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Pulmonary vein stump thrombosis (PVST) is uncommonly encountered postoperative in-situ thrombosis in the stump of pulmonary veins after lung resection. Data regarding the incidence and clinical behaviour of PVST are scarce. Thus, this study aims to investigate the incidence, clinical characteristics and outcome of PVST after lung resection in patients with lung cancer. Follow-up enhanced chest computed tomography (CT) scans acquired after the surgery were retrospectively reviewed to determine PVST presence for patients with lung cancer who underwent lung resection in two tertiary referral centres. Out of the 1885 patients with lung cancer who underwent lobectomy or more extensive lung resection, PVST was observed in 37 patients (2.0%) on their follow-up chest CT. Most stump thrombi were observed in the left superior pulmonary vein [35 (94.6%)] and in patients who underwent left upper lobectomy [34 (91.9%)]. At the last CT follow-up of each patient, 33 (89.2%) exhibited complete resolution, three partial resolution and one stabilization. Eleven (29.7%) patients received anticoagulant therapy after the diagnosis. The rate of complete PVST resolution did not differ significantly between the anticoagulation and nonanticoagulation groups. None of the PVST patients experienced systemic embolic events, regardless of anticoagulation. The PVST incidence diagnosed at routine chest CT follow-up following lung cancer surgery was 2%. PVST was characterized by a benign clinical course without progression and systemic embolization, regardless of anticoagulation. However, further studies are required to determine individualized therapeutic strategies, including anticoagulation.

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/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.

Differential leukocyte counts of pleural fluid are routinely recommended for the early diagnosis and management of exudative pleural effusions. Rapid automated cellular analysis agrees strongly with standard manual microscopic counts and has become a reality in many clinical laboratories. However, discordant results sometimes observed between automated and manual analyses raise concern about using automated analysis to aid prompt differential diagnosis. This study aimed to evaluate the real-world disagreement between automated and manual leukocyte analyses in exudative pleural effusions and to investigate whether the discordant results occur in specific cellular ranges or randomly. We conducted a retrospective study of patients who were diagnosed with parapneumonic pleural effusions (PPE), tuberculous pleural effusions (TPE), and malignant pleural effusions (MPE) between September 2018 and December 2020. Differential and predominant leukocyte counts were performed using an automated XN-350 analyzer with a two-part differential count consisting of polymorphonuclear (PMN) and mononuclear (MN) leukocytes and a manual method with Wright-stained cytospin slides. We compared the two methods on cases of 109 PPEs, 50 TPEs, and 116 MPEs. Although the overall correlation between the two methods for differential leukocyte counts was excellent, there were etiologic variations; MPEs showed a lower correlation compared to PPEs and TPEs. Automated-PMN predominance almost corresponded to manual cytospin-neutrophilic predominance. In contrast, ~10% of the automated-MN predominance did not correspond with the cytospin-lymphocytic predominance. These discrepancies occurred most in the automated-MN% range of 51% to 60%, followed by 61% to 70%. The PMN% range ≥50% and30% on the automated analysis reliably corresponds to the neutrophilic and lymphocytic predominance, respectively. However, the MN% range of 51% to 70% may not coincide with lymphocytic predominance on manual cytospin analysis. This range leaves the potential cause of exudative pleural effusions open.

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.

Hyewon Seo,1 Yun Su Sim,2 Kyung Hoon Min,3 Jae Ha Lee,4 Byung-Keun Kim,5 Yeon Mok Oh,6 Seung Won Ra,7 Tae-Hyung Kim,8 Yong Il Hwang,9 Jeong-Woong Park10 1Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Kangnam Sacred Heart Hospital, Seoul, Republic of Korea; 3Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea; 4Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea; 5Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea; 6Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 7Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 8Division of Pulmonary and Critical Care Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea; 9Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea; 10Department of Allergy, Pulmonary and Critical Care Medicine, Gachon University Gil Medical Center, Incheon, Republic of KoreaCorrespondence: Jeong-Woong Park, Department of Allergy, Pulmonary and Critical Care Medicine, Gachon University Gil Medical Center, Namdong-daero 774 beon-gil, Namdong, Incheon, 21565, Republic of Korea, Tel +82-10-5574-0164, Fax +82-32-469-4320, Email jwpark@gilhospital.comPurpose: Data regarding the relationship between microbiologic features and comorbidities in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are limited. The aim of this study was to correlate microbiologic findings with comorbidities in patients with moderate to severe AECOPD.Patients and Methods: This multicenter observational study included patients with AECOPD seen at 28 hospitals in South Korea between January 2015 and December 2018, and the data were retrospectively collected. Pathogens were examined in patients with either pulmonary or extrapulmonary comorbidities, and compared to those of patients without comorbidities. The relationship between pathogen type and the number of comorbidities was also evaluated.Results: Bacterial infections (178 [37.2%] vs 203 [28.7%], p = 0.002) and co-infections with bacteria and viruses (65 [13.6%] vs 57 [8.1%], p = 0.002) were more prevalent in patients with pulmonary comorbidities. Bacterial pathogens (280 [34.7%] vs 101 [26.7%], p=0.006) were detected at a higher rate in patients with extrapulmonary comorbidities. Previous pulmonary tuberculosis (PTB), bronchiectasis, and diabetes mellitus were risk factors for bacterial infection, and congestive heart failure was a risk factor for bacterial and viral co-infection. As the number of comorbidities increased, the risk of bacterial infection increased considerably. Pseudomonas aeruginosa was more frequently identified in patients with previous PTB (57 [15.3%] vs 59 [7.4%], p < 0.001) and bronchiectasis (33 [19.6%] vs 83 [8.3%], p < 0.001).Conclusion: AECOPD patients with comorbidities were more likely to experience infection-related exacerbations compared to those without comorbidities. As the overall number of comorbidities increased, the risk of bacterial infection increased significantly.Keywords: chronic obstructive pulmonary disease, acute exacerbation, comorbidity, bacteria, virus

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.

Tyrosinase is a key enzyme that has long been considered as a biomarker for melanoma as it catalyzes the oxidation of tyrosine and l-DOPA in melanogenesis. Recent studies also suggest a link between tyrosinase activity and Parkinson’s disease; however, the mechanism of tyrosinase-mediated melanin formation in the brain is poorly understood. To better understand this connection, more advanced tools for the detection of tyrosinase in the brain are required. Herein, we successfully designed and synthesized a tyrosinase-targeting Gd(iii)-based MR contrast agent Tyr-GBCA 1. Tyr-GBCA 1 was synthesized by linking m-hydroxyphenyl to Gd-DOTA via a self-immolative linker. Tyr-GBCA 1 shows a 21% increase in the T(1) relaxation rate (R(1)) in the presence of tyrosinase in artificial cerebral spinal fluid. Furthermore, Tyr-GBCA 1 is unreactive to hydrogen peroxide, which is a potential interferent in oxidation-based tyrosinase sensing systems. The reaction mechanism of the probe was studied by electrospray ionization (ESI) mass spectrometry and supports the cleavage of a reaction site.

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.

Extracellular pH is important in clinical measurements due to its correlation to cell metabolism and disease progression. In MRI, T(1)/T(2) ratiometric analysis and other methods have been previously applied to quantify pH using conventional pulse sequences. However, for nanoparticle-based approaches, heterogeneity in size and surface functionalization tends toward qualitative rather than quantitative results. To address this limitation, we developed a novel DNA-based MRI contrast agent, pH-DMRCA, which utilizes a highly programmable and reproducible nanostructure. The pH-DMRCA is a dendritic DNA scaffold that is functionalized with a pH-responsive MRI-sensitive construct, Gd(NP-DO3A), at the end of each DNA arm. We first evaluated the r(1) and r(2) response of our pH-DMRCA over a range of pH values (pH = 5–9) to establish a relaxometric model of pH. These MRI-based assessments of pH were validated in a separate set of samples using a pH electrode (n = 18) and resulted in a good linear correlation (R(2) = 0.99, slope = 0.98, intercept = 0). A Bland–Altman analysis of the results also showed reasonable agreement between the calculated pH and measured pH. Moreover, these pH comparisons were consistent across three different pH-DMRCA concentrations, demonstrating concentration-independence of the method. This MRI-based pH quantification methodology was further verified in human blood plasma. Given the versatility of the DNA-based nanostructures, the contrast agent has a potential to be applied to a wide variety of imaging applications where extracellular pH is important including cancer, stroke, cardiovascular disease, and other important diseases.

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.

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.

Predicting drug–drug interactions (DDIs) is an important step during drug development to avoid unexpected side effects. Cytochrome P450 (CYP) 3A4 is the most abundant human hepatic phase I enzyme, which metabolizes >50% of therapeutic drugs. Therefore, it is essential to test the potential of a drug candidate to induce CYP3A4 expression or inhibit its activity. Recently, 3-dimensional (3-D) mammalian cell culture models have been adopted in drug discovery research to assess toxicity, DDIs, and pharmacokinetics. In this study, we applied a human 3-D spheroid culture protocol using HepaRG cells combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess its ability to predict CYP3A4 inhibition. Levels of midazolam, a specific substrate of CYP3A4, were used to determine the long-term metabolic capacity of CYP3A4. Midazolam was decreased in the 3-D HepaRG culture system by ∼80% over 7 days, whereas its primary metabolite, 1-hydroxymidazolam, increased by ∼40%. Next, we assessed hepatotoxicity by determining the cytotoxicity of known hepatotoxicants in HepaRG spheroids, HepG2 cells, and primary human hepatocytes. Significant differences in cytotoxicity were detected in the system using 3-D HepaRG spheroids. These results suggest that 3-D HepaRG spheroids are a good model for prediction of CYP inhibition and hepatotoxicity in screening of early drug candidates.

Zinc performs diverse physiological functions, and virtually all living organisms require zinc as an essential trace element. To identify the detailed function of zinc in fungal pathogenicity, we carried out cDNA microarray analysis using the model system of Aspergillus fumigatus, a fungal pathogen. From microarray analysis, we found that the genes involved in gliotoxin biosynthesis were upregulated when zinc was depleted, and the microarray data were confirmed by northern blot analysis. In particular, zinc deficiency upregulated the expression of GliZ, which encodes a Zn2-Cys6 binuclear transcription factor that regulates the expression of the genes required for gliotoxin biosynthesis. The production of gliotoxin was decreased in a manner inversely proportional to the zinc concentration, and the same result was investigated in the absence of ZafA, which is a zinc-dependent transcription activator. Interestingly, we found two conserved ZafA-binding motifs, 5′-CAAGGT-3′, in the upstream region of GliZ on the genome and discovered that deletion of the ZafA-binding motifs resulted in loss of ZafA-binding activity; gliotoxin production was decreased dramatically, as demonstrated with a GliZ deletion mutant. Furthermore, mutation of the ZafA-binding motifs resulted in an increase in the conidial killing activity of human macrophage and neutrophil cells, and virulence was decreased in a murine model. Finally, transcriptomic analysis revealed that the expression of ZafA and GliZ was upregulated during phagocytosis by macrophages. Taken together, these results suggest that zinc plays an important role in the pathogenicity of A. fumigatus by regulating gliotoxin production during the phagocytosis pathway to overcome the host defense system.

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.

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.

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.

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.

2-(2,5-Dimethoxy-4-nitrophenyl)-N-(2-methoxybenzyl)ethanamine (25N-NBOMe, 2C-N-NBOMe, NBOMe-2C-N) is a novel synthetic psychoactive substance of the phenethylamine chemical class. A few metabolism studies have been conducted for 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe, and others, whereas 25N-NBOMe metabolism has not been researched. In this study, the in vitro metabolism of 25N-NBOMe was investigated with human liver microsomes, and the reaction mixture was analyzed using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS). Formation of 14 metabolites (M1-M14) was yielded with incubation of 25N-NBOMe in human liver microsomes in the presence of NADPH. The metabolites were structurally characterized on the basis of accurate mass analysis and MS/MS fragmentation patterns. The biotransformations included hydroxylation, O-demethylation, N-dealkylation, nitro reduction, dehydrogenation, carbonylation, and combinations thereof. Hydroxyl metabolite was the most abundant compound after the phase I process. These results provide helpful information establishing biomarkers in case of 25N-NBOMe ingestion.

1. A novel diacylglyceride acyltransferase-1 (DGAT-1) inhibitor, 2-(4-(4-(5-(2-phenyl-5-(trifluoromethyl) oxazole-4-carboxamido)-1H-benzo[d]imidazol-2-yl)phenyl)cyclohexyl) acetic acid (KR-69232), was synthesized for a potential therapeutic use against several metabolic disorders, such as obesity, insulin resistance, and type II diabetes, characterized by excessive triglycerides (TGs) in the blood. 2. The half-lives against phase I metabolism were measured as 75.3 ± 20.9 min and over 120 min in rat and human liver microsomes, respectively. In Caco-2 cell monolayers, extremely low permeability (0.13 × 10⁻⁶cm/s) was seen in the absorptive direction, predicting limited intestinal absorption of KR-69232. This compound was highly bound to rat and human plasma proteins (99.8%). 3. With the intravenous administration of KR-69232 in rats (1, 2, and 5 mg/kg), non-linear kinetics were observed at the highest dose, with significantly higher systemic clearance, higher volume of distribution, and lower dose-normalized AUC. Following oral administration, it exhibited low bioavailability (10%) and was absorbed slowly (T(max), 3.8-5.2 h) over the dose range. We also confirmed that considerable KR-69232 remained in the intestine at T(max), demonstrating its limited absorption into the systemic circulation.

OBJECTIVE The optimal prognostic model for community-acquired pneumonia (CAP) remains unclear. In this study, we sought to identify independent predictors of 30-day mortality in patients with CAP and to determine whether adding specific prognostic factors to each of the two clinical prediction scores could improve the prognostic yield. METHODS This retrospective study involved 797 CAP patients who had been hospitalized at a tertiary referral center. The patients were categorized into two groups: those who survived and those who had died on or before 30 days after admission. Select clinical parameters were then compared between the two groups. RESULTS During the 30-day period, there were 72 deaths (9%). We constructed two models for a multivariate analysis: one was based on a high CURB-65 score (3-5) and the other on a high pneumonia severity index (PSI) class (V). In both models, a high CURB-65 score or a high PSI class, along with the presence of dyspnea, high Eastern Cooperative Oncology Group (ECOG) performance status (3-4), and a low serum albumin level, were independent predictors of 30-day mortality. In both the CURB-65-based and PSI-based models, the addition of dyspnea, high ECOG performance status, and hypoalbuminemia (

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., We investigated the clinical features of community‐acquired necrotizing pneumonia. Necrotizing change was noted in approximately 10% of the patients with community‐acquired pneumonia (CAP) and was characterized by more severe clinical manifestations and increased need for pleural drainage. Necrotizing change was a predictor of length of hospital stay (LOS) but not of mortality in patients with CAP.

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is associated with metabolic syndromes such as type 2 diabetes mellitus and obesity. A new 11β-HSD1 inhibitor known as 2-(3-benzoyl)-4-hydroxy-1, 1-dioxo-2H-1, 2-benzothiazine-2-yl-1-phenylethanone (KR-66344) is being developed as a therapeutic agent for these metabolic diseases. The purpose of this study was to characterize the pharmacokinetics of KR-66344 to support further preclinical development. KR-66344 showed high liver microsomal stability with T1/2 values >3 h and high permeability with apparent permeability coefficients of 15.2-24.2 × 10(-6) cm/s in Caco-2 cell monolayers. KR-66344 was also strongly bound to plasma proteins (>98%). After intravenous dosing, KR-66344 exhibited low systemic clearance (0.27-0.37 L/h/kg) and a low to moderate volume of distribution at steady state (0.79-0.8 L/kg). The bioavailability and terminal half-lives of KR-66344 following oral administration were 25% and 1.7-3.3 h, respectively. In addition, KR-66344 showed dose-independent pharmacokinetics at 0.5-10 mg/kg in intravenous and oral pharmacokinetic studies.

'Focal necrotizing pneumonia' was defined as a localized type of necrotizing pneumonia characterized by a single or few cavities of low density without rim enhancement on computed tomography (CT) scan. The purpose of this study was to investigate the clinical features and course of patients with focal necrotizing pneumonia, thereby elucidating its clinical relevance.The present study was conducted retrospectively in patients who had been interpreted as having lung abscess or necrotizing pneumonia on CT scan. Clinical and radiological characteristics were compared between the focal necrotizing pneumonia and lung abscess groups.Overall, 68 patients with focal necrotizing pneumonia (n = 35) or lung abscess (n = 33) were included in the present study. The frequency of risk factors for aspiration was significantly lower in the focal necrotizing group, compared with the lung abscess group (14.3% vs 45.5%, P = 0.005). Compared with lung abscess, focal necrotizing pneumonia was observed more commonly in non-gravity-dependent segments (66% vs 36%, P 0.001). In addition, a trend towards more common isolation of aerobes as potential pathogens was observed in the focal necrotizing pneumonia group, compared with the lung abscess group (31% vs 12%, P = 0.08). However, in terms of treatment outcomes, a similar high rate of success was observed in both groups: 97%, respectively.Compared to lung abscess, focal necrotizing pneumonia occurs more commonly in non-gravity-dependent segments with lower incidence of risk factors for aspiration. Similar to lung abscess, the rate of success for treatment of focal necrotizing pneumonia was high.

This study evaluated the pharmacokinetics of the novel TAZ modulator TM-25659 in rats following intravenous and oral administration at dose ranges of 0.5-5 mg/kg and 2-10 mg/kg, respectively. Plasma protein binding, plasma stability, liver microsomal stability, CYP inhibition, and transport in Caco-2 cells were also evaluated. After intravenous injection, systemic clearance, steady-state volumes of distribution, and half-life were dose-independent, with values ranging from 0.434-0.890 mL · h(-1) · kg(-1), 2.02-4.22 mL/kg, and 4.60-7.40 h, respectively. Mean absolute oral bioavailability was 50.9% and was not dose dependent. Recovery of TM-25659 was 43.6% in bile and1% in urine. In pharmacokinetic modeling studies, the three-compartment (3C) model was appropriate for understanding these parameters in rats. TM-25659 was stable in plasma. Plasma protein binding was approximately 99.2%, and was concentration-independent. TM-25659 showed high permeation of Caco-2 cells and did not appear to inhibit CYP450. TM-25659 was metabolized in phase I and II steps in rat liver microsomes. In conclusion, the pharmacokinetics of TM-25659 was characterized for intravenous and oral administration at doses of 0.5-5 and 2-10 mg/kg, respectively. TM-25659 was eliminated primarily by hepatic metabolism and urinary excretion.

SummaryBackgroundAfter the application of chest computed tomography (CT), ground glass opacity (GGO) was introduced as one of major accompanying findings of miliary tuberculosis (MT) in addition to miliary nodules. However, little is known about whether GGO is associated with the clinical manifestations and outcomes of MT. Therefore, the present study examined the clinical relevance of GGO in patients with MT.MethodsChest radiographs and CT scans of MT patients were retrospectively reviewed. Clinical manifestations and outcomes were compared in terms of the extent of GGO revealed by chest CT.ResultsConfirmed 105 MT patients were included. GGO was observed in 70 (67%) patients. MT patients with an extent of GGO >50% (n = 21) had symptoms of shorter duration, more frequent dyspnea, and more pronounced changes in the levels of acute phase reactants. Miliary nodules were less discernible on CT in those with an extent of GGO >50%. MT patients with an extent of GGO >50% were significantly associated with a longer hospital stay (p = 0.02) and with acute respiratory failure (p 50% had more rapidly progressive manifestations and a greater potential for delayed diagnosis and poorer prognosis. Nevertheless, mortality was not higher in confirmed MT patients with an extent of GGO >50% than in those with an extent of GGO ≤50%.