Journal of thoracic disease最新文献

Background: The primary challenge in treating chronic obstructive pulmonary disease (COPD) with anti-inflammatory medications is corticosteroid resistance. Resveratrol (RSV), a natural polyphenolic compound, has garnered significant interest due to its potent antioxidant and anti-inflammatory effects. This research sought to explore the potential impact of RSV on corticosteroid re-sensitization in emphysema mice triggered by cigarette smoke (CS) exposure.

Methods: Western blotting was employed to assess glucocorticoid receptor (GR) and histone deacetylase 2 (HDAC2) levels in lung tissues from individuals with COPD. Lung histomorphology was evaluated in mice with CS exposure and a combination of RSV and budesonide (BUD) treatment. Expression levels of GR and HDAC2 were determined using western blotting, while chemokine (C-X-C motif) ligand 15 (CXCL15) and tumor necrosis factor-alpha (TNF-α) levels were quantified through enzyme-linked immunosorbent assay (ELISA). Furthermore, to explore the broader protective effects of RSV, morphological analyses were conducted on heart and gastrocnemius muscle tissues from CS-exposed mice treated with RSV. Expression levels of GR and HDAC2 were detected, and levels of inflammatory cytokines interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) were quantified. Additionally, the markers associated with myocardial hypertrophy were assessed, including B-type natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC).

Results: In the lung tissues of COPD patients, reduced expression levels of GR and HDAC2 were observed. In a CS-induced emphysema mouse model, BUD's efficacy in inhibiting CXCL15 and TNF-α was diminished, and it failed to restore GR and HDAC2 expression levels in lung tissues. However, combined treatment with RSV and BUD effectively restored the inhibition of CXCL15 and TNF-α production while upregulating GR and HDAC2 expression levels in lung tissue. Additionally, exploratory analyses revealed that gavage administration of RSV in emphysema mice increased GR and HDAC2 expression in the heart and gastrocnemius muscle tissues, reducing inflammation. Additionally, RSV gavage decreased BNP and β-MHC expression levels.

Conclusions: Our study demonstrates that RSV upregulates the expression of GR and HDAC2 in lung tissues, thereby exerting a corticosteroid re-sensitization effect in CS-induced emphysema mice. These findings highlight the potential of RSV as a therapeutic agent to overcome corticosteroid resistance in COPD. While our exploratory analyses suggest that RSV may have broader protective effects, including reducing myocardial hypertrophy and preventing skeletal muscle atrophy in emphysema mice, these findings are preliminary and require further investigation to elucidate the underlying mechanisms and their clinical implications.

Background: Cigarette smoke extract (CSE) induces reactive oxygen species (ROS) generation in human bronchial epithelial cells, leading to mitochondrial dysfunction and subsequently triggering the mitochondrial unfolded protein response (UPR^mt) mediated by the bZIP transcription factor activating transcription factor 4 (ATF-4). This study aimed to investigate whether UPR^mt and ATF-4 are involved in the pathway of mitochondrial function impairment in BEAS-2B cells caused by CSE.

Methods: BEAS-2B bronchial epithelial cells were treated with different concentrations of CSE, and mitochondrial function was detected by JC-1 staining and MitoSoxRed staining. The expression and localisation of translocase of inner mitochondrial membrane 23 (Tim23) and ATF-4 were detected by Western blot method and immunofluorescence staining with laser confocal microscopy.

Results: The study showed decreased membrane potential and mitochondrial ROS accumulation in BEAS-2B cells after CSE treatment, which indicated that CSE caused mitochondrial dysfunction and oxidative stress. The expression of Tim23 was up-regulated after CSE exposure; this alteration hints at a potential activation of mitochondrial stress pathways. The expression of ATF-4 showed a positive correlation with the time of CSE treatment, and the expression in the nucleus was increased, which indicated that CSE altered the expression and localisation of Tim23 and ATF-4.

Conclusions: CSE leads to a decrease in mitochondrial membrane potential and an increase in ROS generation, and triggers alterations in the expression of Tim23 and ATF-4. These findings are consistent with the model that CSE may impair mitochondrial homeostasis, potentially through mechanisms involving mitochondrial stress responses (such as UPR^mt) and ATF-4 signaling.

Background: Electromagnetic navigation bronchoscopy (ENB) is a useful tool for the diagnosis of pulmonary lesions; however, the diagnostic accuracy is usually limited, especially for peripheral pulmonary lesions. To enhance the diagnostic accuracy of ENB for peripheral pulmonary lesions, we developed an innovative modification called intraprocedural computed tomography-guided navigation with ventilatory strategy for atelectasis (ICNVA)-ENB.

Methods: In this single-center prospective cohort study [IDEAL (Idea, Development, Exploration, Assessment, Long-term follow-up) framework stage 2a], we enrolled patients scheduled for ENB-guided pulmonary lesion biopsy. Departing from conventional ENB, navigation planning relied solely on intraoperative O-arm computed tomography (CT) scans acquired after intubation in a hybrid operating room. A standardized ventilation protocol was applied during both CT acquisition and ENB to prevent lung collapse and reduce CT to body divergence (CTBD). There were of 50 consecutive participants were included from March 2022 onward. Iterative technical refinements were documented per IDEAL guidelines, alongside patient demographics and procedural outcomes.

Results: All biopsies were successfully completed. Complications included pneumothorax (n=2) and self-limited bleeding (n=2), none requiring intervention. Four technical adjustments were implemented: (I) initial modifications enhanced procedural safety; (II) use of Wang's needle (MW-319) for puncture tunneling significantly improved targeting accuracy; and (III) reduced CT scan area decreased patient radiation exposure.

Conclusions: ICNVA-ENB demonstrates promising safety and efficacy for peripheral lung lesion biopsy, with iterative refinements optimizing accuracy and reducing risks.

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Background: Prognostic stratification in non-small cell lung cancer (NSCLC) remains challenging due to heterogeneous outcomes. This study aimed to develop and validate a clinically applicable prognostic model using multi-dimensional clinical data to improve survival prediction and support personalized therapeutic decisions.

Methods: We retrospectively enrolled 1,013 patients with histologically confirmed NSCLC treated at at Sichuan Cancer Hospital, Dazhu County People's Hospital and West China Hospital between January 2014 and December 2020. Inclusion criteria comprised adults with untreated, non-metastatic NSCLC, while those with asthma, chronic obstructive pulmonary disease, severe comorbidities, or concurrent malignancies were excluded. We utilized demographic, clinicopathological, and biochemical data, with follow-ups conducted via telephone. Overall survival (OS) was the primary endpoint. Predictors included pulmonary function [forced expiratory volume in one second (FEV1), maximum voluntary ventilation (MVV)], blood biomarkers [total serum bilirubin (TBIL)], and clinicopathological features. Variables were selected via backward stepwise regression with Akaike's information criterion. Performance was assessed using the C-index, calibration curves, decision curve analysis (DCA), and the area under the curve (AUC).

Results: The model was developed using a Cox proportional hazards model on a training set (n=513), tested on an internal set (n=219), and externally validated on a cohort from two other hospitals (n=281). FEV1, MVV, smoking, pathological stage, and TBIL emerged as significant prognostic factors, with C-index values of 0.740, 0.734, and 0.746 in the training, testing, and validation sets, respectively. The AUC values for 3- and 5-year OS predictions exceeded 0.70, highlighting strong model performance. Calibration plots confirmed predictive accuracy across datasets, and DCA highlighted clinical utility, especially in long-term risk stratification.

Conclusions: We developed a prognostic model for NSCLC integrating pulmonary function, biochemical, and clinicopathological data. The prognostic model provides significant clinical implications, facilitating tailored treatment planning and prognostic evaluations for NSCLC patients. Its integration into routine clinical practice could enhance decision-making processes and potentially improve patient outcomes.

Background: Inflammation and immune status are essential in acute respiratory distress syndrome (ARDS), wherein excessive inflammation with severe immunosuppression is associated with a poor prognosis. This study investigated the interleukin-6 (IL-6) and lymphocyte count (Lym) in patients with moderate-to-severe ARDS supported by venovenous extracorporeal membrane oxygenation (VV ECMO), as well as their relationship with prognosis, providing new insights for clinical prognosis evaluation.

Methods: A single-center, retrospective cohort study was conducted using data collected between March 2022 and July 2024. A total of 117 patients with moderate-severe ARDS with VV ECMO support were enrolled in this study. The observational clinical outcome was intensive care unit (ICU) 28-day mortality. Cox proportional hazard regression analysis was used to determine the potential prognostic factors for ICU 28-day mortality. Receiver operating characteristic (ROC) curve analysis was used to evaluate and compare the prognostic factors for 28-day mortality. Kaplan-Meier survival curves were generated to compare the mortality, with log-rank tests used to analyze differences.

Results: Of 117 patients, 60 died in the ICU within 28 days. The survivors had higher Sequential Organ Failure Assessment (SOFA) scores, IL-6, and peak airway pressure (Ppeak), and had lower Lym. According to univariable Cox analysis, baseline SOFA score [hazard ratio (HR): 1.09, 95% confidence interval (CI) 1.02-1.18; P=0.02], baseline norepinephrine (NE) dose (HR: 2.13, 95% CI: 1.30-3.48; P=0.003), baseline lactate (HR: 1.13, 95% CI: 1.07-1.19; P<0.001), baseline static lung compliance (C_stat) (HR: 0.97, 95% CI: 0.95-1.00; P=0.03), baseline IL-6/Lym >138.0 (HR: 4.85, 95% CI: 2.37-9.91; P<0.001), and baseline lactate (HR: 1.09, 95% CI: 1.03-1.15; P=0.003). Baseline IL-6/Lym >138.0 (HR: 4.73, 95% CI: 2.83-8.00; P<0.001) was shown to be an independent prognostic factor for ICU 28-day mortality with multivariate Cox analysis. The best discrimination between survivors and non-survivors was observed with the IL-6/Lym [area under the ROC curve (AUROC): 0.80, 95% CI: 0.69-0.88].

Conclusions: IL-6/Lym may be an independent protective factor for predicting ICU 28-day mortality in patients with moderate-to-severe ARDS supported with VV ECMO. The conclusions of the study need to be further confirmed by a multicenter prospective study.

Background: The Modified Early Warning Score (MEWS) is a valuable tool for predicting in-hospital mortality, yet it is seldom applied to acute type A aortic dissection (AAAD). This study aimed to evaluate the predictive accuracy of MEWS at different times within the first 24 hours after AAAD surgery, and to investigate the association between MEWS trajectories and postoperative mortality.

Methods: This retrospective study included 279 patients who underwent AAAD surgery from January 2020 to December 2022. MEWS was calculated at 0, 4, 8, 12, 16, 20, and 24 hours postoperatively. Predictive value for mortality was assessed using receiver operating characteristic (ROC) curves. Latent class growth modeling (LCGM) was applied to classify MEWS trajectories and analyze their association with postoperative mortality.

Results: Among 279 AAAD patients, the in-hospital mortality rate was 13.3%. MEWS was higher in the death group at all postoperative time points (P<0.05). The highest predictive accuracy occurred at 12 hours postoperatively [area under the curve (AUC) =0.758, cutoff =4]. LCGM identified three MEWS trajectories, with the highest-risk trajectory associated with a 45.9% incidence of mortality.

Conclusions: MEWS is a reliable early indicator of postoperative mortality in AAAD patients. Persistently high MEWS trajectories is strongly associated with increased mortality risk, supporting its use in early risk stratification and postoperative management.

Background: Non-intubated thoracic surgery (NITS) is a promising alternative to conventional double-lumen endotracheal tube (DLT) surgery, aiming to reduce airway trauma and accelerate recovery. However, its impact on the patient's subjective experience, particularly after discharge, is not well-documented. This study aimed to compare the perioperative recovery and patient-reported outcomes between NITS and DLT surgery, utilizing electronic patient-reported outcomes (ePROs) as a key measurement tool for postoperative symptom surveillance.

Methods: In this prospective, single-center cohort study, 60 patients scheduled for thoracoscopic resection between March and December 2023 were consecutively allocated to either the NITS group (n=30) or the DLT group (n=30). Both groups received standardized perioperative nursing care, while the NITS group additionally received targeted breathing training and enhanced intra-/postoperative respiratory support. ePROs covering nine symptom domains were collected daily during hospitalization and on postoperative days 7 and 30 after discharge. Conventional surgical metrics were also recorded. Between-group comparisons were performed using independent-samples t-tests or chi-square tests as appropriate.

Results: Compared to the DLT group, NITS significantly reduced median hospital stay (3.47 vs. 5.37 days; P<0.001), chest tube duration (1.57 vs. 2.60 days; P=0.001), and drainage volume (49.7 vs. 71.0 mL; P=0.02). On postoperative day 7, NITS patients reported significantly lower scores for pain, cough, dyspnea, sleep disturbance, fatigue, somnolence, distress, mobility difficulty and activity limitation (all P≤0.001); improvements in cough, fatigue, somnolence, distress, and activity limitation remained significant at day 30 (all P<0.05).

Conclusions: NITS combined with enhanced recovery protocol is a feasible and safe approach that enhances early recovery while enabling proactive, personalized outpatient symptom management.

Background: Severe chronic obstructive pulmonary disease (COPD) naturally progresses over time and is associated with increased mortality. During the coronavirus disease 2019 (COVID-19) pandemic, many surgical procedures were postponed, but the full impact of these delays remains unclear. Our aim was to evaluate the consequences of delayed lung volume reduction surgery (LVRS) treatment.

Methods: This study was conducted as a retrospective observational study. Patients who had LVRS postponed six months or more due to the COVID-19 pandemic at a national university centre were included. Data were obtained from an institutional database. Patients were re-evaluated before surgery using lung function tests, a 6-minute walking test (6MWT), and blood gas analysis. Increased symptoms, mortality, and infections were recorded. All surviving patients were reassessed for treatment indication in a multidisciplinary team (MDT) meeting.

Results: A total of 67 patients had their scheduled LVRS treatment postponed due to the pandemic. Of these 16% were infected with COVID-19. Four patients (6%) died before secondary evaluation. Mean time from outpatient clinic referral to surgery date was 398 (±161) days. Forced expiratory volume in one second (FEV1) significantly decreased by 0.1 L (P<0.001), while diffusion capacity of the lung for carbon monoxide (DLCO) remained unchanged. Performance in the 6MWT worsened by 29.9 m (P<0.001), and oxygen saturation decreased by 1.3% (P=0.046). Symptom worsening was experienced in 39% of patients. Clinical deterioration rendered 5% of patients unfit for surgery, while 86% remained fit for surgery. No patients were excluded due to COVID-19 infection.

Conclusions: The delay of LVRS due to the COVID-19 pandemic led to a decrease in lung function, 6MWT performance, and oxygen saturation. Although the majority of patients remained fit for surgery, the postponement resulted in cancellation of procedures due to clinical deterioration and contributed to waiting list mortality. This patient group is vulnerable to further deterioration over time and timely treatment should be prioritized.