Higher Serum Albumin Research Articles

O1-4-4 - Association of the bevacizumab pharmacokinetics with efficacy and toxicity in advanced non-small cell lung cancer

Biomarkers predicting the efficacy and toxicity of bevacizumab (Bev) have not yet been established. We conducted this pharmacokinetic study to elucidate the role of plasma concentration of Bev as a biomarker to predict outcome in the treatment of patients with lung cancer. Patients with non-squamous non-small cell lung cancer who were treated using tri-weekly Bev (15mg/kg) with platinum-doublet chemotherapy were enrolled. Plasma samples were collected from all patients before the administration of every dose of Bev until disease progression or treatment discontinuation owing to toxicity. Plasma concentrations of Bev were analyzed via nano-surface and molecular-orientation limited proteolysis coupled with liquid chromatography-mass spectrometry. Between July 2010 and May 2014, 30 patients were enrolled in this study. Majority of the patients received pemetrexed with cisplatin or carboplatin (24 patients, 80%) and others received paclitaxel with carboplatin. The trough concentrations of Bev after first administration (day 22) were 63.19 ± 19.57 µg/mL. Trough concentrations gradually increased until the six cycle of Bev and reached a steady state. Plasma concentrations of Bev did not decrease until disease progression in patients with a long treatment period. Higher mean plasma concentrations of Bev correlated with female sex (p = 0.034) and high serum albumin levels (p = 0.034). Patients who received pemetrexed had higher mean concentrations of Bev (p = 0.038) than those who received paclitaxel. The response rate and progression-free survival did not correlate with the plasma concentration of Bev. Proteinuria (≥Grade 2) correlated with higher concentrations of Bev. Our study demonstrated that various types of chemotherapy influenced the concentrations of Bev, and a higher concentration of Bev may predict the incidence of proteinuria.

Increasing selective bilirubin removal by hypercross-linked polystyrene hemosorbents

A high efficiency of indirect bilirubin removal from systems modelling blood plasma by polymers of various structures and, most importantly, by hemocompatible hypercross-linked polystyrenes such as Styrosorb is demonstrated. Approaches to increasing the selectivity of hypercross-linked polystyrenes for the removal of bilirubin from biological fluids with a high serum albumin content were found, making them promising materials for the manufacture of hemosorption columns effective for hepatitis therapy and other conditions caused by a high bilirubin content in the blood plasma.

Predictive implications of albumin and C-reactive protein for progression to pneumonia and poor prognosis in Stenotrophomonas maltophilia bacteremia following allogeneic hematopoietic stem cell transplantation

BackgroundStenotrophomonas maltophilia (S. maltophilia) bacteremia causes significant morbidity and mortality in immunocompromised hosts. However, incidence and risk factors for mortality in S. maltophilia bacteremia following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain controversial. The primary aim of this study is to clarify factors associated with poor prognosis of allo-HSCT recipients with S. maltophilia bacteremia.MethodsFrom January 2005 to December 2014, patients with hematological diseases and S. maltophilia bacteremia at a single transplantation center in Japan were examined for incidence and 90-day mortality. Prognostic factors associated with 90-day mortality among allo-HSCT recipients were analyzed by log-rank test, and significant variables in the univariate analysis were included in the multivariate Cox proportional-hazards regression model.ResultsA total of 65 patients, including 47 patients undergoing allo-HSCT, developed S. maltophilia bacteremia. The incidence of S. maltophilia bacteremia was significantly higher in allo-HSCT recipients compared to patients not receiving allo-HSCT (6.53 vs. 0.36 per 100 admissions, respectively; p < 0.01). The overall 90-day mortality in allo-HSCT recipients was 43%. Independent risk factors for 90-day mortality were low serum albumin (<3.0 g/dl) (HR = 10.86; 95% CI, 3.27–36.12) and high serum C-reactive protein (CRP) (≥10.0 mg/dl) (HR = 3.28; 95% CI, 1.00–10.72). Among 9 patients with both high CRP and low albumin, 5 had pneumonia at the onset of bacteremia and the remaining 4 patients developed pneumonia in a median of 3 days (range, 1 to 8 days) even under effective treatment. All 9 patients eventually died in a median of 2 days (range, 2 to 32 days). The probabilities of developing pneumonia in patients with or without high CRP and low albumin levels were 100% (9/9) and 10.5% (4/38), respectively (p < 0.01).ConclusionsAllo-HSCT recipients had higher rates of S. maltophilia bacteremia than did patients not receiving allo-HSCT. High serum CRP and low serum albumin at the onset of bacteremia are predictive of disease progression to pneumonia and poor prognosis.

Malnutrition, inflamation and atherosclerosis (MIA syndrome) in patients with end stage renal disease on maintenance hemodialysis (a single centre experience)

BackgroundInflammation and malnutrition play an important role in endothelial dysfunction, atherosclerosis and excessive cardiovascular morbidity and mortality in ESRD patients Aim of the studyThe primary objective is to determine the prevalence of inflammation, malnutrition and atherosclerosis in patients on maintenance haemodialysis. Secondary objective was to determine the association for atherosclerosis with inflammation and malnutrition. Patient and methodsOne hundred and one adult patients with end stage renal disease on maintenance haemodialysis who are met with the exclusion criteria were enrolled in this cross sectional study from haemodialysis unit of Baghdad teaching hospital over the period of July/2015 − June 2016. All patients were thoroughly examined and many variables were evaluated (age, gender, blood pressure, diabetes mellitus, serum lipid profile, smoking habits, serum albumin, CRP, calcium, Phosphate, Parathyroid hormone and haemoglobin measurements). All patients underwent a carotid Doppler ultrasound study. ResultsAtherosclerosis was present in 65.3%: 58.4% of patients had malnutrition and 43.6% had inflammation. The association for atherosclerosis and high CRP and low serum albumin is strong and independent of other atherosclerosis risk factors. There is significant inverse and independent correlation between CRP and albumin. ConclusionInflammation (high serum CRP) and malnutrition (low serum albumin) in patients on haemodialysis are significantly associated with carotid atherosclerosis. Inflammation was more prevalent in the malnourished patients than in those with normal nutritional status.

Higher serum albumin was related with diabetes incidence and the impact of BMI changes: Based on cohort study of 18,384 Chinese male elderly

AimsAlbumin (ALB) was a useful marker of nutrition and general health status. However, the conclusion about the association between ALB and diabetes was inconsistent, and little information was known about the elderly. MethodsA cohort study based on 18,384 army cadres was conducted Beijing, from 2009 to 2013. ResultsThe mean age of the total 18,384 participants was 71±14years, and the mean ALB concentration was 44.33±3.94g/L at baseline. Diabetes incident showed an increasing trend according to the four ALB concentration groups, from 2.054% to 2.811% for incident. Cox regression showed that participants with higher ALB concentration were at increased HRs for diabetes incident. The HRs of ALB (per SD) and ALB concentration for diabetes were 1.125 (95% CI: 1.024–1.231) and 1.029 (95% CI: 1.007–1.051) respectively in the adjusted model. Also the HRs were closely related with BMI changes. For those who had a BMI changes<−1.00kg/m2, the HRs were lower and not statistically significant, and for those with increasing BMI during an average of 4years' follow-up, the HRs were higher. ConclusionThere was a positive and independent association between baseline ALB concentrations with diabetes incident among Chinese male elderly, and this association was closely related with BMI changes.

Anti-EGFR antibody conjugated silica nanoparticles as probes for lung cancer detection.

A well-designed nanosystem [anti-epidermal growth factor receptor-MB-encapsulated thiol-terminated silica nanoparticles (EGFR/MB-SHSi) complexes] containing silica nanoparticles and near-infrared fluorescence dye (NIRF) methylene blue (MB) was established as a tumor-targeted probe for potential lung cancer detection. The anti-EGFR/MB-SHSi complexes exhibited desirable and homogenous particle size, high bovine serum albumin stability, low hemolytic activity, neutral surface charges and negligible cytotoxicity in vitro. Furthermore, the results of confocal laser scanning microscopy and flow cytometry confirmed that the EGFR-targeted function induced high and specific cellular uptake of anti-EGFR/MB-SHSi complexes. In vivo investigation of nude mice bearing A549 tumor xenografts revealed that anti-EGFR/MB-SHSi complexes possessed strong tumor target ability. These observations indicated that anti-EGFR/MB-SHSi complexes may be a safe and tumor-targeting probe for the detection of cancer.

Cell surface dynamics and cellular distribution of endogenous FcRn.

A major role for FcRn is the salvage of pinocytosed IgG and albumin from a degradative fate in lysosomes. FcRn achieves this by binding IgG in a pH-dependent manner in acidic endosomes and recycling it to the plasma membrane to be released at neutral pH. This is important in maintaining high serum IgG and albumin levels and has the potential to be exploited to modulate the pharmacokinetics of antibody-based therapeutics. Although FcRn is responsible for the recycling of IgG, the dynamic behaviour of endogenous FcRn is not well understood. Our data shows that the majority of endogenous receptor is distributed throughout the endosomal system and is present only at a low percentage on the plasma membrane at steady state. A significant fraction of FcRn at the cell surface appears to be endocytosis resistant while the remainder can undergo rapid endocytosis. To maintain surface levels of the receptor, endocytosed FcRn is replaced with FcRn from the internal pool. This unexpected complexity in FcRn cell surface dynamics has led us to propose a model for FcRn trafficking that should be taken into account when targeting FcRn at the cell surface for therapeutic purposes.

Serum albumin levels and depression in people living with Human Immunodeficiency Virus infection: a cross-sectional study

BackgroundLower serum albumin levels and depression are common among HIV-infected persons. High serum albumin levels may provide protection against depression through its defensive role in inflammation and infection. We tested the hypothesis of an independent relationship between serum albumin levels and depressive symptoms in a cohort of HIV-infected persons. MethodsA cross-sectional survey was conducted among 310 HIV-infected persons (176 men and 134 women) aged 20–60years residing in the Kathmandu Valley, Nepal. The bromocresol green method was used to measure serum albumin levels and the Beck Depression Inventory method was used to measure depressive symptoms, with a cut off score of 20 or higher indicating likely depression. The relationship between serum albumin levels and depressive symptoms was assessed using both multiple linear regression analysis and multiple logistic regression analysis, with adjustment for sociodemographic, cardiovascular, life-style, and HIV-related clinical and treatment confounding factors. ResultsSerum albumin levels were inversely associated with depressive symptoms scores (beta for 1 unit change in serum albumin levels: β=−3.91; p=0.001) for the total participant sample. This inverse association was significant in both men (β=−3.93; p=0.009) and women (β=−4.47; p=0.03). A significantly decreased risk of depression was observed among participants with the highest serum albumin levels, with odds ratio and 95% CI for those with >5.0g/dL versus <4.0g/dL of 0.22 (0.06–0.80) (p=0.01). ConclusionSerum albumin levels were inversely associated with depressive symptoms scores in HIV-infected persons.

Incidence and diagnosis of Acute kidney injury in hospitalized adult patients: a retrospective observational study in a tertiary teaching Hospital in Southeast China

BackgroundAcute kidney injury (AKI) places a heavy burden on the healthcare system in China and is usually misdiagnosed. However, there are limited studies that have described the epidemiology and diagnosis of AKI in China. The aim of this study was to describe the incidence and diagnosis of AKI in hospitalized adult patients in a tertiary teaching hospital in southeast China.MethodsAll adult patients hospitalized from October 1, 2013 to September 30, 2014 in the First Affiliated Hospital of Nanjing Medical University were screened using the Lab Administration Network. AKI definition and staging were based on the KDIGO AKI criteria. Demographic characteristics, laboratory examination, clinical data, and clinical outcomes of AKI patients were recorded and analyzed.ResultsThe incidence of AKI was 1.6% (1401/87196). The 30-day mortality was 35.3%. AKI stage 1, 2, 3 and RRT accounted for 38.0% (532/1401), 22.0% (309/1401), 40.0% (560/1401), and 16.3% (228/1401) of patients, respectively. The Renal, other Internal Medicine, Surgery, and ICU Departments accounted for 7.4%, 37.1%, 30.1%, and 25.4% of AKI patients, respectively. The timely diagnosis rate, delayed diagnosis rate, and missed diagnosis rate were 44% (616/1401), 3.3% (46/1401), and 52.7% (739/1401), respectively. Patients hospitalized in the Renal Department had the highest AKI diagnosis rate (89.3%, 88/103), while missed diagnosis rate of the surgical patients was as high as 75.1% (317/422). Multivariable logistic regression analysis indicated that presence of tumors, higher serum albumin, and AKI stage 1 were associated with failure to timely diagnose AKI, whereas presence of chronic kidney disease, oliguria, higher blood urea nitrogen, and greater number of organ failures correlated with earlier diagnosis.ConclusionsAKI was characterized by a high incidence, high short-term mortality, and high missed diagnosis rate in hospitalized adult patients in our hospital. Interventions for improving diagnosis of AKI are urgently needed.

Risks and benefits of phase I trials: Eighteen-year experience from a single institution.

e18146 Background: Phase I trials are a critical component of drug development; yet are considered non-therapeutic. This leads to recruitment barriers due to provider and patient discomfort. The largest meta-analysis of phase I studies has previously shown a response rate (RR) of 10.6%. Herein we report the results from our institution. Methods: Records of patients enrolled on phase I trials at our institution from January 1999 to December 2016 were reviewed. Recorded data included adverse events (AE); treatment related responses and deaths. Kaplan-Meier analysis and t-test were performed on the reviewed data. Results: During this period 774 patients were accrued on 64 phase I trials [43.8% cytotoxic, 45.3% biological, 6.2% both and 4.7% viral agents]. Primary cancer diagnoses included colorectal (25.2%), ovarian (17.6%), lung (7.8%), uterine (6.6%) and breast (6.1%). In total, 609 patients were evaluable for response, 41.1% had stable disease (SD) and overall RR was 7.7% (complete RR = 1.0%). Patients with overall clinical benefit (SD+response) had lower mean baseline WBC (4.83 vs 5.94 k/uL, p = 0.0008), ANC (2.92 vs 4.12 k/uL, p = 0.00007), platelets (209 vs 246 k/uL, p = 0.00007), LDH (280 vs 346 U/L, p = 0.0055) and higher serum albumin (3.97 vs 3.86 g/dL, p = 0.011) as compared to patients with progressive disease. Grade 3/4 non-hematological and hematological AE were seen in 28.5% and 19.9% patients, respectively. Treatment-related mortality was 0.8%. Patients with baseline LDH below the median (247 U/L) for the cohort had a higher median survival (312 days vs 201 days, p &lt; 0.001, HR 0.61 95% CI 0.51-0.73). The median and mean duration on study were 56 and 87 days, respectively. Conclusions: This is one of the largest single-institution series of phase I oncology trials. Our RR of 7.7% [95% CI 5.9-10.1%] falls within the 95% CI of the RR of a majority of third line (and greater) chemotherapy regimens for solid tumors. Thus, the concept of 'non-therapeutic' nature of phase I studies needs reconsideration.

Benefit of second-line chemotherapy for advanced biliary tract cancer.

e15621 Background: Second-line chemotherapy (2LCTX) is increasingly applied in patients (pts) with advanced biliary tract cancer (aBTC), although no randomized trial has so far demonstrated the benefit of this intervention over best supportive care (BSC) alone. In the absence of randomized data, we thus conducted a comparative effectiveness analysis of survival outcomes in aBTC pts treated with BSC±2LCTX. Methods: In this single-center cohort study, we retrospectively included 80 pts with metastatic, recurrent, or inoperable aBTC who completed 1st-line CTX at our department between 2003 and 2016. Thirty-eight of these pts (48%) received 2LCTX+BSC (Fluoropyrimidine (FP) mono: n = 26 (68%), FP-based combination CTX: n = 9 (24%), Others: n = 3 (8%)). Primary endpoint was 18-month overall survival (OS). An inverse-probability-of-treatment-weighted analysis (IPTW) was implemented to rigorously account for imbalances in prognostic variables between the two study groups. Results: During a median follow-up of 14.8 months, we observed 49 deaths. Six-month, 12-month, and 18-month OS estimates were 77%, 53% and 23% in the BSC+2LCTX group, and 29%, 21%, and 14% in patients in the BSC group, for a univariable hazard ratio (HR) for OS of 0.36 (95%CI: 0.20-0.64, p = 0.001). However, pts receiving 2LCTX+BSC had a significantly higher prevalence of favorable prognostic variables, such as a higher Karnofsky Index (p = 0.0001), lower serum bilirubin (p = 0.03), higher hemoglobin (p = 0.002), and higher serum albumin (p = 0.0007). After careful adjustment for these imbalances using IPTW, 2LCTX+BSC was not associated with an OS benefit over BSC alone (Adjusted HR = 0.62, 95%CI: 0.30-1.29, p = 0.201). In IPTW analysis, 6-, 12-, and 18-month OS were 51%, 33% and 14% in the BSC+2LCTX group, and 35%, 29%, and 19% in patients in the BSC group. The beneficial association of 2LCTX with OS was highly time-dependent, with IPTW HRs of 0.07 (p = 0.002), 0.42 (p = 0.05), and 0.53 (p = 0.11) after 3, 6, and 12 months, respectively. Conclusions: Within the limitations of a non-randomized study, our data support the concept that 2LCTX is associated with a short-term OS benefit in pts with aBTC.

Association of the bevacizumab pharmacokinetics with efficacy and toxicity in advanced non-squamous non-small cell lung cancer: Kumamoto Thoracic Oncology Study Group (KTOSG) 1003 study.

e20559 Background: Biomarkers predicting the efficacy and toxicity of bevacizumab (Bev) have not yet been established. Therefore we conducted this pharmacokinetic study to elucidate the role of plasma concentration of Bev as a biomarker to predict outcome in the treatment of patients with lung cancer. Methods: This multicenter prospective pharmacokinetic study was conducted among nine centers in Kumamoto Prefecture, Japan. Patients with non-squamous non-small cell lung cancer who were treated using tri-weekly Bev (15mg/kg) with platinum-doublet chemotherapy were enrolled. Plasma samples were collected from all patients before the administration of every dose of Bev until disease progression or treatment discontinuation owing to toxicity. Plasma concentrations of Bev were analyzed via nano-surface and molecular-orientation limited proteolysis coupled with liquid chromatography-mass spectrometry. Results: Between July 2010 and May 2014, 30 patients were enrolled in this study. Majority of the patients received pemetrexed with cisplatin or carboplatin (24 patients, 80%) and others received paclitaxel with carboplatin. The trough concentrations of Bev after first administration (day 22) were 63.19 ± 19.57 μg/mL. Trough concentrations gradually increased until the six cycle of Bev and reached a steady state. Plasma concentrations of Bev did not decrease until disease progression in patients with a long treatment period. Higher mean plasma concentrations of Bev correlated with female sex (p = 0.034) and high serum albumin levels (p = 0.034). Patients who received pemetrexed had higher mean concentrations of Bev (p = 0.038) than those who received paclitaxel. The response rate and progression-free survival did not correlate with the plasma concentration of Bev. Proteinuria (≥Grade 2) correlated with higher concentrations of Bev. Conclusions: Our study demonstrated that various types of chemotherapy influenced the concentrations of Bev, and a higher concentration of Bev may predict the incidence of proteinuria. In addition, clearance of Bev did not change after long treatment period until disease progression. Clinical trial information: 000007630.

Risk assessment based on the Risk Index for Serious Adverse Events (SAEs) in phase I trials.

e14032 Background: Although patients (pts) in phase I trials may have expectations about their chance to benefit, they sometimes experience serious adverse events (SAEs). These events impact on their quality of life negatively as well as their clinical management and survival, if once occurred, regardless of timing of occurrence or relation to study drugs. Therefore, paying close attention for pts who are more likely to experience SAEs may be required; however, little is known about which clinical features are related to SAEs in phase I trials. The aim of this study is to construct a risk index for SAEs prediction. Methods: We collected medical records of 418 pts with solid tumor who participated in phase I trials for the first time and were treated at our hospital from January 2011 to December 2015. The time to first SAE (TTS), defined as the time from registration to first SAE, was analyzed. Stepwise Cox regression model was applied to screen out the factors to build a risk index. Internal validation was performed using a bootstrap procedure. Results: Four hundred and seven pts were analyzed for building a risk index. Median age was 63 years (range 22-81). Predominant primary tumor site was gastrointestinal cancer (65.1%), followed by lung cancer (8.4%) and genitourinary cancer (5.7%). A total of 251 pts (61.7%) were treated with small molecule compounds, while 136 pts (33.4%) were treated with antibody therapy including immune therapy. A total of 101 pts (24.8%) experienced SAEs included 18 events related to study drugs. Four independent risk factors (use of antibody therapy, 60 &lt; age &lt; 70, higher serum albumin concentration and lower serum alkaline phosphatase concentration), identified by stepwise Cox regression model, were combined into simple ternary risk index that stratified pts into low- (n = 93), intermediate- (n = 175) and high-risk group (n = 139). Hazard ratios for high-risk and intermediate-risk relative to low-risk group and their 95% confidence intervals were 5.25 (2.64-10.42; high-risk) and 2.00 (0.99-4.07; intermediate-risk). Conclusions: Risk assessment based on the risk index for SAEs may be useful for patient management in phase I trials. Further research is needed to validate this risk index.

Longitudinal Associations among Renal Urea Clearance-Corrected Normalized Protein Catabolic Rate, Serum Albumin, and Mortality in Patients on Hemodialysis.

There are inconsistent reports on the association of dietary protein intake with serum albumin and outcomes among patients on hemodialysis. Using a new normalized protein catabolic rate (nPCR) variable accounting for residual renal urea clearance, we hypothesized that higher baseline nPCR and rise in nPCR would be associated with higher serum albumin and better survival among incident hemodialysis patients. Among 36,757 incident hemodialysis patients in a large United States dialysis organization, we examined baseline and change in renal urea clearance-corrected nPCR as a protein intake surrogate and modeled their associations with serum albumin and mortality over 5 years (1/2007-12/2011). Median nPCRs with and without accounting for renal urea clearance at baseline were 0.94 and 0.78 g/kg per day, respectively (median within-patient difference, 0.14 [interquartile range, 0.07-0.23] g/kg per day). During a median follow-up period of 1.4 years, 8481 deaths were observed. Baseline renal urea clearance-corrected nPCR was associated with higher serum albumin and lower mortality in the fully adjusted model (Ptrend<0.001). Among 13,895 patients with available data, greater rise in renal urea clearance-corrected nPCR during the first 6 months was also associated with attaining high serum albumin (≥3.8 g/dl) and lower mortality (Ptrend<0.001); compared with the reference group (a change of 0.1-0.2 g/kg per day), odds and hazard ratios were 0.53 (95% confidence interval, 0.44 to 0.63) and 1.32 (95% confidence interval, 1.14 to 1.54), respectively, among patients with a change of <-0.2 g/kg per day and 1.62 (95% confidence interval, 1.35 to 1.96) and 0.76 (95% confidence interval, 0.64 to 0.90), respectively, among those with a change of ≥0.5 g/kg per day. Within a given category of nPCR without accounting for renal urea clearance, higher levels of renal urea clearance-corrected nPCR consistently showed lower mortality risk. Among incident hemodialysis patients, higher dietary protein intake represented by nPCR and its changes over time appear to be associated with increased serum albumin levels and greater survival. nPCR may be underestimated when not accounting for renal urea clearance. Compared with the conventional nPCR, renal urea clearance-corrected nPCR may be a better marker of mortality.

Analysis of Factors Associated with Death in Maintenance Hemodialysis Patients: A Multicenter Study in China.

Background:Patients on hemodialysis have a high-mortality risk. This study analyzed factors associated with death in patients on maintenance hemodialysis (MHD). While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death.Methods:Participants were selected from 16 blood purification centers in China from January 2012 to December 2014. Patients’ data were collected retrospectively. Based on survival status, the participants were divided into two groups: survival group and the death group. Logistic regression analysis was performed to determine factors associated with all-cause mortality.Results:In total, 4104 patients (57.58% male, median age 59 years) were included. Compared with the survival group, the death group had more men and more patients with diabetic nephropathy (DN) and hypertensive nephropathy. The patients preceding death also had lower levels of diastolic blood pressure, hemoglobin, serum albumin, serum calcium, serum phosphate, Kt/V, and higher age. Multivariate analysis revealed that male sex (odd ratio [OR]: 1.437, 95% confidence interval [CI]: 1.094–1.886), age (OR: 1.046, 95% CI: 1.036–1.057), and presence of DN (OR: 1.837, 95% CI: 1.322–2.552) were the risk factors associated with mortality. High serum calcium (OR: 0.585, 95% CI: 0.346–0.989), hemoglobin (OR: 0.974, 95% CI: 0.967–0.981), albumin (OR: 0.939, 95% CI: 0.915–0.963) levels, and dialysis with noncuffed catheter (OR: 0.165, 95% CI: 0.070–0.386) were protective factors based on a multivariate analysis.Conclusions:Hemodialysis patients preceding death had lower hemoglobin, albumin, and serum calcium levels. Multivariate analysis showed that male sex, age, DN, low hemoglobin, low albumin, and low serum calcium were associated with death in hemodialysis patients.

Risks and benefits of phase I liver dysfunction studies: should patients with severe liver dysfunction be included in these trials?

Introduction The goal of organ dysfunction Phase I trials is to characterize the safety and pharmacokinetics of novel agents in cancer patients with liver or kidney dysfunction, but the clinical benefit is not well established. Methods We reviewed 170 patients across 15 liver dysfunction studies at our institution, grouped based on the NCI-Organ Dysfunction Working Group criteria or Child-Pugh Score. Results The median survival for the entire cohort was two months and just one month amongst patients with severe liver dysfunction. Patients with normal or mild liver dysfunction, absence of tumor in liver, good performance status, higher serum albumin and lower bilirubin, aspartate transaminase and alkaline phosphatase had improved survival by univariate analysis. Serum albumin and liver function classification remained significant by multivariate analysis. Conclusion Given poor survival of patients with liver dysfunction, we need better criteria, such as albumin levels, for optimally selecting patients for liver dysfunction studies.

Protein adsorption of dialdehyde cellulose-crosslinked chitosan with high amino group contents

Crosslinked chitosan was prepared by Schiff base formation between the aldehyde groups of dialdehyde cellulose (DAC) and the amino groups of chitosan and a subsequent reduction. DAC was obtained through periodate oxidation of cellulose and solubilization in hot water at 100°C for 1h. Three grades of DAC-crosslinked chitosan were prepared by adding various amounts DAC. The degrees of crosslinking as determined by amino group content were 3.8, 8.3, and 12.1%, respectively. DAC-crosslinked chitosan showed higher stability in the pH 2–9 range and no cytotoxicity was identified over the course of a 21-day long-term stability test. Also, DAC-crosslinked chitosan showed remarkably high bovine serum albumin (BSA) adsorption capacity at pH 5.5 as a result of the increased amino group content, due to the reaction between DAC and chitosan molecular chains occurring at multiple points even though DAC-crosslinked chitosan showed a lower degree of crosslinking.

Solution-blown nylon 6-chitosan core-shell nanofiber for highly efficient affinity adsorption

A facile spinning-based strategy was developed to fabricate chitosan (CS) surface nanofiber-based affinity membranes for protein adsorption. The core–shell nanofiber mat of nylon 6–CS was prepared via coaxial solution blowing process. The nanofibers have a diameter range of 60–300 nm. The core–shell structure was confirmed by transmission electron microscopy, and CS was observed as a thin layer that uniformly adhered to the core. The dye ligand of cibacron blue F3GA (CB F3GA) was further covalently immobilized on the nanofibers with a content of 425 µmol/g. The pristine and CB F3GA-attached mats were studied in protein adsorption. High bovine serum albumin adsorption capacities of 91.9 and 219.6 mg/g were obtained for pristine and CB F3GA-attached mats, respectively. Given its properties of high flux rate and low pressure drop, CB F3GA-attached nylon 6–CS nanofiber mat meets the requirements of highly effective affinity membrane chromatography. Copyright © 2016 John Wiley & Sons, Ltd.

Acute Myeloid Leukemia with Erythroid Predominance: A Reassessment Using Criteria Revised in the 2016 World Health Organization Classification

In the updated 2016 revision of WHO classification, pure erythroid leukemia (PEL) is still viewed as a sole entity without any change of definition. However, erythroleukemia (erythroid/myeloid type) (previously defined as myeloid neoplasms with erythroid predominance [EP] and myeloblasts ≥ 20% or < 20% but ≥ 20% of nonerythroid cells) has been removed. The former is now recognized as acute myeloid leukemia, not otherwise specified (AML-NOS), and the latter as no longer acute erythroid leukemia (AEL) but MDS.Such a change in the updated classification provides us the rationale to conduct this cohort study of patients with AML with EP (AML-EP). We report the impact on survival outcomes and the risk factors for mortality in these patients based on the 2016 WHO classification. A total cohort of 97 consecutive cases of acute myeloid leukemia with erythroid predominance (AML-EP) between 2000 and 2015 was enrolled. Following 2016 WHO classification, AML-EP patients were classified into four groups (Figure 1). Nine PEL patients had more dismal outcomes (median OS: 1 month) as compared with non-PEL patients (Figure 2) and showed more bone marrow fibrosis, worse performance status (PS) and higher serum lactate dehydrogenase (LDH) at diagnosis. In the univariate analysis, risks of death were PEL diagnosis, worse cytogenetic risks, bone marrow fibrosis, leukocytosis, anemia, hypoalbuminemia, high (LDH), and poor PS. In the multivariate analysis, independent predictors of death were PEL diagnosis (adjusted hazards ratio [AHR] 3.00, 95% confidence interval [CI] 1.02¡V8.88, p = 0.029), very poor cytogenetic risk by IPSS-R (AHR 2.73, 95% CI 1.22¡V6.11, p = 0.014), hypoalbuminemia (< 3.7 g/dl) (AHR 2.30, 95% CI 1.09¡V4.83, p = 0.028) and high serum LDH (≥ 250 U/L) (AHR 2.31, 95% CI 1.25¡V4.28, p = 0.008). Based on the karyotype, patients were stratified to different cytogenetic risk groups according to the United Kingdom Medical Research Council (UKMRC) criteria for AML, the revised United Medical Research Council (UKMRC-R) criteria for AML, the International Prognostic Scoring System (IPSS) for MDS, the revised International Prognostic Scoring System (IPSS-R) and the presence or absence of monosomal karyotypes. Cytogenetic risks groups determined by UKMRC-R showed the best ability to predict survival outcomes of AML-EP patients (Figure 3). The outcome of PEL was independently much worse than that of non-PEL. Allogeneic HSCT was administered to 10 patients (one PEL, one AML-MRC, three AML-NOS and five MDS cases), whose disease statuses at transplantation were refractory disease for one and complete remission for nine. As compared to supportive care, the mortality among AML-EP patients did not differ from that of the patients receiving allogenic hematopoietic stem cell transplantation, curative chemotherapy or non-curative chemotherapy.In conclusion, after the 2016 WHO classification was published, only PEL were kept as belonging to neoplasms originated from neoplastic erythroid lineage. This retrospective cohort study reports the clinical features, biological data and survival outcomes of patients with AML-EP and identified PEL diagnosis, very poor cytogenetic risk group of IPSS-R, high serum LDH and low serum albumin as independent predictors for death. Cytogenetic risks groups determined by UKMRC-R showed the best ability to predict survival outcomes of AML-EP patients. The outcome of PEL was independently much worse than that of non-PEL. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

High Prevalence of Diastolic Dysfunction in Incident Patients on Peritoneal Dialysis: Association with Low Thyroid Hormones

Background/Aims: Diastolic dysfunction (DD) and low levels of thyroid hormones (TH) are frequent found in chronic kidney disease; both are associated with all-cause and cardiovascular mortality. However, a link between them has not yet been established. The aim of this study was to analyze DD as a surrogate marker of fibrosis and its association with TH in incident patients on peritoneal dialysis (PD). Methods: A cross-sectional study with 183 incident patients on PD with preserved ejection fraction was performed. Clinical and demographic data were registered. Serum total and free (t/f) triiodothyronine (T3), thyroxin (T4), and thyroid stimulating hormone levels were determined by RIA kits, albumin and high-sensitivity C-reactive protein by conventional assays. Transthoracic 2D echocardiogram was performed for evaluation of left ventricular (LV) mass and ejection fraction. DD was evaluated using pulsed-wave tissue Doppler imaging. Results: Patients were 43 ± 12, 42% with diabetes mellitus (DM). Some degree of DD was found in 62% of patients; 18% had grade I DD, 8% grade II DD and 36% grade III DD. Patients with grade III DD were more likely to have diabetes, older, high LV mass and low serum albumin, t/fT3 and tT4 levels. In logistic multivariate regression analysis, it was found that diabetes (B = -0.86, 95% CI 0.182-0.992, p < 0.05), hypertension (B = -0.95, 95% CI 0.184-0.817, p = 0.01) and tT3 (B = -1.94, 95% CI 0.023-0.876, p < 0.05) were associated with grade III DD. Conclusions: High prevalence of grade III DD was found in incident patients on PD. In addition to DM and hypertension, tT3 was found to be an independent risk factor for grade III DD and more studies are needed to understand the reasons as to why this association is present.