Diagnostic outcomes of radial endobronchial ultrasound bronchoscopy guided by manual navigation in the evaluation of peripheral pulmonary lesions: An observational study.

BACKGROUND AND AIMS: Manual navigation (MN), drawing a bronchoscopic road map simply by looking at the consecutive computed tomography (CT), is feasible and economical. However, scant data about the use of MN in radial endobronchial ultrasound (r-EBUS) bronchoscopy have been documented till now. We aimed to evaluate the diagnostic performance of r-EBUS bronchoscopy guided by MN for diagnosing peripheral pulmonary lesions (PPLs) and to determine clinical factors affecting the diagnostic yield. METHODS: We performed a retrospective, cohort study of consecutive patients with PPLs who underwent r-EBUS bronchoscopic biopsy via guidance of MN from May 2020 to June 2021 in our Respiratory Endoscopic Division. The overall diagnostic yield of MN-guided r-EBUS, the factors affecting the yield, and the diagnostic performance for malignancy were evaluated. RESULTS: A total of 102 patients (103 lesions) were evaluated. The overall diagnostic yield of MN-guided r-EBUS was 82.0%, and it ranged from 79.6% to 82.5%, assuming the undermined cases were all positive cases (79.6%) or negatives (82.5%). The sensitivity of MN-guided r-EBUS for malignancy was 71.4%, ranging from 68.2% to 71.4%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 67.3%, ranging from 63.8% to 69.0%. The multivariate logistic regression showed that "bronchus sign on CT" was the only predictor of the overall diagnostic yield (odds ratio = 11.5, 95% confidence interval: 1.9-70.9, P = 0.009). CONCLUSIONS: MN-guided r-EBUS is feasible in diagnosing PPLs, especially for lesions with bronchus sign on CT.

Iodine-125 seed brachytherapy combined with pembrolizumab for advanced non-small-cell lung cancer after failure of first-line chemotherapy: A report of two cases and literature review.

Although immunotherapy regimens for advanced non-small-cell lung cancer (NSCLC) improve survival in selected sub-populations, their efficacy remains far from ideal due to underlying resistance; therefore, multimodal combination strategies are needed to optimize their efficacy. In our report, two patients with advanced NSCLC with negative targetable mutations, who had failed first-line chemotherapy were treated with combined therapy of computed tomography (CT)-guided percutaneous iodine-125 seed implantation and pembrolizumab. After combination treatment, both patients achieved partial response (PR), and sustained a long progression-free survival (PFS) without obvious therapy-related adverse reactions. Iodine-125 seeds bring no long-term adverse events and effectively amplify anti-tumor immune response induced by immunotherapy; thus, this combined therapy might be a promising alternative for NSCLC.

Endobronchial removal of the peripherally located foreign body with the ultrathin bronchoscopy and ultrathin cryoprobe guided by a manual navigating method: A case report.

RATIONAL: The bronchoscope is a preferential method used to remove airway foreign bodies, but for those located in the distal lumen of bronchus with long-time retention, how to remove them remains an intractable problem. PATIENT CONCERNS: A 57-year-old male presented with 2-week history of intermittent hemoptysis. Chest CT upon admission revealed a high-density opacity incarcerated in the distal basal segment of the left lower lobe, along with obstructive pneumonia. DIAGNOSES: The patient was diagnosed as foreign body aspiration. INTERVENTIONS: We firstly used a manual navigating method to draw a bronchoscopic map according to the thin-section CT. Then we adopted ultrathin bronchoscope (UTB) to remove the peripherally located foreign body. OUTCOMES: UTB successfully found the foreign body incarcerated in LB10ciiß under the guidance of manual navigation, but it was too tender to be extracted completely by forceps, and it was even pushed further away. Then 1.1 mm ultrathin cryoprobe was used, with an activation time of 4 seconds, the chili was frozen and completely removed. LESSONS: This first combined application of manual navigating method, UTB and ultrathin cryoprobe, successfully extracted foreign bodies lodged in the distal airways and thus avoided thoracic surgery.

Risk factors associated with radiolucent foreign body inhalation in adults: a 10-year retrospective cohort study.

BACKGROUND: Foreign body aspiration (FBA) is a serious condition with high morbidity and mortality rates. Although chest radiography is generally the first radiologic modality used in diagnosis, a substantial percentage of foreign bodies are radiolucent in adults with diagnosis challenging. METHODS: Retrospective review of adult patients with FBA diagnosed by flexible electronic bronchoscopy from 2012 to 2022 collecting demographics, history, hospital presentation, radiographic, and operative details. Risk factors associated with radiolucent foreign body inhalation in adults were explored using appropriate statistical methods. RESULTS: Between 1 January 2012 and 1 January 2022, 114 adult patients diagnosed with FBA were enrolled. The median age of participants was 65 years (IQR 52-74). Multidetector computed tomography (MDCT) examinations identified 28 cases (25%) showing direct visualization of the foreign body (defined as the radiopaque group) and 86 cases (75%) in the radiolucent group. Multivariable stepwise linear regression analysis showed increased odds of radiolucent foreign body inhalation in adults associated with pneumonic patches in MDCT (OR 6.99; 95% CI 1.80-27.22; P = 0.005) and plants/meat foreign bodies (OR 6.17; 95% CI 1.12-33.96; P = 0.04). A witnessed choking history (OR 0.02; 95% CI 0-0.14; P < 0.001) was a protective factor of radiolucent foreign body inhalation in adults. CONCLUSIONS: Unlike radiopaque FBA, in those presenting with a suspected radiolucent foreign body aspiration, the diagnosis is far more challenging. Risk factors such as lacking a choking history, non-resolving pneumonia (pneumonic patches) in MDCT findings, and plants/meat foreign bodies may help in the early diagnosis of radiolucent foreign body inhalation in adults. Further prospective multicenter studies should be conducted to validate the findings.

Efficacy of rapid on-site cytological evaluation (ROSE) by a pulmonologist in determining specimen adequacy and diagnostic accuracy in interventional diagnosis of lung lesions.

OBJECTIVE: To evaluate the efficacy of rapid on-site cytological evaluation (ROSE) in determining specimen adequacy and diagnostic accuracy in the interventional diagnosis of lung lesions. METHODS: This retrospective study included 127 consecutive cases of lung lesions, which were sampled by bronchoscopy or transthoracic fine needle aspiration, and diagnosed on ROSE followed by histopathology. ROSE was performed by a trained pulmonologist and the diagnosis of ROSE was compared with the final diagnosis. RESULTS: The sensitivity of ROSE in determining adequacy of specimens was 97.5% and specificity in determining inadequacy was 85.7%. The diagnostic efficacy of ROSE for assessing malignancy (sensitivity of 94.5% and specificity of 100%) and non-malignancy (sensitivity of 97.8% and specificity of 100%) was excellent. The sensitivity of ROSE for diagnosing small cell carcinoma (100%) was highest, followed by adenocarcinoma (89.2%) and squamous cell carcinoma (75.0%). Performance of ROSE by a trained pulmonologist also determined tuberculosis with a high diagnostic sensitivity (83.3%) and specificity (100%). CONCLUSIONS: A trained pulmonologist can reliably carry out ROSE to ensure the adequacy of the sample, distinguish between malignancy and non-malignancy, and make a preliminary diagnosis in a large number of cases.

Solution anode glow discharge optical emission spectrometry: Volatile hydride introduction from the gas jet nozzle cathode for ultrasensitive determination of lead.

An ultrasensitive method for the determination of Pb was developed by coupling solution anode glow discharge-optical emission spectrometry (SAGD-OES) with hydride generation (HG). Compared to solution cathode glow discharge, the introduction of analytes yielded via HG from the discharge cathode into the microplasma was demonstrated to be easily performed by SAGD in which the gas jet nozzle served as cathode and further enhanced sensitivity for Pb determination was achieved. The susceptibility of SAGD-OES to the matrix-induced interferences in the analysis of real samples was significantly improved owing to the coupling of HG. After a thorough optimization of the HG-SAGD-OES system parameters, the developed system achieved Pb detection limit of 0.061 ng mL-1, with the corresponding relative standard deviation being <2.2% at analyte concentrations of 50 ng mL-1. The potential application of this method was validated by successfully analyzing three certified reference materials (CRMs: GBW07311, GBW07312, and GBW07601a (GSH-1)) and human blood samples.

Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease.

BACKGROUND: Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aimed to investigate the factors affecting the progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia. METHODS: Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher's exact test. Logistic regression analysis was performed to explore the risk factors for disease progression. RESULTS: Seventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 [51, 70] vs. 37 [32, 41] years, U = 4.932, P = 0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ = 9.291, P = 0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 [37.8, 38.6] vs. 37.5 [37.0, 38.4]°C, U = 2.057, P = 0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ = 5.611, P = 0.028) and respiratory rate (34 [18, 48] vs. 24 [16, 60] breaths/min, U = 4.030, P = 0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 [14.3, 64.8] vs. 10.6 [1.9, 33.1] mg/L, U = 1.315, P = 0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62 ±â€Š6.60 vs. 41.27 ±â€Š4.55 g/L, U = 2.843, P = 0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ = 16.01, P = 0.001). Multivariate logistic analysis indicated that age (odds ratio [OR], 8.546; 95% confidence interval [CI]: 1.628-44.864; P = 0.011), history of smoking (OR, 14.285; 95% CI: 1.577-25.000; P = 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036-78.147, P = 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942-40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098-50.000; P = 0.003), and C-reactive protein (OR, 10.530; 95% CI: 1.224-34.701, P = 0.028) were risk factors for disease progression. CONCLUSIONS: Several factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature at admission, respiratory failure, albumin, and C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.

A case of Aspergillus tracheobronchitis in a patient with chronic obstructive pulmonary disease.

Aspergillus tracheobronchitis (AT) is a unique form of invasive pulmonary aspergillosis, which is commonly found in patients with impaired immunity. Early-stage AT presents in a nonspecific way, both clinically and radiographically, thereby delaying diagnosis and resulting in a high mortality. Owing to impaired mucociliary clearance, previous nonfungal infections, and administration of corticosteroids, among other aspects, patients with chronic obstructive pulmonary disease (COPD) are predisposed to AT, although they are mostly immunocompetent. AT in COPD patients has not been well recognized and the condition is often misdiagnosed or missed. We herein report a case of AT diagnosed in a male with past COPD, with the features of pseudomembranous AT upon bronchoscopy. This contradicts the opinion that pseudomembranous AT is found in severely immunocompromised hosts with hematologic malignancies.

Regulation of CD4(+) T cells by pleural mesothelial cells via adhesion molecule-dependent mechanisms in tuberculous pleurisy.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been demonstrated to be expressed on pleural mesothelial cells (PMCs), and to mediate leukocyte adhesion and migration; however, little is known about whether adhesion molecule-dependent mechanisms are involved in the regulation of CD4(+) T cells by PMCs in tuberculous pleural effusion (TPE). METHODS: Expressions of ICAM-1 and VCAM-1 on PMCs, as well as expressions of CD11a and CD29, the counter-receptors for ICAM-1 and VCAM-1, respectively, expressed on CD4(+) T cells in TPE were determined using flow cytometry. The immune regulations on adhesion, proliferation, activation, selective expansion of CD4(+) helper T cell subgroups exerted by PMCs via adhesion molecule-dependent mechanisms were explored. RESULTS: Percentages of ICAM-1-positive and VCAM-1‒positive PMCs in TPE were increased compared with PMC line. Interferon-γ enhanced fluorescence intensity of ICAM-1, while IL-4 promoted VCAM-1 expression on PMCs. Percentages of CD11a(high)CD4(+) and CD29(high)CD4(+) T cells in TPE significantly increased as compared with peripheral blood. Prestimulation of PMCs with anti‒ICAM-1 or ‒VCAM-1 mAb significantly inhibited adhesion, activation, as well as effector regulatory T cell expansion induced by PMCs. CONCLUSIONS: Our current data showed that adhesion molecule pathways on PMCs regulated adhesion and activation of CD4(+) T cells, and selectively promoted the expansion of effector regulatory T cells.

Prognostic value of K-RAS mutations in patients with non-small cell lung cancer: a systematic review with meta-analysis.

K-RAS gene mutations have been found in 20-30% of non-small cell lung cancer and occur most commonly in adenocarcinoma, however, there was no definitive conclusion about the prognostic role of K-RAS mutations in NSCLC. Herein we performed a systematic review of the literatures with meta-analysis to assess K-RAS mutations' prognostic value in NSCLC. After a methodological assessment, survival data from published studies were aggregated. Combined hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated in terms of overall survival. 41 trials (6939 patients) were included in the analysis, the overall HR was 1.45 (95% CI: 1.29-1.62), showing that K-RAS mutations have an unfavorable impact on survival of patients with NSCLC. Then a subgroup analysis was performed about ethnicity, the combined HR was 1.97 (95% CI: 1.58-2.44) for Asians, and 1.37 (95% CI: 1.25-1.5) for non-Asians. In subgroup analysis of histology, the HR was 1.39 (95% CI: 1.24-1.55) for adenocarcinoma, suggesting that K-RAS mutations were correlated with shortened survival for adenocarcinoma. When the subgroup analysis was conducted according to disease stage, K-RAS mutations were poor prognostic factors in early stages: stage I (1.81; 95% CI: 1.36-2.39) and stage I-IIIa (1.68; 95% CI: 1.11-2.55), but not in advanced stage (IIIb-IV) (1.3; 95% CI: 0.99-1.71). At last, in subgroup analysis about test methods, all of the four methods: PCR-MSOP (1.73; 95% CI: 1.35-2.2), PCR-DGGE (1.27; 95% CI: 1.01-1.62), PCR-RFLP (1.88; 95% CI: 1.42-2.49) and PCR-seq (1.34; 95% CI: 1.14-1.58) showed statistically significant impact on survival of NSCLC patients. In conclusion, this meta-analysis suggests that K-RAS mutations are associated with a worse overall survival in patients with NSCLC, especially in patients with adenocarcinoma and early stage.

Differentiation and immune regulation of IL-9-producing CD4+ T cells in malignant pleural effusion.

RATIONALE: IL-9-producing CD4(+) T cells (Th9 cells) have been reported to be involved in inflammation and immune diseases. However, the involvement of Th9 cells in malignancy has not been investigated. OBJECTIVES: To elucidate the mechanism by which Th9 cells differentiate in malignant pleural effusion (MPE) and to explore the immune regulation of Th9 cells on lung cancer cells. METHODS: Distribution of Th9 cells in relation to Th17 and Th1 cells in both MPE and blood were determined. The effects and mechanisms of proinflammatory cytokines and regulatory T cells on differentiation of Th9 cells in vitro were explored. The impacts and signal transductions of IL-9, IL-17, and IFN-γ on lung cancer cell lines were also investigated. MEASUREMENTS AND MAIN RESULTS: The numbers of Th9, Th17, and Th1 cells were all increased in MPE when compared with blood. The increase in Th9 cells in MPE was due to the promotion by cytokines and regulatory T cells. By activating STAT3 signaling, both IL-9 and IL-17 substantially promoted the proliferation and migratory activity of lung cancer cells, whereas IFN-γ, which activated STAT1 signaling, was noted to suppress lung cancer cell proliferation and migration. IFN-γ could induce lung cancer cell apoptosis. Moreover, IL-9 and IFN-γ, but not IL-17, could strongly facilitate intercellular adhesion of lung cancer cells to pleural mesothelial cell monolayers. CONCLUSIONS: Our data revealed that Th9 cells were increased in MPE and that Th9 cells exerted an important immune regulation on lung cancer cells in human tumor environment.

Interleukin 22-producing CD4+ T cells in malignant pleural effusion.

Th22 cells have been reported to be involved in human cancers. However, differentiation and immune regulation of Th22 cells in malignant pleural effusion (MPE) remain unknown. We noted that Th22 cell numbers were increased in MPE, and that IL-22 substantially promoted the proliferation and migratory activity of A549 cells. Moreover, IL-22 could strongly facilitate intercellular adhesion of A549 cells to pleural mesothelial cell monolayers. Our data revealed that the increase in Th22 cells in MPE was due to pleural cytokines and chemokines, and that Th22 exerted an important immune regulation on cancer cells in human pleural malignant environment.

Differentiation and recruitment of Th9 cells stimulated by pleural mesothelial cells in human Mycobacterium tuberculosis infection.

Newly discovered IL-9-producing CD4(+) helper T cells (Th9 cells) have been reported to contribute to tissue inflammation and immune responses, however, differentiation and immune regulation of Th9 cells in tuberculosis remain unknown. In the present study, our data showed that increased Th9 cells with the phenotype of effector memory cells were found to be in tuberculous pleural effusion as compared with blood. TGF-ß was essential for Th9 cell differentiation from naïve CD4(+) T cells stimulated with PMA and ionomycin in vitro for 5 h, and addition of IL-1ß, IL-4 or IL-6 further augmented Th9 cell differentiation. Tuberculous pleural effusion and supernatants of cultured pleural mesothelial cells were chemotactic for Th9 cells, and this activity was partly blocked by anti-CCL20 antibody. IL-9 promoted the pleural mesothelial cell repairing and inhibited IFN-γ-induced pleural mesothelial cell apoptosis. Moreover, pleural mesothelial cells promoted Th9 cell differentiation by presenting antigen. Collectively, these data provide new information concerning Th9 cells, in particular the collaborative immune regulation between Th9 cells and pleural mesothelial cells in human M. tuberculosis infection. In particular, pleural mesothelial cells were able to function as antigen-presenting cells to stimulate Th9 cell differentiation.

Differentiation and recruitment of IL-22-producing helper T cells stimulated by pleural mesothelial cells in tuberculous pleurisy.

RATIONALE: IL-22-producing helper T cells (Th22 cells) have been reported to be involved in tuberculosis infection. However, differentiation and immune regulation of Th22 cells in tuberculous pleural effusion (TPE) remain unknown. OBJECTIVES: To elucidate the mechanism by which Th22 cells differentiate and recruit into the pleural space. METHODS: The distribution and phenotypic features of Th22 cells in both TPE and blood were determined. The impacts of proinflammatory cytokines and antigen presentation by pleural mesothelial cells (PMCs) on Th22-cell differentiation were explored. The chemoattractant activity of chemokines produced by PMCs for Th22 cells was observed. MEASUREMENTS AND MAIN RESULTS: Th22 cells were significantly higher in TPE than in blood. IL-1ß, IL-6, and/or tumor necrosis factor-α promoted Th22-cell differentiation from CD4(+) T cells. It was found that PMCs expressed CCL20, CCL22, and CCL27, and that TPE and PMC supernatants were chemotactic for Th22 cells. This activity was partly blocked by anti-CCL20, anti-CCL22, and anti-CCL27 antibodies. IL-22 and IL-17 significantly improved PMC wound healing. Moreover, PMCs were able to stimulate CD4(+) T-cell proliferation and Th22-cell differentiation by presenting tuberculosis-specific antigen. CONCLUSIONS: The overrepresentation of Th22 cells in TPE may be due to pleural cytokines and to PMC-produced chemokines. Our data suggest a collaborative loop between PMCs and Th22 cells in TPE. In particular, PMCs were able to function as antigen-presenting cells to stimulate CD4(+) T-cell proliferation and Th22-cell differentiation.