The quick sepsis-related organ failure score has limited value for predicting adverse outcomes in sepsis patients with liver cirrhosis

Jeongsuk Son,Sunhui Choi,Jin Won Huh,Chae-Man Lim,Younsuck Koh,Kang Mo Kim,Ju Hyun Shim,Young-Suk Lim,Sang-Bum Hong 대한내과학회 2020 The Korean Journal of Internal Medicine Vol.35 No.4

Background/Aims: The quick Sepsis-related Organ Failure Assessment (qSOFA) is a newly developed risk stratification tool, which has been presented along with a new sepsis definition, to classify infected patients outside of the intensive care unit (ICU). We evaluated the clinical usefulness of qSOFA for predicting adverse outcomes in sepsis patients with liver cirrhosis. Methods: We performed a retrospective cohort study to assess the utility of qSOFA in sepsis patients with liver cirrhosis for whom medical emergency teams (METs) were activated in general wards at an academic tertiary care hospital between March 2008 and December 2015. qSOFA, Systemic inflammatory response syndrome (SIRS), modified early warning score (MEWS), and sequential (sepsis- related) organ failure assessment (SOFA) scores were calculated according to data at MET activation. Results: Of 188 patients, 69 (36.7%) had a qSOFA score of 0 or 1 point and 119 (63.3%) had ≥ 2 points. The areas under the receiver operating characteristic curve (AUROC) for ICU transfer on the SOFA (AUROC, 0.691; 95% confidence interval [CI], 0.615 to 0.767) or MEWS (AUROC, 0.663; 95% CI, 0.586 to 0.739) were significantly higher compared to those for qSOFA (AUROC, 0.589; 95% CI, 0.507 to 0.671) or SIRS (AUROC, 0.533; 95% CI, 0.451 to 0.616). Conclusions: Our findings suggest that qSOFA score may have limited utility in predicting adverse outcomes in sepsis patients with liver cirrhosis at MET activation. Either MEWS or another screening tool is needed for detecting early sepsis in these patients.

Deep Learning-based Classification of Respiratory Sounds and Its Clinical Value

( Yoonjoo Kim ),( Jeongsuk Koh ),( Seongdae Woo ),( Songi Lee ),( Dahyun Kang ),( Dongil Park ),( Jeongeun Lee ),( Sungsoo Jung ),( Chaeuk Chung ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.-

Introduction Auscultation of respiratory sound is a non-invasive and relatively simple diagnostic method that can be performed anytime, but the information provided is quite useful. Breath sound information markedly improves the accuracy of diagnosis and monitoring of disease status. Despite these advantages, auscultation has a major limitation, subjectivity. Since the interpretation of respiratory sounds requires significant expertise and clinical experience, doctors in training sometimes misidentify respiratory sounds. To overcome such a drawback, we developed an automated classification system of respiratory sounds. Method 2840 respiratory sounds were recorded by a digital stethoscope in a real clinical setting. Three pulmonologists classified them and 1918 sounds including normal sounds, crackles, wheezes, rhonchi were selected. We applied deep learning convolutional neural network (CNN) to identify the classified database. We developed the predictive model for respiratory sound classifcation combining pretrained image feature extractor of series, respiratory sound, and CNN classifer. To evaluate the accuracy of human auscultation ability and compare it with our predictive model, 70 participants were asked to listen to classified sounds and identify them. Result Deep learning-based classification model detected abnormal sounds with an accuracy of 86.5% and the AUC of 0.93. It further classifed abnormal lung sounds into crackles, wheezes, or rhonchi with an overall accuracy of 85.7% and a mean AUC of 0.92. Meanwhile, the accuracy of human auscultation was different depending on the group; 60.3% for medical students, 53.4% for interns, 68.8% for residents, and 80.1% for fellows. Conclusion This respiratory sound classification model using deep learning is expected to complement the limitation of inaccurate auscultation of clinicians and help the rapid diagnosis and appropriate treatment of respiratory diseases. In addition, this model will be useful to meet the current medical demands such as non-face-to-face care due to COVID-19 and telemedicine in hard-to-reach area.

Tri-iodothyronine (T3) as a Prognostic Factor for Patients with Advanced NSCLC Receiving Immune Checkpoint Inhibitors

( Yoonjoo Kim ),( Jeongsuk Koh ),( Seongdae Woo ),( Songi Lee ),( Dahyun Kang ),( Dongil Park ),( Chaeuk Chung ),( Jeongeun Lee ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.-

Introduction Endocrine hormones such as thyroxine and estrogen are known to influence the tumor progression and response to treatment. Despite the importance of ICIs (immune checkpoint inhibitors) in the treatment of advanced NSCLC, few studies have explored the effects of endocrine hormones on NSCLC receiving ICI therapy. Biomarkers like PD-L1 expression in the tumor have been developed to predict the treatment response to ICI. However, only several markers have been clinically verified using standard measurement techniques. We investigated the effects of baseline endocrine hormones in advanced NSCLC on ICI treatment and discovered an easily measurable and useful predictor. Method 156 patients with advanced NSCLC who received PD-1/PD-L1 inhibitors, excluding those with positive driver mutations, were retrospectively analyzed. We collected their clinical information and baseline laboratory findings including endocrine hormones, cytokines, CBC parameters, blood chemistry panels from peripheral blood. We identified the relationship between endocrine hormones and clinical outcomes (OS, PFS, best response), liver metastasis, and other blood markers. Result Shorter PFS was independently associated with liver metastasis, higher cortisol, lower Hb, while shorter OS was associated with liver metastasis, lower T3, higher LDH, lower albumin. According to T3 level, a newly found predictor, patients were divided into two groups, and patients with low T3 levels exhibited shorter PFS, OS, and worse best response. And we confirmed a significant association between the low T3 level and liver metastasis, a negative predictive marker for the treatment response of ICI in NSCLC. Conclusion This study shows that the baseline T3 level, relatively underrated in its clinical importance, is associated with the prognosis and response to ICIs in advanced NSCLC. The specific mechanism is probably related to the decreased function of the liver and the systemic inflammation induced by the interaction with other biomarkers such as IL-6, ACTH, cortisol, C-peptide, Hb, LDH, albumin.

Bronchitis Mimicking Squamous Cell Carcinoma: A Case Report

( Yoonjoo Kim ),( Jeongsuk Koh ),( Dahyun Kang ),( Dongil Park ),( Jeongeun Lee ),( Heesun Park ),( Chaeuk Chung ) 대한결핵 및 호흡기학회 2020 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.128 No.-

Introduction Chronic inflammation can increase cancer risk and various types of inflammatory cells are present within cancer. Inflammation recruits inflammatory cells around epithelial cells, and severe inflammation can cause epithelial cell detachment and cell shape alteration. Thus, the differential diagnosis is sometimes difficult when the pathology specimen contains serious inflammation. Case A 60-year-old male was referred with 2-week history of hemoptysis, cough, and sputum without fever, chill. He was a 30 pack-year ex-smoker. On initial examination, Chest CT revealed diffuse lobar and segmental bronchial wall thickening and luminal narrowing of left lung, suggesting endobronchial tumor spread. 1L, 7, and 9R lymph nodes were enlarged, suggesting metastasis. Bronchoscopy indicated tumorous lesion mixed with mucosal ulceration in lingular segment. Pathology demonstrated high possibility of squamous cell cancer with mucosal inflammation. Immunohistochemistry revealed that epithelial cells were positive for p63 and CK5/6 and had Ki-67 index of 50%. He was treated with antibiotics for 7-day, and symptoms were improved. In follow-up bronchoscopy after 3-week, tumorous lesion of lingular segment was markedly improved and pathology showed mild chronic inflammation without cancer cells. Follow-up CT also showed that diffuse bronchial wall thickenings were significantly improved and the size and extent of LNs enlargement returned. PET-CT showed no evidence of malignancy. For 3-years follow-up, bronchoscopy and CT showed no manifestation of cancer. Discussion In this case, clinical data and initial examinations suggested the diagnosis of lung cancer. However, based on 3-year clinical course and pathologic reviews, we concluded the initial lesion was more likely bronchitis mimicking lung cancer. Also, it is difficult to completely rule out the possibility of early cancer lesions being eliminated by severe inflammation of bronchial walls. In such a case, it might be difficult to make an accurate diagnosis with only initial examinations. Therefore, careful pathology review and follow-up studies are required.

EGFR-TKI Induces Autophagic Flux and Ferritin Accumulation in PC9/GR Cells

( Yoonjoo Kim ),( Jeongsuk Koh ),( Dahyun Kang ),( Dongil Park ),( Jeongeun Lee ),( Heesun Park ),( Chaeuk Chung ) 대한결핵 및 호흡기학회 2020 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.128 No.0

Introduction Despite the development of immunotherapy, EGFR-TKI resistance is one of the most important issues in lung cancer treatment. Autophagy is known to have opposite functions in cancer depending on the situation. Before the establishment of cancer, autophagy acts as suppressor by degrading misfolded proteins. But in the established cancer cells, autophagy functions as survival mechanism. Ferritin is an important member of antioxidant system because it stores iron in nontoxic form. Altered expression of ferritin has been described in many cancers. In this study, we investigated the effect of EGFR-TKI on autophagy and ferritin in EGFR-TKI resistant cells. Method We treated EGFR-TKI resistant lung adenocarcinoma cell line, PC9/GR cells, with EGFR-TKI or control. mCherry-EGFP-LC3B plasmid was transfected by Lipofectamine 2000. Cultured cells were fixed with 4% paraformaldehyde at room temperature, permeabilized with 0.1% Triton X-100 and blocked with 3% FBS in PBS. Following overnight incubation with antibodies, immunofluorescence(IF) was detected using a fluorescence microscope. For an electron microscope(EM), we dehydrated tissues in ethanol and propylene oxide series, embedded in Epon 812 mixture, and polymerized in an oven at 70°C for 24 h. Scanning Transmission Electron Microscpe and Energy Dispersive X-ray spectroscopy was conducted by Monochromated Cs-corrected ARM200F. Result The result of IF study showed PC9/GR cells treated with EGFR-TKI had more autophagic flux than the control. EM scans confirmed PC9/GR cells treated with EGFR-TKI had more double-membrane autophagosomes. And we found PC9/GR cell treated with EGFR-TKI had clusters of high-density particles consisted of Fe atoms. So we concluded PC9/GR cell treated with EGFR-TKI has ferritin accumulation in the cytoplasm. Conclusion We concluded EGFR-TKI significantly induced autophagic flux and ferritin accumulation in PC9/GR cells. Targeting autophagy might be helpful for suppressing the EGFR-TKI resistance and further study about the relationship between ferritin and autophagy in EGFR-TKI resistant cells will be required.

Predictor for deteriorating ward patient with repetitive Medical Emergency Team activation

( Jin Won Huh ),( Ju-ry Lee ),( Youn-kyoung Jung ),( Jin-mi Lee ),( Yujung Shin ),( Sunhui Choi ),( Jeongsuk Son ),( Eun-joo Choi ),( Da Hye Kim ),( Younsuck Koh ),( Chae-man Lim ),( Sang-bum Hong ) 대한결핵 및 호흡기학회 2018 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.126 No.-

Purpose: Recurrent clinical deterioration and repetitive activation of Medical Emergency Team (MET) may be associated with poor outcome. The purpose of this study is to analyze the clinical characteristics of patients with repetitive MET activation and to predict the repetitive MET activation at first MET activation. Methods: We retrospectively reviewed the data of deteriorating patients who were contacted to the MET of Asan Medical Center from Jan 2012 to Nov 2016. The repetitive MET activation means the case of activation within 72 hours after the first MET activation. Results: A total of 7,470 patients were included during the study period. Of these patients, 892 (11.9%) experienced repetitive MET activation. ICU admission rate (49.0% vs. 27.8%, p<0.001) and in-hospital mortality rate (51.7% vs. 36.6%, p<0.001) were higher in the repetitive MET activation group than in the group who were once MET activation. The repetitive MET activation were independently associated with hematologic malignancies (OR: 1.45, 95% CI: 1.13-1.90), activation by respiratory distress(OR: 1.51, 95% CI: 1.20-1.89), airway suctioning (OR: 1.57, 95% CI: 1.24-1.98), apply of Bipap (OR: 1.97, 95% CI: 1.20-3.22), high SOFA (OR: 1.11, 95% CI: 1.07-1.15), and high SpO2/FiO2 score (OR: 1.14, 95% CI: 1.05-1.24) at first MET activation. Conclusion: These risk factors may be useful to identify patients at risk of repetitive MET activation at first MET activation, and then we could classify the high risk group and apply the aggressive intervention for better outcome.