The prognostic impact of severe grade immune checkpoint inhibitor related pneumonitis in non-small cell lung cancer patients.

Objective: To compare the prognostic differences between non-small cell lung cancer (NSCLC) patients with mild and severe checkpoint inhibitor-associated pneumonitis (CIP), and explore the causes of death and prognostic risk factors in NSCLC patients with severe CIP. Methods: A retrospective study of a cohort of 116 patients with unresectable stage III or IV NSCLC with any grade CIP from April 2016 to August 2022 were conducted. To analyze the clinical characteristics of patients with different CIP grades, patients were divided into mild CIP group (grade 1-2, n=49) and severe CIP group (grade 3-5, n=67) according to the grade of CIP. To explore the OS-related risk factors in the severe CIP group, the patients were divided into a good prognosis (GP) group (≥ median OS, n=30) and a poor prognosis (PP) group (< median OS, n=37) based on whether their overall survival (OS) were greater than median OS. Baseline clinical and laboratory data were collected for analysis. Results: The median OS of all NSCLC patients combined with CIP was 11.4 months (95%CI, 8.070-16.100), The median OS for mild CIP and severe CIP was 22.1 months and 4.4 months respectively (HR=3.076, 95%CI, 1.904-4.970, P<0.0001). The results showed that the most common cause of death among severe CIP patients in the PP group was CIP and the most common cause in the GP group was tumor. The univariate regression analysis showed that suspension of antitumor therapy was a risk factor for poor prognosis (OR=3.598, 95%CI, 1.307-9.905, p=0.013). The multivariate logistic regression analysis showed that suspension of anti-tumor therapy (OR=4.24, 95%CI, 1.067-16.915, p=0.040) and elevated KL-6 (OR=1.002, 95%CI, 1.001-1.002, p<0.001) were independent risk factors for poor prognosis. Conclusion: In conclusion, patients with severe CIP had a poor prognosis, especially those with elevated KL-6, and the main cause of death is immune checkpoint inhibitor-associated pneumonitis complicated with infection. In addition, anti-tumor therapy for severe CIP patients should be resumed in time and should not be delayed for too long.

Rapid removal of Rhodamine B by phosphoric acid-modified activated carbon derived from rape straw.

A series of activated carbon was obtained from rape straw by chemical modification with phosphoric acid (H3PO4). The activated carbon was characterized and the adsorption capacity for Rhodamine B (RhB) from water was analysed. The SEM images showed that PRC-40 is a porous material and the BET analysis revealed a high surface area of 1720 m2/g with the coexistence of micropores and mesopores. The FTIR spectra determined the presence of oxygenated functional groups at its surface. The XPS spectra revealed that the content of carboxyl and metaphosphate groups in the modified activated carbon significantly increased, and this is conducive to the adsorption reaction. The XRD pattern showed the amorphous nature of carbon. The effect of significant parameters, such as the concentration of H3PO4 for modification and pH value, has been discussed. The kinetic data showed that the pseudo-second-order model is predominant. Besides, the Langmuir model was compatible well with the equilibrium data, and the maximum adsorption capacity of the activated carbon modified by H3PO4 was 2882.84 mg/g. Therefore, agricultural waste and rape straw can be used to prepare effective adsorbents for the application with the removal of dye from wastewater.

Identification of Chinese baijiu from the same brand based on a graphene quantum dots fluorescence sensing array.

The identification of Chinese baijiu is crucial to regulating the international market and maintaining legitimate rights, as the popularity, influence and awareness of baijiu are growing. A graphene quantum dot (GQD) based fluorescence sensor array is designed in this paper. Upon using only GQDs as a single sensing element, combining three different solvents improves the sensing array's detection sensitivity while simplifying material preparation and experimental detection. Adding organic substances creates intermolecular forces between the GQDs and the solvent, causing the fluorescence intensity to change. The sensor array was able to distinguish 21 types of organic matter, different ratios of quaternary mixed organic materials and 17 types of baijiu of the same brand. It also showed excellent performance in the detection of species in blind samples, with the machine learning algorithm successfully distinguishing baijiu from five other distilled spirits. The experiment provides guidance for the practical application of GQDs and provides a simple but effective reference for sensor arrays to detect baijiu.

Successful management of Epstein­Barr virus­associated severe checkpoint inhibitor­related pneumonitis: A case report.

A novel current treatment, immunotherapy, is normally effective for pulmonary lymphoepithelial carcinoma (pLELC). However, it is frequently accompanied by responses such as immune checkpoint inhibitor-associated pneumonitis (CIP), a rare immune adverse reaction that may be fatal in severe cases. pLELC is known to be linked to Epstein-Barr virus (EBV), while associations between EBV and CIP in clinical settings have rarely been reported. A 57-year-old male patient with pLELC presented at our hospital with cough, expectoration, fever and dyspnea following his third course of immunotherapy at another hospital. Diagnosis of grade 4 CIP was confirmed. Simultaneously, a rapid increase in the EBV titer and response of CIP to corticosteroids were observed. The corticosteroids and antiviral drugs were then increased. In spite of his severe condition, the patient recovered within eight days. After discontinuing antiviral drugs, chest computed tomography indicated rapid lesion progression and significantly increased bilateral multiple metastases. To our knowledge, the present study was the first to report a case of CIP caused by EBV during immune checkpoint inhibitor treatment. It indicates that EBV may be associated with CIP development. As immunotherapy has off-target effects, clinicians should remain aware of combined corticosteroids and antivirals in similar cases.

Organic acid-induced triple fluorescent emission carbon quantum dots identification of distilled liquor.

An acid-sensitive carbon dot fluorescence sensing array was investigated for the differentiated recognition of distilled spirits. Due to the electrostatic interactions between CDs and organic acids, organic acids affect the protonation and fluorescence properties of CDs, which in turn modify the CDs triple fluorescence emission. The regular linear variation of the fluorescence sensor was found under acidic conditions (3.0 < pH < 6.2). A comprehensive study of acids with selectivity, different concentrations (0.1 mM, 1 mM, 10 mM, 40 mM), different types (8 species) and mixed acids (formic acid and acetic acid), and good quantification capability for acetic acid (0.01-1 mM). Demonstrating good recognition ability of the sensor array for complex analyte. On this basis, the fluorescence sensor array was applied to the classification and recognition of liquors. LDA has realized the identification of 16 kinds of Baijiu and 21 kinds of distilled liquors with an accuracy of 100%.

A Risk-Scoring Model for Severe Checkpoint Inhibitor-Related Pneumonitis: A Case-Control Study.

BACKGROUND AND OBJECTIVE: Checkpoint inhibitor-related pneumonitis (CIP) is one of the most common serious and fatal adverse events associated with immune checkpoint inhibitors (ICIs). The study sought to identify risk factors of all-grade and severe CIP and to construct a risk-scoring model specifically for severe CIP. METHODS: This observational, retrospective case-control study involved 666 lung cancer patients who received ICIs between April 2018 and March 2021. The study analyzed patient demographic, preexisting lung diseases, and the characteristics and treatment of lung cancer to determine the risk factors for all-grade and severe CIP. A risk score for severe CIP was developed and validated in a separate patient cohort of 187 patients. RESULTS: Among 666 patients, 95 patients were afflicted with CIP, of which 37 were severe cases. Multivariate analysis revealed age ≥ 65 years, current smoking, chronic obstructive pulmonary disease, squamous cell carcinoma, prior thoracic radiotherapy, and extra-thoracic radiotherapy during ICI were independently associated with CIP events. Five factors, emphysema (odds ratio [OR] 2.87), interstitial lung disease (OR 4.76), pleural effusion (OR 3.00), history of radiotherapy during ICI (OR 4.30), and single-agent immunotherapy (OR 2.44) were independently associated with severe CIP and were incorporated into a risk-score model (score ranging 0-17). The area under the model receiver operating characteristic curve for the model was 0.769 in the development cohort and 0.749 in the validation cohort. CONCLUSIONS: The simple risk-scoring model may predict severe CIP in lung cancer patients receiving ICIs. For patients with high scores, clinicians should use ICIs with caution or strengthen the monitoring of these patients.

Case report: Spontaneous remission in lung carcinoma with a late relapse after adjuvant immunotherapy: Exceptional tumor micro-environment.

Spontaneous remission (SR) of local recurrence after adjuvant immunotherapy has rarely been reported, and the underlying mechanism is poorly understood. Herein, we reported a patient with stage cT2aN2M0 squamous cell lung carcinoma who received neoadjuvant and adjuvant treatment with nivolumab plus chemotherapy. The patient experienced a late relapse in the subcarinal lymph node seven months after the last dosage of treatment but achieved SR in the next three months without additional antitumor therapy. The complete response lasted for eleven months and counting. Notably, high copies of pathogenic microorganisms were detected in the patient's bronchoalveolar lavage fluid along with the recurrence but disappeared after SR. The patient also experienced a lymph node puncture-induced fever but had no other symptoms. A longitudinal analysis of infiltrated immune cells in the recurrent lymph node was performed by multiplex immunofluorescence and whole transcriptome sequencing, which revealed that CD8+ T cells were recruited during the initial relapse, specifically in the stromal area, then migrated into the tumor tissue, and continued to increase after elimination of tumor cells. Meanwhile, the initial recruitment of CD8+ T cells was coupled with a higher proportion of B cells, and the abundant neutrophil population was synchronous with the infiltration of CD8+ T cells into tumor cells. This is the first report on an Non-small cell lung cancer (NSCLC) patient with a late relapse after adjuvant immune checkpoint inhibitor (ICI) therapy who achieved SR. Our case highlights the complexity and plasticity of antitumor immunity and is expected to help find efficient strategies against the resistance of ICI treatment.

Identification of the Unique Clinical and Genetic Features of Chinese Lung Cancer Patients With EGFR Germline Mutations in a Large-Scale Retrospective Study.

BACKGROUND: Epidemiological surveys have suggested that lung cancer has inherited susceptibility and shows familial aggregation. However, the distribution and prevalence of epidermal growth factor receptor (EGFR) germline variants and their roles in lung cancer genetic predisposition in Chinese population remain to be elucidated. METHODS: In this study, EGFR germline and somatic variants were retrospectively reviewed from the next-generation sequencing results of 31,906 patients with lung cancer. Clinical information was also collected for patients with confirmed EGFR germline mutations. RESULTS: A total of 22 germline EGFR variants were identified in 64 patients with lung cancer, accounting for 0.2% of the total cases studied. Five patients were diagnosed as multiple primary carcinomas. Family history was documented in 31.3% (20/64) of patients, 55% of which were diagnosed as lung cancer. G863D was the most frequent EGFR germline mutation, followed by P848L, D1014N, and K757R. Somatic EGFR-sensitive mutations were identified in 51.6% of patients with germline EGFR mutations. The proportion of L858R mutation, exon 19 deletion, and rare sensitive mutation was 50%, 17.6%, and 32.4%, respectively. D1014N and T790M mutations were common in young patients. The family members of patients with P848L, R776H, V769M, and V774M mutations were more commonly diagnosed with cancers. A total of 19 patients were confirmed to have received EGFR tyrosine kinase inhibitors (TKIs), but the response to EGFR-TKIs differed among patients with different EGFR mutations. CONCLUSION: Chinese patients with lung cancer harbored unique and dispersive EGFR germline mutations and showed unique clinical and genetic characteristics, with varied response patterns to EGFR-TKI treatment.

Comprehensive Analysis of the Immune Microenvironment in Checkpoint Inhibitor Pneumonitis.

Background: While immune checkpoint inhibitors (ICIs) are a beacon of hope for non-small cell lung cancer (NSCLC) patients, they can also cause adverse events, including checkpoint inhibitor pneumonitis (CIP). Research shows that the inflammatory immune microenvironment plays a vital role in the development of CIP. However, the role of the immune microenvironment (IME) in CIP is still unclear. Methods: We collected a cohort of NSCLC patients treated with ICIs that included eight individuals with CIP (CIP group) and 29 individuals without CIP (Control group). CIBERSORT and the xCell algorithm were used to evaluate the proportion of immune cells. Gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) were used to evaluate pathway activity. The ridge regression algorithm was used to analyze drug sensitivity. Results: CIBERSORT showed significantly upregulated memory B cells, CD8+ T cells, and M1 Macrophages in the CIP group. The number of memory resting CD4+ T cells and resting NK cells in the CIP group was also significantly lower than in the Control group. The XCell analysis showed a higher proportion of Class-switched memory B-cells and M1 Macrophages in the CIP group. Pathway analysis showed that the CIP group had high activity in their immune and inflammatory response pathways and low activity in their immune exhaustion related pathway. Conclusions: In this study, we researched CIP patients who after ICIs treatment developed an inflammatory IME, which is characterized by significantly increased activated immune cells and expression of inflammatory molecules, as well as downregulated immunosuppressive lymphocytes and signaling pathways. The goal was to develop theoretical guidance for clinical guidelines for the treatment of CIP in the future.