Development and validation of a nomogram for predicting in-hospital mortality of intensive care unit patients with liver cirrhosis.

BACKGROUND: Liver cirrhosis patients admitted to intensive care unit (ICU) have a high mortality rate. AIM: To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis. METHODS: We extracted demographic, etiological, vital sign, laboratory test, comorbidity, complication, treatment, and severity score data of liver cirrhosis patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and electronic ICU (eICU) collaborative research database (eICU-CRD). Predictor selection and model building were based on the MIMIC-IV dataset. The variables selected through least absolute shrinkage and selection operator analysis were further screened through multivariate regression analysis to obtain final predictors. The final predictors were included in the multivariate logistic regression model, which was used to construct a nomogram. Finally, we conducted external validation using the eICU-CRD. The area under the receiver operating characteristic curve (AUC), decision curve, and calibration curve were used to assess the efficacy of the models. RESULTS: Risk factors, including the mean respiratory rate, mean systolic blood pressure, mean heart rate, white blood cells, international normalized ratio, total bilirubin, age, invasive ventilation, vasopressor use, maximum stage of acute kidney injury, and sequential organ failure assessment score, were included in the multivariate logistic regression. The model achieved AUCs of 0.864 and 0.808 in the MIMIC-IV and eICU-CRD databases, respectively. The calibration curve also confirmed the predictive ability of the model, while the decision curve confirmed its clinical value. CONCLUSION: The nomogram has high accuracy in predicting in-hospital mortality. Improving the included predictors may help improve the prognosis of patients.

Miniaturized tri-notched wideband bandpass filter with ultrawide upper stopband suppression.

Stepped impedance resonator (SIR) and its derivative resonators are widely used in the design of microwave filters. However, many spurious modes will be introduced into the stopband, resulting in lower upper stopband suppression and performance degradation. Based on the principle of slit line, a method to enhance the upper stopband suppression is proposed and verified by a miniaturized tri-notched wideband bandpass filter based on stub loaded ring resonator (SLRR) and shorted-stub loaded SIR (SSLSIR). The wideband is formed by coupling SLRR and interdigital lines, which has a rectangular DGS on the back of the substrate. Three notched bands with controllable positions in the passband can be produced by inserting two different SSLSIRs inside and outside the SLRR. Four slit lines are loaded on the low impedance stub of SSLSIR to adjust the high-order modes close to the transmission zeros (TZs). The operating frequency of the filter is 2.2-7.6 GHz, and the three notched bands are located at 2.97 GHz, 5.75 GHz and 6.46 GHz, respectively. The measurement results show that the - 20 dB enhanced upper stopband of the filter can reach 32 GHz, which proves that the filter has the characteristic of ultrawide upper stopband suppression while keeping the miniaturization.

Hygroscopicity of internally mixed particles composed of (NH4)2SO4 and citric acid under pulsed RH change.

In this research, we applied a pulsed RH controlling system and a rapid scan vacuum FTIR spectrometer (PRHCS-RSVFTIR) to investigate hygroscopicity of internally mixed (NH4)2SO4(AS)/citric acid (CA) particles. The water content and efflorescence ratio of AS in the particles and ambient relative humidity (RH) as a function of time were obtained with a subsecond time resolution. The hygroscopic behavior of AS aerosols in two different RH control processes (equilibrium and RH pulsed processes) showed that AS droplets crystallize with RH ranging from 42% to 26.5%. It was found that the half-life time ratio between the water content in the CA particles and the gas phase under RH pulsed change was greater than one under low RH conditions (<40% RH), indicating the significant water transfer limitation due to the high viscosity of CA aerosols at low RH, especially at RH<20%. In addition, water diffusion constants between 10-12 m2 s-1 and 10-13 m2 s-1 in micron size CA aerosols were obtained in a sub-second and second timescale. The addition of AS enhanced the water transfer limitation in the mixed aerosols. The efflorescence relative humidity (ERH) of the mixed particles with AS/CA by molar ratio 3:1 was found between 22.7% and 5.9%, which was much lower than AS particles. No efflorescence process was observed for the 1:1 mixed particles, indicating that CA greatly suppressed nucleation of AS. Our results have shown that the PRHCS-RSVFTIR is effective to simulate hygroscopicity and water transport of aerosols under fast variations in RH in atmosphere.

The Endophytic Fungus Phomopsis liquidambari Increases Nodulation and N2 Fixation in Arachis hypogaea by Enhancing Hydrogen Peroxide and Nitric Oxide Signalling.

The continuous cropping obstacles in monoculture fields are a major production constraint for peanuts. Application of the endophytic fungus Phomopsis liquidambari has increased peanut yields, and nodulation and N2 fixation increases have been considered as important factors for P. liquidambari infection-improved peanut yield. However, the mechanisms involved in this process remain unknown. This work showed that compared with only Bradyrhizobium inoculation, co-inoculation with P. liquidambari significantly elevated endogenous H2O2 and NO levels in peanut roots. Pre-treatment of seedlings with specific scavengers of H2O2 (CAT) and NO (cPTIO) blocked P. liquidambari-induced nodulation and N2 fixation. CAT not only suppressed the P. liquidambari-induced nodulation and N2 fixation, but also suppressed the enhanced H2O2 and NO generation. Nevertheless, the cPTIO did not significantly inhibit the induced H2O2 biosynthesis, implying that H2O2 acted upstream of NO production. These results were confirmed by observations that exogenous H2O2 and sodium nitroprusside (SNP) reversed the inhibition of P. liquidambari-increased nodulation and N2 fixation by the specific scavengers. The transcriptional activities of the symbiosis-related genes SymRK and CCaMK of peanut-Bradyrhizobium interactions also increased significantly in response to P. liquidambari, H2O2 and SNP treatments. The pot experiment further confirmed that the P. liquidambari infection-enhanced H2O2 and NO signalling pathways were significantly related to the increase in peanut nodulation and N2 fixation. This is the first report that endophytic fungus P. liquidambari can increase peanut-Bradyrhizobium interactions via enhanced H2O2/NO-dependent signalling crosstalk, which is conducive to the alleviation of continuous cropping obstacles via an increase in nodulation and N2 fixation.

Excessive intraoperative blood loss independently predicts recurrence of hepatocellular carcinoma after liver transplantation.

BACKGROUND: Several studies have investigated the effect of intraoperative blood loss (IBL) on recurrence of tumors. However, the independent effect of IBL on oncological outcome after liver transplantation (LT) for hepatocellular carcinoma (HCC) is unclear. METHODS: A total of 479 patients who underwent LT for HCC from January 2001 to December 2012 at our institution were enrolled in this retrospective study. Kaplan-Meier and Cox regression methods were used to assess the recurrence rate, as well as its risk factors. Stratified analysis was performed to further examine the effect of IBL on HCC recurrence according to different characteristics of tumors. We also investigated the independent risk factors for excessive IBL using logistic regression analysis. RESULTS: The median follow-up was 28 months (range, 1-131 months). Kaplan-Meier analysis with the log-rank test according to IBL at per liter intervals showed that IBL > 4 L was significantly associated with a higher recurrence rate (P < 0.001). Multivariate analysis identified that IBL > 4 L (P < 0.001; hazard ratio [HR] = 2.32, 95 % confidence interval [CI] = 1.60-3.36) was an independent risk factor for post-LT HCC recurrence, as well as age < 60 years, exceeding Milan criteria, α-fetoprotein levels > 400 ng/mL, and micro- and macrovascular invasion. IBL > 4 L (P < 0.001; HR = 2.45, 95 % CI = 1.64-3.66) was also independently associated with early (within 1 year) recurrence after LT. Furthermore, a significant correlation between IBL > 4 L and vascular invasion (P = 0.019) was found. IBL > 4 L was independently associated with HCC recurrence for patients with vascular invasion, but not for patients without vascular invasion. Finally, we found that the presence of ascites, model for end-stage liver disease score, and operation time were independent risk factors for IBL > 4 L. CONCLUSIONS: Excessive IBL is an independent predictor of HCC recurrence after LT, especially in patients with vascular invasion.

Validation of a criteria-specific long-term survival prediction model for hepatocellular carcinoma patients after liver transplantation.

The aim of this study was to validate a criteria-specific long-term survival prediction model (MHCAT) in a large cohort of hepatocellular carcinoma (HCC) patients after liver transplantation (LT) in China. Independent risk factors in MHCAT were retrospectively analysed for HCC patients recorded in the China Liver Transplant Registry. Survival predictions for each patient were calculated using MHCAT scores and the Metroticket formula separately, and the prediction efficacy of MHCAT and Metroticket was compared using the area under ROC curve (c-statistic). A total of 1371 LTs for HCC were analysed in the study, with a median follow-up of 22.2 months (IQR 6.1-72.4 months). The proportions meeting the Milan, UCSF, Fudan and Hangzhou criteria were 34.4%, 39.7%, 44.2% and 51.9%, respectively. The c-statistics for MHCAT predictions of 3- and 5-year survival rates of HCC recipients were 0.712-0.727 and 0.726-0.741, respectively. Among these patients, 1298 LTs for HCC were ultimately selected for the comparison analysis for prediction efficacy. The c-statistic of MHCAT for predictions of 3-year survival with reference to the Milan, UCSF and Fudan criteria was significantly increased compared with that for Metroticket (p < 0.05). In conclusion, MHCAT can effectively predict long-term survival for HCC recipients after LT.

Up-regulation of long non-coding RNA Sox2ot promotes hepatocellular carcinoma cell metastasis and correlates with poor prognosis.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA Sox2ot is up-regulated in some tumors. However, the contributions of Sox2ot to hepatocellular carcinoma (HCC) remain largely unknown. METHODS: In the present study, expression of lncRNA Sox2ot was evaluated by quantitative real-time PCR in tumor tissues and adjacent non-tumor tissues in 84 HCC patients. The association of lncRNA Sox2ot expression with clinicopathological features and the prognosis of HCC patients were also analyzed. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. Small interfering RNA assay was used to explore the function of lncRNA Sox2ot on HCC cell migration and invasion. RESULTS: lncRNA Sox2ot expression level was significantly higher in HCC tissues compared with adjacent non-tumor tissues (P<0.05). High expression of lncRNA Sox2ot was associated with histological grade, TNM stage, and vein invasion. The 5-year overall survival of high lncRNA Sox2ot expression group was significantly shorter than that of low lncRNA Sox2ot expression group (P<0.05). The multivariate Cox regression analysis indicated that lncRNA Sox2ot expression was an independent prognostic factor for overall survival. In addition, the metastasis ability of HCC cells was significantly decreased by knocking down lncRNA Sox2ot expression. CONCLUSIONS: The results suggested that lncRNA Sox2ot played crucial roles in promoting HCC cell migration and invasion, and might represent a novel prognostic biomarker for HCC.

Criteria-specific long-term survival prediction model for hepatocellular carcinoma patients after liver transplantation.

AIM: To establish a model to predict long-term survival of hepatocellular carcinoma (HCC) patients after liver transplantation (MHCAT). METHODS: Two hundred and twenty-three patients with HCC were followed for at least six years to identify independent risk factors for long-term survival after liver transplantation (LT). The criteria for HCC liver transplantation included the Milan, University of California San Francisco, Hangzhou and Shanghai Fudan criteria. The Cox regression model was used to build MHCAT specifying these criteria. A survival analysis was carried out for patients with high or low risk. RESULTS: The one-, three- and five-year cumulative survival of HCC patients after LT was 78.9%, 53.2% and 46.4%, respectively. Of the HCC patients, the proportion meeting the Hangzhou and Fudan criteria was significantly higher than the proportion meeting the Milan criteria (64.6% vs 39.5%, 52.0% vs 39.5%, P < 0.05). Moreover, the proportion meeting the Hangzhou criteria was also significantly higher than the proportion meeting other criteria (P < 0.01). Pre-operative alfa-fetoprotein level, intraoperative blood loss and retransplantation were common significant predictors of long-term survival in HCC patients with reference to the Milan, University of California San Francisco and Fudan criteria, whereas in MHCAT based on the Hangzhou criteria, total bilirubin, intraoperative blood loss and retransplantation were independent predictors. The c-statistic for MHCAT was 0.773-0.824, with no statistical difference among these four criteria. According to the MHCAT scoring system, patients with low risk showed a higher five-year survival than those with high risk (P < 0.001). CONCLUSION: MHCAT can effectively predict long-term survival for HCC patients, but needs to be verified by multi-center retrospective or randomized controlled trials.

Reconstruction of the middle hepatic vein tributary in adult right lobe living donor liver transplantation.

BACKGROUND: In adult-to-adult living donor liver transplantation (LDLT), the use of a right lobe graft without the middle hepatic vein (MHV) can cause hepatic congestion and disturbance of venous drainage. To solve this problem, we successfully used cadaveric venous allografts preserved in 4 °C University of Wisconsin (UW) solution within 10 days as interposition veins for drainage of the paramedian portion of the right lobe in adult LDLT. METHODS: From June 2007 to January 2008, 11 adult LDLT patients received modified right liver grafts. The major MHV tributaries (greater than 5 mm in diameter) of 9 cases were preserved and reconstructed using cadaveric interposition vein allografts that had been stored for 1 to 10 days in 4 °C UW solution. The regeneration of the paramedian sector of the grafts and the patency of the interposition vein allografts were examined by Doppler ultrasonography after the operation. RESULTS: MHV tributaries were reconstructed in 9 recipients. Only 1 recipient died of renal failure and severe pulmonary infection on day 9 after transplantation without any hemiliver venous outflow obstruction. The other 8 recipients achieved long-term survival with a median follow-up of 30 months. The cumulative patency rates of the 8 recipients were 63.63% (7/11), 45.45% (5/11), 45.45% (5/11) and 36.36% (4/11) at 3, 6, 12 and 24 months, respectively. Regeneration of the paramedian sectors was equivalent. CONCLUSION: The cadaveric venous allograft preserved in 4 °C UW solution within 10 days serves as a useful alternative for interposition veins in facilitating implantation of a right lobe graft and guarantees outflow of the MHV.

Suppression of allograft rejection by Tim-1-Fc through cross-linking with a novel Tim-1 binding partner on T cells.

Engagement of T-cell immunoglobulin mucin (Tim)-1 on T cells with its ligand, Tim-4, on antigen presenting cells delivers positive costimulatory signals to T cells. However, the molecular mechanisms for Tim-1-mediated regulation of T-cell activation and differentiation are relatively poorly understood. Here we investigated the role of Tim-1 in T-cell responses and allograft rejection using recombinant human Tim-1 extracellular domain and IgG1-Fc fusion proteins (Tim-1-Fc). In vitro assays confirmed that Tim-1-Fc selectively binds to CD4(+) effector T cells, but not dendritic cells or natural regulatory T cells (nTregs). Tim-1-Fc was able to inhibit the responses of purified CD4(+) T cells that do not express Tim-4 to stimulation by anti-CD3/CD28 mAbs, and this inhibition was associated with reduced AKT and ERK1/2 phosphorylation, but it had no influence on nTregs. Moreover, Tim-1-Fc inhibited the proliferation of CD4(+) T cells stimulated by allogeneic dendritic cells. Treatment of recipient mice with Tim-1-Fc significantly prolonged cardiac allograft survival in a fully MHC-mismatched strain combination, which was associated with impaired Th1 response and preserved Th2 and nTregs function. Importantly, the frequency of Foxp3(+) cells in splenic CD4(+) T cells was increased, thus shifting the balance toward regulators, even though Tim-1-Fc did not induce Foxp3 expression in CD4(+)CD25(-) T cells directly. These results indicate that Tim-1-Fc can inhibit T-cell responses through an unknown Tim-1 binding partner on T cells, and it is a promising immunosuppressive agent for preventing allograft rejection.

A single-center retrospective analysis of liver transplantation on 255 patients with hepatocellular carcinoma.

BACKGROUND: Liver transplantation (LT) was advocated as a salvage treatment of choice for patients with unresectable hepatocellular carcinoma (HCC). This study was designed to assess the eligibility of LT criteria for patients with HCC and to analyze the factors influencing the recurrence of HCC following LT, aiming to further improve the efficacy of LT for patients with HCC. METHODS: Clinical data of 255 patients with HCC who underwent LT between December 2001 and December 2007 at Shanghai Changzheng Hospital, China were retrospectively analyzed. RESULTS: Among these cases, 75 patients were within the Milan criteria and 180 were beyond it; 110 patients were within the University of California, San Francisco (UCSF) criteria, while 145 were beyond it. The difference in overall survival rates was not only significant between the patients within and beyond the Milan criteria but also between patients within and beyond the UCSF criteria. Tumor-node-metastasis (TNM) staging, portal vein tumor thrombus (PVTT), and the pre-operative alpha-fetoprotein (AFP) level were independent risk factors affecting the overall survival and post-operative recurrence-free survival rates of patients with HCC. Pathological staging and pre-operative local treatment of HCC had no obvious correlation with the post-operative recurrence-free survival rate. CONCLUSION: LT is an effective treatment modality for HCC. The UCSF criteria did not show better effectiveness than the Milan criteria. TNM staging, PVTT, and the pre-operative AFP level are closely related to the recurrence of HCC following LT.

Prediction of survival after liver transplantation for chronic severe hepatitis B based on preoperative prognostic scores: a single center's experience in China.

BACKGROUND: The aim of this study was to estimate the utility of a preoperative model of end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) score in predicting the prognosis after othotopic liver transplantation (OLT) for chronic severe hepatitis B (CSHB) and explore the prognostic factors. METHODS: The outcome of 137 patients who underwent OLT using donors after cardiac death (DCDs) for CSHB in our center was reviewed retrospectively. Survival analysis was performed using the Kaplan-Meier method; the log-rank test was used for univariate analysis; and the Cox proportional hazards regression model was used for prognostic factors screening. RESULTS: The overall mortality rate was 33.6% (46/137); and 1-month, 6-month, 1-year, and 5-year patient survival rates were 75.8, 72.0, 71.0, and 60.1%, respectively. Most patients (33/46) died during the first month after OLT. The area under the curve values generated by the receiver operating characteristics curves were 0.82 [95% confidence interval (CI) 0.72-0.92] and 0.68 (95% CI 0.58-0.79), respectively (P < 0.01), for the MELD and CTP models in predicting 1-month mortality after OLT. Patients with a preoperative MELD score <33.8 or a CTP score <12.5 had significantly better prognosis than those with higher scores (P < 0.05). Other mortality predictors include hepatic encephalopathy, preoperative infection, serum creatinine > or = 1.5 mg/dl. CONCLUSIONS: The MELD score was more efficient than the CTP score for evaluating the short-term prognosis in patients with CSHB undergoing OLT using DCDs, which should be taken into consideration during graft allocation.

Liver transplant recipients with portal vein thrombosis: a single center retrospective study.

BACKGROUND: Portal vein thrombosis (PVT) used to be a contraindication for liver transplantation (LT). This obstacle has been delt with following the improvement of LT-related techniques and therapeutic approaches to thrombosis. But the effect of PVT on LT outcomes is still controversial. We reviewed retrospectively the outcome of LT patients with PVT as well as risk factors and surgical management according to PVT grades. METHODS: A total of 465 adult LTs were performed from December 2002 through December 2006. Operative findings and the result of preoperative ultrasonography and imaging were reviewed for PVT grading (Yerdel grading). Comparison of risk factors, variables associated with perioperative period and prognosis between recipients with and without PVT is based on the grades. RESULTS: In the 465 LTs, 42 were operatively confirmed to have PVT (9.0%) (19 recipients with grade 1, 14 with grade 2, 7 with grade 3, and 2 with grade 4). Increased age and treatment of portal hypertension were associated with PVT. Grade 1 or 2 PVT was treated by direct anastomosis or single thrombectomy. In grade 3 PVT patients, the donor PV was directly anastomosed to the dilated branch of the recipient portal venous system or to the distal open superior mesenteric vein through an interposition vein graft if needed. Grade 4 PVT was managed by our modified cavoportal hemitransposition technique. The comparison between PVT patients and controls showed no significant difference in operative duration and blood transfusion (P>0.05). The flow rate of the PV was lower in the PVT patients (48.881+/-12.788 cm/s) than in the controls (57.172+/-21.715 cm/s, P<0.05). The PVT patients had such postoperative complications as renal failure and PV rethrombosis (P<0.05). The 1-year survival rates in PVT and non-PVT patients were 78.6% and 76.4% respectively (P>0.05); the 3-year survival rates were 58.8% and 56.4% respectively (P>0.05). CONCLUSIONS: PVT is not contraindicated for LT if it is graded. PVT recipients may have post-transplantation complications like renal failure and PV rethrombosis, and operative difficulty and patient survival are similar to those in recipients without PVT. Development of therapeutic approaches and accumulation of experience in dealing with PVT further improve the outcomes of LT in PVT recipients.

Prevention of hepatitis B virus reinfection after orthotopic liver transplantation.

BACKGROUND: Hepatitis B virus reinfection is an important problem after liver transplantation. The aim of this study was to discuss the prevention of hepatitis B virus reinfection following orthotopic liver transplantation. METHODS: Sixty-eight cases of chronic fulminant hepatitis B, end-stage liver cirrhosis, and liver carcinoma complicated with HBV cirrhosis were given anti-viral drugs before and after transplantation to prevent hepatitis B virus reinfection. Lamivudine was administered in 2 patients, lamivudine+hepatitis B immunoglobulin (HBIG) in 63, and adefovir+HBIG in 3. The measurement of serum HBV, HBV DNA, liver biopsy immunohistochemistry and clinical study were performed. RESULTS: In 1 of the 2 patients who developed reinfection after lamivudine administration, serum HBsAg, HBeAb, HBcAb, HBV DNA were positive and liver biopsy immunohistochemistry showed HBsAg phenotype. In 2 of 63 patients who developed reinfection after use of lamivudine+HBIG, serum HBsAg, HBeAb, HBcAb were positive and liver biopsy immunohistochemistry showed HBsAg phenotype. Serum HBV DNA was positive in one of them. Three patients developed no reinfection with HBV after use of adefovir. CONCLUSIONS: Orthotopic liver transplantation is effective in the treatment of HBV-infected diseases. Lamivudine+HBIG or adefovir+HBIG could effectively prevent hepatitis B virus reinfection.