Infliximab for parenchymal neuro-Behçet's syndrome: case series and meta-analysis.

OBJECTIVES: This study aims to evaluate the efficacy and safety of infliximab (IFX) in patients with parenchymal neuro-Behçet's syndrome (p-NBS). METHODS: We retrospectively analysed eleven p-NBS patients treated with IFX at our institution and combined them with studies from database searches for a meta-analysis. Pooled estimates of clinical response (complete and partial remission) and MRI improvement at months 3, 6, and 12 were calculated. RESULTS: One patient achieved CR and the other ten patients achieved PR at our institution. 8 studies (77 patients) were included in the meta-analysis. At 3, 6, and 12 months, 97% (95%CI 61.9-100%), 89.6% (95%CI 45.9-100%), 100% (95%CI 96.0-100%) of patients showed clinical response and 100% (95%CI 89.7-100%), 89.1% (95% CI 26.3-100%), 99.5% (95% CI 96.0-100%) of patients showed radiological improvement, respectively. Severe adverse events were observed in 7 patients. CONCLUSIONS: IFX was effective and relatively safe for p-NBS. Patients should be re-evaluated after 3 months of IFX to determine further therapy.

Ankylosing Spondylitis and the Risk of Lung Cancer: A Meta-Analysis and Mendelian Randomization.

Background: It remains uncertain whether ankylosing spondylitis is associated with an increased risk of lung cancer. Methods: We conducted a meta-analysis to comprehensively evaluate the correlation between ankylosing spondylitis and lung cancer based on existing literature. Eligible studies were identified by searching the PubMed, Web of Science, Embase, and Cochrane Library before 26 March 2021. Subgroup analyses based on regions were also carried out. To further explore their causality, a two-sample Mendelian randomization analysis was performed, with 25 ankylosing spondylitis-related single nucleotide polymorphisms derived from the largest sample genome-wide association study of ankylosing spondylitis (ebi-a-GCST005529, 22,647 individuals). The inverse variance-weighted method was applied to estimate the causality, and the pleiotropy was assessed utilizing the Mendelian randomization-Egger regression approach. Results: The meta-analysis including seven studies, with a total of 39,186 individuals, suggested no significant association between ankylosing spondylitis and lung cancer (relative risk, 1.10; 95% confidence interval, 0.89-1.36; I2, 61.8%). After excluding one study leading to high heterogeneity, we found that ankylosing spondylitis was associated with a 19% increased risk of lung cancer (relative risk, 1.19; 95% confidence interval, 1.01-1.40; I2, 0.0%). Subgroup analyses suggested that ankylosing spondylitis was not associated with increased risks of lung cancer in neither European (relative risk, 1.05; 95% confidence interval, 0.80-1.39; I2, 0.0%) nor non-European (relative risk, 1.14; 95% confidence interval, 0.84-1.55; I2, 79.6%) patients. Nevertheless, the Mendelian randomization results indicated that genetically determined ankylosing spondylitis was causally correlated with a remarkably increased risk of lung cancer among European populations (odds ratio, 1.26; 95% confidence interval, 1.07-1.48). Subgroup analyses further elucidated that genetically determined ankylosing spondylitis was causally associated with a notably higher risk of only squamous cell lung cancer (odds ratio, 1.39; 95% confidence interval, 1.05-1.83), rather than lung adenocarcinoma (odds ratio, 1.18; 95% confidence interval, 0.91-1.54). In addition, the results indicated the absence of pleiotropy. Conclusion: The results of both modified meta-analysis and Mendelian randomization analysis suggested that ankylosing spondylitis was likely to be correlated with the development of lung cancer. Further research is warranted to clarify the specific mechanism regarding the causality between the two diseases.

Univariable and Multivariable Two-Sample Mendelian Randomization Investigating the Effects of Leisure Sedentary Behaviors on the Risk of Lung Cancer.

Leisure sedentary behaviors (LSB) are widespread, and observational studies have provided emerging evidence that LSB play a role in the development of lung cancer (LC). However, the causal inference between LSB and LC remains unknown. Methods: We utilized univariable (UVMR) and multivariable two-sample Mendelian randomization (MVMR) analysis to disentangle the effects of LSB on the risk of LC. MR analysis was conducted with genetic variants from genome-wide association studies of LSB (408,815 persons from UK Biobank), containing 152 single-nucleotide polymorphisms (SNPs) for television (TV) watching, 37 SNPs for computer use, and four SNPs for driving, and LC from the International Lung Cancer Consortium (11,348 cases and 15,861 controls). Multiple sensitivity analyses were further performed to verify the causality. Results: UVMR demonstrated that genetically predisposed 1.5-h increase in LSB spent on watching TV increased the odds of LC by 90% [odds ratio (OR), 1.90; 95% confidence interval (CI), 1.44-2.50; p < 0.001]. Similar trends were observed for squamous cell lung cancer (OR, 1.97; 95%CI, 1.31-2.94; p = 0.0010) and lung adenocarcinoma (OR, 1.64; 95%CI 1.12-2.39; p = 0.0110). The causal effects remained significant after adjusting for education (OR, 1.97; 95%CI, 1.44-2.68; p < 0.001) and body mass index (OR, 1.86; 95%CI, 1.36-2.54; p < 0.001) through MVMR approach. No association was found between prolonged LSB spent on computer use and driving and LC risk. Genetically predisposed prolonged LSB was additionally correlated with smoking (OR, 1.557; 95%CI, 1.287-1.884; p < 0.001) and alcohol consumption (OR, 1.010; 95%CI, 1.004-1.016; p = 0.0016). Consistency of results across complementary sensitivity MR methods further strengthened the causality. Conclusion: Robust evidence was demonstrated for an independent, causal effect of LSB spent on watching TV in increasing the risk of LC. Further work is necessary to investigate the potential mechanisms.

Profiling Tumor Immune Microenvironment of Non-Small Cell Lung Cancer Using Multiplex Immunofluorescence.

This study attempted to profile the tumor immune microenvironment (TIME) of non-small cell lung cancer (NSCLC) by multiplex immunofluorescence of 681 NSCLC cases. The number, density, and proportion of 26 types of immune cells in tumor nest and tumor stroma were evaluated, revealing some close interactions particularly between intrastromal neutrophils and intratumoral regulatory T cells (Treg) (r2 = 0.439, P < 0.001), intrastromal CD4+CD38+ T cells and CD20-positive B cells (r2 = 0.539, P < 0.001), and intratumoral CD8-positive T cells and M2 macrophages expressing PD-L1 (r2 = 0.339, P < 0.001). Three immune subtypes correlated with distinct immune characteristics were identified using the unsupervised consensus clustering approach. The immune-activated subtype had the longest disease-free survival (DFS) and demonstrated the highest infiltration of CD4-positive T cells, CD8-positive T cells, and CD20-positive B cells. The immune-defected subtype was rich in cancer stem cells and macrophages, and these patients had the worst prognosis. The immune-exempted subtype had the highest levels of neutrophils and Tregs. Intratumoral CD68-positive macrophages, M1 macrophages, and intrastromal CD4+ cells, CD4+FOXP3- cells, CD8+ cells, and PD-L1+ cells were further found to be the most robust prognostic biomarkers for DFS, which were used to construct and validate the immune-related risk score for risk stratification (high vs. median vs. low) and the prediction of 5-year DFS rates (23.2% vs. 37.9% vs. 43.1%, P < 0.001). In conclusion, the intricate and intrinsic structure of TIME in NSCLC was demonstrated, showing potency in subtyping and prognostication.