Showing papers on "Serum albumin published in 2023"

Structure-Activity Relationship of pH-Sensitive Doxorubicin-Fatty Acid Prodrug Albumin Nanoparticles.

Abstract: Albumin has emerged as a versatile drug carrier. To harness albumin as a carrier for doxorubicin (DOX), we synthesized three acid-labile DOX prodrugs using stearic acid (SA), oleic acid (OA), and linoleic acid (LA) as the albumin-binding motif, respectively. Different from conventional albumin nanodrugs (such as Abraxane, with a drug loading of 10%), the DOX prodrugs assembled albumin nanoparticles (NPs) have an ultrahigh drug loading (>35%). Noteworthy, we demonstrated that the saturation of fatty acids exerted great influence on colloidal stability of prodrug NPs, thus affecting their in vivo pharmacokinetics, tumor accumulation and antitumor efficacy. Furthermore, the hydrazone bond-bridged DOX prodrugs could remain intact in the bloodstream but allow DOX to be released in the acidic tumor environment, resulting in improved antitumor efficacy and safety. Our work gives novel insights into the structure-to-efficacy relationship of albumin-bound fatty acid prodrugs and provides a simple strategy for advanced albumin-bound nanomedicines.

Human Serum Albumin: From Molecular Aspects to Biotechnological Applications

Abstract: Human serum albumin (HSA), the most abundant protein in plasma, is a monomeric multidomain macromolecule that represents the main determinant of plasma oncotic pressure and the principal modulator of fluid distribution between body compartments [...].

The association between serum albumin and long length of stay of patients with acute heart failure: A retrospective study based on the MIMIC-IV database

Abstract: Background The purpose of this article is to assess the relationship between serum albumin level and long length of stay (LOS) of inpatients with acute heart failure (AHF) in the intensive care unit (ICU). Methods We retrospectively analyzed data of 2280 patients with AHF from the medical information mart for intensive care IV (the MIMIC-IV) database. Multivariate logistic regression was performed to evaluate the association between serum albumin and long LOS, and the development of the predictive model was based on independent predictors of long LOS. Results According to the statistical results, A negative linear relationship was presented between albumin and long LOS of AHF patients in the ICU (P for trend <0.001), and serum albumin could predict long LOS (AUC 0.649, 95%CI 0.616–0.683, P <0.001). Based on independent predictors, including respiratory failure (OR 1.672, 95%CI 1.289–2.169, P<0.001), WBC (OR 1.046, 95%CI 1.031–1.061, P<0.001), creatinine (OR 1.221, 95%CI 1.098–1.257, P<0.001), glucose (OR 1.010, 95%CI 1.007–1.012, P<0.001), lactic acid (OR 1.269, 95%CI 1.167–1.381, P<0.001), and albumin (OR 0.559, 95%CI 0.450–0.695, P<0.001), identified by multivariable logistic regression analysis, we developed the nomogram to predict the probability of long LOS of AHF patients in the ICU. The nomogram accurately predicted the probability of long LOS (AUC 0.740, 95%CI 0.712–0.768, P<0.001). The calibration suggested the predictive probability was highly consistent with the actual probability of long LOS. Decision curve analysis (DCA) also suggested that the nomogram was applicable in the clinic. Conclusion Serum albumin level was negatively associated with LOS among AHF patients. The predictive model based on serum albumin has predictive value for evaluating the length of stay in AHF patients.

Maternal serum ischemia-modified albumin (IMA), total-sulphydryl concentrations, and some subclinic inflammatory markers in hyperemesis gravidarum (HG).

Abstract: This study investigates the relationship between Ischemia Modified Albumin and Total-Sulphydryl levels with some subclinical inflammatory markers in patients with hyperemesis gravidarum.A total of 258 pregnant women, 137 with hyperemesis gravidarum and 121 low-risk pregnancies, were included in this case-control study. The patients were divided into three groups according to the severity of hyperemesis gravidarum as mild (n = 53), moderate (n = 41) and severe (n = 43).Serum Ischemia Modified Albumin levels were statistically different from the control group (P < 0.001). Among the subgroups, the highest Ischemia Modified Albumin value was observed in the severe hyperemesis gravidarum group, and the highest Total-Sulphydryl level was observed in the mild hyperemesis gravidarum group (P < 0.001). Serum potassium levels were higher in the control group (P < 0.001). While a negative correlation was observed between Ischemia Modified Albumin and Total-Sulphydryl, a positive correlation was observed in Platelet crit, C-reactive protein, and ketonuria. As the severity of the disease increases, Ischemia Modified Albumin, which is an oxidative stress factor, increases, and Total-Sulphydryl levels decrease (p < 0.001). Logistic regression analysis revealed that a one-unit increase in Ischemia Modified Albumin resulted in a statistically significant 1.9-fold increase in the risk of Severe hyperemesis gravidarum (OR 1.92, 95% CI 1.008-1.956; P = 0.01) CONCLUSION: This study shows that there is a condition in the pathophysiology of hyperemesis gravidarum, with an increase in Ischemia Modified Albumin and a decrease in Total-Sulphydryl levels, and oxidative stress occurs. It was important to detect increased Ischemia Modified Albumin and decreased antioxidant values in relation to the inflammatory factors that were effective in the severe hyperemesis gravidarum group.

The Role of Ischemia-modified Albumin and Ischemia-Modified Albumin to Albumin Ratios in Patients with Alopecia Areata

Abstract: Introduction Objective To investigate the role of ischemia-modified albumin (IMA) and IMA/albumin levels in patients with AA. Methods The present prospective crossectional study includes patients ≥18 who were admitted to the Dermatology and Venerology Department of Hitit University Hospital between April 1, 2021, and September 30, 2021. 70 patients participated in the study (n=34 for the study group and n=36 for the control group). Demographic features, clinical characteristics, IMA, and IMA/albumin levels were compared between the groups. The study group was divided into subgroups based on the number of patches, disease duration, and the number of disease attacks. IMA and IMA/albumin levels were compared between each subgroup. Results The study and control groups were similar with regard to demographic features and clinical characteristics. Significant differences were observed between the mean IMA and IMA/albumin ratio (p=0.004 and 0.012, respectively). The study subgroups were comparable in the number of patches, disease duration, and number of disease attacks. Conclusion Although oxidative stress is an important component in the etiology of AA, IMA and IMA/albumin may not be useful in the prediction of disease severity in patients with AA.

A generalizable strategy for crosslinkable albumin-based hydrogels and application as potential anti-tumor nanoplatform

Abstract: Albumin-based hydrogels have emerged as promising nanoparticle systems for the effective delivery of hydrophobic anticancer drugs. Anti-cancer drugs often cause some adverse effects, such as toxicity and rapid clearance by mononuclear phagocytic systems. Herein, a new strategy of synthesizing N-hydroxysuccinimide (NHS)-activated linker to form crosslinkable albumin-based hydrogels (CABH) is reported. The CABH favored physiochemical characteristics improvement of doxorubicin (Dox) and drug release. The CABH was constructed depending on the crosslinking reaction between NHS activated glycerol and albumin. The size of CABH was approximately 200 nm examined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). It was found that the particle size and size distribution of the CABH remained stable in neutral PBS for 1 week. Dox loaded CABH would be controllably released in weak acidic environment verified by in vitro release and in vitro cell imaging. The Dox loaded hydrogel results in significant killing in the case of acidic culture medium. Our work provides a crosslinking method to formulate albumin nanoplatform and improve the size, stability, drug loading capacity and controlled release, which throws light on the potential application in drug delivery. Graphical Abstract

Prognostic Role of Serum Albumin in Predicting 30-Day Mortality in Patients with Infections in Emergency Department: A Prospective Study

Abstract: Background: Infections in emergency departments (EDs) are insidious clinical conditions characterised by high rates of hospitalisation and mortality in the short-to-medium term. The serum albumin, recently demonstrated as a prognostic biomarker in septic patients in intensive care units, could be an early marker of severity upon arrival of infected patients in the ED. Aim: To confirm the possible prognostic role of the albumin concentration recorded upon arrival of patients with infection. Methods: A prospective single-centre study was performed in the ED of the General Hospital of Merano, Italy, between 1 January 2021 and 31 December 2021. All enrolled patients with infection were tested for serum albumin concentration. The primary outcome measure was 30-day mortality. The predictive role of albumin was assessed by logistic regression and decision tree analysis adjusted for Charlson comorbidity index, national early warning score, and sequential organ failure assessment (SOFA) score. Results: 962 patients with confirmed infection were enrolled. The median SOFA score was 1 (0–3) and the mean serum albumin level was 3.7 g/dL (SD 0.6). Moreover, 8.9% (86/962) of patients died within 30 days. Albumin was an independent risk factor for 30-day mortality with an adjusted hazard ratio of 3.767 (95% CI 2.192–6.437), p < 0.001. Decision tree analysis indicated that at low SOFA scores, albumin had a good predictive ability, indicating a progressive mortality risk reduction in concentrations above 2.75 g/dL (5.2%) and 3.52 g/dL (2%). Conclusions: Serum albumin levels at ED admission are predictive of 30-day mortality in infected patients, showing better predictive abilities in patients with low-to-medium SOFA scores.

Nasal Polyposis and Serum Albumin: Systemic Effects of Local Inflammation

Abstract: Introduction The genesis of chronic rhinosinusitis is always a topic of debate. A polyp is a pale, edematous tissue emerging mostly from the middle meatus. An epithelial injury caused by continuous inflammation of the nasal mucosa is considered to be a possible cause of the genesis of nasosinusal polyps. Objective To understand the link between serum albumin levels and nasal polyposis. Methods A retrospective study of 180 consecutive patients between January 2016 and January 2020 at our center. We then divided the patients into three age- and gender-matched groups: 60 patients with chronic rhinosinusitis with nasal polyposis, 60 patients with chronic rhinosinusitis without nasal polyposis, and a control group with 60 patients. No patient had a history of any pathology that could alter serum albumin. We then compared the level of serum albumin between the three groups. Results The group of patients with rhinosinusitis and nasal polyposis consisted of 60 patients with a serum albumin value of 4.49 ± 0.29 g/dL, whereas in the control group, the serum albumin value was 4.67 ± 0.2 g/dL. We found a significant difference between the group with nasal polyposis and the other two groups evaluated: chronic rhinosinusitis without nasal polyposis (p<0.001) and the control group (p<0.001). Conclusions Lower levels of serum albumin can be seen in patients with chronic rhinosinusitis with nasal polyposis. Further studies should aim to apply its value since it is a non-expensive marker, to the follow-up of those patients or even to stratify them according to their endotype.

The effect of serum uric acid, bilirubin and albumin levels on antioxidant status in HIV-negative immunocompetent cryptococcal meningitis patients with post-infectious inflammatory response syndrome.

Abstract: Oxidative imbalances have been observed in various neurological diseases. Despite the microbiological control in cryptococcal meningitis (CM), a proportion of previously healthy patients experience a clinical deterioration known as post-infectious inflammatory response syndrome (PIIRS). However, the antioxidant status in PIIRS remains unclear. In this study, we found that the serum antioxidant status of HIV-negative immunocompetent CM patients during PIIRS episodes was lower than that of healthy controls. There was a relationship between baseline serum indirect bilirubin levels and the development of PIIRS, and serum uric acid levels may indicate the severity of the disease during PIIRS episodes. Oxidative stress may play a role in the development of PIIRS.

Influence of Preoperative Serum Albumin on Acute Kidney Injury after Aortic Surgery for Acute Type A Aortic Dissection: A Retrospective Cohort Study

Abstract: There are relatively few articles on the relationship between serum albumin and acute kidney injury (AKI). Therefore, the objective of this research was to study the relationship between serum albumin and AKI in patients who were undergoing surgery for acute type A aortic dissection. Methods: We retrospectively collected data from 624 patients attending a Chinese hospital between January 2015 and June 2017. The target independent variable was serum albumin measured before surgery after hospital admission, and the dependent variable was AKI, defined in accordance with the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Results: The mean age of these 624 selected patients was 48.5 ± 11.1 years, and almost 73.7% were male. A nonlinear association was detected between serum albumin and AKI; the turning point was 32 g/L. The risk of AKI decreased gradually as the serum albumin level increased up to 32 g/L (adjusted OR = 0.87; 95% CI 0.82–0.92; p < 0.001). When the serum albumin level exceeded 32 g/L, the level of serum albumin was not associated with the risk of AKI (OR = 1.01, 95% CI 0.94–1.08; p = 0.769). Conclusions: The findings suggest that preoperative serum albumin below 32 g/L was an independent risk factor for AKI in patients undergoing surgery for acute type A aortic dissection. Trial registration: A retrospective cohort study.

Evaluation of Albumin and Ischemia Modified Albumin Levels in Children with Acute Malnutrition

Abstract: Background: Children are significantly more likely to be malnourished due to their special nutritional needs for growth. Ischemia Modified Albumin (IMA) is a new marker of ischemia that occurs when serum albumin comes in contact with the heart's ischemic tissues. IMA has been used to measure several acute conditions but has never been used to measure acute malnutrition in children. This study aims to examine albumin and IMA in malnourished children to see if they can be used as markers of malnutrition in children. Materials and Methods: 84 children were examined (41 boys and 43 girls, mean age (SD): 6.18 (3.89); range: 0.92-16.75 years) who were referred to the hospital from 20 October to May 20, 2020. A physician performed nutrition examinations on children. BMI of less than 18.5 was considered malnourished children. The hypothesis of the normality of variables was accepted with the Kolmogorov–Smirnov test. To study the difference in variables means at groups, the T-test and Phi-Correlation were used. The ANCOVA was used to study the relationship between variables and Albumin and IMA values at different levels. Results: The amount of albumin in the study group ranged from 4.10 to 5.15 (mean ± SD 4.82± 0.17), and the IMA range in the study group was 0.56 to 1.25 (mean ± SD 0.74± 0.13). The amount of albumin in the control group ranged from 4.19 to 5.19 (mean ± SD 4.83± 0.18), and the IMA range in the control group was 0.44 to 1.11 (mean ± SD 0.67± 0.13). No significant difference was observed between the albumin values (p-value = 0.752) between malnourished and healthy children. However, the IMA level in malnourished children was significantly higher (p-value = 0.19) than in healthy children. Conclusions: Although albumin was not significantly different between the two groups, the IMA of malnour-ished children was significantly higher than that of healthy children. This result means that IMA can be used as a marker for malnutrition in children. This study is a preliminary study showing that IMA can be used as a malnutrition marker in children with malnutrition and we believe that it will contribute to the literature.

Albumin Is a Component of the Esterase Status of Human Blood Plasma

Abstract: The esterase status of blood plasma can claim to be one of the universal markers of various diseases; therefore, it deserves attention when searching for markers of the severity of COVID-19 and other infectious and non-infectious pathologies. When analyzing the esterase status of blood plasma, the esterase activity of serum albumin, which is the major protein in the blood of mammals, should not be ignored. The purpose of this study is to expand understanding of the esterase status of blood plasma and to evaluate the relationship of the esterase status, which includes information on the amount and enzymatic activity of human serum albumin (HSA), with other biochemical parameters of human blood, using the example of surviving and deceased patients with confirmed COVID-19. In experiments in vitro and in silico, the activity of human plasma and pure HSA towards various substrates was studied, and the effect of various inhibitors on this activity was tested. Then, a comparative analysis of the esterase status and a number of basic biochemical parameters of the blood plasma of healthy subjects and patients with confirmed COVID-19 was performed. Statistically significant differences have been found in esterase status and biochemical indices (including albumin levels) between healthy subjects and patients with COVID-19, as well as between surviving and deceased patients. Additional evidence has been obtained for the importance of albumin as a diagnostic marker. Of particular interest is a new index, [Urea] × [MDA] × 1000/(BChEb × [ALB]), which in the group of deceased patients was 10 times higher than in the group of survivors and 26 times higher than the value in the group of apparently healthy elderly subjects.

Coelenterazine Indicators for the Specific Imaging of Human and Bovine Serum Albumins

Abstract: Albumin assays in serum are important for the prognostic assessment of many life-threatening diseases, such as heart failure, liver disease, malnutrition, inflammatory bowel disease, infections, and kidney disease. In this study, synthetic coelenterazine (CTZ) indicators are developed to quantitatively illuminate human and bovine serum albumins (HSA and BSA) with high specificity. Their functional groups were chemically modified to specifically emit luminescence with HSA and BSA. The CTZ indicators were characterized by assaying the most abundant serum proteins and found that the CTZ indicators S6 and S6h were highly specific to HSA and BSA, respectively. Their colors were dramatically converted from blue, peaked at 480 nm, to yellowish green, peaked at 535 nm, according to the HSA–BSA mixing ratios, wherein the origins and mixing levels of the albumins can be easily determined by their colors and peak positions. The kinetic properties of HSA and BSA were investigated in detail, confirming that the serum albumins catalyze the CTZ indicators, which act as pseudo-luciferases. The catalytic reactions were efficiently inhibited by specific inhibitors, blocking the drug-binding sites I and II of HSA and BSA. Finally, the utility of the CTZ indicators was demonstrated through a quantitative imaging of the real fetal bovine serum (FBS). This study is the first example to show that the CTZ indicators specify HSA and BSA with different colors. This study contributes to the expansion of the toolbox of optical indicators, which efficiently assays serum proteins in physiological samples. Considering that these CTZ indicators immediately report quantitative optical signals with high specificity, they provide solutions to conventional technical hurdles on point-of-care assays of serum albumins.

Significance of levels of serum proteins and serum lipids as prognostic indicators in mortality of burn patients

Abstract: Background: Burn mortality is significant because of the higher metabolic and physiological abnormalities; it causes more so than because of the actual injury. Since these abnormalities persist throughout the clinical course of burns, it is believed that both the trend of change and absolute values of the serum proteins and serum lipids have an impact on the prognosis and outcome. Aims and Objectives: This study aimed to find whether serum albumin, globulin, total protein, cholesterol, and triglyceride levels are clinically relevant to determine the mortality of a burn patient and thereby the patient’s outcome. Materials and Methods: The current prospective analytical study was carried out in patients who were admitted to the burn unit, Department of Surgery, Shyam Shah Medical College, and associated Sanjay Gandhi Memorial Hospital, Rewa (M.P.), during the period of April 1, 2021–June 30, 2022 (15 months), and the results were analyzed. Results: In the present study, a total of 112 patients were studied and followed up. Among them, 86% (96/112) of total patients were survivors who were discharged/DOR in stable condition and 14% (16/112) of total patients expired during the course of treatment. It could be statistically inferred that the increase in values of albumin, globulin, total protein, and cholesterol during the clinical course reduces mortality with serum albumin acting as the best predictor with the highest sensitivity of 100% and specificity of 100% and cholesterol the least. Conclusion: It could be statistically inferred that the increase in values of albumin, globulin, total protein, and cholesterol during the clinical course reduces mortality with serum albumin acting as the best predictor and cholesterol the least.

Assessment of the Predictive Value of Preoperative Serum Albumin and Postoperative Albumin Drop (ΔAlb) for Complications after Pancreas Surgery: A Single-Center Cross-Sectional Study

Abstract: Background: Serum albumin has been shown to be predictive of complications after various gastrointestinal operations. The present study aimed to assess whether preoperative serum albumin and serum albumin drop on postoperative day 1 are associated with postoperative complications after pancreatic surgery. Methods: A single-center cross-sectional study was performed. All patients who underwent pancreatectomy between January 2010 and June 2019 and had preoperative serum albumin value and serum albumin value on postoperative day 1 were included. ΔAlb was defined as the difference between preoperative serum albumin and serum albumin on postoperative day 1. Binary logistic regressions were performed to determine independent predictors of postoperative complications. Results. A total of 185 patients were included. Pancreatoduodenectomies were performed in 133 cases, left pancreatectomies in 36, and other pancreas operations in 16. The preoperative serum albumin value was found to be an independent predictor of complications (OR 0.9, 95%CI 0.9–1.0, p = 0.041), whereas ΔAlb was not significantly associated with postoperative complications (OR 1.0, 95%CI 0.9–1.1, p = 0.787). The threshold of 44.5 g/L for preoperative albumin level was found to have the highest combined sensitivity and specificity based on the maximum Youden index. Patients with preoperative albumin < 44.5 g/L had a higher incidence of postoperative complications and higher median comprehensive complication index than patients with preoperative albumin ≥ 44.5 g/L. Conclusions: This study highlighted that preoperative serum albumin is an independent predictor of postoperative complications after pancreas surgery.

Effects of amino acids and albumin administration on albumin metabolism in surgically stressed rats.

Abstract: BACKGROUND Nutritional therapy and administration of albumin preparations are common in post-surgical patients. However, the effects of these interventions on albumin metabolism are unclear. We elucidated the effect of postoperative exogenous albumin and/or hypocaloric parenteral nutrition administration on albumin metabolism. METHODS Sprague-Dawley rats underwent surgery involving intestinal rubbing followed by intestinal exposure. Subsequently, they were administered experimental solutions for 48 hours and their blood samples collected at 24 and 48 hours, and livers excised at 48 hours. Based on experimental solutions, rats were divided into five groups: non-surgical (Non-surg), GE (glucose and electrolyte solution), AGE (amino acids, glucose, and electrolyte solution), GE+Alb (rat serum albumin), and AGE+Alb. Their plasma albumin concentrations; albumin fractional synthesis rate (ALB FSR); redox state of albumin, indicated by MA ratio (mercaptoalbumin/total albumin); and mRNA expression of albumin and hepatocyte nuclear factor-1 (HNF-1) in the liver were measured. RESULTS GE and AGE groups showed significant decline in plasma albumin concentrations. ALB FSR was significantly enhanced in AGE group compared to GE group. mRNA expression of albumin was similar to ALB FSR in all groups and of HNF-1 was significantly decreased in GE+Alb and AGE+Alb groups compared to Non-surg group. The redox state of albumin in AGE group was similar to Non-surg group, suggesting that AGE administration maintained the physiological redox state of albumin. This effect was not observed in AGE+Alb group. CONCLUSION Administration of amino acids comprising hypocaloric parenteral nutrition post-surgery augmented ALB FSR and maintained physiological redox state of albumin only without simultaneous albumin administration. This article is protected by copyright. All rights reserved.

Prevalence of anti‐egg albumin antibodies in cerebrospinal fluid of patients with mild and severe Alzheimer’s Disease. Correlation with gender and incidence of anti‐casein antibodies and AGEs.

Abstract: Alzheimer’s Disease (A.D.) is a multifactorial process. Advanced glycation end products (AGEs) have been correlated with disease development1. Additionally, high concentrations of antibodies against the food derived antigens egg‐albumin and bovine casein, have been detected in patients with Alzheimer’s disease in preliminary research presented by our team, previously (AAIC 2018).

Controlled Temporal Release of Serum Albumin Immobilized on Gold Nanoparticles.

Abstract: Proteins adsorbed to gold nanoparticles (AuNPs) form bioconjugates and are critical to many emerging technologies for drug delivery, diagnostics, therapies, and other biomedical applications. A thorough understanding of the interaction between the immobilized protein and AuNP is essential for the bioconjugate to perform as designed. Here, we explore a correlation between the number of solvent-accessible thiol groups on a protein and the protein desorption rate from the AuNP surface in the presence of a competing protein. The chemical modification of human serum albumin (HSA) was carried out to install additional free thiols using Traut's reagent and create a library of HSA analogues by tailoring the molar excess of the Traut's reagent. We pre-adsorbed HSA variants onto the AuNP surface, and the resulting bioconjugates were then exposed to IgG antibody, and protein exchange was monitored as a function of time. We found that the rate of HSA displacement from the AuNP correlated with the experimentally measured number of accessible free thiol groups. Additionally, bioconjugates were synthesized using thiolated analogues of bovine serum albumin (BSA) and suspended in serum as a model for a complex sample matrix. Similarly, desorption rates with serum proteins were modulated with solvent-accessible thiols on the immobilized protein. These results further highlight the key role of Au-S bonds in the formation of protein-AuNP conjugates and provide a pathway to systematically control the number of free thiols on a protein, enabling the controlled release of protein from the surface of AuNP.

Study the effect of a drug depakene (Valproic acid) in the serum levels of immune proteins in albino male rats.

Abstract: This study aimed to investigate the effect of administration of depakene (valproic acid)(VPA) (15 mg/Kg of body weight, orally) on serum protein levels, including immune proteins, because its functions and the importance of these proteins in the body and they are overlapping, and that was by measured protein levels before and after treatment as concentrations of total protein (Tp), albumin and globulin in normal male rats and in rats that treated with VPA drug along the period of experiment (30) days. The results showed a significant decrease (P<0.05) in concentrations of total protein and albumin in comparison with normal control group, whereas did not observe significant differences (P<0.05) in globulin concentration compared with normal control group, despite of, there was a little decrease in globulin concentration in rats group that administrated the drug under study but non-significant. It could be concluded of the present study that the VPA drug have an greater side effects on concentration and function of proteins in serum, and subsequently, may extending these effects to comprise its effect on the immunity, osmotic pressure, blood volume, nutrients exchange between the blood and tissues, glomerular infiltration rate, transport many of materials and hormones, and several of physiological and biochemical functions which correlated with the serum proteins

A pre-operative high-protein diet can improve the serum albumin levels of patients undergoing total knee arthroplasty

Abstract: To the Editor: Malnutrition is associated with an increased risk of complications after total knee arthroplasty (TKA), including persistent wound drainage, delay of wound healing, superficial surgical site and even deep periprosthetic joint infections, and intensive care unit admission.[1] Albumin (ALB) is the most abundant protein in human plasma and is considered a reliable and sensitive biomarker of nutritional status and malnutrition. Like malnutrition, low serum ALB levels are not only associated with various post-operative complications following TKA including pulmonary infection, renal impairment, superficial and deep infections, unplanned intubation, and even mortality; but also associated with increased treatment costs, longer length of stay and higher risk of readmission.[2] Human albumin solution (HAS) is frequently used to correct hypoproteinemia. However, a study including >1 million patients from 510 hospitals in the United States showed that HAS use was associated with an increased risk of thromboembolic, acute renal failure, and intensive care unit admission.[3] Furthermore, HAS is expensive, placing a substantial financial burden on health care systems. Pre-operatively correcting hypoalbuminemia and increasing ALB levels may be an effective way to reduce postoperative ALB use due to the elective nature of TKA. Therefore, this study was performed to illustrate the effect of pre-operative ALB levels on human ALB use and to determine the effect of a high-protein diet during the preoperative waiting period on serum ALB levels in patients scheduled to undergo TKA. This was a single-center retrospective study, which was approved by the Ethics Committee of West China Hospital of Sichuan University (No. 2020–804), and registered in the Chinese Clinical Trial Registry (ChiCTR2000034978). The participants of the study consisted of two cohorts. First, patients (n = 660) who underwent primary TKA due to primary osteoarthritis or rheumatoid arthritis in our hospital from January to December 2019 were enrolled to investigate the effect of pre-operative ALB levels on HAS use. Second, patients (n = 88) who underwent primary TKA from January to July 2020 were included to evaluate the effect of a high-protein diet on pre-operative serum ALB levels; those patients were educated to eat a high-protein diet during the pre-operative waiting period. The criterion for post-operative use of HAS was serum ALB concentration under 35 g/L. Patients were excluded if they had been diagnosed with hemophilia, tuberculous arthritis, liver and/ or kidney disease, or if relevant data about them were missing. When a patient decided to undergo TKA for severe knee osteoarthritis or rheumatoid arthritis at the outpatient clinic, admission time was booked. The patient's diet and nutritional status were assessed according to the levels of hemoglobin (Hb) and serum ALB. If Hb <140 g/L or ALB <45 g/L, the patients with body mass index (BMI) < 25 kg/m2 were informed that they needed to increase the proportion of protein in their diet during the pre-operative waiting period to prepare for the surgery. The recommended daily diet was as follows: at least three eggs (fried eggs were not recommended) and 50 g lean meat, which contains approximately 35 g of protein. For the 2019 cohort, data were collected on demographic characteristics including sex, age, BMI; clinical characteristics including diagnosis, and comorbidities such as hypertension and diabetes; results of laboratory tests on the day of admission such as Hb, serum ALB, and HAS use. For the 2020 cohort, in addition to the previously mentioned demographic and clinical characteristics, data were also collected during the waiting period before admission and the results of laboratory tests on the day of outpatient visit, including ALB, globulin Hb, hematocrit (HCT), biomarkers of liver and kidney function, and lipid metabolism. Continuous variables were presented as the mean ± standard deviation, while categorical variables were shown as the frequency (proportion). The relationship between HAS use (treated as a binary variable) and pre-operative serum ALB levels (treated as a continuous variable) was expressed as the relative risk (RR) with a 95% confidence interval (CI). A crude model of HAS use regarding pre-operative serum ALB levels was built using univariate analyses. Logistic regression analyses were used to adjust for other variables. The correlations among the covariates included in the logistic regression were quantified by Spearman's rank correlation analysis. Furthermore, restrictive cubic spline regression analyses were used to detect the dose-response relationships between serum ALB levels tested on the day of admission and post-operative ALB use. The dose response was analyzed with R version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria). The paired-samples t test was used to compare the difference of biomarkers between admission and outpatient visits. P < 0.05 was considered as statistical significance. All data analyses were performed using SPSS version 21 software (IBM, Armonk, NY, USA). A total of 748 patients were included, of whom 660 patients underwent TKA from January to December 2019 while 88 patients underwent the procedure from January to July 2020, and among them, 4 (4.5%) patients were diagnosed with rheumatoid arthritis of the knee. Among patients from the 2019 cohort, 97 (14.7%) were treated with HAS. For patients recruited in 2020, the mean pre-operative waiting period was 39.05 ± 22.78 days. The baseline demographic and clinical characteristics of the 2019 cohort are shown in Supplementary Table 1, https://links.lww.com/CM9/B97, while those from the 2020 cohort are presented in Supplementary Table 2, https://links.lww.com/CM9/B98. Spearman's rank correlation analyses showed that the absolute value of the rank correlation coefficient among covariates included in logistic regression analyses ranged from 0 to 0.375, which meant that correlations among the variables were low and that variables met the requirements for logistic regression analyses [Supplementary Figure 1, https://links.lww.com/CM9/B94]. Several statistical models including different covariates were built to evaluate the impact of pre-operative ALB levels at admission on post-operative HAS use in primary TKA [Supplementary Table 3, https://links.lww.com/CM9/B99]. The univariate analysis (crude model) showed that higher pre-operative ALB levels were associated with a lower risk of post-operative HAS use (RR = 0.720, 95% CI 0.665–0.778, P < 0.001). After adjusting for demographic variables (age, sex, and BMI) and clinical characteristics in the logistic regression analysis step-by-step (models 1, 2, and 3), high pre-operative ALB levels remained significantly associated with a lower risk of HAS use [Supplementary Table 3, https://links.lww.com/CM9/B99]. In addition, a negative dose-response relationship was observed between pre-operative ALB levels and the risk of post-operative HAS use (Poverall < 0.001; Pnon-linear = 0.186; Supplementary Figure 2, https://links.lww.com/CM9/B95). As shown in Table 1, the mean ALB level on the day of admission was significantly higher than the level tested on the day of outpatient visit (46.04 ± 2.49 g/L vs. 42.79 ± 4.09 g/L; P < 0.001), while there were no significant differences between admission and outpatient visits in the levels of globulin, Hb, HCT, and fasting blood glucose, as well as in the biomarkers of liver and kidney function and lipid metabolism (all P > 0.05). Table 1 - The effect of high-protein diet on different biomarkers in patients undergoing primary TKA from the 2020 cohort. Biomarkers Outpatient visit (n = 88) Pre-op (n = 88) P values Nutritional status ALB (g/L) 42.79 ± 4.09 46.04 ± 2.49 <0.001 Globulin (g/L) 28.29 ± 4.59 27.64 ± 3.81 0.158 Hb (g/L) 134.63 ± 12.59 136.34 ± 11.48 0.069 HCT (L/L) 0.41 ± 0.38 0.42 ± 0.32 0.585 Liver function Total bilirubin (μmol/L) 10.29 ± 3.98 10.57 ± 3.98 0.569 Direct bilirubin (μmol/L) 3.01 ± 1.49 2.91 ± 1.11 0.496 Indirect bilirubin (μmol/L) 7.24 ± 2.97 7.65 ± 3.14 0.273 Total bile acid (μmol/L) 4.17 ± 2.11 3.67 ± 2.77 0.157 ALT (IU/L) 27.55 ± 20.31 24.08 ± 13.76 0.107 AST (IU/L) 23.21 ± 5.95 22.61 ± 7.65 0.438 ALP (IU/L) 97.17 ± 29.17 93.26 ± 25.48 0.090 GGT (IU/L) 35.45 ± 30.92 33.68 ± 26.85 0.473 Kidney function Serum urea (μmol/L) 5.69 ± 1.72 5.94 ± 1.78 0.082 Serum creatinine (μmol/L) 66.66 ± 17.58 66.53 ± 16.37 0.876 eGFR (mL ·min–1 1.73 m–2) 88.22 ± 18.82 88.69 ± 17.04 0.493 Serum uric acid (μmol/L) 316.58 ± 103.51 310.40 ± 109.96 0.549 Lipid metabolism Triglyceride (mmol/L) 1.57 ± 0.60 1.47 ± 0.84 0.261 Cholesterin (mmol/L) 4.88 ± 0.90 5.01 ± 0.96 0.150 HDL-C (mmol/L) 1.35 ± 0.35 1.39 ± 0.34 0.103 LDL-C (mmol/L) 2.82 ± 0.69 2.92 ± 0.69 0.118 Other Creatine kinase (IU/L) 101.36 ± 63.63 91.56 ± 41.43 0.079 Lactic dehydrogenase (IU/L) 196.59 ± 26.02 192.02 ± 38.81 0.438 HBDH (IU/L) 155.17 ± 22.89 150.65 ± 32.98 0.329 Fasting blood glucose (mmol/L) 5.63 ± 1.26 5.46 ± 0.86 0.208 Data are presented as mean ± standard deviation.ALB: Albumin; ALP: Alkaline phosphatase; ALT: Alanine transferase; AST: Aspartate transferase; eGFR: Estimated glomerular filtration rate; GGT: Glutamyl transpeptidase; Hb: Hemoglobin; HCT: Hematocrit; HDL-C: High-density lipoprotein cholesterol; HBDH: Hydroxybutyrate dehydrogenase; LDL-C: Low-density lipoprotein cholesterol; Pre-op: Preoperative; TKA: Total knee arthroplasty. Serum ALB levels are associated with long-term mortality in the general population, especially for the elderly, and with post-operative course and mortality for patients with geriatric hip fracture.[4] In addition, although serum ALB < 35 g/L is usually considered as malnutrition or hypoproteinemia, our study revealed a negative dose-dependent relationship between pre-operative serum ALB levels and post-operative HAS use, consistent with a study showing that lower pre-operative ALB levels are associated with higher treatment costs.[2] In our patients, approximately 35 g of dietary protein (approximately 0.5 g/kg body weight) was added to the daily diet, which resulted in an increase of approximately 3.2 g in serum ALB from the day of outpatient visit to admission (an average of 39.05 ± 22.78 days). Several studies have previously evaluated the effects of a high-protein diet. High-protein diet (1.07–1.60 g/kg body weight/day) lasting for 6 to 12 months was an effective and safe way to reduce weight: high protein produced satiety and increased energy expenditure.[5] Our study showed that a high-protein diet had no significant impact on biomarkers of liver, kidney, or lipid metabolism. A high-protein diet lasting for approximately 34 months had no significant effect on the biomarkers of cardiometabolic health and vascular function in overweight participants.[6] Our study presents several limitations. First, we excluded patients with renal and hepatic diseases and therefore, the safety of a high-protein diet for those patients must be assessed further because of its potential effects on renal function. Second, although we educated patients in detail, some patients may have not strictly followed our suggestions during the pre-operative waiting period. In conclusion, lower pre-operative serum ALB levels were associated with an increased risk of post-operative HAS use with a negative dose-response relationship in TKA. A high-protein diet during the waiting period before surgery admission may be a useful way to improve ALB levels in these patients. Supplementary file, https://links.lww.com/CM9/B96 Acknowledgements The authors thank A. Chapin Rodríguez, PhD, from Creadu-cate Enterprises Ltd. for editing the English text of a draft of this manuscript. Funding This study was supported by a grant from the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (No. ZYJC18039). Conflicts of interest None.

Changes in serum albumin concentrations over 7 days in medical inpatients with and without nutritional support. A secondary post-hoc analysis of a randomized clinical trial

Abstract: Abstract Background Serum albumin concentrations are frequently used to monitor nutritional therapy in the hospital setting but supporting studies are largely lacking. Within this secondary analysis of a randomized nutritional trial (EFFORT), we assessed whether nutritional support affects short-term changes in serum albumin concentrations and whether an increase in albumin concentration has prognostic implications regarding clinical outcome and response to treatment. Methods We analyzed patients with available serum albumin concentrations at baseline and day 7 included in EFFORT, a Swiss-wide multicenter randomized clinical trial that compared individualized nutritional therapy with usual hospital food (control group). Results Albumin concentrations increased in 320 of 763 (41.9%) included patients (mean age 73.3 years (SD ± 12.9), 53.6% males) with no difference between patients receiving nutritional support and controls. Compared with patients with decrease in albumin concentrations, those with an increase had a lower 180-day mortality [74/320 (23.1%) vs . 158/443 (35.7%); adjusted odds ratio 0.63, 95% CI 0.44 to 0.90; p = 0.012] and a shorter length of hospital stay [11.2 ± 7.3 vs . 8.8 ± 5.6 days, adjusted difference − 2.2 days (95%CI -3.1 to -1.2)]. Patients with and without an increase in albumin concentrations from baseline to day 7 showed a similar response to nutritional support. Conclusion Results from this secondary analysis indicate that nutritional support did not increase short-term concentrations of albumin, and changes in albumin did not correlate with response to nutritional interventions. However, an increase in albumin concentrations was associated with better clinical outcomes. Repeated in-hospital albumin measurements in the short-term is, thus, not indicated for monitoring of patients receiving nutritional support but provides prognostic information. Trail Registration: ClinicalTrials.gov Identifier: NCT02517476

To study the correlation between serum albumin level and outcome in patients admitted with acute ischemic stroke

Abstract: Background Stroke is becoming an important cause of premature death and disability in low- income and middle-income countries like India, largely driven by demographic changes and enhanced by the increasing prevalence of the key modiable risk factors. Despite early initiation of treatment protocols, there may be long lasting debilitating sequel. Therefore, there has been a search for neuroprotective agents which might improve the prognosis of stroke. Methods Study was conducted at MGM Medical College and Hospital, Navi-Mumbai where in 75 patients admitted with acute ischemic stroke selected for the study. Proper consent was taken from the patients after checking the inclusion criteria. Their serum albumin levels were checked at the time of admission and discharge and Modied Rankin score was calculated to assess functional status. Results The mean serum albumin levels at the time of admission was 3.86 ± 0.49 g/dL and the mean serum albumin levels at discharge were 3.95 ± 0.47 g/dL. Approximately 73.32% of the cases had MRS score up to 3 had serum albumin levels of 4.0 to 4.49 g/dL and 27% had MRS score more than 3 had albumin level 3 – 3.99 g/dL. Conclusion It is concluded that low serum albumin levels are associated with poor functional outcomes as reected by an increase in MRS score. Thus, in general, low serum albumin levels are associated with worse functional outcomes.

High albumin clearance predicts the minimal change nephrotic syndrome relapse

Abstract: Background: Although albuminuria leakage that occurs in minimal change nephrotic syndrome (MCNS) may be related to the disease state, albumin kinetics in MCNS has never been evaluated. In this study, we investigated albumin kinetics in adult Japanese patients with MCNS by the estimated 24-h albumin clearance (eC ALB ) and examined the association between eC ALB and relapse. Methods: We retrospectively identified 103 adult patients with a histological diagnosis of MCNS from four hospitals in Japan (2010–2020). The primary outcome is the first relapse in 2 years after complete remission (CR) following corticosteroid therapy. The estimated 24-h albumin clearance (eC ALB ) [µL/min] was defined as (2.71828 log(0.0445 + 0.9488*log(urinary protein) [g/24h]/(serum albumin [g/dL] × 1440 [min/24 h]) for women and (2.71828 log(−0.1522 + 0.9742*log(urinary protein) [g/24h]/(serum albumin [g/dL] × 1440 [min/24 h]) for men. Results: Relapse was observed in 44 patients (103 kidney biopsy samples; 42.7%). The mean patient age was 41.0 years. Patients had an estimated glomerular filtration rate (eGFR) of 71.0 mL/min/1.73 m 2 , urinary protein excretion (UPE) of 6.8 g/day, serum albumin of 1.4 g/dL, and eC ALB of 2.27 μL/min. eC ALB was strongly associated with hypoalbuminemia, severe proteinuria, lipid abnormalities, and coagulopathy. In the multivariable analysis, a high eC ALB was significantly associated with relapse after adjusting for age, eGFR, time to CR, and UPE (adjusted hazard ratio = 5.027, 95% confidence interval 1.88–13.47, P = 0.001). Conclusions: This study revealed that eC ALB , which could substitute albumin kinetics, reflected the severity of MCNS, and a high eC ALB was associated with recurrence.

Binding characteristics of Bruton’s tyrosine kinase inhibitor ibrutinib with bovine serum albumin: multi-spectroscopic combined with molecular simulation

Abstract: Abstract Ibrutinib, as an oral Bruton’s tyrosine kinase inhibitor, has highly potent, covalent irreversible, and other characteristics. In this work, the binding characteristics of ibrutinib with bovine serum albumin were investigated using multi-spectroscopic techniques and molecular simulations. The findings demonstrated that ibrutinib could quench the endogenous fluorescence of bovine serum albumin by static quenching mode, meanwhile bovine serum albumin could also quench the fluorescence of ibrutinib. In the binding process of ibrutinib with bovine serum albumin, ibrutinib caused a bathochromic shift in the absorption band of bovine serum albumin, further indicating that ibrutinib and bovine serum albumin formed a ground state ibrutinib and bovine serum albumin complex. It is confirmed that ibrutinib has a strong affinity to bovine serum albumin due to the binding constant of more 104 M−1. Experimental findings showed that ibrutinib resulted in the decrease in the hydrophobicity or the enhancement in the polarity of the surroundings around Tyr and Trp residues of bovine serum albumin and diminishing in α-helix and β-sheet content of bovine serum albumin. The findings from site-competition experiments confirmed that the binding site of ibrutinib onto bovine serum albumin was the same as that of ibuprofen, that is, ibrutinib bound to the site II' site of bovine serum albumin, which was verified by molecular docking. The findings from thermodynamic analysis revealed that ibrutinib spontaneously bound onto bovine serum albumin through an enthalpy-driven and the driving forces included hydrogen bonding and van der Waals forces being the dominating forces. The findings from molecular dynamics simulation confirmed that some residues such as ARG-208, ALA-209, ALA-212, LEU-326, and LYS-350 made major contributions in ibrutinib and bovine serum albumin complexation.