Low immediate postoperative platelet count is associated with hepatic insufficiency after hepatectomy

AIM: To investigate the relationship between low immediate postoperative platelet count and perioperative outcome after liver resection in patients with hepatocellular carcinoma (HCC).METHODS: In a cohort of 565 consecutive hepatitis B-related HCC patients who underwent major liver resection, the characteristics and clinical outcomes after liver resection were compared between patients with immediate postoperative platelet count < 100 × 10⁹/L and patients with platelet count ≥ 100 × 10⁹/L. Risk factors for postoperative hepatic insufficiency were evaluated by multivariate analysis.RESULTS: Patients with a low immediate postoperative platelet count (< 100 × 10⁹/L) had more grade III-V complications (20.5% vs 12.4%, P = 0.016), and higher rates of postoperative liver failure (6.8% vs 2.6%, P = 0.02), hepatic insufficiency (31.5% vs 21.2%, P < 0.001) and mortality (6.8% vs 0.5%, P < 0.001), compared to patients with a platelet count ≥ 100 × 10⁹/L. The alanine aminotransferase levels on postoperative days 3 and 5, and bilirubin on postoperative days 1, 3 and 5 were higher in patients with immediate postoperative low platelet count. Multivariate analysis revealed that immediate postoperative low platelet count, rather than preoperative low platelet count, was a significant independent risk factor for hepatic insufficiency.CONCLUSION: A low immediate postoperative platelet count is an independent risk factor for hepatic insufficiency. Platelets can mediate liver regeneration in the cirrhotic liver.     

Prognostic value of M30/M65 for outcome of hepatitis B virus-related acute-on-chronic liver failure

AIM: To determine the prognostic value of circulating indicators of cell death in acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B virus (HBV) infection as the single etiology.METHODS: Full length and caspase cleaved cytokeratin 18 (detected as M65 and M30 antigens) represent circulating indicators of necrosis and apoptosis. M65 and M30 were identified by enzyme-linked immunosorbent assay in 169 subjects including healthy controls (n = 33), patients with chronic hepatitis B (CHB, n = 55) and patients with ACLF (n = 81). According to the 3-mo survival period, ACLF patients were defined as having spontaneous recovery (n = 33) and non-spontaneous recovery which included deceased patients and those who required liver transplantation (n = 48).RESULTS: Both biomarker levels significantly increased gradually as liver disease progressed (for M65: P < 0.001 for all; for M30: control vs CHB, P = 0.072; others: P < 0.001 for all). In contrast, the M30/M65 ratio was significantly higher in controls compared with CHB patients (P = 0.010) or ACLF patients (P < 0.001). In addition, the area under receiver operating characteristic curve (AUC) analysis demonstrated that both biomarkers had diagnostic value (AUC ≥ 0.80) in identifying ACLF from CHB patients. Interestingly, it is worth noting that the M30/M65 ratio was significantly different between spontaneous and non-spontaneous recovery in ACLF patients (P = 0.032). The prognostic value of the M30/M65 ratio was compared with the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores at the 3-mo survival period, the AUC of the M30/M65 ratio was 0.66 with a sensitivity of 52.9% and the highest specificity of 92.6% (MELD:AUC = 0.71; sensitivity, 79.4%; specificity, 63.0%; Child-Pugh: AUC = 0.77; sensitivity, 61.8%; specificity, 88.9%).CONCLUSION: M65 and M30 are strongly associated with liver disease severity. The M30/M65 ratio may be a potential prognostic marker for spontaneous recovery in patients with HBV-related ACLF.     

Risk factors for acute kidney injury following coronary artery bypass graft surgery in a Chinese population and development of a prediction model

BACKGROUNDAcute kidney injury (AKI) after coronary artery bypass graft (CABG) surgery is associated with significant morbidity and mortality. This retrospective study aimed to establish a risk score for postoperative AKI in a Chinese population.METHODSA total of 1138 patients undergoing CABG were collected from September 2018 to May 2020 and divided into a derivation and validation cohort. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multivariable logistic regression analysis was used to determine the independent predictors of AKI, and the predictive ability of the model was determined using a receiver operating characteristic (ROC) curve.RESULTSThe incidence of cardiac surgery–associated acute kidney injury (CSA-AKI) was 24.17%, and 0.53% of AKI patients required dialysis (AKI-D). Among the derivation cohort, multivariable logistic regression showed that age ≥ 70 years, body mass index (BMI) ≥ 25 kg/m², estimated glomerular filtration rate (eGFR) ≤ 60 mL/min per 1.73 m², ejection fraction (EF) ≤ 45%, use of statins, red blood cell transfusion, use of adrenaline, intra-aortic balloon pump (IABP) implantation, postoperative low cardiac output syndrome (LCOS) and reoperation for bleeding were independent predictors. The predictive model was scored from 0 to 32 points with three risk categories. The AKI frequencies were as follows: 0−8 points (15.9%), 9−17points (36.5%) and ≥ 18 points (90.4%). The area under of the ROC curve was 0.730 (95% CI: 0.691−0.768) in the derivation cohort. The predictive index had good discrimination in the validation cohort, with an area under the curve of 0.735 (95% CI: 0.655−0.815). The model was well calibrated according to the Hosmer-Lemeshow test (P = 0.372). CONCLUSIONThe performance of the prediction model was valid and accurate in predicting KDIGO-AKI after CABG surgery in Chinese patients, and could improve the early prognosis and clinical interventions.     

High expression of CD11c indicates favorable prognosis in patients with gastric cancer

AIM: To determine the relationship between CD11 c expression level and prognosis in patients with gastric cancer(GC).METHODS: This retrospective survival study was performed from July 31,2008 to June 30,2014. Our study inclusion criteria included all the patients with GC who underwent surgical resection between January 1998 and December 2009 in the Third Affiliated Hospital of Soochow University. CD11 c expression levels in 140 patients with GC at different UICC stages were evaluated using immunohistochemistry,and GC tissues from 16 cases were further verified by q RTPCR. The χ2 test was used to compare the patientand disease-related factors between the low CD11 c expression group and the high expression group. Univariate probabilities of overall survival(OS) and disease-free survival(DFS) were assessed using the Kaplan-Meier method. The log rank test was used to compare survival curves. Different multivariate COX models were used to estimate the association between CD11 c expression and both death and recurrence riskin GC patients.RESULTS: The average CD11 c expression level was 5.1 ± 1.8/high power field(HPF) in 10 gastritis samples,4.5 ± 2.3/HPF in 10 gastric polyp samples and 9.7 ± 6.3/HPF in 140 gastric cancer samples,respectively. The CD11 c expression level was significantly decreased from UICC stage Ⅰ to stage Ⅳ(stage Ⅰ: 16.0 ± 7.4,stage Ⅱ: 10.4 ± 5.5,stage Ⅲ: 9.4 ± 6.1,stage Ⅳ: 5.3 ± 3.2,P 0.001). Patients in the high CD11 c expression group had a greater 3- and 5-year OS probability and longer median survival time compared with the low CD11 c expression group,(67.7% vs 39.2%; 51.4% vs 29.0%; 67.0 mo vs 28.0 mo; χ2 = 6.80,P = 0.009),and had a greater 3- and 5-year DFS probability and longer median DFS time(63.7% vs 24.0%; 49.1% vs 11.9%; 64.0 mo vs 18.0 mo; χ2 = 15.39,P 0.001). Patients with high CD11 c high expression had a reduced risk of death(HR = 0.56,95%CI: 0.33-0.98,P 0.05) and relapse(HR = 0.39,95%CI: 0.23-0.67,P 0.01) compared with patients with low CD11 c expression after adjustment of potential confounders,with the exception of tumor size. However,the protective effect related to death(HR = 0.90,95%CI: 0.49-1.67,P = 0.749) and relapse(HR = 0.65,95%CI: 0.36-1.19,P = 0.160) disappeared when tumor size was incorporated into the model.CONCLUSION: High expression of CD11 c decreased the risk of death and relapse,and may be regarded as an alternative indicator of favorable prognosis in patients with GC.     

Chronic Liver Failure-Sequential Organ Failure Assessment is better than the Asia-Pacific Association for the Study of Liver criteria for defining acute-on-chronic liver failure and predicting outcome

AIM: To compare the utility of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) and Asia-Pacific Association for the Study of Liver (APASL) definitions of acute-on-chronic liver failure (ACLF) in predicting short-term prognosis of patients with ACLF.METHODS: Consecutive patients of cirrhosis with acute decompensation were prospectively included. They were grouped into ACLF and no ACLF groups as per CLIF-SOFA and APASL criteria. Patients were followed up for 3 mo from inclusion or mortality whichever was earlier. Mortality at 28-d and 90-d was compared between no ACLF and ACLF groups as per both criteria. Mortality was also compared between different grades of ACLF as per CLIF-SOFA criteria. Prognostic scores like CLIF-SOFA, Acute Physiology and Chronic Health Evaluation (APACHE)-II, Child-Pugh and Model for End-Stage Liver Disease (MELD) scores were evaluated for their ability to predict 28-d mortality using area under receiver operating curves (AUROC).RESULTS: Of 50 patients, 38 had ACLF as per CLIF-SOFA and 19 as per APASL criteria. Males (86%) were predominant, alcoholic liver disease (68%) was the most common etiology of cirrhosis, sepsis (66%) was the most common cause of acute decompensation while infection (66%) was the most common precipitant of acute decompensation. The 28-d mortality in no ACLF and ACLF groups was 8.3% and 47.4% (P = 0.018) as per CLIF-SOFA and 39% and 37% (P = 0.895) as per APASL criteria. The 28-d mortality in patients with no ACLF (n = 12), ACLF grade 1 (n = 11), ACLF grade 2 (n = 14) and ACLF grade 3 (n = 13) as per CLIF-SOFA criteria was 8.3%, 18.2%, 42.9% and 76.9% (χ² for trend, P = 0.002) and 90-d mortality was 16.7%, 27.3%, 78.6% and 100% (χ² for trend, P < 0.0001) respectively. Patients with prior decompensation had similar 28-d and 90-d mortality (39.3% and 53.6%) as patients without prior decompensation (36.4% and 63.6%) (P = NS). AUROCs for 28-d mortality were 0.795, 0.787, 0.739 and 0.710 for CLIF-SOFA, APACHE-II, Child-Pugh and MELD scores respectively. On multivariate analysis of these scores, CLIF-SOFA was the only significant independent predictor of mortality with an odds ratio 1.538 (95%CI: 1.078-2.194).CONCLUSION: CLIF-SOFA criteria is better than APASL criteria to classify patients into ACLF based on their prognosis. CLIF-SOFA score is the best predictor of short-term mortality.     

Restoring the Treg cell to Th17 cell ratio may alleviate HBV-related acute-on-chronic liver failure

AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bili     

Age-related differences in response to peginterferon alfa-2a/ribavirin in patients with chronic hepatitis C infection

AIM: To evaluate the safety and efficacy of pegylated interferon alfa-2a and ribavirin therapy in elderly patients with chronic hepatitis C infection.METHODS: Patients characteristics, treatment results and safety profiles of 4859 patients with hepatitis c virus (HCV) infection receiving treatment with pegylated interferon alfa-2a and ribavirin were retrieved from a large ongoing German multicentre non-interventional study. Recommended treatment duration was 24 wk for GT 2 and GT 3 infection and 48 wk for GT 1 and GT 4 infection. Patients were stratified according to age (< 60 years vs ≥ 60 years). Because of limited numbers of liver biopsies for further assessment of liver fibrosis APRI (aspartate aminotransferase - platelet ratio index) was performed using pre-treatment laboratory data.RESULTS: Out of 4859 treated HCV patients 301 (6.2%) were ≥ 60 years. There were more women (55.8% vs 34.2%, P < 0.001) and predominantly GT 1 (81.4% vs 57.3%, P < 0.001) infected patients in the group of patients aged ≥ 60 years and they presented more frequently with metabolic (17.6% vs 4.5%, P < 0.001) and cardiovascular comorbidities (32.6% vs 6.7%, P < 0.001) and significant fibrosis and cirrhosis (F3/4 31.1% vs 14.0%, P = 0.0003). Frequency of dose reduction and treatment discontinuation were significantly higher in elderly patients (30.9% vs 13.7%, P < 0.001 and 47.8% vs 30.8%, P < 0.001). Main reason for treatment discontinuation was “virological non-response” (26.6% vs 13.6%). Sustained virological response (SVR) rates showed an age related difference in patients with genotype 1 (23.7% vs 43.7%, P < 0.001) but not in genotype 2/3 infections (57.7% vs 64.6%, P = 0.341). By multivariate analysis, age and stage of liver disease were independent factors of SVR.CONCLUSION: Elderly HCV patients differ in clinical characteristics and treatment outcome from younger patients and demand special attention from their practitioner.     

Retrospective analysis of pacritinib in patients with myelofibrosis and severe thrombocytopenia

Thrombocytopenia is common in patients with myelofibrosis (MF) and is a well-established adverse prognostic factor. Both of the approved Janus kinase (JAK) inhibitors, ruxolitinib and fedratinib, can worsen thrombocytopenia and have not been evaluated in patients with severe thrombocytopenia (platelet counts <50×10⁹/L). Pacritinib, a novel JAK2/interleukin-1 receptor-associated kinase 1 inhibitor, has been studied in two phase III trials (PERSIST-1 and PERSIST-2), both of which enrolled patients with MF and severe thrombocytopenia. In order to better characterize treatment outcomes for this population with advanced disease, we present a retrospective analysis of efficacy and safety data in the 189 patients with severe thrombocytopenia treated in the PERSIST studies. The proportion of patients in the pacritinib group meeting efficacy endpoints was greater than in the BAT group for ≥35% spleen volume reduction (23% vs. 2%, P=0.0007), ≥50% modified Total Symptom Score reduction (25% vs. 8%, P=0.044), and self-reported symptom benefit (“much” or “very much” improved; 25% vs. 8%, P=0.016) at the primary analysis time point (week 24). The adverse event profile of pacritinib was manageable, and dose modification was rarely required. There was no excess in bleeding or death in pacritinib-treated patients. These results indicate that pacritinib is a promising treatment for patients with MF who lack safe and effective therapeutic options due to severe thrombocytopenia.     

Associations between low-density lipoprotein cholesterol and haemorrhagic stroke

OBJECTIVETo investigate the associations between the blood concentrations of low-density lipoprotein cholesterol (LDL-C) and the clinical features of haemorrhagic stroke.METHODSThis study analysed the data from patients with acute haemorrhagic stroke at a comprehensive stroke centre from 2013 to 2018. Patients were stratified into three groups according to their baseline LDL-C levels: < 70, 70 to < 100 and ≥ 100 mg/dL. We used multivariate logistic regression models to analyse the associations between LDL-C and the risks of having severe neurological deficits (National Institute Health Stroke Scale [NIHSS] scores ≥ 15) and unfavourable outcomes (modified Rankin Scale [mRS] scores>2) at discharge.RESULTSSix-hundred and six patients were analysed. Their median age was 58 years. Among the patients, 75 (12%) patients had LDL-C levels < 70 mg/dL, 194 (32%) patients had LDL-C levels between 70 to < 100 mg/dL and the other 337 (56%) patients had LDL-C levels ≥ 100 mg/dL. Patients with higher LDL-C levels were less likely to suffer severe neurological deficits (LDL-C: 70 to < 100 vs. < 70 mg/dL, adjusted odds ratio [OR]: 0.29, 95% CI: 0.15–0.57; LDL-C: ≥ 100 vs. < 70 mg/dL, adjusted OR = 0.27, 95% CI: 0.15–0.51) and to have unfavourable outcomes at discharge (LDL-C: 70 to < 100 vs. < 70 mg/dL, adjusted OR = 0.50, 95% CI: 0.29–0.87 and LDL-C: ≥ 100 vs. < 70 mg/dL, adjusted OR = 0.46, 95% CI: 0.28–0.78). CONCLUSIONSAn LDL-C level < 70 mg/dL was independently associated with severe neurological deficits of haemorrhagic stroke and may increase the risks of unfavourable outcomes at discharge.

Hyperlipidaemia, especially increased levels of low-density lipoprotein cholesterol (LDL-C), is an independent risk factor for acute ischaemic stroke (AIS).^{[1, 2]} In a cohort study with 27,937 healthy women, subjects with LDL-C ≥ 151 mg/dL had a hazard ratio (HR) of 1.85 to experience an AIS within 11 years relative to those with an LDL-C < 96 mg/dL, where the 95% confidence interval (CI) was 1.22 to 2.80. ^[3]Lipid-lowering therapy is one of the critical strategies for both primary and secondary prevention of AIS.^[4,5] A meta-analysis of the AIS prevention studies indicated that lipid-lowering therapy was associated with lower risks of AIS in the primary (risk ratio (RR): 0.70, 95% CI: 0.60–0.82; P < 0.001) and the secondary (RR: 0.80, 95% CI: 0.70-0.90; P < 0.001) prevention settings. ^[6] Additionally, a meta-analysis in the setting of atherosclerosis coronary heart disease (CHD) also showed that with every 39 mg/dL decrease in the LDL-C levels, the risks of major adverse cardiovascular events (including CHD death, nonfatal myocardial infarction, AIS or unstable angina requiring hospitalization) appeared to be 24% lower (adjusted HR = 0.76, 95% CI: 0.63–0.91; P = 0.0025).^[7] Our prior study found that achieving an LDL-C < 70 mg/dL may be effective in inhibiting the progression of carotid atherosclerosis plaques in patients with AIS. ^[8]However, lower LDL-C levels might increase the risks of intracranial haemorrhage (ICH). LDL-C < 90 mg/dL was associated with a higher risk of haemorrhage transformation after AIS, which was attributable to large artery atherothrombosis: the risks were increased by 54.0% with each 39 mg/dL decrease in the LDL-C levels (adjusted odds ratio (OR): 0.46 per 39 mg/dL increase, 95% CI: 0.22–0.98). ^[9] A case-control study found the LDL-C level was significantly lower in patients with ICH compared to the controls (114 vs. 128 mg/dL; P = 0.016).^[10] A post hoc analysis of the SPARCL study also found that patients with LDL-C < 70 mg/dL had a trend of increased risks of ICH relative to those with LDL-C ≥ 100 mg/dL (HR = 1.28, 95% CI: 0.78–2.09). ^[11] Above all, the target value of LDL-C to be achieved through lipid-lowering therapy is still unclear due to the potential risks of ICH. We carried out a single-centre retrospective cohort study to investigate the associations between the LDL-C levels (< 70, 70 to < 100 and ≥ 100 mg/dL) and the outcomes of haemorrhagic stroke to provide preliminary information about safe targets for lipid-lowering therapy.     

First-line endoscopic treatment with over-the-scope clips significantly improves the primary failure and rebleeding rates in high-risk gastrointestinal bleeding: A single-center experience with 100 cases

AIM To evaluate rebleeding, primary failure(PF) and mortality of patients in whom over-the-scope clips(OTSCs) were used as first-line and second-line endoscopic treatment(FLET, SLET) of upper and lower gastrointestinal bleeding(UGIB, LGIB).METHODS A retrospective analysis of a prospectively collected database identified all patients with UGIB and LGIB in a tertiary endoscopic referral center of the University of Freiburg, Germany, from 04-2012 to 05-2016(n= 93) who underwent FLET and SLET with OTSCs. The complete Rockall risk scores were calculated from patients with UGIB. The scores were categorized as or ≥ 7 and were compared with the original Rockall data. Differences between FLET and SLET were calculated. Univariate and multivariate analysis were performed to evaluate the factors that influenced rebleeding after OTSC placement.RESULTS Primary hemostasis and clinical success of bleeding lesions(without rebleeding) was achieved in 88/100(88%) and 78/100(78%), respectively. PF was significantly lower when OTSCs were applied as FLET compared to SLET(4.9% vs 23%, P = 0.008). In multivariate analysis, patients who had OTSC placement as SLET had a significantly higher rebleeding risk compared to those who had FLET(OR 5.3; P = 0.008). Patients with Rockall risk scores ≥ 7 had a significantly higher in-hospital mortality compared to those with scores 7(35% vs 10%, P = 0.034). No significant differences were observed in patients with scores or ≥ 7 in rebleeding and rebleeding-associated mortality.CONCLUSION Our data show for the first time that FLET with OTSC might be the best predictor to successfully prevent rebleeding of gastrointestinal bleeding compared to SLET. The type of treatment determines the success of primary hemostasis or primary failure.     

Impact of body mass index for patients undergoing pancreaticoduodenectomy

AIM: To evaluate the impact of body mass index (BMI) on short and long term results after pancreaticoduodenectomies (PD).METHODS: A consecutive series of PDs performed at the Karolinska University Hospital from 2004 till 2010 were retrieved from our prospective database. The patients were divided by BMI into overweight/obese (O; BMI ≥ 25 kg/m²) and controls (C; BMI < 25 kg/m²). Demographics, peri-operative data, morbidity, mortality, pancreatic fistula (PF) rate, length of stay (LOS), hospital costs, histology, and survival were analyzed. An additional sub analysis of survival was performed in patients with a diagnosis of pancreatic ductal adenocarcinoma (PDAC) and divided in underweight, normal-weight, overweight and obese.RESULTS: A total of 367 PDs were included (O = 141/C = 226). No differences were found between O and C regarding demographics, peri-operative data, costs, morbidity or mortality. O was associated with higher intra-operative blood loss (1392 ± 115 mL vs 1121 ± 83 mL; P = 0.01), rate of PF (20% vs 9.5%; P = 0.006) and marginally longer LOS (18 ± 0.9 d vs 15 ± 1.1 d; P = 0.05). An increasing risk for PF was observed with increasing BMI. The 1, 3 and 5 years survival rate was similar in O and C in PDAC (68.7%, 26.4% and 8.8% vs 66.1%, 30.9% and 17.9% respectively; P = 0.9). When the survival was analyzed using 4 different categories of BMI (underweight, normal, overweight and obese), a trend was seen toward a difference in survival, with a worse prognosis for the underweight and obese patients compared to normal weight and overweight patients.CONCLUSION: Overweight increases the risk for intra-operative bleeding and PF, but do not otherwise alter short or long term outcome after PD for pancreatic cancer.     

Outcomes of autologous bone marrow mononuclear cell transplantation in decompensated liver cirrhosis

AIM: To determine the long-term efficacy of autologous bone marrow mononuclear cells (BM-MNCs) transplantation in terms of improving liver function and reducing complications in patients with decompensated cirrhosis.METHODS: A total of 47 inpatients with decompensated liver cirrhosis were enrolled in this trial, including 32 patients undergoing a single BM-MNCs transplantation plus routine medical treatment, and 15 patients receiving medical treatment only as controls. Forty-three of 47 patients were infected with hepatitis B virus. Bone marrow of 80-100 mL was obtained from each patient and the BM-MNCs suspension was transfused into the liver via the hepatic artery. The efficacy of BM-MNCs transplantation was monitored during a 24-mo follow-up period.RESULTS: Liver function parameters in the two groups were observed at 1 mo after BM-MNCs transfusion. Prealbumin level was 118.3 ± 25.3 mg/L vs 101.4 ± 28.7 mg/L (P = 0.047); albumin level was 33.5 ± 3.6 g/L vs 30.3 ± 2.2 g/L (P = 0.002); total bilirubin 36.9 ± 9.7 mmol/L vs 45.6 ± 19.9 mmol/L (P = 0.048); prothrombin time 14.4 ± 2.3 s vs 15.9 ± 2.8 s (P = 0.046); prothrombin activity 84.3% ± 14.3% vs 74.4% ± 17.8% (P = 0.046); fibrinogen 2.28 ± 0.53 g/L vs 1.89 ± 0.44 g/L (P = 0.017); and platelet count 74.5 ± 15.7 × 10⁹/L vs 63.3 ± 15.7 × 10⁹/L (P = 0.027) in the treatment group and control group, respectively. Differences were statistically significant. The efficacy of BM-MNCs transplantation lasted 3-12 mo as compared with the control group. Serious complications such as hepatic encephalopathy and spontaneous bacterial peritonitis were also significantly reduced in BM-MNCs transfused patients compared with the controls. However, these improvements disappeared 24 mo after transplantation.CONCLUSION: BM-MNCs transplantation is safe and effective in patients with decompensated cirrhosis. It also decreases the incidence of serious complications.     

Identification of Concurrent Bacterial Infection in Adult Patients with Dengue

We aim to construct a diagnostic model for bacterial coinfection in dengue patients (Dengue Dual Infection Score [DDIS]); 2,065 adult dengue patients (mean age = 41.9 ± 17.2 years, 58.4% male, 83 patients with bacterial coinfection) seen at a university hospital from January of 2005 to February of 2010 were studied. The DDIS was created by assigning one point to each of five risk factors for bacterial coinfection: pulse rate ≥ 90 beats/minute, total white cell count ≥ 6 × 10⁹/L, hematocrit < 40%, serum sodium < 135 mmol/L, and serum urea ≥ 5 mmol/L. The DDIS identified bacterial coinfection (derivation set area under the curve = 0.793, 95% confidence interval = 0.732–0.854; validation set area under the curve = 0.761, 95% confidence interval = 0.637–0.886). A DDIS of ≥ 4 had a specificity of 94.4%, whereas a DDIS of ≥ 1 had a sensitivity of 94.4% for bacterial coinfection. The DDIS can help to select dengue patients for early bacterial cultures and empirical antibiotics.     

Novel clinical risk scoring model for predicting mortality in patients with necrotizing fasciitis: The MNF scoring system

Necrotizing fasciitis (NF) is a life-threatening soft tissue infection that rapidly progresses and requires urgent surgery and medical therapy. If treatment is delayed, the likelihood of an unfavorable outcome, including death, is significantly increased. The goal of this study was to develop and validate a novel scoring model for predicting mortality in patients with NF. The proposed system is hereafter referred to as the Mortality in Necrotizing Fasciitis (MNF) scoring system. A total of 1503 patients with NF were recruited from 3 provincial hospitals in Thailand during January 2009 to December 2012. Patients were randomly allocated into either the derivation cohort (n = 1192) or the validation cohort (n = 311). Clinical risk factors used to develop the MNF scoring system were determined by logistic regression. Regression coefficients were transformed into item scores, the sum of which reflected the total MNF score. The following 6 clinical predictors were included: female gender; age > 60 years; white blood cell (WBC) ≤5000/mm³; WBC ≥ 35,000/mm³; creatinine ≥ 1.6 mg/dL, and pulse rate > 130/min. Area under the receiver operating characteristic curve (AuROC) analysis showed the MNF scoring system to have moderate power for predicting mortality in patients with NF (AuROC: 76.18%) with good calibration (Hosmer-Lemeshow χ²: 1.01; P = .798). The positive likelihood ratios of mortality in patients with low-risk scores (≤2.5) and high-risk scores (≥7) were 11.30 (95% confidence interval [CI]: 6.16–20.71) and 14.71 (95%CI: 7.39–29.28), sequentially. When used to the validation cohort, the MNF scoring system presented good performance with an AuROC of 74.25%. The proposed MNF scoring system, which includes 6 commonly available and easy-to-use parameters, was shown to be an effective tool for predicting mortality in patients with NF. This validated instrument will help clinicians identify at-risk patients so that early investigations and interventions can be performed that will reduce the mortality rate among patients with NF.     

Laparoscopic gastric bypass vs sleeve gastrectomy in obese Korean patients

AIM: To compare the mid-term outcomes of lapa-roscopic sleeve gastrectomy(LSG) and laparoscopic Roux-en-Y gastric bypass(LRYGB) in obese Korean patients. METHODS: All consecutive patients who underwent either LSG or LRYGB with primary to treat morbid obesity between January 2011 and December 2012 were retrospectively reviewed. Patients with a body mass index(BMI) ≥ 30 kg/m2 with inadequately controlled obesity-related comorbidities(e.g., diabetes, obstructive sleep apnea, hypertension, or obesityrelated arthropathy) or BMI ≥ 35 kg/m2 were considered for bariatric surgery according to the International Federation for the Surgery of Obesity-Asia Pacific Chapter Consensus statements in 2011. The decision regarding the procedure type was made on an individual basis following extensive discussion with the patient about the specific risks associated with each procedure. All operative procedures were performed laparoscopically by a single surgeon experienced in upper gastrointestinal surgeries. Baseline demographics, perioperative surgical outcomes, and postoperative anthropometric data from a prospectively established database were thoroughly reviewed and compared between the two surgical approaches.RESULTS: One hundred four patients underwent LSG, and 236 underwent LRYGB. Preoperative BMI in the LSG group was significantly higher than that of the LRYGB group(38.6 kg/m2 vs 37.2 kg/m2, P = 0.024). Patients with diabetes were more prevalent in the LRYGB group(18.3% vs 35.6%, P = 0.001). Operating time and hospital stay were significantly shorter in the LSG group compared with the LRYGB group(100 min vs 130 min, P 0.001; 1 d vs 2 d, P = 0.003), but the incidence of perioperative complications was similar between the groups(P = 0.351). The mean percentage of excess weight loss(%EWL) was 71.2% for LRYGB, while it was 63.5% for LSG, at mean follow-up periods of 18.0 and 21.0 mo, respectively(P = 0.073). The %EWL at 1, 3, 6, 12, 18, 24, and 36 mo was equivalentbetween the groups. Four patients required surgical revision after LSG(4.8%), while revision was only required in one case following LRYGB(0.4%; P = 0.011).CONCLUSION: Both LSG and LRYGB are effective procedures that induce comparable weight loss in the mid-term and similar surgical risks, except for the higher revision rate after LSG.     

Prognostic value of perioperative leukocyte count in resectable gastric cancer

AIM: To investigate the prognostic significance of perioperative leukopenia in patients with resected gastric cancer.METHODS: A total of 614 eligible gastric cancer patients who underwent curative D2 gastrectomy and adjuvant chemotherapy were enrolled in this study. The relationship between pre- and postoperative hematologic parameters and overall survival was assessed statistically, adjusted for known prognostic factors.RESULTS: The mean white blood cell count(WBC) significantly decreased after surgery, and 107/614(17.4%) patients developed p-leukopenia, which was defined as a preoperative WBC ≥ 4.0 × 109/L and postoperative WBC 4.0 × 109/L, with an absolute decrease ≥ 0.5 × 109/L. The neutrophil count decreased significantly more than the lymphocyte count. P-leukopenia significantly correlated with poor tumor differentiation and preoperative WBC. A higher preoperative WBC and p-leukopenia were independent negative prognostic factors for survival [hazard ratio(HR) = 1.602, 95% confidence interval(CI): 1.185-2.165; P = 0.002, and HR = 1.478, 95%CI: 1.149-1.902; P = 0.002, respectively] after adjusting for histology, Borrmann type, p TNM stage, vascular or neural invasion, gastrectomy method, resection margins, chemotherapy regimens, and preoperative WBC count. The patients with both higher preoperative WBC and p- leukopenia had a worse prognosis compared to those with lower baseline WBC and no p-leukopenia(27.5 mo vs 57.3 mo, P 0.001). CONCLUSION: Preoperative leukocytosis alone or in combination with postoperative leukopenia could be independent prognostic factors for survival in patients with resectable gastric cancer.     

Prognosis of acute-on-chronic liver failure patients treated with arti?cial liver support system

AIM: To establish a new model for predicting survival in acute-on-chronic liver failure (ACLF) patients treated with an artificial liver support system.METHODS: One hundred and eighty-one ACLF patients who were admitted to the hospital from January 1, 2012 to December 31, 2014 and were treated with an artificial liver support system were enrolled in this retrospective study, including a derivation cohort (n = 113) and a validation cohort (n = 68). Laboratory parameters at baseline were analyzed and correlated with clinical outcome. In addition to standard medical therapy, ACLF patients underwent plasma exchange (PE) or plasma bilirubin adsorption (PBA) combined with plasma exchange. For the derivation cohort, Kaplan-Meier methods were used to estimate survival curves, and Cox regression was used in survival analysis to generate a prognostic model. The performance of the new model was tested in the validation cohort using a receiver-operator curve.RESULTS: The mean overall survival for the derivation cohort was 441 d (95%CI: 379-504 d), and the 90- and 270-d survival probabilities were 70.3% and 58.3%, respectively. The mean survival times of patients treated with PBA plus PE and patients treated with PE were 531 d (95%CI: 455-605 d) and 343 d (95%CI: 254-432 d), respectively, which were significantly different (P = 0.012). When variables with bivariate significance were selected for inclusion into the multivariate Cox regression model, number of complications, age, scores of the model for end-stage liver disease (MELD) and type of artificial liver support system were defined as independent risk factors for survival in ACLF patients. This new prognostic model could accurately discriminate the outcome of patients with different scores in this cohort (P < 0.001). The model also had the ability to assign a predicted survival probability for individual patients. In the validation cohort, the new model remained better than the MELD.CONCLUSION: A novel model was constructed to predict prognosis and accurately discriminate survival in ACLF patients treated with an artificial liver support system.     

Effect of a neutrophil elastase inhibitor on ventilator-induced lung injury in rats

Objective

We hypothesized that pretreatment with sivelestat therapy could attenuate ventilator-induced lung injury (VILI) and lung inflammation in a rat model.

Methods

The neutrophil elastase inhibitor was administered intraperitoneally 30 min before and at the initiation of ventilation. The rats were categorized as (I) sham group; (II) VILI group; (III) sivelestat group; (IV) early sivelestat group. Wet-to-dry weight ratio, bronchoalveolar lavage fluid (BALF) neutrophil and protein, tissue malondialdehyde (MDA) and histologic VILI scores were investigated.

Results

The ratio of wet-to-dry weight, BALF neutrophil and protein, tissue MDA and VILI scores were significantly increased in the VILI group compared to the sham group [3.85±0.32 vs. 9.05±1.02, P<0.001; (0.89±0.93)×10⁴ vs. (7.67±1.41)×10⁴ cells/mL, P<0.001; 2.34±0.47 vs. 23.01±3.96 mg/mL, P<0.001; 14.43±1.01 vs. 36.56±5.45 nmol/mg protein, P<0.001; 3.78±0.67 vs. 7.00±1.41, P<0.001]. This increase was attenuated in the early sivelestat group compared with the sivelestat group [wet-to-dry ratio: 6.76±2.01 vs. 7.39±0.32, P=0.032; BALF neutrophil: (5.56±1.13)×10⁴ vs. (3.89±1.05)×10⁴ cells/mL, P=0.021; BALF protein: 15.57±2.32 vs. 18.38±2.00 mg/mL, P=0.024; tissue MDA: 29.16±3.01 vs. 26.31±2.58, P=0.049; VILI scores: 6.33±1.41 vs. 5.00±0.50, P=0.024].

Conclusions

Pretreatment with a neutrophil elastase inhibitor attenuates VILI in a rat model.     

Carfilzomib or bortezomib in combination with cyclophosphamide and dexamethasone followed by carfilzomib maintenance for patients with multiple myeloma after one prior therapy: results from a multicenter,phase II,randomized, controlled trial (MUKfive)

The proteasome inhibitors, carfilzomib and bortezomib, are widely used to treat myeloma but head-to-head comparisons have produced conflicting results. We compared the activity of these proteasome inhibitors in combination with cyclophosphamide and dexamethasone (KCd vs. VCd) in second-line treatment using fixed duration therapy and evaluated the efficacy of carfilzomib maintenance. MUKfive was a phase II controlled, parallel group trial that randomized patients (2:1) to KCd (n=201) or VCd (n=99); responding patients on carfilzomib were randomized to maintenance carfilzomib (n=69) or no further treatment (n=72). Primary endpoints were: (i) very good partial response (non-inferiority, odds ratio [OR] 0.8) at 24 weeks, and (ii) progression-free survival. More participants achieved a very good partial response or better with carfilzomib than with bortezomib (40.2% vs. 31.9%, OR=1.48, 90% confidence interval [CI]: 0.95, 2.31; non-inferior), with a trend for particular benefit in patients with adverse-risk disease. KCd was associated with higher overall response (partial response or better, 84.0% vs. 68.1%, OR=2.72, 90% CI: 1.62, 4.55, P=0.001). Neuropathy (grade ≥3 or ≥2 with pain) was more common with bortezomib (19.8% vs. 1.5%, P<0.0001), while grade ≥3 cardiac events and hypertension were only reported in the KCd arm (3.6% each). The median progression-free survival in the KCd arm was 11.7 months vs. 10.2 months in the VCd arm (hazard ratio [HR]=0.95, 80% CI: 0.77, 1.18). Carfilzomib maintenance was associated with longer progression-free survival, median 11.9 months vs. 5.6 months for no maintenance (HR 0.59, 80% CI: 0.46-0.77, P=0.0086). When used as fixed duration therapy in first relapase, KCd is at least as effective as VCd, and carfilzomib is an effective maintenance agent. This trial was registered with International Standard Randomised Controlled Trial Number (ISRCTN) identifier: ISRCTN17354232.     

Outcomes of liver transplantation for end-stage biliary disease: A comparative study with end-stage liver disease

AIM: To evaluate the outcomes of patients with endstage biliary disease(ESBD) who underwent liver transplantation, to define the concept of ESBD, the criteria for patient selection and the optimal operation for decision-making.METHODS: Between June 2002 and June 2014, 43 patients with ESBD from two Chinese organ transplantation centres were evaluated for liver transplantation. The causes of liver disease were primary biliary cirrhosis(n = 8), cholelithiasis(n = 8), congenital biliary atresia(n = 2), graft-related cholangiopathy(n = 18), Caroli's disease(n = 2), iatrogenic bile duct injury(n = 2), primary sclerosing cholangitis(n = 1), intrahepatic bile duct paucity(n = 1) and Alagille's syndrome(n = 1). The patients with ESBD were compared with an end-stage liver disease(ESLD) case control group during the same period, and the potential prognostic values of multiple demographic and clinical variables were assessed. The examined variables included recipient age, sex, pre-transplant clinical status, pre-transplant laboratory values, operation condition and postoperative complications, as well as patient and allograft survival rates. Survival analysis was performed using Kaplan-Meier curves, and the rates were compared using log-rank tests. All variables identified by univariate analysis with P values 0.100 were subjected to multivariate analysis. A Cox proportional hazard regression model was used to determine the effect of the study variables on outcomes in the study group.RESULTS: Patients in the ESBD group had lower model for end-stage liver disease(MELD)/paediatric end-stage liver disease(PELD) scores and a higher frequency of previous abdominal surgery compared to patients in the ESLD group(19.2 ± 6.6 vs 22.0 ± 6.5, P = 0.023 and 1.8 ± 1.3 vs 0.1 ± 0.2, P = 0.000). Moreover, theoperation time and the time spent in intensive care were significantly higher in the ESBD group than in the ESLD group(527.4 ± 98.8 vs 443.0 ± 101.0, P = 0.000, and 12.74 ± 6.6 vs 10.0 ± 7.5, P = 0.000). The patient survival rate in the ESBD group was not significantly different from that of the ESBD group at 1, 3 and 5 years(ESBD: 90.7%, 88.4%, 79.4% vs ESLD: 84.9%, 80.92%, 79.0%, χ2 = 0.194, P = 0.660). The graftsurvival rates were also similar between the two groups at 1, 3 and 5 years(ESBD: 90.7%, 85.2%, 72.7% vs ESLD: 84.9%, 81.0%, 77.5%, χ2 = 0.003, P = 0.958). Univariate analysis identified MELD/PELD score(HR = 1.213, 95%CI: 1.081-1.362, P = 0.001) and bleeding volume(HR = 0.103, 95%CI: 0.020-0.538, P = 0.007) as significant factors affecting the outcomes of patients in the ESBD group. However, multivariate analysis revealed that MELD/PELD score(HR = 1.132, 95%CI: 1.005-1.275, P = 0.041) was the only negative factor that was associated with short survival time.CONCLUSION: MELD/PELD criteria do not adequately measure the clinical characteristics and staging of ESBD. The allocation system based on MELD/PELD criteria should be re-evaluated for patients with ESBD.