Effect of a Team Approach to Pressure Injury Management over 5 Years in a Tertiary Hospital.

OBJECTIVE: The authors' facility established a novel integrated wound care team (IWCT), which included the implementation of a strict treatment algorithm by the patients' attending providers and a specialized wound care team led by a plastic surgeon. Investigators then retrospectively analyzed clinical outcomes of pressure injury (PI) management by the IWCT over 5 years. METHODS: The authors performed a retrospective chart review and periodic statistical analysis of the data for all patients with PI referred to the IWCT in the authors' center from May 2015 to April 2019. Data including patients' demographic information, first and last consultation dates, referring department, PI stage, site of PI, and Braden Scale scores were collected and analyzed. RESULTS: Patients (N = 15,556) did not differ significantly in age, sex, or Braden Scale score. A preimplementation/postimplementation analysis of PI data before and after establishing the IWCT showed that the incidence of stage 3 or 4 PIs had significantly decreased during the study period (19.1% vs 15.2%, P < .05). Conversely, the incidence of stage 1 PIs significantly increased in the same period (38.0% vs 57.4%, P < .05). The proportion of completely healed PIs also increased, and the median treatment period was significantly shortened (P < .05). CONCLUSIONS: Implementation of the IWCT in a tertiary hospital setting led to a significant increase in early-stage PI detection and a decrease in severe PIs.

Targeted Next-Generation Sequencing Analysis for Recurrence in Early-Stage Lung Adenocarcinoma.

BACKGROUND: Despite surgical resection, early lung adenocarcinoma has a recurrence rate of 20-50%. No clear predictive markers for recurrence of early lung adenocarcinoma are available. Targeted next-generation sequencing (NGS) is rarely used to identify recurrence-related genes. We aimed to identify genetic alterations that can predict recurrence, by comparing the molecular profiles of patient groups with and without recurrence. METHODS: Tissues from 230 patients with resected stage I-II lung adenocarcinoma (median follow-up: 49 months) were analyzed via targeted NGS for 207 cancer-related genes. The recurrence-free survival according to the number and type of mutation was estimated using the Kaplan-Meier method. Independent predictive biomarkers related to recurrence were identified using the Cox proportional hazards model. RESULTS: Recurrence was observed in 64 patients (27.8%). In multivariate analysis adjusted for age, sex, smoking history, stage, surgical mode, and visceral pleural invasion, the CTNNB1 mutation and fusion genes (ALK, ROS1, RET) were negative prognostic factors for recurrence in early-stage lung adenocarcinoma (HR 4.47, p = 0.001; HR 2.73, p = 0.009). EGFR mutation was a favorable factor (HR 0.51, p = 0.016), but the CTNNB1/EGFR co-mutations were negative predictors (HR 19.2, p < 0.001). TP53 mutation was a negative predictor compared with EGFR mutation for recurrence (HR 5.24, p = 0.02). CONCLUSIONS: Targeted NGS can provide valuable information to predict recurrence and identify patients at high recurrence risk, facilitating selection of the treatment strategy among close monitoring and adjuvant-targeted therapy. Larger datasets are required to validate these findings.

Ultra-Low-Dose Spectral CT Based on a Multi-level Wavelet Convolutional Neural Network.

Spectral computed tomography (CT) based on a photon-counting detector (PCD) is a promising technique with the potential to improve lesion detection, tissue characterization, and material decomposition. PCD-based scanners have several technical issues including operation in the step-and-scan mode and long data acquisition time. One straightforward solution to these issues is to reduce the number of projection views. However, if the projection data are under-sampled or noisy, it would be challenging to produce a correct solution without precise prior information. Recently, deep-learning approaches have demonstrated impressive performance for under-sampled CT reconstruction. In this work, the authors present a multilevel wavelet convolutional neural network (MWCNN) to address the limitations of PCD-based scanners. Data properties of the proposed method in under-sampled spectral CT are analyzed with respect to the proposed deep-running-network-based image reconstruction using two measures: sampling density and data incoherence. This work presents the proposed method and four different methods to restore sparse sampling. We investigate and compare these methods through a simulation and real experiments. In addition, data properties are quantitatively analyzed and compared for the effect of sparse sampling on the image quality. Our results indicate that both sampling density and data incoherence affect the image quality in the studied methods. Among the different methods, the proposed MWCNN shows promising results. Our method shows the highest performance in terms of various evaluation parameters such as the structural similarity, root mean square error, and resolution. Based on the results of imaging and quantitative evaluation, this study confirms that the proposed deep-running network structure shows excellent image reconstruction in sparse-view PCD-based CT. These results demonstrate the feasibility of sparse-view PCD-based CT using the MWCNN. The advantage of sparse view CT is that it can significantly reduce the radiation dose and obtain images with several energy bands by fusing PCDs. These results indicate that the MWCNN possesses great potential for sparse-view PCD-based CT.

Development of a senior-specific, citizen-oriented healthcare service system in South Korea based on the Canadian 48/6 model of care.

BACKGROUND: In the age of aging, Korea's current medical delivery system threatens to increase the number of medical and caring refugees. This study attempts to develop an integrated senior citizen-oriented healthcare service system in which daily care, professional care, and rehabilitation are organically organized between medical institutions and local communities, thereby meeting the daily life needs of the elderly and inducing well-being, wellness, and well-dying. METHODS: To develop the integrated healthcare system, data collection and analyses were conducted through a systematic review, literature review, benchmarking, focus group interviews, and expert consultation. RESULTS: The senior-specific, citizen-oriented healthcare service system developed in this study is designed to screen patients aged 65 or older within 24 h of being admitted, using the Geriatric Screening for Care-10. If there is reason for concern as a result of the screening, further evaluation is performed through assessment. Doctors and nurses create a care plan and a discharge plan based on the results from the screening and assessment. The nurse further uses the screening to monitor the patient's condition before discharge. Based on the screening results at the time of discharge, a transitional care plan is prepared and provided to elderly patients and/or their families. This process enables a systematic link between medical institutions and community resources, aiming for the continuous management of health issues. It also establishes a multidisciplinary treatment plan that considers patients and their families so that diseases common to the elderly are diagnosed and treated promptly. CONCLUSIONS: The most important issue for the elderly is to be able to live healthily and independently for the rest of their lives through well-being, wellness, and well-dying. The senior-specific, citizen-oriented healthcare service proposed in this study is an integrated medical treatment system for elderly users the implementation of which requires the daily care, professional care, and rehabilitation of elderly members of society to be organically organized according to the role of the patients, their families, and the caregiver.

Restoration of Full Data from Sparse Data in Low-Dose Chest Digital Tomosynthesis Using Deep Convolutional Neural Networks.

Chest digital tomosynthesis (CDT) provides more limited image information required for diagnosis when compared to computed tomography. Moreover, the radiation dose received by patients is higher in CDT than in chest radiography. Thus, CDT has not been actively used in clinical practice. To increase the usefulness of CDT, the radiation dose should reduce to the level used in chest radiography. Given the trade-off between image quality and radiation dose in medical imaging, a strategy to generating high-quality images from limited data is need. We investigated a novel approach for acquiring low-dose CDT images based on learning-based algorithms, such as deep convolutional neural networks. We used both simulation and experimental imaging data and focused on restoring reconstructed images from sparse to full sampling data. We developed a deep learning model based on end-to-end image translation using U-net. We used 11 and 81 CDT reconstructed input and output images, respectively, to develop the model. To measure the radiation dose of the proposed method, we investigated effective doses using Monte Carlo simulations. The proposed deep learning model effectively restored images with degraded quality due to lack of sampling data. Quantitative evaluation using structure similarity index measure (SSIM) confirmed that SSIM was increased by approximately 20% when using the proposed method. The effective dose required when using sparse sampling data was approximately 0.11 mSv, similar to that used in chest radiography (0.1 mSv) based on a report by the Radiation Society of North America. We investigated a new approach for reconstructing tomosynthesis images using sparse projection data. The model-based iterative reconstruction method has previously been used for conventional sparse sampling reconstruction. However, model-based computing requires high computational power, which limits fast three-dimensional image reconstruction and thus clinical applicability. We expect that the proposed learning-based reconstruction strategy will generate images with excellent quality quickly and thus have the potential for clinical use.

Extracellular vesicle-derived DNA for performing EGFR genotyping of NSCLC patients.

Tumor cells shed an abundance of extracellular vesicles (EVs) to body fluids containing bioactive molecules including DNA, RNA, and protein. Investigations in the field of tumor-derived EVs open a new horizon in understanding cancer biology and its potential as cancer biomarkers as well as platforms for personalized medicine. This study demonstrates that successfully isolated EVs from plasma and bronchoalveolar lavage fluid (BALF) of non-small cell lung cancer (NSCLC) patients contain DNA that can be used for EGFR genotyping through liquid biopsy. In both plasma and BALF samples, liquid biopsy results using EV DNA show higher accordance with conventional tissue biopsy compared to the liquid biopsy of cfDNA. Especially, liquid biopsy with BALF EV DNA is tissue-specific and extremely sensitive compared to using cfDNA. Furthermore, use of BALF EV DNA also demonstrates higher efficiency in comparison to tissue rebiopsy for detecting p.T790 M mutation in the patients who developed resistance to EGFR-TKIs. These finding demonstrate possibility of liquid biopsy using EV DNA potentially replacing the current diagnostic methods for more accurate, cheaper, and faster results.

Cumulative smoking dose affects the clinical outcomes of EGFR-mutated lung adenocarcinoma patients treated with EGFR-TKIs: a retrospective study.

BACKGROUND: Although lung adenocarcinoma with activating epidermal growth factor receptor (EGFR) mutations is common in never smokers, one-third of the patients are ever-smokers. We aimed to investigate the effect of cumulative smoking dose(CSD) on clinical outcomes, including progression-free survival (PFS) and overall survival (OS), in patients with EGFR-mutated lung adenocarcinoma receiving EGFR-tyrosine kinase inhibitors (TKIs). METHODS: We retrospectively analyzed 142 patients with EGFR-mutation positive advanced or recurrent lung adenocarcinoma who were administered gefitinib, erlotinib, afatinib, and osimertinib. These patients were classified based on their CSD as never smokers, light smokers (≤10 pack-years [PYs]), moderate smokers (11-30 PYs), and heavy smokers (> 30 PYs). PFS and OS were analyzed according to smoking subgroups via Kaplan-Meier curves. RESULTS: Among the 142 patients, 91 (64.1%), 12 (8.5%), 22 (15.5%), and 17 (12%) were never, light, moderate, and heavy smokers, respectively. CSD was inversely associated with median PFS in a statistically significant dose-dependent manner (11.8 months (mo), 11.0 mo, 7.4 mo, and 3.9 mo; p < 0.001). Statistically significant negative association was observed between CSD and median OS (33.6 mo, 26.3 mo, 20 mo, and 8.9 mo; p < 0.001). In the multivariate analysis adjusted for age, sex, performance status, stage, and timing of EGFR-TKIs, CSD was an independent predictive factor for disease progression (hazard ratio [HR], 4.00; 95% confidence interval [CI], 1.95-8.23; p = 0.012) and OS (HR, 3.9; 95% CI, 1.84-8.28; p < 0.001). CONCLUSION: CSD is an important predictive and prognostic factor in patients with EGFR-mutated lung adenocarcinoma, and associated smoking-related gene signatures might affect the outcomes.

Liquid biopsy using the supernatant of a pleural effusion for EGFR genotyping in pulmonary adenocarcinoma patients: a comparison between cell-free DNA and extracellular vesicle-derived DNA.

BACKGROUND: EGFR genotyping in pulmonary adenocarcinoma patients who develop pleural effusions is mostly performed using cytology or cell block slides with low sensitivity. Liquid biopsy using the supernatant of pleural effusions may be more effective because they contain many components released by cancer cells. Extracellular vesicles (EVs) are known to carry oncogenic double-stranded DNA that is considered a notable biomarker. Here, we investigate the efficiency of liquid biopsy using cell-free DNA (cfDNA) and extracellular vesicle-derived DNA (EV-derived DNA) from the supernatant of pleural effusions for EGFR genotyping in patients with pulmonary adenocarcinoma. METHODS: Fifty pleural effusion samples from patients with pulmonary adenocarcinoma were evaluated. The supernatant, after removing the cell pellet by centrifugation, was used for liquid biopsy, and EVs were isolated from the pleural effusion by ultracentrifugation. EV-derived DNA and cfDNA were extracted separately, and EGFR genotyping was performed by the PNA clamping method. RESULTS: Among 32 patients who were EGFR-tyrosine kinase inhibitor (TKI) naïve with a known tissue EGFR genotype, liquid biopsy using EV-derived DNA from the pleural effusion supernatant showed 100% matching results with tissue EGFR genotyping in 19 EGFR mutant cases and detected three additional EGFR mutations in patients with wild-type (WT) tissue. Liquid biopsy using cfDNA from pleural effusion supernatants missed two cases of tissue-based EGFR mutations and found two additional EGFR mutation cases. In 18 patients who acquired resistance to EGFR-TKI, EGFR genotyping using EV-derived DNA from the pleural effusion supernatant detected the T790 M mutation in 13 of 18 (72.2%) patients, and this mutation was detected in 11 (61.1%) patients using cfDNA. By contrast, only three patients were found to present the T790 M mutation when using cell block or cytology slides. CONCLUSIONS: Liquid biopsy using the supernatant of pleural effusions showed significantly improved results for EGFR genotyping compared to those using conventional cell block or cytology samples. Liquid biopsy using EV-derived DNA is promising for EGFR genotyping, including T790 M detection in pulmonary adenocarcinoma patients who develop pleural effusions.

Feasibility study of shutter scan acquisition for region of interest (ROI) digital tomosynthesis.

Dose reduction techniques have been studied in medical imaging. We propose shutter scan acquisition for region of interest (ROI) imaging to reduce the patient exposure dose received from a digital tomosynthesis system. A prototype chest digital tomosynthesis (CDT) system (LISTEM, Wonju, Korea) and the LUNGMAN phantom (Kyoto Kagaku, Japan) with lung nodules 8, 10, and 12 mm in size were used for this study. A total of 41 projections with shutter scan acquisition consisted of 21 truncated projections and 20 non-truncated projections. For comparison, 41 projections using conventional full view scan acquisition were also acquired. Truncated projections obtained by shutter scan acquisition were corrected by proposed image processing procedure to remove the truncation artifacts. The image quality was evaluated using the contrast to noise ratio (CNR), coefficient of variation (COV), and figure of merit (FOM). We measured the dose area product (DAP) value to verify the dose reduction using shutter scan acquisition. The ROI of the reconstructed image from shutter scan acquisition showed enhanced contrast. The results showed that CNR values of 8 and 12 mm lung nodules increased by 6.38% and 21.21%, respectively, and the CNR value of 10 mm lung nodule decreased by 3.63%. COV values of the lung nodules were lower in a shutter scan image than in a full view scan image. FOM values of 8, 10, and 12 mm lung nodules increased by 3.06, 2.25, and 2.33 times, respectively. This study compared the proposed shutter scan and conventional full view scan acquisition. In conclusion, using a shutter scan acquisition method resulted in enhanced contrast images within the ROI and higher FOM values. The patient exposure dose of the proposed shutter scan acquisition method can be reduced by limiting the field of view (FOV) to focus on the ROI.

Development of the Korean framework for senior-friendly hospitals: a Delphi study.

BACKGROUND: Aging is an inevitable part of life. One can maintain well-being and wellness even after discharge and/or transition if his or her functional decline is minimized, sudden decline is prevented, and functioning is promoted during hospitalization. Caring appropriately for elderly patients requires the systematic application of Senior-Friendly Hospital principles to all operating systems, including medical centres' organization and environment, as well as patient treatment processes. The Senior-Friendly Hospital framework is valid and important for patient safety and quality improvement. This study aimed to make recommendations regarding the development of the Korean Framework for Senior-Friendly Hospitals for older patients' care management, patient safety interventions, and health promotion, via a Delphi survey. METHODS: Two rounds of Delphi surveying were conducted with 15 participants who had at least 3 years' experience in accreditation surveying and medical accreditation standards, survey methods, and accreditation investigator education. In each round, we calculated statistics describing each standard's validity and feasibility. RESULTS: The Korean Framework for Senior-Friendly Hospitals included 4 Chapters, 11 categories, and 67 standards through consensus of the Senior-Friendly Hospitals task force and experts' peer review. After the two rounds of Delphi surveying, validity evaluation led to no changes in standards of the Senior-Friendly Hospitals; however, the number of standards showing adequate validity decreased from 67 to 58. Regarding feasibility, no changes were necessary in the standards; however, the number of categories showing adequate feasibility decreased from 11 to 8 and from 67 to 30, respectively. The excluded categories were 3.2, 4.2, and 4.3 (service, transportation, and signage and identification). The highest feasibility values were given to standards 2.1.1, 4.1.4, and 4.1.6. The highest feasibility score was given to standard 2.4.2. CONCLUSIONS: The Korean Framework for Senior-Friendly Hospitals needs to include 4 Chapters, 8 categories, and 30 standards. The Accreditation Program for Healthcare Organizations should include Senior-Friendly Hospitals -relevant standards considering Korea's medical environment.

Detection of EGFR and KRAS Mutation by Pyrosequencing Analysis in Cytologic Samples of Non-Small Cell Lung Cancer.

EGFR and KRAS mutations are two of the most common mutations that are present in lung cancer. Screening and detecting these mutations are of issue these days, and many different methods and tissue samples are currently used to effectively detect these two mutations. In this study, we aimed to evaluate the testing for EGFR and KRAS mutations by pyrosequencing method, and compared the yield of cytology versus histology specimens in a consecutive series of patients with lung cancer. We retrospectively reviewed EGFR and KRAS mutation results of 399 (patients with EGFR mutation test) and 323 patients (patients with KRAS mutation test) diagnosed with lung cancer in Konkuk University Medical Center from 2008 to 2014. Among them, 60 patients had received both EGFR and KRAS mutation studies. We compared the detection rate of EGFR and KRAS tests in cytology, biopsy, and resection specimens. EGFR and KRAS mutations were detected in 29.8% and 8.7% of total patients, and the positive mutation results of EGFR and KRAS were mutually exclusive. The detection rate of EGFR mutation in cytology was higher than non-cytology (biopsy or resection) materials (cytology: 48.5%, non-cytology: 26.1%), and the detection rate of KRAS mutation in cytology specimens was comparable to non-cytology specimens (cytology: 8.3%, non-cytology: 8.7%). We suggest that cytology specimens are good alternatives that can readily substitute tissue samples for testing both EGFR and KRAS mutations. Moreover, pyrosequencing method is highly sensitive in detecting EGFR and KRAS mutations in lung cancer patients.

Comparison study of reconstruction algorithms for prototype digital breast tomosynthesis using various breast phantoms.

Digital breast tomosynthesis (DBT) is a recently developed system for three-dimensional imaging that offers the potential to reduce the false positives of mammography by preventing tissue overlap. Many qualitative evaluations of digital breast tomosynthesis were previously performed by using a phantom with an unrealistic model and with heterogeneous background and noise, which is not representative of real breasts. The purpose of the present work was to compare reconstruction algorithms for DBT by using various breast phantoms; validation was also performed by using patient images. DBT was performed by using a prototype unit that was optimized for very low exposures and rapid readout. Three algorithms were compared: a back-projection (BP) algorithm, a filtered BP (FBP) algorithm, and an iterative expectation maximization (EM) algorithm. To compare the algorithms, three types of breast phantoms (homogeneous background phantom, heterogeneous background phantom, and anthropomorphic breast phantom) were evaluated, and clinical images were also reconstructed by using the different reconstruction algorithms. The in-plane image quality was evaluated based on the line profile and the contrast-to-noise ratio (CNR), and out-of-plane artifacts were evaluated by means of the artifact spread function (ASF). Parenchymal texture features of contrast and homogeneity were computed based on reconstructed images of an anthropomorphic breast phantom. The clinical images were studied to validate the effect of reconstruction algorithms. The results showed that the CNRs of masses reconstructed by using the EM algorithm were slightly higher than those obtained by using the BP algorithm, whereas the FBP algorithm yielded much lower CNR due to its high fluctuations of background noise. The FBP algorithm provides the best conspicuity for larger calcifications by enhancing their contrast and sharpness more than the other algorithms; however, in the case of small-size and low-contrast microcalcifications, the FBP reduced detectability due to its increased noise. The EM algorithm yielded high conspicuity for both microcalcifications and masses and yielded better ASFs in terms of the full width at half maximum. The higher contrast and lower homogeneity in terms of texture analysis were shown in FBP algorithm than in other algorithms. The patient images using the EM algorithm resulted in high visibility of low-contrast mass with clear border. In this study, we compared three reconstruction algorithms by using various kinds of breast phantoms and patient cases. Future work using these algorithms and considering the type of the breast and the acquisition techniques used (e.g., angular range, dose distribution) should include the use of actual patients or patient-like phantoms to increase the potential for practical applications.

3D Visualization of Developmental Toxicity of 2,4,6-Trinitrotoluene in Zebrafish Embryogenesis Using Light-Sheet Microscopy.

Environmental contamination by trinitrotoluene is of global concern due to its widespread use in military ordnance and commercial explosives. Despite known long-term persistence in groundwater and soil, the toxicological profile of trinitrotoluene and other explosive wastes have not been systematically measured using in vivo biological assays. Zebrafish embryos are ideal model vertebrates for high-throughput toxicity screening and live in vivo imaging due to their small size and transparency during embryogenesis. Here, we used Single Plane Illumination Microscopy (SPIM)/light sheet microscopy to assess the developmental toxicity of explosive-contaminated water in zebrafish embryos and report 2,4,6-trinitrotoluene-associated developmental abnormalities, including defects in heart formation and circulation, in 3D. Levels of apoptotic cell death were higher in the actively developing tissues of trinitrotoluene-treated embryos than controls. Live 3D imaging of heart tube development at cellular resolution by light-sheet microscopy revealed trinitrotoluene-associated cardiac toxicity, including hypoplastic heart chamber formation and cardiac looping defects, while the real time PCR (polymerase chain reaction) quantitatively measured the molecular changes in the heart and blood development supporting the developmental defects at the molecular level. Identification of cellular toxicity in zebrafish using the state-of-the-art 3D imaging system could form the basis of a sensitive biosensor for environmental contaminants and be further valued by combining it with molecular analysis.

P-glycoprotein confers acquired resistance to 17-DMAG in lung cancers with an ALK rearrangement.

BACKGROUND: Because anaplastic lymphoma kinase (ALK) is dependent on Hsp90 for protein stability, Hsp90 inhibitors are effective in controlling growth of lung cancer cells with ALK rearrangement. We investigated the mechanism of acquired resistance to 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), a geldanamycin analogue Hsp90 inhibitor, in H3122 and H2228 non-small cell lung cancer cell lines with ALK rearrangement. METHODS: Resistant cell lines (H3122/DR-1, H3122/DR-2 and H2228/DR) were established by repeated exposure to increasing concentrations of 17-DMAG. Mechanisms for resistance by either NAD(P)H/quinone oxidoreductase 1 (NQO1), previously known as a factor related to 17-DMAG resistance, or P-glycoprotein (P-gp; ABCB1/MDR1) were queried using RT-PCR, western blot analysis, chemical inhibitors, the MTT cell proliferation/survival assay, and cellular efflux of rhodamine 123. RESULTS: The resistant cells showed no cross-resistance to AUY922 or ALK inhibitors, suggesting that ALK dependency persists in cells with acquired resistance to 17-DMAG. Although expression of NQO1 was decreased in H3122/DR-1 and H3122/DR-2, NQO1 inhibition by dicumarol did not affect the response of parental cells (H2228 and H3122) to 17-DMAG. Interestingly, all resistant cells showed the induction of P-gp at the protein and RNA levels, which was associated with an increased efflux of the P-gp substrate rhodamine 123 (Rho123). Transfection with siRNA directed against P-gp or treatment with verapamil, an inhibitor of P-gp, restored the sensitivity to the drug in all cells with acquired resistance to 17-DMAG. Furthermore, we also observed that the growth-inhibitory effect of 17-DMAG was decreased in A549/PR and H460/PR cells generated to over-express P-gp by long-term exposure to paclitaxel, and these cells recovered their sensitivity to 17-DMAG through the inhibition of P-gp. CONCLUSION: P-gp over-expression is a possible mechanism of acquired resistance to 17-DMAG in cells with ALK rearrangement.

Effective DQE (eDQE) and dose to optimize radiographic technical parameters: a survey of pediatric chest X-ray examinations in Korea.

OBJECTIVE: The purpose of this study was to investigate the effect of various technical parameters for dose optimization in pediatric chest radiological examinations by evaluating effective dose and effective detective quantum efficiency (eDQE). MATERIALS AND METHODS: For tube voltages ranging from 40 to 90 kV in 10 kV increments at the focus-to-detector distance (FDD) of 100, 110, 120, 150, 180 cm, the eDQE was evaluated at same effective dose. RESULTS: The eDQE was considerably higher without the use of the grid on equivalent effective dose. This indicates that the reduction of scatter radiation did not compensate for the loss of absorbed effective photons in the grid. The eDQE increased with increasing FDD because of the greater effective modulation transfer function (eMTF) with lower focal spot blurring. However, most of the major hospitals in Korea employed a short FDD of 100 cm with the grid. The entrance surface air kerma values for the hospitals of this survey exceeded the Korean reference level of 100 µGy. CONCLUSIONS: The different reference levels might be appropriate for the same examination conducted on children of different ages. Also, it is necessary to refine the technical parameters to perform pediatric chest examinations.

Identification and characterization of proteins isolated from microvesicles derived from human lung cancer pleural effusions.

Microvesicles (MVs, also known as exosomes, ectosomes, microparticles) are released by various cancer cells, including lung, colorectal, and prostate carcinoma cells. MVs released from tumor cells and other sources accumulate in the circulation and in pleural effusion. Although recent studies have shown that MVs play multiple roles in tumor progression, the potential pathological roles of MV in pleural effusion, and their protein composition, are still unknown. In this study, we report the first global proteomic analysis of highly purified MVs derived from human nonsmall cell lung cancer (NSCLC) pleural effusion. Using nano-LC-MS/MS following 1D SDS-PAGE separation, we identified a total of 912 MV proteins with high confidence. Three independent experiments on three patients showed that MV proteins from PE were distinct from MV obtained from other malignancies. Bioinformatics analyses of the MS data identified pathologically relevant proteins and potential diagnostic makers for NSCLC, including lung-enriched surface antigens and proteins related to epidermal growth factor receptor signaling. These findings provide new insight into the diverse functions of MVs in cancer progression and will aid in the development of novel diagnostic tools for NSCLC.

A prospective phase 2 study of expeditious EGFR genotyping and immediate therapeutic initiation through extracellular vesicles (EV)-based bronchoalveolar lavage fluid (BALF) liquid biopsy in advanced NSCLC patients.

Background: In our previous study, epidermal growth factor receptor (EGFR) genotyping using extracellular vesicles (EV)-derived DNA isolated from bronchoalveolar lavage fluid (BALF) was proven to be highly concordant with conventional tissue-based genotyping and its turn-around-time (TAT) was only 1-2 days. On this background, we prospectively validated the performance of EV-based BALF liquid biopsy for EGFR genotyping in the real practice of advanced non-small cell lung cancer (NSCLC) patients. Methods: After screening 120 newly diagnosed stage III-IV NSCLC patients, 51 cases were detected as EGFR-mutated by EV-based BALF EGFR genotyping and 40 patients were enrolled for gefitinib treatment. BALF EV were isolated by ultracentrifuge method and EGFR genotyping was performed with PCR-based PNA-clamping assisted fluorescence melting curve analysis. The objective response rate, progression-free survival (PFS), TAT, time to treatment initiation (TTI), and concordance rate were analyzed with clinical parameters. Results: There was only one false positive case among the 120 screened patients and the overall concordance rate between tissue biopsy and EV-based BALF liquid biopsy was 99.2% including the subtype of EGFR mutations. TAT for EV-based BALF EGFR genotyping was 1.9±1.1 days, while tissue-based TAT was 12.1±7.2 days (P<0.001). EGFR genotyping was determined even before obtaining histopathologic report in most cases. TTI in BALF EGFR genotyping was faster than tissue genotyping (7.8±6.5 vs. 13.8±12.9 days). Therapeutic outcomes of response rate and PFS were almost similar to tissue-based results. Conclusions: We demonstrated, for the first time, that EV-based BALF liquid biopsy should be an excellent platform for expeditious EGFR genotyping and rapid therapeutic intervention even before obtaining the result of histopathology in advanced NSCLC patients.

Nailfold capillaroscopy findings of interstitial pneumonia with autoimmune features.

BACKGROUND/AIMS: We evaluated nailfold capillaroscopy (NFC) of interstitial pneumonia with autoimmune features (IPAF) and compared it with that of patients with connective tissue disease-interstitial lung disease (CTD-ILD) and idiopathic interstitial pneumonia (IIP). METHODS: Patients with newly diagnosed as ILD were evaluated using NFC. Baseline demographic, clinical, serological, and high-resolution CT findings were collected. NFC was semi-quantitatively scored with six domains ranging from 0 to 18. In addition, the overall patterns (scleroderma/non-scleroderma patterns) were determined. RESULTS: A total of 81 patients (31 with CTD-ILD, 18 with IPAF, and 32 with IIP) were included. The non-specific interstitial pneumonia pattern was the most common ILD pattern in the CTD-ILD and IPAF groups, whereas the usual interstitial pneumonia pattern was the most common in the IIP group. The semi-quantitative score of the CTD-ILD group was higher than that of the IPAF or IIP groups (5.8 vs 4.2 vs 3.0, p < 0.001, respectively). Giant capillaries and haemorrhages were more frequently present in the CTD-ILD and IPAF groups than in the IIP group. A scleroderma pattern was present in 27.8% of the IPAF group, whereas none of the IIP patients showed a scleroderma pattern. CONCLUSION: NFC findings may be useful in classifying patients with ILD into CTD-ILD/IPAF/IIP.

Validation of a postinjection transmission method for actual rat brain PET.

PURPOSE: Postinjection transmission positron emission tomography (PET) may be useful for shortening the total scan time. In this study, the effect of post-transmission scanning was assessed using PET on a phantom (NU4) and actual rat brain. METHODS: Transmission was performed using (57)Co for 15 min. After a 15-min pre-transmission scan, emission PET was performed in list mode for 1 h, followed by an additional 15-min post-transmission scan. To compare the pre-transmission and post-transmission results, we measured nonuniformity, the recovery coefficient, and the spillover ratio (SOR) using NU4 and rat phantoms. The authors also assessed cerebral glucose metabolism using (18)F-fluorodeoxyglucose (FDG) PET and the binding potential for (18)F-fluorinated N-3-fluoropropyl-2-ß-carboxymethoxy-3-ß-(4-iodophenyl)nortropane (FP-CIT) in rat brain for differences between pre-transmission and post-transmission scanning. RESULTS: Nonuniformity and the SORs for air and water were comparable on the pre-transmission and post-transmission scans. With FDG-PET, after attenuation and scatter corrections no differences were observed in the brain regions on the pre-transmission and post-transmission scans. With FP-CIT-PET, the binding potentials were also not significantly different. CONCLUSIONS: In the present study, we validated a post-transmission method for PET of the rat brain. Post-transmission PET was reliable, and the results were comparable to those of pre-transmission PET. Post-transmission PET eliminates the early tracer uptake time in the PET imaging, making it possible to determine uptake in the conscious subject, which may provide more realistic, "normal" metabolic measurements. Thus, post-transmission PET may be a useful option for increasing the number of subjects who can be evaluated.

Pulmonary alveolar proteinosis as an unusual pattern of lung involvement in Sjögren syndrome.

Primary Sjögren syndrome (pSS) is an autoimmune disease that is characterized by infiltration of lymphocytes in exocrine glands, followed by hypofunction of the glands. Dry mouth and eyes are main symptoms, but there are various extraglandular manifestations in pSS. Nine to 75% of patients have pulmonary involvement such as interstitial lung diseases. Pulmonary alveolar proteinosis (PAP) is also a kind of autoimmune disorder, characterized by the presence of anti-granulocyte/macrophage colony-stimulating factor antibody. A 45-year-old nonsmoking woman was admitted with dyspnea and dry cough. She was diagnosed as having PAP, based on characteristic computed tomography, bronchoalveolar lavage, and lung biopsy findings. At the same time, she was diagnosed with pSS, based on dry mouth, xerophthalmia, positive anti-Ro/La antibodies, and scintigraphic finding of salivary glands. Whole lung lavages and monthly intravenous cyclophosphamide had slight improvement in PAP.