Nomogram for Predicting Efficacy and Prognosis After Chemotherapy for Advanced NSCLC.

PURPOSE: One major issue is the therapeutic effect following chemotherapy for non-small cell lung cancer (NSCLC). Although numerous risk factors have been identified and novel therapies have been developed, improving patient overall survival (OS) remains a crucial postoperative issue. This study aimed to develop a nomogram for accurately predicting the OS of patients with Stage III-IV NSCLC treated with chemotherapy. METHODS: The Department of Respiration at Tangdu Hospital, Air Force Medical University, prospectively collected data on 321 patients between January 2018 and December 2023. A week before treatment, the platelet-to-lymphocyte ratio (PLR), the neutrophil-to-lymphocyte ratio (NLR), and seven autoantibodies were measured using Youden's index, which was obtained using the ROC curve. The formula was used to compute the values of PLR and NLR. After using multifactor Cox regression analysis to identify risk factors, a nomogram was produced regarding the therapeutic effect following chemotherapy. The performance of the nomogram was assessed using a bootstrapped-concordance index and calibration plots. RESULT: It was determined that NLR, sex-determining region Y-box 2 (SOX2), adenosine triphosphate binding RNA deconjugase 4-5 (GBU4-5), and MAGE family member A1 (MAGEA1) were significantly associated factors that could be combined to accurately predict the therapeutic effect following chemotherapy. Utilizing these risk indicators, we were able to develop a nomogram that predicted the patients' survival at 1, 3, and 5 years. At 3 years, the area under the curve representing the expected survival probability was 0.762 (95% confidence interval 0.66-0.87). With a bootstrapped-concordance index of 0.762, the nomogram demonstrated good calibration. CONCLUSIONS: Our nomogram proved to be a valuable instrument in accurately predicting the overall survival of patients.

The impact of inflammatory cells on lung function in asthmatics in a cross sectional retrospect study.

Background: Limited data exists on the impact of inflammatory cells and clinical characteristics on lung function in individuals with asthma. Objective: The objective is to examine the correlation between increased inflammatory cells, asthma symptoms, and lung function in patients with asthma in a clinical setting. Methods: A retrospective cohort study was conducted on 234 individuals suspected of having asthma in Xian, China between January 2008 and December 2021. Of those, 143 patients with complete clinical feature and lung function data were enrolled to examine the relationship between increased inflammatory cells, asthma symptoms, and lung function. Basic characteristics, blood eosinophil count, blood neutrophil count, blood platelet count, blood C-reactive protein (CRP), and comprehensive lung function analysis were evaluated at each inpatient for the 143 adult asthmatics. The association between inflammatory cells and clinical parameters with pulmonary function was compared. Results: The results of the study showed that individuals in the alcohol intake group had elevated blood eosinophil count compared to those in the non-alcohol intake group (P = 0.024). Long-acting inhaled beta 2 agonists and antibiotic therapy were associated with lower blood eosinophil count (P = 0.021 and P = 0.049, respectively) compared to other therapy. There was a independent association between blood eosinophil counts and FEV1 pre- and post-therapy in asthma but there was a markedly correlation between blood eosinophil counts and FEV1/FVC pre-and post-therapy in Asthma (P = 0.007). Blood neutrophil counts were inversely correlated with FEV1/FVC after treatment (P = 0.032). Night onset in asthma was positively correlated with blood neutrophil counts, while fever was negatively correlated with blood CRP (P = 0.028). Platelet counts >300 × 109/L after treatment were significantly associated with a decline in FEV (<0.001) in patients with asthma. Elevated blood eosinophil count was independently associated with clinical features in asthma. Conclusions: Based on the study's findings, there is a significant decline in FEV1/FVC among individuals with elevated blood eosinophil count, both pre- and post-bronchodilator while there was a independent relationship between blood eosinophil counts and FEV1 pre-and post-therapy in asthma. This suggests that increased levels of eosinophils may independently associated contribute to reduced lung function in asthma patients.

A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate vs. levofloxacin for community-acquired pneumonia in adult patients.

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.

Effectiveness and safety of Buzzy device in needle-related procedures for children under twelve years of age: A systematic review and meta-analysis.

BACKGROUND: Pain transcends simple physiology, encompassing biological, emotional, psychological, and social facets. Children show pronounced immediate and enduring responses to pain-related procedures. The aim of this meta-analysis is to investigate the efficacy and safety of the Buzzy device for needle-related procedures in children aged twelve years or younger. METHODS: PubMed, Web of Science, and Embase were searched from inception to July 2023. Only randomized controlled trials utilizing the Buzzy device for needle-related procedures in children under twelve years old were included. Two reviewers independently conducted study selection, data extraction, and risk of bias assessment. Random-effects models were utilized, and analyses were performed using mean differences or standardized mean differences as well as risk ratios. RESULTS: A total of 19 studies were included, involving 2846 participants (Buzzy = 1095, Control = 1751). Compared to no intervention, the Buzzy device significantly reduced pain response [self-report SMD = -1.90 (-2.45, -1.36), parental SMD = -3.04 (-4.09, -1.99), observer SMD = -2.88 (-3.75, -2.02)] and anxiety scores [self-report SMD = -1.97 (-3.05, -0.88), parental SMD = -2.01 (-2.93, -1.08), observer SMD = -1.92 (-2.64, -1.19)]. Compared to virtual reality (VR), the Buzzy device reduced self-reported anxiety levels SMD = -0.47 (-0.77, -0.17), and compared to distraction cards, the Buzzy device reduced parental and observer-reported pain [parental SMD = -0.85 (-1.22, -0.48), observer SMD = -0.70 (-1.00, -0.40)] and anxiety [parental SMD = -0.96 (-1.46, -0.47), observer SMD = -0.91 (-1.40, -0.42)]. Subgroup analysis results showed that procedure type, patient age, measurement scales used, and distance of operation were not the reason of heterogeneity. The summarized first puncture attempt success rate did not differ from other interventions. There were no significant adverse events in the included studies. CONCLUSION: The Buzzy device reduces pain and anxiety in children during needle procedures, ensuring success and safety. Additionally, the effectiveness of the Buzzy device in reducing pain during venipuncture is superior when compared to its effectiveness during intramuscular injections.

The application of artificial intelligence for Rapid On-Site Evaluation during flexible bronchoscopy.

Background: Rapid On-Site Evaluation (ROSE) during flexible bronchoscopy (FB) can improve the adequacy of biopsy specimens and diagnostic yield of lung cancer. However, the lack of cytopathologists has restricted the wide use of ROSE. Objective: To develop a ROSE artificial intelligence (AI) system using deep learning techniques to differentiate malignant from benign lesions based on ROSE cytological images, and evaluate the clinical performance of the ROSE AI system. Method: 6357 ROSE cytological images from 721 patients who underwent transbronchial biopsy were collected from January to July 2023 at the Tangdu Hospital, Air Force Medical University. A ROSE AI system, composed of a deep convolutional neural network (DCNN), was developed to identify whether there were malignant cells in the ROSE cytological images. Internal testing, external testing, and human-machine competition were used to evaluate the performance of the system. Results: The ROSE AI system identified images containing lung malignant cells with the accuracy of 92.97% and 90.26% on the internal testing dataset and external testing dataset respectively, and its performance was comparable to that of the experienced cytopathologist. The ROSE AI system also showed promising performance in diagnosing lung cancer based on ROSE cytological images, with accuracy of 89.61% and 87.59%, and sensitivity of 90.57% and 94.90% on the internal testing dataset and external testing dataset respectively. More specifically, the agreement between the ROSE AI system and the experienced cytopathologist in diagnosing common types of lung cancer, including squamous cell carcinoma, adenocarcinoma, and small cell lung cancer, demonstrated almost perfect consistency in both the internal testing dataset (κ = 0.930) and the external testing dataset (κ = 0.932). Conclusions: The ROSE AI system demonstrated feasibility and robustness in identifying specimen adequacy, showing potential enhancement in the diagnostic yield of FB. Nevertheless, additional enhancements, incorporating a more diverse range of training data and leveraging advanced AI models with increased capabilities, along with rigorous validation through extensive multi-center randomized control assays, are crucial to guarantee the seamless and effective integration of this technology into clinical practice.

Interleukin-36 receptor antagonist stimulation in vitro inhibits peripheral and lung-resident T cell response isolated from patients with ventilator-associated pneumonia.

Interleukin-36 (IL-36) cytokine family members play an immunomodulatory function to immune cells through IL-36 receptor signaling pathway. However, the regulatory role of IL-36 exerted on T cells is not completely elucidated in patients with ventilator-associated pneumonia (VAP). For this purpose, this study enrolled 51 VAP patients and 27 controls. IL-36 levels were measured by ELISA. The mRNA levels of IL-36 receptor subunits were determined by real-time PCR. CD4+ and CD8+ T cells were enriched, and stimulated with recombinant IL-36 receptor antagonist (IL-36RA). The influence of IL-36RA on transcription factors and cytokine secretions by CD4+ T cells was investigated. The modulatory function of IL-36RA on CD8+ T cells was assessed by measuring target cell death and cytokine secretions. There were no significant differences in serum IL-36 levels between VAP patients and controls. Only IL-36RA, but not IL-36α, IL-36ß, or IL-36γ, in bronchoalveolar lavage fluid was elevated in infection site of VAP patients. IL-36 receptor subunits in CD4+ and CD8+ T cells were comparable between VAP patients and controls. 10 ng/mL of IL-36RA stimulation dampened peripheral effector CD4+ T cell response isolated from both VAP patients and controls. Target cell death mediated by CD8+ T cells isolated from BAFL of VAP patients was suppressed by 100 ng/mL of IL-36RA stimulation in vitro. The down-regulations of perforin, granzyme B, interferon-γ, tumor necrosis factor-α, and Fas ligand following IL-36RA stimulation in vitro were responsible for reduced CD8+ T cell-mediated cytotoxicity. IL-36RA revealed an immunosuppressive property for T cell response in vitro, and may be involved in the protective mechanism in VAP patients.

Application of rapid on-site evaluation combined with flexible bronchoscopy in the diagnosis of lung lesions.

BACKGROUND: Pathology is considered the gold standard for the diagnosis of lung lesions, but the pathological result is relatively lagging and cannot provide real-time guidance for the biopsy procedure. OBJECTIVE: To investigate the potential application of rapid on-site evaluation (ROSE) during flexible bronchoscopy (FB) in the evaluation and diagnosis of lung lesions. PATIENTS AND METHODS: Consecutive patients who underwent FB for the diagnosis of lung lesions between August 2022 and February 2023 were included in this retrospective study. 294 patients underwent FB with ROSE, while 304 patients underwent FB without ROSE. The final pathological results and the number of patients undergoing repeat biopsies were recorded in both groups. Specifically, we conducted separate statistical analysis for patients undergoing different biopsy methods, including the endobronchial biopsy (EBB), radial probe endobronchial ultrasound transbronchial lung biopsy with guide sheath (r-EBUS-GS-TBLB), and the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to study the detailed roles that ROSE plays under different biopsy methods. RESULTS: The adequacy rate of biopsy specimens from the non-ROSE group was significantly lower than that of the ROSE group (259/281 = 92.17 % vs. 263/268 = 98.13 %, p = 0.001). Meanwhile, fewer patients underwent repeat biopsies in the ROSE group compared to the non-ROSE group (2/294 = 0.68 % vs. 10/304 = 3.29 %, p = 0.023). For the ROSE group, the consistency between ROSE diagnoses and final pathological diagnoses was 94.40 % (κ = 0.886), with 95.58 % for benign diseases and 93.55 % for malignant diseases. CONCLUSION: The utility of ROSE during FB increases the adequacy rate of biopsy specimens and thus decreases the need for repeat biopsies in patients with lung lesions to get a definite diagnosis. Moreover, the high consistency between ROSE diagnoses and final pathological diagnoses suggests that ROSE is a reliable tool for optimizing the diagnosis of lung lesions.

Profibrogenic macrophage-targeted delivery of mitochondrial protector via exosome formula for alleviating pulmonary fibrosis.

Pulmonary fibrosis (PF) is a devastating lung disease with limited treatment options. During this pathological process, the profibrogenic macrophage subpopulation plays a crucial role, making the characterization of this subpopulation fundamentally important. The present study revealed a positive correlation between pulmonary macrophages with higher mitochondrial mass (Mømitohigh) and fibrosis. Among the Mømitohigh subpopulation of CD206+ M2, characterized by higher expression of dynamin 1-like (Drp1), as determined by flow cytometry and RNA-seq analysis, a therapeutic intervention was developed using an exosome-based formula composed of pathfinder and therapeutics. A pathfinder exosome called "exosomeMMP19 (ExoMMP19)", was constructed to display matrix metalloproteinase-19 (MMP19) on the surface to locally break down the excessive extracellular matrix (ECM) in the fibrotic lung. A therapeutic exosome called "exosome therapeutics (ExoTx)", was engineered to display D-mannose on the surface while encapsulating siDrp1 inside. Prior delivery of ExoMMP19 degraded excessive ECM and thus paved the way for ExoTx to be delivered into Mømitohigh, where ExoTx inhibited mitochondrial fission and alleviated PF. This study has not only identified Mømitohigh as profibrotic macrophages but it has also provided a potent strategy to reverse PF via a combination of formulated exosomes.

Endobronchial Lipoma: A Rare Cause of Bronchial Stenosis or Obstruction.

Endobronchial lipoma (EL) is a rare benign tumor characterized by tracheobronchial smooth-surfaced mass, often resulting in bronchial obstruction without standard guidelines for management. This study seeks to clarify the clinical features and interventions of EL, aiming to improve its diagnosis and outcomes. A retrospective review was conducted on 28516 outpatients treated between January 2015 and December 2019 at the Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital of Air Force Medical University to collect patients diagnosed with EL. Their clinical, bronchoscopic, chest imaging, and histopathological features along with management were analyzed. Among the patients reviewed, nine were histopathologically diagnosed with EL, comprising seven males and two females. All EL patients exhibited noticeable symptoms, including cough (in eight patients), dyspnea (in six patients), fever (in three patients), expectoration (in two patients), chest pain (in two patients), hemoptysis (in one patient), and fatigue (in one patient). Chest CT abnormalities included endobronchial mass (in four patients), inflammatory exudation (in three patients), atelectasis (in three patients), and infiltration or consolidation (in two patients). In three patients, imaging showed fat density, directly leading to the diagnosis of EL. The EL lesions were distributed with six in the right lung and three in the left lung, all located within the first three subdivisions of the tracheobronchial tree. Treatment approaches varied, with one patient undergoing combined bronchoscopic resection and surgery. The remaining patients received bronchoscopic intervention such as electrosurgical snare resection, argon plasma coagulation (APC), cryotherapy, and holmium laser. Histopathological analysis confirmed the EL diagnosis. Finally, the mass removal restored bronchus patency. Taken together, EL symptoms lack specificity, necessitating reliance on histopathology for EL accurate diagnosis. Bronchoscopic interventions emerge as the preferred option for EL management, surpassing surgical approaches.