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.Clinical characteristics and progression risk factors for patients with monoclonal gammopathy of undetermined significance.
Ai GUAN ; Kai Ni SHEN ; Lu ZHANG ; Xin Xin CAO ; Wei SU ; Dao Bin ZHOU ; Jian LI
Chinese Journal of Hematology 2023;44(2):137-140
Objective: To analyze the clinical presentation and progression risk factors of patients with monoclonal gammopathy of undetermined significance (MGUS) in China. Methods: We retrospectively assessed the clinical features and disease progression of 1 037 patients with monoclonal gammopathy of undetermined significance between January 2004 and January 2022 at Peking Union Medical College Hospital. Results: A total of 1 037 patients were recruited in the study, including 636 males (63.6%) , with a median age of 58 (18-94) years. The median concentration of serum monoclonal protein was 2.7 (0-29.4) g/L. The monoclonal immunoglobulin type was IgG in 380 patients (59.7%) , IgA in 143 patients (22.5%) , IgM in 103 patients (16.2%) , IgD in 4 patients (0.6%) , and light chain in 6 patients (0.9%) . 171 patients (31.9%) had an abnormal serum-free light chain ratio (sFLCr) . According to the Mayo Clinic model for risk of progression, the proportion of patients in the low-risk, medium-low-risk, medium-high risk, and high-risk groups were 254 (59.5%) , 126 (29.5%) , 43 (10.1%) , and 4 (0.9%) , respectively. With a median follow-up of 47 (1-204) months, 34 of 795 patients (4.3%) had disease progression, and 22 (2.8%) died. The overall progression rate was 1.06 (0.99-1.13) /100 person-years. Patients with non-IgM MGUS have a markedly higher disease progression rate per 100 person-years than IgM-MGUS (2.87/100 person-years vs 0.99/100 person-years, P=0.002) . The disease progression rate per 100 person-years in non-IgM-MGUS patients of Mayo classification low-risk, medium-low risk and medium-high risk groups were 0.32 (0.25-0.39) /100 person-years, 1.82 (1.55-2.09) /100 person-years, and2.71 (1.93-3.49) /100 person-years, which had statistically difference (P=0.005) . Conclusion: In comparison to non-IgM-MGUS, IgM-MGUS has a greater risk of disease progression. The Mayo Clinic progression risk model applies to non-IgM-MGUS patients in China.
Male
;
Humans
;
Middle Aged
;
Aged
;
Aged, 80 and over
;
Monoclonal Gammopathy of Undetermined Significance
;
Retrospective Studies
;
Risk Factors
;
Immunoglobulin Light Chains
;
Disease Progression
9.Application of discrete event simulation model in analysis on cost-effectiveness of epidemiology screening.
Jia Min WANG ; Qiu Ping LIU ; Chao GONG ; Ming Lu ZHANG ; Pei GAO ; Xun TANG ; Yong Hua HU
Chinese Journal of Epidemiology 2023;44(3):463-469
Discrete event simulation (DES) model is based on individual data, by which discrete events over time are simulated to reflect disease progression. The effects of individual characteristics on disease progression could be considered in the DES model. Moreover, unlike state-transition models, DES model without setting of fixed cycle can contribute to more accurate estimation of event time, especially in the evaluation of the long-term effectiveness of screening strategies for complex diseases in which time dimension needs to be considered. This article introduces the general principles, construction steps, analytic methods and other relevant issues of the DES model. Based on a research case of estimating the cost-effectiveness of screening for abdominal aortic aneurysms in women aged 65 years and above in the United Kingdom, key points in applications of the DES model in analysis on effectiveness of complex disease screening are discussed in detail, including model construction and analysis and interpretation of the results. DES model can predict occurring time of discrete events accurately by establishing the distribution function of their occurring time and is increasingly used to evaluate the screening strategies for complex diseases in which time dimension needs to be considered. In the construction of DES model, it is necessary to pay close attention to the clear presentation of model structure and simulation process and follow the relevant reporting specification to conduct cost-effectiveness analysis to ensure the transparency and repeatability of the research.
Humans
;
Female
;
Cost-Benefit Analysis
;
Cost-Effectiveness Analysis
;
Disease Progression
10.Depressive symptoms are not associated with risks of rapid renal function decline or chronic kidney disease in middle-aged and elderly with normal kidney function: a longitudinal investigation.
Meng Di YANG ; Hong Tao YIN ; Jie Yu ZHEN ; Yu Lu DING ; Yu Jie WANG ; Lin Nan SUN ; Feng Ying HE ; Dong Hu ZHEN
Journal of Southern Medical University 2023;43(2):225-231
OBJECTIVE:
To explore the association between depressive symptoms and the risks of rapid decline in renal function and chronic kidney disease (CKD) in middle-aged and elderly with normal kidney function.
METHODS:
The residents aged 40- 75 years with eGFR≥60 mL·min-1·1.73 m-2 without proteinuria in Lanzhou region, who participated in the "REACTION" study carried out in 2011, were selected and followed up in 2014. A total of 4961 individuals with complete and qualified data from the two surveys were included in the subsequent analysis. Based on PHQ-9 questionnaire scores, the baseline population was divided into two groups with and without depressive symptoms. Cox proportional hazard analysis was used to compare the incidences of rapid renal function decline and CKD between the two groups and study the association of depressive symptoms with the risk of these renal conditions.
RESULTS:
PHQ-9 questionnaire scores were not found to correlate with baseline SCr, ALB, UACR or eGFR levels among the participarts (P>0.05). After a mean follow-up time of 3.4±0.6 years, 33.9% of the participants with depressive symptoms at baseline experienced a rapid decline in renal function and 3.6% progressed to CKD. During the follow-up, the incidence of rapid decline in renal function and the risk of developing CKD were not found to correlate with depressive symptoms in these participants (P>0.05) regardless of the type of the depressive syndromes.
CONCLUSION
Depressive symptoms are not associated with the risks of rapid renal function decline or progression to CKD in middle-aged and elderly with normal kidney function.
Aged
;
Middle Aged
;
Humans
;
Cohort Studies
;
Depression
;
Glomerular Filtration Rate
;
Disease Progression
;
Renal Insufficiency, Chronic/epidemiology*
;
Kidney/physiology*
;
Risk Factors

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