Deep Learning With Chest Radiographs for Making Prognoses in Patients With COVID-19: Retrospective Cohort Study.

BACKGROUND: An artificial intelligence (AI) model using chest radiography (CXR) may provide good performance in making prognoses for COVID-19. OBJECTIVE: We aimed to develop and validate a prediction model using CXR based on an AI model and clinical variables to predict clinical outcomes in patients with COVID-19. METHODS: This retrospective longitudinal study included patients hospitalized for COVID-19 at multiple COVID-19 medical centers between February 2020 and October 2020. Patients at Boramae Medical Center were randomly classified into training, validation, and internal testing sets (at a ratio of 8:1:1, respectively). An AI model using initial CXR images as input, a logistic regression model using clinical information, and a combined model using the output of the AI model (as CXR score) and clinical information were developed and trained to predict hospital length of stay (LOS) ≤2 weeks, need for oxygen supplementation, and acute respiratory distress syndrome (ARDS). The models were externally validated in the Korean Imaging Cohort of COVID-19 data set for discrimination and calibration. RESULTS: The AI model using CXR and the logistic regression model using clinical variables were suboptimal to predict hospital LOS ≤2 weeks or the need for oxygen supplementation but performed acceptably in the prediction of ARDS (AI model area under the curve [AUC] 0.782, 95% CI 0.720-0.845; logistic regression model AUC 0.878, 95% CI 0.838-0.919). The combined model performed better in predicting the need for oxygen supplementation (AUC 0.704, 95% CI 0.646-0.762) and ARDS (AUC 0.890, 95% CI 0.853-0.928) compared to the CXR score alone. Both the AI and combined models showed good calibration for predicting ARDS (P=.079 and P=.859). CONCLUSIONS: The combined prediction model, comprising the CXR score and clinical information, was externally validated as having acceptable performance in predicting severe illness and excellent performance in predicting ARDS in patients with COVID-19.

Correction: Deep Learning With Chest Radiographs for Making Prognoses in Patients With COVID-19: Retrospective Cohort Study.

[This corrects the article DOI: 10.2196/42717.].

Erratum: Correction of Affiliations in the Article "Establishment of a Nationwide Korean Imaging Cohort of Coronavirus Disease 2019".

This corrects the article on p. e413 in vol. 35, PMID: 33258333.

Imaging and Clinical Features of COVID-19 Breakthrough Infections: A Multicenter Study.

Background Since vaccines against COVID-19 became available, rare breakthrough infections have been reported despite their high efficacies. Purpose To evaluate the clinical and imaging characteristics of patients with COVID-19 breakthrough infections and compare them with those of unvaccinated patients with COVID-19. Materials and Methods In this retrospective multicenter cohort study, the authors analyzed patient (aged ≥18 years) data from three centers that were registered in an open data repository for COVID-19 between June and August 2021. Hospitalized patients with baseline chest radiographs were divided into three groups according to their vaccination status. Differences between clinical and imaging features were analyzed using the Pearson χ2 test, Fisher exact test, and analysis of variance. Univariable and multivariable logistic regression analyses were used to evaluate associations between clinical factors, including vaccination status and clinical outcomes. Results Of the 761 hospitalized patients with COVID-19, the mean age was 47 years and 385 (51%) were women; 47 patients (6%) were fully vaccinated (breakthrough infection), 127 (17%) were partially vaccinated, and 587 (77%) were unvaccinated. Of the 761 patients, 412 (54%) underwent chest CT during hospitalization. Among the patients who underwent CT, the proportions without pneumonia were 22% of unvaccinated patients (71 of 326), 30% of partially vaccinated patients (19 of 64), and 59% of fully vaccinated patients (13 of 22) (P < .001). Fully vaccinated status was associated with a lower risk of requiring supplemental oxygen (odds ratio [OR], 0.24 [95% CI: 0.09, 0.64; P = .005]) and lower risk of intensive care unit admission (OR, 0.08 [95% CI: 0.09, 0.78; P = .02]) compared with unvaccinated status. Conclusion Patients with COVID-19 breakthrough infections had a significantly higher proportion of CT scans without pneumonia compared with unvaccinated patients. Vaccinated patients with breakthrough infections had a lower likelihood of requiring supplemental oxygen and intensive care unit admission. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Schiebler and Bluemke in this issue.

Impact of Mediastinal Lymphadenopathy on the Severity of COVID-19 Pneumonia: A Nationwide Multicenter Cohort Study.

BACKGROUND: We analyzed the differences between clinical characteristics and computed tomography (CT) findings in patients with coronavirus disease 2019 (COVID-19) to establish potential relationships with mediastinal lymphadenopathy and clinical outcomes. METHODS: We compared the clinical characteristics and CT findings of COVID-19 patients from a nationwide multicenter cohort who were grouped based on the presence or absence of mediastinal lymphadenopathy. Differences between clinical characteristics and CT findings in these groups were analyzed. Univariate and multivariate analyses were performed to determine the impact of mediastinal lymphadenopathy on clinical outcomes. RESULTS: Of the 344 patients included in this study, 53 (15.4%) presented with mediastinal lymphadenopathy. The rate of diffuse alveolar damage pattern pneumonia and the visual CT scores were significantly higher in patients with mediastinal lymphadenopathy than in those without (P < 0.05). A positive correlation between the number of enlarged mediastinal lymph nodes and visual CT scores was noted in patients with mediastinal lymphadenopathy (Spearman's ρ = 0.334, P < 0.001). Multivariate analysis showed that mediastinal lymphadenopathy was independently associated with a higher risk of intensive care unit (ICU) admission (odds ratio, 95% confidence interval; 3.25, 1.06-9.95) but was not significantly associated with an increased risk of in-hospital death in patients with COVID-19. CONCLUSION: COVID-19 patients with mediastinal lymphadenopathy had a larger extent of pneumonia than those without. Multivariate analysis adjusted for clinical characteristics and CT findings revealed that the presence of mediastinal lymphadenopathy was significantly associated with ICU admission.

Association of coffee drinking with all-cause and cause-specific mortality in over 190,000 individuals: data from two prospective studies.

We examined the association of coffee drinking with all-cause and cause-specific mortality in a pooled analysis of two Korean prospective cohort studies: The Korea National Health and Nutrition Examination Survey and the Korean Genome and Epidemiology Study. We included 192,222 participants, and a total of 6057 deaths were documented. Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs), and the HRs were combined using a random-effects model. Coffee drinking was associated with a lower risk of all-cause mortality [HR (95% CI) = 0.84 (0.77-0.92), for ≥3 cups/day of coffee drinking versus non-drinkers; p for trend = 0.004]. We observed the potential benefit of coffee drinking for mortality due to cardiovascular disease, respiratory disease, and diabetes, but not for cancer mortality. Overall, we found that moderate coffee drinking was associated with a lower risk of death in population-based cohort analysis of Korean adults.

Prognostic Implications of CT Feature Analysis in Patients with COVID-19: a Nationwide Cohort Study.

BACKGROUND: Few studies have classified chest computed tomography (CT) findings of coronavirus disease 2019 (COVID-19) and analyzed their correlations with prognosis. The present study aimed to evaluate retrospectively the clinical and chest CT findings of COVID-19 and to analyze CT findings and determine their relationships with clinical severity. METHODS: Chest CT and clinical features of 271 COVID-19 patients were assessed. The presence of CT findings and distribution of parenchymal abnormalities were evaluated, and CT patterns were classified as bronchopneumonia, organizing pneumonia (OP), or diffuse alveolar damage (DAD). Total extents were assessed using a visual scoring system and artificial intelligence software. Patients were allocated to two groups based on clinical outcomes, that is, to a severe group (requiring O2 therapy or mechanical ventilation, n = 55) or a mild group (not requiring O2 therapy or mechanical ventilation, n = 216). Clinical and CT features of these two groups were compared and univariate and multivariate logistic regression analyses were performed to identify independent prognostic factors. RESULTS: Age, lymphocyte count, levels of C-reactive protein, and procalcitonin were significantly different in the two groups. Forty-five of the 271 patients had normal chest CT findings. The most common CT findings among the remaining 226 patients were ground-glass opacity (98%), followed by consolidation (53%). CT findings were classified as OP (93%), DAD (4%), or bronchopneumonia (3%) and all nine patients with DAD pattern were included in the severe group. Uivariate and multivariate analyses showed an elevated procalcitonin (odds ratio [OR], 2.521; 95% confidence interval [CI], 1.001-6.303, P = 0.048), and higher visual CT scores (OR, 1.137; 95% CI, 1.042-1.236; P = 0.003) or higher total extent by AI measurement (OR, 1.048; 95% CI, 1.020-1.076; P < 0.001) were significantly associated with a severe clinical course. CONCLUSION: CT findings of COVID-19 pneumonia can be classified into OP, DAD, or bronchopneumonia patterns and all patients with DAD pattern were included in severe group. Elevated inflammatory markers and higher CT scores were found to be significant predictors of poor prognosis in patients with COVID-19 pneumonia.

Cases of high lying azygos arch and its embryological consideration.

PURPOSE: This study aimed to report cases of high-lying azygos arch and discuss the embryological basis of its development by a thorough evaluation of the anatomical features assessed using computed tomography (CT) images. METHODS: This study was approved by our institutional review board. We retrospectively reviewed chest CT images between November 2011 and November 2018. To determine high-lying azygos arch, we set the upper margin of the T4 vertebral body as the reference level. Regarding the embryological development of high-lying azygos arch, we retrospectively reviewed the CT images of 105 patients with tracheal bronchus to identify the location of the azygos arch. RESULTS: We noted that on three cases CT images, the azygos arch was located higher than the upper margin of the right main bronchus, and drained into the proximal superior vena cava (SVC) at a level higher than the conventional T4 or T5 vertebral level. All 105 patients with right tracheal bronchus showed azygos arch above the tracheal bronchus. CONCLUSION: This variation in the location of the azygos arch can mimic pathological lesion on plain radiographs, and, therefore, it is important to be aware of high-lying azygos arch. Our findings show that the azygos arch may have possibly migrated downward during embryological development.

Establishment of a Nationwide Korean Imaging Cohort of Coronavirus Disease 2019.

BACKGROUND: The Korean Society of Thoracic Radiology (KSTR) recently constructed a nation-wide coronavirus disease 2019 (COVID-19) database and imaging repository, referred to the Korean imaging cohort of COVID-19 (KICC-19) based on the collaborative efforts of its members. The purpose of this study was to provide a summary of the clinico-epidemiological data and imaging data of the KICC-19. METHODS: The KSTR members at 17 COVID-19 referral centers retrospectively collected imaging data and clinical information of consecutive patients with reverse transcription polymerase chain reaction-proven COVID-19 in respiratory specimens from February 2020 through May 2020 who underwent diagnostic chest computed tomography (CT) or radiograph in each participating hospital. RESULTS: The cohort consisted of 239 men and 283 women (mean age, 52.3 years; age range, 11-97 years). Of the 522 subjects, 201 (38.5%) had an underlying disease. The most common symptoms were fever (n = 292) and cough (n = 245). The 151 patients (28.9%) had lymphocytopenia, 86 had (16.5%) thrombocytopenia, and 227 patients (43.5%) had an elevated CRP at admission. The 121 (23.4%) needed nasal oxygen therapy or mechanical ventilation (n = 38; 7.3%), and 49 patients (9.4%) were admitted to an intensive care unit. Although most patients had cured, 21 patients (4.0%) died. The 465 (89.1%) subjects underwent a low to standard-dose chest CT scan at least once during hospitalization, resulting in a total of 658 CT scans. The 497 subjects (95.2%) underwent chest radiography at least once during hospitalization, which resulted in a total of 1,475 chest radiographs. CONCLUSION: The KICC-19 was successfully established and comprised of 658 CT scans and 1,475 chest radiographs of 522 hospitalized Korean COVID-19 patients. The KICC-19 will provide a more comprehensive understanding of the clinical, epidemiological, and radiologic characteristics of patients with COVID-19.

Atypical bronchus in the right lower lobe: Computed tomography-based analysis.

INTRODUCTION: The aim of this study was to define the subsuperior bronchus (B*) and reestablish the bronchial anatomy of the right lower lobe (RLL) by assessment of atypical bronchi. MATERIALS AND METHODS: Chest computed tomography (CT) scans of 500 consecutive patients were retrospectively evaluated. All CT scans were acquired with 64-slice scanners. Atypical bronchi in the RLL were classified on the basis of running direction and shape: lateral (Lat), posterolateral (PL), posterior (Post), Lat + PL, and PL + Post. We classified an atypical bronchus in the basal segmental bronchus (BSB) stem running posteriorly or posterolaterally as B* and a para-lateral bronchus running laterally as Para-B8. The B* posts running posteriorly were named P1, and those running medially P2. RESULTS: Atypical BSB bronchi Lat, PL, and Post arose from B8, B9, and B10, respectively. All Lat + PL bronchi arose from B8 or B9, and all PL + Post from B9 or B10. When an atypical bronchus arose from one of the BSB pair, none arose from the other. Atypical bronchi forming B* and Para-B8 arose from the stem spreading the connatural BSBs. The P2 post coexisted with another atypical stem bronchus originating from B8, 9, 10, or higher. CONCLUSIONS: The first subsegmental bronchi of B8, B9, and B10 are Lat, PL, and Post, respectively. Lat + PL and PL + Post bronchi at the BSB level could result from fusion of an atypical bronchus during downward migration. The stem B* and Para-B8 could result from arrested downward migration of atypical bronchi. This information is useful for RLL segmentectomy.

Clinical significance of evaluating coronary atherosclerosis in adult patients with hypertrophic cardiomyopathy who have chest pain.

OBJECTIVE: Chest pain is a common symptom in patients with hypertrophic cardiomyopathy (HCM), causing difficulty determining whether there is coexistent coronary artery disease (CAD). We investigated whether coronary computed tomography angiography (CCTA) can assess the prevalence and clinical significance of CAD in adult patients with HCM showing chest pain through longitudinal follow-up. METHODS: In 238 adult patients with HCM, who underwent CCTA for chest pain, we analyzed the degree of stenosis and adverse plaque characteristics (APCs) as CCTA variables. Three prediction models for adverse cardiovascular events (ACEs: all-cause mortality, myocardial infarction, unstable angina, heart failure, implantable cardioverter-defibrillator implantation, and stroke) were assessed using the combination of clinical risk factors, echocardiographic parameters, and CCTA variables. RESULTS: The prevalence of obstructive CAD (≥ 50% in luminal stenosis) and APC was 14.7% and 18.9%, respectively. During the follow-up period (median, 37 months; range, 2-108 months), there were 31 occurrences of ACEs (13.0%). Using multivariate Cox regression analysis, age, atrial fibrillation, low ejection fraction, obstructive CAD, and APCs were associated with ACEs (all p < 0.05). Among the prediction models for ACEs, the area under the curve (AUC) was higher (AUC = 0.92) when CCTA variables were added to the clinical (AUC = 0.84) and echocardiographic factors (AUC = 0.88) (p < 0.001). CONCLUSIONS: Using CCTA, about 20% of symptomatic HCM patients were associated with clinically significant atherosclerosis. Adding these CCTA variables to the clinical and echocardiographic variables may increase the predictions of ACEs; therefore, evaluating coronary atherosclerosis using CCTA may be helpful for symptomatic HCM patients. KEY POINTS: • Chest pain in adult patients with hypertrophic cardiomyopathy (HCM) remains challenging to distinguish from coronary artery disease. • Coronary computed tomography angiography (CCTA) can assess the severity and characteristics of coronary atherosclerosis in symptomatic HCM patients. • Adding CCTA variables to clinical and echocardiographic factors may increase the predictions of adverse cardiac events in HCM patients, and thus evaluating coronary atherosclerosis using CCTA may be helpful for HCM patients with chest pain.

Protective effects of diphenyleneiodonium, an NADPH oxidase inhibitor, on lipopolysaccharide-induced acute lung injury.

NADPH oxidase (NOX) plays an important role in inflammatory response by producing reactive oxygen species (ROS). The inhibition of NOX has been shown to induce anti-inflammatory effects in a few experimental models. The aim of this study was to investigate the effects of diphenyleneiodonium (DPI), a NOX inhibitor, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a rat model. Sprague-Dawley rats were intraperitoneally administered by DPI (5 mg/kg) 30 minutes after intratracheal instillation of LPS (3 mg/kg). After 6 hours, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The NOX activity in lung tissue was significantly increased in LPS-treated rats. It was significantly attenuated by DPI. DPI-treated rats showed significant reduction in the intracellular ROS, the number of inflammatory cells, and cytokines (TNF-α and IL-6) in BALF compared with LPS-treated rats. In lung tissue, DPI-treated rats showed significantly decreased malondialdehyde content and increased activity of glutathione peroxidase and superoxide dismutase compared with LPS-treated rats. Lung injury score, myeloperoxidase activity, and inducible nitric oxide synthase expression were significantly decreased in DPI-treated rats compared with LPS-treated animals. Western blotting analysis demonstrated that DPI significantly suppressed LPS-induced activation of NF-κB and ERK1/2 and SAPK/JNK in MAPK pathway. Our results suggest that DPI may have protective effects on LPS-induced ALI thorough anti-oxidative and anti-inflammatory effects which may be due to inactivation of the NF-κB, ERK1/2, and SAPK/JNK pathway. These results suggest the therapeutic potential of DPI as an anti-inflammatory agent in ALI.

Discrepancies between coronary CT angiography and invasive coronary angiography with focus on culprit lesions which cause future cardiac events.

OBJECTIVES: To evaluate the clinical significance of discrepant lesions between coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) in a longitudinal study. METHODS: In 220 patients with suspected coronary artery disease (CAD) who underwent both 256-row CCTA and ICA, the obstructive CAD (≥ 50% stenosis) on CCTA was compared with that on ICA as the reference standard. We analysed the causes of the discrepancy between CCTA and ICA. During a 40-month follow-up period, major adverse cardiac events (MACE) were assessed. RESULTS: Discordance between CCTA and ICA was observed in 121 of the 3166 coronary artery segments (3.8%). Common causes were calcification (45.9%) and positive remodelling (PR) (29.6%) in 83 false positive lesions, and noise (40.0%) and motion artefact (37.8%) in 38 false negative lesions. MACE occurred in seven lesions among the discrepant lesions; six among the 29 PR lesions (20.7%) and one among the 53 calcified lesions (1.9%). With respect to the prediction power of MACE in an intermediate stenosis, the CCTA-related value including PR was higher than the ICA-related value. CONCLUSIONS: PR was a frequent cause of MACE among the false positive lesions on CCTA. Therefore, the presence of PR on CCTA may suggest clinical significance, although it can be missed by ICA. KEY POINTS: • Compared to ICA, PR in CCTA may be cause of false positive lesion. • CCTA-related value including PR shows higher prediction power of MACE than ICA-related value. • PR reflects atherosclerotic burden that can be related to cardiac events. • PR in CCTA should be observed carefully, even if it is false positive.

Anatomic variations of lower extremity venous system in varicose vein patients: demonstration by three-dimensional CT venography.

Background Understanding the anatomy of the lower extremity veins is essential for successful varicose vein treatment. Computed tomography (CT) venography may be used to obtain a comprehensive overview and detailed information regarding this. Purpose To describe anatomic variations of the lower extremity venous system in patients with varicose veins, using three-dimensional (3D) CT venography. Material and Methods A total of 810 limbs in 405 patients with suspected varicose veins were prospectively referred to undertake CT venography and included in our study population retrospectively. The CT venography images were evaluated by consensus of two cardiovascular radiologists. Anatomical variations of the lower extremity venous system and their incidence were analyzed. Specifically, the number of tributaries at saphenofemoral junction, relative location of the great saphenous vein (GSV) with respect to the common femoral artery bifurcation, pattern of saphenopopliteal junction, and end of thigh extension from the small saphenous vein (SSV) were assessed. Results The most frequent number of tributaries joining the GSV was four (44.4%, 360/810). Only 0.7% (6/810) of the limbs demonstrated unusual location of the GSV between the bifurcated superficial and deep femoral arteries. The most common pattern of veins at the saphenopopliteal junction was a larger caliber of saphenopopliteal junction than thigh extension from SSV (43.8%, 355/810), end of which joining the femoral vein directly (41.0%, 288/703). Conclusion CT venography with 3D reconstruction can be used to understand the anatomy of lower extremity veins and how their variations contribute to varicose veins.

PFAS and their association with the increased risk of cardiovascular disease in postmenopausal women.

Cardiovascular diseases (CVD) are one of the major causes of death globally. In addition to traditional risk factors such as unhealthy lifestyles (smoking, obesity, sedentary) and genetics, common environmental exposures, including persistent environmental contaminants, may also influence cardiovascular disease risk. Per- and polyfluoroalkyl substances (PFAS) are a class of highly fluorinated chemicals used in household consumer and industrial products known to persist in our environment for years, causing health concerns that are now linked to endocrine disruptions and related outcomes in women, including interference of the cardiovascular and reproductive systems. In postmenopausal women, higher levels of PFAS are observed than in premenopausal women due to the cessation of menstruation, which is crucial for PFAS excretion. Because of these findings, we explored the association between Perfluorooctanoic acid (PFOA), Perfluorooctane sulfonate (PFOS), Perfluorobutanesulfonic acid (PFBS) in postmenopausal women from our previously established CVD study. We used liquid chromatography with tandem mass spectrometry (LC-MS-MS), supported by machine learning approaches, and the detection and quantification of serum metabolites and proteins. Here, we show that PFOS can be a good predictor of coronary artery disease, while PFOA can be an intermediate predictor of coronary microvascular disease. We also found that the PFAS levels in our study are significantly associated with inflammation-related proteins. Our findings may provide new insight into the potential mechanisms underlying the PFAS-induced risk of cardiovascular diseases in this population.

Chest Radiography of Tuberculosis: Determination of Activity Using Deep Learning Algorithm.

BACKGROUND: Inactive or old, healed tuberculosis (TB) on chest radiograph (CR) is often found in high TB incidence countries, and to avoid unnecessary evaluation and medication, differentiation from active TB is important. This study develops a deep learning (DL) model to estimate activity in a single chest radiographic analysis. METHODS: A total of 3,824 active TB CRs from 511 individuals and 2,277 inactive TB CRs from 558 individuals were retrospectively collected. A pretrained convolutional neural network was fine-tuned to classify active and inactive TB. The model was pretrained with 8,964 pneumonia and 8,525 normal cases from the National Institute of Health (NIH) dataset. During the pretraining phase, the DL model learns the following tasks: pneumonia vs. normal, pneumonia vs. active TB, and active TB vs. normal. The performance of the DL model was validated using three external datasets. Receiver operating characteristic analyses were performed to evaluate the diagnostic performance to determine active TB by DL model and radiologists. Sensitivities and specificities for determining active TB were evaluated for both the DL model and radiologists. RESULTS: The performance of the DL model showed area under the curve (AUC) values of 0.980 in internal validation, and 0.815 and 0.887 in external validation. The AUC values for the DL model, thoracic radiologist, and general radiologist, evaluated using one of the external validation datasets, were 0.815, 0.871, and 0.811, respectively. CONCLUSION: This DL-based algorithm showed potential as an effective diagnostic tool to identify TB activity, and could be useful for the follow-up of patients with inactive TB in high TB burden countries.

Primary pulmonary synovial sarcoma with delayed diagnosis in a 69-year-old man: A case report.

RATIONALE: Primary pulmonary synovial sarcoma is a rare malignant pulmonary tumor accompanied by calcifications in approximately 15% of cases. These calcifications usually have a fine, stippled appearance; coarse shapes have seldom been reported. Moreover, the presence of coarse calcifications often suggests benign tumors, which vastly differ in treatment. We present a rare case of primary pulmonary sarcoma with coarse intratumoral calcifications, the diagnosis of which was delayed because of its radiologic appearance. PATIENT CONCERNS: A computed tomography (CT) scan of a 69-year-old man with right upper quadrant (RUQ) pain revealed an incidental mass at the base of the right lower lobe, the margin of which was not well described with respect to the liver, and intratumoral coarse calcification was noted. Initially, the lesion was believed to be hepatic, and magnetic resonance imaging (MRI) was performed. Based on its imaging features, the mass was thought to be a pulmonary lesion, and a preliminary diagnosis of a benign lesion, such as a hamartoma or granuloma, was made. Four months after the initial CT scan, the patient's RUQ pain had aggravated; however, no change in the mass was observed on follow-up CT. DIAGNOSIS: The final diagnosis was primary pulmonary sarcoma, proven by surgical biopsy. INTERVENTIONS: Wedge resection of the right lower lobe was performed, and the patient received adjuvant chemotherapy. OUTCOMES: The patient's RUQ pain improved, and no recurrence or metastasis has been reported to date. LESSONS: This case describes a rare presentation of a primary pulmonary synovial sarcoma with coarse intratumoral calcifications and the MRI features of the lesion. Intratumoral coarse calcifications often suggest benign lesions, such as hamartomas or post-inflammatory granulomas; however, as malignant lesions cannot be completely excluded, other radiologic and clinical features should be considered carefully. Focal areas of enhancement and eccentric calcification distribution might suggest malignant lesions such as primary pulmonary synovial sarcoma. Furthermore, despite not being used routinely, MRI scans might be helpful because advanced MRI techniques, such as diffusion-weighted imaging, can help distinguish malignant lesions from benign lesions. If the clinical course of a patient suggests malignancy, a more aggressive biopsy strategy should be considered.

NAD+ Metabolism Generates a Metabolic Vulnerability in Endocrine-Resistant Metastatic Breast Tumors in Females.

Approximately 70% of human breast cancers express estrogen receptor-α (ERα), providing a potential target for endocrine therapy. However, 30% to 40% of patients with ER+ breast cancer still experience recurrence and metastasis, with a 5-year relative overall survival rate of 24%. In this study, we identified nicotinamide phosphoribosyltransferase (NAMPT), an important enzyme in nicotinamide adenine dinucleotide (NAD+) metabolism, to be increased in metastatic breast cancer (MBC) cells treated with fulvestrant (Fulv). We tested whether the blockade of NAD+ production via inhibition of NAMPT synergizes with standard-of-care therapies for ER+ MBC in vitro and in vivo. A synergistic effect was not observed when KPT-9274 was combined with palbociclib or tamoxifen or when Fulv was combined with other metabolic inhibitors. We show that NAMPT inhibitor KPT-9274 and Fulv works synergistically to reduce metastatic tumor burden. RNA-sequencing analysis showed that NAMPT inhibitor in combination with Fulv reversed the expression of gene sets associated with more aggressive tumor phenotype, and metabolomics analysis showed that NAMPT inhibition reduced the abundance of metabolites associated with several key tumor metabolic pathways. Targeting metabolic adaptations in endocrine-resistant MBC is a novel strategy, and alternative approaches aimed at improving the therapeutic response of metastatic ER+ tumors are needed. Our findings uncover the role of ERα-NAMPT crosstalk in MBC and the utility of NAMPT inhibition and antiestrogen combination therapy in reducing tumor burden and metastasis, potentially leading to new avenues of MBC treatment.

E-cadherin as a predictive marker of brain metastasis in non-small-cell lung cancer, and its regulation by pioglitazone in a preclinical model.

It remains unclear whether patients with non-small-cell lung cancer (NSCLC) develop brain metastasis during or after standard therapy. We attempted to identify biological markers that predict brain metastasis, and investigated how to modulate expression of such markers. A case-control study of patients who were newly diagnosed with NSCLC and who had developed brain metastasis during follow-up was conducted between 2004 and 2009. These patients were compared with a control group of patients who had NSCLC but no evidence of brain metastasis. Immunohistochemical analysis of expression of Ki-67, p53, Bcl-2, Bax, vascular endothelial growth factor, epidermal growth factor receptor, caspase-3, and E-cadherin was conducted. The methylation status of the genes for O(6)-methylguanine-DNA-methyltransferase, tissue inhibitor of matrix metalloproteinase (TIMP)-2, TIMP-3, and death-associated protein-kinase was also determined, by use of a methylation-specific polymerase chain reaction. A significantly increased risk of developing brain metastasis was associated with the presence of primary tumors with low E-cadherin expression in patients with NSCLC. We also investigated the effects of pioglitazone, a peroxisome proliferator-activated receptor γ-activating drug, in tumor-bearing mouse models. We found that E-cadherin expression was proportional to pioglitazone exposure time. Interestingly, pioglitazone pretreatment before cancer cell inoculation prevented loss of E-cadherin expression and reduced expression of MMP9 and fibronectin, compared with the control group. E-cadherin expression could be a predictor of brain metastasis in patients with NSCLC. Preventive treatment with pioglitazone may be useful for modulating E-cadherin expression.

Lower Dietary Calcium Intake is Associated with a Higher Risk of Mortality in Korean Adults.

BACKGROUND: Calcium, one of the most abundant minerals in the human body, has a pivotal role in human physiology. However, only a few studies have examined the association of dietary calcium intake with mortality in a population with low calcium intake. OBJECTIVE: The aim of this study was to examine the association of dietary calcium intake with risk of all-cause and cause-specific mortality among Korean adults with low calcium intake. DESIGN: This study was a prospective cohort study. PARTICIPANTS/SETTING: The analysis was conducted using data from 44,327 eligible Korean adults aged 19 years and older who participated in the Korea National Health and Nutrition Examination Survey 2007-2015. Dietary calcium intake was assessed using 1-day 24-hour recall data. MAIN OUTCOME MEASURES: The main outcomes of this study were mortality from all causes, cancer, cardiovascular disease, respiratory disease, and all other causes combined. The outcome was ascertained through linkage to the death registry compiled by Statistics Korea with the use of the resident registration number. STATISTICAL ANALYSES PERFORMED: Weighted Cox proportional hazard models were used to estimate the hazard ratios and 95% CIs of the all-cause and cause-specific mortality according to dietary calcium intake. RESULTS: During a mean follow-up of 7.28 person-years, 1,889 deaths were ascertained. After multivariable adjustment, the hazard ratios for all-cause mortality for the second quintile to the highest quintile of dietary calcium intake, respectively, compared with the first quintile were 0.86 (95% CI 0.73 to 1.00), 0.82 (95% CI 0.69 to 0.98), 0.85 (95% CI 0.69 to 1.03), and 0.78 (95% CI 0.64 to 0.96) (P for trend from the lowest to the highest quintile = .04). There were no statistically significant associations between dietary calcium intake and risk of mortality from cancer, cardiovascular, or respiratory disease. CONCLUSIONS: In this large prospective cohort study of Korean adults, lower dietary calcium intake was associated with a higher risk of all-cause mortality.