Simultaneous rapid detection of glycyrrhizin and sennoside A in Daiokanzoto samples by lateral flow immunoassay.

INTRODUCTION: Glycyrrhizin (GLY) and sennoside A (SA) are characteristic bioactive marker compounds of the Kampo medicine Daiokanzoto. Their accurate detection in blends of Rhei rhizoma and Glycyrrhizae radix of several species (4:1 or 4:2) is essential for quality control and to ensure therapeutic efficacy. A rapid, efficient assay can significantly facilitate their detection. OBJECTIVE: To establish a rapid qualitative assay for GLY and SA detection, a lateral flow immunoassay (LFA) was developed using specific monoclonal antibody (mAb) nanoparticles. METHODOLOGY: This assay harnesses the competitive binding of mAb nanoparticles to the immobilized analytes on test strips and free analytes in the samples. Two conjugates for detecting GLY and SA, GLY-bovine serum albumin and SA-human serum albumin, were separately immobilized on the test zones of LFA strips. The detection mechanism is reliant on the visual detection of color changes in the test zones. RESULTS: When GLY and SA were present in samples, they contended with the immobilized conjugates on the strip to bind with the mAb nanoparticles and produced distinct color patterns in the test zones. The limits of detection of the assay for GLY and SA were both 3.13 µg/mL. The capability of the LFA was substantiated using plant samples and Daiokanzoto, and its alignment with indirect competitive ELISA results was confirmed. CONCLUSION: The introduced LFA is a groundbreaking procedure that offers a rapid, straightforward, and sensitive method for simultaneously detecting GLY and SA in Daiokanzoto samples. It is instrumental in ensuring product quality.

Biological Activity of Extracts of Red and Yellow Fruits of Cornus mas L.-An In Vitro Evaluation of Antioxidant Activity, Inhibitory Activity against α-Glucosidase, Acetylcholinesterase, and Binding Capacity to Human Serum Albumin.

Although extracts are broadly used in order to support the treatment of numerous diseases, only in a limited number of cases is the process of applying and establishing their mechanisms of action scientifically analyzed. Fruits of Cornelian cherry are an abundant source of iridoids, anthocyanins, flavonols and phenolic acids. The aim of the present study was to evaluate the in vitro bioactivity of red and yellow Cornelian cherry fruits' extracts. The biological potential of extracts, in a broad sense, involved antioxidant activity in relation to phosphatidylcholine liposomes, inhibitory ability against α-glucosidase and acetylcholinesterase enzymes, as well as interactions with human serum albumin. Studies showed that both extracts were more effective in protecting liposome membranes against free radicals produced by AAPH in an aqueous environment due to the fact that they can be better eliminated by the hydrophilic components of the extracts than those produced by UVB radiation. Extracts exhibited inhibitory activity against acetylcholinesterase and α-glucosidase, wherein loganic acid extract showed noncompetitive inhibition of the enzyme. Moreover, extracts binded to albumin mainly through hydrogen bonds and van der Waals forces. Taken together, red and yellow cherry fruits' extracts exhibit diverse biological properties and can be exploited as a source of natural therapeutic agents.

The effects of Fushen Granule on the composition and function of the gut microbiota during Peritoneal Dialysis-Related Peritonitis.

BACKGROUND: Peritoneal dialysis (PD) is an acknowledged treatment for patients with irreversible kidney failure. The treatment usually causes peritoneal dialysis-related peritonitis (PDRP), a common complication of PD that can lead to inadequate dialysis, gastrointestinal dysfunction, and even death. Recent studies indicated that Fushen Granule (FSG), a Chinese herbal formula, improves the treatment of PD. However, the mechanism of how FSG plays its role in the improvement is still unclear. Gut microbiota has been closely related to the development of various diseases. We carried out a randomized controlled trial to assess whether FSG can modulate the gut microbiota during PDRP treatment. METHODS: Forty-two PDRP patients were recruited into the clinical trial, and they were randomly divided into control(CON), probiotics(PRO) or Fushen granule group(FSG). To check whether FSG improve the PD treatment, we assessed the clinical parameters, including albumin(ALB), hemoglobin(HGB), blood urea nitrogen(BUN) and creatinine(CR). Fecal samples were collected before hospitalization and discharge, and stored at -80°C within 1 hour. And we assessed the microbial population and function by applying the 16S rRNA gene sequencing and functional enrichment analysis. RESULTS: Compared to control group, ALB is improved in both probiotics and FSG groups, while HGB is increased but BUN and CR is reduced in FSG group. Sequencing of 16S rRNA genes revealed that FSG and PRO affected the composition of the microbial community. FSG significantly increased a abundant represented by Bacteroides, Megamonas and Rothia, which was significantly correlated with the improvements in carbohydrate and amino acid metabolism. CONCLUSIONS: This study demonstrates that FSG ameliorates the nutritional status and improves the quality of life by enriching beneficial bacteria associated with metabolism. These results indicate that FSG as alternative medicine is a promising treatment for patients with PDRP.

Hypocalcaemia and calcium intake in pregnancy: A research protocol for critical analysis of risk factors, maternofoetal outcomes and evaluation of diagnostic methods in a third-category health facility, Cameroon.

INTRODUCTION: Hypocalcaemia in pregnancy remains a major health issue, particularly in the developing world where daily calcium intakes are suboptimal. This electrolyte imbalance can lead to severe maternofoetal and childhood consequences. Calcium supplementation, amongst others, contributes significantly to meeting calcium demands in pregnancy. With ionised calcaemia as the gold standard for diagnosis, total calcaemia and albumin-corrected calcaemia in other pathological states have been found to overestimate the burden of hypocalcaemia. The main objectives of this study are to describe the blood calcium level (total, albumin corrected, and ionised calcaemia) and associated maternofoetal outcomes while identifying determinants of calcium supplementation and ionised hypocalcaemia. This study will also evaluate the sensitivity and specificity of albumin corrected calcaemia as a diagnostic tool for hypocalcaemia (ionised calcaemia as the gold standard) among pregnant women in the Nkongsamba Regional Hospital, Cameroon. METHODS: Our study will target a total of 1067 term pregnant women who shall be included consecutively into the study as they arrive the maternity of the Nkongsamba Regional Hospital for their last antenatal care visit. Data shall be collected using a semi-structured interview-administered questionnaire and blood samples collected for total plasma calcium, albumin and serum ionized calcium assays. Additional data will be collected at birth (maternal and foetal variables; foetal outcomes evaluated as secondary outcomes). Total calcaemia and albuminemia shall be measured by atomic absorption spectrophotometry, while ionised calcaemia will be measured by ion-selective electrode potentiometry(using MSLEA15-H electrolyte analyzer) per standard BIOLABO and MSLEA15 protocols, respectively. Data will be analysed using the statistical softwares epi-Info version 7.2.2.16 and STATA version 16. EXPECTED RESEARCH OUTCOME: This study will present a more precise estimate of the burden of hypocalcaemia in late pregnancy as well as identify and analyse the different factors associated with calcium supplementation and ionised hypocalcaemia among term pregnant women in a developing world setting. Maternofoetal outcomes associated with hypocalcaemia will be determined as well as the sensitivity and specificity of total and albumin-corrected calcaemia in diagnosing hypocalcaemia. Our findings will contribute significantly to designing or strengthening interventions to control this electrolyte imbalance.

Prognostic Significance of the Controlling Nutritional Status (CONUT) Score in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab after Failure of Prior Tyrosine Kinase Inhibitors.

PURPOSE: The controlling nutritional status (CONUT) score, consisting of albumin, lymphocytes and total cholesterol, is a validated, objective tool for nutritional assessment. Patients with advanced cancer frequently have malnutrition in association with cachexia and chronic inflammation. We explored the prognostic significance of the CONUT score in patients with advanced renal cell carcinoma receiving nivolumab. MATERIALS AND METHODS: This retrospective study included 60 patients with stage IV renal cell carcinoma treated with nivolumab after failure of prior tyrosine kinase inhibitors at 2 cancer centers between 2016 and 2019. Associations of the CONUT score with progression-free survival, cancer specific survival and tumor shrinkage rate were assessed. RESULTS: The median (range) CONUT score was 2 (0-10). During followup periods 29 and 14 patients exhibited disease progression and died of cancer, respectively. Both progression-free survival and cancer specific survival were significantly stratified by CONUT scores of 0 to 1, 2 to 4 and 5 or more (p=0.002). A CONUT score of 5 or more (versus score 0 to 1) was independently associated with unfavorable progression-free survival (HR 5.18, p=0.003) and cancer specific survival (HR 15.34, p=0.014), as was the absence of prior nephrectomy (HR 4.23, p=0.004 and HR 6.57, p=0.001, respectively). C-indices of the CONUT score for predicting progression-free survival and cancer specific survival were 0.694 and 0.737, respectively. The CONUT score was significantly associated with the best response to nivolumab with the median tumor shrinkage rate of -23%, +8% and +24% for CONUT scores of 0 to 1, 2 to 4 and 5 or more, respectively (p=0.021). CONCLUSIONS: The CONUT score may be useful to predict the clinical outcomes and therapeutic response in patients with advanced renal cell carcinoma receiving nivolumab.

Kinetic and structural characterization of therapeutic albumin chemical functionalization using complementary mass spectrometry techniques.

Protein conjugates such as antibody-drugs conjugates (ADCs) represents the next generation of therapeutic proteins. They allow to combine the biological properties of the protein format with the characteristics of the conjugated ligands. The reaction implemented to couple ligands to the peptide backbone represents a crucial aspect of the production of protein conjugates, influencing the nature and the heterogeneity of the conjugates obtained. Here, we report the concomitant use of MALDI-TOF MS and LC-MS/MS analysis to investigate the chemical functionalization of human serum albumin (HSA) by the intermediate of lysine residues, previously used to generate biopharmaceutical agents for medical imaging. A kinetic was performed by collecting samples after different reaction times and analyzing them using the two techniques. MALDI-TOF MS analyses allowed estimating the number of conjugated ligands in a robust manner and assess the global functionalization kinetic on the intact protein level. Results demonstrated a maximum of 38 modified residues out of the 59 lysines available showing the limitation of the chemical functionalization. Consequently, LC-MS/MS analysis provided a site-specific characterization of the residues undergoing chemical modification. Data exhibited unique properties due to the presence of the ligands which allowed to identify without ambiguity the residues exhibiting different modification rate and enabled the identification of the unmodified lysine. Results were compared to the structure of HSA described from crystallography data. The comparison strongly suggested that accessibility is influencing the residues respective reactivity. The relevant complementarity of the different techniques could be emphasized in order to perform an extensive characterization concerning the evolution of the primary structure of the protein during the chemical reaction, providing an improved insight on the conjugation process and offering the potentiality to tune the reaction.

Free vitamin D levels in steroid-sensitive nephrotic syndrome and healthy controls.

INTRODUCTION: Body stores of vitamin D are measured as "total" serum 25-hydroxy vitamin D (25(OH)D). Its largest component is protein bound and lost in urine in nephrotic syndrome (NS). Our study investigates whether "free" 25(OH)D levels are a better guide to bone health and need for vitamin D supplementation in patients with steroid-sensitive NS (SSNS). METHODS: A cross-sectional study was performed in children with SSNS and healthy controls. Blood was tested for albumin, creatinine, calcium, phosphate, ALP, total and free (by direct ELISA) 25(OH)D, iPTH, and urine for protein-creatinine ratio. RESULTS: Seventy-nine NS patients (48 in relapse, 31 in remission) and 60 healthy controls were included. The levels of total 25(OH)D were significantly different (lowest in NS relapse and highest in controls) (p < 0.001). Corrected calcium and phosphate levels were normal, and there were no differences in free 25(OH)D, ALP, or iPTH levels between groups. Only total and not free 25(OH)D correlated significantly and negatively with urinary protein creatinine ratios (rs = - 0.42 vs. 0.04). Free 25(OH)D values of 3.75 and 2.85 pg/ml corresponded to total 25(OH)D levels of 20 and 12 ng/ml, respectively, in healthy controls. CONCLUSION: These results confirm that total 25(OH)D levels are low in NS and related to degree of proteinuria. However levels of free 25(OH)D, ALP, and iPTH did not change in relapse or remission in comparison with healthy controls. Our results suggest that in proteinuric renal diseases, free 25(OH)D rather than total 25(OH)D levels should be used to diagnose vitamin D deficiency and guide therapy.

Improved survival prediction and comparison of prognostic models for patients with hepatocellular carcinoma treated with sorafenib.

BACKGROUND: The 'Prediction Of Survival in Advanced Sorafenib-treated HCC' (PROSASH) model addressed the heterogeneous survival of patients with hepatocellular carcinoma (HCC) treated with sorafenib in clinical trials but requires validation in daily clinical practice. This study aimed to validate, compare and optimize this model for survival prediction. METHODS: Patients treated with sorafenib for HCC at five tertiary European centres were retrospectively staged according to the PROSASH model. In addition, the optimized PROSASH-II model was developed using the data of four centres (training set) and tested in an independent dataset. These models for overall survival (OS) were then compared with existing prognostic models. RESULTS: The PROSASH model was validated in 445 patients, showing clear differences between the four risk groups (OS 16.9-4.6 months). A total of 920 patients (n = 615 in training set, n = 305 in validation set) were available to develop PROSASH-II. This optimized model incorporated fewer and less subjective parameters: the serum albumin, bilirubin and alpha-foetoprotein, and macrovascular invasion, extrahepatic spread and largest tumour size on imaging. Both PROSASH and PROSASH-II showed improved discrimination (C-index 0.62 and 0.63, respectively) compared with existing prognostic scores (C-index ≤0.59). CONCLUSIONS: In HCC patients treated with sorafenib, individualized prediction of survival and risk group stratification using baseline prognostic and predictive parameters with the PROSASH model was validated. The refined PROSASH-II model performed at least as good with fewer and more objective parameters. PROSASH-II can be used as a tool for tailored treatment of HCC in daily practice and to define pre-planned subgroups for future studies.

Bone Mineral Metabolism Status, Quality of Life, and Muscle Strength in Older People.

As the relationship between vitamin D and various diseases or health conditions has become known, interest in the contribution of vitamin D to overall health-related quality of life (QoL) has increased. We examined the relationship between vitamin D status and QoL in 273 participants aged 65 years and older. Serum levels of total calcium, phosphorus, intact parathyroid hormone, albumin, and 25-hydroxyvitaminD3 were analyzed. We also recruited data for QoL, physical activity, nutritional impairment, and muscular strength. Ninety percent of the subjects were classified as vitamin D deficient or insufficient. Participants with higher serum 25(OH)D3, calcium, phosphorous, and Alb levels were significantly less likely to self-report depression or anxiety after adjustment (p = 0.009, p = 0.005, p = 0.003, and p = 0.005, respectively). Additionally, we found an association between lower levels of albumin and self-reported problems with mobility or usual activities (p = 0.01). We also found associations between better muscle strength and higher levels of vitamin D, calcium, phosphorous, and albumin (p = 0.006, p = 0.003, p = 0.004 and p = 0.002, respectively). Overall, our data provide evidence that serum vitamin D and Alb levels are negatively related to self-reported anxiety or depression, usual activities, mobility, and three dimensions of QoL in older adults. Furthermore, vitamin D levels are positively related to hand grip strength in adults over 65 years old.

Novel Predictive Models of Early Death Less Than 1 Year in Patients With Metastatic Renal Cell Carcinoma After Treatment With First-line Tyrosine Kinase Inhibitors.

BACKGROUND: We aimed to develop a modified International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model that can predict early death less than 1 year in patients with metastatic renal cell carcinoma (mRCC) after receiving first-line tyrosine kinase inhibitors (TKIs). PATIENTS AND METHODS: We retrospectively reviewed records of patients with mRCC treated with first-line TKIs at our institution between 2007 and 2012. The primary endpoint was the rate of early death within 1 year after first-line TKI administration. We determined statistically significant factors predicting early death by performing multiple logistic regression. The modified IMDC model 1 was developed using new variables in addition to the risk criteria of the IMDC model, and model 2 was developed using new variables irrespective of the risk classification of IMDC model. RESULTS: Early mortality within 1 year of first-line TKI treatment was 19.7% (n = 98) in 462 patients. Although the C-index of the IMDC model for early death was 0.655, the C-index of model 1, which includes 5 variables (previous nephrectomy, body mass index, multiple metastases, previous metastasectomy, and serum albumin level) in addition to the Heng criteria, was 0.823. The C-index of model 2, which includes 7 variables (hemoglobin, neutrophil level, and the 5 variables of model 1) was 0.822. Of note, there was no significant difference in net reclassification index between the 2 models. CONCLUSION: This is the first study suggesting novel prediction models for early death less than 1 year in patients with mRCC treated with first-line TKI.

Development of an on-line analytical platform to screen haptens in shuxuening injection based on high-performance liquid chromatography coupled with ion-trap multistage mass spectrometry and human serum albumin fluorescence detection.

Shuxuening injection (SXNI), one of the traditional Chinese medicine injections (TCMI), is widely used for the treatment of cardiovascular diseases in the clinic. However, its allergic reactions have impeded the clinical applications of SXNI, such adverse reactions have not been well understood due to the lack of methods for detecting haptens. In this study, a high-performance liquid chromatography-diode-array detector-multi-stage mass spectrometry-human serum albumin-fluorescence detector (HPLC-DAD-MSn-HSA-FLD) system was established to identify and screen haptens for the first time. Flavones, flavonols and their glycosides in SXNI showed strong HSA binding ability in different degrees. Fifteen of these compounds were used to study the association of HSA binding ability and sensitizability using isothermal titration calorimetry (ITC) and fluorescence techniques, furthermore, RBL-2H3 cell experiments were conducted to verify the results. It was found that ginkgolides showed no sensitizability, while flavones and flavonol aglycones showed stronger sensitizability than their glycosides. The system was proven to be precise, stable and reproducible, which lays a foundation for screening haptens in SXNI and relevant samples.

Impact of Branched-Chain Amino Acid Granule Therapy in Patients with Hepatocellular Carcinoma Who Have Normal Albumin Levels and Low Branched-Chain Amino Acid to Tyrosine Ratios.

Serum albumin has been reported to be a useful indicator of liver function and branched-chain amino acid (BCAA) therapy is associated with a lower incidence of hepatocellular carcinoma (HCC). We investigated the impact of BCAA granule therapy on overall survival and disease-specific survival in patients with normal albumin levels and low BCAA to tyrosine ratio (BTR)s who had treatment-naïve HCC. Overall survival and disease-specific survival was analyzed in 78 patients with HCC who were treated (n = 27) or not treated (n = 51) with BCAAs. Twenty-six patients died during the follow-up period. There were 19, 5, and 2 patients who died due to HCC, hepatic failure, and non-liver-related disease, respectively. Multivariate analysis for factors associated with overall survival indicated that BCAA therapy was independently associated with good prognosis in patients with HCC (hazard ratio [HR], 0.317; 95% confidence interval [CI], 0.123-0.813; P = 0.017). In addition, multivariate analysis using competing risks methods indicated that BCAA therapy is independently associated with reduction of disease-specific mortality (HR, 0.216; 95% CI, 0.068-0.689; P = 0.001). In conclusion, BCAA therapy improved both overall survival and disease-specific survival in HCC patients with low BTRs despite having normal albumin levels.

Analysis of Recombinant Human Serum Albumin Extraction and Degradation in Transgenic Rice Extracts.

Transgenic plant systems have successfully been used to express recombinant proteins, including rice seed-expressed recombinant human serum albumin (rHSA), without the risk of contamination of human pathogens. Developing an efficient extraction process is critical as the step determines recombinant protein concentration and purity, quantity of impurities, and process volume. This article evaluates the effect of pH and time on the extraction and stability of rHSA. The amount of rHSA in clarified extract after 60 min of solubilization increased with pH from 0.9 mg/g (pH 3.5) to 9.6 mg/g (pH 6.0), but not over time as 10 min was sufficient for solubilization. Total soluble protein in extracts also increased with pH from 3.9 mg/g (pH 3.5) to 19.7 mg/g (pH 6.0) in clarified extract. Extraction conditions that maximized rHSA purity were not optimal for rHSA stability and yield. Extraction at pH 3.5 resulted in high purity (78%), however, rHSA degraded over time. Similar purities (78%) were observed in pH 4.0 extracts yet rHSA remained stable. rHSA degradation was not observed in pH 4.5 and 6.0 extracts but higher native protein concentrations decreased purity. Strategies such as pH and temperature adjustment were effective for reducing rHSA degradation in pH 3.5 rice extracts. Low temperature pH 3.5 extraction retained high purity (97%) and rHSA stability. While seed-expressed recombinant proteins are known to be stable for up to 3 years, the degradation of rHSA was notably extensive (56% within 60 min) when extracted at low pH. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:681-691, 2018.

Validation of the albumin-bilirubin grade-based integrated model as a predictor for sorafenib-failed hepatocellular carcinoma.

BACKGROUND & AIMS: Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC) but is challenging after treatment failure. Appropriate criteria for enrolling patients into second-line trials are still limited. In this study, we aimed to establish more objective criteria based on Albumin-Bilirubin (ALBI) grade to select patients with better post-progression survival (PPS) for second-line treatment. METHODS: Consecutive 404 advanced HCC patients receiving sorafenib were retrospectively enrolled. All patients were in Child-Pugh class A and BCLC stage C with either portal vein invasion or extrahepatic metastasis at the beginning of sorafenib treatment. Radiological evaluation based on mRECIST criteria and clinical assessments with compliance were performed on schedule. RESULTS: During the median follow-up period of 5.8 months, 310 patients developed progressive disease (PD) and 350 deaths occurred. The PD patients were randomized into derivation and validation cohorts by a 1:1 ratio. The independent predictors of poor PPS in derivation cohort were ALBI grade 3 at PD (hazard ratio [HR]=3.24, P = .002), new extrahepatic lesions (NEH) (HR=1.75, P = .011), and early PD within 4 months (HR=1.88, P = .037). ALBI-PD criteria were proposed by incorporating these three risk factors. In the validation cohort, PPS could be independently predicted by presence of early PD, NEH as well as ALBI grade 3 at PD. Patients within ALBI-PD criteria had significant longer median PPS than those beyond it even in Child-Pugh A (9.7 vs 4.9 months, P = .005) subpopulations. CONCLUSIONS: The ALBI-PD criteria can differentiate PPS and stratify the patients with advanced HCC for the second-line trials or salvage therapy.

Fibroblast growth factor 23 in untreated nephrotic syndrome.

AIM: Despite its importance in bone and cardiovascular disease in subjects with kidney disease, there are no data on fibroblast growth factor 23 (FGF23) perturbations in nephrotic syndrome. We evaluated FGF23 and markers of mineral bone metabolism in subjects with untreated NS. METHODS: In this cross-sectional study, we measured circulating levels of FGF23, 25-hydroxy vitamin D [25(OH)D], 1,25 di-hydroxy vitamin D [1,25(OH)2 D], serum albumin, serum calcium, phosphorus, creatinine and intact parathyroid hormone (iPTH) in 101 patients with adults onset NS and 40 healthy controls. We examined the correlation between FGF23 and markers of mineral bone metabolism. RESULTS: Compared to healthy controls, subjects with NS showed reduced levels of 25(OH)D (21.76 ± 10.18 vs 35.74 ± 40.27 nmol/L, P = 0.001), 1,25(OH)2 D (median; 37.80 vs 73.13 pmol/L, P = 0.0001) and FGF23 (37.81 ± 20.42 vs 48.20 ± 11.60 pg/mL, P = 0.004) levels. Serum phosphorus levels were marginally, but significantly higher in subjects with nephrotic syndrome compared to healthy controls (P = 0.004). Serum iPTH levels were significantly higher in subjects with NS compared to healthy controls (52.24 ± 39.58 vs 37.90 ± 14.60 pg/mL, P = 0.028). CONCLUSIONS: We conclude that FGF23 is reduced in subjects with NS compared to healthy controls. The reduced levels of Vitamin D, and urinary losses may contribute to lower levels of FGF23 in NS.

Prognostic scores for sorafenib-treated hepatocellular carcinoma patients: A new application for the hepatoma arterial embolisation prognostic score.

BACKGROUND: No prognostic classification is currently used for patients treated with systemic therapies for Hepatocellular Carcinoma (HCC). METHODS: We retrospectively analysed data from patients treated with sorafenib for HCC from five centres in France and in the United Kingdom (UK). The training set comprised data from two centres and the validation set from three. Variables independently associated with Overall Survival (OS) in the training set were used to build the SAP (Sorafenib Advanced HCC Prognosis) score. The score was tested in the validation set, then compared with other prognostication systems. RESULTS: The training set and validation set included 370 and 468 patients respectively. In the training set, variables independently associated with OS in multivariable analysis were: performance status (PS) >0, alpha-fetoprotein (AFP) >400 ng/ml, tumour size >7 cm, bilirubin >17 µmol/l and albumin <36 g/l. The SAP score was built giving one point to each abnormal variable, and three classes were constructed. The SAP score was significantly associated with OS in the training set, with median OS of 14.9 months for SAP A, 7.2 months for SAP B and 2.5 months for SAP C (P < 0.001). In the validation set, the SAP score was significantly associated with OS, and showed greater discriminative abilities than Barcelona Clinic Liver Cancer (BCLC) and albumin-bilirubin (ALBI) scores. However, the hepatoma arterial embolisation prognostic (HAP) score showed greater discriminative abilities than the SAP score. CONCLUSION: In European patients treated with sorafenib, the HAP was the most discriminant prognostic score and may facilitate stratification in trials and inform clinical decision making.

The Effect of Intradialytic Intralipid Therapy in Pediatric Hemodialysis Patients.

OBJECTIVE: Growth of children on maintenance hemodialysis is poor. Oral nutritional supplements are the preferred way to augment nutrition; however, many children have difficulties adhering to prescribed oral supplements. In our unit, we have been utilizing intralipid (IL) therapy as nutritional supplement during hemodialysis sessions. The aim of this study was to assess the safety, efficacy, and benefits of intradialytic IL therapy. DESIGN: A retrospective chart review. SUBJECTS: Fifteen pediatric hemodialysis patients receiving intradialytic IL therapy for at least 3 months from July 2011 through July 2014. MAIN OUTCOME MEASURE: For each patient, anthropometric measurements and laboratory nutritional parameters were compared prior to and at the end of IL therapy. Anthropometric measurements evaluated were dry weight, height, body mass index (BMI), and BMI corrected for height age. Laboratory nutritional parameters evaluated were albumin, normalized protein catabolic rate, predialysis blood urea nitrogen, transferrin, cholesterol, and triglyceride levels. Adverse events during therapy were also noted. RESULTS: Significant improvement was noted in albumin levels, predialysis blood urea nitrogen, and normalized protein catabolic rate during therapy (P = .02; P = .03; P = .03, respectively). Six patients (37.5%) improved their weight standard deviation score, and eight patients (50%) improved their BMI standard deviation score though not statistically significant (P = .59; P = .9, respectively). No significant side effects were noted. CONCLUSIONS: Administration of IL alone during hemodialysis is well tolerated with beneficial effects on nutritional parameters. The provision of IL alone is relatively cheap and does not require additional resources. In conjunction with other measures of nutritional support, it can help improve nutritional status of pediatric hemodialysis patients.

Prevalence of fat-soluble vitamin (A, D, and E) and zinc deficiency in patients with cirrhosis being assessed for liver transplantation.

PURPOSE: To evaluate the prevalence of fat-soluble vitamin (A, D, and E) and zinc deficiency in patients with cirrhosis being assessed for liver transplantation and the correlations between vitamin deficiencies, nutritional markers, and severity of liver disease. METHODS: This is a single centre retrospective study. Serum vitamin A, D, E, and zinc levels were collected in adult patients being assessed for liver transplantation between January and July 2012. Patient and liver disease demographics, nutritional markers, Child-Pugh score, and MELD-Na score were collected. Fisher's exact test and multiple variable logistic regression was used for statistical analysis. RESULTS: A total of 109 adult patients were assessed for liver transplantation during the 6-month period. The mean patient age was 54 ± 10 years and 66% were males. Mean BMI was 27 ± 6 kg/m2, pre-albumin was 0.10 ± 0.07 g/L, albumin was 33 ± 6 g/L, total bilirubin was 48 ± 61 mmol/L, MELD-Na score was 16 ± 5 (range 6-33), and 15% had hepatocellular carcinoma. The Child-Pugh score was A in 29%, B in 54%, and C in 17%. The causes of liver disease were hepatitis C in 36%, alcohol in 20%, non-alcoholic fatty liver disease in 17%, and other in 27%. The mean vitamin A level was 0.88 ± 0.86 umol/L, D was 69 ± 52 nmol/L, E was 24 ± 17 umol/L, and zinc was 477 ± 145 ug/L. Vitamin A deficiency was prevalent in 77%, D in 63%, E in 37%, and zinc in 84%. On multiple variable analysis, low albumin (OR = 0.78, 95% CI = 0.65-0.94, p = 0.0069) was a predictor of vitamin A deficiency ; cholestatic liver enzyme elevation (OR = 3.53, 95%CI = 1.40-8.89, p = 0.0073) and low albumin (OR = 0.83, 95%CI = 0.73-0.94, p = 0.0032) were predictors of vitamin D deficiency ; low albumin (OR = 0.85, 95% CI = 0.74-0.97, p = 0.015) was a predictor of vitamin E deficiency ; and age (OR = 0.83, 95% CI = 0.72-0.96, p = 0.012), low albumin (OR = 0.59, 95% CI = 0.42-0.84, p = 0.0036), and high MELD-Na (1.43, 95% CI = 1.05-1.94, p = 0.021) were predictors of zinc deficiency. Vitamin A (p = 0.0034), D (p = 0.020), E (p = 0.012), and zinc (p<0.001) deficiency correlated with a higher Child-Pugh. CONCLUSION: Low albumin was a recurrent predictor of fat-soluble vitamin (A, D, and E) and zinc deficiency while other predictors varied depending on the vitamin or mineral. Further studies need to be conducted on fat-soluble vitamin and zinc supplementation in deficient patients with cirrhosis to assess clinical outcomes.