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OBJECTIVE To establish a method to detect the blood concentration of ibrutinib and apply it to the clinic. METHODS Using zanubrutinib as internal standard， the concentration of ibrutinib was detected by high performance liquid chromatography （HPLC） after plasma samples were processed by solid-phase extraction. The separation was performed on an Agilent 5 TC-C18（2） column with acetonitrile-0.5% potassium dihydrogen phosphate solution （43∶57， V/V） as the mobile phase at a flow rate of 1 mL/min， a detection wavelength of 260 nm， a column temperature of 40 ℃ ， a sample size of 20 μL， and a run time of 25 min. The concentration of ibrutinib was measured in the plasma of 9 patients with non-Hodgkin’s lymphoma 2 h after drug administration on the 30th day by the above method. RESULTS The linear range of the assayed mass concentration of ibrutinib was 10-500 ng/mL （R 2＝0.998 9）， the lower limit of quantification was 10 ng/mL， and the RSDs of the intra-batch and inter-batch precision tests were not higher than 12.77%. The recoveries of the extraction were 74.80% and 97.70%， with both RSDs＜2.90%， and the RSDs of the stability tests were not higher than 7.10%. The peak plasma concentrations of 9 patients were 15.341-279.628 ng/mL. CONCLUSIONS The established HPLC method is simple and rapid， and can be used for the determination of ibrutinib concentration in plasma samples.
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Objective:To explore the prognostic value of lymphocyte subsets in adult hemophagocytic syndrome (HPS).Methods:A total of 172 adult HPS patients diagnosed in 8 medical centers from January 2013 to August 2020 were selected for the study, of whom 87 were male (50.6%, 87/172), and 85 were female (49.4%, 85/172), with 68 survivors and 104 deaths. The clinical data were summarized, and variables such as lymphocyte subsets, immunoglobulin characteristics and fibrinogen were retrospectively analyzed, and the correlation between the mentioned variables and patient prognosis was analyzed. The optimal cut-off values of continuous variables were calculated by MaxStat, and the prognostic factors of HPS patients were screened based on the Cox proportional hazard regression model.Results:The median age of HPS patients was 56 (42, 66) years old, and the 5-year cumulative survival rate was 37.4% (37.4/100). The median age, platelet and albumin were 48 (27, 63) years, 84×10 9/L and 32.3 g/L in the survival group, and 59 years, 45.5×10 9/L, and 27.3 g/L in the death group, respectively. The differences between the two groups was statistically significant ( Z=?3.368, P=0.001; Z=?3.156, P=0.002; Z=?3.431, P=0.001). Patients with differentiated cluster 8+(CD8+)<11.1%, CD3+<64.9%, CD4+>51%, and CD4/CD8 ratio>2.18 had poor prognosis (χ 2=7.498, P=0.023; χ 2=4.169, P=0.041; χ 2=4.316, P=0.038; χ 2=9.372, P=0.002). Multivariable analysis showed that CD4/CD8 ratio, age, fibrinogen and hemoglobin were independent prognostic factors in HPS patients ( HR=2.435, P=0.027; HR=5.790, P<0.001; HR=0.432, P=0.018; HR=0.427, P=0.018). Conclusion:Peripheral blood lymphocyte subsets can be used to evaluate the prognosis of patients with HPS; CD4/CD8 ratio, age, fibrinogen, and hemoglobin are independent prognostic factors in HPS patients.
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Objective:To explore the prognostic influencing factors of adult lymphoma-associated hemophagocytic syndrome (LAHS) based on multicenter data.Methods:The clinical data of 86 LAHS patients diagnosed in 9 medical centers of Huaihai Lymphoma Working Group from January 2015 to August 2020 were retrospectively analyzed. The optimal cut-off value of continuous variables was obtained based on MaxStat algorithm. Cox proportional hazard regression model was used for univariate and multivariate analyses. Kaplan-Meier method was used for survival analysis, and log-rank test was performed.Results:Among the 86 adult LAHS patients, 50 (58.1%) were males and 36 (41.9%) were females, the median age of the patients was 57 years old (19-76 years old), and the median overall survival (OS) time was 1.67 months (95% CI 0.09- 3.24 months). The most common pathologic type was diffuse large B-cell lymphoma (58 cases, 67.44%). Based on MaxStat algorithm, the optimal cut-off values of age, albumin, serum creatinine, lactate dehydrogenase, fibrinogen and platelet count were 64 years old, 30.1 g/L, 67 μmol/L, 1 045 U/L, 4.58 g/L and 72×10 9/L, respectively. Multivariate analysis showed that patient's age, lactate dehydrogenase, albumin and fibrinogen levels were independent influencing factors for OS (all P < 0.05). Conclusions:LAHS is dangerous and progresses quickly. Patients with age ≥ 64 years old, lactate dehydrogenase ≥ 1 045 U/L, fibrinogen ≥ 4.58 g/L and albumin < 30.1 g/L have poor survival.
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Objective:To analyze the relationship of fractional exhaled nitric oxide(FeNO)levels with eosinophils(EOS), C-reactive protein(CRP), procalcitonin(PCT)levels in elderly patients with asthma-chronic obstructive pulmonary disease overlap(ACO).Methods:A retrospective study was conducted.According to the inclusion criteria, 60 elderly patients with ACO admitted in Fujian Geriatric Hospital from May 2016 to May 2019 were enrolled in the ACO group.During the same period, 60 patients with bronchial asthma were included in the asthma group, 60 patients with chronic obstructive pulmonary disease(COPD)were recruited in the COPD group, and 60 people taking health examination were included in the health group.Levels of FeNO, EOS, CRP and PCT were detected and compared between the groups.Correlations of FeNO levels with EOS and inflammatory factors were analyzed by the Spearman correlation.Results:The group with asthma alone showed the highest levels of FeNO, followed by the ACO group, the COPD group and the healthy group( F=970.235, P=0.000). The ACO group had the highest levels of EOS, CRP and PCT, followed by the COPD group, the asthma group and the healthy group( F=103.74, 76.648 and 57.042, P=0.000). Spearman bivariate correlation analysis showed that FeNO levels were positively correlated with levels of EOS, CRP and PCT in the asthma, COPD and ACO groups(the asthma group: r=0.646, 0.326 and 0.497, P=0.000, 0.014 and 0.000; the COPD group: r=0.398, 0.613 and 0.432, P=0.009, 0.000 and 0.001 the ACO group: r=0.654, 0.573 and 0.516, P=0.000, 0.000 and 0.000). Conclusions:High levels of FeNO are found in elderly patients with ACO.Levels of FeNO are positively correlated with EOS, CRP and PCT levels in peripheral blood, and can be used as a sensitive index for airway hyperinflammatory responses.
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Objective To explore the correlation between volumetric capnography(VCap)and traditional pulmonary function in chronic obstructive pulmonary disease(COPD),so as to assess whether VCap can be used as alternative indicators for the evaluation of COPD severity when some of the elderly COPD patients do not accomplish the traditional pulmonary function tests.Methods 960 patients admitted to Fujian Geriatric Hospital from June 2008 to June 2015 and undergoing pulmonary function tests were included in the study.They were divided into 2 groups of the COPD group(640 cases)and the control group(320 cases).The pulmonary function of COPD group was divided into 4 subgroups(Ⅰ~Ⅳ).All persons received tests of traditional pulmonary function and VCap.The correlations between VCap and traditional pulmonary function indexes and between VCap and COPD severity were observed.Results The differences in Vm25-50/VT,Vm50-75/VT,dC/dV3,SR23 of VCap between the 4 subgroups(COPDⅠ~COPDⅣ)and control group were statistically significant(all P0.05).The difference in CO2 max between the COPD Ⅲ group(severe or more severe group)and control group was statistically significant(t=6.91 and 4.65,all P0.555,P<0.05).The specificity of Vm25-50/VT of VCap for the diagnosis of COPD was best,but its sensitivity was poor than other indexes of VCap.The indexes with both high sensitivity and high specificity were Vm50-75/VT and dC/dV3.Conclusions When the patients with COPD manifest the mild airflow limited,Vm25-50/VT,Vm50-75/VT,dC/dV3 and SR23 of VCap are gradually increased with abnormal VCap figures when the illness progressed.The CO2max of VCap might be one of the indexes for assessing the severity of severe or more severe COPD.