Clinical Characteristics and Prognosis of 76 Lung Adenocarcinoma Patients Harboring EGFR Mutations with Pleural Effusion at Initial Diagnosis: A Single-center Retrospective Study / 中国肺癌杂志

BACKGROUND@#Malignant pleural effusion is one of the common clinical manifestations of patients with lung adenocarcinoma. Patients with pleural effusion at the initial diagnosis of lung adenocarcinoma usually indicate poor prognosis. Epidermal growth factor receptor (EGFR) mutations mainly occur in patients with lung adenocarcinoma. Patients with different mutant subtypes have different prognosis. The clinical characteristics and prognostic factors of patients with EGFR mutated lung adenocarcinoma of different molecular subtypes combined with pleural effusion at initial diagnosis are still unclear. This study was designed to explore the clinical characteristics and prognostic factors of these patients in order to provide management recommendations for them.@*METHODS@#A retrospective analysis of the clinical characteristics, treatment, outcomes and progression-free survival (PFS) of first-line treatment in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis admitted to Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital from January 2012 to June 2021 was performed. Pearson's chi-square test or Fisher's exact test were performed for comparison between groups. Kaplan-Meier method was performed for survival analysis and Cox proportional risk regression model was performed for multivariate analysis.@*RESULTS@#76 patients met the inclusion criteria in this study. The incidences of EGFR classical mutations 19del, 21L858R and non-classical mutations were 46.0%, 38.2% and 15.8%, respectively among these patients. There was no significant difference between the three mutations in terms of gender, age, presence of dyspnea at presentation, whether other distant metastases were combined, site of pleural effusion, volume of pleural effusion, presence of other combined effusions, tumor-node-metastasis (TNM) stage, presence of other gene mutations, and treatment of pleural effusion (P>0.05). In patients with EGFR classical mutations 19del or 21L858R or non-classical mutations subtype, the proportion of chemotherapy in first-line regimens were 17.1%, 20.7% and 58.3%, respectively (P=0.001); and first-line disease control rates were 94.3%, 75.9% and 50%, respectively (P=0.003); pleural effusion control rates were 94.3%, 79.3% and 66.7%, respectively (P=0.04); PFS were 287 d, 327 d and 55 d, respectively (P=0.001). Univariate analysis showed that EGFR mutation subtype, control of pleural effusion, first-line treatment agents, and first-line treatment efficacy were significantly associated with PFS (P<0.05). Cox multifactorial analysis showed that only EGFR mutation subtype and first-line treatment efficacy were independent prognostic factors for PFS (P<0.05).@*CONCLUSIONS@#PFS was significantly better for classical mutations than for non-classical mutations in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis. Improving the efficacy of first-line therapy is the key to improve the prognosis of these patients.

Characteristics and Clinical Implication of UGT1A1 Heterozygous Mutation in Tumor / 中国肺癌杂志

BACKGROUND@#The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear.@*METHODS@#A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization.@*RESULTS@#There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not.@*CONCLUSIONS@#In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.

The Effects and Management of Viral Pneumonia on Lung Cancer Patients / 中国肺癌杂志

The worldwide epidemic of three coronaviruses and one influenza virus in 21st century have seriously threatened human health. Infection with these viruses can cause respiratory symptoms. The patients with lung cancer are more susceptible to viral infection and have a worse prognosis due to the advanced age and the systemic immunosuppressive state caused by malignancy itself and the anticancer treatments. In addition, without sufficient clinical awareness, a missed diagnosis of viral pneumonia may occur due to the fever and respiratory symptoms caused by lung cancer and its secondary diseases. Furthermore, control measures against viral outbreaks may interfere with routine diagnosis and treatment of lung cancer patients. Therefore, scientific protection and individualized management of lung cancer patients are particularly important during virus epidemic prevention and control. Here, we systematically reviewed the epidemiological and clinical characteristics of viral pneumonia, its impact on patients with lung cancer and the differential diagnosis of lung cancer-related respiratory manifestations, aiming to provide guidance for the individual management of lung cancer patients during the prevention and control of viral pneumonia epidemic.

A Single Center, Retrospective Analysis of Prognosis in Non-small Cell Lung Cancer Patients with Peritoneal Carcinomatosis / 中国肺癌杂志

BACKGROUND@#Peritoneal carcinomatosis is a rare clinical event in lung cancer and the prognosis is very poor. There are limited data on what factors predict peritoneal progression and affect the outcome. The aim of this study is to investigate investigate the factors associated with peritoneal carcinomatosis.@*METHODS@#The patients with non-small cell lung cancer (NSCLC) from the Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital were eligible for retrospective analysis between August 2010 and August 2018. Clinical factors such as age, gender, histology, pleural effusion and gene mutations with epidermal growth factor receptor/anaplastic lymphoma kinase/ROS proto-oncogene 1 receptor tyrosine kinase (EGFR/ALK/ROS1) were analyzed. Overall survival (OS) was calculated by the Kaplan-Meier method.@*RESULTS@#1.44% (12/836) patients in this study developed peritoneal carcinomatosis and 12 patients with adenocarcinoma had metachronous NSCLC diagnosis and PC. Malignant pleural effusion rates at baseline and at PC diagnosis were separately 50% (6/12) and 100.0% (12/12). Among the 12 patients, 9 patients harbored EGFR/ALK/ROS1 mutation. The outcome of patients with EGFR/ALK/ROS1 mutation was significantly better than that of patients without EGFR/ALK/ROS1 mutation, the mOS1 and mOS2 were separately 26.0 months and 6.0 months versus 10.0 months and 1.5 months (P<0.05). The mOS2 of patients with aggressive treatment after PC diagnosis was 6.0 months, significantly better than 1.0 month of patients with best supportive care (P<0.05). The mOS2 of the patients with angiogenesis inhibitors based-treatment after PC diagnosis was 8.5 months, significantly longer than that of patients with other treatments (P<0.05).@*CONCLUSIONS@#Adenocarcinoma and malignant pleural effusion are highly associated with peritoneal carcinomatosis in patients with advanced NSCLC. Aggressive treatment for lung cancer with PC is encouraged when possible. More patients with PC may benefit from the treatment strategies with angiogenesis inhibitors. Further prospective trials are urgently needed.

Retrospective Analysis of Risk Factors for Venous Thromboembolism in 283 Patients with Lung Cancer during Systemic Therapy / 中国肺癌杂志

BACKGROUND@#Patients with lung cancer have high risk of developing venous thromboembolism (VTE), which has been shown to have a significant impact on mortality. This study was to identify the incidence of VTE in lung cancer patients during systemic therapy and to analyze the risk factors associated with it.@*METHODS@#We retrospectively analyzed the cases of 283 patients with lung cancer who received systemic therapy in the Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital, from January 2016 to December 2018. Chi-square test and multivariate analyses were used to assess the correlation between clinical features and VTE.@*RESULTS@#Of the patients we observed, 34 developed VTE, with an incidence of 12.01% (34/283). In patients with lower extremity varicose vein (LVV), there was an increase in the incidence of VTE (50.00% vs 9.89%, P=0.001). The incidence VTE in patients with distant metastasis was higher than that in patients without distant metastasis, and higher than that in patients with tumor-free (14.05% vs 14.00% vs 2.08%, P=0.024). The incidence of VTE in patients with active tumor was also significantly higher than that in patients without it (16.93% vs 8.18%, P=0.025). Patients with hypoalbuminemia (albumin 0.3 µg/mL) developed more VTE than those without did (17.93% vs 5.80%, P=0.006). There were no significant correlations between pathological types, blood cell count before systemic therapy including leukocyte, hemoglobin and platelet, or antiangiogenic drugs and VTE. Multivariate analysis showed that LVV, hypoalbuminemia and elevated level of D-dimer were independent risk factors of VTE.@*CONCLUSIONS@#LVV, serum albumin and D-dimer level may be potential and more effective predictors of VTE in lung cancer patients during systemic therapy. Basing on these factors, new predictive model can be built, and further study to validate its efficacy is required.

Clinical research of Yiqi-Huoxue decoction combined with conventional treatment on patients with diabetic kidney disease / 国际中医中药杂志

Objective To study the clinical effect of Yiqi-Huoxue decoction on inflammatory factors and renal function with diabetic kidney disease (DN). Methods A total of 95 patients with DN were divided into the control group (n=47) and the treatment group (n=48) randomly. The control group were treated with conventional medicine, and the treatment group were treated with conventional medicine combined with Yiqi-Huoxue decoction. The two groups were treated for 12 weeks. The clinical efficacy of the two groups after treatment were compared. The serum IL-8, TNF-α, CRP and BUN, SCr, UAER of the two groups before and after treatment were compared. The adverse reactions of the two groups during treatment were compared. Results The total efficacy rate of the treatment group was 87.5％ (42/48), significantly higher than 51.1％(24/47) of the control group (χ2=14.866, P<0.01). After treatment, the serum L-8 (7.23 ± 2.84 ng/L vs. 11.63 ± 7.20 ng/L, t=3.933), TNF-α (16.71 ± 1.05 ng/L vs. 18.35 ± 1.20 ng/L, t=7.093), CRP (5.63 ± 1.21 mg/L vs. 6.70 ± 1.38 mg/L, t=4.021) of the treatment groupwere significantly lower than those of the control group (P<0.05). After treatment, the BUN (6.03 ± 0.66 mmol/L vs. 8.12 ± 0.78 mmol/L, t=14.109), SCr (90.17 ± 14.30 mmol/L vs. 101.34 ± 18.81 mmol/L, t=3.263), UAER (0.64 ± 0.19 g/24 h vs. 0.96 ± 0.22 g/24h, t=7.592) of the treatment groupwere significantly lower than those of the control group (P<0.01). The adverse reactions rates of treatment group was 6.3％ (3/48), control group was 8.5％ (4/47), and there was no significantly differences between two groups (χ2=0.178, P=0.673). Conclusions The Yiqi-Huoxue decoction for patients with DN has a good efficacy and low adverse reactions, can reduce the inflammatory factors, improve the inflammatory state and renal function, and it was worthy clinical application.

Impact of the Pretreatment or Posttreatment NLR and PLR on the Response of First Line Chemotherapy and the Outcomes in Patients with Advanced Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), indexes of systemic inflammation, have been associated with worse survival for many types of cancer. The aim of this study is to investigate the impact of NLR and PLR on overall survival (OS) and to explore the value of changes in the NLR and PLR with treatment as a response indicator in non-small cell lung cancer (NSCLC).@*METHODS@#A total of 68 NSCLC patients in Peking University Third Hospital were eligible for retrospective analysis between April 2008 and April 2015. The pretreatment and posttreatment NLR and PLR in all patients were calculated based on complete blood counts. Potential prognostic factors such as age, gender, performance status, histology, stage, response to chemotherapy, NLR and PLR were analyzed. NLR and PLR were assessed at baseline and during chemotherapy treatment. OS was calculated by the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to determine the associations of the PLR, NLR and clinical features with OS.@*RESULTS@#Among the 68 cases, the values of the posttreatment NLR after two cycles of chemotherapy (NLR2) and the pretreatment NLR (NLR0) were (2.69±2.06) and (3.94±2.12), respectively. NLR2 was significantly lower than NLR0 (P=0.000). There was no difference between the pretreatment PLR (PLR0) and the posttreatment PLR after two cycles of chemotherapy (PLR2) (P0.05). According to univariate analysis, the OS was significantly associated with NLR0, PLR0, NLR2, the response of 2 and 4 cycles of first line chemotherapy, status and regimens of second line treatment (P0.05). The multivariate analysis showed that NLR0 (P=0.004), the response with 4 cycles of first line chemotherapy (P=0.022) and status of second line treatment (P=0.007) were independent prognostic indicators in the 68 patients.@*CONCLUSIONS@#The study showed that NLR0 was well connected with outcomes and NLR2 was well connected with the response to first line chemotherapy in patients with advanced non-small cell lung cancer. Therefore, NLR may be a biomarker for predicting the outcomes and response of first line chemotherapy and a potential target for management of non-small cell lung cancer.

Post-exercise heart rate recovery relates to exercise capacity and prognosis in ST- elevation myocardial infarction treated with primary PCI / 中国介入心脏病学杂志

Objective To investigate the relation of post-exercise heart rate recovery(HRR)with exercise capacity, and the predictive value on long-term prognosis in patients of ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Methods A total of 260 patients were investigated from July 2011 to December 2014. All the patients were conducted cardiopulmonary exercise testing(CPET)within 30 days after STEMI, and heart rate recovery at 1 minute (HRR1)were calculated. The correlation between HRR with exercise tolerance was analysed. The median followup duration was 55 months(42,72), and the cardiovascular endpoint events were collected. Results The mean HRR1 was 26.0±12.2 beats in the whole study population who completed CPET.(1)HRR1 was positively correlated to peak oxygen uptake(VO2peak)(r=0.129, P<0.001).Multiple linear regression analysis demonstrated that VO2peak was independently positively associated with HRR1. (2) Cardiovascular endpoint events occurred in 60 cases (23.1%). Single factor screening through Cox regression model showed that decreased HRR1 (HRR1 ≤ 12 beats)(P=0.010)significantly correlated with the cardiovascular endpoint events. After adjusted by multiple factors, the risk of cardiovascular endpoint events in the group of decreased HRR(HRR1 ≤ 12 beats)was 2.671 times as the group of HRR1>12 beats. Conclusions Decreased HRR1 is associated with lower exercise tolerance, and it shows signifi cant prognostic values in increasing cardiovascular endpoint events in STEMI patients treated with primary PCI.

Development of chemical defense medicine Driven by Biotechnology / 国际药学研究杂志

The health service of chemical defense medicine is an important guarantee for national security, which has been expanded from dealing with traditional pure chemical warfare to current medical treatment of poisoning caused by public chemical accident, chemical terrorist attack, or future potential toxic agents at the boundary of chemistry and biology. The most recent scientific and technical disciplines, such as synthetic biology, pharmaceutical bioinformatics, nanotechnology, or drug/device combinatorial technology, should be utilized greatly to enhance the ability of the health service of the chemical defense medicine. And it is also important to establish and improve such management practice of emergence medicine as shelf life extension program or emergency use authorization.