Low Serum Albumin Concentration Research Articles

The Significance of Albumin Concentration and some of its Altered Forms in Iraqi Patients with Chronic Hepatitis B Virus

Background: The liver synthesizes albumin, a pivotal protein with approximately 60-65% of total plasma proteins. During ischemic attacks linked to oxidative stress, reactive oxygen species, and acidosis, the properties of albumin undergo alterations. This leads to generation of ischemia-modified albumin, which is characterized by a diminished metal-binding capacity, particularly for transition metals like copper, nickel, and cobalt. Objectives: This study aimed to assess the significance of serum albumin and ischemia-modified albumin concentrations in Iraqi individuals with hepatitis B virus Methods: A case control study consisted of 50 patients with hepatitis B were recruited from Gastroenterology hospital in the Medical city/ Baghdad/ Iraq, during the period January to February in 2023, The patients group included males and females; whose ages ranged from 18 years to 77 years with a mean value 44 year. Meanwhile the study group consisted of 50 age- and sex-matched normal healthy individuals. Albumin concentration was determined in the serum samples, using a Biosystems kit, and ischemia modified albumin concentration were measured through the albumin cobalt binding test. The ischemia modified albumin/ [albumin] ratio and Ischemia modified albumin index were then calculated. Statistical Analysis: results were reported as a mean value ± standard deviation. The differences were considered highly significant if (p < (0.001), and significant where (p = (0.002) and (p = (0.033) Results: lower serum albumin concentration was measured in the patients group, while the mean value of ischemia modified albumin concentration in the patients' group and healthy control were 0.466 ± 0.114 absorbance unit & 0.395 ± 0.070 absorbance unit, respectively, with a statistically significant increase (P < 0.001). The ischemia modified albumin ratio in the hepatitis B patients and control groups were 0.172 ± 0.073 and 0.117 ± 0.050, respectively, showing a significant increase as well (P < 0.001). Additionally, the ischemia modified albumin index in the patients and the control groups were 0.491 ± 0.167 & 0.390 ± 0.131, respectively, with a statically significant increase (p<0.001) in the patients group. Conclusion: In the patients’ group with hepatitis B, serum albumin concentration is decreased, while the level of ischemia modified albumin, ischemia modified albumin ratio, and ischemia modified albumin index are increased. The elevation in ischemia modified albumin, ischemia modified albumin ratio, and ischemia modified albumin index were more prominent in younger patients and those with albumin concentration less than 4g/dl. Moreover, the prevalence of hepatitis B is higher in men compared to women.

Functional and prognostic impacts of serum albumin with thoracic arterial calcification among asymptomatic individuals

Although several studies have demonstrated the cardiovascular (CV) implication of hypoalbuminemia and arterial calcification among hemodialysis patients, little is known regarding their cardiac correlates and relevant CV outcomes in asymptomatic individuals. We assessed the potential CV interrelation between serum albumin (SA) and aortic calcification. Among 2,723 asymptomatic individuals underwent cardiovascular health check-up, we assessed serum albumin (SA) level, thoracic aortic calcification (TAC) and coronary artery calcification (CAC) by multi-detector computed tomography, and ultrasound-determined carotid plaque burden. We related these measures to cardiac structure/function and CV outcomes. Lower SA level was associated with higher TAC score and volume rather than carotid plaque or coronary calcification burden in fully adjusted models. By categorizing the study population into 4 groups by SA (>, ≤ 4.6 mg/dL) and presence of TAC, subjects classified into low SA/TAC(+) category were oldest with highest prevalent CV disease. Both lower SA and TAC(+) were independently associated with impaired myocardial systolic/diastolic mechanics and higher CV events during a median of 6.6 years (IQR: 5.1, 6.8 years) follow-up. Participants classified into low SA/TAC(+) category showed highest risk for CV events (adjusted HR: 3.78 [95% CI: 2.11, 6.77], high SA/TAC[-] as reference) in fully adjusted Cox model. Among symptom-free individuals, TAC was closely associated with low SA concentration in relation to unfavorable cardiac mechanics and may serve as a useful prognosticator for adverse CV events.

Duodenal and colonic mucosal S100A8/A9 (calprotectin) expression is increased and correlates with the severity of select histologic lesions in dogs with chronic inflammatory enteropathy

BackgroundCalprotectin, a damage-associated molecular pattern protein of the S100/calgranulin family, is a potential marker of gastrointestinal inflammation in dogs and mainly originates from activated macrophages and granulocytes. Increased calprotectin concentrations are reported in feces and serum samples from dogs with chronic inflammatory enteropathy (CIE), but mucosal calprotectin expression has not been extensively investigated in canine CIE. Thus, we aimed to evaluate gastrointestinal mucosal concentrations of calprotectin in 62 dogs (44 dogs with CIE compared to 18 healthy Beagles) using a particle-enhanced turbidimetric immunoassay method. Additionally, we assessed the relationship of gastric, duodenal, jejunal, ileal, and colonic mucosal calprotectin levels with the clinical disease severity (canine clinical inflammatory bowel disease activity index, CIBDAI), histopathologic findings, clinical outcome, and serum albumin concentrations to further evaluate the potential of calprotectin as a biomarker for CIE.ResultsMucosal calprotectin concentrations in dogs with CIE were significantly higher in the duodenum (median: 276.2 μg/g) and colon (median: 298.2 μg/g) compared to healthy controls (median: 94.3 μg/g, P = 0.0039; and median: 112.0 μg/g, P = 0.0061). Similar numerical differences in the ileum and cecum were not statistically significant, and mucosal calprotectin concentrations correlated significantly among the different gastrointestinal segments. Histologic lesion severity was linked to mucosal calprotectin concentrations for inflammatory and structural histology criteria in the duodenum and colon (all P < 0.05). Higher mucosal calprotectin levels in the duodenum and across all segments correlated with lower serum albumin concentrations (both P < 0.05); duodenal mucosal calprotectin concentrations were more than sixfold higher in hypoalbuminemic dogs (median: 1441 µg/g, n = 4) than normoalbuminemic dogs (median: 227 µg/g, n = 40). There was no significant association of mucosal calprotectin levels with CIBDAI scores or individual clinical outcomes.ConclusionsThese results show that duodenal and colonic mucosal calprotectin concentrations are increased in dogs with CIE, providing further supporting evidence for the diagnostic potential of fecal calprotectin (presumably reflecting mucosal) concentrations and in dogs with CIE. Further longitudinal research is needed to assess changes in mucosal calprotectin concentrations with clinical response to treatment vs. mucosal disease remission and to determine the clinical utility of fecal calprotectin concentrations to diagnose and monitor dogs with CIE in clinical practice.

Long-term prognostic effect of serum albumin concentration in diabetic patients with stable coronary artery disease: A multicenter cohort study.

Diabetes and insulin resistance alter the physiological state of serum albumin (SA), which is a prognostic marker for stable coronary artery disease (CAD). However, whether the SA concentration is associated with long-term cardiovascular (CV) outcomes in diabetic patients with stable CAD remains unclear. In total, 1148 patients were retrospectively identified from a nationwide multicenter cohort study on patients with stable CAD. They were categorized into four groups according to their diabetes mellitus (DM) status and SA concentration (cutoff: 4 g/dL). The patients' mean age was 62.5 years, and 83.5% were male. Of the total patients, 405 were included in group 1 (SA ≥ 4/non-DM), 322 in group 2 (SA < 4/non-DM), 201 in group 3 (SA ≥ 4/ DM), and 220 in group 4 (SA < 4/DM). Group 4 had the oldest age and a higher prevalence of prior myocardial infarction and stroke. During the median 4.5-year follow up (interquartile range: 1.5-6.7 year), the highest and lowest survival rates in terms of all-cause and CV mortality were found in groups 1 and 4, respectively. However, no prognostic differences were noted in nonfatal stroke and myocardial infarction among the groups. The data were consistent after covariate adjustment. Using group 1 as the reference, HRs (95% CIs) for all-cause mortality in groups 2, 3, and 4 were 3.64 (1.22-10.83), 3.26 (0.95-11.33), and 5.74 (1.92-16.95), respectively, and those for CV mortality were 2.8 (0.57-13.67), 2.62 (0.40-17.28), and 6.15 (1.32-28.58), respectively. In diabetic patients with stable CAD, a low SA concentration (<4 g/dL) was associated with increased long-term mortality regardless of all-cause or CV reasons but not nonfatal CV events.

Exploration of the factors affecting different delirium subtypes in hospitalized COVID-19 patients: a multicentre cross-sectional study

During the COVID-19 pandemic, delirium became a major complication that worsened patient outcomes. However, the factors influencing the severity of delirium in patients with COVID-19 have not been determined. We conducted this study to detect influencing factors associated with subtypes of delirium in patients with COVID-19. We included 1774 adult inpatients with COVID-19 from January to February 2023 at 7 sites in China. And used the 3 min Confusion Assessment Method and the Richmond Agitation-Sedation Scale for site assessment to identify and classify subtypes of delirium. Laboratory data were obtained from the Hospital Information System. After multivariate analysis, hypoactive delirium was significantly associated with age, the serum albumin concentration, frailty and sarcopenia, and health and nutritional status. Mixed delirium was significantly associated with age, D-dimer level, sarcopenia, health status and nutritional status. Additionally, hyperactive delirium was significantly associated with age, procalcitonin levels, frailty status and health status. Our findings suggest that poor nutritional status and low serum albumin concentration can help detect patients at high risk of developing hypoactive and mixed delirium. Additionally, clinical staff should pay more attention to patients with inflammatory conditions to assess and detect delirium because many influencing factors are involved in the common pathological mechanism of inflammation.

Dysregulated serum concentrations of fat-soluble vitamins in dogs with chronic enteropathy.

In inflammatory bowel disease (IBD) of humans, nutrient malabsorption can result in fat-soluble vitamin deficiency, especially of vitamin D. In veterinary species, decreased concentrations of vitamin D are relatively common in dogs with chronic enteropathy (CE), but data on the status of other fat-soluble vitamins (FSVs) is lacking. Determine the serum concentrations of retinol, vitamin D, and α-tocopherol in dogs with CE compared with healthy dogs and compare clinical, clinicopathologic variables between CE and healthy dogs to detect associations with decreased FSVs concentrations. Eighteen client-owned dogs with CE and 33 healthy dogs. Serum 25-hydroxyvitamin D (25[OH]D), serum retinol and α-tocopherol concentrations were compared between groups. Correlations and multiple regression modeling were used to examine the relationship between serum 25(OH)D, retinol, and α-tocopherol concentrations and clinical and clinicopathological variables. Dogs with low serum albumin concentrations were more likely to have lower 25(OH)D concentrations than dogs with normal serum albumin concentration. Dogs with CE had higher serum concentrations of retinol, and variable α-tocopherol concentrations. The cause of these dysregulated vitamin concentrations is unclear and requires further study. Dogs with severe forms of CE should be monitored for decreased concentrations of 25(OH)D. Additional studies are needed to evaluate the clinical relevance and the possible benefit of vitamin D supplementation in these patients.

Significant Association of Serum Albumin With the Severity of Coronary Microvascular Dysfunction Using Dynamic CZT-SPECT.

Both low serum albumin (SA) concentration and coronary microvascular dysfunction (CMD) are risk factors for the development of heart failure (HF). We hypothesized that SA concentration is associated with myocardial flow reserve (MFR) and implicated in pathophysiological mechanism of HF. We retrospectively studied 454 patients undergoing dynamic cardiac cadmium-zinc-telluride myocardial perfusion imaging from April 2018 to February 2020. The population was categorized into three groups according to SA level (g/dL): Group 1: >4, Group 2: 3.5-4, and Group 3: <3.5. Myocardial blood flow (MBF) and myocardial flow reserve (MFR, defined as stress/rest MBF ratio) were compared. The mean age of the whole cohort was 66.2 years, and 65.2% were men. As SA decreased, stress MBF (mL min-1 g-1) and MFR decreased (MBF: 3.29 ± 1.03, MFR: 3.46 ± 1.33 in Group 1, MBF: 2.95 ± 1.13, MFR: 2.51 ± 0.93 in Group 2, and MBF: 2.64 ± 1.16, MFR: 1.90 ± 0.50 in Group 3), whereas rest MBF (mL min-1 g-1) increased (MBF: 1.05 ± 0.42 in Group 1, 1.27 ± 0.56 in Group 2, and 1.41 ± 0.61 in Group 3). After adjusting for covariates, compared with Group 1, the odds ratios for impaired MFR (defined as MFR < 2.5) were 3.57 (95% CI: 2.32-5.48) for Group 2 and 34.9 (95% CI: 13.23-92.14) for Group 3. The results would be similar if only regional MFR were assessed. The risk prediction for CMD using SA was acceptable, with an AUC of 0.76. Low SA concentration was associated with the severity of CMD in both global and regional MFR as well as MBF.

Venous Thromboembolism in Peritoneal Mesothelioma: Uncovering the Hidden Risk.

Venous thromboembolism (VTE) is a common complication in patients with abdominal malignancies. Despite known associations between pleural mesothelioma and increased VTE risk, the characteristics of VTE in patients with peritoneal mesothelioma (PeM) remain undescribed. Patients treated for PeM were retrospectively identified from our institutional database. The frequency of VTE was assessed and logistic regression modeling was employed to assess VTE risk factors. The association between VTE and overall survival was also ascertained. Recommended thromboprophylaxis for patients who underwent surgery at our institution comprised a single preoperative dose of prophylactic anticoagulation, followed by daily dosing for fourweeks postoperatively. Among 120 PeM patients, 26 (21.7%) experienced VTE, including 19/91 (20.9%) surgical patients, 4/23 (17.4%) patients who received systemic therapy, and 3/6 (50%) patients who underwent observation (p=0.21). Most events were symptomatic (n=16, 62%) and were attributable to pulmonary emboli (n=16, 62%). The 90-day postoperative VTE rate was 4.4% (4/91), including 1 of 60 patients who underwent index surgical intervention at our institution and 3 patients with surgery elsewhere. A low serum albumin concentration was associated with VTE in non-surgical patients (odds ratio 0.12, confidence interval [CI] 0.02-0.72; p=0.03). No significant difference in overall survival was observed between patients with and without VTE (median 46.0 months [CI 24.9-67.0] vs. 55.0 months [CI 27.5-82.5]; hazard ratio 0.98 [CI 0.54-1.81], p=0.98). A high risk of VTE was observed in PeM patients, warranting suspicion throughout the disease trajectory. Postoperative VTE rates were within acceptable limits with 4-week thromboprophylaxis.

Uremic xerosis among patients on maintenance hemodialysis: Prevalence and correlation with clinical and laboratory markers

Xerosis, characterized by dry skin, is a frequent manifestation in patients undergoing maintenance hemodialysis. Understanding the prevalence of xerosis in this population and exploring its associations with various clinical and laboratory parameters is crucial for comprehensive patient care. The present study aimed to estimate the prevalence of xerosis in patients undergoing maintenance hemodialysis and to investigate the association between xerosis and various clinical and laboratory parameters, with a specific focus on serum copeptin as a surrogate for antidiuretic hormone.&#x0D; Methods. This cross-sectional observational study was conducted at the Hemodialysis Clinic of the Basrah Nephrology and Transplantation Center from March 1, 2022, to September 1, 2022. The prevalence of xerosis and its correlation with clinical characteristics and serum copeptin status were analyzed.&#x0D; Results. The study findings indicate that among the 48 patients undergoing maintenance hemodialysis, with an average age of 59.8 ± 8.8 years, 60.4% presented with xerosis. Serum copeptin levels, measuring 3.8 ± 2 ng/mL, showed a significant association with diuretic usage and serum parathyroid hormone (PTH) (p &lt; 0.001 and p = 0.031, respectively). Notably, no correlations were observed with other demographic or laboratory parameters, despite the tendency of serum copeptin levels to be higher in females and patients with low serum albumin and PTH concentrations.&#x0D; Conclusions. In summary, xerosis was prevalent in 60.4% of patients undergoing maintenance hemodialysis and demonstrated a positive correlation with diuretic use and serum PTH levels.

Role of Albumin as a Targeted Drug Carrier in the Management of Rheumatoid Arthritis: A Comprehensive Review.

An endogenous transporter protein called albumin interacts with the Fc receptor to provide it with multiple substrate-binding domains, cell membrane receptor activation, and an extended circulating half-life. Albumin has the remarkable ability to bind with receptors viz. secreted protein acidic and rich in cysteine (SPARC) and scavenger protein-A (SR-A) that are overexpressed during rheumatoid arthritis (RA), enabling active targeting of the disease site instead of requiring specialized substrates to be added to the nanocarrier. RA, a chronic autoimmune illness, is characterized by the presence of a severe inflammatory response. RA patients have low serum albumin concentration, which signifies the high uptake of albumin at the inflammatory sites, giving a rationale to use albumin as a drug carrier for RA therapy. Albumin has the capacity for both passive and active targeting. It is an abundantly available protein in the bloodstream showing excellent cellular compatibility, degradability in biological tissues, nonantigenicity, and safety. There are three strategies of albumin mediated drug delivery as encapsulating therapeutics in albumin nanoparticles, chemically conjugating drugs with functional proteins, and albumin itself which is used as a targeting ligand to deliver drugs specifically to cells or tissues that express albumin-binding receptors. In the current review, an attempt has been made to highlight the significant evidence of albumin as a drug delivery carrier for the safe and effective management of RA. Evidence has been provided in the form of recent research advances, clinical trials, and patents. Additionally, this review will outline the prospective for the potential utilization of albumin as a drug vehicle for RA and suggest possible future avenues to provide the perspective for subsequent studies.

#4914 LOW LEAN BODY TISSUE IS AN INDEPENDENT RISK FACTOR FOR KIDNEY DISEASE PROGRESSION AND MORTALITY IN PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE

Abstract Background and Aims Lean tissue mass is a marker of good health and is associated with a lower risk of death in patients without chronic kidney disease (CKD). A potentially underestimated risk factor for impaired renal function is low serum albumin concentration. Previous studies have shown that even small decreases in serum albumin concentration levels are strongly associated with cardiovascular disease, heart failure, impaired kidney function, and mortality in vulnerable populations. An association between low lean body tissue with mortality in patients with stage 4 and 5 CKD has recently been demonstrated. The aim of this study was to evaluate the effect of lean body tissue index (LTI) measured by multifrequency bioelectrical impedance analysis (BIA) on kidney disease progression and mortality in a cohort of patients with stage 4 and 5 CKD. Method We performed a retrospective observational cohort study that included patients with stage 4 and 5 CKD who were referred to the Advanced Chronic Kidney Disease outpatient clinic at our centre between January 2014 and December 2020, in whom a baseline measurement of body composition by using BIA was performed in the first 6 months of follow-up. Baseline clinical and laboratory parameters (serum creatinine, glomerular filtration rate, serum albumin, hemoglobin, cholesterol, triglycerides, calcium, phosphorus, PTH and CRP) were defined as those observed at the time of BIA measurement. Low lean tissue was defined as having LTI values below the 10th centile adjusted by age and sex. Renal survival was defined as the absence of need of renal replacement therapy (RRT) at the end of follow-up. Results The study included 145 patients who had a mean age of 72 ± 11.8 years, 69.7% were males, with a mean GFR measured by CKD-EPI of 20.4 ± 4.7 ml/min, mean albumin of 4.1 ± 0.3 g/dl and median urine albumin-creatinine ratio (uACR)of 413 mg/g (IQR 98-1341). The mean body mass index of the population was 30.1 ± 6.1 kg/m2, and BIA showed a mean LTI of 15.4 ± 3.9 kg/m2 and fat tissue index (FTI) of 14.1 ± 6.8 kg/m2. Nineteen patients (13.1%) had low LTI. Patients with low LTI were younger (65.9 ± 12.8 vs 73 ± 11.4 years, p = 0.013) and had higher uACR (1444 [484-1815] vs 318 [68-1188] mg/g, p = 0.002) with no differences in sex, GFR, and other laboratory parameters. After a mean follow-up of 27.7 months (IQR 15.3-45.4), 72 (49.7%) showed CKD progression to RRT and 55 patients (37.9%) died. The Kaplan-Meier survival analysis showed that patients with low LTI had a worse renal survival (log-rank 5.5, p = 0.019) and overall survival (log-rank 7.6, p = 0.006). The multivariate Cox regression analysis showed that low LTI (HR 2.28, 95% CI 1.12-4.62), lower GFR (HR 0.86, 95% CI 0.81-0.92) and higher uACR (HR 1.001, CI 95% 1-1.001) were independent risk factors for CKD progression to ESKD, while low LTI (HR 3.16, 95% CI 1.42-7.05), age (HR 1.09, CI 95% 1.05-1.13) and serum albumin (HR 0.31, CI 95% 0.13-0.77) were the factors that were independently associated with mortality. Conclusion Low lean body tissue index measured by multifrequency bioelectrical impedance analysis is and independent risk factor for CKD progression and mortality in stage 4-5 CKD. Close monitoring of nutritional status by BIA should be followed in these patients to provide timely and adequate nutritional interventions that might help in improving patient outcomes.

Pretreatment Vitamin D Concentrations Do Not Predict Therapeutic Outcome to Anti-TNF Therapies in Biologic-Naïve Patients With Active Luminal Crohn's Disease.

Vitamin D has a regulatory role in innate and adaptive immune processes. Previous studies have reported that low pretreatment vitamin D concentrations are associated with primary non-response (PNR) and non-remission to anti-TNF therapy. This study aimed to assess whether pretreatment 25-hydroxyvitamin D concentrations predicted PNR and non-remission to infliximab and adalimumab in patients with active luminal Crohn's disease. 25-Hydroxyvitamin D concentrations were measured in stored baseline samples from 659 infliximab- and 448 adalimumab-treated patients in the Personalised Anti-TNF Therapy in Crohn's disease (PANTS) study. Cut-offs for vitamin D were deficiency <25 nmol/L, insufficiency 25-50 nmol/L, and adequacy/sufficiency >50 nmol/L. About 17.1% (189/1107; 95% CI, 15.0-19.4) and 47.7% (528/1107; 95% CI, 44.8-50.6) of patients had vitamin D deficiency and insufficiency, respectively. 22.2% (246/1107) of patients were receiving vitamin D supplementation. Multivariable analysis confirmed that sampling during non-summer months, South Asian ethnicity, lower serum albumin concentrations, and non-treatment with vitamin D supplementation were independently associated with lower vitamin D concentrations. Pretreatment vitamin D status did not predict response or remission to anti-TNF therapy at week 14 (infliximab Ppnr = .89, adalimumab Ppnr = .18) or non-remission at week 54 (infliximab P = .13, adalimumab P = .58). Vitamin D deficiency was, however, associated with a longer time to immunogenicity in patients treated with infliximab, but not adalimumab. Vitamin D deficiency is common in patients with active Crohn's disease. Unlike previous studies, pretreatment vitamin D concentration did not predict PNR to anti-TNF treatment at week 14 or nonremission at week 54.

P662 Pre-treatment vitamin D concentrations do not predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease

Abstract Background Vitamin D has a regulatory role in innate and adaptive immune processes. Previous small studies have reported that low pre-treatment vitamin D concentrations are associated with primary non-response and shorter drug persistence to anti-TNF therapy. We sought to assess whether pre-treatment 25-hydroxyvitamin D concentrations predicted primary non-response and non-remission to infliximab and adalimumab in patients with Crohn’s disease recruited to the PANTS (Personalised Anti-TNF Therapy in Crohn’s disease) study. Methods We used composite endpoints using the Harvey Bradshaw Index (HBI) in adults and the short paediatric Crohn’s disease activity index (sPCDAI) in children, corticosteroid use, and C-reactive protein (CRP) to define primary non-response (Figure 1). Remission was defined as CRP of ≤3 mg/L and HBI of ≤4 points (short paediatric Crohn’s disease activity index ≤15 in children), without corticosteroid therapy or exit for treatment failure. 25-hydroxyvitamin D concentrations were measured in stored baseline serum samples and cut-offs for vitamin D status were: deficiency &amp;lt; 25nmol/L, insufficiency 25-50nmol/L and adequacy/sufficiency &amp;gt; 50nmol/L. Results Samples from 659/898 infliximab (526 Remicade; 133 biosimilar CT-P13) and 448/605 adalimumab (448 Humira) treated patients included in the effectiveness analysis of the PANTS study were included. Overall, 17.1% (189/1107; 95% confidence interval [CI] 15.0 - 19.4%) and 47.7% (528/1107; 95% CI 44.8 - 50.6%) patients had vitamin D deficiency and insufficiency, respectively. At baseline, 22.2% (246/1107) patients were receiving some form of vitamin D supplementation. Multivariable linear regression analysis confirmed that baseline sampling during non-summer months (Figure 2), South Asian ethnicity, lower serum albumin concentrations, higher HBI and nontreatment with vitamin D supplements were independently associated with lower vitamin D concentrations (Figure 3). Primary non-response at week 14 and non-remission at week 54 occurred in 19.3% (116/600; 95% CI 16.4 - 22.7%) and 58.8% (351/597; 95% CI 54.8- 62.7%) patients treated with infliximab and 25.3% (100/396; 95% CI 21.2- 29.8%) and 65.3% (246/377; 95% CI 60.3- 69.9%) of patients treated with adalimumab, respectively. Pre-treatment vitamin D status did not predict response or remission status to anti-TNF therapy at week 14 (infliximab Ppnr = 0.87, adalimumab Ppnr = 0.18) or non-remission at week 54 (infliximab P = 0.12, adalimumab P = 0.59) (Figure 4). Conclusion Vitamin D deficiency is common in patients with active Crohn’s disease. Unlike previous studies, pre-treatment serum 25-hydroxyvitamin D concentration did not predict primary non-response to anti-TNF treatment at week 14 or non-remission at week 54.

ASSOCIATIONS OF THE SERUM ALBUMIN CONCENTRATION AND SEQUENTIAL ORGAN FAILURE ASSESSMENT SCORE AT DISCHARGE WITH 1-YEAR MORTALITY IN SEPSIS SURVIVORS: A RETROSPECTIVE COHORT STUDY.

Introduction: This study was performed to investigate the predictors of 1-year mortality at discharge in sepsis survivors. Methods: This study was a retrospective analysis of patients with sepsis and septic shock at a single center. Patients who survived hospitalization for sepsis or septic shock between January 2016 and December 2017 were included in this study. Age, sex, body mass index, laboratory results such as blood cell count, C-reactive protein (CRP) and albumin levels, the Sequential Organ Failure Assessment (SOFA) score at the time of discharge and site of infection were compared between the survivors and nonsurvivors at 1 year postdischarge. Multivariate logistic regression was performed to identify the predictors of 1-year mortality. Results: During the study period, 725 sepsis patients were included in the analysis, 64 (8.8%) of whom died within the first year. The nonsurvivors were older and had a lower body mass index and a higher SOFA score at discharge than the survivors ( P < 0.05). Among the laboratory results at discharge, hemoglobin, platelet counts, and albumin concentrations were lower in the nonsurvivors than in the survivors, whereas CRP was higher in the nonsurvivors than in the survivors. In the multivariate logistic regression analysis, serum albumin <2.5 mg/dL and SOFA score ≥2 at discharge were identified as independent prognostic factors for 1-year mortality (odds ratio, 2.616; 95% confidence interval, 1.437-4.751 for albumin <2.5 mg/dL and 2.106, 1.199-3.801 for SOFA score ≥2, respectively). Conclusions: A low serum albumin concentration of <2.5 mg/dL and a high SOFA score of ≥2 at the time of discharge were prognostic factors for 1-year mortality in survivors of sepsis.

Prognostic Impact of Lymphocyte-to-C-Reactive Protein Ratio in Patients Who Underwent Surgical Resection for Pancreatic Cancer.

Increasing evidence indicates that increased systemic inflammation is correlated with poorer cancer-specific survival in various cancer types. This study aimed to evaluate the prognostic value of various combinations of inflammatory factors in patients who underwent surgical resection for pancreatic cancer (PC). We retrospectively analyzed 97 consecutive patients with PC who underwent pancreatectomy. We assessed the predictive impact for recurrence using a combination of 5 inflammatory markers and focused on the lymphocyte-C-reactive protein ratio (LCR) to elucidate its prognostic and predictive value for recurrence-free survival (RFS) and overall survival (OS) in univariate and multivariate analyses using the Cox proportional hazards model. Low preoperative LCR was correlated with low serum hemoglobin, low serum albumin concentration, high frequency of microscopic vascular invasion, and high frequency of microscopic perineural invasion. The low LCR group had significantly worse RFS and OS. Lower preoperative LCR was an independent predictor of shorter RFS and OS in this cohort. Preoperative LCR is a novel and convenient prognostic marker for patients with PC. Patients with low LCR may require more favorable intensive therapy.

Predictors of early remission of proteinuria in adult patients with minimal change disease: a retrospective cohort study

Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein < 0.3 g/day (or g/gCr) was observed in 104 (96.3%) patients. Of 97 patients with remission within 6 month of IST, 42 (43.3%) developed relapse defined as ≥ 1.0 g/day (or g/gCr) or dipstick urinary protein of ≥ 2+. Serum albumin concentration was significantly associated with remission (multivariable-adjusted hazard ratio [95% confidence interval] per 1.0 g/dL, 0.57 [0.37, 0.87]), along with eGFR (per 30 mL/min/1.73 m2: 1.43 [1.08, 1.90]), whereas they were not associated with relapse. A multivariable-adjusted model showed that patients with high eGFR level (≥ 60 mL/min/1.73 m2) and low albumin concentration (≤ 1.5 g/dL) achieved significantly early remission, whereas those with low eGFR (< 60 mL/min/1.73 m2) and high albumin concentration (> 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.

Resistance to Erythropoiesis-Stimulating Agents among Patients on Hemodialysis Is Typically Transient

Introduction: This study examines factors associated with erythropoiesis-stimulating agent (ESA) hyporesponsiveness, the duration of ESA hyporesponsiveness, the frequency of new episodes, and variation across countries. Methods: We used international Dialysis Outcomes and Practice Patterns Study data from 2015 to 2018 (N = 26,656) to investigate changes in ESA Resistance Index (ERI), calculated as epoetin dose divided by [hemoglobin × body weight] in patients on hemodialysis. We illustrated the proportion of patients who moved to other ERI quintiles over 12 months, and we studied the incidence and duration of ESA resistance. We examined case-mix factors associated with quintiles of ERI. Results: Most patients migrated out of their original ERI quintile within 4 months. Only 22% of patients in the top quintile of ERI at baseline (4.4% of all patients) remained in the top quintile during all 12 months of follow-up. A total of 42% of patients manifested an upper-quintile ERI during at least 1 month. Median duration of a new episode of ESA resistance was 2 months. Catheter hemoaccess, elevated C-reactive protein, lower transferrin saturation, lower serum albumin concentration, and recent hospitalization occurred more frequently among patients in the highest ERI quintile at baseline. ERI values were highest in the USA, Italy, and Mideastern nations and lowest in Russia and Japan. Discussion/Conclusion: It is a misconception to envision a sizable, fixed segment of the population with permanent resistance to ESA – resistance fluctuates frequently. The implications of these findings for prescription of ESAs and of hypoxia-inducible factor-prolyl hydroxylase inhibitors are discussed.

Human serum albumin in neurodegeneration.

Serum albumin (SA) exists in relatively high concentrations, in close contact with most cells. However, in the adult brain, except for cerebrospinal fluid (CSF), SA concentration is relatively low. It is mainly produced in the liver to serve as the main protein of the blood plasma. In the plasma, it functions as a carrier, chaperon, antioxidant, source of amino acids, osmoregulator, etc. As a carrier, it facilitates the stable presence and transport of the hydrophobic and hydrophilic molecules, including free fatty acids, steroid hormones, medicines, and metal ions. As a chaperon, SA binds to and protects other proteins. As an antioxidant, thanks to a free sulfhydryl group (-SH), albumin is responsible for most antioxidant properties of plasma. These functions qualify SA as a major player in, and a mirror of, overall health status, aging, and neurodegeneration. The low concentration of SA is associated with cognitive deterioration in the elderly and negative prognosis in multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). SA has been shown to be structurally modified in neurological conditions such as Alzheimer's disease (AD). During blood-brain barrier damage albumin enters the brain tissue and could trigger epilepsy and neurodegeneration. SA is able to bind to the precursor agent of the AD, amyloid-beta (Aβ), preventing its toxic effects in the periphery, and is being tested for treating this disease. SA therapy may also be effective in brain rejuvenation. In the current review, we will bring forward the prominent properties and roles of SA in neurodegeneration.

Clinicopathological Characteristics and Outcomes of PLA2R-Associated Membranous Nephropathy in Seropositive Patients Without PLA2R Staining on Kidney Biopsy

Phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) with circulating serum autoantibodies to PLA2R (SAb+) but no deposits of PLA2R antigen in glomerular tissue by immunofluorescence (GAg-) has been reported. However, little is known about the clinicopathological characteristics or prognosis of this subtype of MN. Retrospective cohort study. 130 SAb+ patients in China with biopsy-proven MN who had follow-up data and received immunosuppressive therapy. The median follow-up was 16 (IQR, 9-25) months. PLA2R antigen detection by immunofluorescence staining of kidney biopsy specimens. Complete remission (CR) was defined as proteinuria levels<0.3 g/d and a >50% decreasecompared with a previously established baseline. Partial remission (PR) was defined as proteinuria levels<3.5 g/d and a >50% decrease compared with a previously established baseline. The kidney function outcome was defined as a >40% decrease in estimated glomerular filtration rate (eGFR) at the end of the study compared with baseline. Kaplan-Meier analysis of PR and CR comparing SAb+/GAg+ and SAb+/GAg- patients. Cox proportional hazards models to examine these associations were adjusted for confounders. Among 130 SAb+ patients with PLA2R-associated MN, 18 were GAg-. Compared with SAb+/GAg+ patients, those who were SAb+/GAg- presented with more severe kidney injury as evidenced by higher SAb titer, greater proteinuria, lower serum albumin concentrations, lower eGFR (all P< 0.05), and more severe disease with higher chronicity scores (P< 0.001) on kidney biopsies. SAb+/GAg- patients exhibited a significantly lower probability of PR (P< 0.001) and CR (P= 0.03) and were more likely to experience a >40% decrease in eGFR (P= 0.008) than patients who were SAb+/GAg+. After adjusting for clinical and pathologic variables available at the time of biopsy, compared with SAb+/GAg+ patients, SAb+/GAg- patients had a lower rate of experiencing remission (hazard ratio, 0.32 [95% CI, 0.15-0.68]; P= 0.003) and a higher rate of the >40% eGFR decrease outcome (hazard ratio, 7.66 [95% CI, 1.54-38.08]; P= 0.01). Retrospective study, small sample size, and lack of a uniform approach to treatment. Seropositive PLA2R-associated MN without PLA2R staining on kidney biopsy may represent a distinct clinical subtype with more severe disease and a worse prognosis. GAg- is independently associated with poor response to treatment and >40% eGFR decrease in seropositive PLA2R-associated MN.

Admission serum albumin concentrations and response to nutritional therapy in hospitalised patients at malnutrition risk: Secondary analysis of a randomised clinical trial.

SummaryBackgroundHistorically, admission serum albumin concentrations have been considered useful biochemical markers for nutrition assessment. However, there is a lack of randomised trial data investigating whether low albumin concentrations are helpful for identifying patients benefitting from nutritional support.MethodsThis study was a secondary analysis of the EFFORT trial, a Swiss-wide multicentre, randomised controlled trial comparing individualised nutritional support with usual care nutrition in medical inpatients from April 1, 2014, to February 1, 2018. 1389 of 2028 patients at nutritional risk with available albumin concentrations on admission were included. The primary endpoint was all-cause mortality within 30 and 180 days. Patients were stratified into groups of low or normal albumin based on the albumin cut-off of 30 g/L. ClinicalTrials.gov number, NCT02517476.Findings1389 patients (mean age, 73.1 (SD 3.5) years; 747 (53.8%) men) were included and 676 (48.7%) had low serum albumin concentrations at admission (<30 g/L). Mortality at 180 days was significantly increased in the low albumin group compared with patients with normal albumin concentrations (219/676 (32.4%) vs. 162/713 (22.7%), fully adjusted HR 1.4, 95%CI 1.11 to 1.77, p = 0.005]. Effects of nutritional support on 30-day mortality were similar for patients with low compared to patients with normal albumin concentrations (HR 0.68, 95%CI 0.44 to 1.05 vs. HR 0.70, 95%CI 0.41 to 1.20), with no evidence for a subgroup effect (p for interaction=0.97).InterpretationBased on this secondary analysis of a randomised trial, low admission serum albumin concentrations in hospitalised, non-critically ill, medical patients at nutritional risk had prognostic implications and indicated higher mortality risk but were not helpful in selecting patients for nutritional interventions.FundingThe Swiss National Science Foundation (SNSF) (PP00P3_150531) and the Research Council of the Kantonsspital Aarau (1410.000.058 and 1410.000.044) provided funding for the EFFORT trial