Publications by authors named "Chang Ho Kim"

216 Publications

The role of CECR1 in the immune-modulatory effects of butyrate and correlation between ADA2 and M1/M2 chemokines in tuberculous pleural effusion.

Int Immunopharmacol 2021 Apr 12;96:107635. Epub 2021 Apr 12.

Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, Republic of Korea. Electronic address:

Objectives: The Cat Eye Syndrome Critical Region, Candidate 1 (CECR1) gene encoding adenosine deaminase 2 (ADA2) is mainly expressed by macrophages. Given the immunomodulatory functions of butyrate, we examined the effect of butyrate on CECR1 expression of macrophages and the relationship between ADA2 and M1/M2 macrophages-associated chemokines in pleural fluid of patients with tuberculous pleural effusion (TPE).

Methods: Expression of CECR1 was evaluated in lipopolysaccharide (LPS)-stimulated and/or butyrate treated THP-1 cells. The role of CECR1 on butyrate-induced immune response was evaluated using siRNA transfected THP-1 cells. M1/M2 chemokines and ADA2 were measured in pleural fluid of patients with TPE.

Results: Butyrate promoted the expression of CECR1 and M2-macrophage markers in THP-1 cells. CECR1 was found to be involved in regulating M2 polarization in THP-1 cells treated with LPS and butyrate. Among chemokines measured in pleural fluid of patients with TPE, there was a significant negative correlation between CCL21 and ADA2 levels and between CCL25 and ADA2 levels, and a significant positive correlation between TGF-β and ADA2 levels and between IL-22 and ADA2 levels.

Conclusions: CECR1 played an important role in the butyrate-modulated inflammatory responses in LPS-stimulated THP-1 cells. ADA2 may exert anti-inflammatory effects during the process of pleural inflammation in patients with TPE.
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http://dx.doi.org/10.1016/j.intimp.2021.107635DOI Listing
April 2021

Clinical relevance of emphysema in patients hospitalized with community-acquired pneumonia: clinical features and prognosis.

Clin Respir J 2021 Apr 7. Epub 2021 Apr 7.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.

Introduction: Few studies have investigated the influence of emphysema on clinical features of patients presenting with community-acquired pneumonia (CAP).

Objectives: The aim of this study was to examine the clinical and microbiological features of patients with both CAP and emphysema.

Methods: This retrospective study included patients with CAP who underwent computed tomography (CT) scan at the time of presentation. Patients were allocated into emphysema and control groups, and clinical variables were compared between the 2 groups. The emphysema group was further divided into 3 subgroups (mild, moderate, and severe) according to the extent of emphysema on CT scan. The clinical variables of each subgroup were compared with the control group.

Results: Of 1676 patients, 431 patients (25.7%) were classified into the emphysema group. CAP patients with emphysema were more likely to have a high CURB-65 score and pneumonia severity index and a lower incidence of complicated parapneumonic effusion or empyema. The emphysema group exhibited longer hospital stay. In addition, 30-day mortality in the severe emphysema group was significantly higher compared with the control group. As etiological agents, Streptococcus pneumoniae, Pseudomonas aeruginosa, Enterobacteriaceae, and multi-drug resistant pathogens were significantly more common in the emphysema group compared with the control group.

Conclusions: The presence of emphysema in CAP patients was associated with a more severe form of CAP, a longer hospital stay, and a lower incidence of complicated parapneumonic effusion or empyema. Moreover, CAP patients with severe emphysema exhibited higher 30-day mortality than those without emphysema.
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http://dx.doi.org/10.1111/crj.13370DOI Listing
April 2021

Unique Metabolic Profiles of Korean Rice According to Polishing Degree, Variety, and Geo-Environmental Factors.

Foods 2021 Mar 26;10(4). Epub 2021 Mar 26.

Center for Food and Bioconvergence, Research Institute for Agriculture and Life Sciences, Department of Agricultural Biotechnology, CALS, Seoul National University, Seoul 08826, Korea.

The precise determination of the chemical composition in crops is important to identify their nutritional and functional value. The current study performed a systematic delineation of the rice metabolome, an important staple in Asia, to investigate the following: (1) comparative features between brown and white rice; (2) variety-specific composition (Ilpum vs. Odae); and (3) cultivation of region-dependent metabolic content. Global metabolic profiling and data-driven statistics identified the exclusive enrichment of compounds in brown rice compared to white rice. Next, the authors investigated a variety-governed metabolic phenotype among various geo-environmental factors. Odae, the early-ripening cultivar, showed higher contents of most chemicals compared to the late-ripening cultivar, Ilpum. The authors identified regional specificity for cultivation among five areas in Korea which were characterized by polishing degree and cultivar type. Finally, the current study proposes a possible linkage of the region-specific metabolic signatures to soil texture and total rainfall. In addition, we found tryptophan metabolites that implied the potential for microbe-host interactions that may influence crop metabolites.
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http://dx.doi.org/10.3390/foods10040711DOI Listing
March 2021

Quantifying Physiological Biomarkers of a Microwave Brain Stimulation Device.

Sensors (Basel) 2021 Mar 8;21(5). Epub 2021 Mar 8.

Center for Medical Convergence Metrology, Korea Research Institute of Standards and Science, Daejeon 34113, Korea.

Physiological signals are immediate and sensitive to neural and cardiovascular change resulting from brain stimulation, and are considered as a quantifying tool with which to evaluate the association between brain stimulation and cognitive performance. Brain stimulation outside a highly equipped, clinical setting requires the use of a low-cost, ambulatory miniature system. The purpose of this double-blind, randomized, sham-controlled study is to quantify the physiological biomarkers of the neural and cardiovascular systems induced by a microwave brain stimulation (MBS) device. We investigated the effect of an active MBS and a sham device on the cardiovascular and neurological responses of ten volunteers (mean age 26.33 years, 70% male). Electroencephalography (EEG) and electrocardiography (ECG) were recorded in the initial resting-state, intermediate state, and the final state at half-hour intervals using a portable sensing device. During the experiment, the participants were engaged in a cognitive workload. In the active MBS group, the power of high-alpha, high-beta, and low-beta bands in the EEG increased, and the power of low-alpha and theta waves decreased, relative to the sham group. RR Interval and QRS interval showed a significant association with MBS stimulation. Heart rate variability features showed no significant difference between the two groups. A wearable MBS modality may be feasible for use in biomedical research; the MBS can modulate the neurological and cardiovascular responses to cognitive workload.
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http://dx.doi.org/10.3390/s21051896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962824PMC
March 2021

Clinical usefulness of deep learning-based automated segmentation in intracranial hemorrhage.

Technol Health Care 2021 Feb 26. Epub 2021 Feb 26.

Department of Emergency Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.

Background: Doctors with various specializations and experience order brain computed tomography (CT) to rule out intracranial hemorrhage (ICH). Advanced artificial intelligence (AI) can discriminate subtypes of ICH with high accuracy.

Objective: The purpose of this study was to investigate the clinical usefulness of AI in ICH detection for doctors across a variety of specialties and backgrounds.

Methods: A total of 5702 patients' brain CTs were used to develop a cascaded deep-learning-based automated segmentation algorithm (CDLA). A total of 38 doctors were recruited for testing and categorized into nine groups. Diagnostic time and accuracy were evaluated for doctors with and without assistance from the CDLA.

Results: The CDLA in the validation set for differential diagnoses among a negative finding and five subtypes of ICH revealed an AUC of 0.966 (95% CI, 0.955-0.977). Specific doctor groups, such as interns, internal medicine, pediatrics, and emergency junior residents, showed significant improvement with assistance from the CDLA (p= 0.029). However, the CDLA did not show a reduction in the mean diagnostic time.

Conclusions: Even though the CDLA may not reduce diagnostic time for ICH detection, unlike our expectation, it can play a role in improving diagnostic accuracy in specific doctor groups.
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http://dx.doi.org/10.3233/THC-202533DOI Listing
February 2021

Genetic Polymorphisms in Activating Transcription Factor 3 Binding Site and the Prognosis of Early-Stage Non-Small Cell Lung Cancer.

Oncology 2021 Feb 24:1-9. Epub 2021 Feb 24.

Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery.

Methods: A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated.

Results: Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00-1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46-0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes.

Conclusions: In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC.
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http://dx.doi.org/10.1159/000514131DOI Listing
February 2021

Impact of immune checkpoint gene CD155 Ala67Thr and CD226 Gly307Ser polymorphisms on small cell lung cancer clinical outcome.

Sci Rep 2021 Jan 19;11(1):1794. Epub 2021 Jan 19.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea.

This study was conducted to investigate the impact of genetic variants of immune checkpoint genes on the treatment outcome in small cell lung cancer (SCLC). In the present study, 261 platinum doublet-treated SCLC patients were enrolled. A total of 96 polymorphisms in 33 immune checkpoint-related genes were selected, and their association with chemotherapy response and survival outcomes were analyzed. Among the polymorphisms studied, CD155 rs1058402G > A (Ala67Thr, A67T) and CD226 rs763361C > T (Gly307Ser, G307S) were significantly associated with SCLC treatment outcome. The rs1058402G > A had a worse chemotherapy response and overall survival (under a dominant model, adjusted odds ratio [aOR] = 0.52, 95% confidence interval [CI] = 0.27-0.99, P = 0.05; adjusted hazard ratio [aHR] = 1.55, 95% CI = 1.12-2.14, P = 0.01, respectively). The rs763361C > T had better chemotherapy response and overall survival (under a dominant model, aOR = 2.03, 95% CI = 1.10-3.75, P = 0.02; aHR = 0.69, 95% CI = 0.51-0.94, P = 0.02, respectively). When the rs1058402GA/AA and rs763361CC genotypes were combined, the chemotherapy response and overall survival were significantly decreased as the number of bad genotypes increased (aOR = 0.52, 95% CI = 0.33-0.81, Ptrend = 0.004; aHR = 1.48, 95% CI = 1.19-1.84, Ptrend = 4 × 10, respectively). The 3-D structural model showed that CD155 A67T created a new hydrogen bond and structural change on CD155. These changes resulted in extending the distance and losing the hydrogen bonds between CD155 and CD226, thus weakening CD155/CD226 binding activity. In conclusion, CD155 rs1058402G > A and CD226 rs763361C > T may be useful for predicting the clinical outcomes of SCLC patients after chemotherapy.
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http://dx.doi.org/10.1038/s41598-021-81260-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815735PMC
January 2021

Pulmonary arteriovenous malformation (PAVM) embolization: prediction of angiographically-confirmed recanalization according to PAVM Diameter changes on CT.

CVIR Endovasc 2021 Jan 18;4(1):16. Epub 2021 Jan 18.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: To assess pulmonary arteriovenous malformation (PAVM) recanalization after embolization based on PAVM diameter changes on computed tomography (CT), with pulmonary angiography used as a gold standard.

Methods: A retrospective review was done of patients from 2008 to 2019 with a PAVM treated with endovascular embolization. The treatment outcome was determined by conventional angiography. Follow-up pulmonary angiography was performed when recanalization was suspected on CT, or embolization of all lesions in multiple PAVM patients could not be completed in a single session. Patients who had no preprocedural or follow-up CT were excluded. Draining vein, feeding artery, and venous sac diameter were measured on CT, and diameter reduction rates were compared with the widely-used, binary 70 % criteria.

Results: Forty-one patients with 114 PAVMs were treated during the study period. Eight patients with 50 PAVMs met the inclusion criteria. Mean vein, artery, and venous sac diameter reduction rates were as follows: 59.2 ± 9.3 %, 47.5 ± 10.6 %, and 62.6 ± 13.2 %, respectively, in the occluded group and 5.4 ± 19.5 %, 11.3 ± 17.7 %, and 26.8 ± 14.2 %, respectively, in the recanalized group. The area under the receiver operating characteristic curves for PAVM recanalization for the draining vein was 1.00, showing a better result than the artery (0.97) and sac (0.99). Patients showed > 42 % draining vein diameter reduction in the occluded group and < 32 % in the recanalized group. The widely-used 70 % criteria showed low specificity for predicting recanalization (draining vein, 7.3 %; venous sac, 41.7 %) but 100 % sensitivity for both the draining vein and venous sac.

Conclusions: The widely-used 70 % binary criteria showed limited performance in predicting outcomes in this angiographically-confirmed case series. Further investigations are warranted to establish a strategy for detecting recanalization after PAVM embolization.
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http://dx.doi.org/10.1186/s42155-021-00207-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813953PMC
January 2021

Etiological Distribution and Morphological Patterns of Granulomatous Pleurisy in a Tuberculosis-prevalent Country.

J Korean Med Sci 2021 Jan 4;36(1):e10. Epub 2021 Jan 4.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.

The cause of epithelioid granulomatous inflammation varies widely depending on the affected organ, geographic region, and whether the granulomas morphologically contain necrosis. Compared with other organs, the etiological distribution and morphological patterns of pleural epithelioid granulomas have rarely been investigated. We evaluated the final etiologies and morphological patterns of pleural epithelioid granulomatous inflammation in a tuberculosis (TB)-prevalent country. Of 83 patients with pleural granulomas, 50 (60.2%) had confirmed TB pleurisy (TB-P) and 29 (34.9%) had probable TB-P. Four patients (4.8%) with non-TB-P were diagnosed. With the exception of microbiological results, there was no significant difference in clinical characteristics and granuloma patterns between the confirmed TB-P and non-TB-P groups, or between patients with confirmed and probable TB-Ps. These findings suggest that most pleural granulomatous inflammation (95.2%) was attributable to TB-P in TB-endemic areas and that the granuloma patterns contributed little to the prediction of final diagnosis compared with other organs.
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http://dx.doi.org/10.3346/jkms.2021.36.e10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781852PMC
January 2021

Clinical implication of minimal presence of solid or micropapillary subtype in early-stage lung adenocarcinoma.

Thorac Cancer 2021 01 24;12(2):235-244. Epub 2020 Nov 24.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.

Background: We investigated the clinical features and surgical outcomes of lung adenocarcinoma with minimal solid or micropapillary (S/MP) components, with a focus on stage IA.

Methods: We enrolled 506 patients with lung adenocarcinoma who underwent curative resection in this study. Clinical features and surgical outcomes were compared between the groups with and without the S/MP subtype (S/MP+ and S/MP-, respectively), and between the group with an S/MP proportion of ≤5% (S/MP5) and the S/MP-.

Results: The S/MP subtype was present in 247 patients (48.8%); 129 (25.5%) were grouped as the S/MP5 group. The S/MP+ and S/MP5 groups had larger tumors, higher frequency of lymph node metastasis, and more advanced stages of disease than the S/MP- group (P < 0.001, all comparisons). Pleural, lymphatic, and vascular invasions occurred more frequently in the S/MP+ and S/MP5 groups (P < 0.001, all comparisons for S/MP+ vs. S/MP-; P ≤ 0.01, all comparisons for S/MP5 vs. S/MP-). The S/MP+ and S/MP5 groups showed a shorter time to recurrence and cancer-related death than the S/MP- group(P < 0.001, both comparisons). For stage I, the presence or absence of the S/MP subtype defined prognostic subgroups better than the stage IA/IB classification. Notably, in the multivariate analysis, the minimal S/MP component was a significant predictor of recurrence, even in stage IA.

Conclusions: The presence of the minimal S/MP component was a significant predictor of poor prognosis after surgery, even in stage IA patients. Clinical trials to evaluate the advantages of adjuvant chemotherapy for this subset of patients and further investigations to understand underlying biological mechanisms of poor prognosis are needed.

Key Points: Significant findings of the study: We demonstrated that only minimal presence of solid or micropapillary component was profoundly associated with aggressive clinicopathological features and poor prognosis after complete resection even in stage IA lung adenocarcinoma.

What This Study Adds: Our results suggest that minimal presence of these subtypes is a strong prognostic factor which should be taken into account in the risk assessment for adjuvant chemotherapy in lung adenocarcinoma.
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http://dx.doi.org/10.1111/1759-7714.13754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812076PMC
January 2021

Laboratory and radiological discrimination between tuberculous and malignant pleural effusions with high adenosine deaminase levels.

Korean J Intern Med 2020 Sep 29. Epub 2020 Sep 29.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background/aims: Pleural fluid adenosine deaminase (ADA) levels are useful in discriminating tuberculous pleural effusions (TPEs) from malignant pleural effusions (MPEs). However, some patients with MPE exhibit high-ADA levels, which may mimic TPEs. There is limited data regarding the differential diagnosis between high-ADA MPE and high-ADA TPE. This study aimed to identify the predictors for distinguishing high-ADA MPEs from high-ADA TPEs.

Methods: Patients with TPE and MPE with pleural fluid ADA levels ≥40 IU/L were included in this study. Clinical, laboratory, and radiological data were compared between the two groups. Independent predictors and their diagnostic performance for high-ADA MPEs were evaluated using multivariate logistic regression analysis and receiver operating characteristic curve.

Results: A total of 200 patients (high-ADA MPE, n = 30, and high-ADA TPE, n = 170) were retrospectively included. In the multivariate analysis, pleural fluid ADA, pleural fluid carcinoembryonic antigen (CEA), and pleural nodularity were independent discriminators between high-ADA MPE and high-ADA TPE groups. Using pleural ADA level of 40-56 IU/L (3 points), pleural CEA level ≥6 ng/mL (6 points), and presence of pleural nodularity (3 points) for predicting high-ADA MPEs, a sum score ≥6 points yielded a sensitivity of 90%, specificity of 96%, positive predictive value of 82%, negative predictive value of 98%, and area under the receiver operating characteristic curve of 0.965.

Conclusions: A scoring system using three parameters may be helpful in guiding the differential diagnosis between high-ADA MPEs and high-ADA TPEs.
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http://dx.doi.org/10.3904/kjim.2020.246DOI Listing
September 2020

Ultrasound-guided Percutaneous Needle Biopsy for Small Pleural Lesions: Diagnostic Yield and Impact of CT and Ultrasound Characteristics.

AJR Am J Roentgenol 2020 Oct 7. Epub 2020 Oct 7.

Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, South Korea.

Ultrasound (US)-guided percutaneous pleural needle biopsy (PCPNB) is widely used to evaluate pleural lesions, though has variable diagnostic accuracy. To assess the diagnostic yield of US-guided PCPNB for small (≤ 2 cm) pleural lesions and the impact of CT and US morphologic and technical factors. 103 patients (73 men, 30 women; age, 60.8±13.3 years) who underwent US-guided PCPNB of a small pleural lesion by a single experienced operator from July 2013 to December 2019 were retrospectively analyzed. Final diagnosis was established via histopathological results, including from repeat US-guided and CT-guided biopsies, as well as imaging and clinical follow-up. Pleural morphology and thickness were assessed on CT and US, and needle pathway length throughout the pleura was measured on US. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. The association between diagnostic yield with imaging and technical factors was evaluated. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal CT pleural thickness cutoff value. Multivariable logistic regression was performed to identify independent predictors of diagnostic yield. Diagnostic accuracy, sensitivity, specificity, PPV, and NPV of US-guided PCPNB were 85.4%, 84.8%, 100%, 100%, and 21.1%, respectively. Diagnostic, compared with non-diagnostic, procedures more commonly (p≤0.002) exhibited nodular morphology on CT (96.4% vs. 3.6%) and US (97.3% vs. 2.7%,), greater pleural thickness on CT (7.5 mm vs. 3.2 mm) and US (7.4 mm vs. 3.0 mm), and greater needle pathway length (11.0 mm vs. 6.1 mm). Optimal CT pleural thickness cut-off value was 4.5 mm. Diagnostic yield was 96.4% for nodular CT lesions, 95.0% for diffuse CT lesions with thickness ≥4.5 mm, 55.6% for diffuse CT lesions with thickness <4.5 mm, and 100.0% for diffuse CT lesions with nodular US morphology. Nodular US morphology (p=0.002) and needle pathway length (p=0.035) were independent predictors of diagnostic yield. US-guided PCPNB has excellent diagnostic accuracy for small pleural lesions; imaging characteristics influence this accuracy. US-guided PCPNB is highly likely to be diagnostic for small pleural lesions with nodular morphology on CT or US, or with pleural thickness ≥4.5 mm.
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http://dx.doi.org/10.2214/AJR.20.24120DOI Listing
October 2020

Coronavirus disease 2019 pneumonia may present as an acute exacerbation of idiopathic pulmonary fibrosis.

J Thorac Dis 2020 Jul;12(7):3902-3904

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

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http://dx.doi.org/10.21037/jtd-20-1658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399424PMC
July 2020

Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer.

Oncology 2020 13;98(12):897-904. Epub 2020 Aug 13.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: This study was conducted to investigate the association between genetic variants in one-carbon metabolism and survival outcomes of surgically resected non-small cell lung cancer (NSCLC).

Methods: We genotyped 41 potentially functional variants of 19 key genes in the one-carbon metabolism pathway among 750 NSCLC patients who underwent curative surgery. The association between genetic variants and overall survival (OS)/disease-free survival (DFS) were analyzed.

Results: Among the 41 single-nucleotide polymorphisms (SNPs) analyzed, 4 SNPs (MTHFD1L rs6919680T>G and rs3849794T>C, MTR rs2853523C>A, and MTHFR rs4846049G>T) were significantly associated with survival outcomes. MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (adjusted hazard ratio [aHR] = 0.73, 95% confidence interval [CI] = 0.54-0.99, p = 0.04) and worse OS (aHR = 2.14, 95% CI = 1.13-4.07, p = 0.02), respectively. MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.41, 95% CI = 1.08-1.83, p = 0.01; and aHR = 1.97, 95% CI = 1.10-3.53, p = 0.02, respectively). When the patients were divided according to histology, the associations were significant only in squamous cell carcinoma (SCC), but not in adenocarcinoma (AC). In SCC, MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (aHR = 0.64, 95% CI = 0.41-1.00, p = 0.05) and worse OS (aHR = 2.77, 95% CI = 1.11-6.91, p = 0.03), respectively, and MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.73, 95% CI = 1.17-2.56, p = 0.01; and aHR = 2.78, 95% CI = 1.12-6.88, p = 0.03, respectively).

Conclusions: Our results suggest that the genetic variants in the one-carbon metabolism pathway could be used as biomarkers for predicting the clinical outcomes of patients with early-stage NSCLC.
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http://dx.doi.org/10.1159/000509658DOI Listing
December 2020

Expression of key regulatory genes in necroptosis and its effect on the prognosis in non-small cell lung cancer.

J Cancer 2020 11;11(18):5503-5510. Epub 2020 Jul 11.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Accumulating evidence suggests that necroptosis, or programmed necrotic cell death, may play a significant role in cancer. We evaluated the expression of key molecules in necroptosis and their association with clinical features and prognosis in NSCLC. A total of 253 NSCLC patients (96 squamous cell carcinoma [SCC] cases and 157 adenocarcinoma [AC] cases) who underwent curative resection were included. Tumor tissues and corresponding normal tissues were investigated for relative mRNA expression levels of , , and . Difference in disease free survival (DFS) was analyzed according to the expression levels of these molecules in tumor tissues. NSCLC tissues had significantly lower expression of , , and than normal tissues ( = 1 x 10, = 8 x 10, and = 4 x 10, respectively). In subgroup analysis, SCCs had significantly lower , , and expression ( = 5 x 10, = 3 x 10, = 1 x 10, respectively), and ACs had significantly lower and expression ( = 0.01 and = 6 x 10, respectively) than normal tissues. Low expression of , , and in tumors was associated with a worse DFS (HR = 1.71, = 0.01; HR = 1.53, = 0.04; and HR = 1.53, = 0.04, respectively) in a multivariate analysis. In SCC, none of the , , and expression was significantly associated with DFS. However, in AC, low expression of , , and was significantly associated with worse DFS (HR = 1.67, = 0.03; HR = 1.70, = 0.03; and HR = 1.81, = 0.02, respectively). Key regulatory genes in necroptosis, , , and , were downregulated in NSCLC, and their lower expression in NSCLC may be used to predict early recurrence after curative resection, especially in AC.
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http://dx.doi.org/10.7150/jca.46172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391199PMC
July 2020

Effect of genetic variation in Notch regulator DTX1 on SCLC prognosis compared with the effect on NSCLC prongosis.

Thorac Cancer 2020 09 22;11(9):2698-2703. Epub 2020 Jul 22.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.

Deltex-1 (DTX1) is a negative regulator of the Notch signaling pathway. Here, we investigated the clinical effect of DTX1 rs1732786A > G, which is associated with better prognosis in patients with early-stage non-small cell lung cancer (NSCLC), in 261 patients with small cell lung cancer (SCLC). DTX1 rs1732786A > G was associated with a significantly worse chemotherapy response and lower overall survival in the codominant model (odds ratio = 0.42, 95% confidence interval [CI]: 0.26-0.66, P = 2 × 10 ; hazard ratio = 1.47, 95% CI: 1.17-1.84, P = 0.001, respectively). An in vitro luciferase assay was performed, and the 1732786G allele demonstrated significantly higher promoter activity than the 1732786A allele (P = 2 × 10 ). In summary, DTX1 rs1732786A > G was associated with poor prognosis in patients with SCLC as opposed to patients with NSCLC. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: DTX1 rs1732786A > G was associated with better prognosis in patients with early-stage non-small cell lung cancer (NSCLC) in our previous study. WHAT THIS STUDY ADDS: DTX1 rs1732786A > G was associated with a significantly worse chemotherapy response and lower overall survival in small cell lung cancer (SCLC).
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http://dx.doi.org/10.1111/1759-7714.13566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471053PMC
September 2020

Clinical Impact of N-Terminal Prohormone of Brain Natriuretic Peptide on Patients Hospitalized with Community-Acquired Pneumonia.

Am J Med Sci 2020 10 2;360(4):383-391. Epub 2020 Jun 2.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.

Background: Risk stratification is important for the management of community-acquired pneumonia (CAP). The present study aimed to investigate the clinical impact of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) on prognosis and to identify clinical characteristics associated with NT-proBNP elevation in CAP patients.

Methods: This retrospective study included patients hospitalized for CAP at a tertiary referral center and who underwent measurement plasma NT-proBNP levels. Based on 30-day mortality, patients (n = 1,821) were divided into 2 groups, survivors (n = 150) and nonsurvivors (n = 1,671), and clinical and laboratory findings were compared.

Results: In multivariate analysis, blood levels of NT-proBNP (>942.5 pg/mL), albumin (<3.3 g/dL), and troponin I (>0.018 ng/mL) independently predicted 30-day mortality. Of these blood biomarkers, NT-proBNP exhibited the highest C-statistic, followed by albumin. NT-proBNP level/CURB-65 score and NT-proBNP level/pneumonia severity index (PSI) class exhibited significantly higher C-statistics than CURB-65 score and PSI class alone, respectively. The 3-test combinations of CURB-65 score/NT-proBNP level/albumin level and PSI class/NT-proBNP level/albumin level exhibited significantly higher C-statistics than the 2-test combinations. NT-proBNP elevation was associated with increased age, heart disease and chronic kidney disease and NT-proBNP levels only weakly or moderately correlated with other blood biomarkers.

Conclusions: NT-proBNP level was a useful marker for the prediction of 30-day mortality in patients hospitalized with CAP, and provided additional prognostic value to PSI or CURB-65 alone.
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http://dx.doi.org/10.1016/j.amjms.2020.05.042DOI Listing
October 2020

Comparison of biochemical parameters and chemokine levels in pleural fluid between patients with anergic and non-anergic tuberculous pleural effusion.

Tuberculosis (Edinb) 2020 07 13;123:101940. Epub 2020 May 13.

Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, South Korea; Kyungpook National University Bio-Medical Research Institute, Daegu, South Korea. Electronic address:

Pleural fluid (PF) immune response in anergic tuberculous pleural effusion (TPE) patients is poorly understood. This study aimed to compare PF biochemical parameters and chemokine levels between anergic and non-anergic TPE patients. Chemokine arrays, cytokine measurements, and flow cytometry were performed in 58 patients (TPE [non-anergic (n = 32) and anergic (n = 10)] and malignant pleural effusion (MPE) [n = 16]). PF adenosine deaminase 2 (ADA2) levels were significantly lower in anergic TPE patients than in non-anergic TPE patients (p = 0.048). Among the 40 chemokines tested, PF CCL27 levels were significantly higher in anergic TPE patients than in non-anergic TPE and MPE patients (p < 0.001). The percentage of CD4CCR10T cells in PF was higher in anergic TPE patients than in non-anergic TPE and MPE patients (p = 0.001). We reported here that CCL27/CCR10 interactions might contribute to pathophysiology in anergic TPE. PF CCL27 and CD4CCR10T cells may help in diagnosing TPE in patients with moderate elevation of PF ADA levels.
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http://dx.doi.org/10.1016/j.tube.2020.101940DOI Listing
July 2020

Electrocardiographic changes as a prognostic tool for hospitalized patients with pulmonary embolism.

Thromb Res 2020 08 19;192:61-63. Epub 2020 Mar 19.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

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http://dx.doi.org/10.1016/j.thromres.2020.03.013DOI Listing
August 2020

Idiopathic Pleural Effusions: Characteristics and Discrimination From Cytology-Negative Malignant Pleural Effusions.

Am J Med Sci 2020 09 25;360(3):236-242. Epub 2020 Apr 25.

Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, Republic of Korea. Electronic address:

Background: The etiology of pleural effusions often remained unknown notwithstanding surgical pleural biopsy and further clinical observation. A better understanding of clinical characteristics of patients with idiopathic pleural effusion (IPE) may improve the ability to differentiate between IPEs and cytology-negative malignant pleural effusions (MPEs) and facilitate the identification of patients requiring invasive investigation. However, little is known about the clinical factors that can help distinguish patients with IPE from those with cytology-negative MPE.

Materials And Methods: Patients who were diagnosed with IPE or cytology-negative MPE between 2010 and 2017 were enrolled in this retrospective study. Clinical, laboratory and radiologic characteristics were compared between patients with IPE and cytology-negative MPE. Diagnostic performances of predictors for IPE were assessed using receiver operating characteristic curves.

Results: Of 146 patients undergoing pleural biopsy owing to cytology-negative pleural effusion of uncertain cause, MPE was confirmed in 54 patients. IPE was ultimately diagnosed in 22 patients. Multivariate analysis demonstrated that a minimal amount of pleural effusion (odds ratio [OR] = 12.41, P = 0.039), presence of pleural nodularity (OR = 0.01, P < 0.001) and pleural fluid carcinoembryonic antigen levels less than 14 ng/mL (OR = 87.59, P = 0.002) were independent factors for distinguishing IPEs from cytology-negative MPEs. A combination of the absence of pleural nodularity with pleural fluid carcinoembryonic antigen levels less than 14 ng/mL yielded an area under the curve of 0.94 (sensitivity = 91% and specificity = 96%).

Conclusions: Using these readily available parameters to identify IPE in patients with cytology-negative exudative effusion of unknown cause can help guide decision-making when choosing to perform an invasive pleural biopsy or to take a conservative approach.
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http://dx.doi.org/10.1016/j.amjms.2020.04.020DOI Listing
September 2020

Characteristics and survival impact of polymorphonuclear leucocyte-predominant malignant pleural effusions secondary to lung cancer.

Clin Respir J 2020 Apr 15. Epub 2020 Apr 15.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Introduction: In comparison with mononuclear leucocyte (MNL)-predominant malignant pleural effusions (MPEs), polymorphonuclear leucocyte (PMNL)-predominant MPEs have rarely been investigated and may be associated with a poorer prognosis.

Objectives: To investigate the characteristics and survival impact of PMNL-predominant MPEs secondary to lung cancer.

Methods: This retrospective study included patients with MPE secondary to lung cancer, which were classified into the PMNL- and MNL-predominant groups according to cellular predominance in the pleural fluid. Clinical, hematological, radiological, and pleural fluid data were compared between the groups, and the survival impact of PMNL predominance in MPE was evaluated.

Results: Of the 193 MPEs included, 37 (19%) were characterised by PMNL predominance. Compared to the MNL-predominant group, the PMNL-predominant group showed significantly poorer patient performances (P = .001), higher white blood cell counts (P = .009), higher neutrophil counts, higher blood neutrophil-to-lymphocyte ratio (P = .046), higher serum C-reactive protein (P = .003), lower serum albumin (P < .001), lower pleural fluid pH (P = .002) and higher pleural fluid lactate dehydrogenase (P = .029) levels. In contrast, most clinical and radiological findings, including the duration of symptoms, showed no significant intergroup differences. A shift towards MNL predominance was observed in only 38% of the PMNL-predominant patients who underwent repeat thoracentesis. Overall survival of the PMNL-predominant group was significantly shorter than the MNL-predominant group (P = .003).

Conclusions: PMNL predominance in MPEs secondary to lung cancer may be observed in variable phases with respect to the duration of symptoms and the time of thoracentesis. Overall, PMNL-predominant MPEs were associated with more advanced stages and poorer survival outcomes, compared to MNL-predominant MPEs.
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http://dx.doi.org/10.1111/crj.13195DOI Listing
April 2020

Polymorphisms in Glycolysis-Related Genes Are Associated with Clinical Outcomes of Paclitaxel-Cisplatin Chemotherapy in Non-Small Cell Lung Cancer.

Oncology 2020 6;98(7):468-477. Epub 2020 Apr 6.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea,

Objective: This study was conducted to investigate whether polymorphisms in glycolysis-related genes are associated with clinical outcomes of patients with advanced-stage non-small cell lung cancer (NSCLC) undergoing chemotherapy.

Methods: A total of 377 patients with NSCLC were enrolled. Sixty-five single-nucleotide polymorphisms in 26 genes involved in the glycolytic pathway were evaluated. The associations of the variants with the chemotherapy response and overall survival (OS) were analyzed.

Results: Among the 65 variants investigated, PFKL rs2073436C>G and GPI rs7248411C>G significantly correlated with clinical outcomes after chemotherapy in multivariate analyses. PFKL rs2073436C>G was significantly associated with both a worse response to chemotherapy (adjusted odds ratio [aOR] = 0.64, 95% CI = 0.45-0.90, p = 0.01) and a worse OS (adjusted hazard ratio [aHR] = 1.35, 95% CI = 1.14-1.61, p = 0.001). GPI rs7248411C>G was significantly associated with both a better chemotherapy response (aOR = 1.58, 95% CI = 1.07-2.23, p = 0.02) and a better OS (aHR = 0.80, 95% CI = 0.66-0.98, p = 0.03). When stratified by tumor histology, PFKL rs2073436C>G was significantly associated with OS only in squamous cell carcinoma, whereas GPI rs7248411C>G exhibited a significant association with the chemotherapy response and OS only in adenocarcinoma.

Conclusion: This result suggests that the PFKL rs2073436C>G and GPI rs7248411C>G are useful for predicting the clinical outcome of first-line paclitaxel-cisplatin chemotherapy in NSCLC.
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http://dx.doi.org/10.1159/000504175DOI Listing
July 2020

Clinical characteristics and outcome in patients with pulmonary embolism undergoing coronary angiography.

Vasc Med 2020 04 7;25(2):157-159. Epub 2020 Feb 7.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Korea.

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http://dx.doi.org/10.1177/1358863X19900239DOI Listing
April 2020

The effect of susceptibility variants, identified in never-smoking female lung cancer cases, on male smokers.

Korean J Intern Med 2020 07 30;35(4):929-935. Epub 2019 Dec 30.

Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.

Background/aims: Genome wide and candidate gene association studies have identified polymorphisms associated with the risk of lung cancer in never-smokers. This study was conducted to evaluate the association between 11 polymorphisms identified in female never smokers and the lung cancer risk in male smokers.

Methods: This study included 714 lung cancer patients and 626 healthy controls. The polymorphisms were genotyped using SEQUENOM MassARRAY iPLEX assay or Taq-Man assay.

Results: Two polymorphisms were associated with the risk of lung cancer in male smokers, as in female never smokers. Male smokers carrying the rs4975616 variant allele had a significantly decreased risk of lung cancer (in a codominant model: odds ratio, 0.77; 95% confidence interval, 0.61 to 0.96; p = 0.02). The rs9387478 polymorphism also reduced lung cancer risk in male smokers (in a codominant model: odds ratio, 0.85; 95% confidence interval, 0.73 to 0.997; p = 0.046). In a stratified analysis, the association between these polymorphisms and the risk of lung cancer was predominant in lighter smokers and for cases of adenocarcinoma.

Conclusion: These results suggest that a subset of polymorphisms known to be associated with the risk of lung cancer in female never smokers is also associated with the risk of lung cancer in male smokers.
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http://dx.doi.org/10.3904/kjim.2018.417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373985PMC
July 2020

Sarcoidosis presenting pulmonary subsolid nodules that mimic lung adenocarcinoma in a patient with history of uveitis and arrhythmia: a case report.

Ann Transl Med 2019 Sep;7(18):496

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Sarcoidosis is an idiopathic systemic granulomatous disorder that can involve any organ, although the lung is the most commonly affected site; moreover, it may affect multiple organs simultaneously or serially over a long time span. Diagnosing sarcoidosis can be a challenge in cases presenting an isolated extra-thoracic lesion at the early stage of disease. Pulmonary nodular lesion, a rare radiologic finding, may also lead to delayed diagnosis of sarcoidosis. We reported a case of atypical pulmonary nodular sarcoidosis that was suspected as lung adenocarcinoma, which was diagnosed about 20 years after initial isolated extra-thoracic manifestation occurred.
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http://dx.doi.org/10.21037/atm.2019.08.98DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803198PMC
September 2019

Polymorphism in ASCL1 target gene DDC is associated with clinical outcomes of small cell lung cancer patients.

Thorac Cancer 2020 01 5;11(1):19-28. Epub 2019 Nov 5.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: Achaete-scute homolog 1 (ASCL1) is a basic helix-loop-helix transcription factor and is essential in the differentiation of neuroendocrine cells and neural tissues. ASCL1 is frequently overexpressed in small cell lung cancer (SCLC) and plays a crucial role in the pathogenesis of SCLC.

Methods: This study was conducted to identify the association between single nucleotide polymorphisms (SNPs) in ASCL1 target genes and clinical outcomes of patients with SCLC after chemotherapy. A total of 261 patients diagnosed with SCLC were enrolled in this study. The association between 103 SNPs in 58 ASCL1 target genes and the response to chemotherapy and survival of patients with SCLC were analyzed.

Results: Among the 103 SNPs, 10 SNPs were significantly associated with the response to chemotherapy, and 19 SNPs were associated with OS in multivariate analyses. Among these, Dopa Decarboxylase (DDC) rs12666409A>T was significantly associated with both a worse response to chemotherapy and worse OS (adjusted odds ratio [aOR] = 0.40, 95% CI = 0.18-0.90, P = 0.03; adjusted hazard ratio [aHR] = 1.52, 95% CI = 1.10-2.10, P = 0.01, respectively, under a dominant model). In a stage-stratified analysis, the association was significant only in the extensive disease subgroup (aOR = 0.19, 95% CI = 0.06-0.60, P = 0.01; aHR = 1.73, 95% CI = 1.16-2.56, P = 0.01, respectively, under a dominant model), but not in the limited disease subgroup.

Conclusion: The results of our study suggest that DDC rs12666409A>T may be useful markers for predicting the clinical outcomes of patients with SCLC undergoing chemotherapy.
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http://dx.doi.org/10.1111/1759-7714.13212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938757PMC
January 2020

Clinical and radiological features of pulmonary tuberculosis in patients with idiopathic pulmonary fibrosis.

Respir Investig 2019 Nov 25;57(6):544-551. Epub 2019 Sep 25.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, South Korea.

Background: Data regarding the radiological and clinical features of pulmonary tuberculosis (PTB) in patients with idiopathic pulmonary fibrosis (IPF) are limited. Accordingly, the aim of this study was to investigate the clinico-radiological features of PTB in patients with IPF.

Methods: Clinico-radiological variables were retrospectively compared between PTB patients with and without IPF (TB-IPF and TB-control, respectively), and computed tomography (CT) findings were compared between the TB-IPF group and patients with nontuberculous mycobacterial lung disease and IPF (NTM-IPF).

Results: Of 609 IPF patients, 28 (4.6%) were diagnosed with PTB. In the TB-IPF group, incidental radiological finding was the most common presenting manifestation, and the rate of treatment success was significantly lower than in the TB-control group. On CT scan, the typical locations of reactivated PTB were significantly less often involved in the TB-IPF group than in the TB-control group. The TB-IPF group exhibited a significantly lower frequency of centrilobular nodules and a higher rate of consolidation-predominant pattern than did the TB-control group. CT findings in the TB-IPF group were similar to those in the NTM-IPF group.

Conclusions: Incidental radiological findings were the most common presenting manifestations in TB-IPF patients, who were more likely to present with atypical PTB manifestations on CT scan and who experienced poorer treatment outcomes.
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http://dx.doi.org/10.1016/j.resinv.2019.08.001DOI Listing
November 2019

Differential diagnosis between lymphoma-associated malignant pleural effusion and tuberculous pleural effusion.

Ann Transl Med 2019 Aug;7(16):373

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.

Background: Lymphoma-associated malignant pleural effusions (L-MPE) can mimic tuberculous pleural effusion (TPE) characterized by lymphocytic exudate with high adenosine deaminase (ADA) levels. Furthermore, the low cytological yield of L-MPE makes differentiation between L-MPE and TPE more challenging. However, there are few data regarding differential diagnosis of L-MPE and TPE.

Methods: All consecutive patients diagnosed with L-MPE or TPE between January 2011 and December 2016 were retrospectively recruited using the Electronic Medical Record database. Clinical symptoms and laboratory and pleural fluid data [including serum lactate dehydrogenase (LDH), C-reactive protein, and pleural fluid ADA levels] were compared between L-MPE and TPE. Useful variables in the differential diagnosis of L-MPE and TPE were evaluated by multivariate logistic regression analysis.

Results: Seventeen patients with L-MPE and 216 patients with TPE were included in this study. In the multivariate analysis, fever was negatively associated with L-MPE [odds ratio (OR): 0.175, 95% confidence interval (CI): 0.033-0.941, P=0.042], while serum LDH levels were positively associated with L-MPE (OR: 1.005, 95% CI: 1.003-1.007, P<0.001). Serum LDH >460 U/L provided a sensitivity of 76% and a specificity of 81% to distinguish L-MPE and TPE. In contrast, serum C-reactive protein and pleural fluid ADA levels were not significantly different between the groups.

Conclusions: Patients with L-MPE and TPE present very similar clinical, laboratory, and pleural fluid characteristics. Fever and serum LDH levels may be helpful in guiding the differential diagnosis of L-MPE and TPE. Lymphoma should be kept in mind in the differential diagnosis in patients with lymphocytic pleural effusion and high ADA levels.
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http://dx.doi.org/10.21037/atm.2019.07.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736794PMC
August 2019

Vibrational spectroscopy and imaging with non-resonant coherent anti-Stokes Raman scattering: double stimulated Raman scattering scheme.

Opt Express 2019 Aug;27(16):23558-23575

We introduce a new coherent anti-Stokes Raman scattering (CARS) suppression scheme based on measuring a non-resonant CARS loss signal by three-beam (pump-Stokes-depletion) double stimulated Raman scattering (SRS) processes, which can be potentially of use for super-resolution Raman microscopy. In the converging configuration with employing both pump-depletion and Stokes-depletion SRS processes, we obtained approximately 94% suppression of non-resonant CARS signal, which is about 1.5 times more efficient than that with the parallel configuration with pump-Stokes and pump-depletion SRS processes. Such an enhanced suppression efficiency in the converging configuration results from a simultaneous loss of photons both in the pump and Stokes beams by double SRS processes, leading to an efficient suppression of the pump-Stokes-pump CARS signal. Based on the present method, we further propose two potential applications: (1) non-resonant background-free CARS imaging and (2) label-free super-resolution Raman imaging, and carry out simple numerical simulations to show their feasibility.
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http://dx.doi.org/10.1364/OE.27.023558DOI Listing
August 2019