[Effect of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer and chronic obstructive pulmonary disease].

Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with Ⅲ-Ⅳ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.

[Clinical characteristics of hepatic flare and efficacy of antiviral therapy in pregnant women with chronic hepatitis B virus infection].

Objective: To analyze the clinical characteristics of hepatic flare and evaluate efficacy of antiviral treatment in pregnant women with chronic HBV infection. Methods: A single-center, open-label, prospective study was conducted, and pregnant women with chronic HBV infection were enrolled. Liver function, HBV serum markers and HBV DNA of pregnant women with chronic HBV infection were reviewed during every 4 to 12 weeks of gestation period. The proportion and clinical characteristics of hepatitis flare during pregnancy were observed. Logistic regression analysis was used to predict hepatic flare in pregnant women with chronic HBV infection. Antiviral therapy with telbivudine (LdT) or tenofovir dipivoxil (TDF) was used to treat hepatic flare during pregnancy. Sequential entecavir (ETV) or TDF was applied after the delivery. Treatment course and drug withdrawal in pregnant women with hepatic flare was the same as those of the general patients with chronic hepatitis B. Liver function, HBV serum markers and HBV DNA were measured in pregnant women with hepatic flare at different time points (4, 12, 24 and 52 weeks). A t-test was used to compare the hepatic flare in pregnant women with and without hepatitis group. HBsAg and HBeAg were used to quantify the receiver operating characteristic (ROC) curve of pregnant women with hepatic flare during pregnancy. Area under the ROC curve was used to calculate the optimal cut-off value corresponding to the maximum sensitivity and specificity of the ROC curve. Results: Of the 220 pregnant women with chronic HBV infection, 55 (25%) had hepatitis flare during pregnancy and received antiviral treatment. Among the 55 women with hepatic flare during gestation, 47 (85.46%) had hepatic flare in the mid-second trimester (12-24 weeks); average peak value of alanine aminotransferase (ALT) was 220.62 U/L, and the average peak value of ALT in 32 cases (58.18%) of pregnant women with hepatic flare was between 2-5 × ULN. HBsAg and HBeAg quantification were significantly lower in pregnant women with hepatic flare during pregnancy than with non-hepatitis (t = -3.745, P < 0.001; t = -2.186, P = 0.030). Multivariate logistic regression analysis showed that pregnant women with HBeAg < 3.065 log10 s/co were 7.576 times more likely to have hepatic flare during pregnancy (95% confidence interval: 3.779-15.190). ALT normalization, undetectable HBV DNA levels, HBeAg loss and HBeAg seroconversion in 55 pregnant women with hepatic flare at 52-week treatment was 100% (55/55), 74.55% (41/55), 47.27% (26/55) and 41.82% (23/55), respectively. HBsAg quantification at 52 weeks was significantly lower than baseline HBsAg quantification (3.32 + 0.37) log(10) IU/ml and (3.95 + 0.40) log(10) IU/ml; t = 8.465, P < 0.001). Conclusion: Hepatic flare often occurs in the second trimester of pregnancy in pregnant women with chronic HBV infection and baseline HBeAg quantification is an independent predictor of hepatic flare. HBeAg seroconversion rate increased at 52 weeks after antiviral therapy.

[The comparison of liver inflammation and fibrosis between chronic HBV and HCV infection].

Objective: To explore the difference of liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection and chronic hepatitis C virus (HCV) infection, and to investigate the relationship between hepatic pathology and alanine aminotransferase (ALT). Methods: 57 patients with chronic HCV infection and 346 patients with chronic HBV infection who were hospitalized at Shengjing Hospital of China Medical University from January 2012 to September 2016 were enrolled. In chronic HBV infection, including 88 cases whose ALT were more than two times of upper limited of normal (ALT≥2×ULN) and 258 cases whose ALT were less than two times of upper limited of normal (ALT < 2×ULN).All the patients were underwent liver biopsy. Chronic HBV infection (ALT≥2×ULN and ALT < 2×ULN) and chronic HCV infection were compared respectively. Statistical analyses were performed using a Univariate χ²-test and Mann-Whitney U test for comparison. Correlations between variables were analyzed using Spearman's rank correlation. Results: In chronic HBV infection group, 169 cases (48.8%) had inflammation grade≥2 (G≥2), 98 cases (28.3%) had fibrosis stage≥2 (S≥2), 81 cases (23.4%) with G≥2 and S≥2.In the ALT < 2×ULN group, there were 109 cases (42.2%) with G≥2, 62 cases (24%) with S≥2, 49 cases (19%) with G≥2 and S≥2. In the ALT≥2×ULN group, 60 cases (68.2%) with G≥2, 35 cases (39.8%) with S≥2, 31 cases (35.2%) with G≥2 and S≥2. The grade of inflammation and fibrosis have significantly different between ALT≥2×ULN group and ALT < 2×ULN group (χ² = 17.66, χ² = 8.06, P < 0.01). In chronic HCV infection group, 47 cases (82.5%) with G≥2, 20 cases (35.1%) with S≥2, 20 cases (35.1%) with G≥2 and S≥2. ALT had no correlation with inflammation and fibrosis (P > 0.05). The grade of inflammation was significantly different between chronic HCV infection and chronic HBV infection whose ALT < 2×ULN (χ² = 30.19, P < 0.01) but the fibrosis have no difference (χ² = 2.96, P > 0.05). Compared with chronic HBV infection whose ALT≥2×ULN, both inflammation and fibrosis had no significantly different (χ² = 3.65, χ² = 0.32, P > 0.05 respectively). Conclusion: In chronic HBV infection whose ALT < 2×ULN, about 30%-40% liver tissue with significant necroinflammation and /or fibrosis. About 80% chronic HCV infection with significant necroinflammation, and the grade of inflammation has no correlation with ALT. The grade of inflammation has significantly different between chronic HCV infection group and chronic HBV infection group whose ALT < 2×ULN.

A nomogram for predicting overall survival in patients with type II endometrial carcinoma: a retrospective analysis and multicenter validation study.

OBJECTIVE: Type II endometrial cancer (EC) is associated with high risk of metastasis and poor prognosis. We aimed to develop a nomogram for predicting survival probability in patients with type II EC. PATIENTS AND METHODS: Data from a total of 4,117 patients with confirmed type II EC were pulled from the Surveillance, Epidemiology, and End Results (SEER) database, and were randomly divided into a training set and an internal verification set. A nomogram was constructed based on the training set. The concordance index (C-index), area under the ROC curve, and calibration plots were used to evaluate the identification and calibration of the nomogram. The SEER internal validation set and the Chinese multicenter data set (74 patients) were used to verify discriminations and corrections of the model. RESULTS: Multivariate analysis indicated that age, marital status, tumor size, T stage, N stage, M stage, surgery, radiotherapy, and chemotherapy were independent factors affecting the prognosis of type II EC patients (p<0.001). The corresponding nomogram has showed excellent calibration and discrimination (C-index [95% CI], 0.752 [0.738-0.766]). The model was verified in the internal verification set (0.760 [0.739-0.781]) and the Chinese multicenter set (0.784 [0.607-0.961]). In addition, the AUC further confirmed the accuracy of the nomogram in predicting survival. The calibration curve of OS within 5 years confirmed good calibration of the nomogram. CONCLUSIONS: This model and the corresponding risk classification system may provide useful tools for clinicians to evaluate the long-term prognosis of patients and carry out personalized clinical evaluation.

[Clinical analysis of 30 cases of Castleman disease with different types of thoracic involvement].

Objective: To improve the clinical understanding of Castleman disease (CD) with different types of thoracic involvement, including their clinical features, radiological and pathological findings, diagnosis and current treatment strategies. Methods: Retrospective analysis of 30 patients diagnosed with CD with thoracic involvement and hospitalized between June 2009 and May 2019 in The First Affiliated Hospital of Guangzhou Medical University was performed. Patients were divided into three groups for subsequent analysis based on the clinical data: CD with bronchiolitis obliterans (BO) , unicentric Castleman disease (UCD) without BO, and multicentric Castleman disease (MCD) without BO. Results: Among the 30 patients, there were 5 (16.7%) patients diagnosed with BO, 18 (60.0%) patients had UCD without BO and 7 (23.3%) patients had MCD without BO. The average age of MCD without BO patients was significantly older than that of BO and UCD without BO patients[ (49.29±5.39) ys vs (27.20±3.76) ys and (37.17±2.87) ys; P=0.005 and 0.034, respectively) ]. Pulmonary symptoms were commonly seen in BO group (100%) and MCD without BO group (71.4%) . while no pulmonary symptoms were seen in UCD without BO group. Key abnormal laboratory findings were erythrocyte sedimentation rate (ESR) increase (40%in BO group and 57.1% in MCD without BO group) and hypoxia (60% in BO group and 28.6% in MCD without BO group) . Other abnormal laboratory findings seen in MCD without BO group included anemia and IgG increase (both 57.1%) . Notably, all patients in BO group had extremely severe mixed ventilation dysfunction in the lung function test. CT scan showed lung parenchyma involvement in BO group (100%) , in UCD without BO group (11.1%) featured by solitary pulmonary nodule and in MCD without BO group (57.1%) featured by diffuse lesions in bilateral lungs. The size of lymph nodes was significantly smaller in MCD without BO group comparing to that in BO group and UCD without BO group[short diameter (1.83±0.51) cm vs (4.73±1.63) cm and (3.62±0.26) cm; P=0.006 and 0.011, respectively]. All patients (100%) in the BO group had a pathological type of transparent vascular variant while the same pathological type accounts for 88.9% in UCD without BO patients. The predominantly pathological type (57.1%) was plasma cell variant in the MCD without BO group. Oral ulcers presented in all patients in BO group but were relieved after the mass resection and immunomodulatory therapy, but the pulmonary symptoms were still progressively aggravated. Thoracoscopic mass excision was the main treatment for UCD without BO patients while chemotherapy, immunomodulatory and targeted therapy were commonly used for MCD without BO treatment. Conclusion: The age, clinical symptom, laboratory finding, lung function, imaging manifestation, pathology, treatment and prognosis were different among the three groups. This classification could improve clinical understanding of the disease.