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Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that regulate gene expression. We investigated whether variants in BET genes are associated with survival outcomes for lung cancer. To do this, the associations between 77 variants in BET family genes and survival outcomes were analyzed in 773 non‐small‐cell lung cancer (NSCLC) patients who underwent surgery (349 and 424 patients in the discovery and validation cohorts, respectively). We found that six variants were significantly associated with overall survival (OS) in the discovery cohort, and one variant (rs2506711C>T) was replicated in the validation cohort. BRD3 rs2506711C>T is located in the repressed area and has a strong linkage disequilibrium with rs2427964C>T in the promoter region. BRD3 rs2427964C>T was significantly associated with worse OS in the discovery cohort, validation cohort, and combined analysis. In a luciferase assay, promoter activity in the BRD3 rs2427964 T allele was significantly higher than that in the BRD3 rs2427964 C allele, which selectively bound with the transcriptional repressor SIN3A. Knockdown of BRD3 with BRD3‐specific siRNA decreased the proliferation and migration of lung cancer cells while also increasing the rate of apoptosis. These results suggest that BRD3 rs2427964C>T increases BRD3 expression through increased promoter activity, which is associated with poor prognosis for lung cancer., In this study, we investigated the association of BET gene variants with survival of patients with non‐small‐cell lung cancer (NSCLC). We observed that the rs2427964C>T SNP in the BRD3 promoter region was associated with poorer survival outcome. BRD3 promoter activity was higher in rs2427964_T than in rs2427964_C, which selectively bound with the transcriptional repressor SIN3A. Additionally, BRD3 silencing decreased the proliferation and migration of NSCLC cells. Our data suggest that elevated BRD3 expression regulated by rs2427964C>T leads to reduced overall survival in patients with NSCLC.

Background: Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea.Methods: A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma–COPD (ACO) and pure COPD was performed.Results: We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were detected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016).Conclusion: Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.

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.

Introduction Patients with aspiration pneumonia (AP) exhibit higher mortality than those with non-AP. However, data regarding predictors of short-term prognosis in patients with community-acquired AP are limited. Methods Patients hospitalized with community-acquired pneumonia (CAP) were retrospectively classified into aspiration pneumonia (AP) and non-AP groups. The AP patients were further divided into nonsurvivors and survivors by 30-day mortality, and various clinical variables were compared between the groups. Results Of 1249 CAP patients, 254 (20.3%) were classified into the AP group, of whom 76 patients (29.9%) died within 30 days. CURB-65, pneumonia severity index (PSI), and Infectious Diseases Society of America/American Thoracic Society criteria for severe CAP (SCAP) showed only modest prognostic performance for the prediction of 30-day mortality (c-statistics, 0.635, 0.647, and 0.681, respectively). Along with the PSI and SCAP, Eastern Cooperative Oncology Group performance status (ECOG-PS) and blood biomarkers, including, N-terminal of prohormone brain natriuretic peptide (NT-proBNP) and albumin, were independent predictors of 30-day mortality. In models based on clinical prediction rules, including CURB-65, PSI, and SCAP, the addition of ECOG-PS further improved their c-statistics compared to the clinical prediction rules alone. In the four combinations based on SCAP, ECOG-PS, and two blood biomarkers (NT-proBNP and albumin), the c-statistics further increased to reach approximately 0.8. Conclusions CURB-65, PSI, and SCAP exhibited only modest discriminatory power in predicting the 30-day mortality of patients with community-acquired AP. The addition of performance status and blood biomarkers, including NT-proBNP and albumin, further increased prognostic performance, showing good predictive accuracy in the SCAP-based model.

The clinical relevance of concomitant deep vein thrombosis (DVT) in patients with pulmonary embolism remains controversial. The aim of the present study was to assess clinical characteristics of patients with isolated pulmonary embolism, thereby investigating isolated pulmonary embolism related clinical factors. Patients hospitalized for pulmonary embolism who underwent DVT workup within 3 days of pulmonary embolism diagnosis were retrospectively classified into two groups: patients with isolated pulmonary embolism and patients with DVT-associated pulmonary embolism (DVT-PE). The clinical, laboratorial and radiological parameters were compared between the two groups. Of 1012 patients, 322 (31.8%) presented with isolated pulmonary embolism, and 690 (68.2%) presented with DVT-PE. In a multivariate analysis, female sex was an independent factor for predicting isolated pulmonary embolism [odds ratio (OR) 1.69, 95% confidence interval (CI) 1.26-2.26, P < 0.001], whereas cancer (OR 0.64, 95% CI 0.43-0.96, P = 0.031), leg pain or swelling (OR 0.08, 95% CI 0.04-0.18, P < 0.001), and central pulmonary embolism (OR 0.44, 95% CI 0.32-0.59, P < 0.001) were negatively associated with isolated pulmonary embolism. There were no significant differences between the two groups with regard to risk stratification and short-term prognosis of pulmonary embolism, including adverse outcomes and pulmonary embolism related in-hospital mortality. Of pulmonary embolism patients who underwent imaging tests for DVT, approximately 32% presented with isolated pulmonary embolism. Isolated pulmonary embolism was positively associated with female sex, whereas it was negatively associated with cancer, leg pain or swelling, and central pulmonary embolism. The presence or absence of concomitant DVT did not influence the severity and short-term prognosis of pulmonary embolism.

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, 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. 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.

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.

To understand the relationship between carbon or nitrogen utilization and iron homeostasis, we performed an iron uptake assay with several deletion mutants with partial defects in carbon or nitrogen metabolism. Among them, some deletion mutants defective in carbon metabolism partially and the MEP2 deletion mutant showed lower iron uptake activity than the wild type. Mep2 is known as a high-affinity ammonia transporter in Saccharomyces cerevisiae. Interestingly, we found that nitrogen starvation resulted in lower iron uptake activity than that of wild-type cells without downregulation of the genes involved in the high-affinity iron uptake system FET3/FTR1. However, the gene expression of FRE1 and CTR1 was downregulated by nitrogen starvation. The protein level of Ctr1 was also decreased by nitrogen starvation, and addition of copper to the nitrogen starvation medium partially restored iron uptake activity. However, the expression of MAC1, which is a copper-responsive transcriptional activator, was not downregulated by nitrogen starvation at the transcriptional level but was highly downregulated at the translational level. Mac1 was downregulated dramatically under nitrogen starvation, and treatment with MG132, which is an inhibitor of proteasome-dependent protein degradation, partially attenuated the downregulation of Mac1. Taken together, these results suggest that nitrogen starvation downregulates the high-affinity iron uptake system by degrading Mac1 in a proteasome-dependent manner and eventually downregulates copper metabolism.

This study was conducted to explore whether polymorphisms of glucose transporter 3 (GLUT3) gene affect the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. Four single nucleotide polymorphisms (SNPs) in GLUT3 were investigated in a total of 782 patients with NSCLC who underwent curative surgery. The association of the SNPs with overall survival (OS) and disease free survival (DFS) was analyzed. Among the four SNPs investigated, GLUT3 rs7309332C>T was significantly associated with OS and DFS in multivariate analyses. The SNP was associated with significantly worse OS (adjusted hazard ratio [aHR] = 1.62, 95% confidence interval [CI] = 1.04–2.53, P = 0.03, under recessive model), and worse DFS (aHR = 1.64, 95% CI = 1.18–2.29, P = 0.003, under recessive model). When stratified by tumor histology, the association between the GLUT3 rs7309332C>T and OS/DFS was not limited to either squamous cell carcinoma (SCC) or adenocarcinoma (AC), although the significant association remained only in AC for OS (P = 0.40 for SCC and P = 0.04 for OS) and only in SCC for DFS (P = 0.03 for SCC and P = 0.08 for OS). When AC patients were stratified according to EGFR mutation status, the SNP was significantly associated with DFS in patients with EGFR mutant tumors (aHR = 2.47, 95% CI = 1.15–5.30, P = 0.02, under recessive model), but not in those with EGFR wild-type tumors. This study suggests that genetic variation in GLUT3 may be useful in predicting survival of patients with early stage NSCLC.

Background: Data regarding community-acquired pneumonia (CAP) identified on chest computed tomography (CT) but not on chest radiography (CR) are limited. Objectives: The present study aimed to investigate the clinical and radiological features of these patients. Methods: We retrospectively compared the clinical characteristics, etiological agents, treatment outcomes, and CT findings between CAP patients with negative CR and positive CT findings (negative CR group) and those with positive CR as well as CT findings (control group). Results: Of 1,925 patients, 94 patients (4.9%) were included in the negative CR group. Negative CR findings could be attributed to the location of the lesions (e.g., those located in the dependent lung) and CT pattern with a low attenuation, such as ground-glass opacity (GGO). The negative CR group was characterized by a higher frequency of aspiration pneumonia, lower incidences of complicated parapneumonic effusion or empyema and pleural drainage, and lower blood levels of inflammatory markers than the control group. On CT, the negative CR group exhibited higher rates of GGO- and bronchiolitis-predominant patterns and a lower rate of consolidation pattern. Despite shorter length of hospital stay in the negative CR group, 30-day and in-hospital mortalities were similar between the two groups. Conclusions: CAP patients with negative CR findings are characterized by lower blood levels of inflammatory markers, a higher incidence of aspiration pneumonia, and a lower incidence of complicated para­pneumonic effusion or empyema than those with positive CR findings. Chest CT scan should be considered in suspected CAP patients with a negative CR, especially in bedridden patients.

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 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.

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., Graphical Abstract

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.

Background Data regarding predictors of the outcome for patients with community-acquired complicated parapneumonic effusion (CPPE) or empyema are insufficient. Method Patients with community-acquired pneumonia (CAP) were classified into CPPE or empyema and control groups based on pleural fluid analysis and microbiological data. The patients with CPPE or empyema were further divided into longer and shorter length of stay (LOS) groups, and clinical characteristics, pleural fluid data, and computed tomographic (CT) findings were compared between the two groups. Result Of outcome variables, LOS was significantly longer in CPPE or empyema group than in the control group (13 days [interquartile range, 10-17 days] versus 8 days [6-12 days], p < 0.001), whereas 30-day mortality and in-hospital mortality were not significantly different between the two groups. Patients with CPPE or empyema were divided into the shorter (≤ 13 days) and longer LOS (≥ 14 days) groups. Multivariate analysis demonstrated that pneumonia severity index (PSI) class IV-V (odds ratio [OR] 2.79, 95% CI 1.35-5.76, p=0.006), increased attenuation of extrapleural fat (OR 2.26, 95% CI 1.06-4.80, p=0.034), and air bubbles in pleural space (OR 3.93, 95% CI 1.03-14.98, p=0.045) were independent predictors of prolonged LOS in CAP patients with CPPE or empyema. Conclusion Increased attenuation of extrapleural fat and air bubbles in pleural space assessed with CT and PSI class IV-V independently predicted prolonged LOS in CAP patients with CPPE or empyema. These findings may be helpful to identify patients who need more intensive evaluation and intervention.

BACKGROUND. Ultrasound (US)-guided percutaneous pleural needle biopsy (PCPNB) is widely used to evaluate pleural lesions, although its diagnostic accuracy is variable. OBJECTIVE. The purpose of this study is 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. METHODS. A total of 103 patients (73 men and 30 women; mean [± SD] age, 68.0 ± 13.3 years) who underwent US-guided PCPNB of a small pleural lesion performed by a single experienced operator from July 2013 to December 2019 were retrospectively analyzed. Final diagnosis was established via histopathologic results, including findings 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, PPV, and NPV were calculated. The association of diagnostic yield with imaging and technical factors was evaluated. 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. RESULTS. The diagnostic accuracy, sensitivity, specificity, PPV, and NPV of US-guided PCPNB were 85.4%, 84.8%, 100.0%, 100.0%, and 21.1%, respectively. Diagnostic, compared with nondiagnostic, procedures more commonly (p ≤ .002) revealed nodular morphology on CT (96.4% vs 3.6%) and US (97.3% vs 2.7%,), greater pleural thickness on CT (7.5 vs 3.2 mm) and US (7.4 vs 3.0 mm), and a greater needle pathway length (11.0 vs 6.1 mm). The optimal cutoff value for pleural thickness on CT was 4.5 mm. Diagnostic yield was 96.4% for nodular lesions, 95.0% for diffuse lesions that had a thickness of 4.5 mm or greater on CT, 55.6% for diffuse lesions that had a thickness less than 4.5 mm on CT, and 100% for diffuse lesions on CT that had nodular morphology on US. Nodular morphology on US (p = .002) and needle pathway length (p = .04) were independent predictors of diagnostic yield. CONCLUSION. US-guided PCPNB has excellent diagnostic accuracy for small pleural lesions; imaging characteristics influence this accuracy. CLINICAL IMPACT. US-guided PCPNB is highly likely diagnostic for small pleural lesions with nodular morphology on either CT or US or with a pleural thickness of 4.5 mm or greater.

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 × 10−4, 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.

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.

The outcome of coronavirus disease 2019 (COVID-19) is associated with organ damage, however, the information about the relationship between acute kidney injury (AKI) and COVID-19 is still rare. We evaluated the clinical features and prognosis of COVID-19 patients with AKI according to the AKI severity. Medical data of hospitalized COVID-19 patients in two university-based hospitals during an outbreak in Daegu, South Korea, were retrospectively analyzed. AKI and its severity were defined according to the Acute Kidney Injury Network. Of the 164 hospitalized patients with COVID-19, 30 patients (18.3%) had AKI, 14, 4, and 12 patients had stage 1, 2, and 3, respectively. The median age was significantly higher in AKI patients than in non-AKI patients (75.5 vs. 67.0 years, p = 0.005). There were 17 deaths (56.7%) among AKI patients, 4 (28.6%), 1 (25.0%), and 12 (100.0%), respectively. In-hospital mortality was higher in AKI patients than in non-AKI patients (56.7% vs. 20.8%, p &lt, 0.001). After adjusting for potential confounding factors, stage 3 AKI was associated with higher mortality than either non-AKI or stage 1 AKI (hazard ratio (HR) = 3.62 (95% confidence interval (CI) = 1.75&ndash, 7.48), p = 0.001, HR = 15.65 (95% CI = 2.43&ndash, 100.64), p = 0.004). Among the AKI patients, acute respiratory distress syndrome and low serum albumin on admission were considered independent risk factors for stage 3 AKI (both p &lt, 0.05). Five patients with stage 3 AKI underwent dialysis and eventually died. In conclusion, COVID-19 patients with severe AKI had fatal outcomes.

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.

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 × 10−4; 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 × 10−7). 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)., DTX1 rs1732786A>G was associated with better prognosis in patients with early‐stage non‐small cell lung cancer, in the previous study. DTX1 rs1732786A>G was associated with a significantly worse chemotherapy response and lower overall survival in small cell lung cancer.

Background We conducted this study to identify regulatory variants in cancer-related pathway genes which can predict clinical outcomes of chemotherapy in advanced NSCLC, using a comprehensive list of regulatory SNPs prioritized by RegulomeDB. Methods A total of 509 potentially functional SNPs in cancer-related pathway genes were evaluated. The SNPs were analyzed in a discovery set (n = 198), and an independent validation set (n = 181). The associations of the SNPs with chemotherapy response and overall survival (OS) were analyzed. Results In the discovery set, 95 SNPs were significantly associated with clinical outcomes. Among the 95 SNPs, only rs10414193A > G in the intronic region of ARID3A, an eQTL for LKB1, was consistently associated with chemotherapy response and OS in the validation set. In combined analysis, the rs10414193A > G was significantly associated with worse response to chemotherapy (adjusted odds ratio = 0.63, 95% CI = 0.47–0.85, P = 0.002), and with worse OS (adjusted hazard ratio = 1.25, 95% CI = 1.08–1.45, P = 0.004). Luciferase assay showed a significantly higher LKB1 promoter activity associated with rs10414193G allele compared with rs10414193A allele (P = 0.0009). Conclusions Our results suggest that rs10414193A > G may be useful for the prediction of clinical outcomes of chemotherapy in advanced NSCLC.

Background Data on the relationship between the clinical and microbiological features of community-acquired pneumonia (CAP) and its computed tomography (CT) findings are limited. The aim of the present study was to investigate the clinic-microbiological features of patients with CAP presenting with ground-glass opacity (GGO) and centrilobular nodules or tree-in-bud pattern on CT images. Methods Patients with CAP who underwent a CT scan at presentation were retrospectively classified using CT findings into consolidation, GGO and bronchiolitis groups. These 3 groups were compared in terms of clinical parameters and microbiological data. Results A total of 40 patients (2.4%) were allocated to the bronchiolitis group and 46 (2.8%) to the GGO group. The most common pathogen in the bronchiolitis group was Mycoplasma pneumoniae, which was significantly more frequently isolated in this group. The bronchiolitis group was characterized by a higher percentage of cough, a lower percentage of chest pain and lower blood levels of inflammatory markers. Common pathogens in the GGO group were not significantly different from those in the other 2 groups. Unlike that observed in the consolidation group, complicated parapneumonic effusion or empyema was not observed in the bronchiolitis or GGO group. Outcome variables were similar in the 3 groups. Conclusions The bronchiolitis group was characterized by a higher frequency of M. pneumoniae and a less severe form of CAP. The GGO and consolidation groups was similar with respect to causative microorganisms and the clinical features of CAP. No patient in the bronchiolitis or GGO group exhibited complicated parapneumonic effusion or empyema.

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with 20 μM bosentan+200 μM rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.

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 ( 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.

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, P460 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.

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.

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

BACKGROUND: Data regarding clinical and radiological features of patients with pulmonary thromboembolism (PTE) and concomitant chronic respiratory disease (CRD) are limited. Accordingly, the aim of the present study was to investigate clinico-radiological features of this patient population. METHODS: Patients with PTE were retrospectively classified into one of two groups: those with and without CRD. Clinical characteristics, blood biomarkers, and computed tomographic (CT) findings were compared between the groups. RESULTS: Of 1,207 PTE patients included, CRD was detected in 128 (11%). The most common CRD was chronic obstructive pulmonary disease [41 (32%)], followed by bronchial anthracofibrosis [32 (25%)]. In multivariate analysis, unprovoked PTE [odds ratio (OR) 1.99, 95% confidence interval (CI): 1.29–3.05, P=0.002], dyspnea (OR 1.54, 95% CI: 1.11–2.34, P=0.041), lower respiratory tract infection (LRTI) (OR 3.90, 95% CI: 2.13–7.14, P

The NBOMe family is a group of new psychoactive substances (NPSs). In this study, the fragmentation patterns of NBOMe derivatives were analyzed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). The MS/MS spectral data was used to establish a molecular networking map for NBOMe derivatives. The fragmentation patterns of nine NBOMe derivatives were interpreted on the basis of their product ion spectral data. NBOMe derivatives generally showed similar product ion spectral patterns; among them, the halogen-substituted methoxybenzyl ethanamine type derivatives showed a characteristic product ion of a radical cation. Molecular network analysis of the MS/MS data revealed that all NBOMe derivatives formed one integrated networking cluster that discriminated them from other types of NPSs. NBOMe derivatives were spiked into human urine and identified by connection to the NBOMe database network. Furthermore, the NBOMe compounds that were not registered in the database were also recognized as an NBOMe-related substance by molecular networking. These results demonstrate the potential of using molecular networking-based screening methods for designer drugs, and the proposed method would be useful in forensic or doping analysis.

Background and objective Few studies have analysed a large number of patients with necrotizing pneumonia (NP) diagnosed based on computed tomography (CT) scans. The aim of the present study was to document the incidence and clinical features of NP in patients with community-acquired pneumonia (CAP). Methods This retrospective study was conducted on CAP patients who had been admitted to a tertiary referral centre and who had available enhanced CT scan images. Patients were allocated into NP and non-NP groups, and they were compared with respect to various clinical variables. Results Of the 830 patients included in the present study, necrotizing change was observed in 103 patients (12%). Patients with NP experienced more symptoms of pneumonia, had higher blood levels of inflammatory markers and more often required pleural drainage compared to patients with non-NP. Although the use of mechanical ventilation, vasopressor infusion, 30-day mortality, in-hospital mortality and clinical deterioration did not differ between the NP and non-NP groups, the median length of hospital stay (LOS) was significantly longer in the NP group. Multivariate analysis using Cox proportional hazards model showed that necrotizing change independently predicted LOS in patients with CAP. Conclusion NP affects approximately one-tenth of hospitalized CAP patients. It may be associated with more severe clinical manifestations and may increase the need for pleural drainage. NP was found to be an independent predictor of LOS, but not of mortality in CAP patients.

Aim Nonalcoholic hepatic fat accumulation has been hypothesized to be associated with alterations in gut microbiota composition, although mechanistic explanations for this link are largely insufficient. The aim of this study was to elucidate the microbiota-driven mechanisms involved in the development of nonalcoholic hepatic steatosis. Methods and Results Ob/ob mice and their wild-type lean control mice were fed an AIN-93G diet for 12 weeks. Faecal microbiota composition, faecal bile acid (BA) profile and intestinal and hepatic markers of BA metabolism were analysed. Ob/ob mice had significantly less faecal taurine-conjugated BAs compared to their lean controls. The proportions of butyrate-producing bacteria were lower in ob/ob mice compared to those in lean mice. Intestinal expression of farnesoid X receptor (FXR) mRNA was significantly higher, whereas hepatic expression of cholesterol-7α-hydroxylase 1 (CYP7A1) and small heterodimer partner (SHP) were significantly lower in ob/ob mice compared to those in control mice. Conclusion Microbiota-associated BAs deconjugation may induce nonalcoholic fatty liver disease (NAFLD) by activating intestinal FXR signalling and blocking hepatic FXR-SHP pathway, thereby accelerating fat synthesis. Significance and Impact of the Study We provided evidences that changes in the gut microbiota and their metabolites can alter the profile of BAs, thereby providing a mechanism by which an altered microbiota profile contributes to the development of NAFLD.

The problem of new psychoactive substance (NPS) abuse, which includes synthetic cannabinoids, is emerging globally, and the cardiotoxicity of these synthetic cannabinoids has not yet been evaluated extensively. In the present study, we investigated the effects of synthetic cannabinoids on the cytotoxicity, human Ether-a-go-go-related gene (hERG) channel, action potential duration (APD), and QT interval. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that JWH-030 was more cytotoxic than JWH-210, JWH-250, and RCS4 in H9c2 cells at 0.1 μM. In addition, the cytotoxicity was associated with its pro-apoptotic effects as evidenced by the increase in caspase-3 levels. We demonstrated that a cannabinoid receptor type 2 (CB2) antagonist, AM630, inhibited JWH-030-induced cytotoxicity, whereas a CB1 antagonist, rimonabant, did not. Furthermore, fluorescence polarization assay showed JWH-030 to block the hERG channel (half-maximal inhibitory concentration, IC50 was 88.36 μM). JWH-030 significantly reduced the APD at 90% repolarization (APD90) in rabbit Purkinje fibers and decreased the left ventricular end diastolic pressure (LVEDP) in Langendorff-perfused Sprague-Dawley (SD) rat hearts at 30 μM. In addition, the electrocardiogram (ECG) measurement revealed that the intravenous injection of JWH-030 (0.5 mg kg−1) prolonged the QT interval in SD rats. These results suggest that JWH-030 is cytotoxic and its cytotoxicity is mediated by its action on the CB2 receptor; it prolongs the QT interval by regulating ion current channels and APD.

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 CD4

Background Malignant pleural effusion (MPE) occasionally demonstrates neutrophilic predominance, commonly found in parapneumonic pleural effusion (PPE). In comparison with lymphocytic MPE, neutrophilic MPE may have different characteristics associated with a more intense inflammatory response and poor prognosis. These characteristics of neutrophilic MPE may lead to inappropriate management and delayed diagnosis. Moreover, the limited diagnostic yield of microbiologic and cytologic tests makes early differential diagnosis between neutrophilic MPE and PPE more challenging. This study investigated objective laboratory findings to help distinguish neutrophilic MPE from PPE. Materials and Methods A retrospective study was conducted on patients with neutrophilic MPE and PPE. Routine blood and pleural fluid data of the 2 groups were compared, and the diagnostic performances of predictors for neutrophilic MPE were assessed using receiver-operating characteristic curves. Results Forty-one and 140 patients with neutrophilic MPE and PPE, respectively, were included. In final analysis, serum C-reactive protein, pleural fluid neutrophil-to-lymphocyte ratio, and pleural fluid carcinoembryonic antigen were significantly different between the 2 groups. With cut-off values of C-reactive protein 8.0 ng/mL, the presence of any 2 or more parameters provided an area under the curve of 0.928 (95% CI, 0.851-0.999), yielding a sensitivity of 88%, specificity of 98%, positive predictive value of 92% and negative predictive value of 96% for identifying MPE. Conclusions MPE should be considered even in patients with neutrophilic exudative effusion, especially if at least 1 predictor for neutrophilic MPE is present. Our results may help guide differentiation of neutrophilic MPE from PPE.

Disopyramide as an antiarrhythmic agent has been used for treating ventricular tachycardia and metabolized into its major metabolite, mono-isopropyl-disopyramide, by CYP3A4. We developed a novel, selective, highly sensitive, accurate, rapid method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of disopyramide and mono-isopropyl-disopyramide in rat plasma. This study is the first report for the assay validation using LC-MS/MS in biological fluids after simple protein-precipitation method. The most sensitive signals by multiple reaction monitoring (MRM) showed at m/z 340.2 → 239.2 and 298.2 → 239.2 with same fragment ion for disopyramide and mono-isopropyl-disopyramide, respectively. The lower limit of quantification (LLOQ) was determined at 2 ng/mL for both analytes and the linear concentration ranges were found to be 2–2000 ng/mL for disopyramide and 2–1000 ng/mL for mono-isopropyl-disopyramide. Finally, this assay was successfully applied to pharmacokinetic analysis of disopyramide and mono-isopropyl-disopyramide after oral and intravenous administration of disopyramide.

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.

Pseudomembranous tracheitis (PMT) is a rare condition characterized by pseudomembrane formation in the tracheobronchial tree that may be associated with infectious and noninfectious processes. However, PMT attributed to Mycoplasma pneumoniae ( M. pneumoniae ), a common atypical respiratory infectious pathogen, has not been reported till date. Here, we report about a 29-year-old woman with complaints of severe persistent cough and radiographic deterioration despite antibiotics administration for pneumonia at an outside facility. She was finally diagnosed as having PMT with bilateral diffuse bronchiolitis caused by M. pneumoniae infection. The diagnosis was made based on a bronchoscopic finding of a pseudomembrane that partially covered the membranous portion of the upper and middle trachea, a positive polymerase chain reaction (PCR) test with bronchial aspirate, and a positive serological test for M. pneumoniae without detection of any other causative pathogen through an extensive workup. Her symptoms and radiographic findings improved in response to moxifloxacin and corticosteroid treatment. This case is a rare presentation of M. pneumoniae infection complicating PMT in a young adult without any known risk factors.