Association between protein intake, serum albumin and blood eosinophil in US asthmatic adults.

Background: Presently, numerous studies have indicated that protein consumption and levels of blood albumin serve as important biomarkers for a range of respiratory illnesses. However, there have been few investigations into the correlation between protein consumption, serum albumin, and asthma. Methods: Our analysis incorporated 2509 asthmatics from the 2011-2018 NHANES dataset. The investigation employed three linear regression models and XGBoost model to investigate the potential link between protein intake, serum albumin levels, and blood eosinophil counts (BEOC) in patients with asthma. The trend test, generalized additive model (GAM), and threshold effect model were utilized to validate this correlation. As well, we undertook stratified analyses to look at the correlation of serum albumin with BEOC among distinct populations. Results: In the univariable regression model, which did not account for any covariates, we observed a positive correlation between protein intake and BEOC. However, univariable and multivariable regression analyses all suggested a negative connection of serum albumin with BEOC in asthma populations. In Model C, which took into account all possible factors, BEOC dropped by 2.82 cells/uL for every unit increase in serum albumin (g/L). Additionally, the GAM and threshold effect model validated that serum albumin and BEOC showed an inverted U-shaped correlation. Conclusion: Our investigation discovered there was no independent link between asthmatics' protein intake and BEOC. However, we observed an inverted U-shaped relationship between serum albumin levels and BEOC, suggesting a possible relationship between the overall nutritional status of asthmatics and immune system changes. Our findings provide new directions for future research in the field of asthma management and therapy.

Case report: Endobronchial closure of postoperative bronchopleural fistula with embolization coil: a sandwich-like approach.

Background: Embolization Coil has been reported to effectively treat postoperative bronchopleural fistula (BPF). Little detailed information was available on computer tomography (CT) imaging features of postoperative BPF and treating procedures with pushable Embolization Coil. Objective: We aimed to specify the imaging characteristics of postoperative BPFs and present our experience treating them with the pushable Embolization Coil. Methods: Six consecutive patients (four males and two females aged 29-56 years) diagnosed with postoperative BPF receiving bronchoscopic treatment with the pushable Nester® Embolization Coil (Cook Medical, Bloomington, Indiana) were included in this single-center, retrospective study. Multiplanar reconstruction of multidetector CT scans was reviewed for the presence, location, size, and radiological complications of each BPF, including air collection, pneumothorax, bronchiectasis, and chest tube. Using standardized data abstraction forms, demographic traits and clinical outcomes were extracted from the medical files of these patients. Results: The underlying diseases for lung resection surgery were pulmonary tuberculosis (n = 3), lung adenocarcinoma (n = 2), and pulmonary aspergillosis (n = 1). All patients had air or air-fluid collection with chest tubes on radiological findings. Multiplanar reconstruction identified the presence of postoperative BPF in all patients. Five fistulas were central, located proximal to the main or lobar bronchus, while one was peripheral, distant from the lobar bronchus. Fistula sizes ranged from 0.8 to 5.8 mm. Subsequent bronchoscopy and occlusion testing confirmed fistula openings in the bronchial stump: right main bronchus (n = 1), right upper lobe (n = 2), and left upper lobe (n = 3). The angioplasty catheter-based procedure allows precise fistula occlusion "like a sandwich" with the pushable Embolization Coil. Five patients with BPF sizes ranging from 0.8 to 1.5 mm were successfully treated with a pushable Embolization Coil, except for one with a BPF size of 5.8 mm. No adverse events or complications were observed throughout follow-up, ranging from 29 to 1,307 days. Conclusion: The pushable Nester® Embolization Coil seems a minimally invasive, cost-effective, and relatively easy-to-perform bronchoscopic treatment for postoperative BPF with a size less than 2 mm. Further studies are required to ensure the use of pushable Embolization Coil in treating postoperative BPF.

Relationship between triglyceride-glucose index and blood eosinophils among asthmatic individuals in the USA.

BACKGROUND: Presently, the majority of investigations primarily evaluate the correlation between triglyceride-glucose index (TyGI) with lung diseases, such as asthma. However, they did not delve into the correlation between TyGI and inflammatory responses related to the disease. Few studies have explored the association between TyGI and blood eosinophil count (BEOC). Thus, National Health and Nutrition Examination Survey (NHANES) data were used in this study to evaluate the correlation between TyGI and BEOC in individuals with asthma. METHODS: This study investigated 3902 individuals with asthma. Linear regression analysis was performed to investigate the association between TyGI and BEOC in patients with asthma. Subsequently, the GAM and threshold effect models were used to validate the presence of either a nonlinear or linear association between TyGI and BEOC. Finally, stratified analyses were conducted to ascertain the correlations between different subgroups. RESULTS: Four linear regression models confirmed a positive linear correlation between TyGI and BEOC in patients with asthma. In Model D, which controlled for all covariates, BEOC increased by 12.44 cells/uL for every extra unit of TyGI. The GAM and threshold effect models further verified the positive linear correlation between TyGI and BEOC. The XGBoost model indicated that the six most significant variables influencing BEOC, in order of relative importance, were age, cholesterol level, body mass index (BMI), poverty-to-income ratio (PIR), BNEUC, and TyGI. CONCLUSIONS: In patients with asthma, the study discovered a linear positive correlation between TyGI and BEOC. This indicates a potential connection between TyGI and alterations in the immune status of individuals with asthma, which may help detect abnormalities in a timely manner and provide a reference for clinical decision-making. This study offers fresh insights for the future exploration of the management and treatment of asthma.

The novel DNA methylation marker FIBIN suppresses non-small cell lung cancer metastasis by negatively regulating ANXA2.

OBJECTIVES: The clinical T1 stage solid lung cancer with metastasis is a serious threat to human life and health. In this study, we performed RNA sequencing on T1 advanced-stage lung cancer and adjacent tissues to identify a novel biomarker and explore its roles in lung cancer. METHODS: Quantitative reversed-transcription PCR, reverse transcription PCR and Western blot, MSP and Methtarget were utilized to evaluate FIBIN expression levels at both the transcriptional and protein levels as well as its methylation status. Differential target protein was evaluated for relative and absolute quantitation by isobaric tags. Co-IP was performed to detect the interactions between target protein. Precise location and expression levels of target proteins were revealed by immunofluorescence staining and component protein extraction using specific kits, respectively. RESULTS: We reported that FIBIN was frequently silenced due to promoter hypermethylation in lung cancer. Additionally, both in vitro and in vivo experiments confirmed the significant anti-proliferation and anti-metastasis capabilities of FIBIN. Mechanistically, FIBIN decreased the nuclear accumulation of ß-catenin by reducing the binding activity of GSK3ß with ANXA2 while promoting interaction between GSK3ß and ß-catenin. CONCLUSION: Our findings firstly identify FIBIN is a tumor suppressor, frequently silenced due to promoter hypermethylation. FIBIN may serve as a predictive biomarker for progression or metastasis among early-stage lung cancer patients.

Recombinant Slit2 attenuates tracheal fibroblast activation in benign central airway obstruction by inhibiting the TGF-ß1/Smad3 signaling pathway.

Airway fibrosis is among the pathological manifestations of benign central airway obstruction noted in the absence of effective treatments and requires new drug targets to be developed. Slit guidance ligand 2-roundabout guidance receptor 1 (Slit2-Robo1) is involved in fibrosis and organ development. However, its significance in airway fibrosis has not yet been reported. The study explored how the recombinant protein Slit2 functions in transforming growth factor-ß1 (TGF-ß1)-mediated airway fibrosis in vivo and in vitro. In this study, Slit2 expression initially increased in the tracheal granulation tissues of patients with tracheobronchial stenosis but decreased in the fibrotic tissue. In primary rat tracheal fibroblasts (RTFs), recombinant Slit2 inhibited the expression of extracellular matrices such as Timp1, α-SMA, and COL1A2, whereas recombinant TGF-ß1 promoted the expression of Robo1, α-SMA, and COL1A2. Slit2 and TGF-ß1 played a mutual inhibitory role in RTFs. Slit2 supplementation and Robo1 downregulation inhibited excessive extracellular matrix (ECM) deposition induced by TGF-ß1 in RTFs via the TGF-ß1/Smad3 pathway. Ultimately, exogenous Slit2 and Robo1 knockdown-mediated attenuation of airway fibrosis were validated in a trauma-induced rat airway obstruction model. These findings demonstrate that recombinant Slit2 alleviated pathologic tracheobronchial healing by attenuating excessive ECM deposition. Slit2-Robo1 is an attractive target for further exploring the mechanisms and treatment of benign central airway obstruction.

Endobronchial optical coherence tomography helps to estimate the cartilage damage of the central airway in TBTB patients.

Purpose: At present, there are few examination methods used to evaluate tracheobronchial cartilage damage. In our study, we explored whether endobronchial optical coherence tomography (EB-OCT) can be used to estimate central airway cartilage damage in tracheobronchial tuberculosis (TBTB) patients. Methods: In our study, we used the OCTICS Imaging system to perform EB-OCT scanning for TBTB patients. The thickness of the central airway wall and cartilage was measured by the OCTICS software system workstation. Results: There were 102 TBTB patients included in our study cohort. Their EB-OCT images of the central airway cartilage showed that abnormal cartilage manifests as thinning of the cartilage, cartilage damage, cartilage destruction, and even cartilage deficiency. The cartilage morphology becomes irregular and discontinuous. Some parts of the cartilage become brighter in grayscale. The intima of the cartilage is thickened and discontinuous, and the boundary with submucosa and mucosa is unclear. Conclusion: Our study conducted EB-OCT examination of the central airway cartilage of TBTB patients in vivo for the first time. EB-OCT helps to estimate the cartilage damage of the central airway in TBTB patients to some extent.

NLRP3-inflammasome inhibition by MCC950 attenuates cardiac and pulmonary artery remodelling in heart failure with preserved ejection fraction.

AIMS: The purpose of this study was to evaluate the role of the NLRP3-inflammasome in heart failure with preserved ejection fraction (HFpEF). MAIN METHODS: Serum inflammatory cytokines were detected in patients with heart failure. Correlation analysis was performed to investigate the relationship between serum inflammatory cytokines and left ventricular diastolic function. A 'two-hit' (metabolic stress and mechanical stress) mouse model of HFpEF was established. Furthermore, MCC950 was used to determine the role of NLRP3-inflammasome inhibition in cardiac and pulmonary artery remodelling in HFpEF mice. KEY FINDINGS: Compared with heart failure patients with reduced ejection fraction, patients with HFpEF have significantly elevated serum inflammatory cytokine levels. Serum NLRP3 and interleukin-1ß levels were positively correlated with the diastolic function of HFpEF. In the HFpEF mouse model, the inhibition of the NLRP3-inflammasome by MCC950 improved exercise intolerance, glucose intolerance, and left ventricular diastolic function, but had no significant effect on systolic function. Meanwhile, MCC950 attenuated the release of inflammatory cytokines, cardiomyocyte hypertrophy and cardiac fibrosis. Mechanistically, the potential protective effects of MCC950 are achieved by inhibiting activation of the NLRP3-IL-1ß pathway and cascade expansion of downstream inflammatory cytokines. Additionally, the inhibition of NLRP3-inflammasome by MCC950 reduced pulmonary artery pressure and improved pulmonary artery remodelling in HFpEF. SIGNIFICANCE: The NLRP3-inflammasome plays a considerable role in inflammation and cardiac and pulmonary artery remodelling in HFpEF by activating the cascade reaction of inflammatory cytokines. This study is the first to comprehensively elucidate the role of the NLRP3-inflammasome in HFpEF, and will provide reference for future study.

Imaging Progression Under Low Respiratory Viral Load of SARS-CoV-2 Omicron Variant Infection: A Retrospective Study in China.

Purpose: To investigate the computed tomography (CT) findings of SARs-CoV-2 Omicron variant in relation to respiratory viral loads determined by cycle threshold values in reverse-transcription polymerase chain reaction (RT-PCR). Materials and Methods: From October 2022 to November 2022, 74 hospitalized patients with Omicron were included in this retrospective study. The radiological features, CT involvement scores in relation to the respiratory viral load, and factors associated with imaging progression (IP) after the RT-PCR results turned negative were analyzed. Results: The most common CT patterns of Omicron were multiple round-like or patchy ground-glass opacity (GGO) or mixed GGO in the peripheral or diffuse areas. The grading of CT involvement scores exhibited an inverse pattern compared to viral loads from day 1 to day 8 and from day 13 to day 20 after diagnosis. Among the 65 patients with complete imaging data, 45 (69.23%) showed IP with clinical warning indicators of disease exacerbation negative in 34 and positive in 11. Patients with IP were older than those with non-IP (NIP); the erythrocyte sedimentation rates, procalcitonin levels, and D-dimer levels on admission of patients with IP were significantly higher than those of patients with NIP, whereas the immunoglobulin (Ig) G antibody level on admission and CT involvement score on initial CT of patients with IP were significantly lower than those of patients with NIP (all P < 0.05). Conclusion: For patients with Omicron, the IP of lung abnormalities is common when the viral load decreases. Under these circumstances, paying attention to clinical warming indicators of disease progression may contribute to better patient management and the mitigation of severe pneumonia.

MXene-incorporated C60NPs and Au@Pt with dual-electric signal outputs for accurate detection of Mycobacterium tuberculosis ESAT-6 antigen.

Rapid and effective detection of Mycobacterium tuberculosis (MTB) is the crux of minimizing tuberculosis (TB) spread. Consequently, a new electrochemical aptasensor based on dual-signal output for ultrasensitive detection of MTB early secreted antigenic target 6 (ESAT-6) antigen was developed. Especially, a new nanocomposite MXene/C60NPs/Au@Pt was synthesized for signal generation and amplification. In this biosensing architecture, dual independent signal outputs were achieved by coupling the electrochemical redox activity of fullerene nanoparticles (C60NPs) with the effective electrocatalytic activity of Au@Pt nanoparticles. MXene possesses a large specific surface area, allowing densely loaded of these two electroactive materials, further improved sensing capability. In addition, specific ESAT-6 antigen binding aptamers were attached to Au@Pt to create the tracer label. With a typical sandwich format along with the introduction of the gold nanoparticle-loaded molybdenum disulfide (MoS2-Au) as the sensing interface, the limit of detection (LOD) of the proposed aptasensor was 2.88 fg mL-1 (DPV measurement) and 13.50 fg mL-1 (IT measurement), respectively, with a broad linear range of 100 fg mL-1 to 50 ng mL-1. Significantly, it exhibited better specificity and accuracy with a sensitivity of 97.5% and a specificity of 96.7% to distinguish healthy donors, other lung diseases and TB patients compared to commercial ELISA assay, holding a promising prospect in clinical diagnosis.

Relationship between serum iron and blood eosinophil counts in asthmatic adults: data from NHANES 2011-2018.

Background: So far, quite a few studies have revealed that systemic iron levels are related to asthmatic inflammatory reactions. And most studies have focused on the correlation between systemic iron levels and asthma, with inconsistent findings. Yet, few studies have investigated the connection between serum iron and blood eosinophil counts. Hence, we have explored the connection between serum iron and blood eosinophil counts in asthmatics by utilizing data from NHANES. Methods: A total of 2549 individuals were included in our study after screening NHANES participants from 2011 to 2018. The linear regression model and XGBoost model were used to discuss the potential connection. Linear or nonlinear association was further confirmed by the generalized additive model and the piecewise linear regression model. And we also performed stratified analyses to figure out specific populations. Results: In the multivariable linear regression models, we discovered that serum iron levels were inversely related to blood eosinophil counts in asthmatic adults. Simultaneously, we found that for every unit increase in serum iron (umol/L), blood eosinophil counts reduced by 1.41/uL in model 3, which adjusted for all variables excluding the analyzed variables. Furthermore, the XGBoost model of machine learning was applied to assess the relative importance of chosen variables, and it was determined that vitamin C intake, age, vitamin B12 intake, iron intake, and serum iron were the five most important variables on blood eosinophil counts. And the generalized additive model and piecewise linear regression model further verify this linear and inverse association. Conclusion: Our investigation discovered that the linear and inverse association of serum iron with blood eosinophil counts in asthmatic adults, indicating that serum iron might be related to changes in the immunological state of asthmatics. Our work offers some new thoughts for next research on asthma management and therapy. Ultimately, we hope that more individuals become aware of the role of iron in the onset, development, and treatment of asthma.

Azvudine and mortality in patients with coronavirus disease 2019: A retrospective cohort study.

OBJECTIVES: Several studies have found that azvudine (FNC) can inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication both in vivo and in vitro. However, the effect of FNC on the risk of death in patients with coronavirus disease 2019 (COVID-19) is unclear. This study aims to investigate the effect of FNC on the risk of death in patients with coronavirus disease 2019 (COVID-19). METHODS: Charts of consecutive patients hospitalized at five hospitals in Chongqing with confirmed COVID-19. The primary outcome of the study was 28-day mortality. Secondary outcomes were: ICU admission rates, length of hospital and ICU stay, and also the range of mechanical ventilation days when admission. We compared primary outcome in patients who received FNC with those in patients who did not, using a multivariable model with inverse probability weighting according to the propensity score. RESULTS: We included 1,110 patients in our study cohort. Of the 236 patients treated with FNC, 30 died within 28 days (12.7%), and of the 874 patients not treated with FNC, 206 died within 28 days (23.6%). In the crude, unadjusted analysis, a significant beneficial effect of FNC in terms of the 28-day mortality (OR 0.472, 95% CI 0.312-0.714; p < 0.001) in the overall population was detected. The adjusted odds ratio by multivariate analysis was (OR 0.498, 95% CI 0.287-0.864; p = 0.013). In the multivariate analysis with inverse probability weighting according to the propensity score, a significantly beneficial effect of FNC in terms of the 28-day mortality was further confirmed (OR 0.754, 95% CI 0.614-0.925; p = 0.007). Moreover, multivariable propensity-score analyses with matching also yielded similar results (OR 0.438, 95% CI 0.246-0.778; p = 0.005). CONCLUSION: Our results reveal that in patients with COVID-19, FNC administration was associated with a significantly reduced 28-day mortality.

GATA6 promotes fibrotic repair of tracheal injury through NLRP3 inflammasome-mediated epithelial pyroptosis.

Tracheal injury is a challenging emergency condition that is characterized by the abnormal repair of the trachea. GATA6, a well-established transcription factor, plays a crucial role in tissue injury and epithelial regenerative repair. This study aims to evaluate the role of GATA6 in NF-κB-mediated NLRP3 inflammasome activation and pyroptosis after tracheal injury. Tracheal tissues and serum samples were collected from clinical patients and a rat model of tracheal injury. Upon GATA6 knockdown or overexpression, BEAS-2B and rat tracheal epithelial (RTE) cells were treated with lipopolysaccharides and nigericin before being co-cultured with primary tracheal fibroblasts. The changes of NLRP3 inflammasome activation and pyroptosis and their underlying mechanisms were detected. Additionally, the role of GATA6 downregulation in tracheal injury was verified in rats. GATA6 expression and NLRP3 inflammasome activation were upregulated following tracheal injury in the epithelium of granulation tissues. GATA6 silencing inhibited NLRP3 priming, NLRP3 inflammasome activation, and pyroptosis in BEAS-2B and RTE cells. Mechanistically, GATA6 was determined to have bound to the promoter region of NLRP3 and synergistically upregulated NLRP3 promoter activity with NF-κB. Furthermore, GATA6 overexpression promoted epithelial-mesenchymal transition via modulating the NF-κB/NLRP3 pathway. Epithelial NLRP3 inflammasome activation triggered ECM production in fibroblasts, which was suppressed by GATA6 knockdown and induced by GATA6 overexpression. Finally, the downregulation of GATA6 alleviated NLRP3 inflammasome-mediated pyroptosis induced by tracheal injury in rats, thereby reducing tracheal stenosis, inflammation, and fibrosis. GATA6 promotes fibrotic repair in tracheal injury through NLRP3 inflammasome-mediated epithelial pyroptosis, making it a potential biological therapeutic target for tracheal injury.

Lower geriatric nutritional risk index is associated with a higher risk of all-cause mortality in patients with chronic obstructive pulmonary disease: a cohort study from the National Health and Nutrition Examination Survey 2013-2018.

OBJECT: Malnutrition negatively affects patients with chronic obstructive pulmonary disease (COPD). This study aimed to explore the potential association between malnutrition, as defined by the Geriatric Nutritional Risk Index (GNRI), and all-cause mortality in patients with COPD using the National Health and Nutrition Examination Survey (NHANES). METHOD: The data of 579 adults with COPD during NHANES 2013-2018 were analysed. Each patient was assigned to one of the two groups according to GNRI values: normal nutritional status (GNRI>98) and malnutrition status (GNRI≤98). Survival curves and Cox regressions were applied to evaluate the association between nutritional status and mortality. RESULTS: Overall, the mean age was 63.4±0.5 years, and 53.9% of the patients were women. The prevalence of malnutrition was 6.6%, and the Kaplan-Meier curves for all-cause mortality according to nutritional status showed that malnutrition was associated with a higher incidence of all-cause mortality. The Cox regression analysis found that in the unadjusted model, the HR was 2.30 (95% CI 1.24 to 4.27, p=0.01). In the fully adjusted model, the adjusted HR was 2.47 (95% CI 1.36 to 4.5, p=0.003). Furthermore, subgroup analysis revealed that the risk of death due to malnutrition increased more than threefold in the low education and cancer subgroups. CONCLUSION: A low GNRI was an independent risk factor for all-cause mortality in patients with COPD.

Deep learning predicts malignancy and metastasis of solid pulmonary nodules from CT scans.

In the clinic, it is difficult to distinguish the malignancy and aggressiveness of solid pulmonary nodules (PNs). Incorrect assessments may lead to delayed diagnosis and an increased risk of complications. We developed and validated a deep learning-based model for the prediction of malignancy as well as local or distant metastasis in solid PNs based on CT images of primary lesions during initial diagnosis. In this study, we reviewed the data from multiple patients with solid PNs at our institution from 1 January 2019 to 30 April 2022. The patients were divided into three groups: benign, Ia-stage lung cancer, and T1-stage lung cancer with metastasis. Each cohort was further split into training and testing groups. The deep learning system predicted the malignancy and metastasis status of solid PNs based on CT images, and then we compared the malignancy prediction results among four different levels of clinicians. Experiments confirmed that human-computer collaboration can further enhance diagnostic accuracy. We made a held-out testing set of 134 cases, with 689 cases in total. Our convolutional neural network model reached an area under the ROC (AUC) of 80.37% for malignancy prediction and an AUC of 86.44% for metastasis prediction. In observer studies involving four clinicians, the proposed deep learning method outperformed a junior respiratory clinician and a 5-year respiratory clinician by considerable margins; it was on par with a senior respiratory clinician and was only slightly inferior to a senior radiologist. Our human-computer collaboration experiment showed that by simply adding binary human diagnosis into model prediction probabilities, model AUC scores improved to 81.80-88.70% when combined with three out of four clinicians. In summary, the deep learning method can accurately diagnose the malignancy of solid PNs, improve its performance when collaborating with human experts, predict local or distant metastasis in patients with T1-stage lung cancer, and facilitate the application of precision medicine.

High density lipoprotein-cholesterol is inversely associated with blood eosinophil counts among asthmatic adults in the USA: NHANES 2011-2018.

Background: A growing number of research strongly suggest that metabolic syndrome and dyslipidemia contribute to the establishment of a pro-inflammatory state in asthma, according to accumulating data. However, the majority of recent research has focused on the association between lipids and asthma in children and adolescents, with contradictory findings. Consequently, we analyzed the relationship between serum lipid and blood eosinophil counts using data from the NHANES in the USA. Methods: After screening the individuals from the 2011 to 2018 NHANES survey, a total of 2,544 out of 39156 participants were eligible for our study. The potential association was discussed using the linear regression model, XGBoost algorithm model, generalized additive model, and two-piecewise linear regression model. In addition, we ran stratified analysis to identify specific demographics. Results: After adjusting for covariates, the result indicated that blood eosinophil counts decreased by 45.68 (-68.56, -22.79)/uL for each additional unit of HDL-C (mmol/L). But serum LDL-C, total cholesterol or triglyceride was not correlated with blood eosinophil counts. Furthermore, we used machine learning of the XGBoost model to determine LDL-C, age, BMI, triglyceride, and HDL-C were the five most critical variables in the blood eosinophil counts. The generalized additive model and two-piecewise linear regression model were used to further identify linear relationship between the serum HDL-C and blood eosinophil counts. Conclusions: Our study elucidated a negative and linear correlation between serum HDL-C and blood eosinophil counts among American asthmatic adults, suggesting that serum HDL-C levels might be associated with the immunological condition of asthmatic adults. There was no correlation between serum LDL-C, total cholesterol, or triglyceride levels and blood eosinophil counts.

Central nervous system efficacy of rezivertinib (BPI-7711) in advanced NSCLC patients with EGFR T790M mutation: A pooled analysis of two clinical studies.

BACKGROUND: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) which revealed the systematic and central nervous system (CNS) antitumor activities for EGFR T790M-mutated advanced NSCLC in previous clinical studies and is further analyzed here. METHODS: Eligible patients from the previous phase I and phase IIb studies of rezivertinib were included for pooled analysis. Post-progressive patients who received a prescribed dosage (≥180 mg) of rezivertinib orally once daily were included in full analysis set (FAS), while those with stable, asymptomatic CNS lesions, including measurable and non-measurable ones at baseline were included in CNS full analysis set (cFAS). Patients with measurable CNS lesions were included in CNS evaluable for response set (cEFR). BICR-assessed CNS objective response rate (CNS-ORR), CNS disease control rate (CNS-DCR), CNS duration of response (CNS-DoR), CNS progression-free survival (CNS-PFS), and CNS depth of response (CNS-DepOR) were evaluated. RESULTS: 355 patients were included in FAS, among whom 150 and 45 patients were included in cFAS and cEFR. This pooled analysis showed the CNS-ORR was 32.0% (48/150; 95% CI: 24.6-40.1%) and the CNS-DCR was 42.0% (63/150; 95% CI: 34.0-50.3%) in cFAS, while that in cEFR were 68.9% (31/45; 95% CI: 53.4-81.8%) and 100% (45/45; 95% CI: 92.1-100.0%). In cEFR, the median CNS-DepOR and the mean of CNS-DepOR were -52.0% (range: -100.0 to 16.1%) and -46.8% (95% CI: -55.5 to -38.1%). In cFAS, the median CNS-DoR and CNS-PFS were 13.8 (95% CI: 9.6-not calculable [NC]) and 16.5 (95% CI: 13.7-NC) months. CONCLUSIONS: Rezivertinib demonstrated encouraging clinical CNS efficacy among advanced NSCLC patients with EGFR T790M mutation and CNS metastases.

Association between serum folate levels and blood eosinophil counts in American adults with asthma: Results from NHANES 2011-2018.

Background: To date, many researches have investigated the correlation of folate and asthma occurrence. Nevertheless, few studies have discussed whether folate status is correlated with dis-ease severity, control or progression of asthma. So, we explored the correlation of serum folate and blood eosinophil counts in asthmatic adults to gain the role of folate in the control, progression, and treatment of asthma. Methods: Data were obtained from the 2011-2018 NHANES, in which serum folate, blood eosinophils, and other covariates were measured among 2332 asthmatic adults. The regression model, XGBoost algorithm model, and generalized linear model were used to explore the potential correlation. Moreover, we conducted stratified analyses to determine certain populations. Results: Among three models, the multivariate regression analysis demonstrated serum folate levels were negatively correlated with blood eosinophil counts among asthmatic adults with statistical significance. And we observed that blood eosinophil counts decreased by 0.20 (-0.34, -0.06)/uL for each additional unit of serum folate (nmol/L) after adjusting for confounders. Moreover, we used the XGBoost Algorithm model to identify the relative significance of chosen variables correlated with blood eosinophil counts and observed the linear relationship between serum folate levels and blood eosinophil counts by constructing the generalized linear model. Conclusions: Our study indicated that serum folate levels were inversely associated with blood eosinophil counts in asthmatic adult populations of America, which indicated serum folate might be correlated with the immune status of asthmatic adults in some way. We suggested that serum folate might affect the control, development, and treatment of asthma. Finally, we hope more people will recognize the role of folate in asthma.