Colloid Osmotic Pressure Research Articles

Synthesis and Physicochemical Properties of Poly(2‐Alkyl‐2‐Oxazoline)‐Conjugated Hemoglobins as an Artificial O2 Carrier: Comparison with Polyethylene Glycol Conjugates

AbstractPolyethylene glycol (PEG) is a biocompatible polymer extensively employed to prolong blood circulation and mitigate the immunogenicity of the protein therapeutics. Nonetheless, there are reports of anti‐PEG antibody production. Poly(2‐alkyl‐2‐oxazoline) (PROx) exhibits analogous immunological stealth properties and represents a potential substitute for PEG. This study details the synthesis of PROx‐conjugated hemoglobins (PROxm‐Hbs, R = Me, Et) as artificial O2 carriers, functioning as red blood cell (RBC) substitutes, and evaluates their O2 affinities and solution properties. The average number of polymers bound is designed to be 6 or 11. The O2 affinities (P50) of PMeOxm‐Hbs and PEtOxm‐Hbs are ascertained as 9 Torr, comparable to those of PEG‐conjugated Hbs (PEGm‐Hbs). The PEtOx6‐HbT, synthesized under an N2 atmosphere, exhibited a low O2 affinity (P50 = 57 Torr). Through the admixture of PEtOx6‐Hb and PEtOx6‐HbT, the P50 value of the formulation to range from 9 to 57 Tor can be tailored as desired. The colloid osmotic pressures and viscosities of PMeOxm‐Hb and PEtOxm‐Hb solutions are lower than those of the corresponding PEGm‐Hb solutions. Furthermore, the PROx conjugates evinced no cytotoxicity against normal cells. PMeOxm‐Hbs and PEtOxm‐Hbs, characterized by their appropriate O2 affinities and solution properties, present themselves as promising alternative materials to RBCs.

Low-Volume Ex Situ Lung Perfusion System for Single Lung Application in a Small Animal Model Enables Optimal Compliance With "Reduction" in 3R Principles of Animal Research.

Ex situ lung perfusion (ESLP) is used for organ reconditioning, repair, and re-evaluation prior to transplantation. Since valid preclinical animal models are required for translationally relevant studies, we developed a 17mL low-volume ESLP for double- and single-lung application that enables cost-effective optimal compliance "reduction" of the 3R principles of animal research. In single-lung mode, ten Fischer344 and Lewis rat lungs were subjected to ESLP and static cold storage using STEEN or PerfadexPlus. Key perfusion parameters, thermal lung imaging, blood gas analysis (BGA), colloid oncotic pressure (COP), lung weight gain, histological work-up, and cytokine analysis were performed. Significant differences between perfusion solutions but not between the rat strains were detected. Most relevant perfusion parameters confirmed valid ESLP with homogeneous lung perfusion, evidenced by uniform lung surface temperature. BGA showed temperature-dependent metabolic activities with differences depending on perfusion solution composition. COP is not decisive for pulmonary oedema and associated weight gain, but possibly rather observed chemokine profile and dextran sensitivity of rats. Histological examination confirmed intact lung architecture without infarcts or hemorrhages due to optimal organ procurement and single-lung application protocol using our in-house-designed ESLP system.

Is there reversible dimerization of albumin in blood plasma? And does it matter?

Most albumin in blood plasma is thought to be monomeric with some 5% covalently dimerized. However, many reports in the recent biophysics literature find that albumin is reversibly dimerized or even oligomerized. We review data on this from X-ray crystallography and diverse biophysical techniques. The number-average molecular weight of albumin would be increased by dimerization, affecting size-dependent filtration processes of albumin such as at the glycocalyx of the capillary endothelium and the podocyte slit-diaphragm of the renal glomerulus. If correct, and depending on characteristics of the process, such as Kd, reversible dimerization of albumin in plasma would have major implications for normal physiology and medicine. We present quantitative models of the impact of dimerization on albumin molecular forms, on the number-average molecular weight of albumin, and estimate the effect on the colloid osmotic pressure of albumin. Dimerization reduces colloid osmotic pressure as total albumin concentration increases below that expected in the absence of dimerization. Current models of albumin filtration by the renal glomerulus would need revision to account for the dynamic size of albumin molecules filtered. More robust biophysical data are needed to give a definitive answer to the questions posed and we suggest possible approaches to this.

Fundamental equations and hypotheses governing glomerular hemodynamics.

The glomerular filtration rate (GFR) is the outcome of glomerular hemodynamics, influenced by a series of parameters: renal plasma flow, resistances of afferent arterioles and efferent arterioles (EAs), hydrostatic pressures in the glomerular capillary and Bowman's capsule, and plasma colloid osmotic pressure in the glomerular capillary. Although mathematical models have been proposed to predict the GFR at both the single-nephron level and the two-kidney system level using these parameters, mathematical equations governing glomerular filtration have not been well-established because of two major problems. First, the two-kidney system-level models are simply extended from the equations at the single-nephron level, which is inappropriate in epistemology and methodology. Second, the role of EAs in maintaining the normal GFR is underappreciated. In this article, these two problems are concretely elaborated, which collectively shows the need for a shift in epistemology toward a more holistic and evolving way of thinking, as reflected in the concept of the complex adaptive system (CAS). Then, we illustrate eight fundamental mathematical equations and four hypotheses governing glomerular hemodynamics at both the single-nephron and two-kidney levels as the theoretical foundation of glomerular hemodynamics. This illustration takes two steps. The first step is to modify the existing equations in the literature and establish a new equation within the conventional paradigm of epistemology. The second step is to formulate four hypotheses through logical reasoning from the perspective of the CAS (beyond the conventional paradigm). Finally, we apply the new equation and hypotheses to comprehensively analyze glomerular hemodynamics under different conditions and predict the GFR. By doing so, some concrete issues are eliminated. Unresolved issues are discussed from the perspective of the CAS and a desinger's view. In summary, this article advances the theoretical study of glomerular dynamics by 1) clarifying the necessity of shifting to the CAS paradigm; 2) adding new knowledge/insights into the significant role of EAs in maintaining the normal GFR; 3) bridging the significant gap between research findings and physiology education; and 4) establishing a new and advanced foundation for physiology education.

Tangential flow filtration facilitated fractionation of polymerized human serum albumin: Insights into the effects of molecular size on biophysical properties.

Human serum albumin (HSA) is currently used as a plasma expander (PE) to increase blood volume during hypovolemic conditions, such as blood loss. However, its effectiveness is suboptimal in septic shock and burn patients due to their enhanced endothelial permeability, resulting in HSA extravasation into the tissue space leading to edema, and deposition of toxic HSA-bound metabolites. Hence, to expand HSA's applicability toward treating patients with compromised endothelial permeability, HSA has been previously polymerized to increase its molecular size thus compartmentalizing the polymerized HSA (PolyHSA) molecules in the vascular space. Previous studies bracketed PolyHSA between 100 kDa and 0.2 μm. In this research, PolyHSA was synthesized at two cross-link densities 43:1 and 60:1 (i.e., molar ratios of glutaraldehyde to HSA) and subsequently fractionated via tangential flow filtration (TFF) into two narrower brackets: bracket A (500 kDa and 0.2 μm) and bracket B (50-500 kDa). PolyHSA within the same size bracket at different cross-link densities exhibited similar solution viscosity, zeta potential, and osmolality but differed in hydrodynamic diameter. At the same cross-link density, the PolyHSA A bracket showed higher viscosity, lowered zeta potential, and a larger hydrodynamic diameter compared with the PolyHSA B bracket while maintaining osmolality. Interestingly, PolyHSA 43:1 B, PolyHSA 60:1 A, and PolyHSA 60:1 B brackets exhibited colloid osmotic pressure similar to HSA, indicating their potential to serve as PEs.

Pathophysiology and pregnancy outcomes of ascites in preeclampsia-a scoping review.

Preeclampsia is a multisystem disorder associated with defective trophoblast invasion, maternal syndrome, and capillary endothelial leak. The presence of ascites/third space fluid accumulation increases the risk of maternal morbidity and mortality. The current criteria/guidelines of preeclampsia do not establish the presence of ascites as a marker of severity or recognize the timing and need for early delivery despite associated complications. Medline and Embase databases were searched to identify relevant literature, reported up to December 2023, regarding the pathophysiology, pregnancy outcome, and management of preeclampsia complicated with ascites. A total of 5 studies on pathophysiology and eight on pregnancy outcomes met the inclusion criteria, with 41 case reports on ascites in preeclampsia. The etiopathogenesis for the development of ascites in preeclampsia includes endothelial damage, capillary hyperpermeability, release of vasoconstrictive agents, reduced intravascular oncotic pressure, and raised intraabdominal pressure. The presence of ascites represents the extreme form of microvascular damage, which also correlates with the raised sFlt-1 levels in this condition. The adverse pregnancy outcomes include increased risk of congestive heart failure, eclampsia, renal failure, disseminated intravascular coagulation, acute respiratory distress syndrome, and maternal death. The presence of ascites in preeclampsia is associated with the deterioration of the maternal condition. Hence, it is indicative of preeclampsia with severe features and requires vigilant monitoring, and prompt delivery may be considered.

Nephrotic syndrome and adrenoleukodystrophy in a 5-year-old boy.

Nephrotic syndrome is a common condition characterized by filtration of large amounts of protein, hypoalbuminemia, reduced plasma oncotic pressure, sodium retention, and edema. The mechanism responsible for sodium retention in this condition is still controversial. Two different pathophysiological pathways have been proposed to explain edema formation: activation of neurohumoral effector mechanisms, including the renin-angiotensin-aldosterone system, or abnormal intrinsic/primary renal sodium retention. A 5-year-old boy with X-linked adrenoleukodystrophy presented with bilateral leg swelling, massive proteinuria, and hypoalbuminemia. Minimal change disease was diagnosed. The patient was initially treated with corticosteroids and experienced several relapses. The progression of fractional excretion of sodium correlated with proteinuria and undetectable aldosterone levels. This unusual finding suggests that the mechanism of tubular sodium avidity in this child with mineralocorticoid insufficiency was independent of the renin-angiotensin-aldosterone system.

The Relationship Between Hyperalbuminemia and Unscheduled Medical Visits: A Retrospective Cohort Study.

Introduction Hyperalbuminemia, defined as elevated serum albumin levels, may influence healthcare utilization, particularly unscheduled medical visits. The sympathetic nervous system (SNS) regulates serum albumin, which is crucial for maintaining oncotic pressure and substance transport. SNS instability, linked to chronic diseases, can impact albumin levels. This study investigates the association between hyperalbuminemia and unscheduled medical visits in community hospital outpatient departments, aiming to establish its potential as a predictor of healthcare utilization. Methods This retrospective cohort study utilized electronic medical records from Unnan City Hospital, Japan, from September 2021 to August 2023. Participants were over 15 years old and had albumin data available, excluding those with acute albumin conditions. The case group consisted of 321 hyperalbuminemia patients (serum albumin ≥ 5 g/dL), matched monthly with 16 controls. Data on demographics, chronic diseases, and unscheduled medical visits were collected. Multivariate logistic regression analyzed the association between hyperalbuminemia and unscheduled medical visits. Results Among 716 participants, the hyperalbuminemia group (mean age 59.13 years) was younger than the non-hyperalbuminemia group (mean age 74.36 years). Hyperalbuminemia patients had a higher BMI, pulse rate, and prevalence of diabetes, dyslipidemia, and brain stroke. Significant associations were found between hyperalbuminemia and unscheduled medical visits (OR 2.35, 95% CI 1.56-3.53, p < 0.001), age, BMI, pulse rate, and brain stroke. Conclusion Hyperalbuminemia is significantly associated with increased unscheduled medical visits in rural outpatient settings. Routine serum albumin assessments can aid in risk stratification and personalized care, potentially reducing acute healthcare needs. Future research should explore underlying mechanisms and broader populations to enhance clinical applications.

The new formula for cell supply in tissues with the help of blood circulation is a fact. Let's talk about the consequences of this

For more than a century, circulatory physiologists have been working on their field by cultivating their own knowledge and creating a framework of their own principles. Separatism in science, however, has a bad prognosis because the laws of nature are the same in all disciplines. After the misguided development in this period, there is an urgent need to reorganise the Theory of Microcirculation. I. LAW AND ORDER IN THE THEORY OF MIKROZIRKULATION: It is important to know that in fluid mechanics one cannot simply write equations as one pleases. There is „law and order“ in science, especially in this sense that the laws of nature and the peculiarities of fluid mechanics must be observed in the theory of microcirculation in tissue also. When one writes an equation, that equation belongs only to a specific tissue model and, conversely, to a specific tissue model belongs 100% to a single equation specific to that model. In this context, the Starling equation only applies to interstitials with infinite compliance. II. METHOD: A porous tube like the blood capillary must be calculated correctly by approximating the capillary length slice by slice by "finite elements" to an equivalent circuit diagram. III. RESULTS: The results are surprising because a) In the closed interstitium the porous capillary automatically finds an equilibrium for different values of blood pressure (PCA-PCV) over the whole capillary b) The pressure at the capillary beginning PCA, the pressure at the capillary end PCV, the capillary conductance Kfμ and the colloid osmotic pressure difference Δπ=COP give a new relationship for the local flow through the capillary wall Jvμ: Jvμ=Mfμ(PCA -PCV)+Σ njμ.Δπjμ. (j=1 to N) (1) In this equation, the interstitial hydraulic pressure Pi=IFP is missing because it is derived from the pressure PCA and Pi is not an active parameter. However, Pi is reduced by the amount COP=Δπ. In the state of equilibrium the second summand results to zero, so that the local current Jvμ through the capillary wall is independent of the COP=Δπ: Jvμ=Mfμ(PCA-PCV), (2) Piμ=Nfμ(PCA-PCV)-Δπ. (3) IV. CONCLUSIONS: The colloid osmotic pressure of the blood COP does not appear in the tissues as an opponent of the blood pressure, rather the COP supports the supply of the cells. In the lungs, COP enables respiration; in the whole body, the COP effect against the development of oedema is of extraordinary importance. Since the early days of circulatory physiology 125 years ago, circulatory physiologists have believed that this function of COP is possible because, according to Starling's equation, COP as an opponent of blood pressure Pc would reduce filtration into the interstitium. However, COP also enables these effects as an opponent of interstitial fluid pressure (IFP). To understand this, it is first important to understand the situation with IFP. The IFP is a passive parameter and arises from the summative effect of the blood pressure Pc and the COP=(πc-πi), see equation (3). According to the definition Pressure= Force / Area, (4) there is no independent force in the interstitium that could cause spontaneous IFP. In the previous theory of microcirculation, the wrong tissue approximation was used, the wrong equation was calculated, and there was an irrational idea of how interstitial fluid pressure (IFP) arises and how it must be measured. They also used the wrong method to determine CFC. How could one arrive at a correct result in this case? The damage that the Starling teaching has done in 125 years cannot be overlooked. No Fundings. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Glomerular Hemodynamics During Recovery from Renal Ischemia-Reperfusion Injury Addressed with Micropuncture in Rats

Objective: To establish the physical basis for low GFR in ischemic renal injury (IR) and determine whether abnormalities in GFR determinants persist after renal recovery. Method: IR was generated in male and female Wistar Froemter rats by clamping both renal pedicles for 60 minutes. Controls had same surgery without pedicle clamp. Glomerular hemodynamics were assessed by renal micropuncture (MP) after 1 day, 1 week, or 4 weeks. Single nephron GFR (SNGFR) was paired with tubular stop-flow (PSF) and free-flow pressure (PFF) in each nephron. Afferent Starling pressure (EFPa) is PSF-PFF. Glomerular capillary pressure (PGC) was computed from PSF, PFF and plasma oncotic pressure. ANOVA factors included IR, sex, time point and date of experiment (nested). Inter-nephron heterogeneity was extracted from normalized root-square difference between each data point and the mean for that animal. (total n=349 nephrons, 47 rats). Results: [Formula: see text] Summary and conclusion: The physical cause of low GFR in IR was low EFPa, which resulted from low PGC with normal PFF in all animals except 1. The injured kidney manifest elevated inter-nephron variability for all variables. Mean values for SNGFR and intra-renal pressures returned to normal in the “recovered” kidney, but variability between nephrons did not return to normal. Female rats had lower baseline SNGFR and PGC than males but the hemodynamic patterns during IR and renal recovery were not differentiable by sex (excluding one female outlier with high PFF). Despite “normal” GFR and PGC, the “recovered” kidney is not a “normal” kidney. NIH NIDDK R01 132690. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

13 Thromboelastographic Coagulation Assessment in Burn Patients Receiving Plasma Inclusive Resuscitation

Abstract Introduction As resuscitative strategies in burn patients are re-evaluated, a consensus has not been reached on the role for colloids, as lactated ringers remain the fluid of choice with variable use of colloids. Colloids, such as fresh frozen plasma (FFP), may be effective at maintaining oncotic pressure, resupplying coagulation factors, mitigating coagulopathy, and treating the endothelium. This work aims to characterize the coagulation profile of burn patients treated with plasma inclusive resuscitation (PIR) using rapid thromboelastography (rTEG) by comparing it to burn patients primarily resuscitated with crystalloids alone. Methods Patients admitted to a regional burn center who had greater than 20% total body surface area (TBSA) burns that received PIR were included in the study. Patients admitted with burn injuries and resuscitated primarily with lactated ringers were included in the comparison group. Demographic data and blood samples were collected at 4 time points: baseline, before FFP, immediately following the initial unit of FFP, and following the completion of consecutive units of FFP. Samples collected from patients that received LR only were approximated to the FFP group time points. Coagulation parameters were measured using rTEG in blood samples. Descriptive analysis was used to compare demographic and burn injury characteristics at admission. A mixed effects model was used to compare the two groups through the observation period overall and at each time point. Results There were 35 patients in the FFP group and 15 patients in the comparison group. The groups were primarily male (74.3% vs 73.3%), and there was no difference in demographics, TBSA (34.0% (27.0-48.5) vs 33.0% (26.5-46.5, p=0.82)), Baux score, inhalation injury, and mortality rate (28.6% vs 26.7%, p=0.99). Major coagulation markers of rTEG (k, α-angle, MA, and ly30) were not different between these groups and were within normal ranges. The R time in the crystalloid group was greater than the normal range at all 4 time points. There were significant differences in R time at pre-FFP (30.0(25.0-32.5) secs vs 48.0 (36.0-54.0) secs, p&amp;lt; 0.001) and after all units (27.5(20.9-33.8) secs vs 48.0(48.0-54.0) secs, p&amp;lt; 0.0001) when compared to the FFP group where R time was in the normal range. Conclusions Plasma inclusive burn resuscitation did not result in hypercoagulability or changes in lysis when compared to patients primarily resuscitated with crystalloids. The elevated R time in the crystalloid group, which was not seen in the FFP group, may be due to the lack of replenishment in coagulation factors that FFP would provide. Further understanding of PIR’s role in the inflammatory response is needed to evaluate its impact during resuscitation. Applicability of Research to Practice Plasma inclusive resuscitation may be another tool to treat the multifactorial nature of burn shock and burn induced coagulopathy.

Optimization of cardiopulmonary bypass prime fluid to preserve microcirculatory perfusion during on-pump coronary artery bypass graft surgery: PRIME study protocol for a double-blind randomized trial

BackgroundAcute microcirculatory perfusion disturbances and organ edema are important factors leading to organ dysfunction during cardiac surgery with cardiopulmonary bypass (CPB). Priming of the CPB system with crystalloid or colloid fluids, which inevitably leads to hemodilution, could contribute to this effect. However, there is yet no optimal evidence-based strategy for this type of priming. Hence, we will investigate different priming strategies to reduce hemodilution and preserve microcirculatory perfusion.MethodsThe PRIME study is a single-center double-blind randomized trial. Patients undergoing elective coronary artery bypass graft surgery with CPB will be randomized into three groups of prime fluid strategy: (1) gelofusine with crystalloid, (2) albumin with crystalloid, or (3) crystalloid and retrograde autologous priming. We aim to include 30 patients, 10 patients in each arm. The primary outcome is the change in microcirculatory perfusion. Secondary outcomes include colloid oncotic pressure; albumin; hematocrit; electrolytes; fluid balance and requirements; transfusion rates; and endothelial-, glycocalyx-, inflammatory- and renal injury markers. Sublingual microcirculatory perfusion will be measured using non-invasive sidestream dark field video microscopy. Microcirculatory and blood measurements will be performed at five consecutive time points during surgery up to 24 h after admission to the intensive care unit.DiscussionPRIME is the first study to assess the effect of different prime fluid strategies on microcirculatory perfusion in cardiac surgery with CPB. If the results suggest that a specific crystalloid or colloid prime fluid strategy better preserves microcirculatory perfusion during on-pump cardiac surgery, the current study may help to find the optimal pump priming in cardiac surgery.Trial registrationClinicalTrials.gov NCT05647057. Registered on 04/25/2023. ClinicalTrials.gov PRS: Record Summary NCT05647057, all items can be found in the protocol.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Inadvertent intraoperative hypothermia

Hemostasis plays a critical role in surgical procedures and is essential for a successful outcome. Advances in hemostatic agents offer new approaches to controlling bleeding thereby making surgeries safer. The appropriate choice of these agents is crucial. Volume replacement, another integral part of Patient Blood Management (PBM), maintains adequate tissue perfusion, preventing cellular damage. Individualization in fluid administration is vital with the choice between crystalloids and colloids depending on each case. Colloids, unlike crystalloids, increase oncotic pressure, contributing to fluid retention in the intravascular space. Understanding these aspects is essential to ensure safe and effective surgery, minimizing complications related to blood loss and maintaining the patient's hemodynamic status.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Intraoperative hemostasis and volume replacement

Hemostasis plays a critical role in surgical procedures and is essential for a successful outcome. Advances in hemostatic agents offer new approaches to controlling bleeding thereby making surgeries safer. The appropriate choice of these agents is crucial. Volume replacement, another integral part of Patient Blood Management (PBM), maintains adequate tissue perfusion, preventing cellular damage. Individualization in fluid administration is vital with the choice between crystalloids and colloids depending on each case. Colloids, unlike crystalloids, increase oncotic pressure, contributing to fluid retention in the intravascular space. Understanding these aspects is essential to ensure safe and effective surgery, minimizing complications related to blood loss and maintaining the patient's hemodynamic status.

The effect of Channa striata, Moringa oleifera, and Curcuma xanthorrhiza extract on accelerating recovery in a ventilated patient with hemorrhagic shock grade 3 due to prolonged retained placenta: a case report

BackgroundMost of critically ventilated patients with severe hemorrhagic shock experience metabolic acidosis, hypoalbuminemia, electrolyte imbalance, and increased production of free radical. Channa striata has a high content of albumin, an essential binding protein that contributes to homeostasis, and when combined with Moringa oleifera and Curcuma xanthorrhiza, they act as powerful antioxidants. Administration of C. striata, M. oleifera, and C. xanthorrhiza extract orally may benefit patient with hemodynamic issues, including significant blood loss.Case reportA 40-year-old Indonesian woman came to emergency department with decreased consciousness resulting from hemorrhagic shock grade 3 due to prolonged placenta retention for 10 days after delivery of her third child. She had an emergency hysterectomy and was sent to the intensive care unit with a hemoglobin level of 4.2 gr/dL, despite already receiving two bags of packed red blood cells during operation, and she continued with four more bags within her first day in the intensive care unit. The patient was ventilated, was supported by vasopressors, and had a low albumin level of 2.1 gr/dL. Her hemodynamic profile was difficult to stabilize, with persistent gastric residue and periodic urine output less than 1 cc/kg/hour, thereby slowing the ventilator and vasopressor weaning process. Oral supplementation of C. striata, M. oleifera, and C. xanthorrhiza was given in the second day divided in three doses every 6 hours. After the second dose, gastric residue started to subside and disappeared after the third dose. The patient’s condition improved in the next 24 hours; she was extubated and discharged from the hospital in the fourth day.ConclusionThis is the first case report describing the effect of C. striata, M. oleifera, and C. xanthorrhiza extract in a patient with severe hemorrhagic shock due to a prolonged placenta. Accelerated recovery showed the possibility benefit of C. striata, M. oleifera, and C. xanthorrhiza extract in stabilizing oncotic pressure, neutralizing free radicals, and preventing further damage in hypoxic cells.

Effect of maternal serum albumin level on birthweight and gestational age: an analysis of 39200 singleton newborns.

Serum albumin plays a pivotal role in regulating plasma oncotic pressure and modulating fluid distribution among various body compartments. Previous research examining the association between maternal serum albumin levels and fetal growth yielded limited and inconclusive findings. Therefore, the specific influence of serum albumin on fetal growth remains poorly understood and warrants further investigation. A retrospective study involved 39200 women who had a singleton live birth at a tertiary-care academic medical center during the period from January 2017 to December 2020. Women were categorized into four groups according to the quartile of albumin concentration during early pregnancy: Q1 group, ≤41.0 g/L; Q2 group, 41.1-42.6 g/L; Q3 group, 42.7-44.3 g/L and Q4 group, >44.3 g/L. The main outcome measures were mid-term estimated fetal weight, birthweight and gestational age. Multivariate linear and logistic regression analysis were performed to detect the independent effect of maternal serum albumin level on fetal growth after adjusting for important confounding variables. In the crude analysis, a significant inverse correlation was found between early pregnancy maternal serum albumin levels and fetal growth status, including mid-term ultrasound measurements, mid-term estimated fetal weight, birthweight, and gestational age. After adjustment for a number of confounding factors, mid-term estimated fetal weight, birthweight, and birth height decreased significantly with increasing albumin levels. Compared to the Q2 group, the Q4 group had higher rates of preterm birth (aOR, 1.16; 95% CI, 1.01-1.34), small-for-gestational-age (aOR, 1.27; 95% CI, 1.11-1.45) and low birthweight (aOR, 1.41; 95% CI, 1.18-1.69), and lower rate of large-for-gestational-age (aOR, 0.85; 95% CI, 0.78-0.94). Moreover, to achieve the optimal neonatal outcome, women with higher early pregnancy albumin levels required a greater reduction in albumin levels in later pregnancy stages. A higher maternal serum albumin level during early pregnancy was associated with poor fetal growth, with the detrimental effects becoming apparent as early as the mid-gestation period. These findings provided vital information for clinicians to predict fetal growth status and identify cases with a high risk of adverse neonatal outcomes early on.

The clinical significance of hypoalbuminaemia

Albumin is a relatively small molecule with a radius of 7.5nm and a molecular weight of 65kDa. It is the most abundant protein in plasma, accounting for 60-75% of its oncotic pressure. Its concentration in plasma is merely one static measurement reflecting a dynamic and complex system of albumin physiology, and is the net result of several different processes, one or more of which may become deranged by disease or its treatment. It is also unsurprising that hypoalbuminaemia has proved to be an indicator of morbidity and mortality risk since the underlying conditions which cause it, including protein energy malnutrition, crystalloid overload, inflammation, and liver dysfunction are themselves risk factors. In some cases, its underlying cause may require treatment but mostly it is just a parameter to be monitored and used as one measure of clinical progress or deterioration. While malnutrition, associated with a low protein intake, may be a contributory cause of hypoalbuminaemia, in the absence of inflammation and/or dilution with crystalloid its development in response to malnutrition alone is slow compared with the rapid change caused by inflammatory redistribution or dilution with crystalloids. Other significant causes include liver dysfunction and serous losses. These causal factors may occur singly or in combination in any particular case. Treatment is that of the underlying causes and associated conditions such as a low plasma volume, not of hypoalbuminaemia per se.

The Changes in Relative Blood Volume during Dialysis Are Characterized by Ultrafiltration Rate and Predialysis Blood Test Values

Introduction: Continuous monitoring of relative blood volume (percentage BV) in hemodialysis (HD) is critical for determining dry weight and preventing intradialytic hypotension. However, the cause of the BV variation remains unknown. This research aimed to examine factors that influence the percentage BV. Methods: We devised a formula based on coefficients (“a,” “τ,” and “b”) to predict changes in percentage BV. “a” denotes a significant decrease in percentage BV in the early stages of HD. “τ” represents the transition from early to late phase of HD. “b” denotes the slope of the decrease in percentage BV in the late phase of HD. We measured the percentage BV in 18 patients with end-stage renal disease. The coefficients were estimated by fitting experimental data from patients using a least squares optimization algorithm. A correlation analysis of these parameters and patient predialysis data was performed. Results: Ultrafiltration rate (UFR) was found to be negatively correlated with “b” (r = −0.851, p < 0.01). However, UFR was not significantly related to “a.” Predialysis serum total protein level was negatively correlated with “a” (r = −0.531, p = 0.042). Predialysis serum albumin and predialysis sodium were not significantly correlated with “a” and “τ.” Plasma osmolarity did not have a significant relationship with “a” and “τ.” Discussion/Conclusion: UFR influenced the decrease in percentage BV in the late phase but did not influence the decrease of percentage BV in the early phase. “a” was associated with predialysis serum total protein level but not with plasma osmolality or predialysis sodium. This implies that colloid oncotic pressure is important for plasma refilling immediately after dialysis begins. During the change of percentage BV, the decrease in the early phase of dialysis was not related to UFR, but related to other parameters, especially predialysis total protein level. A decrease in the late phase of dialysis is related to UFR.

The role of serum albumin in critical illness, predicting poor outcomes, and exploring the therapeutic potential of albumin supplementation.

Serum albumin (ALB) plays a vital role in maintaining oncotic pressure and contributing to hemodynamic stability, with low levels associated with adverse outcomes in critically ill patients. This study aimed to assess the association between serum ALB concentrations and poor outcomes and the possible benefits of ALB supplementation. A retrospective study involving 300 intensive care unit (ICU) patients. Albumin levels were recorded upon admission and throughout the stay, and patients were categorized based on a cutoff of 2.49 g/dl. The associations between low ALB levels and mortality were assessed using regression analysis. Additionally, it investigated the association of albumin supplementation with patient outcomes and mortality in specific patient populations. The mean age was 54.9 years, with 68% having sepsis. Patients with low baseline ALB concentrations exhibited higher overall mortality (71% vs. 52%) and 28-day mortality (50% vs. 39%). Adjusted analyses confirmed associations with mortality. Albumin supplementation was administered to 53% of the patients. Its use demonstrated potential benefits, particularly in reducing mortality, when given to specific groups, such as sepsis and hypoalbuminemia patients. The study confirms that low serum albumin levels are strongly associated with higher mortality rates in ICU patients. Albumin supplementation showed potential benefits, particularly in patients with sepsis and low albumin levels. Further analyses explored the dosage-response relationship and identified potential groups that would benefit from albumin supplementation. Albumin can play a major role in predicting mortality in critically ill patients. Moreover, ALB supplementation may improve survival, especially in resource-limited settings. Future research should refine protocols through clinical trials for optimal survival in critically ill patients.

A bioengineered artificial interstitium supports long-term islet xenograft survival in nonhuman primates without immunosuppression.

Cell-based therapies hold promise for many chronic conditions; however, the continued need for immunosuppression along with challenges in replacing cells to improve durability or retrieving cells for safety are major obstacles. We subcutaneously implanted a device engineered to exploit the innate transcapillary hydrostatic and colloid osmotic pressure generating ultrafiltrate to mimic interstitium. Long-term stable accumulation of ultrafiltrate was achieved in both rodents and nonhuman primates (NHPs) that was chemically similar to serum and achieved capillary blood oxygen concentration. The majority of adult pig islet grafts transplanted in non-immunosuppressed NHPs resulted in xenograft survival >100 days. Stable cytokine levels, normal neutrophil to lymphocyte ratio, and a lack of immune cell infiltration demonstrated successful immunoprotection and averted typical systemic changes related to xenograft transplant, especially inflammation. This approach eliminates the need for immunosuppression and permits percutaneous access for loading, reloading, biopsy, and recovery to de-risk the use of "unlimited" xenogeneic cell sources to realize widespread clinical translation of cell-based therapies.