The role of bidirectional associations between depression, anxiety, and emotional exhaustion on turnover intention among nurses: a multicenter cross-sectional study in China.

BACKGROUND: A high turnover rate in nursing has become a global concern. Mental health issues may increase the turnover intention of nurses and lead to turnover behaviors. However, very little is known about the role of bidirectional associations between emotional exhaustion and depression/anxiety on turnover intention. This study aimed to examine the associations among depression, anxiety, emotional exhaustion and turnover intention, and to test the role of bidirectional associations between depression, anxiety, and emotional exhaustion on turnover intention among nurses. METHODS: An online multicenter cross-sectional study was conducted in Hunan Province, China, from December 2021 to February 2022. The questionnaire collected data from the Turnover Intention Scale, the Emotional Exhaustion Scale, the Patient Health Questionnaire-2, and the Generalized Anxiety Disorder Scale-2, as well as sociodemographic information. Data analysis was performed by univariate analysis, Pearson correlation analysis, multiple linear regression analysis, and structural equation modeling. RESULTS: The average turnover intention score among Chinese nurses was 14.34 ± 3.75. The prevalence of depression and anxiety was 25.9% and 22.3%, respectively. Depression (r = 0.378, P < 0.001), anxiety (r = 0.391, P < 0.001), and emotional exhaustion (r = 0.532, P < 0.001) were positively associated with turnover intention. Emotional exhaustion partially mediated the associations between depression/anxiety and turnover intention, with both mediating effects accounting for 60.7%. The mediating ratios of depression/anxiety on the associations between emotional exhaustion and turnover intentions were 17.6% and 16.5%, respectively. CONCLUSIONS: Depression, anxiety, and emotional exhaustion showed significant positive effects on turnover intention among nurses. Emotional exhaustion played a partial mediation role between depression/anxiety and turnover intention, while depression/anxiety played no significant mediation role between emotional exhaustion and turnover intention.

Turnover intention and its associated factors among nurses: a multi-center cross-sectional study.

Aim: The purpose of our study was to assess the turnover intention of nurses in China and examine the associated factors. Background: Since the world population ages, the demand for nurses has kept growing, and the shortage of nurses and high turnover rates are concerned with the quality of care. Thus, understanding nurses' turnover intention and the relevant factors could provide nurse managers with strategies to address the modifiable factors to decrease the turnover rate of nurses. Methods: A multi-center cross-sectional study was conducted on a total of 1,854 nurses working in 15 hospitals in China. Data were collected using a self-designed demographic questionnaire, the Turnover Intention Scale, the Job Satisfaction Scale, the Pay Level Satisfaction Scale, the Interpersonal Conflict at Work Scale, and a single question on the sense of belonging to the hospital. Results: Most nurses (n = 1286, 69.4%) had a high level of turnover intention. Multilevel logistic regression analysis demonstrated that nurses being single (OR = 1.366, p < 0.05), with a junior college or below (OR = 0.381, p < 0.01), being a clinical nurse (OR = 1.913, p < 0.01), having higher pay level (OR = 0.596, p < 0.001), having higher job satisfaction (OR = 0.406, p < 0.001), having conflicts with colleagues (OR = 1.400, p < 0.05), and having a higher sense of belonging to the hospital (OR = 0.532, p < 0.001) proved to affect nurses' turnover intention. Conclusion: This study extended the knowledge about the factors associated with nurses' intention to leave, which led to the turnover of nurses, and is one of the main contributors to the current shortage of nurses. Implications for nursing management: This study provided new approaches to decreasing the turnover rate of nurses. Effective management strategies may mitigate nurses' turnover intention.

Rgl-exomiR-7972, a novel plant exosomal microRNA derived from fresh Rehmanniae Radix, ameliorated lipopolysaccharide-induced acute lung injury and gut dysbiosis.

Plant-derived exosome-like nanoparticles (ELNs) have been proposed as a novel therapeutic tool for preventing human diseases. However, the number of well-verified plant ELNs remains limited. In this study, the microRNAs in ELNs derived from fresh Rehmanniae Radix, a well-known traditional Chinese herb for treating inflammatory and metabolic diseases, were determined by using microRNA sequencing to investigate the active components in the ELNs and the protection against lipopolysaccharide (LPS)-induced acute lung inflammation in vivo and in vitro. The results showed that rgl-miR-7972 (miR-7972) was the main ingredient in ELNs. It exerted stronger protective activities against LPS-induced acute lung inflammation than catalpol and acteoside, which are two well-known chemical markers in this herb. Moreover, miR-7972 decreased the production of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α), reactive oxygen species (ROS) and nitric oxide (NO) in LPS-exposed RAW264.7 cells, thereby facilitating M2 macrophage polarization. Mechanically, miR-7972 downregulated the expression of G protein-coupled receptor 161 (GPR161), activating the Hedgehog pathway, and inhibited the biofilm form of Escherichia coli via targeting virulence gene sxt2. Therefore, miR-7972 derived from fresh R. Radix alleviated LPS-induced lung inflammation by targeting the GPR161-mediated Hedgehog pathway, recovering gut microbiota dysbiosis. It also provided a new direction for gaining novel bioactivity nucleic acid drugs and broadening the knowledge on cross-kingdom physiological regulation through miRNAs.

Comparative efficacy and acceptability of non-pharmacological interventions for depression among people living with HIV: A protocol for a systematic review and network meta-analysis.

BACKGROUND: Improving depression is critical to the success of HIV treatment. Concerns about the adverse effects of pharmacotherapy have led to non-pharmacological treatments for depression in people living with HIV (PLWH) becoming increasingly popular. However, the most effective and acceptable non-pharmacological treatments for depression in PLWH have not yet been determined. This protocol for a systematic review and network meta-analysis aims to compare and rank all available non-pharmacological treatments for depression in PLWH in the global network of countries as well as in the network of low-income and middle-income countries (LMICs) only. METHODS: We will include all randomized controlled trials of any non-pharmacological treatments for depression in PLWH. The primary outcomes will consider efficacy (the overall mean change scores in depression) and acceptability (all-cause discontinuation). Published and unpublished studies will be systematically searched through the relevant databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL, ProQuest, and OpenGrey), international trial registers, and websites. There is no restriction by language and publication year. All study selection, quality evaluation, and data extraction will be independently conducted by at least two investigators. We will perform a random-effects network meta-analysis to synthesize all available evidence for each outcome and obtain a comprehensive ranking of all treatments for the global network of countries as well as for the network of LMICs only. We will employ validated global and local approaches to evaluate inconsistency. We will use OpenBUGS (version 3.2.3) software to fit our model within a Bayesian framework. We will evaluate the strength of evidence using the Confidence in Network Meta-Analysis (CINeMA) tool, a web application based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. ETHICS AND DISSEMINATION: This study will use secondary data and therefore does not require ethical approval. The results of this study will be disseminated through peer-reviewed publication. TRIAL REGISTRATION: PROSPERO registration number: CRD42021244230.

Comparative efficacy and acceptability of non-pharmacological interventions for depression in people living with HIV: A systematic review and network meta-analysis.

BACKGROUND: Treatment for depression in people living with HIV has increasingly turned to non-pharmacological treatments due to the adverse reactions of pharmacotherapy. However, it remains unclear which non-pharmacological treatment is the most effective and acceptable for depression in people living with HIV. OBJECTIVE: To compare and rank the efficacy and acceptability of different non-pharmacological treatments for depression in people living with HIV. DESIGN: A systematic review and Bayesian network meta-analysis. METHODS: We systematically searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, PsycArticles, CINAHL, ProQuest, OpenGrey, and international trial registers for published and unpublished studies from their inception to September 1, 2022, and searched key conference proceedings from January 1, 2020, to September 25, 2022. We searched for randomized controlled trials of any non-pharmacological treatments for depression in adults living with HIV (≥18 years old). Primary outcomes were efficacy (mean change scores in depression) and acceptability (all-cause discontinuation). We used a random-effects network meta-analysis model to synthesize all available evidence. The methodological quality of the included studies was assessed using the Cochrane Collaboration Risk of Bias Tool. We registered this study in PROSPERO, number CRD42021244230. RESULTS: A total of 53 randomized controlled trials were included in this network meta-analysis involving seven non-pharmacological treatments for depression in people living with HIV. For efficacy, mind-body therapy, interpersonal psychotherapy, cognitive-behavioral therapy, supportive therapy, and education were significantly more effective than most control conditions (standardized mean differences ranged from -0.96 to -0.36). Rankings probabilities indicated that mind-body therapy (79%), interpersonal psychotherapy (71%), cognitive-behavioral therapy (62%), supportive therapy (57%), and education (57%) might be the top five most significantly effective treatments for depression in people living with HIV, in that order. For acceptability, only supportive therapy and interpersonal psychotherapy were significantly less acceptable than most control conditions (odds ratios ranged from 1.92 to 3.43). Rankings probabilities indicated that education might be the most acceptable treatment for people living with HIV (66%), while supportive therapy (26%) and interpersonal psychotherapy (10%) might rank the worst. The GRADE assessment results suggested that most results were rated as "moderate" to "very low" for the confidence of evidence. CONCLUSIONS: Our study confirmed the efficacy and acceptability of several non-pharmacological treatments for depression in people living with HIV. These results should inform future guidelines and clinical decisions for depression treatment in people living with HIV.

Implications of m6A methylation and microbiota interaction in non-small cell lung cancer: From basics to therapeutics.

N6-methyladenine (m6A) is one of the most common RNA epigenetic modifications in all higher eukaryotes. Increasing evidence demonstrated that m6A-related proteins, acted as oncogenes or tumor suppressors, are abnormally expressed in the cell lines and tissues of non-small cell lung cancer (NSCLC). In addition, lung as the special immune organ contacts with the outer environments and thereby inevitably suffers from different types of microbial pathogen attack. Those microbial pathogens affect the development, progression, and clinical outcomes of NSCLC via altering host m6A modification to disrupt pulmonary immune homeostasis and increase the susceptibility; conversely, host cells modulate m6A modification to repress bacterial colonization. Therefore, m6A harbors the potential to be the novel biomarkers and targets for predicting poor prognosis and chemotherapy sensitivity of patients with lung cancer. In this paper, we provided an overview of the biological properties of m6A-modifying enzymes, and the mechanistic links among lung microbiota, m6A modification and NSCLC. Although the flood of novel m6A-related inhibitors represents many dramatic improvements in NSCLC therapy, their efficacy and toxicity in NSCLC are explored to address these pivotal gaps in the field.

The Role of Respiratory Flora in the Pathogenesis of Chronic Respiratory Diseases.

Large quantities of bacteria, including Firmicutes, Actinobacteria, and Bacteroidetes, colonize the surface of the respiratory mucosa of healthy people. They interact and coexist with the local mucosal immune system of the human airway, maintaining the immune stability and balance of the respiratory system. While suffering from chronic respiratory diseases, the microbial population in the airway changes and the proportion of Proteobacteria is increased in patients with asthma. The abundance of the microbial population in patients with chronic obstructive pulmonary disease (COPD) is decreased, and conversely, the proportion of Firmicutes and Proteobacteria increased. The diversity of airway microorganisms in cystic fibrosis (CF) patients is decreased, while pathogenic bacteria and conditional pathogenic bacteria are proliferated in large numbers. The proportion of Firmicutes and Proteobacteria is increased in patients with upper airway cough syndrome (UACS), which replaces the dominance of Streptococcus and Neisseria in the pharynx of a normal population. Therefore, a clear understanding of the immune process of the airway flora and the immune dysfunction of the flora on the pathogenesis of chronic respiratory diseases can provide new ideas for the prevention and treatment of human respiratory diseases.

A Biological Insight into the Susceptibility to Influenza Infection in Junior Rats by Comprehensive Analysis of lncRNA Profiles.

Long noncoding RNAs (lncRNAs) have been reported to participate in regulating many biological processes, including immune response to influenza A virus (IAV). However, the association between lncRNA expression profiles and influenza infection susceptibility has not been well elucidated. Here, we analyzed the expression profiles of lncRNAs, miRNAs, and mRNAs among IAV-infected adult rat (IAR), normal adult rat (AR), IAV-infected junior rat (IJR), and normal junior rat (JR) by RNA sequencing. Compared with differently expressed lncRNAs (DElncRNAs) between AR and IAR, 24 specific DElncRNAs were found between IJR and JR. Then, based on the fold changes and P value, the top 5 DElncRNAs, including 3 upregulated and 2 downregulated lncRNAs, were chosen to establish a ceRNA network for further disclosing their regulatory mechanisms. To visualize the differentially expressed genes in the ceRNA network, GO and KEGG pathway analysis was performed to further explore their roles in influenza infection of junior rats. The results showed that the downregulated DElncRNA-target genes were mostly enriched in the IL-17 signaling pathway. It indicated that the downregulated lncRNAs conferred the susceptibility of junior rats to IAV via mediating the IL-17 signaling pathway.

Improvement of the ultra-low-frequency active vertical vibration isolator with geometric anti-spring structure for absolute gravimetry.

For absolute gravimeters, which play important roles in geophysics and geological exploration, an ultra-low-frequency vertical vibration isolator is necessary to achieve the required measurement precision. A novel active vibration isolator that uses a geometric anti-spring (GAS) structure has been proposed by our team at Tsinghua University previously, but its performance is mainly limited by the large-scale drift in the detection signal of the system. In this paper, after a brief theoretical introduction to the overall system, recent improvements in this novel vibration isolator are presented. The main improvements to the isolator are the use of new blades in the GAS structure and the addition of an extra compensation circuit to eliminate the drift. The improved prototype has a resonance period of 29.2 s and a continuous working time of several days, as compared with the resonance period of 19.2 s and a working time lasting only several minutes of the previous prototype. Experiments show that the improved prototype performs well in the homemade T-1 laser-interferometry absolute gravimeter. The standard error of the mean (SEM) of a 50-drop measurement performed in Tsinghua University is reduced significantly from 404 µGal (1 µGal = 1 × 10-8 m s-2) without the vibration isolator to 10.8 µGal with the improved prototype at its best level. Additionally, the SEM of a 50-set measurement (including 800 drops) lasting for 25 h achieves 5.9 µGal with the improved prototype.

Multiple Immune Features-Based Signature for Predicting Recurrence and Survival of Inoperable LA-NSCLC Patients.

INTRODUCTION: The immune status of the tumor microenvironment is extremely complex. One single immune feature cannot reflect the integral immune status, and its prognostic value was limited. We postulated that the immune signature based on multiple immuno-features could markedly improve the prediction of post-chemoradiotherapeutic survival in inoperable locally advanced non-small-cell lung cancer (LA-NSCLC) patients. METHODS: In this study, 100 patients who were diagnosed as having inoperable LA-NSCLC between January 2005 and January 2016 were analyzed. A five immune features-based signature was then constructed using the nested repeat 10-fold cross validation with least absolute shrinkage and selection operator (LASSO) Cox regression model. Nomograms were then established for predicting prognosis. RESULTS: The immune signature combining five immuno-features was significantly associated with overall survival (OS) and progression-free survival (PFS) (P = 0.002 and P = 0.014, respectively) in patients with inoperable LA-NSCLC, and at a cutoff of -0.05 stratified patients into two groups with 5-year OS rates of 39.8 and 8.8%, and 2-year PFS rates of 22.2 and 5.5% for the high- and low-immune signature groups, respectively. Integrating immune signature, we proposed predictive nomograms that were better than the traditional TNM staging system in terms of discriminating ability (OS: 0.692 vs. 0.588; PFS: 0.672 vs. 0.586, respectively) or net weight classification (OS: 32.96%; PFS: 9.22%), suggesting that the immune signature plays a significant role in improving the prognostic value. CONCLUSION: Multiple immune features-based immune signature could effectively predict recurrence and survival of inoperable LA-NSCLC patients and complemented the prognostic value of the TNM staging system.

Early response evaluation using primary tumor and nodal imaging features to predict progression-free survival of locally advanced non-small cell lung cancer.

Prognostic biomarkers that can reliably predict early disease progression of non-small cell lung cancer (NSCLC) are needed for identifying those patients at high risk for progression, who may benefit from more intensive treatment. In this work, we aimed to identify an imaging signature for predicting progression-free survival (PFS) of locally advanced NSCLC. Methods: This retrospective study included 82 patients with stage III NSCLC treated with definitive chemoradiotherapy for whom both baseline and mid-treatment PET/CT scans were performed. They were randomly placed into two groups: training cohort (n=41) and testing cohort (n=41). All primary tumors and involved lymph nodes were delineated. Forty-five quantitative imaging features were extracted to characterize the tumors and involved nodes at baseline and mid-treatment as well as differences between two scans performed at these two points. An imaging signature was developed to predict PFS by fitting an L1-regularized Cox regression model. Results: The final imaging signature consisted of three imaging features: the baseline tumor volume, the baseline maximum distance between involved nodes, and the change in maximum distance between the primary tumor and involved nodes measured at two time points. According to multivariate analysis, the imaging model was an independent prognostic factor for PFS in both the training (hazard ratio [HR], 1.14, 95% confidence interval [CI], 1.04-1.24; P = 0.003), and testing (HR, 1.21, 95% CI, 1.10-1.33; P = 0.048) cohorts. The imaging signature stratified patients into low- and high-risk groups, with 2-year PFS rates of 61.9% and 33.2%, respectively (P = 0.004 [log-rank test]; HR, 4.13, 95% CI, 1.42-11.70) in the training cohort, as well as 43.8% and 22.6%, respectively (P = 0.006 [log-rank test]; HR, 3.45, 95% CI, 1.35-8.83) in the testing cohort. In both cohorts, the imaging signature significantly outperformed conventional imaging metrics, including tumor volume and SUVmax value (C-indices: 0.77-0.79 for imaging signature, and 0.53-0.73 for conventional metrics). Conclusions: Evaluation of early treatment response by combining primary tumor and nodal imaging characteristics may improve the prediction of PFS of locally advanced NSCLC patients.

Tumor Subregion Evolution-Based Imaging Features to Assess Early Response and Predict Prognosis in Oropharyngeal Cancer.

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rapidly increasing. Disease stage and smoking history are often used in current clinical trials to select patients for deintensification therapy, but these features lack sufficient accuracy for predicting disease relapse. Our purpose was to develop an imaging signature to assess early response and predict outcomes of OPSCC. Methods: We retrospectively analyzed 162 OPSCC patients treated with concurrent chemoradiotherapy, equally divided into separate training and validation cohorts with similar clinical characteristics. A robust consensus clustering approach was used to spatially partition the primary tumor and involved lymph nodes into subregions (i.e., habitats) based on 18F-FDG PET and contrast CT imaging. We proposed quantitative image features to characterize the temporal volumetric change of the habitats and peritumoral/nodal tissue between baseline and midtreatment. The reproducibility of these features was evaluated. We developed an imaging signature to predict progression-free survival (PFS) by fitting an L1-regularized Cox regression model. Results: We identified 3 phenotypically distinct intratumoral habitats: metabolically active and heterogeneous, enhancing and heterogeneous, and metabolically inactive and homogeneous. The final Cox model consisted of 4 habitat evolution-based features. In both cohorts, this imaging signature significantly outperformed traditional imaging metrics, including midtreatment metabolic tumor volume for predicting PFS, with a C-index of 0.72 versus 0.67 (training) and 0.66 versus 0.56 (validation). The imaging signature stratified patients into high-risk versus low-risk groups with 2-y PFS rates of 59.1% versus 89.4% (hazard ratio, 4.4; 95% confidence interval, 1.4-13.4 [training]) and 61.4% versus 87.8% (hazard ratio, 4.6; 95% confidence interval, 1.7-12.1 [validation]). The imaging signature remained an independent predictor of PFS in multivariable analysis adjusting for stage, human papillomavirus status, and smoking history. Conclusion: The proposed imaging signature allows more accurate prediction of disease progression and, if prospectively validated, may refine OPSCC patient selection for risk-adaptive therapy.

18F-Fluorodeoxyglucose positron emission tomography may not visualize radiation pneumonitis.

BACKGROUND: Radiation pneumonitis is a common and potentially fatal complication of radiotherapy (RT). Some patients with radiation pneumonitis show increases in uptake of fluorodeoxyglucose (FDG) on positron emission tomography (PET), but others do not. The exact relationship between radiation pneumonitis and 18F-FDG PET findings remains controversial. METHODS: We used an animal model of radiation pneumonitis involving both radiation and simulated bacterial infection in Wistar rats. Treatment groups (10 rats/group) were as follows: control, RT-only, lipopolysaccharide (LPS)-only, and RT+LPS. All rats had micro-PET scans at 7 weeks after RT (or sham). Histologic, immunohistochemical, and biochemical analyses were performed to evaluate potential mechanisms. RESULTS: Irradiated rats had developed radiation pneumonitis at 7 weeks after RT based on pathology and CT scans. Maximum and mean standardized uptake values (SUVmax and SUVmean) at that time were significantly increased in the LPS group (P < 0.001 for both) and the RT+LPS group (P < 0.001 for both) relative to control, but were not different in the RT-only group (P = 0.156 SUVmax and P = 0.304 SUVmean). The combination of RT and LPS increased the expression of the aerobic glycolysis enzyme PKM2 (P < 0.001) and the glucose transporter GLUT1 (P = 0.004) in lung tissues. LPS alone increased the expression of PKM2 (P = 0.018), but RT alone did not affect PKM2 (P = 0.270) or GLUT1 (P = 0.989). CONCLUSIONS: Aseptic radiation pneumonitis could not be accurately assessed by 18F-FDG PET, but was visualized after simulated bacterial infection via LPS. The underlying mechanism of the model of bacterial infection causing increased FDG uptake may be the Warburg effect.

The Kinetic Changes of Systemic Inflammatory Factors during Bevacizumab Treatment and Its Prognostic Role in Advanced Non-small Cell Lung Cancer Patients.

Background: Bevacizumab combined with chemotherapy is still one of the standard options for treatment of advanced non-small cell lung cancer (NSCLC) patients without driver mutations. Serum inflammatory factors, representing the systemic immune status, are shown to have complicated relationships with tumor angiogenesis, and proved to be associated with survival of advanced NSCLC patients. However, the information from the baseline factors is relatively limited, which cannot reflect the dynamic changes of systemic immune status during bevacizumab treatment. We, thus, attempted to evaluate longitudinal kinetics of systemic inflammatory factors during treatment of bevacizumab and to explore their predictive role in treatment response and patient outcomes in advanced NSCLC. Method: Systemic inflammatory factors (neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), neutrophil×platelet/lymphocyte (SII) and lymphocyte/monocyte (LMR)) and clinical variables were collected and analyzed from 161 advanced NSCLC patients treated with bevacizumab. Mixed effect regression models were first performed for longitudinal analysis of the changes of serum inflammatory factors during bevacizumab treatment. Then, univariate and multivariate Cox models were used for overall survival (OS) and progression free survival (PFS) analyses to determine the independent prognostic factors. Results: In the first 6 cycles of bevacizumab treatment, patients with complete response/partial response (CR/PR) had a -0.11, -0.066, -0.15, and 0.073 change every 2 cycles in transformed NLR (95%CI: -0.19--0.03, p=0.008), PLR (95%CI: -0.12--0.013, p=0.015), SII (95%CI: -0.23--0.05, p<0.001) and LMR (95%CI: 0.049-0.14, p=0.036), respectively, compared to patients with progressive disease (PD). With respect to analysis of the longitudinal changes before progression, patients experienced a significant increase in transformed NLR (Coef=0.09, 95%CI: 0.019-0.17, p=0.014), PLR (Coef=0.05, 95%CI: 0.002-0.10, p=0.04), and SII (Coef=0.091, 95%CI: 0.015-0.17, p=0.019), but a decrease in transformed LMR (Coef=-0.08, 95%CI: -0.14-0.018, p=0.012). On multivariate Cox model analyses, decrease of LMR (HR=0.62, 95% CI: 0.4-0.96, p=0.033) was shown to be the independent risk factor for PFS; and low level of baseline LMR (HR=0.4, 95% CI: 0.17-0.94, p=0.036), increase of NLR (HR=2.36, 95%CI: 1.25-4.44, p=0.008), and decrease of LMR (HR=0.42, 95%CI: 0.18-0.97, p=0.041) were the independent risk factors for death. Conclusion: The activation of systemic immune status evaluated by the kinetic changes of serum inflammatory factors was associated with good response to bevacizumab; however, the suppressive status may indicate the resistance to bevacizumab. Dynamic changes of systemic inflammatory factors also had prognostic value in predicting outcomes of advanced NSCLC patients treated with bevacizumab.

Delineating the pattern of treatment for elderly locally advanced NSCLC and predicting outcomes by a validated model: A SEER based analysis.

INTRODUCTION: Locally advanced nonsmall-cell lung cancer (LA-NSCLC) represented a highly heterogeneous group, with more than half of the patients aged ≥65 years at the time of diagnosis. However, the optimal treatment for elderly LA-NSCLC patients was still not defined. METHODS: A total of 33530 elderly patients (≥65 years) diagnosed with LA-NSCLC from 2004 to 2014 were identified from Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Locally advanced nonsmall-cell lung cancer patients aged 65-74 years were more frequently treated with chemoradiotherapy (CRT) (40%), while patients aged ≥75 years received more best supportive care (BSC) (36%). For age group of 65-74 years, patients who had surgery with or without (neo)adjuvant therapy had a median survival of 28 months, CRT 15 months, radiotherapy (RT) alone 6 months, chemotherapy alone 11 months, and BSC 3 months; while for patients aged ≥ 75 years, the median OS was 20, 13, 7, 9, and 2, respectively. Besides, independent clinicopathological factors were integrated into nomograms for OS and CSS prediction, C-indexes achieved 0.692 and 0.698, respectively. Importantly, the discrimination of nomogram was superior to that of the American Joint Committee on Cancer TNM classification (0.742 vs 0.572 for training set and 0.731 vs 0.565 for validation set). CONCLUSION: For elderly patients with LA-NSCLC, the curative-intent treatment (surgery or CRT) conferred better survival compared to chemotherapy alone, RT alone and BSC. The proposed nomograms based on independent clinicopathological variables may be practical and helpful for precise evaluation of patient prognosis, and guiding the individualized treatment for elderly LA-NSCLC.

Prognostic value of delta inflammatory biomarker-based nomograms in patients with inoperable locally advanced NSCLC.

OBJECTIVE: Inflammation plays critical roles in tumor growth and progression, and can be adversely affected by chemotherapy and radiotherapy. However, there have been few studies on the prognostic value of delta (Δ) inflammatory biomarkers before and after chemoradiotherapy in patients with locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: In this study, pre/post-treatment and Δ inflammatory biomarkers of 370 patients who were diagnosed as having inoperable LA-NSCLC in Shandong Cancer Hospital between January 2005 and January 2016 were analyzed. Nomograms were then established for predicting prognosis. RESULTS: Median overall survival (OS) and progression free survival (PFS) for all patients were 28.1 (range 1.9-129.0) months and 11.1 (range 1.7-58.7) months, respectively. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) significantly increased and the lymphocyte-to-monocyte ratio (LMR) significantly decreased during the concurrent chemoradiotherapy course (P < 0.001, P < 0.001, and P < 0.001, respectively). Multivariate analysis revealed that pre-LMR, ΔNLR, and minimum absolute lymphocyte counts were independent predictors of OS (P = 0.027, P = 0.012, and P = 0.015, respectively) and post-LMR, post-NLR, and ΔNLR were independent predictors of PFS (P = 0.014, P = 0.001, and P = 0.036, respectively). Nomograms for OS and PFS were established by combining all significant inflammatory markers and clinicopathological characteristics. The concordance indexes for OS and PFS were 0.709 and 0.688, respectively. CONCLUSION: Post-treatment and Δ inflammatory biomarkers may have more prognostic significance than baseline measurements of inflammatory biomarkers in LA-NSCLC patients. The proposed nomograms based on the dynamic inflammatory biomarkers and clinicopathological factors may be practical and widely available for evaluating the prognosis of patients with inoperable LA-NSCLC.

Local therapy combined with chemotherapy versus chemotherapy for postoperative oligometastatic non-small-cell lung cancer.

Aim: To compare the efficacy and toxicity of local therapy plus chemotherapy versus chemotherapy in non-small-cell lung cancer (NSCLC) patients with oligometastases after surgery. Patients & methods: A total of 152 patients with oligometastases after surgery were enrolled. Data of patient survival, treatment response and toxicities were compared between the groups receiving local ablative therapy plus chemotherapy and chemotherapy alone. Results: Compared with chemotherapy, the combination treatment conferred better progression-free survival, objective response rate and disease control rate (10 vs 7 months; 66.7 vs 31.9%; 94.3 vs 80.9%, respectively), but with more grade ≥3 adverse events. Besides, the overall survival was not significantly different (19 vs 20 months). Conclusion: The addition of local therapy to chemotherapy improved progression-free survival, objective response rate and disease control rate, but not overall survival in postoperative oligometastatic non-small-cell lung cancer.

Integrative nomogram of CT imaging, clinical, and hematological features for survival prediction of patients with locally advanced non-small cell lung cancer.

OBJECTIVES: To determine the integrative value of clinical, hematological, and computed tomography (CT) radiomic features in survival prediction for locally advanced non-small cell lung cancer (LA-NSCLC) patients. METHODS: Radiomic features and clinical and hematological features of 118 LA-NSCLC cases were firstly extracted and analyzed in this study. Then, stable and prognostic radiomic features were automatically selected using the consensus clustering method with either Cox proportional hazard (CPH) model or random survival forest (RSF) analysis. Predictive radiomic, clinical, and hematological parameters were subsequently fitted into a final prognostic model using both the CPH model and the RSF model. A multimodality nomogram was then established from the fitting model and was cross-validated. Finally, calibration curves were generated with the predicted versus actual survival status. RESULTS: Radiomic features selected by clustering combined with CPH were found to be more predictive, with a C-index of 0.699 in comparison to 0.648 by clustering combined with RSF. Based on multivariate CPH model, our integrative nomogram achieved a C-index of 0.792 and retained 0.743 in the cross-validation analysis, outperforming radiomic, clinical, or hematological model alone. The calibration curve showed agreement between predicted and actual values for the 1-year and 2-year survival prediction. Interestingly, the selected important radiomic features were significantly correlated with levels of platelet, platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR) (p values all < 0.05). CONCLUSIONS: The integrative nomogram incorporated CT radiomic, clinical, and hematological features improved survival prediction in LA-NSCLC patients, which would offer a feasible and practical reference for individualized management of these patients. KEY POINTS: • An integrative nomogram incorporated CT radiomic, clinical, and hematological features was constructed and cross-validated to predict prognosis of LA-NSCLC patients. • The integrative nomogram outperformed radiomic, clinical, or hematological model alone. • This nomogram has value to permit non-invasive, comprehensive, and dynamical evaluation of the phenotypes of LA-NSCLC and can provide a feasible and practical reference for individualized management of LA-NSCLC patients.

Local ablative therapy with or without chemotherapy for non-small-cell lung cancer patients with postoperative oligometastases.

BACKGROUND: The optimal treatment strategy for patients with non-small-cell lung cancer (NSCLC) with postoperative oligometastases is poorly defined. This two-institution analysis sought to retrospectively compare the efficacy and toxicity of local ablative treatment plus chemotherapy vs local treatment alone in patients with NSCLC who developed oligometastases after surgery. PATIENTS AND METHODS: Among patients who underwent surgery for stage I-III NSCLC, 163 patients with oligometastases were enrolled between 2005 and 2016 in this study. All patients had ≤5 metachronous metastases with a disease-free interval (DFI) of ≥6 months after surgery. Patients with a second primary cancer, local recurrence, or driver mutations were excluded. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), failure patterns, and treatment-related toxicities were compared between groups receiving local ablative treatment plus chemotherapy and local treatment alone. RESULTS: A total of 105 patients who underwent local ablative therapy combined with chemotherapy and 58 patients who received local ablative therapy alone were included in this study. The median follow-up was 19 (range, 1.5-107) months. The combination therapy group had a higher ORR than the local therapy alone group (66.7% vs 46.5%, P=0.012), while the median PFS was 10 vs 7 months (P=0.006) and the median OS was 19 vs 18.5 months (P=0.498), respectively. By multivariate analysis, combination therapy and DFI ≥24 months were associated with superior PFS. Age was the only independent prognostic factor for OS (P<0.001). The incidences of grade ≥3 adverse events were higher in the combination treatment group. CONCLUSION: Local ablative therapy plus chemotherapy conferred higher ORR and prolonged PFS but did not improve OS in NSCLC patients with postoperative oligometastases. Further prospective and randomized trials are urgently needed to validate these findings.