1.Blood Lymphocytes as a Prognostic Factor for Stage III Non-Small Cell Lung Cancer with Concurrent Chemoradiation
Yong-Hyub KIM ; Yoo-Duk CHOI ; Sung-Ja AHN ; Young-Chul KIM ; In-Jae OH ; Taek-Keun NAM ; Jae-Uk JEONG ; Ju-Young SONG
Chonnam Medical Journal 2024;60(1):40-50
We aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). This is a secondary study of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29-0.97). In multivariate analysis, patient age (p=0.014) and gross tumor volume (GTV, p=0.031) were significant factors associated with overall survival, while TLC reduction (p=0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p=0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. Immunohistochemical analysis of programmed death ligand 1 and CD8 expression on T cells was performed on 84 patients. CD8 expression was not significantly associated with the pretreatment lymphocyte count (p=0.673), and PDL1 expression was not significantly associated with OS or PFS. Univariate analysis revealed that high CD8 expression in TILs was associated with favorable OS and was significantly associated with favorable PFS (p=0.032). TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, in the era of immunotherapy, constraining the volume of the radiation dose to the whole heart must be prioritized for the better survival outcomes.
2.Immune Cells Are DifferentiallyAffected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice
Jung Ah KIM ; Sung-Hee KIM ; Jeong Jin KIM ; Hyuna NOH ; Su-bin LEE ; Haengdueng JEONG ; Jiseon KIM ; Donghun JEON ; Jung Seon SEO ; Dain ON ; Suhyeon YOON ; Sang Gyu LEE ; Youn Woo LEE ; Hui Jeong JANG ; In Ho PARK ; Jooyeon OH ; Sang-Hyuk SEOK ; Yu Jin LEE ; Seung-Min HONG ; Se-Hee AN ; Joon-Yong BAE ; Jung-ah CHOI ; Seo Yeon KIM ; Young Been KIM ; Ji-Yeon HWANG ; Hyo-Jung LEE ; Hong Bin KIM ; Dae Gwin JEONG ; Daesub SONG ; Manki SONG ; Man-Seong PARK ; Kang-Seuk CHOI ; Jun Won PARK ; Jun-Won YUN ; Jeon-Soo SHIN ; Ho-Young LEE ; Ho-Keun KWON ; Jun-Young SEO ; Ki Taek NAM ; Heon Yung GEE ; Je Kyung SEONG
Immune Network 2024;24(2):e7-
Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.
3.The Evaluation of Surrogate Laboratory Parameters for Predicting the Trend of Viral Loads in Patients with Severe Fever with Thrombocytopenia Syndrome:Cross-Correlation Analysis of Time Series
Misun KIM ; Hyunjoo OH ; Sang Taek HEO ; Sung Wook SONG ; Keun Hwa LEE ; Myeong Jin KANG ; Jeong Rae YOO
Infection and Chemotherapy 2022;54(3):470-482
Background:
There is a correlation between the severe fever with thrombocytopenia syndrome (SFTS) viral load and disease severity; however, measurement of viral load is difficult in general laboratory and it takes time to obtain a viral load value. Here, the laboratory parameters for predicting the dynamic changes in SFTS viral load were identified.In addition, we tried to evaluate a specific time point for the early determination of clinical deterioration using dynamic change of laboratory parameters.
Materials and Methods:
This observational study included SFTS patients in Korea (2013 - 2020). Cross-correlation analysis at lagged values was used to determine the temporal correlation between the SFTS viral loads and time-series variables. Fifty-eight SFTS patients were included in the non-severe group (NSG) and 11 in the severe group (SG).
Results:
In the cross-sectional analyses, 10 parameters -white blood cell, absolute neutrophil cell, lymphocyte, platelet, activated partial thromboplastin time (aPTT), C-reactive protein, aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK)- were assessed within 30 days from the onset of symptoms; they exhibited three different correlation patterns: (1) positive, (2) positive with a time lag, and (3) negative. A prediction score system was developed for predicting SFTS fatality based on age and six laboratory variables -platelet, aPTT, AST, ALT, LDH, and CPKin 5 days after the onset of symptoms; this scoring system had 87.5% sensitivity and 86.0% specificity (95% confidence interval: 0.831 - 1.00, P <0.001).
Conclusion
Three types of correlation patterns between the dynamic changes in SFTS viral load and laboratory parameters were identified. The dynamic changes in the viral load could be predicted using the dynamic changes in these variables, which can be particularly helpful in clinical settings where viral load tests cannot be performed. Also, the proposed scoring system could provide timely treatment to critical patients by rapidly assessing their clinical course.
5.Invasive Pneumococcal Disease Caused by Non-Vaccine Type Multidrug-Resistant Streptococcus pneumoniae Transmitted by Close Contact in a Healthy Adult
Jeong Rae YOO ; Suhyun OH ; Jae Geun LEE ; Young Ree KIM ; Keun Hwa LEE ; Sang Taek HEO
Yonsei Medical Journal 2019;60(11):1103-1107
The incidence of vaccine-type Streptococcus pneumoniae carriage and disease have declined in vaccinated children as well as in unvaccinated children and adults. However, diseases caused by non-vaccine type (NVT) S. pneumoniae are increasing. In this study, we report an invasive pneumococcal disease (IPD) caused by NVT multidrug-resistant (MDR) S. pneumoniae transmitted from a vaccinated infant to an unvaccinated healthy woman, and the clinical characteristics of this serotype. A 29-year-old previously healthy woman visited our hospital with fever and headache. She had been breastfeeding her baby for 8 months. She was diagnosed with brain abscess and sinusitis caused by S. pneumoniae. Although the patient had no previous exposure to antibiotics, antibiotic susceptibility test identified the pathogen as MDR. The patient's family members were examined using nasopharyngeal swabs for bacterial culture. The serotype of S. pneumoniae identified from the blood, abscess, and sputum of the patient was 15B/C. After investing the patient's family members, we found that the serotype from nasopharyngeal specimen of her baby was the same. We described an invasive MDR pneumococcal disease in an immunocompetent young adult in the community. IPD likely spread to the patient by close contact with her baby, who harbored S. pneumoniae of NVT. The spread of NVT S. pneumoniae in the post-vaccine era has increased in the community, and resistance pattern for S. pneumoniae of 15B/C changed compared to the pre-pneumococcal conjugate vaccine era. The spread of MDR pathogens causing IPD among family members should be monitored.
Abscess
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Adult
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Anti-Bacterial Agents
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Brain Abscess
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Breast Feeding
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Child
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Epidural Abscess
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Female
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Fever
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Headache
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Humans
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Incidence
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Infant
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Pneumonia
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Serogroup
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Sinusitis
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Sputum
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Streptococcus pneumoniae
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Streptococcus
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Vaccination
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Young Adult
6.Changes in Serotype of Streptococcus pneumoniae After the Introduction of the 13-Valent Pneumococcal Vaccine in a Homogenous Population on Jeju Island
Jeong Rae YOO ; Sang Taek HEO ; Hyunjoo OH ; Suhyun OH ; Young Ree KIM ; Keun Hwa LEE
Infection and Chemotherapy 2019;51(1):67-72
We compared the serotypes of Streptococcus pneumoniae between the pre-pneumococcal conjugate vaccine (PCV)13 era and post-PCV13 era among homogenous inhabitants of an isolated South Korean island. A total of 325 S. pneumoniae strains were isolated. In the pre-PCV13 era, 19A/F, 15A/F, 19B, and 23A serotypes were identified. In the post-PCV13 era, 15 serotypes were identified. The 19F and 23A serotypes showed the highest prevalence in the pre- and post-PCV13 era, respectively. After PCV13 introduction, the PCV 13 serotype coverage rate was decreased (80.0% and 30.5% in the pre- and post-PCV13 eras, respectively), while the proportion of non-PCV 13 serotypes increased.
7.Application of therapeutic plasma exchange in patients having severe fever with thrombocytopenia syndrome
Jeong Rae YOO ; Sun Hyung KIM ; Young Ree KIM ; Keun Hwa LEE ; Won Sup OH ; Sang Taek HEO
The Korean Journal of Internal Medicine 2019;34(4):902-909
BACKGROUND/AIMS:
Severe fever with thrombocytopenia syndrome (SFTS) is a viral hemorrhagic fever with a high fatality rate. However, effective treatments for SFTS cases not responded to supportive therapy have not been established. Herein, we introduced the therapeutic plasma exchange (TPE) in SFTS patients in a tertiary hospital between 2013 and 2015.
METHODS:
TPE was performed in patients with rapidly progressing SFTS. Clinical, laboratory, and virological parameters were compared before and after TPE.
RESULTS:
Among 27 confirmed SFTS patients, two patients were treated with TPE and ribavirin combination in May 2013, then, 14 patients with rapidly progressing SFTS patients were treated with only TPE from June 2013 to September 2015: their median age was 58 years (interquartile range, 50 to 70) and eight (57.1%) were male. Body temperature, pressure-adjusted heart rate, white blood cell and platelet counts, coagulation profile, serum creatinine, and multiple organ dysfunction score improved immediately after TPE. In addition, the mean cyclic threshold value of real-time reverse transcriptase polymerase chain reaction for SFTS virus after TPE (mean ± standard deviation, 31.3 ± 2.9) was significantly higher than that before TPE (26.5 ± 2.9; p < 0.001), indicating that serum viral loads decreased after TPE. Finally, 13 of 14 TPE-treated patients (92.8%) recovered from rapidly progressing SFTS without sequelae.
CONCLUSIONS
SFTS patients treated with TPE showed improvements in clinical, laboratory, and virological parameters. These results suggest that TPE would be a therapeutic modality as rescue therapy in patients with rapidly progressing SFTS.
8.The Impact of Surgical Timing on Pathologic Tumor Response after Short Course and Long Course Preoperative Chemoradiation for Locally Advanced Rectal Adenocarcinoma.
Sea Won LEE ; Jong Hoon LEE ; In Kyu LEE ; Seong Taek OH ; Dae Yong KIM ; Tae Hyun KIM ; Jae Hwan OH ; Ji Yeon BAEK ; Hee Jin CHANG ; Hee Chul PARK ; Hee Cheol KIM ; Eui Kyu CHIE ; Taek Keun NAM ; Hong Seok JANG
Cancer Research and Treatment 2018;50(3):1039-1050
PURPOSE: A pooled analysis of multi-institutional trials was performed to analyze the effect of surgical timing on tumor response by comparing short course concurrent chemoradiotherapy (CCRT) with long course CCRT followed by delayed surgery in locally advanced rectal cancer. MATERIALS AND METHODS: Three hundred patients with cT3-4N0-2 rectal adenocarcinoma were included. Long course patients from KROG 14-12 (n=150) were matched 1:1 to 150 short course patients from KROG 10-01 (NCT01129700) and KROG 11-02 (NCT01431599) according to stage, age, and other risk factors. The primary endpoint was to determine the interval between surgery and the last day of neoadjuvant CCRT which yields the best tumor response after the short course and long course CCRT. Downstaging was defined as ypT0-2N0M0 and pathologic complete response (ypCR) was defined as ypT0N0M0, respectively. RESULTS: Both the long and short course groups achieved lowest downstaging rates at < 6 weeks (long 20% vs. short 8%) and highest downstaging rates at 6-7 weeks (long 44% vs. short 40%). The ypCR rates were lowest at < 6 weeks (both long and short 0%) and highest at 6-7 weeks (long 21% vs. short 11%) in both the short and long course arms. The downstaging and ypCR rates of long course group gradually declined after the peak at 6-7 weeks and those of the short course group trend to constantly increase afterwards. CONCLUSION: It is optimal to perform surgery at least 6 weeks after both the short course and long course CCRT to obtain maximal tumor regression in locally advanced rectal adenocarcinoma.
Adenocarcinoma*
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Arm
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Chemoradiotherapy
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Humans
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Rectal Neoplasms
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Risk Factors
9.Factors associated with hospitalization via emergency department in children with acute bronchiolitis
Tak Keun LEE ; Yeon Young KYONG ; Seon Hee WOO ; Jung Taek PARK ; Young Min OH ; Hyun Ho JUNG ; Se Min CHOI
Pediatric Emergency Medicine Journal 2018;5(2):49-53
PURPOSE: In infants and young children, acute bronchiolitis is a leading cause of hospitalization via emergency departments (EDs). We aimed to investigate factors associated with hospitalization via ED in children with acute bronchiolitis. METHODS: We reviewed medical records of children aged 36 months or younger with acute bronchiolitis who visited the ED from January to December 2017. The following clinical data were collected and analyzed: age, sex, premature birth history, symptoms, fever duration, presence of respiratory distress and radiographic lesion, and inflammatory markers. RESULTS: Of 780 children enrolled, 463 (59.4%) were hospitalized via the ED. The factor associated with the hospitalization were age ≤ 12 months (odd ratio [OR], 45.34; confidence interval [CI], 17.50-117.44), fever lasting ≥ 3 days (OR, 13.66; 95% CI, 6.46-28.87), respiratory rate ≥ 24 breaths per minute (OR, 6.88; 95% CI, 4.21-11.26), radiographic lesion (OR, 5.70; 95% CI, 2.62-12.40), and chest retraction (OR, 2.45; 95% CI, 1.11-5.41). CONCLUSION: In children with acute bronchiolitis who visit EDs, those having younger age, longer fever duration, respiratory distress or radiographic lesion may need hospitalization.
Bronchiolitis
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Child
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Emergencies
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Emergency Medicine
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Emergency Service, Hospital
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Fever
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Hospitalization
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Humans
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Infant
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Infant, Newborn
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Infant, Premature
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Medical Records
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Pediatrics
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Premature Birth
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Respiratory Rate
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Thorax
10.A Rare Case of Lumbar Traumatic Intradiscal Hematoma Followed by Repeatative Occupation Related Minor Trauma
Woo Keun KWON ; Jong Keon OH ; Taek Hyun KWON ; Youn Kwan PARK ; Hong Joo MOON ; Joo Han KIM
Journal of the Korean Society of Traumatology 2018;31(1):38-42
A case of surgically treated intervertebral disc extrusion with intraoperatively confirmed intradiscal hematoma in a 30-year-old physical trainer is presented. Preoperative magnetic resonance imaging revealed downward migrating disc herniation, without definite suggestive findings of intradiscal hematoma. Intervertebral disc herniation with concomitant intradiscal hematoma is extremely rare, but could occur in patients who have excessive axial stress to the spine occupationally. In our case, the patient was an occupational physical trainer who had repetitive minor trauma to the lumbar spine. Although the patient did not have any clear history of major trauma to the spine, the intraoperative findings revealed intradiscal hematoma, which is very rare. The presence of intradiscal hematoma is to be suspected even when preoperative imaging studies shows indefinite findings of hematoma, considering the change in signal intensity of hematoma by time.

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