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Background/Aims Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis. Methods Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to time-of-flight mass spectrometry. Correlation analyses were performed targeting the gut-microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased). Results Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC >0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites. Conclusions Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

ABSTRACTMetabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, and its prevalence has increased worldwide in recent years. Additionally, there is a close relationship between MASLD and gut microbiota-derived metabolites. However, the mechanisms of MASLD and its metabolites are still unclear. We demonstrated decreased indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA) in the feces of patients with hepatic steatosis compared to healthy controls. Here, IPA and IAA administration ameliorated hepatic steatosis and inflammation in an animal model of WD-induced MASLD by suppressing the NF-κB signaling pathway through a reduction in endotoxin levels and inactivation of macrophages. Bifidobacterium bifidum metabolizes tryptophan to produce IAA, and B. bifidum effectively prevents hepatic steatosis and inflammation through the production of IAA. Our study demonstrates that IPA and IAA derived from the gut microbiota have novel preventive or therapeutic potential for MASLD treatment.

ABSTRACTThe liver is rich in innate immune cells, such as natural killer (NK) cells, natural killer T cells, and Kupffer cells associated with the gut microbiome. These immune cells are dysfunctional owing to alcohol consumption. However, there is insufficient data on the association between immune cells and gut microbiome in alcoholic liver disease (ALD). Therefore, the purpose of this study was to evaluate the effects of probiotic strains on NK cells in ALD patients. In total, 125 human blood samples [control (n = 22), alcoholic hepatitis (n = 43), and alcoholic cirrhosis (n = 60]) were collected for flow cytometric analysis. C57BL/6J mice were divided into four groups (normal, EtOH-fed, and 2 EtOH+strain groups [Phocaeicola dorei and Lactobacillus helveticus]). Lymphocytes isolated from mouse livers were analyzed using flow cytometry. The frequency of NK cells increased in patients with alcoholic hepatitis and decreased in patients with alcoholic cirrhosis. The expression of NKp46, an NK cell-activating receptor, was decreased in patients with alcoholic hepatitis and increased in patients with alcoholic cirrhosis compared to that in the control group. The number of cytotoxic CD56dimCD16+ NK cells was significantly reduced in patients with alcoholic cirrhosis. We tested the effect of oral administration P. dorei and L. helveticus in EtOH-fed mice. P. dorei and L. helveticus improved liver inflammation and intestinal barrier damage caused by EtOH supply and increased NK cell activity. Therefore, these observations suggest that the gut microbiome may ameliorate ALD by regulating immune cells.

Abstract The metabolites of gut microbiota show favorable therapeutic effects on nonalcoholic fatty liver disease (NAFLD), but the active metabolites and mechanisms against NAFLD have not been documented. The aim of the study was to investigate the active metabolites and mechanisms of gut microbiota against NAFLD by network pharmacology. We obtained a total of 208 metabolites from the gutMgene database and retrieved 1256 targets from similarity ensemble approach (SEA) and 947 targets from the SwissTargetPrediction (STP) database. In the SEA and STP databases, we identified 668 overlapping targets and obtained 237 targets for NAFLD. Thirty-eight targets were identified out of those 237 and 223 targets retrieved from the gutMgene database, and were considered the final NAFLD targets of metabolites from the microbiome. The results of molecular docking tests suggest that, of the 38 targets, mitogen-activated protein kinase 8-compound K and glycogen synthase kinase-3 beta-myricetin complexes might inhibit the Wnt signaling pathway. The microbiota-signaling pathways-targets-metabolites network analysis reveals that Firmicutes, Fusobacteria, the Toll-like receptor signaling pathway, mitogen-activated protein kinase 1, and phenylacetylglutamine are notable components of NAFLD and therefore to understanding its processes and possible therapeutic approaches. The key components and potential mechanisms of metabolites from gut microbiota against NAFLD were explored utilizing network pharmacology analyses. This study provides scientific evidence to support the therapeutic efficacy of metabolites for NAFLD and suggests holistic insights on which to base further research.

Diet and lifestyle are crucial factors that influence the susceptibility of humans to nonalcoholic fatty liver disease (NAFLD). Personalized diet patterns chronically affect the composition and activity of microbiota in the human gut; consequently, nutrition-related dysbiosis exacerbates NAFLD via the gut–liver axis. Recent advances in diagnostic technology for gut microbes and microbiota-derived metabolites have led to advances in the diagnosis, treatment, and prognosis of NAFLD. Microbiota-derived metabolites, including tryptophan, short-chain fatty acid, fat, fructose, or bile acid, regulate the pathophysiology of NAFLD. The microbiota metabolize nutrients, and metabolites are closely related to the development of NAFLD. In this review, we discuss the influence of nutrients, gut microbes, their corresponding metabolites, and metabolism in the pathogenesis of NAFLD.

Over the past decade, scientific evidence for the properties, functions, and beneficial effects of probiotics for humans has continued to accumulate. Interest in the use of probiotics for humans has increased tremendously. Among various microorganisms, probiotics using bacteria have been widely studied and commercialized, and, among them, Lactobacillus is representative. This genus contains about 300 species of bacteria (recently differentiated into 23 genera) and countless strains have been reported. They improved a wide range of diseases including liver disease, gastrointestinal diseases, respiratory diseases, and autoimmune diseases. Here, we intend to discuss in depth the genus Lactobacillus as a representative probiotic for chronic liver diseases.

Background: Molecular screening using next-generation sequencing (NGS) in the pathologic evaluation of lung cancer is considered the standard in clinical practice; hence, we evaluated the diagnostic yields of various sampling methods for NGS. Methods: NGS data from patients with lung cancer at the Pusan National University Hospital (Busan, South Korea), admitted October, 2020-April, 2023, was obtained. The sampling methods by which NGS data was obtained were divided into surgical and nonsurgical. Surgical methods included thoracoscopic surgery, surgical biopsy from the metastatic site, and lymph node excisional biopsy, whereas nonsurgical methods included bronchoscopy procedures and medical thoracoscopic biopsy. Results: In total, we obtained 319 patients' NGS data:150 (47.0%) and 169 (53.0%) was obtained using surgical and nonsurgical methods, respectively. The overall diagnostic yield of NGS analysis was 97.5% for all samples. There were no significant differences in the success rates of deoxyribonucleic acid sequencing between surgical and nonsurgical sampling methods (98.0% vs. 96.4%, p = 0.313). On the other hand, the success rate of ribonucleic acid (RNA) sequencing was significantly lower in the surgical method group (78.0% vs. 92.3%; p < 0.001). Multivariate analysis showed that surgical sampling significantly correlated with RNA sequencing failure (Odd Ratio 4.128, 95% Confidence Interval 1.681-10.133, p = 0.002). Conclusions: Small samples obtained using nonsurgical procedures are suitable for NGS analysis in clinical practice. However, surgical sampling showed a relatively lower success rate for RNA sequencing than nonsurgical sampling. This information may help in the development of protocols to reduce RNA degradation during the surgical process. [ABSTRACT FROM AUTHOR]

Purpose: The use of neoadjuvant anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (TKIs) has not been extensively explored. The current case report highlights the notable pathological complete response (pCR) achieved following neoadjuvant brigatinib therapy in a patient with stage IIIA ALK-positive non-small cell lung cancer (NSCLC). Case presentation: A 32-year-old male presented with incidental lung lesions, ultimately diagnosed as clinical stage T3N1M0, IIIA NSCLC with an ALK gene rearrangement. Following a multidisciplinary discussion, the patient opted for neoadjuvant brigatinib therapy, which significantly reduced the tumor size. Subsequently, surgery with curative intent was performed, revealing pCR with no residual tumor cells. The patient remained disease-free during a 13-month follow-up period. Conclusion: This case report provides compelling evidence of pCR following brigatinib therapy in ALK-positive NSCLC, suggesting that surgery after neoadjuvant therapy with brigatinib may offer a safe and effective approach for patients with ALK-positive NSCLC. [ABSTRACT FROM AUTHOR]

Tracheal leiomyoma is a rare benign tumor, which is composed of transformed cells of mesenchymal origin. We describe a case in which digital tomosynthesis was useful to evaluate a tracheal tumor that was overlooked on initial chest radiographs.

Inflammatory myofibroblastic tumor is a rare benign lesion that accounts for 0.04–1% of all lung tumors and usually appears as a solitary pulmonary nodule or mass. Here, we report the case of an endobronchial inflammatory myofibroblastic tumor in a 21-year-old man with a focus on the imaging findings and a review of previous literature.

Abstract Background Myelolipoma is a rare benign tumor composed of mature adipose and hematopoietic tissues. Most myelolipomas are found in the adrenal glands, whereas intrathoracic myelolipoma is extremely rare. In particular, bronchial myelolipoma without the involvement of lung parenchyma has never been reported. Case presentation A previously healthy 38-year-old male developed dyspnea and a productive cough. Computed tomography revealed an endobronchial mass at the right bronchus intermedius and subsequent atelectasis of the right middle and lower lobes. Flexible bronchoscopy found a total obstruction of the right bronchus intermedius due to an endobronchial tumor. Using a rigid bronchoscope, the endobronchial tumor was resected and the base of the tumor was additionally ablated with a diode laser to prevent recurrence. The removed endobronchial tumor was a 13 mm × 20 mm-sized oval-shaped mass and was pathologically diagnosed as bronchial myelolipoma. Chest radiographs, obtained on the day following the procedure, showed an improvement of atelectasis, and accompanying symptoms were immediately improved. Follow-up bronchoscopy performed after 12 months evidenced no recurrence of the bronchial myelolipoma. Conclusions We used bronchoscopic intervention in patients with solitary bronchial myelolipoma and there was no evidence of recurrence.

Abstract Background Generally, structural destruction of lung parenchyma, such as pulmonary emphysema, is considered to be related to the low diagnostic yields and high complication rates of lung biopsies of peripheral lung lesions. Currently, little is known about the clinical outcomes of using endobronchial ultrasound with a guide sheath (EBUS-GS) to diagnose peripheral lesions in patients with emphysema. Methods This retrospective study was performed to identify the clinical outcomes of EBUS-GS in patients with pulmonary emphysema. This study included 393 consecutive patients who received EBUS-GS between February 2017 and April 2018. The patients were classified according to the severity of their emphysema, and factors possibly contributing to a successful EBUS-GS procedure were evaluated. Results The overall diagnostic yield of EBUS-GS in patients with no or mild emphysema was significantly higher than in those with moderate or severe pulmonary emphysema (78% vs. 61%, P = 0.007). There were no procedure-related complications. The presence of a bronchus sign on CT (P

Abstract Background Virtual bronchoscopy navigation (VBN) is widely used for assistance in the histological examination of lung nodules. However, little is known about the optimal CT radiation dose for VBN. Therefore, we performed an animal study to evaluate the feasibility of low dose CT (LDCT) for VBN. Methods Ten pigs underwent standard dose CT (as a reference) and four different LDCT protocols: LDCT 1, 120 kVp, 15 mAs; LDCT 2, 120 kVp, 8 mAs; LDCT 3, 100 kVp, 7 mAs; and LDCT 4, 100 kVp, 4 mAs. As targets for the VBN, 10 mm virtual lesions were created in the central and peripheral bronchi. To assess the performance of the VBN, the navigation direction (direction of reconstructed pathways to the target) and the number of branching’s (the number of peripheral bronchi to the target) were evaluated. Results The mean effective doses significantly differed across the four LDCTs (P

Background The presence of EGFR mutation in patients with advanced non‐small cell lung cancer (NSCLC) plays an important role in determining the appropriate treatment, response, and survival. Therefore, this study attempted to predict the prognosis of NSCLC patients using data from quantitative mutation measurements. Methods The data of patients with advanced NSCLC who underwent EGFR mutation testing using the peptide nucleic acid (PNA) mediated clamping method at the Pusan National University Hospital from October 2015 to December 2017 were retrospectively analyzed. The efficiency of PNA clamping was determined by measuring the threshold cycle (Ct) value. The ΔCt−1 value (standard Ct value minus sample Ct value) was calculated to quantify EGFR mutation. Results During the study period, 71 patients were treated with EGFR‐tyrosine kinase inhibitors. The cutoff point for the ΔCt−1 value derived from the receiver operating characteristic curve was 5.32. A survival benefit was observed in the group with an ΔCt−1 value > 5.32 or with a common EGFR mutation type compared to the group with an ΔCt−1 value < 5.32. Conclusion EGFR mutation testing using PNA clamping may predict patient survival, especially in patients with common EGFR mutations, such as exon 19 deletion or L858R. A higher ΔCt−1 value correlates with better survival.

Non-alcoholic fatty liver disease (NAFLD) is considered to be a significant health threat globally, and has attracted growing concern in the research field of liver diseases. NAFLD comprises multifarious fatty degenerative disorders in the liver, including simple steatosis, steatohepatitis and fibrosis. The fundamental pathophysiology of NAFLD is complex and multifactor-driven. In addition to viruses, metabolic syndrome and alcohol, evidence has recently indicated that the microbiome is related to the development and progression of NAFLD. In this review, we summarize the possible microbiota-based therapeutic approaches and highlight the importance of establishing the diagnosis of NAFLD through the different spectra of the disease via the gut–liver axis.

A multiplex RT-PCR (mRT-PCR) assay was developed for the detection of the recently reported viruses, Cherry virus A (CVA), Little cherry virus 1 (LChV-1), and Little cherry virus 2 (LChV-2), in cherry plants in Korea. Eight sets of primers were designed for each virus and their specificity was tested by using various combinations of mixed primer sets. From the designed primer sets, one combination was selected and further evaluated to estimate the optimum temperature and detection limits of the mRT-PCR. A newly developed mRT-PCR assay was also tested using 20 cherry samples collected in the field. This mRT-PCR assay may be a useful tool for field surveys of diseases and the rapid detection of these three viruses in cherry plants.

Abstract Background The diagnostic yields and safety profiles of transbronchial lung biopsy have not been evaluated in inexperienced physicians using the combined modality of radial probe endobronchial ultrasound and a guide sheath (EBUS-GS). This study assessed the utility and safety of EBUS-GS during the learning phase by referring to a database of performed EBUS-GS procedures. Methods From December 2015 to January 2017, all of the consecutive patients who underwent EBUS-GS were registered. During the study period, two physicians with no previous experience performed the procedure. To assess the diagnostic yields, learning curve, and safety profile of EBUS-GS performed by these inexperienced physicians, the first 100 consecutive EBUS-GS procedures were included in the evaluation. Results The overall diagnostic yield of EBUS-GS performed by two physicans in 200 patients with a peripheral lung lesion was 73.0%. Learning curve analyses showed that the diagnostic yields were stable, even when the procedure was performed by beginners. Complications related to EBUS-GS occurred in three patients (1.5%): pneumothorax developed in two patients (1%) and resolved spontaneously without chest tube drainage; another patient (0.5%) developed a pulmonary infection after EBUS-GS. There were no cases of pneumothorax requiring chest tube drainage, severe hemorrhage, respiratory failure, premature termination of the procedure, or procedure-related mortality. Conclusions EBUS-GS is a safe and stable procedure with an acceptable diagnostic yield, even when performed by physicians with no previous experience.

We intended to identify favourable metabolite(s) and pharmacological mechanism(s) of gut microbiota (GM) for liver regeneration (LR) through network pharmacology. We utilized the gutMGene database to obtain metabolites of GM, and targets associated with metabolites as well as LR-related targets were identified using public databases. Furthermore, we performed a molecular docking assay on the active metabolite(s) and target(s) to verify the network pharmacological concept. We mined a total of 208 metabolites in the gutMGene database and selected 668 targets from the SEA (1,256 targets) and STP (947 targets) databases. Finally, 13 targets were identified between 61 targets and the gutMGene database (243 targets). Protein-protein interaction network analysis showed that AKT1 is a hub target correlated with 12 additional targets. In this study, we describe the potential microbe from the microbiota (E. coli), chemokine signalling pathway, AKT1 and myricetin that accelerate LR, providing scientific evidence for further clinical trials. [ABSTRACT FROM AUTHOR]

We aimed to develop a decision tree model to improve diagnostic performance of positron emission tomography/computed tomography (PET/CT) to detect metastatic lymph nodes (LN) in non-small cell lung cancer (NSCLC). 115 patients with NSCLC were included in this study. The training dataset included 66 patients. A decision tree model was developed with 9 variables, and validated with 49 patients: short and long diameters of LNs, ratio of short and long diameters, maximum standardized uptake value (SUVmax) of LN, mean hounsfield unit, ratio of LN SUVmax and ascending aorta SUVmax (LN/AA), and ratio of LN SUVmax and superior vena cava SUVmax. A total of 301 LNs of 115 patients were evaluated in this study. Nodular calcification was applied as the initial imaging parameter, and LN SUVmax (≥3.95) was assessed as the second. LN/AA (≥2.92) was required to high LN SUVmax. Sensitivity was 50% for training dataset, and 40% for validation dataset. However, specificity was 99.28% for training dataset, and 96.23% for validation dataset. In conclusion, we have developed a new decision tree model for interpreting mediastinal LNs. All LNs with nodular calcification were benign, and LNs with high LN SUVmax and high LN/AA were metastatic Further studies are needed to incorporate subjective parameters and pathologic evaluations into a decision tree model to improve the test performance of PET/CT.

CONTEXT: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder, and various aspects of COPD may be associated with the severity of pneumonia in such patients. AIMS: We examined the risk factors associated with severe pneumonia in a COPD population. MATERIALS AND METHODS: We performed a retrospective observational study using a prospectively collected database of pneumonia patients who were admitted to our hospital through emergency department between 2008 and 2012. Patients with hospital-acquired pneumonia and those with an immunocompromised status were excluded. RESULTS: Of 148 pneumonia patients with COPD for whom chest computed tomography (CT) scans were available, 106 (71.6%) and 42 (28.4%) were classified as non-severe and severe pneumonia, respectively. Multivariate logistic regression analysis revealed that the severity of airflow limitation [odds ratio (OR), 2.751; 95% confidence interval (CI), 1.074-7.050; P = 0.035] and the presence of emphysema on a chest CT scan (OR, 3.366; 95% CI, 1.104-10.265; P = 0.033) were independently associated with severe pneumonia in patients with COPD. CONCLUSIONS: The severity of COPD including the airflow limitation grade and the presence of pulmonary emphysema were independently associated with the development of severe pneumonia.