2.Predictive Value of Peripheral Blood Biomarkers in the Treatment of Lung Cancer Patients with Anti PD-1 Immunotherapy.
Shu SU ; Xin LV ; Liang QI ; Min WEI ; Baorui LIU ; Lifeng WANG
Chinese Journal of Lung Cancer 2024;26(12):901-909
BACKGROUND:
The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses.
METHODS:
We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed.
RESULTS:
All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline.
CONCLUSIONS
Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.
Humans
;
Lung Neoplasms/metabolism*
;
Interleukin-5/therapeutic use*
;
Tumor Necrosis Factor-alpha/therapeutic use*
;
Retrospective Studies
;
Programmed Cell Death 1 Receptor
;
Biomarkers
;
Immunotherapy
;
Disease Progression
;
B7-H1 Antigen
3.More microinvasive foci in larger tumours of breast ductal carcinoma in situ.
Xiao-Yang CHEN ; Aye Aye THIKE ; Johnathan Xiande LIM ; Boon Huat BAY ; Puay Hoon TAN
Singapore medical journal 2023;64(8):493-496
INTRODUCTION:
Microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. This study aimed to investigate the potential influence of Mi on survival and assess its correlations with clinicopathological parameters, prognosis and molecular markers.
METHODS:
The number of Mi foci in a cohort of 66 DCIS-Mi cases was assessed from haematoxylin and eosin-stained sections. Disease-free survival, clinicopathological parameters and biomarker expression were correlated with the number of Mi foci.
RESULTS:
Higher numbers of Mi foci were found in larger tumours (P = 0.031).
CONCLUSION
Greater extent of DCIS is associated with multifocal Mi.
Humans
;
Female
;
Carcinoma, Intraductal, Noninfiltrating
;
Prognosis
;
Disease-Free Survival
;
Progression-Free Survival
;
Breast Neoplasms
;
Carcinoma, Ductal, Breast/pathology*
;
Neoplasm Invasiveness
4.Does the 2017 global initiative for chronic obstructive lung disease revision really improve the assessment of Chinese chronic obstructive pulmonary disease patients? A multicenter prospective study for more than 5 years.
Yanan CUI ; Yiming MA ; Zhongshang DAI ; Yingjiao LONG ; Yan CHEN
Chinese Medical Journal 2023;136(21):2587-2595
BACKGROUND:
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 proposed a new classification that reclassified many chronic obstructive pulmonary disease (COPD) patients from group D to B. However, there is a paucity of data related to the comparison between reclassified and non-reclassified COPD patients in terms of long-term prognosis. This study aimed to investigate long-term outcomes of them and determine whether the GOLD 2017 revision improved the assessment of COPD patients.
METHODS:
This observational, multicenter, prospective study recruited outpatients at 12 tertiary hospitals in China from November 2016 to February 2018 and followed them up until February 2022. All enrolled patients were classified into groups A to D based on GOLD 2017, and the subjects in group B included patients reclassified from group D to B (group DB) and those remaining in group B (group BB). Incidence rates and hazard ratios (HRs) were calculated for the exacerbation of COPD and hospitalization in each group.
RESULTS:
We included and followed up 845 patients. During the first year of follow-up, the GOLD 2017 classification had a better discrimination ability for different risks of COPD exacerbation and hospitalization than GOLD 2013. Group DB was associated with a higher risk of moderate-to-severe exacerbation (HR = 1.88, 95% confidence interval [CI] = 1.37-2.59, P <0.001) and hospitalization for COPD exacerbation (HR = 2.23, 95% CI = 1.29-3.85, P = 0.004) than group BB. However, during the last year of follow-up, the differences in the risks of frequent exacerbations and hospitalizations between group DB and BB were not statistically significant (frequent exacerbations: HR = 1.02, 95% CI = 0.51-2.03, P = 0.955; frequent hospitalizations: HR = 1.66, 95% CI = 0.58-4.78, P = 0.348). The mortality rates of the two groups were both approximately 9.0% during the entire follow-up period.
CONCLUSIONS
The long-term prognosis of patients reclassified into group B and of those remaining in group B was similar, although patients reclassified from group D to group B had worse short-term outcomes. The GOLD 2017 revision could improve the assessment of Chinese COPD patients in terms of long-term prognosis.
Humans
;
Prospective Studies
;
East Asian People
;
Disease Progression
;
Severity of Illness Index
;
Pulmonary Disease, Chronic Obstructive/epidemiology*
5.In-hospital Mortality and Hospital Outcomes among Adults Hospitalized for Exacerbations of Asthma and COPD in Southern Thailand (2017-2021): A Population-Based Study.
Narongwit NAKWAN ; Kanittha SUANSAN
Chinese Medical Sciences Journal 2023;38(3):228-234
Background Hospitalizations for asthma and chronic obstructive pulmonary disease (COPD) exacerbations frequently occur in Thailand. National trends in hospital outcomes are essential for planning preventive strategies within the healthcare system. We examined temporal trends in in-hospital outcomes, including mortality rate, length of stay (LOS), and expenses for reimbursement in adults hospitalized for asthma and COPD exacerbations in southern Thailand.Methods A retrospective, population-based study on adults hospitalized for exacerbations of asthma and COPD was carried out using data from the National Health Security Office in southern Thailand. Baseline demographic and in-hospital outcome assessments were conducted on 19,459 and 66,457 hospitalizations for asthma and COPD, respectively, between 2017 and 2021.Results Significant reductions in hospital admissions for exacerbations of asthma and COPD were observed over time, particularly in 2020/2021. From 2017 to 2021, the in-hospital mortality rate for asthma rose from 3.2 to 3.7 deaths per 1,000 admissions (P<0.05). The rates for COPD admissions, on the other hand, reduced from 20.3 to 16.4 deaths per 1,000 admissions between 2017 and 2020, but subsequently increased to 21.8 in 2021 (P<0.05). The prominent contributor to the higher mortality rate was found to be increasing age. Nonetheless, the average LOS for both asthma and COPD decreased slightly over the study period. The total expenses for reimbursing exacerbations of asthma and COPD per hospitalisation have risen significantly each year, with a particularly notable increase in 2020/2021.Conclusion During 2017-2021, exacerbations of asthma and COPD in Thailand continued to account for significant in-hospital mortality rates and reimbursement expenses, despite the overall decrease in hospitalizations and slight fluctuations in the LOS.
Adult
;
Humans
;
Retrospective Studies
;
Hospital Mortality
;
Thailand/epidemiology*
;
Pulmonary Disease, Chronic Obstructive
;
Asthma/epidemiology*
;
Hospitals
;
Disease Progression
6.Research Progress of Iron Metabolism in Disease Progression and Drug Resistance of Multiple Myeloma--Review.
Yan-Ying LI ; Liu-Yun ZHANG ; Yun-Hui XIANG ; Juan ZHANG
Journal of Experimental Hematology 2023;31(6):1916-1920
Iron metabolism is involved in the development and drug resistance of many malignancies, including multiple myeloma (MM). Based on recent studies on iron metabolism and MM, this paper reviews the relationship between iron metabolism and disease process of MM in terms of iron overload leading to ferroptosis in MM cells, the role of iron deficiency in oxidative respiration and proliferation of MM cells, and the interaction between ferroptosis and autophagy in the disease process. The mechanisms by which iron metabolism-related substances lead to MM cells' resistance to proteasome inhibitors (PI) through inducing redox imbalance and M2 macrophage polarization are also briefly described, aiming to provide a theoretical basis for the application of iron metabolism-related drugs to the clinical treatment of MM patients.
Humans
;
Autophagy
;
Disease Progression
;
Iron/metabolism*
;
Multiple Myeloma
;
Drug Resistance, Neoplasm
7.Typical hemophagocytic syndrome associated with cytomegalovirus infection in an immunocompetent patient: a case report and literature review.
Fangfang GENG ; Meifang YANG ; Xuan ZHANG ; Hong ZHAO ; De ZHOU ; Jianhua HU
Journal of Zhejiang University. Science. B 2023;24(12):1159-1164
Cytomegalovirus (CMV) infection is currently prevalent in populations throughout the world, and 56%-94% of the global population is seropositive for CMV. CMV infection mainly affects immunocompromised hosts. In these cases, it can cause significant symptoms, tissue-invasive disease, and many sequelae including death (Dioverti and Razonable, 2016). The vast majority of healthy adults with CMV infection experience an asymptomatic course; when symptomatic, it manifests as a mononucleosis-like syndrome in approximately 10% of patients (Sridhar et al., 2018). The gastrointestinal tract and central nervous system appear to be the most frequent sites of severe CMV infection in immunocompetent individuals (Rafailidis et al., 2008). However, CMV infection is relatively rarely recorded in immunocompetent hosts.
Adult
;
Humans
;
Lymphohistiocytosis, Hemophagocytic/complications*
;
Cytomegalovirus Infections/diagnosis*
;
Gastrointestinal Tract
;
Disease Progression
8.Correlation between PAFAH1B3 Expression Level and Risk of Disease Progression After Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients.
Zhe-Yun GU ; Jian TAO ; Yi-Feng CAI ; Ling WANG
Journal of Experimental Hematology 2023;31(2):448-454
OBJECTIVE:
To investigate the association between the expression level of platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3 ) gene in bone marrow CD138+ cells of patients with multiple myeloma (MM) treated with autologous hematopoietic stem cell transplantation (AHSCT) and the prognosis within 2 years.
METHODS:
147 MM patients treated with AHSCT in The First and The Second Affiliated Hospital of Nantong University from May 2014 to May 2019 were included in the study. Expression level of PAFAH1B3 mRNA in bone marrow CD138+ cells of the patients was detected. Patients with disease progression or death during 2 years of follow-up were included in progression group, and the rest were included in good prognosis group. After comparing the clinical data and PAFAH1B3 mRNA expression levels of the two groups, the patients were divided into high PAFAH1B3 expression group and low PAFAH1B3 expression group based on the median PAFAH1B3 mRNA expression level of the enrolled patients. Progression-free survival rate (PFSR) between the two groups was compared by the Kaplan-Meier method. The related factors of prognosis within 2 years were analyzed by univariate analysis and multivariate COX regression analysis.
RESULTS:
At the end of follow-up, there were 13 patients lost to follow-up. Finally, 44 patients were included in the progression group and 90 patients were included in the good prognosis group. Age in the progression group was higher than that in the good prognosis group, the proportion of patients with CR+VGPR after transplantation in the progression group was lower than that in the good prognosis group, and there was a statistical difference between two groups in the cases distribution of ISS stage (all P<0.05). PAFAH1B3 mRNA expression level and the proportion of patients with LDH>250U/L in the progression group were higher than those in the good prognosis group, and platelet count in the progression group was lower than that in the good prognosis group (all P<0.05). Compared with the low PAFAH1B3 expression group, the 2-year PFSR of the high PAFAH1B3 expression group was significantly lower (log-rank χ2=8.167, P=0.004). LDH>250U/L (HR=3.389, P=0.010), PAFAH1B3 mRNA expression (HR=50.561, P=0.001) and ISS stage Ⅲ(HR=1.000, P=0.003) were independent risk factors for prognosis in MM patients, and ISS stage Ⅰ (HR=0.133, P=0.001) was independent protective factor.
CONCLUSION
The expression level of PAFAH1B3 mRNA in bone marrow CD138+ cells is related to the prognosis of MM patients treated with AHSCT, and detecting PAFAH1B3 mRNA expression can bring some information for predicting PFSR and prognostic stratification of patients.
Humans
;
Disease Progression
;
Hematopoietic Stem Cell Transplantation
;
Multiple Myeloma/drug therapy*
;
Prognosis
;
Retrospective Studies
;
Transplantation, Autologous
;
1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics*

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