Promoter-Specific Variants in NeuroD1 and H3K4me3 Coincident Regions and Clinical Outcomes of Small Cell Lung Cancer

Background@#Neurogenic differentiation 1 (NeuroD1) is a representative small cell lung cancer (SCLC) transcription regulator involved in the carcinogenesis and behavior of SCLC.Histone modifications play an important role in transcription, and H3 lysine 4 trimethylation (H3K4me3) is primarily associated with promoter regions. @*Methods@#We investigated the association between single nucleotide polymorphisms (SNPs) in NeuroD1 and H3K4me3 coincident regions, selected using ChIP sequencing (ChIP-seq), and the clinical outcomes of 261 patients with SCLC. @*Results@#Among 230 SNPs, two were significantly associated with both the chemotherapy response and overall survival (OS) of patients with SCLC. RNF145 rs2043268A>G was associated with worse chemotherapy response and OS (under a recessive model, adjusted odds ratio [aOR], 0.50, 95% confidence interval [CI], 0.26–0.94, P = 0.031, and adjusted hazard ratio [aHR], 1.88, 95% CI, 1.38–2.57, P G was also associated with worse chemotherapy response and OS (under a dominant model, aOR, 0.47, 95% CI, 0.23–0.99, P = 0.046, and aHR, 2.03, 95% CI, 1.47–2.82, P G and CINP rs762105A>G were associated with clinical outcomes in patients with SCLC and also affected the promoter activity of each gene.

Host Blood Transcriptional Signatures as Candidate Biomarkers for Predicting Progression to Active Tuberculosis / 결핵및호흡기질환

A recent understanding of the dynamic continuous spectrum of Mycobacterium tuberculosis infection has led to the recognition of incipient tuberculosis, which refers to the latent infection state that has begun to progress to active tuberculosis. The importance of early detection of these individuals with a high-risk of progression to active tuberculosis is emphasized to efficiently implement targeted tuberculosis preventive therapy. However, the tuberculin skin test or interferon-γ release assay, which is currently used for the diagnosis of latent tuberculosis infection, does not aid in the prediction of the risk of progression to active tuberculosis. Thus, a novel test is urgently needed. Recently, simultaneous and systematic analysis of differentially expressed genes using a high-throughput platform has enabled the discovery of key genes that may serve potential biomarkers for the diagnosis or prognosis of diseases. This host transcriptional investigation has been extended to the field of tuberculosis, providing promising results. The present review focuses on recent progress and challenges in the field of blood transcriptional signatures to predict progression to active tuberculosis.

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

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 f luid 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 f luid carcinoembryonic antigen (CEA), and pleural nodularity were independent discriminators between high-ADA MPE and high-ADA TPE groups. Using pleural ADA level of 40 to 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.

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

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 TBP. 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.

Risk factors for abnormal CT findings in preschool children head injuries without neurological deficit

Objective@#This study aimed to apply abnormal computed tomography (CT) findings to help identify clinical and physical characteristics which suggest a traumatic brain injury, in preschool children with mild head injuries but without neurological deficit. @*Methods@#Among the 1,735 preschool children (aged ≤6 years) with head trauma who visited our hospital and underwent CT scans, 1,711 students without severe neurologic deficits were retrospectively assessed via images and electronic records. The relationship between the occurrence of abnormal CT findings and clinical symptoms, physical examination findings, and the conditions of children were assessed using Pearson’s chi-squared test and multivariable logistic regression analysis. @*Results@#Traumatic brain injury with abnormal CT findings were observed in 75 of the 1,711 patients, and the association with brain injury was more prominent among patients who had fallen from a height of ≥1 m, had posttraumatic irritability, or had posttraumatic scalp swelling. @*Conclusion@#Free fall from a height of ≥1 m, posttraumatic irritability, and posttraumatic scalp swelling should be carefully assessed in patients who have suffered a traumatic brain injury and show abnormal CT findings but no neurologic deficits. Regardless of their initial signs, an active test is recommended for children who complain of multiple symptoms. Patients with these risk factors require greater in-depth brain CT examination. Abnormal CT findings are more meaningful in the case of patients with multiple symptoms.

Risk factors for abnormal CT findings in preschool children head injuries without neurological deficit

Objective@#This study aimed to apply abnormal computed tomography (CT) findings to help identify clinical and physical characteristics which suggest a traumatic brain injury, in preschool children with mild head injuries but without neurological deficit. @*Methods@#Among the 1,735 preschool children (aged ≤6 years) with head trauma who visited our hospital and underwent CT scans, 1,711 students without severe neurologic deficits were retrospectively assessed via images and electronic records. The relationship between the occurrence of abnormal CT findings and clinical symptoms, physical examination findings, and the conditions of children were assessed using Pearson’s chi-squared test and multivariable logistic regression analysis. @*Results@#Traumatic brain injury with abnormal CT findings were observed in 75 of the 1,711 patients, and the association with brain injury was more prominent among patients who had fallen from a height of ≥1 m, had posttraumatic irritability, or had posttraumatic scalp swelling. @*Conclusion@#Free fall from a height of ≥1 m, posttraumatic irritability, and posttraumatic scalp swelling should be carefully assessed in patients who have suffered a traumatic brain injury and show abnormal CT findings but no neurologic deficits. Regardless of their initial signs, an active test is recommended for children who complain of multiple symptoms. Patients with these risk factors require greater in-depth brain CT examination. Abnormal CT findings are more meaningful in the case of patients with multiple symptoms.

A single emergency center study for obstructive urinary tract infection with sepsis

Objective@#Unlike common acute urinary tract infections, obstructive urinary tract infections caused by urinary calculus can be fatal because they can progress to sepsis and cause shock or disseminated intravascular coagulation. The evidence of patients with obstructive urinary tract infections caused by urinary tract stones visiting the emergency center is still lacking. @*Methods@#Seventy-seven patients who visited the emergency room with obstructive urinary tract infections caused by urinary calculus from January 2016 to December 2018 were enrolled in this study and divided into two groups: sepsis group and non-sepsis group. @*Results@#The lymphocyte count, platelet count, neutrophil-lymphocyte ratio, serum creatinine, and C-reactive protein were significantly different in the sepsis-positive and negative groups. Percutaneous nephrostomy was also significantly higher in the sepsis-positive group. The area under the receiver operating characteristic curve was calculated to evaluate the ability of the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio to predict a septic urinary tract infection. The neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were 0.659 and 0.550, respectively. Multivariate logistic regression analysis showed that diabetic patients, percutaneous nephrostomy, and serum creatinine were associated with septic obstructive urinary tract infection. @*Conclusion@#In patients with an obstructive urinary tract infection who were referred to the emergency center, diabetic patients and those with high blood urea nitrogen and creatinine levels are at high risk of sepsis. In such cases, rapid diagnosis and treatment, such as percutaneous nephrostomy, are necessary.

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

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. @*Conclusions@#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.

Detection of Deep Vein Thrombosis by Follow-up Indirect Computed Tomography Venography after Pulmonary Embolism / 결핵및호흡기질환

BACKGROUND@#Information regarding the incidence and risk factors for deep vein thrombosis (DVT) detected by follow-up computed tomographic (CT) venography after pulmonary embolism (PE) is sparse. The aim of the present study was to identify the predictors of DVT in follow-up CT images, and to elucidate their clinical significance.@*METHODS@#Patients with PE were classified into the following three cohorts based on the time of indirect CT venography follow-up: within 1 month, 1 to 3 months, and 3 to 9 months after the initial CT scan. Each cohort was subdivided into patients with or without DVT detected by follow-up CT. Clinical variables were compared between the two groups.@*RESULTS@#Follow-up CT revealed DVT in 61% of patients with PE within 1 month, in 15% of patients with PE at 1 to 3 months, and in 9% of patients with PE at 3 to 9 months after the initial CT scan. Right ventricular (RV) dilation on the initial CT (odds ratio [OR], 8.30; 95% confidence interval [CI], 1.89–36.40; p=0.005) and proximal DVT at the initial presentation (OR, 6.93; 95% CI, 1.90–25.20; p=0.003) were found to independently predict DVT in follow-up CT images within 1 month, proximal DVT at the initial presentation was found to independently predict DVT in follow-up CT images at 1 to 3 months (OR, 6.69; 95% CI, 1.53–29.23; p=0.012), and central PE was found to independently predict DVT in follow-up CT images at 3 to 9 months (OR, 4.25; 95% CI, 1.22–4.83; p=0.023) after the initial CT scan. Furthermore, the detection of DVT by follow-up CT independently predicted the recurrence of venous thromboembolism (VTE) (OR, 4.67; 95% CI, 2.24–9.74; p < 0.001).@*CONCLUSION@#Three months after PE, DVT was not detected by follow-up CT in most patients with PE. RV dilation on the initial CT, central PE, and proximal DVT at the initial presentation were found to predict DVT on follow-up CT, which might predict VTE recurrence.

Detection of Deep Vein Thrombosis by Follow-up Indirect Computed Tomography Venography after Pulmonary Embolism / 결핵

BACKGROUND: Information regarding the incidence and risk factors for deep vein thrombosis (DVT) detected by follow-up computed tomographic (CT) venography after pulmonary embolism (PE) is sparse. The aim of the present study was to identify the predictors of DVT in follow-up CT images, and to elucidate their clinical significance. METHODS: Patients with PE were classified into the following three cohorts based on the time of indirect CT venography follow-up: within 1 month, 1 to 3 months, and 3 to 9 months after the initial CT scan. Each cohort was subdivided into patients with or without DVT detected by follow-up CT. Clinical variables were compared between the two groups. RESULTS: Follow-up CT revealed DVT in 61% of patients with PE within 1 month, in 15% of patients with PE at 1 to 3 months, and in 9% of patients with PE at 3 to 9 months after the initial CT scan. Right ventricular (RV) dilation on the initial CT (odds ratio [OR], 8.30; 95% confidence interval [CI], 1.89–36.40; p=0.005) and proximal DVT at the initial presentation (OR, 6.93; 95% CI, 1.90–25.20; p=0.003) were found to independently predict DVT in follow-up CT images within 1 month, proximal DVT at the initial presentation was found to independently predict DVT in follow-up CT images at 1 to 3 months (OR, 6.69; 95% CI, 1.53–29.23; p=0.012), and central PE was found to independently predict DVT in follow-up CT images at 3 to 9 months (OR, 4.25; 95% CI, 1.22–4.83; p=0.023) after the initial CT scan. Furthermore, the detection of DVT by follow-up CT independently predicted the recurrence of venous thromboembolism (VTE) (OR, 4.67; 95% CI, 2.24–9.74; p < 0.001). CONCLUSION: Three months after PE, DVT was not detected by follow-up CT in most patients with PE. RV dilation on the initial CT, central PE, and proximal DVT at the initial presentation were found to predict DVT on follow-up CT, which might predict VTE recurrence.

Comparison of Early and Late Tuberculosis Deaths in Korea

The cause of death in patients with tuberculosis (TB) may differ according to the phase of anti-tuberculosis treatment. However, there are limited data regarding this issue in Korea. We compared the cause of death of TB patients who died during the early intensive and late continuation phase of treatment. Twenty (56%) of the 36 early deaths were due to TB-related causes, whereas 34 (89%) of the 38 late deaths were due to TB-unrelated causes. This finding suggests that TB-related early deaths mainly attributable to delayed diagnosis should be improved to further reduce the overall TB deaths.

Mycobacterium tuberculosis ESAT6 and CPF10 Induce Adenosine Deaminase 2 mRNA Expression in Monocyte-Derived Macrophages / 결핵및호흡기질환

BACKGROUND: Delayed hypersensitivity plays a large role in the pathogenesis of tuberculous pleural effusion (TPE). Macrophages infected with live Mycobacterium tuberculosis (MTB) increase the levels of adenosine deaminase2 (ADA2) in the pleural fluid of TPE patients. However, it is as yet unclear whether ADA2 can be produced by macrophages when challenged with MTB antigens alone. This study therefore evaluated the levels of ADA2 mRNA expression, using monocyte-derived macrophages (MDMs) stimulated with MTB antigens. METHODS: Purified monocytes from the peripheral blood mononuclear cells of healthy volunteers were differentiated into macrophages using granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF). The MDMs were stimulated with early secretory antigenic target protein 6 (ESAT6) and culture filtrate protein 10 (CFP10). The mRNA expression levels for the cat eye syndrome chromosome region, candidate 1 (CECR1) gene encoding ADA2 were then measured. RESULTS: CECR1 mRNA expression levels were significantly higher in MDMs stimulated with ESAT6 and CFP10, than in the unstimulated MDMs. When stimulated with ESAT6, M-CSF-treated MDMs showed more pronounced CECR1 mRNA expression than GM-CSF-treated MDMs. Interferon-γ decreased the ESAT6- and CFP10-induced CECR1 mRNA expression in MDMs. CECR1 mRNA expression levels were positively correlated with mRNA expression of tumor necrosis factor α and interleukin 10, respectively. CONCLUSION: ADA2 mRNA expression increased when MDMs were stimulated with MTB antigens alone. This partly indicates that pleural fluid ADA levels could increase in patients with culture-negative TPE. Our results may be helpful in improving the understanding of TPE pathogenesis.

The Different Effect of VEGF Polymorphisms on the Prognosis of Non-Small Cell Lung Cancer according to Tumor Histology

Vascular endothelial growth factor (VEGF) contributes to tumor angiogenesis. The role of VEGF single nucleotide polymorphisms (SNPs) in lung cancer susceptibility and its prognosis remains inconclusive and controversial. This study was performed to investigate whether VEGF polymorphisms affect survival outcomes of patients with early stage non-small cell lung cancer (NSCLC) after surgery. Three potentially functional VEGF SNPs (rs833061T>C, rs2010963G>C, and rs3025039C>T) were genotyped. A total of 782 NSCLC patients who were treated with surgical resection were enrolled. The association of the SNPs with overall survival (OS) and disease free survival (DFS) was analyzed. In overall population, none of the three polymorphisms were significantly associated with OS or DFS. However, when the patients were stratified by tumor histology, squamous cell carcinoma (SCC) and adenocarcinoma (AC) had significantly different OS (Adjusted hazard ratio [aHR] = 0.76, 95% CI = 0.56–1.03 in SCC; aHR = 1.33, 95% CI = 0.98–1.82 in AC; P for heterogeneity = 0.01) and DFS (aHR = 0.75, 95% CI = 0.58–0.97 in SCC; aHR = 1.26, 95% CI = 1.00–1.60 in AC; P for heterogeneity = 0.004) according to the rs833061T>C genotypes. Our results suggest that the prognostic role of VEGF rs833061T>C may differ depending on tumor histology.

Genetic Variants in the Wnt Signaling Pathway Are Not Associated with Survival Outcome of Non-Small Cell Lung Cancer in a Korean Population

Recently, genetic variants in the WNT signaling pathway have been reported to affect the survival outcome of Caucasian patients with early stage non-small cell lung cancer (NSCLC). We therefore attempted to determine whether these same WNT signaling pathway gene variants had similar impacts on the survival outcome of NSCLC patients in a Korean population. A total of 761 patients with stages I-IIIA NSCLC were enrolled in this study. Eight variants of WNT pathway genes were genotyped and their association with overall survival and disease-free survival were analyzed. None of the eight variants were significantly associated with overall survival or disease-free survival. There were no differences in survival outcome after stratifying the subjects according to age, gender, smoking status, and histological type. These results suggest that genetic variants in the WNT signaling pathway may not affect the survival outcome of NSCLC in a Korean population.

Diffuse Pulmonary Ossification Developing in Patients with End-stage Renal Disease / 대한내과학회지

Diffuse pulmonary ossification (DPO) is a rare condition characterized by chronic metaplastic ossification of the lung parenchyma. DPO is associated with various underlying pulmonary, cardiac, and systemic diseases. However, to our knowledge, DPO has rarely been described in patients with end-stage renal disease undergoing hemodialysis. We describe two cases of DPO diagnosed in long-term hemodialysis patients. Awareness of this rare disorder is required for a better differential diagnosis of cases presenting with bilateral diffuse micronodular lesions, including calcific opacities.

Letter to the editor: Respective Contribution of Liquid and Solid Media to Mycobacterial Yields from Pleural Fluid in Tuberculous Pleural Effusion

No abstract available.

Replication of the results of genome-wide and candidate gene association studies on telomere length in a Korean population

BACKGROUND/AIMS: A number of genome-wide and candidate gene association studies have identified polymorphisms associated with telomere length in Caucasian populations. This study was conducted to determine the impacts of 17 polymorphisms identified in Caucasians on telomere length in a Korean population. METHODS: Ninety-four healthy individuals were enrolled in this study. Relative telomere length of chromosomes from peripheral blood samples was measured using quantitative polymerase chain reaction. RESULTS: Two polymorphisms, rs10936599 of MYNN and rs412658 of ZNF676, were found to be associated w ith telomere length (under dominant model, p = 0.04; under recessive model, p = 0.001). Three polymorphisms, rs2853669, rs7705526, and rs2736108, at the TERT locus were also associated with telomere length (under recessive model, p = 0.01, p = 0.02, and p = 0.01, respectively). The genotypes of the five polymorphisms associated with short telomere length were considered bad genotypes; telomere length was significantly decreased with increasing number of bad genotypes (p= 1.7 x 10(-5)). CONCLUSIONS: We have identified polymorphisms associated with telomere length in a Korean population.

TERT Polymorphism rs2853669 Influences on Lung Cancer Risk in the Korean Population

Short telomeres are known as one of the risk factors for human cancers. The present study was conducted to evaluate the association between 6 polymorphisms, which were related with short telomere length in the Korean population, and lung cancer risk using 1,100 cases and 1,096 controls. Among the 6 polymorphisms, TERT rs2853669 was significantly associated with increased lung cancer risk under a recessive model (odds ratio [OR]=1.38, 95% confidence interval [CI]=1.05-1.81, P=0.02). The effect of rs2853669 on lung cancer risk was significant in younger individuals (OR=1.73, 95% CI=1.18-2.54, P=0.005) and adenocarcinoma (OR=1.50, 95% CI=1.07-2.07, P=0.02). Our results suggest that a common functional promoter polymorphism, TERT rs2853669, may influence both telomere length and lung cancer risk in the Korean population.

Modified Single Port Laparoscopic Cholecystectomy

PURPOSE: Currently, single port laparoscopic cholecystectomy (SLC) is gradually being expanded. However, its operative time and complications are reportedly variable according to the surgeon's expertise and experience. In order to overcome these problems, we introduced surgical methods using a 2 mm sized auxiliary device (NELIS, Korea) in cholecystectomy. METHODS: Between March 2010 and October 2010, laparoscopic cholecystectomy was performed in 53 patients for non-inflammatory gallbladder stones or gallbladder polyps based on the computed tomography findings. Fourteen of 53 consecutive patients underwent SLC and others underwent CLC. The patient's clinical characteristics and operative results were evaluated retrospectively. RESULTS: Comparison of clinical characteristics between SLC and CLC groups indicated that the SLC group included younger patients (p=0.008), however other characteristics (sex, mean body index, and previous abdominal operation history) were not significantly different. Operative outcomesparameters including the intensity of postoperative pain, rate of wound complication, and postoperative hospital stay did not differ significantly between the 2 groups. Operative time of the SLC group was longer than that of the CLC group (p=0.002). However, the operative time was decreased according to the increasing SLC cases. By 3 months, patients in the SLC group reported significantly better cosmesis (p=0.036). CONCLUSION: SLC with an auxiliary device (2 mm, Hold port, NELIS) is technically feasible and might be an alternative method for obtaining a critical view of safety and cosmetic results.

Life-threatening Hemobilia following Removal of a Biliary Stent in a Patient with a Bile Leak / 대한췌담도학회지

Biliary plastic stent induced life-threatening hemobilia is very rare. In this case, hemobilia seriously worsened following removal of a biliary stent, which had been placed for treatment of a postoperative bile leak in a patient who had undergone lateral liver segmentectomy for abdominal trauma. Following placement of the biliary stent, the bile leak improved, but hemobilia and cholangitis developed five days later. To manage the stent malfunction, we removed the biliary stent. However, life-threatening hemobilia developed immediately after removal. Endoscopic hemostasis was impossible; therefore, emergency angiographic embolization and stent graft were performed successfully. In such cases, angiographic embolization and stent-graft placement are effective diagnostic and therapeutic alternatives. When a patient develops hemobilia or cholangitis after biliary stent placement, endoscopists should pay special attention to remove the stent, which might exacerbate hemobilia.