Systemic reserve dysfunction and contrast-associated acute kidney injury following percutaneous coronary intervention.

BACKGROUND: Developing contrast-associated acute kidney injury (CA-AKI) following percutaneous coronary intervention (PCI) is closely related to patient-related risk factors as well as contrast administration. The diagnostic and prognostic roles of neutrophil gelatinase-associated lipocalin (NGAL) in CA-AKI following PCI are not well established. METHODS: Consecutive patients undergoing PCI were enrolled prospectively. CA-AKI was defined as an increase in the serum creatinine level ≥0.3 mg/dL within 48 hours or ≥1.5 times the baseline within 7 days after PCI. Serum NGAL concentrations were determined immediately before and 6 hours after PCI. The participants were classified into four NGAL groups according to the pre- and post-PCI NGAL values at 75th percentile. RESULTS: CA-AKI occurred in 38 (6.4%) of 590 patients. With chronic kidney disease status (hazard ratio [HR] 1.63, 95% confidence interval [CI]: 1.06-2.52), NGAL groups defined by the combination of pre- and 6 h post-PCI values were independently associated with the occurrence of CA-AKI (HR 1.69, 95% CI: 1.16-2.45). All-cause mortality for 29-month follow-ups was different among NGAL groups (log-rank p<0.001). Pre-PCI NGAL levels significantly correlated with baseline cardiac, inflammatory, and renal markers. Although post-PCI NGAL levels increased in patients with larger contrast administration, contrast media made a relatively limited contribution to the development of CA-AKI. CONCLUSION: In patients undergoing PCI, the combination of pre- and post-PCI NGAL values may be a useful adjunct to current risk-stratification of CA-AKI and long-term mortality. CA-AKI is likely caused by systemic reserve deficiency rather than contrast administration itself.

Fast field echo resembling CT using restricted echo-spacing (FRACTURE) MR sequence can provide craniocervical region images comparable to a CT in dogs.

Magnetic resonance imaging (MRI) is essential for evaluating cerebellar compression in patients with craniocervical junction abnormalities (CJA). However, it is limited in depicting cortical bone because of its short T2 relaxation times, low proton density, and organized structure. Fast field echo resembling a computed tomography (CT) scan using restricted echo-spacing (FRACTURE) MRI, is a new technique that offers CT-like bone contrast without radiation. This study aimed to assess the feasibility of using FRACTURE MRI for craniocervical junction (CCJ) assessment compared with CT and conventional MRI, potentially reducing the need for multiple scans and radiation exposure, and simplifying procedures in veterinary medicine. CT and MRI of the CCJ were obtained from five healthy beagles. MRI was performed using three-dimensional (3D) T1-weighted, T2-weighted, proton density-weighted (PDW), single echo-FRACTURE (sFRACTURE), and multiple echo-FRACTURE (mFRACTURE) sequences. For qualitative assessment, cortical delineation, trabecular bone visibility, joint space visibility, vertebral canal definition, overall quality, and artifacts were evaluated for each sequence. The geometrical accuracy, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were quantified. Both sFRACTURE and CT images provided significantly higher scores for cortical delineation and trabecular bone visibility than conventional MRI. Joint space visibility and vertebral canal definition were similar to those observed on CT images, regardless of the MR sequence. In the quantitative assessment, the distances measured on T2-weighted images differed significantly from those measured on CT. There were no significant differences between the distances taken using T1-weighted, PD-weighted, sFRACTURE, mFRACTURE and those taken using CT. T1-weighted and sFRACTURE had a higher SNR for trabecular bone than CT. The CNR between the cortical bone and muscle was high on CT and FRACTURE images. However, the CNR between the cortical and trabecular bones was low in mFRACTURE. Similar to CT, FRACTURE sequences showed higher cortical delineation and trabecular bone visibility than T2-weighted, T1-weighted, and PDW CCJ sequences. In particular, sFRACTURE provided a high signal-to-noise ratio (SNR) of the trabecular bone and a high CNR between the cortical bone and muscle and between the cortical and trabecular bones. FRACTURE sequences can complement conventional MR sequences for bone assessment of the CCJ in dogs.

Radiological features of Stafne mandibular bone cavity in panoramic image and cone beam computed tomography.

BACKGROUND: Stafne mandibular bone cavity (SMBC) is an asymptomatic radiolucent lesion observed in the mandible on X-ray images, with well-defined borders. This lesion does not require treatment, and size changes are very rare. The purpose of this article is to summarize the radiological and clinical features of SMBC, aiming to prevent misinterpretation of this benign lesion as other pathologies and aid in differential diagnosis within the field of dental practice. METHODS: A total of 32 patients who visited our hospital and were radiologically diagnosed with SMBC based on cone-beam computed tomography (CBCT) and panoramic images between 2005 and 2021 were included in this study. Among them, surgical intervention was performed in one case. Gender and age distribution of the patients, radiographic location and size of the lesion, relationship with the mandibular canal in CBCT, presence of cortical bone erosion in the mandibular lingual area in panoramic images, and the amount of residual cortical bone on the affected side in CBCT were investigated. RESULT: Patients were 26 men (81.3%) and 6 women, with a mean age of 54.3 years. The average horizontal and vertical length was 16.6 mm and 10.6 mm. Out of a total of 32 cases, 29 cases were found in the posterior region of the mandibular body, while 3 cases were in the angle of the mandible. Lesions located below the mandibular canal were observed in 29 cases, while lesions involving the mandibular canal were present in 3 cases. Erosion of the mandibular lingual cortical bone was observed in 11 cases (34.4%), while 21 cases (65.6%) showed no erosion on panoramic images. Among the total of 14 cases (43.8%) where the cortical bone on the affected side was invaded, the average residual cortical bone thickness was 1.1 mm. CONCLUSION: SMBC is a benign lesion primarily found in the mandibular angle and posterior body of the mandible. In most cases, treatment is not necessary, and differentiation from other lesions can be achieved by understanding its clinical characteristics and features on panoramic radiographs and CBCT.

Controlling the Chameleonic Behavior and Membrane Permeability of Cyclosporine Derivatives via Backbone and Side Chain Modifications.

Some macrocycles exhibit enhanced membrane permeability through conformational switching in different environmental polarities, a trait known as chameleonic behavior. In this study, we demonstrate specific backbone and side chain modifications that can control chameleonic behavior and passive membrane permeability using a cyclosporin O (CsO) scaffold. To quantify chameleonic behavior, we used a ratio of the population of the closed conformation obtained in polar solvent and nonpolar solvent for each CsO derivative. We found that ß-hydroxylation at position 1 (1 and 3) can encode chameleonicity and improve permeability. However, the conformational stabilization induced by adding an additional transannular H-bond (2 and 5) leads to a much slower rate of membrane permeation. Our CsO scaffold provides a platform for the systematic study of the relationship among conformation, membrane permeability, solubility, and protein binding. This knowledge contributes to the discovery of potent beyond the rule of five (bRo5) macrocycles capable of targeting undruggable targets.

Single-slab 3D double inversion recovery for magnetic resonance brain imaging in clinically healthy dogs.

Introduction: In veterinary medicine, magnetic resonance imaging (MRI) is widely utilized for brain imaging. But the complex structures of brain tissues can give rise to artifacts such as partial volume averaging in conventional sequences. To address this issue, several studies about double inversion recovery (DIR) sequences have been conducted in human medicine. However, published clinical studies about brain MRI using DIR sequences in dogs are currently lacking. The purpose of this study was to evaluate the magnetic resonance features of single-slab 3D DIR sequences in the normal canine brain. Methods: Five healthy Beagle dogs were examined and the following pulse sequences were acquired for each: (1) spin-echo T2-weighted (T2W), (2) fluid attenuated inversion recovery (FLAIR), (3) gray matter (GM) selective, and (4) white matter (WM) selective single-slab 3D DIR sequence. For qualitative analysis, the distinction between gray and white matter of the cerebral cortex, presence and severity of the image artifacts were assessed for each pulse sequence. In addition, reconstructed images of single-slab 3D DIR sequences were qualitatively evaluated. For quantitative analysis, contrast ratios (CRs), signal-to-noise ratios (SNRs), and contrast-to-noise ratios (CNRs) of the GM, WM and cerebrospinal fluid (CSF) were measured for each pulse sequence. Results and Discussion: GM selective 3D DIR was superior to T2W and FLAIR in delineating the boundaries between GM and WM in the overall brain area. Whereas WM selective 3D DIR provided better gray-white matter distinction of the cerebral cortex than T2W and FLAIR at the level of the medulla oblongata, where T2W and FLAIR images exhibited severe partial volume averaging artifacts. In general, the 3D DIR images demonstrated fewer artifacts compared to other sequences, and the reconstructed sagittal and dorsal images of these sequences maintained same spatial resolution as the original transverse images without any image degradation. Both gray and white matter selective 3D DIR sequences effectively suppressed unwanted signals, thereby providing high contrast between gray and white matter. Findings from this study could serve as a foundation for further studies on DIR sequences for the evaluation of brain diseases in dogs.

Radiographic findings of cardiopulmonary structures can predict hypertrophic cardiomyopathy and congestive heart failure in cats.

OBJECTIVE: This study aimed to find the radiographic characteristics for the detection of hypertrophic cardiomyopathy (HCM) and congestive heart failure (CHF) in cats. ANIMALS: Healthy cats (n = 35) and HCM cats with (21) and without (22) CHF. METHODS: On radiography, the cardiac size using vertebral heart score, left atrium enlargement (LAE), and dilation of the pulmonary vessels were assessed. The sensitivity and specificity of the radiographic characteristics regarding LAE were evaluated with the echocardiographic left atrium to aortic root ratio as a reference. RESULTS: In HCM cats, cardiomegaly, LAE, and dilation of the caudal pulmonary artery were found compared with those in healthy cats. The LAE could be predicted using the elevation of the carina with 94.12% specificity but 17.5% sensitivity. When CHF developed, LAE and dilation of the caudal pulmonary vein (PV) were significantly different compared with those in HCM cats without CHF. The distal side of the summated shadow made by the right caudal PV with the ninth rib in HCM cats with CHF was significantly larger than that in HCM cats without CHF and a cut-off value of 5.35 mm was drawn with 75% sensitivity and 100% specificity. CLINICAL RELEVANCE: Although there was an overlapping of radiographic findings between healthy and HCM cats, radiographic assessment of LAE can be useful for predicting HCM and the distal side of the summated shadow made by the right caudal PV with the ninth rib can predict CHF in HCM cats.

Application of endoscopic ultrasound to the descending colon and rectum in normal dogs.

Endoscopic ultrasound (EUS) is a medical procedure in which endoscopy is combined with ultrasonography (US) to compensate for problems associated with the transabdominal US such as large penetration depths, presence of intestinal gas, and acoustic shadowing. This prospective, method comparison, pilot study was performed to assess the feasibility of applying EUS in the colorectal region and to describe the typical EUS features of the descending colon and rectum in healthy dogs. Transabdominal US and EUS with or without the hydrosonography were applied to the descending colon and rectum in 10 clinically healthy Beagle dogs and wall thickness, visibility of the wall layers, and conspicuity of the mucosal and serosal surfaces of the intestinal wall were assessed. Endoscopic ultrasound enabled circumferential evaluation of the colorectal wall and provided better visibility of the wall layers and conspicuity of the mucosal and serosal surfaces without degradation of the image, even in the far-field portion of the colorectal wall, compared to US. Moreover, EUS provided the adequate image quality of the rectum, which was difficult to evaluate with US due to deep scan depth and acoustic shadowing by the pelvis. Meanwhile, the application of hydrosonography to EUS deteriorated the visibility of the wall layers and conspicuity of the intestinal wall. The results of this study demonstrate the feasibility of EUS to assess the colorectal region and its potential application for the evaluation of rectal masses or intrapelvic lesions that are inaccessible by the transabdominal US in dogs.

Contrast-enhanced ultrasonography for evaluation of the blood perfusion of sciatic nerves in healthy dogs.

Blood supply to the peripheral nerves is essential for fulfilling their structural and functional requirements. This prospective, experimental, exploratory study aimed to assess the feasibility of contrast-enhanced ultrasonography (CEUS) for evaluating blood perfusion of the sciatic nerve in normal dogs. Contrast-enhanced ultrasonography examinations were performed on the bilateral sciatic nerves after bolus injection of Sonazoid™ (0.015 mL/kg) in 12 healthy Beagles for 150 s. Then, qualitative assessment of the wash-in timing, degree and enhancement patterns, and quantitative measurement of the peak intensity and time to peak intensity were performed from the sciatic nerve. The results were compared to those obtained from the adductor muscle around the nerve and caudal gluteal artery. After contrast agent injection, the sciatic nerve was enhanced at approximately 13-14 s, immediately after wash-in of the caudal gluteal artery. The peak intensity of the sciatic nerve was significantly lower than that of the caudal gluteal artery and higher than that of the adductor muscle. The time to peak intensity was significantly slower than that of the caudal gluteal artery; but was not significantly different from that of the adductor muscle. There were no significant differences in the peak intensity and time to peak intensity between the left and right sciatic nerves. These results demonstrate the feasibility of CEUS to assess blood perfusion of the sciatic nerve in healthy dogs qualitatively and quantitatively. This result from healthy dogs could serve as a reference for further studies that evaluate the sciatic nerve under pathological conditions.

Association Between Bleeding and New Cancer Detection and the Prognosis in Patients With Myocardial Infarction.

Background Antithrombotic agents to treat patients with acute myocardial infarction can cause bleeding, which may reveal undiagnosed cancer. However, the relationship between bleeding and new cancer diagnosis and the prognostic impact is still unclear. Methods and Results We analyzed the new cancer diagnosis, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and all-cause death of 10 364 patients with acute myocardial infarction without a history of previous cancer in a multicenter acute myocardial infarction registry. During a median of 4.9 years, 1109 patients (10.7%) experienced Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and 338 patients (3.3%) were newly diagnosed with cancer. Bleeding Academic Research Consortium 2, 3, or 5 bleeding was associated with an increased risk of new cancer diagnosis (subdistribution hazard ratio [sHR] 3.29 [95% CI, 2.50-4.32]). In particular, there were robust associations between gastrointestinal bleeding and new gastrointestinal cancer diagnosis (sHR, 19.96 [95% CI, 11.30-29.94]) and between genitourinary bleeding and new genitourinary cancer diagnosis (sHR, 28.95 [95% CI, 14.69-57.07]). The risk of all-cause death was not lower in patients diagnosed with new gastrointestinal cancer after gastrointestinal bleeding (hazard ratio [HR], 4.05 [95% CI, 2.04-8.02]) and diagnosed with new genitourinary cancer after genitourinary bleeding (HR, 2.79 [95% CI, 0.81-9.56]) than in patients newly diagnosed with cancer without previous bleeding. Conclusions Clinically significant bleeding, especially gastrointestinal and genitourinary bleeding, in patients with AMI was associated with an increased risk of new cancer diagnoses. However, the bleeding preceding new cancer detection was not associated with better survival. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02385682 and NCT02806102.

Predictive and Prognostic Value of Serum Neutrophil Gelatinase-Associated Lipocalin for Contrast-Induced Acute Kidney Injury and Long-Term Clinical Outcomes after Percutaneous Coronary Intervention.

Neutrophil gelatinase-associated lipocalin (NGAL) has been proposed as an early marker for estimating the risk of contrast-induced acute kidney injury (CI-AKI). However, the predictive value of baseline serum NGAL levels for CI-AKI remains unclear. Serum NGAL was measured before percutaneous coronary intervention in 633 patients with coronary artery disease. The primary clinical endpoints were a composite of major adverse cardiac and cerebrovascular events (MACCEs; cardiac death, myocardial infarction, stroke, and any revascularization). The mean follow-up duration was 29.4 months. Ninety-eight (15.5%) patients developed CI-AKI. Compared with patients without CI-AKI, baseline serum NGAL was higher in patients with CI-AKI (149.6 ± 88.8 ng/mL vs. 138.0 ± 98.6 ng/mL, p = 0.0279), although serum creatinine and estimated glomerular filtration rate were not different between groups. Patients in the highest tertile of baseline serum NGAL showed a significantly higher rate of MACCEs (10.5% vs. 3.8%, p = 0.02). Using the first tertile as a reference, the adjusted hazard ratios for MACCEs in patients in the second and third tertiles of NGAL were 2.151 (confidence interval (CI) 0.82 to 5.59, p = 0.116) and 2.725 (CI 1.05 to 7.05, p = 0.039), respectively. Baseline serum NGAL is a reliable marker for predicting CI-AKI, and high serum NGAL levels are associated with a higher incidence rate of long term MACCEs.

Entry inhibition of hepatitis B virus using cyclosporin O derivatives with peptoid side chain incorporation.

Hepatitis B virus (HBV) infection is a serious worldwide health problem causing liver cirrhosis and hepatocellular carcinoma. The development of novel therapeutics targeting distinct steps of the HBV life cycle and combination therapy with approved drugs (i.e., nucleot(s)ides, interferon-α) are considered effective strategies for curing HBV. Among these strategies is the development of entry inhibitors that interfere with the host entry step of HBV to prevent viral infection and transmission. Herein, we generated a novel library of cyclosporin O (CsO) derivatives that incorporate peptoid side chains. Twenty-two CsO derivatives were evaluated for membrane permeability, cytotoxicity, and in vitro HBV entry inhibitory activity. The lead compound (i.e., compound 21) showed the greatest potency in the in vitro HBV entry inhibition assay (IC50 = 0.36 ± 0.01 µM) with minimal cytotoxicity. Our peptide-peptoid hybrid CsO scaffold can readily expand chemical diversity and is applicable for screening various targets requiring macrocyclic chemical entities.

Accuracy of genotype imputation based on reference population size and marker density in Hanwoo cattle.

Recently, the cattle genome sequence has been completed, followed by developing a commercial single nucleotide polymorphism (SNP) chip panel in the animal genome industry. In order to increase statistical power for detecting quantitative trait locus (QTL), a number of animals should be genotyped. However, a high-density chip for many animals would be increasing the genotyping cost. Therefore, statistical inference of genotype imputation (low-density chip to high-density) will be useful in the animal industry. The purpose of this study is to investigate the effect of the reference population size and marker density on the imputation accuracy and to suggest the appropriate number of reference population sets for the imputation in Hanwoo cattle. A total of 3,821 Hanwoo cattle were divided into reference and validation populations. The reference sets consisted of 50k (38,916) marker data and different population sizes (500, 1,000, 1,500, 2,000, and 3,600). The validation sets consisted of four validation sets (Total 889) and the different marker density (5k [5,000], 10k [10,000], and 15k [15,000]). The accuracy of imputation was calculated by direct comparison of the true genotype and the imputed genotype. In conclusion, when the lowest marker density (5k) was used in the validation set, according to the reference population size, the imputation accuracy was 0.793 to 0.929. On the other hand, when the highest marker density (15k), according to the reference population size, the imputation accuracy was 0.904 to 0.967. Moreover, the reference population size should be more than 1,000 to obtain at least 88% imputation accuracy in Hanwoo cattle.

High-Temperature-Tolerant Fungus and Oomycetes in Korea, Including Saksenaea longicolla sp. nov.

Global temperatures are steadily increasing, leading to significant changes in microbial diversity and ecology. In the present study, we isolated high-temperature-growing fungi and fungi-like group (Oomycota) strains from freshwater environments of Korea and identified them based on cultural, morphological, and multilocus phylogenetic analyses. As a result, we introduce Saksenaea (Fungi) isolates as a new species, Saksenaea longicolla sp. nov. and record Phytophthora chlamydospora and P. lagoariana (Oomycota) new to Korea. In the growth experiments, they exhibited high-temperature tolerance, which can grow at 35-40 °C but become inactive at 4 °C and below. This study confirms the presence of high-temperature-tolerant fungi and oomycetes in Korea and suggests that the Korean climate conditions are changing in favor of these species. This indicates that climate warming is altering microbial distributions in freshwater environments.

Interplay among Conformation, Intramolecular Hydrogen Bonds, and Chameleonicity in the Membrane Permeability and Cyclophilin A Binding of Macrocyclic Peptide Cyclosporin O Derivatives.

A macrocyclic peptide scaffold with well-established structure-property relationship is desirable for tackling undruggable targets. Here, we adopted a natural macrocycle, cyclosporin O (CsO) and its derivatives (CP1-3), and evaluated the impact of conformation on membrane permeability, cyclophilin A (CypA) binding, and the pharmacokinetic (PK) profile. In nonpolar media, CsO showed a similar conformation to cyclosporin A (CsA), a well-known chameleonic macrocycle, but less chameleonic behavior in a polar environment. The weak chameleonicity of CsO resulted in decreased membrane permeability; however, the more rigid conformation of CsO was not detrimental to its PK profile. CsO exhibited a higher plasma concentration than CsA, which resulted from minimal CypA binding and lower accumulation in red blood cells and moderate oral bioavailability (F = 12%). Our study aids understanding of CsO, a macrocyclic peptide that is less explored than CsA but with greater potential for diversity generation and rational design.

A Transparent Nanopatterned Chemiresistor: Visible-Light Plasmonic Sensor for Trace-Level NO2 Detection at Room Temperature.

The highly selective detection of trace gases using transparent sensors at room temperature remains challenging. Herein, transparent nanopatterned chemiresistors composed of aligned 1D Au-SnO2 nanofibers, which can detect toxic NO2 gas at room temperature under visible light illumination is reported. Ten straight Au-SnO2 nanofibers are patterned on a glass substrate with transparent electrodes assisted by direct-write, near-field electrospinning, whose extremely low coverage of sensing materials (≈0.3%) lead to the high transparency (≈93%) of the sensor. The sensor exhibits a highly selective, sensitive, and reproducible response to sub-ppm levels of NO2 , and its detection limit is as low as 6 ppb. The unique room-temperature NO2 sensing under visible light emanates from the localized surface plasmonic resonance effect of Au nanoparticles, thereby enabling the design of new transparent oxide-based gas sensors without external heaters or light sources. The patterning of nanofibers with extremely low coverage provides a general strategy to design diverse compositions of gas sensors, which can facilitate the development of a wide range of new applications in transparent electronics and smart windows wirelessly connected to the Internet of Things.

Relation of Proprotein Convertase Subtilisin/Kexin Type 9 to Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention.

The pharmacological inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to drastically affect low-density lipoprotein cholesterol levels and associated cardiovascular diseases. However, the potential effectiveness of PCSK9 serum levels as a biomarker for cardiovascular risk remains unclear. Serum PCSK9 levels in patients who underwent percutaneous coronary intervention (PCI) may predict long-term outcomes. PCSK9 levels were measured in 749 consecutive patients with coronary artery disease undergoing PCI. These patients were classified into 2 groups according to their serum levels of PCSK9. The primary end point was a composite of the major adverse cardiac events (MACE), including cardiac death, myocardial infarction, stroke, and any revascularization. The median PCSK9 level was 302.82 ng/ml. During a median follow-up of 28.4 months, a total of 38 (5.1%) MACE was recorded, and 50 (6.7%) patients died from any cause. Multivariate Cox regression analysis showed that compared with a lower serum PCSK9 level, a higher serum PCSK9 level was independently associated with a higher rate of MACE (adjusted hazard ratio 2.290, 95% confidence interval 1.040 to 5.045, p = 0.040) and all-cause death (adjusted hazard ratio 2.511, 95% confidence interval 1.220 to 5.167, p = 0.026). Results were consistent after propensity-score matching (MACE, adjusted HR 2.236, 95% CI 1.011-5.350, p = 0.047; all-cause death, adjusted HR 2.826, 95% CI 1.258-6.349, p = 0.012). Baseline serum PCSK9 levels were associated with long-term cardiovascular clinical outcomes and mortality during the long-term follow-up after PCI in patients with coronary artery disease.

Soluble neprilysin and long-term clinical outcomes in patients with coronary artery disease undergoing percutaneous coronary intervention: a retrospective cohort study.

BACKGROUND: Neprilysin has an essential role in regulating fluid balance and vascular resistance, and neprilysin inhibitors have shown beneficial effects in patients with heart failure. However, the potential predictive value of neprilysin levels as a biomarker for cardiovascular risk remains unclear. The aim of this study was to assess the prognostic value of soluble neprilysin (sNEP) levels in patients with ischemic heart disease. METHODS: Neprilysin levels were measured in 694 consecutive patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). These patients were classified into two groups according to their serum levels of neprilysin and categorized into the lower neprilysin group (n = 348) and the higher neprilysin group (n = 346). The primary clinical endpoint was all-cause mortality, and the secondary endpoint was a composite of major adverse cardiac events (MACE). RESULTS: The median sNEP level was 76.0 pg/ml. The median sNEP levels were higher in patients with left ventricular ejection fraction (LVEF) ≥40% (77.6 pg/ml, interquartile range 46.6-141.3) than in those with LVEF < 40% (70.0 pg/ml, interquartile range 47.1-100.6; P = 0.032). Among all patients, each clinical outcome and MACE did not differ significantly according to the groups divided into median, tertile, or quartile of sNEP levels during a median follow-up of 28.4 months. We did not find a significant relationship between sNEP levels and clinical outcomes in multivariate Cox regression analysis. Among patients with LVEF < 40%, an increased sNEP level was associated with a higher rate of all-cause death (adjusted hazard ratio 2.630, 95% confidence interval 1.049-6.595, P = 0.039). CONCLUSION: Serum sNEP levels are not associated with long-term mortality or cardiovascular outcomes after PCI in patients with CAD. In the LVEF < 40% group, increased sNEP levels may be associated with a higher risk of all-cause death.

Increased Cardiovascular Risk and All-cause Death in Patients with Behçet Disease: A Korean Nationwide Population-based Dynamic Cohort Study.

OBJECTIVE: Behçet disease (BD) is a chronic inflammatory multiorgan disease. An increased risk of cardiovascular disease (CVD) and heightened death rate with BD have been suggested, but to our knowledge, a nationwide large-scale study has not been conducted to date. This study aimed to determine the overall CV risk and death rate in patients with BD versus controls using the Korean National Health Insurance Service claim database. METHODS: Patients with BD (n = 5576) with no previous history of CVD were selected from 2010 to 2014. An age- and sex-matched control population of individuals without BD (n = 27,880) was randomly sampled at a ratio of 5:1. Both cohorts were followed for incident CVD or all-cause death until 2015. RESULTS: The risks of myocardial infarction (HR 1.72, 95% CI 1.01-2.73) and stroke (HR 1.65, 95% CI 1.09-2.50) were significantly higher in patients with BD than in controls. Patients with BD also had a significantly higher risk of all-cause death (HR 1.82, 95% CI 1.40-2.37) compared to controls. CONCLUSION: Korean patients with BD had a higher overall risk of CVD than did those without BD. Therefore, patients with BD must be carefully monitored for the potential development of CVD to ensure that appropriate early treatments are delivered.

Deep Convolutional Neural Network-based Software Improves Radiologist Detection of Malignant Lung Nodules on Chest Radiographs.

Background Multicenter studies are required to validate the added benefit of using deep convolutional neural network (DCNN) software for detecting malignant pulmonary nodules on chest radiographs. Purpose To compare the performance of radiologists in detecting malignant pulmonary nodules on chest radiographs when assisted by deep learning-based DCNN software with that of radiologists or DCNN software alone in a multicenter setting. Materials and Methods Investigators at four medical centers retrospectively identified 600 lung cancer-containing chest radiographs and 200 normal chest radiographs. Each radiograph with a lung cancer had at least one malignant nodule confirmed by CT and pathologic examination. Twelve radiologists from the four centers independently analyzed the chest radiographs and marked regions of interest. Commercially available deep learning-based computer-aided detection software separately trained, tested, and validated with 19 330 radiographs was used to find suspicious nodules. The radiologists then reviewed the images with the assistance of DCNN software. The sensitivity and number of false-positive findings per image of DCNN software, radiologists alone, and radiologists with the use of DCNN software were analyzed by using logistic regression and Poisson regression. Results The average sensitivity of radiologists improved (from 65.1% [1375 of 2112; 95% confidence interval {CI}: 62.0%, 68.1%] to 70.3% [1484 of 2112; 95% CI: 67.2%, 73.1%], P < .001) and the number of false-positive findings per radiograph declined (from 0.2 [488 of 2400; 95% CI: 0.18, 0.22] to 0.18 [422 of 2400; 95% CI: 0.16, 0.2], P < .001) when the radiologists re-reviewed radiographs with the DCNN software. For the 12 radiologists in this study, 104 of 2400 radiographs were positively changed (from false-negative to true-positive or from false-positive to true-negative) using the DCNN, while 56 of 2400 radiographs were changed negatively. Conclusion Radiologists had better performance with deep convolutional network software for the detection of malignant pulmonary nodules on chest radiographs than without. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Jacobson in this issue.

Prognosis and Predictors of Mortality in Patients Suffering Myocardial Infarction With Non-Obstructive Coronary Arteries.

Background Myocardial infarction with nonobstructive coronary arteries ( MINOCA ) is a heterogeneous disease entity. Its prognosis and predictor of mortality remain unclear. This study aimed to compare the prognosis between MINOCA and myocardial infarction with obstructive coronary artery disease and identify factors related to all-cause death in MINOCA using a nation-wide, multicenter, and prospective registry. Methods and Results Among 13 104 consecutive patients enrolled, patients without previous history of significant coronary artery disease who underwent coronary angiography were selected. The primary outcome was 2-year all-cause death. Secondary outcomes were cardiac death, noncardiac death, reinfarction, and repeat revascularization. Patients with MINOCA (n=396) and myocardial infarction with obstructive coronary artery disease (n=10 871) showed similar incidence of all-cause death (9.1% versus 8.8%; hazard ratio [ HR ], 1.04; 95% CI, 0.74-1.45; P=0.83). Risks of cardiac death, noncardiac death, and reinfarction were not significantly different between the 2 groups ( HR , 0.82; 95% CI , 0.53-1.28; P=0.38; HR , 1.55; 95% CI , 0.93-2.56; P=0.09; HR , 1.23; 95% CI , 0.65-2.31; P=0.38, respectively). MINOCA patients had lower incidence of repeat revascularization (1.3% versus 7.2%; HR , 0.17; 95% CI , 0.07-0.41; P<0.001). Results were consistent after multivariable regression and propensity-score matching. In a multivariate model, several significant predictors of all-cause death of MINOCA were found, including the nonuse of renin-angiotensin system blockers ( HR , 2.63; 95% CI , 1.08-6.25; P=0.033) and statins ( HR , 2.17; 95% CI , 1.04-4.54; P=0.039). Conclusions Patients with MINOCA and those with myocardial infarction with obstructive coronary artery disease had comparable clinical outcomes. Use of renin-angiotensin system blockers and statins was associated with lower mortality in patients with MINOCA .