A predictive model for frequent exacerbator phenotype of acute exacerbations of chronic obstructive pulmonary disease.

Background: The frequent exacerbator phenotype of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is characterized by experiencing at least two exacerbations per year, leading to a significant economic burden on healthcare systems worldwide. Although several biomarkers have been shown to be effective in assessing AECOPD severity in recent years, there is a lack of studies on markers to predict the frequent exacerbator phenotype of AECOPD. The current study aimed to develop a new predictive model for the frequent exacerbator phenotype of AECOPD based on rapid, inexpensive, and easily obtained routine markers. Methods: This was a single-center, retrospective study that enrolled a total of 2,236 AECOPD patients. The participants were divided into two groups based on the frequency of exacerbations: infrequent group (n=1,827) and frequent group (n=409). They underwent a complete blood count, as well as blood biochemistry, blood lipid and coagulation testing, and general characteristics were also recorded. Univariate analysis and binary multivariate logistic regression analyses were used to explore independent risk factors for the frequent exacerbator phenotype of AECOPD, which could be used as components of a new predictive model. The receiver operator characteristic (ROC) curve was used to assess the predictive value of the new model, which consisted of all significant risk factors predicting the primary outcome. The nomogram risk prediction model was established using R software. Results: Age, gender, length of stay (LOS), neutrophils, monocytes, eosinophils, direct bilirubin (DBil), gamma-glutamyl transferase (GGT), and the glucose-to-lymphocyte ratio (GLR) were independent risk factors for the frequent exacerbator phenotype of AECOPD. The area under the curve (AUC) of the new predictive model was 0.681 [95% confidence interval (CI): 0.653-0.708], and the sensitivity was 63.6% (95% CI: 58.9-68.2%) and the specificity was 65.0% (95% CI: 60.3-69.6%). Conclusions: A new predictive model based on demographic characteristics and blood parameters can be used to predict the frequency of acute exacerbations in the management of chronic obstructive pulmonary disease (COPD).

EGLIF-CAR-T Cells Secreting PD-1 Blocking Antibodies Significantly Mediate the Elimination of Gastric Cancer.

OBJECTIVE: To investigate the anti-tumor effects of programmed cell death protein 1 (PD-1) scFv-secreting EGFR-chimeric antigen receptor-modified (CAR)-T cells against gastric cancer. METHODS: Second-generation EGFR-CAR-T cells and fourth-generation PD-1 scFv-secreting EGFR-CAR-T cells were engineered. The anti-tumor activities of chimeric antigen receptor-modified (CAR)-T cells were analyzed in vitro by long-term co-culture with gastric cancer cells. The tumor scavenging capacity in vivo was evaluated in xenograft and PDX mouse models. RESULTS: EGFR-CAR-T cells secreting PD-1 scFv showed enhanced long-term tumor cell killing capacity in vitro. These cells also showed significant anti-tumor effect in the subcutaneous xenograft model of gastric cancer as well as in the PDX model, and autocrine PD-1 antibody secretion significantly increased tumor infiltration of the CAR-T cells. CONCLUSION: EGFR-CAR-T cells secreting PD-1 scFv are highly effective against gastric cancer and offer new insights into anti-cancer immunotherapy.

Diagnostic Utility of Interferon-Gamma Release Assay in Tuberculous Lymphadenitis.

Objective The aim of this study was to evaluate the diagnostic performance of T-SPOT.TB for tuberculous lymphadenitis. Methods Suspected tuberculous lymphadenitis patients between September 2010 and September 2018 who had both peripheral blood T-SPOT.TB test and lymph node biopsy were retrospectively enrolled in this study. The cutoff value of T-SPOT.TB test for peripheral blood was set as 24 spot forming cell (SFC)/10 6 periphreral blood monocyte cell (PBMC) according to the instruction of testing kits. The gold standard for diagnosis of TBL was the combination of microbiology results, histopathology results and patient's response to anti-TB treatment. Diagnostic efficacy of T-SPOT.TB was evaluated, including sensitivity, specificity, accuracy, predictive values, and likelihood ratio. Results Among 91 patients who met the inclusion criteria, we excluded 8 cases with incomplete clinical information and 6 cases who lost to follow-up. According to the gold standard, there were 37 cases of true TBL (9 confirmed TBL and 28 probable TBL), 30 cases of non-TBL, and 10 cases of clinically indeterminate diagnosis who were excluded from the final analyses. The T-SPOT.TB tests yielded 43 cases of positive response and 24 cases of negative response. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of peripheral blood T-SPOT.TB for diagnosing TBL were 89.2%, 66.7%, 79.1%, 76.7%, 83.3%, 2.68 and 0.16, respectively. The number of SFCs of T-SPOT.TB in TBL patients [432(134-1264)/10 6 PBMCs] was higher than that in non-TBL patients [0 (0-30) /10 6PBMCs] with a significant difference (Z=-5.306, P <0.001).Conclusion T-SPOT.TB is a rapid and simple diagnostic test for TBL with a high sensitivity and negative predictive value.