Prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros / Smoking prevalence and lung cancer morbimortality in Brazilian states / Prevalencia del tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños

Introdução: O câncer de pulmão é uma doença grave, sendo a segunda maior causa de morte em todo o mundo, entretanto, em alguns países desenvolvidos, tornou-se já a primeira causa de morte. Cerca de 90% dos casos de neoplasia pulmonares são causados pela inalação da fumaça do cigarro. Objetivo: Correlacionar a prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, além de demonstrar a associação destes com sexo e faixa etária. Métodos: Estudo de caráter ecológico acerca da prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, nos períodos de 2013 e 2019, dividida por sexo e faixa etária. Foram utilizados bancos de coleta de dados como o Tabnet e Pesquisa Nacional de Saúde. Resultados: As maiores taxas de mortalidade e internações hospitalares foram do público masculino, em 2013, com taxa de 2,7 e 10, respectivamente, e em 2019 com 3,3 e 11,9, respectivamente. Ademais, a maior prevalência de tabagismo foi encontrada nos homens; entretanto seu índice tem caído, enquanto a quantidade de mulheres tabagistas tem aumentado. A Região Sul demonstrou maiores números de mortalidade em ambos os períodos estudados, com taxas de 4,9 e 5,8 por 100 mil habitantes, e morbidade hospitalar com 19,9 e 23,5 por 100 mil habitantes. Já a Região Norte se configurou com as menores prevalências: em 2013 apresentou taxa de óbito por câncer de pulmão de 1,0 e morbidade hospitalar de 3,5/100 mil habitantes, em 2019 apresentou taxa de mortalidade de 4,6 e internações de 1,6/100 mil habitantes. Os coeficientes de correlação de morbidade hospitalar e prevalência de tabagismo foram R2=0,0628, r=0,251 e p=0,042, enquanto os de mortalidade e prevalência de tabagismo foram R2=0,0337, r=0,183 e p=0,140. Conclusões: Na presente pesquisa, pode-se inferir que houve associação positiva na comparação entre taxa de morbidade hospitalar e prevalência de tabagismo; em contrapartida, não foi possível observar associação positiva na correlação da taxa de mortalidade por câncer de pulmão e prevalência de tabagismo.

Introduction: Lung cancer is a serious disease, being the second leading cause of death worldwide. Moreover, in some developed countries, it has already become the leading cause of death. About 90% of lung cancer cases are caused by cigarette smoking. Objective: To correlate the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states, and to demonstrate their association with sex and age group as well. Methods: An ecological study on the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states between 2013 and 2019, divided by sex and age group. The data collection databases Tabnet and National Health Survey were used. Results: The highest rates of mortality and hospital admissions were among men, in 2013 with a rate of 2.7 and 10, respectively, and in 2019 with 3.3 and 11.9, respectively. In addition, the highest prevalence of smoking was found in men, but this rate has fallen, while the number of women smokers has increased. The South region showed higher mortality rates in both periods studied, with rates of 4.9 and 5.8 per 100,000 inhabitants, and hospital morbidity with 19.9 and 23.5 per 100,000 inhabitants. The North region had the lowest prevalence, where in 2013, it had a death rate from lung cancer of 1.0 and hospital morbidity of 3.5/100 thousand inhabitants, and where in 2019, it had a mortality rate of 4.6 and hospitalizations of 1.6/100 thousand inhabitants. The correlation coefficients for hospital morbidity and smoking prevalence were R2=0.0628, r=0.251 and p=0.042, while for mortality and smoking prevalence, these were R2=0.0337, r=0.183 and p=0.140. Conclusions: In the present study, it can be inferred that there was a positive association between hospital morbidity rate and prevalence of smoking, while it was not possible to observe a correlation between lung cancer mortality rate and prevalence of smoking.

Introducción: El cáncer de pulmón es una enfermedad grave, siendo la segunda causa de muerte en todo el mundo, sin embargo, en algunos países desarrollados, ya se ha convertido en la primera causa de muerte. Alrededor del 90% de los casos de neoplasias pulmonares están causados por la inhalación del humo del cigarrillo. Objetivo: Correlacionar la prevalencia de tabaquismo y la morbimortalidad por cáncer de pulmón en los estados brasileños, además de demostrar la asociación de estos con el género y el grupo de edad. Métodos: estudio ecológico sobre la prevalencia de tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños, dentro de los períodos 2013 y 2019, divididos por sexo y grupo de edad. Se utilizaron bancos de recogida de datos como Tabnet y la Encuesta Nacional de Salud. Resultados: las mayores tasas de mortalidad e ingresos hospitalarios se dieron en el público masculino, en 2013 con una tasa de 2,7 y 10, respectivamente, y en 2019 con 3,3 y 11,9, respectivamente. Además, la mayor prevalencia del tabaquismo se encontró en los hombres, sin embargo, su tasa ha disminuido, mientras que la cantidad de mujeres fumadoras ha aumentado. La región Sur presentó cifras más altas de mortalidad en ambos periodos estudiados, con tasas de 4,9 y 5,8 por 100.000 habitantes, y de morbilidad hospitalaria con 19,9 y 23,5 por 100.000 habitantes. Mientras que la región Norte se configuró con las prevalencias más bajas, en 2013 presentó una tasa de mortalidad por cáncer de pulmón de 1,0 y una morbilidad hospitalaria de 3,5/100.000 habitantes, en 2019 presentó una tasa de mortalidad de 4,6 y hospitalizaciones de 1,6/100.000 habitantes. Los coeficientes de correlación para la morbilidad hospitalaria y la prevalencia del tabaquismo fueron R2=0,0628, r=0,251 y p=0,042, mientras que para la mortalidad y la prevalencia del tabaquismo fueron R2=0,0337, r=0,183 y p=0,140. Conclusiones: En la presente investigación se puede inferir que existe una asociación positiva en la comparación entre la tasa de morbilidad hospitalaria y la prevalencia de tabagismo, en contrapartida, no fue posible observar una asociación positiva en la correlación de la tasa de mortalidad por cáncer de pulmón y la prevalencia de tabagismo.

EGFR-mutated lung adenocarcinoma with choroidal oligometastasis during treatment with gefitinib: a case report.

The patient was a 74-year-old woman who was diagnosed with lung adenocarcinoma, clinical Stage IIIA. Induction chemoradiation was performed followed by right upper lobectomy and lymph node dissection. Because of positive pleural effusion cytology, which was proven after surgery, the patient was diagnosed with pathological Stage IVA with EGFR L858R mutation. At 17 months after the administration of gefitinib, left choroidal metastasis appeared. Stereotactic irradiation and ruthenium small-beam radiation were effective; however, the metastatic lesion showed regrowth 7 months after these treatments. Because the patient's choroidal oligometastasis was resistant to conservative therapy, left ophthalmectomy was performed. EGFR mutations (L858R and E709K) were detected in the resected choroidal tumor. The patient continued to take gefitinib. However, a neoplastic lesion developed on the optic nerve adjacent to the resected posterior eye segment. The lesion was treated with stereotactic radiation, gefitinib was switched to afatinib 30 mg, and the patient remains alive and disease free for 11 months.

Risk factors and prognostic analysis of right ventricular dysfunction after lung resection for NSCLC.

Objectives: Lung cancer is the leading cause of cancer death, and 80-85% of all lung cancer cases are non-small cell lung cancer (NSCLC). Surgical resection is the standard treatment for early-stage NSCLC. However, lung resection, a surgical procedure, can result in complications and increased mortality. Recent studies have shown a significant correlation between complications after lung resection and right ventricular dysfunction. Methods: Transthoracic echocardiography-derived right ventricular-pulmonary artery coupling (RV-PAC) was utilized to assess right ventricular function in these patients. Multivariate logistic regression analysis was also conducted to assess risk factors independently associated with RV-PA uncoupling. The 3- and 5-year cumulative survival rates were estimated with Kaplan-Meier curves, and differences between groups were analyzed using the Mantel-Cox log-rank test. Results: RV-PA uncoupling was defined as a TAPSE/PASP value < 0.67 mm/mm Hg according to spline analysis. The results of multivariable logistic regression analysis indicated that diabetes is an independent risk factor for right ventricular dysfunction after lung resection in patients with NSCLC. Kaplan-Meier analysis revealed a significant decrease in the survival rate of patients with RV-PA uncoupling at both the 3-year follow-up (73% vs 40%, p < 0.001) and 5-year follow-up (64% vs 37%, p < 0.001). Conclusions: After lung resection for NSCLC, the patient's right ventricular function predicts prognosis. Patients with right ventricular dysfunction, particularly those with diabetes mellitus, have a worse prognosis. It is crucial to actively prevent and correct risk factors to reduce the mortality rate in these patients.

Insights into the role of mitophagy in lung cancer: current evidence and perspectives.

Lung cancer, recognized globally as a leading cause of malignancy-associated morbidity and mortality, is marked by its high prevalence and lethality, garnering extensive attention within the medical community. Mitophagy is a critical cellular process that plays a crucial role in regulating metabolism and ensuring quality control within cells. Its relevance to lung cancer has garnered significant attention among researchers and scientists. Mitophagy's involvement in lung cancer encompasses its initiation, progression, metastatic dissemination and treatment. The regulatory landscape of mitophagy is complex, involving numerous signaling proteins and pathways that may exhibit aberrant alterations or mutations within the tumor environment. In the field of treatment, the regulation of mitophagy is considered key to determining cancer chemotherapy, radiation therapy, other treatment options, and drug resistance. Contemporary investigations are directed towards harnessing mitophagy modulators, both inhibitors and activators, in therapeutic strategies, with an emphasis on achieving specificity to minimize collateral damage to healthy cellular populations. Furthermore, molecular constituents and pathways affiliated with mitophagy, serving as potential biomarkers, offer promising avenues for enhancing diagnostic accuracy, prognostic assessment, and prediction of therapeutic responses in lung cancer. Future endeavors will also involve investigating the impact of mitophagy on the composition and function of immune cells within the tumor microenvironment, aiming to enhance our understanding of how mitophagy modulates the immune response to lung cancer. This review aims to comprehensively overview recent advancements about the role of mitophagy in the tumor genesis, progenesis and metastasis, and the impact of mitophagy on the treatment of lung cancer. We also discussed the future research direction of mitophagy in the field of lung cancer.

Severe lupus pneumonitis: A case of life-saving multimodal therapy with rituximab and corticosteroids.

Severe lupus pneumonitis is a rare and life-threatening complication of systemic lupus erythematosus (SLE), characterized by its rapid progression and high mortality rate. This case report describes the clinical trajectory and therapeutic management of a young Aboriginal female with established lupus nephritis who developed severe lupus pneumonitis. Despite her stable renal condition under long-term immunosuppressive treatment, she experienced acute respiratory distress, leading to her admission to the intensive care unit and subsequent mechanical ventilation. The diagnostic process was complicated by the difficulty in obtaining tissue biopsies, necessitating reliance on clinical judgement and radiological evidence to formulate a diagnosis. The patient was treated with pulsed intravenous methylprednisolone followed by rituximab infusions, resulting in significant clinical and radiological improvement. This case highlights the importance of early and intensive immunosuppressive therapy in the management of severe lupus pneumonitis and underscores the utility of a multidisciplinary approach in overcoming diagnostic ambiguities. Furthermore, it contributes to the growing body of evidence supporting the efficacy of rituximab in severe lupus pneumonitis cases, offering insights into potential therapeutic avenues when conventional management strategies are inadequate or unsuitable.

Neutrophil in the suppressed immune microenvironment: Critical prognostic factor for lung adenocarcinoma patients with KEAP1 mutation.

Purpose: It is still unclear whether KEAP1 mutation is detrimental to immunotherapy of lung adenocarcinoma (LUAD) patients, we try to analyse the exact changes in the TME in LUAD patients with KEAP1 mutations and to identify key factors influencing prognosis. Experimental design: A total of 1,029 patients with lung squamous carcinoma (LUSC) or LUAD with data obtained from The Cancer Genome Atlas were included in this study. The TME and OS of patients with LUAD stratified by mutant versus wild-type KEAP1 status were comprehensively measured. Moreover, we classified LUAD patients with KEAP1 mutations into three subtypes, by unsupervised consensus clustering. We further analysed the TME, OS, commutated genes and metabolic pathways of different subgroups. A total of 40 LUAD patients underwent immunotherapy were collected and classified into mutant KEAP1 group and wild-type KEAP1 group. We also conducted immunohistochemical staining in KEAP1-MT groups. Result: Suppressed TME was observed not only in LUAD patients but also in LUSC patients. LUAD patients with mutant KEAP1 underwent immunotherapy had worse PFS than wild-type KEAP1. Unsupervised consensus clustering analysis suggested that the three subtypes of patients exhibited different densities of neutrophil infiltration and had different OS results: cluster 2 patients had significantly higher levels of neutrophils had significantly worse prognoses than those of patients in clusters 1 and 3 and patients with wild-type KEAP1. Univariate and multivariate Cox analyses proved that a high density of neutrophils was significantly associated with worse OS and immunohistochemical staining proved that shorter PFS showed high density of neutrophils. Conclusion: KEAP1 mutation significantly suppresses the tumour immune microenvironment in LUAD patients. LUAD patients with mutant KEAP1 underwent immunotherapy had worse PFS than with wild-type KEAP1. Neutrophils may play an important role in the prognosis of LUAD patients with KEAP1 mutations and may provide a promising therapeutic target.

A case of complete pathological response after comprehensive treatment in a patient with pulmonary adenocarcinoma with synchronous solitary brain metastasis.

Systemic chemotherapy is the standard treatment for non-small cell lung cancer with distant metastases. However, additional local treatment for brain and thoracic lesions is recommended for patients with synchronous solitary brain metastases (SSBM). We report the case of a 71-year-old male diagnosed with pulmonary adenocarcinoma and SSBM. Pathological examination of the brain metastasis showed positive immunostaining for programmed cell death ligand 1 expression. After four cycles of chemotherapy with immune checkpoint inhibitors, right upper lobectomy with ND2a-1 was performed. Pathological examination revealed complete pathological response, and this patient is expected to experience long-term survival.

A new communication approach to encourage lung cancer screening action in rural eligible populations.

Objective: The purpose of this study was to develop an effective communication approach to encourage lung cancer screening action within rural screening-eligible populations. Methods: An iterative research approach using targeted engagement with the priority population was used. Findings were triangulated through multiple methods, including two surveys and concept testing interviews. The Health Belief Model and the Extended Parallel Process Model served as study frameworks. Results: Initial findings suggest that threat levels are high in the priority population and an emphasis on barrier mitigation messaging may drive action. Health campaign posters integrating these findings were developed and tested with the priority population. The new health campaign posters were tested against examples of previously used health campaign posters. Findings suggest that the new health campaign posters were more effective in spurring lung cancer screening motivation and intention to act in the priority population compared to current health campaign poster examples. Conclusion: Messaging focused on gain-framing, inoculation messaging, and barrier mitigation may be more effective in encouraging lung cancer screening action in rural eligible populations. Innovation: This project outlines a systematic process to developing effective, targeted communication approaches using behavior change and persuasive communication frameworks along with engagement from priority populations.

Geriatric Nutritional Risk Index as Prognostic Marker for Elderly Patients With Small Cell Lung Cancer.

Background/Aim: The Geriatric Nutritional Risk Index (GNRI) indicates nutritional status based on serum albumin concentration and ideal body weight. Pretreatment GNRI has been suggested as a prognostic factor for various malignancies. However, little is known about the clinical value of GNRI for small-cell lung cancer (SCLC), especially in elderly patients. Patients and Methods: We retrospectively analyzed 53 elderly (≥71) patients with extensive-disease (ED) SCLC treated with first-line platinum-doublet chemotherapy in relation to the pretreatment GNRI level in a real-world setting. Results: Thirty-six patients with a low GNRI (<92) had statistically poorer progression-free survival (PFS) and overall survival (OS) than 17 patients with a high GNRI (≥92) (median PFS=80 days vs. 133 days, respectively; p=0.002; median OS=123 days vs. 274 days, respectively; p=0.004). In a multivariate analysis, a low GNRI was also an independent poor prognostic factor for PFS [hazard ratio (HR)=0.396; 95% confidence interval (CI)=0.199-0.789; p=0.008] and OS (HR=0.295; 95%CI=0.143-0.608; p<0.001). Conclusion: The GNRI might be a predictive and prognostic marker in elderly patients with ED-SCLC treated with platinum-doublet chemotherapy.

Therapeutic Resistance in G-CSF Producing Lung Cancer With EGFR Mutation.

Background/Aim: Granulocyte colony-stimulating factor (G-CSF)-producing neoplasms are relatively rare; however, little is known on the clinical features of G-CSF-producing lung cancer harboring activating epidermal growth factor receptor (EGFR) mutations. Case Report: A 66-year-old female was definitively diagnosed with G-CSF-producing lung cancer that was positive for EGFR mutations. She repeatedly received epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as osimertinib and afatinib. However, she developed resistance to these molecular-targeting drugs within 2 to 3 months after immediate shrinkage. Thus, the patient was treated with chemoimmunotherapy including bevacizumab, and demonstrated a slight survival benefit. Conclusion: Overall, G-CSF-producing lung cancers positive for EGFR mutations were resistant to different treatment modalities. Clinicians should be attentive to the potential resistance of G-CSF-producing EGFR mutant lung cancer to EGFR-TKI therapy.

Comparing the Effectiveness of Afatinib and Osimertinib for Patients With PD-L1-positive EGFR-mutant Non-small Cell Carcinoma.

Background/Aim: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective for treating non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, higher tumor programmed death ligand-1 (PD-L1) expression is associated with a poor response to EGFR-TKIs, and information on the comparison between afatinib and osimertinib in PD-L1-positive EGFR-mutant NSCLC is scarce. Patients and Methods: We retrospectively analyzed data of patients with PD-L1-positive EGFR-mutant NSCLC to compare the effectiveness of afatinib and osimertinib. Results: A total of 177 patients were included in the study. The Cox proportion hazard model was adjusted for age, sex, performance status, EGFR mutation status, PD-L1 expression level, and brain metastasis, revealing that there was no significant difference in risk for progression [hazard ratio (HR)=0.99, 95% confidence interval (CI)=0.64-1.53] or death (HR=0.96, 95% CI=0.54-1.73) between afatinib and osimertinib. Conclusion: In conclusion, the EGFR-TKI treatment duration and overall survival after the treatment with afatinib or osimertinib were similar in patients with PD-L1-positive EGFR-mutant NSCLC in the present study.

Two Cases of Lung Abscess and Pleuritis in Severe COVID-19 Patients.

We report two patients who were treated with remdesivir, steroids, and tocilizumab for severe coronavirus disease 2019 (COVID-19) and developed lung abscesses and pleuritis. Although complications due to bacterial infections are often reported in COVID-19 patients, these severe infections are rare. Patients receiving tocilizumab are at a high risk of developing serious bacterial infections, and the diagnosis is often delayed because symptoms such as fever and elevated C-reactive protein levels are often minimal. The possibility of complications owing to severe bacterial infections should be considered when treating patients with severe COVID-19.

Computer based visualization of clot structures in extracorporeal membrane oxygenation and histological clot investigations for understanding thrombosis in membrane lungs.

Extracorporeal membrane oxygenation (ECMO) was established as a treatment for severe cardiac or respiratory disease. Intra-device clot formation is a common risk. This is based on complex coagulation phenomena which are not yet sufficiently understood. The objective was the development and validation of a methodology to capture the key properties of clots deposed in membrane lungs (MLs), such as clot size, distribution, burden, and composition. One end-of-therapy PLS ML was examined. Clot detection was performed using multidetector computed tomography (MDCT), microcomputed tomography (µCT), and photography of fiber mats (fiber mat imaging, FMI). Histological staining was conducted for von Willebrand factor (vWF), platelets (CD42b, CD62P), fibrin, and nucleated cells (4', 6-diamidino-2-phenylindole, DAPI). The three imaging methods showed similar clot distribution inside the ML. Independent of the imaging method, clot loading was detected predominantly in the inlet chamber of the ML. The µCT had the highest accuracy. However, it was more expensive and time consuming than MDCT or FMI. The MDCT detected the clots with low scanning time. Due to its lower resolution, it only showed clotted areas but not the exact shape of clot structures. FMI represented the simplest variant, requiring little effort and resources. FMI allowed clot localization and calculation of clot volume. Histological evaluation indicated omnipresent immunological deposits throughout the ML. Visually clot-free areas were covered with leukocytes and platelets forming platelet-leukocyte aggregates (PLAs). Cells were embedded in vWF cobwebs, while vWF fibers were negligible. In conclusion, the presented methodology allowed adequate clot identification and histological classification of possible thrombosis markers such as PLAs.

Gamified Crowdsourcing as a Novel Approach to Lung Ultrasound Data Set Labeling: Prospective Analysis.

BACKGROUND: Machine learning (ML) models can yield faster and more accurate medical diagnoses; however, developing ML models is limited by a lack of high-quality labeled training data. Crowdsourced labeling is a potential solution but can be constrained by concerns about label quality. OBJECTIVE: This study aims to examine whether a gamified crowdsourcing platform with continuous performance assessment, user feedback, and performance-based incentives could produce expert-quality labels on medical imaging data. METHODS: In this diagnostic comparison study, 2384 lung ultrasound clips were retrospectively collected from 203 emergency department patients. A total of 6 lung ultrasound experts classified 393 of these clips as having no B-lines, one or more discrete B-lines, or confluent B-lines to create 2 sets of reference standard data sets (195 training clips and 198 test clips). Sets were respectively used to (1) train users on a gamified crowdsourcing platform and (2) compare the concordance of the resulting crowd labels to the concordance of individual experts to reference standards. Crowd opinions were sourced from DiagnosUs (Centaur Labs) iOS app users over 8 days, filtered based on past performance, aggregated using majority rule, and analyzed for label concordance compared with a hold-out test set of expert-labeled clips. The primary outcome was comparing the labeling concordance of collated crowd opinions to trained experts in classifying B-lines on lung ultrasound clips. RESULTS: Our clinical data set included patients with a mean age of 60.0 (SD 19.0) years; 105 (51.7%) patients were female and 114 (56.1%) patients were White. Over the 195 training clips, the expert-consensus label distribution was 114 (58%) no B-lines, 56 (29%) discrete B-lines, and 25 (13%) confluent B-lines. Over the 198 test clips, expert-consensus label distribution was 138 (70%) no B-lines, 36 (18%) discrete B-lines, and 24 (12%) confluent B-lines. In total, 99,238 opinions were collected from 426 unique users. On a test set of 198 clips, the mean labeling concordance of individual experts relative to the reference standard was 85.0% (SE 2.0), compared with 87.9% crowdsourced label concordance (P=.15). When individual experts' opinions were compared with reference standard labels created by majority vote excluding their own opinion, crowd concordance was higher than the mean concordance of individual experts to reference standards (87.4% vs 80.8%, SE 1.6 for expert concordance; P<.001). Clips with discrete B-lines had the most disagreement from both the crowd consensus and individual experts with the expert consensus. Using randomly sampled subsets of crowd opinions, 7 quality-filtered opinions were sufficient to achieve near the maximum crowd concordance. CONCLUSIONS: Crowdsourced labels for B-line classification on lung ultrasound clips via a gamified approach achieved expert-level accuracy. This suggests a strategic role for gamified crowdsourcing in efficiently generating labeled image data sets for training ML systems.

Green spaces and respiratory, cardiometabolic, and neurodevelopmental outcomes: An individual-participant data meta-analysis of >35.000 European children.

Studies evaluating the benefits and risks of green spaces on children's health are scarce. The present study aimed to examine the associations between exposure to green spaces during pregnancy and early childhood with respiratory, cardiometabolic, and neurodevelopmental outcomes in school-age children. We performed an Individual-Participant Data (IPD) meta-analysis involving 35,000 children from ten European birth cohorts across eight countries. For each participant, we calculated residential Normalized Difference Vegetation Index (NDVI) within a 300 m buffer and the linear distance to green spaces (meters) during prenatal life and childhood. Multiple harmonized health outcomes were selected: asthma and wheezing, lung function, body mass index, diastolic and systolic blood pressure, non-verbal intelligence, internalizing and externalizing problems, and ADHD symptoms. We conducted a two-stage IPD meta-analysis and evaluated effect modification by socioeconomic status (SES) and sex. Between-study heterogeneity was assessed via random-effects meta-regression. Residential surrounding green spaces in childhood, not pregnancy, was associated with improved lung function, particularly higher FEV1 (ß = 0.06; 95 %CI: 0.03, 0.09 I2 = 4.03 %, p < 0.001) and FVC (ß = 0.07; 95 %CI: 0.04, 0.09 I2 = 0 %, p < 0.001) with a stronger association observed in females (p < 0.001). This association remained robust after multiple testing correction and did not change notably after adjusting for ambient air pollution. Increased distance to green spaces showed an association with lower FVC (ß = -0.04; 95 %CI: -0.07, -0.02, I2 = 4.8, p = 0.001), with a stronger effect in children from higher SES backgrounds (p < 0.001). No consistent associations were found between green spaces and asthma, wheezing, cardiometabolic, or neurodevelopmental outcomes, with direction of effect varying across cohorts. Wheezing and neurodevelopmental outcomes showed high between-study heterogeneity, and the age at outcome assessment was only associated with heterogeneity in internalizing problems.. This large European meta-analysis suggests that childhood exposure to green spaces may lead to better lung function. Associations with other respiratory outcomes and selected cardiometabolic and neurodevelopmental outcomes remain inconclusive.

Circulating tumor DNA to guide diagnosis and treatment of localized and locally advanced non-small cell lung cancer.

Liquid biopsy is a minimally invasive method for biomarkers detection in body fluids, particularly in blood, which offers an elevated and growing number of clinical applications in oncology. As a result of the improvement in the techniques for DNA analysis, above all next-generation sequencing (NGS) assays, circulating tumor DNA (ctDNA) has become the most informing tumor-derived material for most types of cancer, including non-small cell lung cancer (NSCLC). Although ctDNA concentration is higher in patients with advanced tumors, it can be detected even in patients with early-stage disease. Therefore, numerous clinical applications of ctDNA in the management of early-stage lung cancer are emerging, such as lung cancer screening, the identification of minimal residual disease (MRD), and the prediction of relapse before radiologic progression. Moreover, a high number of clinical trials are ongoing to better define the impact of ctDNA evaluation in this setting. Aim of this review is to offer a comprehensive overview of the most relevant implementations in using ctDNA for the management of early-stage lung cancer, addressing available data, technical aspects, limitations, and future perspectives.

Sophoricoside ameliorates methicillin-resistant Staphylococcus aureus-induced acute lung injury by inhibiting Bach1/Akt pathway.

BACKGROUND: The lack of effective treatments for methicillin-resistant Staphylococcus aureus (MRSA) infection, which often leads to severe acute lung injury (ALI), poses a grave threat to human life. Sophoricoside (SOP), an isoflavone glycoside abundant in the fruit of traditional Chinese herbal Sophora japonica l., showed anti-inflammatory effects against atopic dermatitis, allergic inflammation, and lipopolysaccharide-induced ALI. However, its effect and underlying mechanism on MRSA-induced ALI remain unclear. PURPOSE: The aim of this study is to assess the protective effect of SOP in MRSA-induced ALI and elucidate its underlying molecular mechanisms. METHODS: In vivo experiments were conducted using wild-type mice to establish MRSA-induced ALI mouse model, and the effects of SOP on ALI were evaluated by hematoxylin-eosin staining, flow cytometry, quantitative real-time polymerase chain reaction, and several biochemical indicators. Adoptive transfer experiments and BTB and CNC homology 1 knockout (Bach1-/-) mice were also utilized in this study. In vitro studies employed murine macrophages RAW264.7 cells, primary bone marrow-derived macrophages (BMDMs), and primary lung macrophages to explore the underlying molecular mechanisms. RESULTS: The administration of SOP ameliorated MRSA-induced ALI by improving pulmonary histological damages, reducing neutrophil infiltration, suppressing oxidative stress levels, and decreasing the expression of inflammatory cytokines. In isolation experiments with ALI mouse lung macrophages and macrophage adoptive transfer experiments, SOP prevented macrophage activation, thereby reducing the production of proinflammatory cytokines. In vitro experiments demonstrated that SOP decreased the expression of inflammatory mediators in lipoteichoic acid (LTA)-stimulated RAW264.7 cells, BMDMs, and primary lung macrophages. Additionally, SOP inhibited protein kinase B (Akt) phosphorylation and treatment with MK2206-a specific inhibitor of Akt-eliminated SOP's ability to suppress LTA-stimulated macrophage inflammation. Furthermore, stimulation with LTA or MRSA up-regulated Bach1 expression; however, deletion of Bach1 abolished the inhibitory effect of SOP on p-Akt activation as well as inflammation and ALI development. CONCLUSION: This study provides the first evidence that SOP effectively mitigates MRSA-induced ALI via suppressing macrophage activation through the inhibition of Bach1/Akt pathway. These findings highlight the potential of SOP as a novel therapeutic agent for treating MRSA-induced ALI.

The hidden link: How oral and respiratory microbiomes affect multiple sclerosis.

BACKGROUND: Extensive research has explored the role of gut microbiota in multiple sclerosis (MS). However, the impact of microbial communities in the oral cavity and respiratory tract on MS is an emerging area of investigation. PURPOSE: We aimed to review the current literature related to the nasal, oral, and lung microbiota in people with MS (PwMS). METHODS: We conducted a narrative review of clinical and preclinical original studies on PubMed that explored the relationship between the bacterial or viral composition of the nasal, lung, and oral microbiota and MS. Additionally, to find relevant studies not retrieved initially, we also searched for references in related review papers, as well as the references cited within the included studies. RESULTS AND CONCLUSIONS: Thirteen studies were meticulously reviewed in three sections; oral microbiota (n = 8), nasal microbiota (n = 3), and lung microbiota (n = 2), highlighting considerable alterations in the oral and respiratory microbiome of PwMS compared to healthy controls (HCs). Genera like Aggregatibacter and Streptococcus were less abundant in the oral microbiota of PwMS compared to HCs, while Staphylococcus, Leptotrichia, Fusobacterium, and Bacteroides showed increased abundance in PwMS. Additionally, the presence of specific bacteria, including Streptococcus sanguinis, within the oral microbiota was suggested to influence Epstein-Barr virus reactivation, a well-established risk factor for MS. Studies related to the nasal microbiome indicated elevated levels of specific Staphylococcus aureus toxins, as well as nasal glial cell infection with human herpes virus (HHV)-6 in PwMS. Emerging research on lung microbiome in animal models demonstrated that manipulating the lung microbiome towards lipopolysaccharide-producing bacteria might suppress MS symptoms. These findings open avenues for potential therapeutic strategies. However, further research is crucial to fully understand the complex interactions between the microbiome and MS. This will help identify the most effective timing, bacterial strains, and modulation techniques.

Pulmonary nodules and the psychological harm they can cause: A scoping review.

More than 1.6 million pulmonary nodules are diagnosed in the United States each year. Although the majority of nodules are found to be benign, nodule detection and the process of ruling out malignancy can cause patients psychological harm to varying degrees. The present study undertakes a scoping review of the literature investigating pulmonary nodule-related psychological harm as a primary or secondary outcome. Online databases were systematically searched to identify papers published through June 30, 2023, from which 19 publications were reviewed. We examined prevalence by type, measurement, associated factors, and behavioral or clinical consequences. Of the 19 studies reviewed, 11 studies investigated distress, anxiety (n = 6), and anxiety and depression (n = 4). Prevalence of distress was 24.0 %-56.7 %; anxiety 9.9 %-42.1 %, and 14.6 %-27.0 % for depression. A wide range of demographic and social characteristics and clinical factors were associated with nodule-related psychological harm. Outcomes of nodule-related harms included experiencing conflict when deciding about treatment or surveillance, decreased adherence to surveillance, adoption of more aggressive treatment, and lower health-related quality of life. Our scoping review demonstrates that nodule-related psychological harm is common. Findings provide evidence that nodule-related psychological harm can influence clinical decisions and adherence to treatment recommendations. Future research should focus on discerning between nodule-related distress and anxiety; identifying patients at risk; ascertaining the extent of psychological harm on patient behavior and clinical decisions; and developing interventions to assist patients in managing psychological harm for better health-related quality of life and treatment outcomes.

Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical. METHODS: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety. FINDINGS: Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1+ PD-1+ CD8+ stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3). CONCLUSIONS: These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation. FUNDING: This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL).