uptake in MOLT4 leukemia tumors, which underscores the complexity of tumor VLA4 regulation in vivo. In conclusion, 89Zr-natalizumab PET may be useful for noninvasive monitoring of tumor VLA4 and may assist in a more rational application of Ab-based therapies for hematologic malignancies.

Predictors of Late Adverse Events in Patients with Surgically Treated Type I Aortic Dissection.

OBJECTIVE: Residual aortic dissection (AD) following DeBakey type I AD repair is associated with a high rate of adverse events that need additional intervention or surgery. This study aimed to identify clinical and early post-operative computed tomography (CT) imaging factors associated with adverse events in patients with type I AD after ascending aorta replacement. METHODS: This single centre, retrospective cohort study included consecutive patients with type I AD who underwent ascending aorta replacement from January 2011 to December 2017 and post-operative CT within three months. The primary outcome was AD related adverse events, defined as AD related death and re-operation due to aortic aneurysm or impending rupture. The location and size of the primary intimal tears, aortic diameter, and false lumen status were evaluated. Regression analyses were performed to identify factors associated with AD related adverse events. A decision tree model was used to classify patients as high or low risk. RESULTS: Of 103 participants (55.43 ± 13.94 years; 49.5% male), 24 (23.3%) experienced AD related adverse events. In multivariable Cox regression analysis, connective tissue disease (hazard ratio [HR] 15.33; p < .001), maximum aortic diameter ≥ 40 mm (HR 4.90; p < .001), and multiple (three or more) intimal tears (HR 7.12; p < .001) were associated with AD related adverse events. The three year cumulative survival free from AD related events was lower in the high risk group with aortic diameter ≥ 40 mm and multiple intimal tears (41.7% vs. 90.9%; p < .001). CONCLUSION: Early post-operative CT findings indicating a maximum aortic diameter ≥ 40 mm and multiple intimal tears may predict a higher risk of adverse events. These findings suggest the need for careful monitoring and more vigilant management approaches in these cases.

Tailored Planning of Surgical Myectomy in Obstructive Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disease characterized by abnormal thickening of the myocardium caused by myocardial disarray and interstitial fibrosis. HCM is associated with sudden cardiac-related events, such as ventricular fibrillation, tachycardia, and syncope. Moreover, left ventricular or midcavity obstruction due to the thickened myocardium can result in severe heart failure and mortality in patients with HCM. Surgical myectomy is a standard treatment option for patients with symptomatic obstructive HCM; however, it is a complex procedure that requires careful planning and execution to avoid complications, such as residual flow obstruction, persistent obliteration of the left ventricular cavity in systole, or iatrogenic ventricular septal defects. Therefore, a thorough understanding of the mechanics of HCM and precise evaluation of the location and extent of the hypertrophic myocardium to be removed are crucial for preoperative planning. Multiphase cardiac CT postprocessing is important for preoperative evaluation and planning of surgical myectomy in patients with HCM. In this review, the authors highlight use of multiphase cardiac CT with step-by-step postprocessing methods to simulate successful surgical myectomy. The transaortic surgeon's view on end-diastolic phase images accurately represents the surgical field. Moreover, myocardial segmentation can be used to generate volume-rendered images and three-dimensional printing. CT evaluation can also assist in identifying concurrent abnormalities, such as mitral valve or papillary muscle abnormalities. In addition to CT, other imaging modalities for preoperative evaluation of HCM and postmyectomy evaluation methods are presented. ©RSNA, 2023 Test Your Knowledge questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

Edoxaban Versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism After TAVR: The ADAPT-TAVR Randomized Clinical Trial.

BACKGROUND: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear. METHODS: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement. RESULTS: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%]; P=0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function. CONCLUSIONS: In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research. REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT03284827.

Impact of new-onset arrhythmia on cardiac reverse remodeling following transcatheter aortic valve replacement: computed tomography-derived left ventricular and atrial strains.

OBJECTIVE: Patients who undergo transcatheter aortic valve replacement (TAVR) are at risk for new-onset arrhythmia (NOA) that may require permanent pacemaker (PPM) implantation, resulting in decreased cardiac function. We aimed to investigate the factors that are associated with NOA after TAVR and to compare pre- and post-TAVR cardiac functions between patients with and without NOA using CT-derived strain analyses. METHODS: We included consecutive patients who underwent pre- and post-TAVR cardiac CT scans six months after TAVR. New-onset left bundle branch block, atrioventricular block, and atrial fibrillation/flutter lasting over 30 days after the procedure and/or the need for PPM diagnosed within 1 year after TAVR were regarded as NOA. Implant depth and left heart function and strains were analyzed using multi-phase CT images and compared between patients with and without NOA. RESULTS: Of 211 patients (41.7% men; median 81 years), 52 (24.6%) presented with NOA after TAVR, and 24 (11.4%) implanted PPM. Implant depth was significantly deeper in the NOA group than in the non-NOA group (- 6.7 ± 2.4 vs. - 5.6 ± 2.6 mm; p = 0.009). Left ventricular global longitudinal strain (LV GLS) and left atrial (LA) reservoir strain were significantly improved only in the non-NOA group (LV GLS, - 15.5 ± 4.0 to - 17.3 ± 2.9%; p < 0.001; LA reservoir strain, 22.3 ± 8.9 to 26.5 ± 7.6%; p < 0.001). The mean percent change of the LV GLS and LA reservoir strains was evident in the non-NOA group (p = 0.019 and p = 0.035, respectively). CONCLUSIONS: A quarter of patients presented with NOA after TAVR. Deep implant depth on post-TAVR CT scans was associated with NOA. Patients with NOA after TAVR had impaired LV reserve remodeling assessed by CT-derived strains. CLINICAL RELEVANCE STATEMENT: New-onset arrhythmia (NOA) following transcatheter aortic valve replacement (TAVR) impairs cardiac reverse remodeling. CT-derived strain analysis reveals that patients with NOA do not show improvement in left heart function and strains, highlighting the importance of managing NOA for optimal outcomes. KEY POINTS: • New-onset arrhythmia following transcatheter aortic valve replacement (TAVR) is a concern that interferes with cardiac reverse remodeling. • Comparison of pre-and post-TAVR CT-derived left heart strain provides insight into the impaired cardiac reverse remodeling in patients with new-onset arrhythmia following TAVR. • The expected reverse remodeling was not observed in patients with new-onset arrhythmia following TAVR, given that CT-derived left heart function and strains did not improve.

Angiographic patterns and temporal changes of arterial lesions in Behcet's disease.

BACKGROUND: Behcet's disease (BD) can entail vascular involvement in various forms including aneurysm. We evaluated the angiographic patterns and changes in arterial lesions over time in BD patients with arterial involvement. METHODS: We reviewed the medical records of BD patients diagnosed with arterial lesions between 1995 and 2018. Angiographic patterns were categorized as stenosis, occlusion, dilatation, or aneurysm. Patients were divided according to symptom duration (<5, 5-10, >10 years). Cox proportional-hazards model was used to evaluate the risk factors for vascular progression. RESULTS: 47 BD patients had arterial involvement in the following patterns: aneurysm (n = 31), stenosis (n = 17), dilatation (n = 13), and occlusion (n = 8). Aneurysm (70.8%) was the most common pattern in 24 patients with short (<5 years) symptom duration. Stenosis was more common (50.0%) in 12 patients with longer symptom durations (>10 years). In 23 patients with follow-up imaging (median, 5.7 years), eight (34.8%) developed 11 new lesions: stenosis (n = 5), dilatation (n = 1), and aneurysm (n = 5). One stenotic lesion progressed to occlusion, and two dilated lesions progressed to aneurysms. Lower extremity involvement and methotrexate use were associated with arterial progression, with hazard ratios of 5.716 (p = 0.029) and 0.101 (p = 0.049), respectively. CONCLUSION: In BD patients with arterial involvement, aneurysm was the most common pattern in earlier stages of BD, while stenosis was more common in later stages of BD. Methotrexate use was associated with lower risk of arterial lesion progression.

Synthesis and characterization of 64Cu- and Cy5.5-labeled tetraiodothyroacetic acid derivatives for tumor angiogenesis imaging.

It was previously reported that tetraiodothyroacetic acid (tetrac) inhibits angiogenesis by binding to the cell surface receptor for thyroid hormone on integrin αVß3. Therefore, we synthesized and evaluated two 64Cu-labeled tetrac derivatives and a Cy5.5-labeled tetrac derivative for tumor angiogenesis imaging. Tetrac was structurally modified to conjugate with 1,4,7,10-tetraazacyclododecane-N,N',N″,N″'-tetraacetic acid (DOTA) via its hydroxy or carboxylic acid end, and the resulting DOTA-conjugated tetrac derivatives were then labeled with 64Cu. Tetrac was also conjugated with Cy5.5 via its carboxylic acid end. All three tetrac derivatives (1-3) exhibited greater inhibitory activity than tetrac against endothelial cell tube formation. The U87MG cell binding of [64Cu]2 showed a time-dependent increase over 24 h and it was inhibited by 38% at 4 h in the presence of tetrac, indicating specificity of [64Cu]2 to the thyroid hormone receptor site on integrin αVß3. Positron emission tomography (PET) images of U87MG tumor-bearing mice injected with [64Cu]1 and [64Cu]2 revealed that high radioactivity accumulated in the tumors, and that the tumor uptake and tumor-to-nontarget uptake ratio were higher in small tumors than in large tumors. In addition, the Cy5.5-labeled tetrac derivative (3) displayed a strong near-infrared (NIR) signal in the tumors. Taken together, these results suggest that these ligands hold promise as imaging agents for visualization of tumor angiogenesis.

RadioGraphics Update: Radiographic and CT Features of Viral Pneumonia.

Editor's Note.-Articles in the RadioGraphics Update section provide current knowledge to supplement or update information found in full-length articles previously published in RadioGraphics. Authors of the previously published article provide a brief synopsis that emphasizes important new information such as technological advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes. Articles in this section are published solely online and are linked to the original article.

Clinical and Radiologic Characteristics of Human Metapneumovirus Infections in Adults, South Korea.

Clinical features of human metapneumovirus (HMPV) infection have not been well documented for adults. We investigated clinical and radiologic features of HMPV infection in 849 adults in a tertiary hospital in South Korea. We classified patients into groups on the basis of underlying diseases: immunocompetent patients, solid tumor patients, solid organ transplantation recipients, hematopoietic stem cell transplant recipients, hematologic malignancy patients, and patients receiving long-term steroid treatment. Of 849 HMPV-infected patients, 756 had community-acquired infections, 579 had pneumonia, and 203 had infections with other pathogens. Mortality rates were highest in hematopoietic stem cell transplantation recipients (22% at 30 days). Older age, current smoking, and underlying disease were associated with HMPV pneumonia. Body mass index and an immunocompromised state were associated with 30-day mortality rates in HMPV-infected patients. Bronchial wall thickening, ground-glass opacity, and ill-defined centrilobular nodules were common computed tomography findings for HMPV pneumonia. Macronodules and consolidation were observed in <50% of patients.

Genomic profiles of lung cancer associated with idiopathic pulmonary fibrosis.

Little is known about the pathogenesis or molecular profiles of idiopathic pulmonary fibrosis-associated lung cancer (IPF-LC). This study was performed to investigate the genomic profiles of IPF-LC and to explore the possibility of defining potential therapeutic targets in IPF-LC. We assessed genomic profiles of IPF-LC by using targeted exome sequencing (OncoPanel version 2) in 35 matched tumour/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling was performed with GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively. Copy number analysis was conducted with CNVkit, with focal events determined by Genomic Identification of Significant Targets in Cancer 2.0, and pathway analysis (KEGG) with DAVID. Germline mutations in TERT (rs2736100, n = 33) and CDKN1A (rs2395655, n = 27) associated with idiopathic pulmonary fibrosis risk were detected in most samples. A total of 410 somatic mutations were identified, with an average of 11.7 per tumour, including 69 synonymous, 177 missense, 17 nonsense, 1 nonstop and 11 splice-site mutations, and 135 small coding indels. Spectra of the somatic mutations revealed predominant C > T transitions despite an extensive smoking history in most patients, suggesting a potential association between APOBEC-related mutagenesis and the development of IPF-LC. TP53 (22/35, 62.9%) and BRAF (6/35, 17.1%) were found to be significantly mutated in IPF-LC. Recurrent focal amplifications in three chromosomal loci (3q26.33, 7q31.2, and 12q14.3) and 9p21.3 deletion were identified, and genes associated with the JAK-STAT signalling pathway were significantly amplified in IPF-LC (P = 0.012). This study demonstrates that IPF-LC is genetically characterized by the presence of somatic mutations reflecting a variety of environmental exposures on the background of specific germline mutations, and is associated with potentially targetable alterations such as BRAF mutations. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Non-Small Cell Lung Cancer with Resistance to EGFR-TKI Therapy: CT Characteristics of T790M Mutation-positive Cancer.

Purpose To evaluate the clinical and CT characteristics of T790M mutation-positive non-small cell lung cancer (NSCLC) after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy failure. Materials and Methods A retrospective study of 304 patients with NSCLC who underwent rebiopsy after first-line EGFR-TKI therapy was conducted. Rebiopsy methods included CT- or fluoroscopy-guided lung biopsies (n = 105), endobronchial US- or bronchofibroscopy-guided biopsies (n = 66), pleural fluid analysis (n = 47), other solid organ biopsies (n = 43), US-guided axillary or supraclavicular lymph node biopsies (n = 31), and cerebrospinal fluid analysis (n = 12). CT findings at the initial diagnosis and rebiopsy were analyzed. Progression-free survival, the duration from the start of TKI therapy to rebiopsy, and survival were calculated. Results At rebiopsy, 144 (47.4%) patients were T790M mutation positive. The percentages of T790M mutation-positive NSCLCs were similar in 106 patients with rebiopsy of the lungs (53 [50%] of 106) and in 77 patients with rebiopsy of the primary lung lesions (36 [47%] of 77). T790M mutation positivity was associated with peripheral tumors (odds ratio [OR], 2.6; P = .01), pleural tag (OR, 5.0; P < .001), and air bronchogram (OR, 4.0; P = .006) at CT after TKI failure. The duration from the start of TKI therapy to rebiopsy was longer in T790M mutation-positive than in T790M mutation-negative patients (20.5 vs 13.6 months; P < .001). Cumulative survival from the time of rebiopsy to the last follow-up was significantly longer in patients with T790M mutation-positive lung cancers (P = .014). However, median survival time after rebiopsy was not statistically different between patients with and those without T790M mutation. Conclusion Peripheral tumor location with vascular convergence, the presence of a pleural tag, and air bronchogram of lung lesions at CT at the time of rebiopsy were significantly associated with T790M mutation in patients with non-small cell lung cancer after first-line epidermal growth factor receptor-tyrosine kinase inhibitor therapy failure. © RSNA, 2018 Online supplemental material is available for this article.

Coronary CT angiography characteristics of OCT-defined thin-cap fibroatheroma: a section-to-section comparison study.

OBJECTIVES: To evaluate whether plaque characteristics as assessed by coronary computed tomography angiography (CCTA) were associated with the presence of a thin-cap fibroatheroma (TCFA)-a precursor of plaque rupture-defined by optical coherence tomography (OCT) in a section-to-section-level comparison. METHODS: From 28 symptomatic patients, 31 coronary lesions were evaluated on 727 cross-sections co-registered by both CCTA and OCT. CCTA plaque characteristics included low attenuation plaque (LAP, <30 HU), napkin ring sign (NRS), positive remodelling (PR, remodelling index ≥1.10), and spotty calcification and plaque area and plaque burden. By OCT, presence of TCFA, lumen area and arc of lipid were determined. RESULTS: OCT revealed a TCFA in 69 (9.4%) sections from 19 (61.2 %) lesions. In per-section analysis, OCT-TCFA showed higher frequency of CCTA-detected LAP (58.0% vs. 18.5%), NRS (31.9% vs. 8.8%) and PR (68.1% vs. 48.0%) and greater plaque burden (70.6% vs. 61.9%) as compared to sections without OCT-TCFA (all p < 0.05). In multivariable analysis, LAP (odds ratio [OR] 4.05, p < 0.001) and NRS (OR 2.47, p = 0.005) were associated with OCT-TCFA. CCTA-measured lumen area correlated well with OCT-measured lumen area (R = 0.859, limits of agreement -0.5 ± 3.7 mm2). CONCLUSIONS: LAP and NRS in CCTA were associated with the presence of OCT-defined TCFA in a section-to-section comparison. KEY POINTS: • CT-defined LAP and NRS were associated with OCT-defined TCFA • OCT-TCFA showed higher frequency of LAP, NRS, PR and greater plaque burden • Non-calcified plaque area was correlated with OCT-measured lipid arc.

Radiographic and CT Features of Viral Pneumonia.

Viruses are the most common causes of respiratory infection. The imaging findings of viral pneumonia are diverse and overlap with those of other nonviral infectious and inflammatory conditions. However, identification of the underlying viral pathogens may not always be easy. There are a number of indicators for identifying viral pathogens on the basis of imaging patterns, which are associated with the pathogenesis of viral infections. Viruses in the same viral family share a similar pathogenesis of pneumonia, and the imaging patterns have distinguishable characteristics. Although not all cases manifest with typical patterns, most typical imaging patterns of viral pneumonia can be classified according to viral families. Although a definite diagnosis cannot be achieved on the basis of imaging features alone, recognition of viral pneumonia patterns may aid in differentiating viral pathogens, thus reducing the use of antibiotics. Recently, new viruses associated with recent outbreaks including human metapneumovirus, severe acute respiratory syndrome coronavirus, and Middle East respiratory syndrome coronavirus have been discovered. The imaging findings of these emerging pathogens have been described in a few recent studies. This review focuses on the radiographic and computed tomographic patterns of viral pneumonia caused by different pathogens, including new pathogens. Clinical characteristics that could affect imaging, such as patient age and immune status, seasonal variation and community outbreaks, and pathogenesis, are also discussed. The first goal of this review is to indicate that there are imaging features that should raise the possibility of viral infections. Second, to help radiologists differentiate viral infections, viruses in the same viridae that have similar pathogenesis and can have similar imaging characteristics are shown. By considering both the clinical and radiologic characteristics, radiologists can suggest the diagnosis of viral pneumonia. ©RSNA, 2018.

The suppressive effect of the three-herb extract mixture on vascular and liver inflammation in atherogenic diet with high fructose-fed mice.

CONTEXT: Cynanchum wilfordii (Maximowicz) Hemsley (Apocynaceae), Arctium lappa L. var. rubescens Frivald (Asteraceae) and Dioscorea opposite Thunb (Dioscoreaceae) root extracts have been widely used as an alternative for intervening obesity. OBJECTIVES: The synergistic effect of three-herb mixture of C. wilfordii, A. lappa and D. opposita was determined on aortic and liver inflammatory responses. MATERIALS AND METHODS: CWE, ALE and DOE were prepared from the root of C. wilfordii, A. lappa and D. opposite by 70% ethanol extraction, respectively. CADE was prepared using a powder mixture of 2 CWE:1 ALE:1 DOE. C57BL/6 mice were fed an atherogenic diet combined with 10% fructose (ATHFR) in the presence of 200 mg/kg/day CWE, ALE, DOE or CADE for 8 weeks (each group, n = 6). Biochemical profiles, protein expression of vascular cell adhesion molecule-1 (VCAM-1) on the aorta and liver were determined. RESULTS: CADE could significantly suppress the protein expression of VCAM-1 in both the aorta and liver (80% reduction) compared to ATHFR-fed mice. Impairment of liver function was significantly ameliorated by CADE supplement, as determined by GOT (60% reduction) and GPT (51% reduction) levels. CONCLUSIONS: CADE should be considered when developing medications to suppress the vascular and liver inflammatory responses for individuals who are either non-responsive or resistant to lipid-lowering drugs.

Intravascular ultrasound-derived morphological predictors of myocardial ischemia assessed by stress myocardial perfusion computed tomography.

BACKGROUND: Although ischemia-guided revascularization improves clinical outcomes, morphological determinants of clinically relevant myocardial ischemia have not been studied. To identify intravascular ultrasound (IVUS)-derived anatomical parameters for predicting myocardial perfusion defect and its extent. METHODS: A total of 103 patients (88 stable and 15 unstable angina) with 153 lesions (angiographic diameter stenosis of 30-80%) underwent stress myocardial perfusion computed tomography (CT) and IVUS pre-procedure. The volume of CT perfusion defect and %CT perfusion defect in the target vessel territories were measured. RESULTS: The CT perfusion defect was seen in 76 (50%) lesions. The independent determinants for the presence of CT perfusion defect were IVUS-minimal lumen area (MLA) (adjusted OR = 0.56, 95% CI = 0.38-0.82), plaque burden (adjusted OR = 1.07, 95% CI = 1.02-1.11) and involvement of left main or left anterior descending artery (adjusted OR = 4.13, 95% CI = 1.75-9.78, all P < 0.05). The CT perfusion defect was predicted by IVUS-MLA <2.28mm2 (sensitivity 74%, specificity 82%) and plaque burden >77% (sensitivity 79%, specificity 78%) as thresholds. The independent determinants for the volume of CT perfusion defect were the involvement of left main or left anterior descending artery (ß = 16.43, standard errors = 4.387, P = 0.020) and a greater plaque burden (ß = 0.56, standard errors = 0.163, P = 0.026). CONCLUSIONS: IVUS-derived morphological parameters were useful to predict the presence of CT perfusion defect and the size of myocardial ischemia that were primarily determined by lesion severity and subtended myocardial territory. © 2016 Wiley Periodicals, Inc.

Humidifier disinfectant-associated lung injury in adults: Prognostic factors in predicting short-term outcome.

OBJECTIVES: To identify clinical and radiologic findings that affect disease severity and short-term prognosis of humidifier disinfectant-associated lung injury in adults and to compare computed tomography (CT) findings between the patients with and without death or lung transplantation. METHODS: Fifty-nine adults (mean age, 34 years; M/F = 12:47) were enrolled in this retrospective study. Medical records and prospective surveillance data were used to assess clinical and radiological factors associated with a poor clinical outcome. Multivariate generalized estimating equation models were used to analyse serial CT findings. Overall cumulative major events including lung transplantation and mortality were assessed using the Kaplan-Meier method. RESULTS: Almost half needed ICU admission (47.5 %) and 17 died (28.8 %). Young age, peripartum and low O2 saturation were factors associated with ICU admission. On initial chest radiographs, consolidation (P < 0.001) and ground-glass opacity (P = 0.01) were significantly noted in patients who required ICU admission. CT findings including consolidation (odds ratio (OR), 1.02), pneumomediastinum (OR, 1.66) and pulmonary interstitial emphysema (OR, 1.61) were the risk factors for lung transplantation and mortality. CONCLUSION: Clinical and radiologic findings are related to the risks of lung transplantation and mortality of humidifier disinfectant-associated lung injury. Consolidation, pneumomediastinum and pulmonary interstitial emphysema were short-term prognostic CT findings. KEY POINTS: • Young age, peripartum and low O 2 saturation were associated with ICU admission. • Consolidation, pneumomediastinum and pulmonary interstitial emphysema were short-term prognostic CT findings. • Consolidation and ground-glass opacity disappeared within 3 months and replaced by centrilobular nodules. • Radiologic findings are related to the outcome of humidifier disinfectant-associated lung injury.

Lung Cancer in Patients With Tuberculous Fibrothorax and Empyema: Computed Tomography and 18F-Fluorodeoxyglucose Positron Emission Tomography Findings.

OBJECTIVE: The aim of this study was to describe the characteristics of lung cancers in patients with tuberculous fibrothorax or empyema. METHODS: We retrospectively evaluated 138 consecutive patients with a diagnosis of lung cancer combined with fibrothorax (n = 127) or empyema (n = 11) from January 2005 to May 2015. All patients underwent computed tomography, and 105 underwent F-fluorodeoxyglucose positron emission tomography. Clinical, pathologic, and computed tomography characteristics and maximum standardized uptake values on positron emission tomography of 76 cancers ipsilateral to the fibrothorax or empyema (group 1) were compared with those of 62 contralateral cancers (group 2). RESULTS: The median age at diagnosis of patients was 70 years, with a male-to-female ratio of 8.9:1. The most common type was squamous cell carcinoma (41.3%) followed by adenocarcinoma (39.1%). Most were in the peripheral lung (70.3%), and half abutted the pleura. The median maximum standardized uptake value was 8.9. Tumors in group 1 were larger (median, 48.5 vs 42.8 mm, P = 0.036) and more advanced (T3 or T4) (P = 0.014) than those in group 2. CONCLUSIONS: Lung cancers ipsilateral to tuberculous fibrothorax or empyema presented larger and advanced T stages, and the diagnosis could be delayed. The most common type cancer was squamous cell carcinoma.

Catabolism of (64)Cu and Cy5.5-labeled human serum albumin in a tumor xenograft model.

Human serum albumin (HSA), the most abundant protein in blood plasma, has been used as a drug carrier for the last few decades. Residualizingly radiolabeled serum albumin has been reported to be avidly taken up by tumors of sarcoma-bearing mice and to most likely undergo lysosomal degradation. In this study, we prepared (64)Cu-1,4,7,10-tetraazacyclododecane-N,N',N″,N'″-tetraacetic acid (DOTA) and Cy5.5-conjugated HSA (dual probe), and evaluated its tumor uptake and catabolism. Two dual probes were prepared using different DOTA conjugation sites of HSA (one via Lys residues and the other via the Cys residue). (64)Cu-DOTA-Lys-HSA-Cy5.5 (dual probe-Lys) exhibited higher uptake by RR1022 sarcoma cells in vitro than (64)Cu-DOTA-Cys-HSA-Cy5.5 (dual probe-Cys). In RR1022 tumor-bearing mice, the two dual probes showed a similar level of tumor uptake, but uptake of dual probe-Lys was reduced in the liver and spleen compared to dual probe-Cys, probably because of the presence of a higher number of DOTA molecules in the former. At 24 and 48 h after injection, dual probe-Lys was intact or partially degraded in blood, liver, kidney, and tumor samples, but (64)Cu-DOTA-Lys was observed in the urine using radioactivity detection. Similarly, Cy5.5-Lys was observed in the urine using fluorescence detection. These results indicate that dual probe-Lys may be useful for predicting the catabolic fate of drug-HSA conjugates.