BACKGROUND: Patients with sepsis with low albumin levels and high red blood cell distribution width levels have poor prognoses. Red blood cell distribution width to albumin ratio (RAR) has recently attracted attention as an innovative inflammation biomarker. We aimed to explore the association between RAR and the prognosis of patients with sepsis.
METHODS: This retrospective observational study included 402 patients meeting the sepsis-3 standards admitted to Yantai Yuhuangding Hospital\'s intensive care units (ICUs) between January 2020 and December 2022. The relationship between RAR and mortality in patients with sepsis was examined using regression analysis, Kaplan-Meier analyses, and a receiver operating characteristic curve. Subgroup and sensitivity analyses were conducted to assess the results\' robustness.
RESULTS: RAR, when considered as a continuous variable, was a significant independent in-hospital mortality risk factor (adjusted odds ratio [OR]: 1.383; 95% confidence interval [CI]: 1.164-1.645; P < 0.001). When considering RAR as a categorical variable, the ORs (95% CIs) of hospital mortality for quartile 2 (Q2), Q3, and Q4 compared with Q1 were 1.027 (0.413-2.551), 3.632 (1.579-8.354), and 4.175 (1.625-10.729), respectively, P < 0.001. Similar outcomes were observed for 28- and 90-day mortalities.
CONCLUSIONS: RAR may indicate clinical prognosis for patients with sepsis in the ICU, potentially providing a low-cost, easily repeatable, and accessible biomarker for risk categorization for these patients.

Red blood cells (RBCs) are vital for transporting oxygen from the lungs to the body\'s tissues through the intricate circulatory system. They achieve this by binding and releasing oxygen molecules to the abundant hemoglobin within their cytosol. The volume of RBCs affects the amount of oxygen they can carry, yet whether this volume is optimal for transporting oxygen through the circulatory system remains an open question. This study explores, through high-fidelity numerical simulations, the impact of RBC volume on advective oxygen transport efficiency through arterioles, which form the area of greatest flow resistance in the circulatory system. The results show that, strikingly, RBCs with volumes similar to those found in vivo are most efficient to transport oxygen through arterioles. The flow resistance is related to the cell-free layer thickness, which is influenced by the shape and the motion of the RBCs: at low volumes, RBCs deform and fold, while at high volumes, RBCs collide and follow more diffuse trajectories. In contrast, RBCs with a healthy volume maximize the cell-free layer thickness, resulting in a more efficient advective transport of oxygen.

Duplicate measure of hemoglobin mass by carbon monoxide (CO)-rebreathing is a logistical challenge as recommendations prompt several hours between measures to minimize CO-accumulation. This study investigated the feasibility and reliability of performing duplicate CO-rebreathing procedures immediately following one another. Additionally, it was evaluated whether the obtained hemoglobin mass from three different CO-rebreathing devices is comparable. Fifty-five healthy participants (22 males, 23 females) performed 222 duplicate CO-rebreathing procedures in total. Additionally, in a randomized cross-over design 10 participants completed three experimental trials, each including three CO-rebreathing procedures, with the first and second separated by 24 h and the second and third separated by 5-10 min. Each trial was separated by >48 h and conducted using either a glass-spirometer, a semi-automated electromechanical device, or a standard three-way plastic valve designed for pulmonary measurements. Hemoglobin mass was 3 ± 22 g lower (p < 0.05) at the second measure when performed immediately after the first with a typical error of 1.1%. Carboxyhemoglobin levels reached 10.9 ± 1.3%. In the randomized trial, hemoglobin mass was similar between the glass-spirometer and three-way valve, but ∼6% (∼50 g) higher for the semi-automated device. Notably, differences in hemoglobin mass were up to ∼13% (∼100 g) when device-specific recommendations for correction of CO loss to myoglobin and exhalation was followed. In conclusion, it is feasible and reliable to perform two immediate CO-rebreathing procedures. Hemoglobin mass is comparable between the glass-spirometer and the three-way plastic valve, but higher for the semi-automated device. The differences are amplified if the device-specific recommendations of CO-loss corrections are followed.

The f-cell ratio of 0.91 is a conversion factor between the hematocrit measured in peripheral blood and the hematocrit obtained by separate measurements of the red blood cell mass and plasma volume. The physiological background of the f-cell ratio is unclear.
Data were retrieved from 155 intravenous infusion experiments where 15-25 mL/kg of crystalloid fluid diluted the blood hemoglobin and plasma albumin concentrations. The hemodilution was converted to plasma dilution using the peripheral hematocrit, and the volume of distribution of exogenous albumin was calculated in 41 volunteers who received 20 % or 5 % albumin by intravenous infusion. Finally, the kinetics of plasma albumin was studied during 98 infusion experiments with 20 % albumin.
Plasma dilution based on hemoglobin and albumin showed a median difference of -0.001 and a mean difference of 0.000 (N = 2184), which demonstrates that these biomarkers indicate the same expandable vascular space. In contrast, exogenous albumin occupied a volume that was 10 % larger than the plasma volume indicated by the anthropometric equations of Nadler et al. and Retzlaff et al. The kinetic analysis identified a secondary compartment that was 450 mL in size and rapidly exchanged albumin with the circulating plasma.
The results suggest that the f-cell ratio is due to rapid exchange of albumin between the plasma and a non-expandable compartment located outside the circulating blood (possibly the liver sinusoids). This means that the hematocrit measured in peripheral blood correctly represents the ratio between the red cell volume and the circulating plasma volume.

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We wanted to determine the influence of total blood volume (BV) and blood lactate quantity on lactate concentrations during incremental exercise. Twenty-six healthy, nonsmoking, heterogeneously trained females (27.5 ± 5.9 ys) performed an incremental cardiopulmonary exercise test on a cycle ergometer during which maximum oxygen uptake (V·O2max), lactate concentrations ([La-]) and hemoglobin concentrations ([Hb]) were determined. Hemoglobin mass and blood volume (BV) were determined using an optimised carbon monoxide-rebreathing method. V·O2max and maximum power (Pmax) ranged between 32 and 62 mL·min-1·kg-1 and 2.3 and 5.5 W·kg-1, respectively. BV ranged between 81 and 121 mL·kg-1 of lean body mass and decreased by 280 ± 115 mL (5.7%, p = 0.001) until Pmax. At Pmax, the [La-] was significantly correlated to the systemic lactate quantity (La-, r = 0.84, p < 0.0001) but also significantly negatively correlated to the BV (r = -0.44, p < 0.05). We calculated that the exercise-induced BV shifts significantly reduced the lactate transport capacity by 10.8% (p < 0.0001). Our results demonstrate that both the total BV and La- have a major influence on the resulting [La-] during dynamic exercise. Moreover, the blood La- transport capacity might be significantly reduced by the shift in plasma volume. We conclude, that the total BV might be another relevant factor in the interpretation of [La-] during a cardio-pulmonary exercise test.

An indispensable precondition for the determination of hemoglobin mass (Hbmass) and blood volume by CO rebreathing is complete mixing of CO in the blood. The aim of this study was to demonstrate the kinetics of CO in capillary and venous blood in different body positions and during moderate exercise. Six young subjects (4 male, 2 female) performed three 2-min CO rebreathing tests in seated (SEA) & supine (SUP) positions as well as during moderate exercise (EX) on a bicycle ergometer. Before, during, and until 15 min after CO rebreathing cubital venous and capillary blood samples were collected simultaneously and COHb% was determined. COHb% kinetics were significantly slower in SEA than in SUP or EX. Identical COHb% in capillary and venous blood were reached in SEA after 5.0 ± 2.3 min, in SUP after 3.2 ± 1.3 min and in EX after 1.9 ± 1.2 min (EX vs. SEA p < .01, SUP vs. SEA p < .05). After 7th min, Hbmass did not differ between the resting positions (capillary: SEA 766 ± 217 g, SUP 761 ± 227 g; venous: SEA 759 ± 224 g, SUP 744 ± 207 g). Under exercise, however, a higher Hbmass (p < .05) was determined (capillary: 823 ± 221 g, venous: 804 ± 226 g). In blood, the CO mixing time in the supine position is significantly shorter than in the seated position. By the 6th minute complete mixing is achieved in either position giving similar Hbmass determinations. CO-rebreathing under exercise conditions, however, leads to ∼7% higher Hbmass values.

Reduced red cell mass is a poor prognostic indicator in chronic kidney disease (CKD) patients. Whilst overt anaemia impacts on the quality of life of patients with CKD, lowered red cell mass may also compromise oxygen delivery to proximal tubular cells and contribute to progressive kidney injury. Epidemiological data from cats with CKD support this hypothesis although controlled interventional studies involving drugs that raise red cell mass in trials designed to test this hypothesis are lacking in both human and veterinary medicine. Recombinant analogues of erythropoietin (EPO) are currently standard of care for human CKD patients where low red cell mass impacts on their quality of life. Resistance to EPO is encountered in 20% to 40% of patients treated, probably due to functional iron deficiency, reflecting the difficulties of managing iron deficiency associated with the chronic inflammation of CKD. Similar issues are likely faced in managing anaemia in feline CKD although published data on the use of human EPO analogues are limited as such treatment in cats risks antibody formation resulting in red cell aplasia and transfusion dependency and so is reserved for late stage cases only. This article reviews the recent alternative therapeutic approach to increase red cell mass using HIF-prolyl hydroxylase inhibitors and explains their mode of action and theoretical advantages over EPO analogues in the context of iron metabolism. The results of human clinical trials and the potential benefit of adopting this approach in feline CKD patients are discussed.

Functional effectiveness of erythrocytes depends on their high deformability that allows them to pass through narrow tissue capillaries. The erythrocytes can deform easily due to discoid shape provided by the stabilization of an optimal cell volume at a given cell surface area. We used mathematical simulation to study the role of transport Na/K-ATPase and transmembrane Na+ and K+ gradients in human erythrocyte volume stabilization at non-selective increase in cell membrane permeability to cations. The model included Na/K-ATPase activated by intracellular Na+, Na+ and K+ transmembrane gradients, and took into account contribution of glycolytic metabolites and adenine nucleotides to cytoplasm osmotic pressure. We found that this model provides the best stabilization of the erythrocyte volume at non-selective increase in the permeability of the cell membrane, which can be caused by an oxidation of the membrane components or mechanical stress during circulation. The volume of the erythrocyte deviates from the optimal value by no more than 10% with a change in the non-selective permeability of the cell membrane to cations from 50 to 200% of the normal value. If only one transmembrane ion gradient is present (Na+), the cell loses the ability to stabilize volume and even small changes in membrane permeability cause dramatic changes in the cell volume. Our results reveal that the presence of two oppositely directed transmembrane ion gradients is fundamentally important for robust stabilization of cellular volume in human erythrocytes.