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Objective:To investigate the safety and efficacy of chemoradiotherapy compared with chemotherapy after R0 excision in pN + esophageal squamous cell carcinoma (ESCC) patients. Methods:A retrospective analysis was performed on the pathological data of 99 pN + ESCC patients who underwent radical esophagectomy with R0 resection in Renmin Hospital of Wuhan University from January 2017 to December 2020. According to postoperative adjuvant treatment methods, the patients were divided into chemo-radiotherapy group ( n=41) and chemotherapy group ( n=58). The main outcome measures were disease-free survival (DFS), overall survival (OS) and the incidences of treatment-related adverse events. Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression model was used to analyze the prognostic factors. Results:The median DFS and OS of 99 patients were 20.0 months and 28.0 months respectively. The 1- and 3-year DFS rates were 60.8% and 34.5% respectively. The 1- and 3-year OS rates were 83.5% and 40.2% respectively. The median DFS was 39.0 months in the chemoradiotherapy group and 10.0 months in the chemotherapy group, and the 1- and 3-year DFS rates were 79.4% vs. 48.3% and 57.3% vs. 24.5% respectively, with a statistically significant difference ( χ2=12.27, P<0.001). The median OS in the chemoradiotherapy group was not reached, and 21.0 months in the chemotherapy group, and the 1- and 3-year OS rates of the chemoradiotherapy group and chemotherapy group were 92.1% vs. 75.9% and 60.8% vs. 27.3%, with a statistically significant difference ( χ2=11.12, P=0.001). Univariate analysis showed that pN stage ( HR=0.58, 95% CI: 0.34-0.97, P=0.038), nerve invasion ( HR=1.88, 95% CI: 1.11-3.20, P=0.020) and adjuvant therapy ( HR=0.37, 95% CI: 0.21-0.67, P<0.001) were independent influencing factors of DFS in pN + ESCC patients. Adjuvant therapy ( HR=0.33, 95% CI: 0.17-0.66, P=0.001) was an independent factor influencing OS in pN + ESCC patients. Multivariate analysis showed that pN stage ( HR=0.54, 95% CI: 0.30-0.97, P=0.038) and adjuvant therapy ( HR=0.38, 95% CI: 0.21-0.69, P=0.001) were independent prognostic factors of DFS. Adjuvant therapy ( HR=0.34, 95% CI: 0.17-0.69, P=0.003) was an independent prognostic factor for OS. During adjuvant therapy, there were statistically significant differences in the incidences of leukopenia [65.85% (27/41) vs. 31.03% (18/58), χ2=11.75, P=0.001], thrombocytopenia [29.27% (12/41) vs. 10.34% (6/58), χ2=5.78, P=0.016], radioactive esophagitis [21.95% (9/41) vs. 0 (0/58), χ2=11.48, P=0.001], and radioactive pneumonia [21.95% (9/41) vs. 0 (0/58), χ2=11.48, P=0.001] between the two groups. Conclusion:Compared with chemotherapy, chemoradiotherapy can significantly improve DFS and OS of pN + ESCC patients with R0 resection after radical surgery, and the adverse reactions can be tolerated. pN stage and adjuvant therapy are independent prognostic factors for DFS, and adjuvant therapy is an independent prognostic factor for OS.
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Objective:To analyze the difference of immune damage between patients with severe fever with thrombocytopenia syndrome (SFTS) and patients with tsutsugamushi disease.Methods:A prospective case-control study was conducted. Thirty-one patients with SFTS and 16 patients with tsutsugamushi disease admitted to the First Affiliated Hospital of Anhui Medical University from October 2014 to June 2017 were enrolled, and another 10 healthy people were enrolled as control. The counts of CD4 + and CD8 + T lymphocytes, and the proportion of CD3 + T lymphocytes, natural kill cells (NK cells), B lymphocytes and plasma cells were detected by flow cytometry. Thirty-four inflammatory mediators were determined by a multiplex Luminex? system synchronously. The differences of lymphocytes and cytokines between the two groups were compared. Results:The proportion of CD3 + T lymphocytes, the counts of CD4 + and CD8 + T lymphocytes in SFTS patients were significantly lower than those in patients with tsutsugamushi disease ( t values were 4.860, 9.411 and 5.030, respectively, all P < 0.01), and the proportion of NK cells and B lymphocytes were significantly higher than those in patients with tsutsugamushi disease ( t values were 2.344 and 5.896, respectively, both P < 0.05). The proportion of plasma cells in peripheral blood of SFTS patients was (7.7±1.2)%, the highest proportion of plasma cells in severe SFTS patients was up to 30%, and all patients showed λ monoclonal cell group in plasma cells. No plasma cells were detected in tsutsugamushi disease patients. The abnormal expressions of interleukin-1 receptor antibody (IL-1RA), interleukin (IL-6, IL-15, IL-10, IL-8), tumor necrosis factor-α (TNF-α), γ-interferon (IFN-γ), granulocyte colony-stimulating factor (G-CSF), eosinophil chemotactic factor (Eotaxin), IFN-γ-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP-1α, MIP-1β), platelet-derived growth factor (PDGF-AA, PDGF-AB/BB), activated regulatory normal T cells and secretion factors (RANTES) were found in patients with SFTS and tsutsugamushi disease. The levels of IL-1RA, IL-6, IL-15, IL-10, TNF-α, IFN-γ, G-CSF, Eotaxin, IL-8, IP-10, MCP-1 and MIP-1α in SFTS patients were significantly higher than those in patients with tsutsugamushi disease ( Z values were 2.312, 2.447, 3.660, 5.444, 1.965, 2.402, 2.402, 2.997, 3.525, 2.481, 3.817, and 2.211, respectively, all P < 0.05), while PDGF-AA, PDGF-AB/BB and RANTES were significantly lower than those in patients with tsutsugamushi disease ( Z values were 3.728, 2.514, 2.649, respectively, all P < 0.05). Correlation analysis showed that RANTES, PDGF-AA and PDGF-AB/BB levels were significantly positively correlated with the level of platelet in patients with SFTS and tsutsugamushi disease (SFTS: r values were 0.223, 0.365, 0.330; tsutsugamushi disease: r values were 0.263, 0.632, 0.407, respectively, all P < 0.05). In SFTS patients, compared with the survival group ( n = 21), the CD3 + and CD4 + T lymphocytes in the death group ( n = 10) significantly decreased, while the plasma cells significantly increased ( t values were 3.980, 3.314 and 26.692, respectively, all P < 0.01); IL-1RA, IL-6, IL-15, IL-10, TNF-α, IFN-γ, G-CSF, Eotaxin, IL-8, IP-10, MCP-1, MIP-1α and MIP-1β significantly increased, while PDGF-AA, PDGF-AB/BB and RANTES significantly decreased ( Z values were 3.930, 4.014, 2.832, 3.592, 2.958, 3.508, 2.578, 3.254, 4.270, 3.465, 2.663, 3.085, 3.107, 3.639, 3.043 and 3.825, respectively, all P < 0.05). Conclusions:The immune function was impaired more seriously in SFTS patients than that in tsutsugamushi disease patients. Excessive humoral immunity and apoptosis of T lymphocytes are closely related to the death in SFTS patients. The detection of CD4 cells, plasma cells and proinflammatory and anti-inflammatory cytokines (e.g. IL-6, IL-10) had great clinical significance for the differentiation and illness evaluation in disease with SFTS or tsutsugamushi disease.
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Objective To analyze the differences of clinical manifestations and organ damage between patients with severe fever with thrombocytopenia syndrome(SFTS)and patients with tsutsugamushi disease,and to investigate the prognostic factors of SFTS.Methods The research was performed on 49 patients with SFTS and 16 patients with tsutsugamushi disease who visited the First Affiliated Hospital of Anhui Medical University from October 2014 to June 2017.The general information of patients including region,age,gender and clinical manifestations were evaluated.Blood routine,liver and kidney function,myocardial enzyme levels,lipase,amylase,electrolytes,C-reactive protein,procalcitonin,prothrombin time(PT)and activated partial thromboplastin time(APTT)were continuously monitored during the course of disease.T test was used for continuous variables of normal distribution,and non-parametric test was used for variables of non-normal distribution.Chi-square test was used for categorical variables.Results The mean age of SFTS patients was 62.1±15.5(ranging from 17 to 87 years)and the mean age of tsutsugamushi patients was 56.1±9.2(ranging from 47 to 73 years).There was no significant difference between the two groups(t=1.47,P=0.147).There were 25 males(51%)in SFTS patients and 8 males(50%)in tsutsugamushi disease patients.There was no significant difference between the two groups(x2=0.005,P=0.943).The incidences of headache,vomiting,superficial lymphadenectasis,disturbance of consciousness,proteinuria,hematuria,pulmonary infection,multiple organ dysfunction and acute pancreatitis in SFTS patients were all significantly higher than those in tsutsugamushi disease patients(x2=8.82,4.38,8.71,11.17,7.88,5.56,4.35,9.43,and 8.13,respectively,P <0.05 or 0.01).The counts of leukocytes(Z=2.73),neutrophils(Z=2.46),lymphocytes(Z=3.15),platelets(Z=4.25),albumin(Z=2.65)and sodium ion(t=2.10)in SFTS patients were all significantly lower than those in patients with tsutsugamushi disease(P <0.05 or 0.01).The levels of aspartate aminotransferase(Z=2.94),lactate dehydrogenase(Z=3.42),creatine kinase(CK)(Z=2.88),amylase(Z=2.11),lipase(Z=2.82),creatinine(Z=2.07)and urea nitrogen(Z=2.50)in fatal SFTS patients were all significantly higher than those in patients with tsutsugamushi disease(P <0.05 or 0.01).Among 49 SFTS patients,16 patients died and 33 patients recovered finally.The age(t=3.33),platelet count(Z=2.55),alanine aminotransferase(ALT)(Z=2.10),aspartate aminotransferase(AST)(Z=2.22),lactate dehydrogenase(Z=2.26),CK(Z=3.50),CK-MB(Z=3.10),creatinine(Z=2.17),urea nitrogen(Z=2.36),and sodium(t=2.65)between the two subgroups had significant differences(P <0.05 or 0.01).Conclusions SFTS is more severe and has high mortality,while tsutsugamushi disease has a better prognosis.Early differential diagnosis and early rational treatment are important to reduce the mortality of patients with SFTS.