Changes in thyroid function in patients with liver failure and their clinical significance:A clinical study of non-thyroidal illness syndrome in patients with liver failure

Background:Non-thyroidal illness syndrome(NTIS)develops in a large proportion of critically ill patients and is associated with high risk for death.We aimed to investigate the correlation between NTIS and liver failure,and the short-term mortality of patients with these conditions.Methods:The clinical data of 87 patients with liver failure were collected retrospectively,73 of them were randomly selected for an observational study and to establish prognostic models,and 14 for model validation.Another 73 sex-and age-matched patients with mild chronic hepatitis were randomly selected as a control group.Serum free triiodothyronine(FT3),free thyroxine(FT4),and thyroid-stimulating hormone(TSH)were measured.The clinical characteristics of patients with liver failure and NTIS were analyzed.The follow-up of patients lasted for 3 months.Additionally,the values for predicting short-term mortality of model for end-stage liver disease(MELD),Child-Turcotte-Pugh(CTP),chronic liver failure-sequential organ failure assessment(CLIF-SOFA)scores,FT3-MELD model,and FT3 were evaluated.Results:The observation group had significantly lower FT3(2.79±0.71 vs.4.43±0.75 pmol/L,P<0.001)and TSH[0.618(0.186-1.185)vs.1.800(1.570-2.590)mIU/L,P<0.001],and higher FT4(19.51±6.26 vs.14.47±2.19 pmol/L,P<0.001)than the control group.NTIS was diagnosed in 49 of the patients with liver failure(67.12%).In the observation group,patients with NTIS had a higher mortality rate than those without(63.27%vs.25.00%,P=0.002).Across the whole cohort,the 3-month mortality was 50.68%.The international normalized ratios(INR)were 2.40±1.41 in survivors and 3.53±1.81 in deaths(P=0.004),the creatinine(Cr)concentrations were 73.27±36.94μmol/L and 117.08±87.98μmol/L(P=0.008),the FT3 concentrations were 3.13±0.59 pmol/L and 2.47±0.68 pmol/L(P<0.001),the MELD scores were 22.19±6.64 and 29.57±7.99(P<0.001),the CTP scores were 10.67±1.53 and 11.78±1.25(P=0.001),and the CLIF-SOFA scores were 8.42±1.68 and 10.16±2.03(P<0.001),respectively.FT3 was negatively correlated with MELD score(r=−0.430,P<0.001).An FT3-MELD model was established by subjecting FT3 concentration and MELD score to logistic regression analysis using the following formula:Logit(P)=−1.337×FT3+0.114×MELD+0.880.The area under the receiver operating characteristic(ROC)curve was 0.827 and the optimal cut-off value was 0.4523.The corresponding sensitivity and specificity were 67.6%and 91.7%.The areas under the ROC curve for FT3 concentration,MELD score,CTP score,and CLIF-SOFA score were 0.809,0.779,0.699,and 0.737,respectively.Conclusions:Patients with liver failure often develop NTIS.FT3-MELD score perform better than CTP and CLIF-SOFA scores in predicting mortality in patients with liver failure.Thus,the FT3-MELD model could be of great value for the evaluation of the short-term mortality of such patients.

Phase Ⅱb trial of in vivo electroporation mediated dualplasmid hepatitis B virus DNA vaccine in chronic hepatitis B patients under lamivudine therapy

AIM To assess the efficacy and safety of in vivo electroporation(EP)-mediated dual-plasmid hepatitis B virus(HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine(LAM) in patients with chronic hepatitis B. METHODS Two hundred and twenty-five patients were randomized to receive either LAM + vaccine(vaccine group, n = 109) or LAM + placebo(control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12(start of treatment with vaccine or placebo, SOT), 16, 24, and 36(end of treatment with vaccine or placebo, EOT). RESULTS In the modified intent-to-treat population, morepatients had a decrease in HBV DNA > 2 log10 IU/m L in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir(ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeA g seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy.

Estimation of Saturated Vapor Pressure from Nucleation Data

Saturated vapor pressure was calculated from the nucleation experimental data using the thermodynamically consistent nucleation theory in which the effect of real gas is considered. The cubic polynomial fit equations of saturation pressure for several substances were obtained based on the calculation. The results of the calculations were compared to those of thermodynamic equilibrium equation and the empirical equation and applied to the predictions of the classical nucleation theory. The results show that the saturation pressures estimated from the nucleation data agree fairly well with those of empirical equations for the substances investigated, and this indicates that the predictions from the classical nucleation theory are close to the experimental data.

Superconvergence of a Combined Mixed Finite Element and Discontinuous Galerkin Method for a Compressible Miscible Displacement Problem

A combined mixed finite element and discontinuous Galerkin method for a compressible miscible displacement problem which includes molecular diffusion and dispersion in porous media is investigated. That is to say, the mixed finite element method with Raviart-Thomas space is applied to the flow equation, and the transport one is solved by the symmetric interior penalty discontinuous Galerkin （SIPG） approximation. Based on projection interpolations and induction hypotheses, a superconvergence estimate is obtained. During the analysis, an extension of the Darcy velocity along the Gauss line is also used in the evaluation of the coefficients in the Galerkin procedure for the concentration.