High risks adverse events associated with usage of aspirin in chronic obstructive pulmonary disease.

BACKGROUND: Despite potential benefits and widespread prescription of aspirin among chronic obstructive pulmonary disease (COPD) patients, limited research has investigated its adverse effects (AEs) in COPD population. METHODS: We conducted a retrospective analysis of adverse drug events (ADEs) reported in the US Food and Drug Administration Adverse Event Reporting System (FAERS) between Q1 2013 and Q2 2022. COPD patients were categorized into two groups based on aspirin use. ADEs related to aspirin use were identified using combined reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC) methods. RESULTS: A total of 56,660 ADEs reports associated with COPD patients were included in the study. Among these reports, 144 adverse events were linked to aspirin use in COPD patients, including fatigue (4.12%), diarrhea (3.13%), dyspnea exertional (2.03%), rhinorrhea (1.99%), weight increased (1.89%) and vomiting (1.84%), muscle spasms (1.79%), cardiac disorder (1.74%), heart rate increased (1.69%) and peripheral swelling (1.59%). Subgroup analysis indicates that age and gender might affect the AEs frequency in COPD patients using aspirin. CONCLUSIONS: Our findings identify 10 most frequently reported ADEs associated with aspirin use in COPD patients, thus offer valuable insights into the AEs of aspirin for safer clinical utilization in COPD management.

Instillation of Amphotericin B by bronchoscopy combined with systemic voriconazole in advanced non-small cell lung cancer patients with chronic cavitary pulmonary aspergillosis: A case series and literature review.

Although the treatment of aspergillosis has been studied for years, the optimal nonsurgical treatment of chronic cavitary pulmonary aspergillosis (CCPA) remains unsatisfactory, especially in lung cancer. We report two advanced non-small cell lung cancer (NSCLC) patients who recovered from CCPA following instillation of Amphotericin B (AmB) by bronchoscopy combined with systemic voriconazole. The first patient was diagnosed with lung adenocarcinoma after right upper lobe resection and was treated with anaplastic lymphoma kinase-targeted therapy. Chest computed tomography (CT) revealed a right pulmonary cavity containing solid materials. The second patient was diagnosed with squamous cell carcinoma and received immunotherapy following surgery, chemotherapy, and radiotherapy. Chest CT tomography revealed a mass in the right lung cavity. Both patients' cultures and next-generation sequencing of their bronchoalveolar lavage (BAL) samples revealed presence of Aspergillus fumigatus. In addition, the galactomannan test of both patients BAL samples was positive. Systemic voriconazole was prescribed based on in vitro susceptibility testing. The chest images and clinical symptoms of both patients did not improve after one month of voriconazole therapy within the therapeutic blood concentration. Considering the low local concentrations of antifungals against CCPA, AmB instillation by bronchoscopy combined with systemic voriconazole was utilized. The chest CT images and clinical symptoms of both patients markedly improved in the following third month. Instillation of AmB combined with systemic voriconazole may be a promising treatment option for NSCLC patients with CCPA who fail voriconazole monotherapy.

Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection.

Polarization of macrophages to different functional states is important for mounting responses against pathogen infections. Macrophages are the major target cells of porcine circovirus type 2 (PCV2), which is the primary causative agent of porcine circovirus-associated disease (PCVAD) leading to immense economic losses in the global swine industry. Clinically, PCV2 is often found to increase risk of other pathogenic infections yet the underlying mechanisms remain to be elusive. Here we found that PCV2 infection skewed macrophages toward a M1 status through reprogramming expression of a subset of M1-associated genes and M2-associated genes. Mechanistically, induction of M1-associated genes by PCV2 infection is dependent on activation of nuclear factor kappa B (NF-κB) and c-jun N-terminal kinase (JNK) signaling pathways whereas suppression of M2-associated genes by PCV2 is via inhibiting expression of jumonji domain containing-3 (JMJD3), a histone 3 Lys27 (H3K27) demethylase that regulates M2 activation of macrophages. Finally, we identified that PCV2 capsid protein (Cap) directly inhibits JMJD3 transcription to restrain expression of interferon regulatory factor (IRF4) that controls M2 macrophage polarization. Consequently, sustained infection of PCV2 facilitates bacterial infection in vitro. In summary, these findings showed that PCV2 infection functionally modulated M1 macrophage polarization via targeting canonical signals and epigenetic histone modification, which contributes to bacterial coinfection and virial pathogenesis.

Prognostic nomogram for predicting long-term cancer-specific survival in patients with lung carcinoid tumors.

BACKGROUND: Lung carcinoid is a rare malignant tumor with poor survival. The current study established a nomogram model for predicting cancer-specific survival (CSS) in patients with lung carcinoid tumors. METHODS: A total of 1956 patients diagnosed with primary lung carcinoid tumors were extracted from the Surveillance, Epidemiology, and End Results database. The specific predictors of CSS for lung carcinoid tumors were identified and integrated to build a nomogram. Validation of the nomogram was conducted using parameters concordance index (C-index), calibration plots, decision curve analyses (DCAs), and the receiver operating characteristic (ROC) curve. RESULTS: Age at diagnosis, grade, histological type, N stage, M stage, surgery of the primary site, radiation of the primary site, and tumor size were independent prognostic factors of CSS. High discriminative accuracy of the nomogram model was shown in the training cohort (C-index = 0.873), which was also testified in the internal validation cohort (C-index = 0.861). In both cohorts, the calibration plots showed good concordance between the predicted and observed CSS at 3, 5, and 10 years. The DCA showed great potential for clinical application. The ROC curve showed superior survival predictive ability of the nomogram model (area under the curve = 0.868). CONCLUSIONS: We developed a practical nomogram that provided independent predictions of CSS for patients with lung carcinoid tumors. This nomogram may have the potential to assist clinicians in prognostic evaluations or developing individualized therapies for patients with this neoplasm.

IgG4-related disease involving polyserous effusions with elevated serum interleukin-6 levels: a case report and literature review.

Immunoglobulin G4-related disease (IgG4-RD) is a recently described immune-mediated fibroinflammatory disease with a characteristic histopathologic appearance that can affect various organs. We report a 43-year-old Chinese female patient with IgG4-RD involving polyserous effusions with reports of worsening exertional dyspnea for 3 months. Laboratory blood tests revealed that serum interleukin (IL)-6, carbohydrate antigens (CA-199 and CA-125), and alpha-fetoprotein levels were significantly increased, but serum IgG4 levels were normal. Repeat pleural effusion and ascite analysis showed lymphocyte-predominant exudates. In addition, computed tomography scan showed massive pleural effusion in the right pleural cavity, abdominal effusion, and some pericardial effusion with a partial compression atelectasis. Further, medical thoracoscopy was performed to examine the pleural cavity and found multiple nodules on the pleura and partly thickened pleura with a reddish color. Histopathologic and immunohistochemical examination revealed marked lymphocytes and IgG4-positive plasma cell infiltration. The patient was finally diagnosed with IgG4-RD according to the comprehensive diagnostic criteria, although the patient presented similar serological and pathological manifestations of Castleman disease (CD). Our case suggests that IgG4-RD may be one of the causes of polyserous effusions and shows the difficulties in differentiating between IgG4-RD and CD.

[The Diagnostic Value of Endobronchial Ultrasound-guided Needle Aspiration Biopsy for Lung or Mediastinal Lymph Node Cancer and Tuberculosis].

OBJECTIVES: To determine the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in diagnosing lung or mediastinal lymph node cancer and tuberculosis. METHODS: Clinical and pathological data of 553 patients who underwent EBUS-TBNA from January 2013 to September 2016 in West China Hospital of Sichuan University were reviewed. The sensitivity, specificity and accuracy of EBUS-TBNA for diagnosing lymph node tumor and tuberculosis of hilar and mediastinal lymph nodes were calculated. RESULTS: The sensitivity, specificity and accuracy of EBUS-TBNA in diagnosing hilar and mediastinal lymph node cancer were 89.2% (263/295), 100% (247/247) and 94.1% (510/542), respectively, compared with 70% (76/117), 97.2% (385/396) and 89.9% (461/513), respectively, for diagnosing tuberculosis identified though granulomatous biopsy. In the 102 cases with acid fast staining and TB-PCR, 63.7% accuracy (58/91), 90.9% (10/11) sensitivity and 66.7% (68/102) specificity were found for any positive findings from acid fast bacilli or TB-DNA. CONCLUSIONS: EBUS-TBNA has high sensitivity and specificity for diagnosing hilar and mediastinal tumor, which can be used in combination with acid fast staining and TB-PCR for diagnosing tuberculosis.

[Diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration combined with Surepath liquid-based cytology test for lung lesions and mediastinal lymphadenopathy].

OBJECTIVE: To explore the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) combined with Surepath liquid-based cytology test for lung and mediastinal lymphadenopathy. METHODS: Eighty EBUS-TBNA cases in West China Hospital of Sichuan University collected from December 2011 to June 2014 were retrospectively analyzed. The conventional smears and Surepath liquid based preparations were reviewed and compared with histological biopsy. Evaluated whether liquid based preparation could improve the satisfactory rate and diagnostic accuracy. RESULTS: This study included 53 men and 27 women, the male to female ratio was 1.96:1.00; the age ranged from 17 to 79 (mean 54) years. One to four lymph node groups were aspirated in each patient, resulting in a total of 109 lymph node groups, including 57 paratracheal, 34 subcarinal, three tracheal bronchial, seven pulmonary and four hilar lymph node groups. The definite locations of four other mediastinal lymph node groups were not known. The overall satisfactory rate of conventional smears and liquid-based cytology test was 90.0% and 92.5%, respectively. By histology, there were 37 cases diagnosed as malignant tumors, nine as tuberculosis, two as sarcoidosis, 11 as unexplained granulomatous inflammation, and 27 as other benign lesions. The sensitivity, specificity and accuracy of conventional cytological smears for tumors were 86.5%, 97.7% and 92.5% respectively; the positive and negative predictive values were 97.0% and 89.4% respectively. The sensitivity, specificity and accuracy of the liquid-based preparation were 89.2%, 97.7% and 93.8% respectively; the positive and negative predictive values were 97.1% and 91.3% respectively. Combining the conventional cytological smears and liquid based preparation, the sensitivity, specificity and accuracy were 91.9%, 97.7% and 95.0% respectively; and the positive and negative predictive values were 97.1% and 93.3% respectively. CONCLUSIONS: EBUS-TBNA is a good method to diagnose lung and mediastinal lymphadenopathy. Surepath liquid based cytology test could improve the sample satisfactory rate, the diagnostic sensitivity and accuracy. If combined with immunocytochemistry it could be useful for further tumor typing. EBUS-TBNA combined with Surepath liquid based preparation is an effective complement for the histologic biopsy.