Low Serum Albumin Concentration Research Articles

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

P612 Mirikizumab Pharmacokinetics and Exposure - Efficacy Relationships in Patients with Ulcerative Colitis

Abstract Background Mirikizumab (miri), a p19-directed IL-23 antibody, demonstrated efficacy in a Phase 2 trial in patients with moderately-to-severely active ulcerative colitis (UC)1 (NCT02589665). Analyses of the pharmacokinetics (PK) of miri and the relationships between exposure and efficacy at Week 12 are reported. Methods Patients were randomised to receive IV placebo, miri 50 mg or 200 mg with possibility of exposure-based dose increases, or miri 600 mg every 4 weeks, with efficacy assessment at Week 12. Serum concentrations of miri were analyzed using population PK methods. Population models were also used to evaluate the relationships between various clinical efficacy measures at Week 12 and miri exposure. The effects of patient factors on both PK and exposure-efficacy relationships were evaluated. Model-based and graphical methods were also used to understand the potential for confounded relationships between miri exposure and efficacy. Results A systemic clearance of 0.023 L/hr was estimated for miri, similar to estimates in healthy subjects and patients with psoriasis. Miri exposure increased in a linear manner. Patients with lower serum albumin concentration or lower body weight tended to have significantly higher clearance or lower volume of distribution, respectively (p&amp;lt;0.01); however, the magnitude of the impact was small and contributed less than 15% to random variability. The model-based exposure-response analyses generally showed that patient factors had a stronger impact on efficacy at Week 12 than miri exposure. Prior biologic experience and baseline rectal bleeding (RB) score had significant impacts (p&amp;lt;0.01) on the estimated placebo effect and maximal miri treatment effect (Emax), respectively. In the clinical response model, the estimated placebo response rate was 20 percentage points higher in biologic naïve vs experienced patients. The estimated response rate at a miri dose of 600mg was 28% higher in patients with a baseline RB≥2. Inclusion of these factors in the exposure-efficacy models caused the estimated EC50 to drop substantially, suggesting that the post-hoc exposure-efficacy relationships are likely confounded based on these patient factors. Graphical evaluations also suggested the presence of confounding factors. Conclusion Miri PK in UC patients was consistent with PK observed in healthy subjects and psoriasis patients. Evaluation of the relationships between miri exposure and efficacy in UC patients accounted for the potential impact of patient factors. Confounding patient factors may distort the true cause-effect relationship between exposure and efficacy and were carefully considered in support of optimal selection of doses for miri Phase 3 studies. Reference 1. Gastroenterology. 2020;158(3):537–549.

Low serum albumin concentration is associated with increased risk of osteoporosis in postmenopausal patients with rheumatoid arthritis

BackgroundThe risk of osteoporosis in patients with rheumatoid arthritis (RA) is frequently overlooked, and investigating a simple indicator in routine care may be beneficial to motivate osteoporosis examination. The aim of this retrospective, case-controlled study was to identify the correlation between serum albumin concentrations and the prevalence of osteoporosis in postmenopausal patients with RA. MethodsThis study enrolled 197 patients who underwent dual-energy X-ray absorptiometry of lumbar spine (LS) and proximal femur without osteoporosis treatment [mean age, 67.5 years; disease duration, 12.8 years; Disease Activity Score assessing 28 joints with C-reactive protein, 2.0; prednisolone dose, 4.9 mg/day (usage, 42.6%); and LS T-score, −1.9]. Patients were classified into 2 groups: osteoporosis, defined as ≥ 1 part bone mineral density T-score ≤ −2.5 or history of fragility fracture of the vertebra or proximal femur (121 patients), and non-osteoporosis (76 patients). Groups were then matched by propensity score using clinical backgrounds affecting bone metabolism. ResultsIn non-matched model, serum albumin concentration was significantly associated with osteoporosis-related factors such as aging, inflammation, physical disability, and glucocorticoid dose. Multivariate logistic regression revealed that serum albumin concentration was independently and significantly associated with osteoporosis risk (odds ratio = 0.22, 95% confidence interval = 0.08, 0.61, p = 0.0033). After propensity score matching, 57 patients for each group showed that in addition to the LS and femoral neck T-scores (p < 0.001), serum albumin concentrations (p = 0.01) remained lower in the osteoporosis group compared to non-osteoporosis group. Receiver operating characteristic curve analysis in non-matched model revealed that when cut-off value of serum albumin concentration for indicating osteoporosis was set at 4.2 g/dl, the area under the curve was 0.69, sensitivity 0.74, and specificity 0.58. ConclusionsLow serum albumin concentration was significantly and independently associated with the prevalence of osteoporosis, which may be considered as one of the osteoporosis-related factors in postmenopausal patients with RA.

Postoperative complications and waiting time for surgical intervention after radiologically guided drainage of intra-abdominal abscess in patients with Crohn's disease.

BackgroundIn patients with active Crohn’s disease (CD), treatment of intra-abdominal abscess usually comprises antibiotics and radiologically guided percutaneous drainage (PD) preceding surgery. The aim of this study was to investigate the risk of postoperative complications and identify the optimal time interval for surgical intervention after PD.MethodsA multicentre, international, retrospective cohort study was carried out. Details of patients with diagnosis of CD who underwent ultrasonography- or CT-guided PD were retrieved from hospital records using international classification of disease (ICD-10) diagnosis code for CD combined with procedure code for PD. Clinical variables were retrieved and the following outcomes were measured: 30-day postoperative overall complications, intra-abdominal septic complications, unplanned intraoperative adverse events, surgical-site infections, sepsis and pathological postoperative ileus, in addition to abscess recurrence. Patients were categorized into three groups according to the length of the interval from PD to surgery (1–14 days, 15–30 days and more than 30 days) for comparison of outcomes.ResultsThe cohort comprised 335 CD patients with PD followed by surgery. Median age was 33 (i.q.r. 24–44) years, 152 (45.4 per cent) were females, and median disease duration was 9 (i.q.r. 3.6–15) years. Overall, the 30-day postoperative complications rate was 32.2 per cent and the mortality rate was 1.5 per cent. After adjustment for co-variables, older age (odds ratio 1.03 (95 per cent c.i. 1.01 to 1.06), P < 0.012), residual abscess after PD (odds ratio 0.374 (95 per cent c.i. 0.19 to 0.74), P < 0.014), smoking (odds ratio 1.89 (95 per cent c.i. 1.01 to 3.53), P = 0.049) and low serum albumin concentration (odds ratio 0.921 (95 per cent c.i. 0.89 to 0.96), P < 0.001) were associated with higher rates of postoperative complications. A short waiting interval, less than 2 weeks after PD, was associated with a high incidence of abscess recurrence (odds ratio 0.59 (95 per cent c.i. 0.36 to 0.96), P = 0.042).ConclusionSmoking, low serum albumin concentration and older age were significantly associated with postoperative complications. An interval of at least 2 weeks after successful PD correlated with reduced risk of abscess recurrence.

A PROSPECTIVE ANALYSIS OF RISK FACTORS, PRESENTATION AND OUTCOME OF LEAKAGE AFTER GASTROINTESTINAL ANASTOMOSES

Background: Despite advancements in modern surgery and postoperative care, disruption of gastrointestinal anastomosis remains the most dreaded complication, even in experienced surgical hands. The cause of leakage is multifactorial consisting of a complete spectrum of pre, intra and postoperative factors. Search for an ideal gastrointestinal anastomosis still remains an unquenched thirst. Study Design: Prospective, hospital based, time bound observational study. Methods: After ethical clearance, 288 consenting adult patients who underwent gastrointestinal anastomosis were observed for risk factors, presentation and outcome of leakage and evaluated using appropriate statistical tools. Results: An overall gastrointestinal anastomotic leak rate of 15.28% with peak incidence at 41-50 years (19.51%) was seen. Peritonitis (p=0.0009, OR=2.9611), COPD (p=0.0181, OR=2.7306), low serum albumin concentration (p=0.0028, OR=3.1442), ASA status of ≥III (p=0.0001, OR=4.0281) and a perioperative blood transfusion requirement of ≥2 units (p=0.0028, OR=3.1442) were the most signicant risk factors associated with leakage. Obstruction (p=0.0160, OR=2.2310), malignancy (p=0.0149, OR=2.6961), steroid therapy (p=0.0176, OR=2.2741), chemoradiation (p=0.0400, OR=2.4889), diabetes (p=0.0427, OR=2.2689), undernutrition (p= 0.0308, OR= 2.1099), anaemia (p=0.0325, OR=2.0183) and sepsis (p=0.0187, OR=2.2702) also showed clear risk augmentation. Risk of leakage was increased with a surgical duration of &gt;4 hours (p=0.0078, OR=2.5610), when anastomosis was done as an emergency procedure (p=0.0427, OR=2.6571) or by a surgeon with expertise of ≤5 years (p=0.0338, OR=2.7733). Neither the level, type, technique of anastomosis; nor the usage of surgical staplers had an impact on leakage. Preoperative bowel preparation and creation of a proximal stoma also had minimal effect on leakage rates; though, the infectious complications that follow were greatly reduced. The most common presentation of anastomotic leak was a suspicious drain output with a mean time of 7.59± 2(2.48) postoperative days; resulting in a prolongation of hospitalization by more than ten days (p&lt;0.0001), along with an increased mortality rate (p&lt;0.0001). Conclusions: Accurately predicting anastomotic leakage still requires more evidence-based information. Even with good risk stratication, many causative factors may not be amenable to immediate correction in the pre-operative period. In such cases, the patient must be considered as a candidate for an enterostomy to help tide the crisis over.

Pharmacokinetic-Pharmacodynamic Model of Vedolizumab for Targeting Endoscopic Remission in Patients With Crohn Disease: Posthoc Analysis of the LOVE-CD Study.

BackgroundHigher serum concentrations of vedolizumab have been associated with improved outcomes in inflammatory bowel disease. It is unclear how vedolizumab exposure is linked to endoscopic remission in Crohn disease (CD). We aimed to develop a pharmacokinetic-pharmacodynamic model linking vedolizumab exposure to endoscopic remission in CD.MethodsData were obtained from the first 110 patients participating in a phase 4 prospective multicenter trial (LOVE-CD; ClinicalTrials.gov identifier: NCT02646683), where vedolizumab was dosed at 300 mg every 8 weeks and serum concentrations and antibodies to vedolizumab were measured before each infusion. Concentration-time profiles were described by a 2-compartment model with parallel linear and nonlinear elimination. A first-order discrete-time Markov model was used to describe the relationship between pharmacokinetic exposure metrics and the probability of endoscopic remission (Simple Endoscopic Score for CD < 4).ResultsLinear clearance was 0.215 L/d, and the volume of distribution of the central compartment was 4.92 L. Linear clearance was higher and vedolizumab exposure was lower in patients with lower serum albumin concentrations, in the presence of antibodies to vedolizumab, and in patients with previous exposure to other biologic therapy. A week 22 vedolizumab concentration of 20.0 mg/L was predicted to yield a 35% probability of achieving endoscopic remission at week 26. Model-based simulations suggested that endoscopic remission rates of 46.5% or 40.0% could be reached with every-4-weeks dosing in patients who were naïve or previously exposed to biologic therapy, respectively.ConclusionsModel-informed dosing of vedolizumab in CD provides a foundation for future research aiming to maximize endoscopic remission rates.

SV-VATS exhibits dual intraoperative and postoperative advantages

BackgroundThe merits of spontaneous ventilation video-assisted thoracic surgery (SV-VATS) are still controversial. Our team retrospectively evaluated the intraoperative and postoperative advantages of this surgical approach, comparing with mechanical ventilation video-assisted thoracic surgery (MV-VATS).MethodsWe did a single center retrospective study at the First Affiliated Hospital of Yunnan Province. 244 patients were eventually assigned to the SV-group and MV-group, and their intraoperative indicators and thoracic surgery postoperative data were included in the comparison.ResultsThe SV-group exhibited markedly less intraoperative bleeding and postoperative thoracic drainage, and the bleeding volume was correlated with the volume and duration of drainage. Further analysis showed that, patients undergoing SV-VATS had less activation of white blood cells and neutrophils after surgery, but they also had lower serum albumin concentrations. Risks of short-term postoperative complications, including inflammatory reactions, malignant arrhythmias, constipation, and moderate or more pleural effusions, were also significantly reduced in the SV-group. Additionally, hospitalization cost was lower in the SV-group than that in the MV-group.ConclusionsSV-VATS is suitable for various types of thoracic surgery, and effectively reduce intraoperative bleeding and postoperative thoracic drainage. With less postoperative inflammatory response, it reduces the risk of short-term postoperative complications. It is also able to help to reduce the financial burden of patients.