Synergistic impact of plasma albumin and cognitive function on all-cause mortality in Chinese older adults: a prospective cohort study.

Background: Hypoalbuminemia and cognitive impairment (CI) each independently increase the mortality risk in older adults. However, these two geriatric syndromes can occur simultaneously. In community-dwelling older adults, is the combination of hypoalbuminemia and CI linked to a higher mortality risk than either condition alone? Objective: We aimed to investigate the association between plasma albumin, cognitive function, and their synergistic effect on mortality in Chinese community-dwelling older adults. Methods: Data from the Chinese Longitudinal Healthy Longevity Survey (2012) included 1,858 participants aged ≥65. Baseline assessments comprised albumin levels and cognitive status. All-cause mortality was confirmed through 2014-2018 surveys. Cox proportional hazards models assessed associations, and restricted cubic splines explored albumin-mortality relationship. Results: During a median follow-up of 48.85 months, 921 deaths. Albumin≥35 g/L vs < 35g/L [HR: 1.33 (95%CI, 1.10, 1.62)] and CI vs normal cognition [HR: 1.69 (95%CI, 1.43, 1.99)] independently predicted mortality. A dose-response relationship with mortality was observed for albumin quartiles (p < 0.001). Each SD increase in MMSE or albumin correlated with 22% and 15% lower mortality risk, respectively. Combined hypoproteinemia and CI increased the mortality risk by 155%, with a notably higher risk in males, those aged <85 years, and individuals living in rural areas. Interaction effects of albumin and CI on mortality were observed (p < 0.001). In the single CI group, older adults had a 61% increased risk of mortality in the hypoproteinaemia group compared with the albumin-normal group. Restricted cubic spline revealed a reverse J-shaped association, particularly for participants without CI. For individuals with CI, albumin levels were inversely associated with mortality risk. Conclusion: Hypoproteinemia and CI, individually and combined, increased all-cause mortality risk in Chinese older adults, with stronger effects observed in males, younger older adults, and those living in rural areas. These findings emphasize the importance of targeted adjustments and early nutrition programs in health prevention and clinical care for older adults.

Fluid distribution during surgery in the flat recumbent, Trendelenburg, and the reverse Trendelenburg body positions.

BACKGROUND: The distribution and elimination of infused crystalloid fluid is known to be affected by general anesthesia, but it is unclear whether changes differ depending on whether the patient is operated in the flat recumbent position, the Trendelenburg ("legs up") position, or the reverse Trendelenburg ("head up") position. METHODS: Retrospective data on hemodilution and urine output obtained during and after infusion of 1-2 L of Ringer's solution over 30-60 min were collected from 61 patients undergoing surgery under general anesthesia and 106 volunteers matched with respect to the infusion volume and infusion time. Parameters describing fluid distribution in the anesthetized and awake subjects were compared by population volume kinetic analysis. RESULTS: General anesthesia decreased the rate constant for urine output by 79% (flat recumbent), 91% (legs up) and 91% (head up), suggesting that laparoscopic surgery per se intensified the already strong anesthesia-induced fluid retention. General anesthesia also decreased the rate constant governing the return of the distributed fluid to the plasma by 32%, 15%, and 70%, respectively. These results agree with laboratory data showing a depressive effect of anesthetic drugs on lymphatic pumping, and further suggest that the "legs up" position facilitates lymphatic flow, whereas the "head up" position slows this flow. Both Trendelenburg positions increased swelling of the "third fluid space". CONCLUSIONS: General anesthesia caused retention of infused fluid with preferential distribution to the extravascular space. Both Trendelenburg positions had a modifying influence on the kinetic adaptations that agreed with the gravitational forces inflicted by tilting to body.

Accelerated lymph flow from infusion of crystalloid fluid during general anesthesia.

BACKGROUND: Kinetic analysis of crystalloid fluid yields a central distribution volume (Vc) of the same size as the expected plasma volume (approximately 3 L) except during general anesthesia during which Vc might be only half as large. The present study examined whether this difference is due to influence of the intravascular albumin balance. METHODS: A population volume kinetic analysis according to a three-compartment model was performed based on retrospective data from 160 infusion experiments during which 1-2.5 L of crystalloid fluid had been infused intravenously over 20-30 min. The plasma dilution based on blood hemoglobin (Hb) and plasma albumin (Alb) was measured on 2,408 occasions and the urine output on 454 occasions. One-third of the infusions were performed on anesthetized patients while two-thirds were given to awake healthy volunteers. RESULTS: The Hb-Alb dilution difference was four times greater during general anesthesia than in the awake state (+ 0.024 ± 0.060 versus - 0.008 ± 0.050; mean ± SD; P < 0.001) which shows that more albumin entered the plasma than was lost by capillary leakage. The Hb-Alb dilution difference correlated strongly and positively with the kinetic parameters governing the rate of fluid transfer through the fast-exchange interstitial fluid compartment (k12 and k21) and inversely with the size of Vc. Simulations suggest that approximately 200 mL of fluid might be translocated from the interstitial space to the plasma despite ongoing fluid administration. CONCLUSIONS: Pronounced plasma volume expansion early during general anesthesia is associated with a positive intravascular albumin balance that is due to accelerated lymphatic flow. This phenomenon probably represents adjustment of the body fluid volumes to anesthesia-induced vasodilatation.

Albumin and Cardioprotection in On-Pump Cardiac Surgery-A Post Hoc Analysis of a Randomized Trial.

OBJECTIVES: To study the quantitative potency of plasma albumin on cardioprotection in terms of creatinine kinase-myocardial band mass (CK-MBm) in on-pump cardiac surgery. DESIGN: Post hoc analysis of a double-blinded randomized clinical trial. SETTING: Single-center study in the Helsinki University Hospital. PARTICIPANTS: A total of 1,386 adult on-pump cardiac surgical patients. INTERVENTION: Administration of 4% albumin (n = 693) or Ringers acetate (n = 693) for cardiopulmonary bypass priming and volume replacement intraoperatively and postoperatively during the first 24 hours. MEASUREMENTS AND MAIN RESULTS: Albumin concentration was measured preoperatively and intraoperatively (after protamine administration), and CK-MBm on the first postoperative morning. Multivariate linear regression analyses were measured in the whole cohort and the Ringer group. Plasma albumin concentration did not differ between the groups preoperatively (Ringer v albumin: 38.3 ± 5.0 g/L v 38.6 ± 4.5 g/L; p = 0.171) but differed intraoperatively (29.5 ± 5.2 g/L v 41.5 ± 6.0 g/L; p < 0.001). Creatinine kinase-myocardial band mass was higher in the Ringer (32.0 ± 34.8 µg/L) than in the albumin group (24.3 ± 33.0 µg/L) (p < 0.001). Aortic cross-clamping time associated with CK-MBm in the whole cohort (standardized ß = 0.376 [95% CI 0.315-0.437], p < 0.001) and the Ringer group (ß = 0.363 [0.273-0.452]; p < 0.001). Albumin administration in the whole cohort (ß = -0.156 [-0.201 to -0.111]; p < 0.001) and high intraoperative albumin concentration in the Ringer group (ß = -0.07 [-0.140 to -0.003]; p = 0.04) associated with reduced CK-MBm. Compared with ischemia-induced increase in CK-MBm, albumin's potency to reduce CK-MBm was 41% in the whole cohort (ß-value ratio of -0.156/0.376) and 19% in the Ringer group (ß-value ratio of -0.07/0.363). CONCLUSION: Both endogenous and exogenous albumin appear to be cardioprotective regarding CK-MBm release in on-pump cardiac surgery.

Study of the f-cell ratio using plasma dilution and albumin mass kinetics.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Assessment of the relationship between plasma fibrinogen-to-albumin ratio and slow coronary flow phenomenon in patients without obstructive coronary artery disease.

BACKGROUND: Prior studies have suggested that the chronic inflammatory response has an important role in the pathophysiology of slow coronary flow phenomenon (SCFP). However, data are scarce regarding the role of plasma fibrinogen-to-albumin ratio (PFAR) in patients having SCFP without obstructive coronary artery disease (CAD). In this study, we investigated the relationship between PFAR and the presence of SCFP in patients without obstructive CAD. METHODS: From January 2021 to January 2023, we consecutively recruited 1085 patients without obstructive CAD according to the diagnostic and exclusion criteria. In total, SCFP was diagnosed in 70 patients. A 1:2 age-matched case-control study was then conducted using comparators without SCFP. Ultimately, this study enrolled 70 patients with angiographically normal coronary arteries and SCFP, along with 140 comparators with angiographically normal coronary arteries and normal coronary flow. Plasma fibrinogen and albumin levels were measured, and the PFAR was then calculated for each patient. RESULTS: PFARs were significantly greater in the SCFP group than in the comparators with normal coronary flow (82.8 ± 15.4 vs 73.1 ± 19.5, p < 0.001). PFAR increased with increasing numbers of vessels affected by SCFP. Multivariate logistic regression analysis showed that PFAR was an independent predictor of SCFP (odds ratio: 1.818, p = 0.015). Receiver operating characteristic (ROC) curve analysis indicated that PFAR showed a better predictive value of SCFP than fibrinogen or albumin, although not significantly (p > 0.05). CONCLUSION: PFAR is an independent predictor of SCFP in patients without obstructive CAD. PAFR could improve the predictive value of SFCP than albumin or fibrinogen alone, but not significantly.

Interpretations of the Role of Plasma Albumin in Prognostic Indices: A Literature Review.

This review assesses how publications interpret factors that influence the serum or plasma albumin (PA) level in prognostic indices, focusing on inflammation and nutrition. On PubMed, a search for "albumin AND prognosis" yielded 23,919 results. From these records, prognostic indices were retrieved, and their names were used as search strings on PubMed. Indices found in 10 or more original research articles were included. The same search strings, restricted to "Review" or "Systematic review", retrieved yielded on the indices. The data comprised the 10 latest original research articles and up to 10 of the latest reviews. Thirty indices had 294 original research articles (6 covering two indices) and 131 reviews, most of which were from recent years. A total of 106 articles related the PA level to inflammation, and 136 related the PA level to nutrition. For the reviews, the equivalent numbers were 54 and 65. In conclusion, more publications mention the PA level as a marker of nutrition rather than inflammation. This is in contrast to several general reviews on albumin and nutritional guidelines, which state that the PA level is a marker of inflammation but not nutrition. Hypoalbuminemia should prompt clinicians to focus on the inflammatory aspects in their patients.

Albumin determined by bromocresol green leads to erroneous results in routine evaluation of patients with chronic kidney disease.

OBJECTIVES: Measurement of plasma albumin is pivotal for clinical decision-making in patients with chronic kidney disease (CKD). Routinely used methods as bromocresol green (BCG) and bromocresol purple (BCP) can suffer from aselectivity, but the impact of aselectivity on the accuracy of plasma albumin results of CKD-patients is still unknown. Therefore, we evaluated the performance of BCG-, BCP- and JCTLM-endorsed immunological methods in patients with various stages of CKD. METHODS: We evaluated the performance of commonly used albumin methods in patients with CKD stages G1 through G5, the latter divided in two groups based on whether they received hemodialysis treatment. In total, 163 patient plasma samples were measured at 14 laboratories, on six different BCG and BCP-platforms, and four different immunological platforms. The results were compared with an ERM-DA-470k-corrected nephelometric assay. The implications on outcome is evaluated by the proportion of patient results <38 g/L for the diagnosis of protein energy wasting. RESULTS: Albumin results determined with BCP- and immunological methods showed the best agreement with the target value (92.7 and 86.2 %, respectively vs. 66.7 % for BCG, namely due to overestimation). The relative agreement of each method with the target value was platform-dependent, with larger variability in agreement between platforms noted for BCG and immunological methods (3.2-4.6 and 2.6-5.3 %) as opposed to BCP (0.7-1.5 %). The stage of CKD had similar effects on the variability in agreement for the three method-groups (0.6-1.8 % vs. 0.7-1.5 % vs. 0.4-1.6 %). The differences between methods cause discrepancies in clinical decision-making, as structurally fewer patients were diagnosed with protein energy wasting upon using BCG-based albumin results. CONCLUSIONS: Our study shows that BCP is fit for the intended use to measure plasma albumin levels in CKD patients from all stages, including patients on hemodialysis. In contrast, most BCG-based platforms falsely overestimate the plasma albumin concentration.

Progression of Blood-Brain Barrier Leakage in Patients with Alzheimer's Disease as Measured with the Cerebrospinal Fluid/Plasma Albumin Ratio Over Time.

Background: Studies have found a disruption of the blood-brain barrier (BBB) in patients with Alzheimer's disease (AD), but there is little evidence of the changes in the BBB over time. The cerebrospinal fluid's (CSF) protein concentration can be used as an indirect measurement for the permeability of the BBB using the CSF/plasma albumin quotient (Q-Alb) or total CSF protein. Objective: In the current study, we wanted to investigate the changes in Q-Alb in patients with AD over time. Methods: A total of 16 patients diagnosed with AD, who had at least two lumbar punctures performed, were included in the current study. Results: The difference in Q-Alb over time did not show a significant change. However, Q-Alb increased over time if the time interval was > 1 year between the measurements. No significant associations between Q-Alb and age, Mini-Mental State Examination, or AD biomarkers were found. Conclusion: The increase in Q-Alb suggests that there is an increased leakage through the BBB, which may become more prominent as the disease progresses. This may be a sign of progressive underlying vascular pathology, even in patients with AD without major vascular lesions. More studies are needed to further understand the role of BBB integrity in patients with AD over time and the association with the progression of the disease.

Kinetics of 5% and 20% albumin: A controlled crossover trial in volunteers.

BACKGROUND: Albumin for intravenous infusion is marketed in two concentrations, 20% and 5%, but how they compare with regard to plasma volume expansion over time is unclear. METHODS: In a prospective crossover study, 12 volunteers received 3 ml kg-1 of 20% albumin and, on another occasion, 12 ml kg-1 of 5% albumin over 30 min. Hence, equivalent amounts of albumin were given. Blood was collected on 15 occasions over 6 h. Mass balance and volume kinetics were used to estimate the plasma volume expansion and the capillary leakage of albumin and fluid based on measurements of blood hemoglobin, plasma albumin, and the colloid osmotic pressure. RESULTS: The greatest plasma volume expansion was 16.0 ± 6.4% (mean ± SD) with 20% albumin and 19.0 ± 5.2% with 5% albumin (p < .03). The volume expansion with 20% albumin corresponded to twice the infused volume. One third of the 5% albumin volume quickly leaked out of the plasma, probably because of the higher colloid osmotic pressure of the volunteer plasma (mean, 24.5 mmHg) than the albumin solution (19.1 mmHg). At 6 h, the capillary leakage amounted to 42 ± 15% and 47 ± 11% of the administered albumin with the 20% and 5% preparations, respectively (p = .28). The corresponding urine outputs were 547 (316-780) ml and 687 (626-1080) ml (median and interquartile range; p = .24). CONCLUSION: The most important difference between the fluids was a dehydrating effect of 20% albumin when the same albumin mass was administered.

Are plasma proteins a valid alternative for assessing nephrotic syndrome in children from low-income countries?

BACKGROUND: A diagnosis of nephrotic syndrome (NS) in children with edema relies on urinary albumin excretion and usually plasma protein (Pprot) and albumin (Palb) concentrations. METHODS: In order to fit laboratory tests to optimal healthcare in low-resource countries, we established correlations between Pprot and Palb in children with NS (217 measurements in 60 patients) and in children with exudative enteropathy and chronic hepatopathy/liver insufficiency (186 measurements in 21 patients); all patients had repeated measurements at various stages of their disease. RESULTS: There was a good correlation between Pprot and Palb in children with idiopathic NS and genetic NS (ICC=0.8, p < 0.0001, 95% CI: 0.8-0.9 and ICC=0.8, p < 0.0001, 95% CI: 0.7-0.8, respectively), whereas the correlation was average (exudative enteropathy) or absent (chronic hepatopathy) in those without renal protein loss. CONCLUSION: Since Palb measurement is around two times more expensive than Pprot measurement, these results suggest giving priority to total Pprot measurement in the diagnosis and follow-up of children with the NS, mainly in low-resource countries.

Lower Plasma Albumin, Higher White Blood Cell Count and High-Sensitivity C-Reactive Protein are Associated with Femoral Artery Intima-Media Thickness Among Newly Diagnosed Patients with Type 2 Diabetes Mellitus.

Introduction: Low albumin levels, high levels of high-sensitivity C-reactive protein (hs-CRP), and high white blood cell count were risk factors for changes in arterial intima-media thickness (IMT). Femoral artery IMT damages were one of the common peripheral artery type 2 diabetes. This study was conducted to determine the association between femoral artery IMT and plasma albumin, hs-CRP levels, and white blood cell count in newly diagnosed patients with type 2 diabetes mellitus (nT2D). Materials and Methods: From January 2015 to May 2020, 306 patients with nT2D were recruited for this cross-sectional descriptive study at Vietnam's National Endocrinology Hospital. We measured IMT by Doppler ultrasound. Results: There was a statistically significant difference in albumin, hs-CRP levels, hs-CRP-to-albumin ratio, and white blood cell counts between three different IMT groups namely normal IMT, thick IMT, and atherosclerosis (p = 0.003, p = 0.001, p = 0.001 and p = 0.049, respectively). In the multivariate linear regression analysis, white blood cell count, and hs-CRP levels showed a significantly positive correlation to IMT (standardized B and p of 0.17, 0.015 and 0.163, 0.024, respectively), but albumin levels were a significantly negative correlation to IMT (standardized B = -0.151, p = 0.029). The multivariate logistic regression analysis showed that albumin (OR = 0.79, 95% CI 0.65-0.90, p = 0.018), hs-CRP (OR = 1.09, 95% CI 1.01-1.18, p = 0.026), and white blood cell count (OR = 1.36, 95% CI 1.03-1.81, p = 0.033) had correlation to atherosclerosis of femoral artery. Conclusion: Reduced plasma albumin, elevated hs-CRP, and white blood cell count associated with IMT increased the odds for atherosclerosis of femoral artery among nT2D.

Impact of C-reactive protein and albumin levels on short, medium, and long term mortality in patients with diffuse large B-cell lymphoma.

Objectives and study design: In this population-based study of 602 patients, we amended C-reactive protein (CRP) and plasma albumin (PA) levels around the diagnosis of diffuse large B-cell lymphoma (DLBCL) to the International Prognostic Index (IPI) and assessed 0-90, 91-365, and +365-day survival.Results: The CRP did not contribute to the IPI's prognostic or discriminatory ability, regardless of time period, particularly not in models with PA. In contrast, the PA was an important contributor, especially in the 0-90 day period, but also up to one year after the diagnosis. For day 0-90, the model with the IPI only had an Area Under the Receiver Operating Characteristics (AUROC) of 0.742, whereas the IPI with PA as a continuous variable rendered an AUROC of 0.841. Especially the lower PA quartile (18-32 g/L) contributed to the worse prognosis.Conclusions: The amendment of PA to the IPI may significantly improve the short-term prognostic and discriminative ability.Key messagesThe amendment of the plasma albumin (PA) level to the International Prognostic Index significantly improved the prediction of mortality up to one year after the diagnosis of diffuse large B-cell lymphoma.It was especially the lower quartile of the PA level (18-32 g/L) that contributed to the worse prognosis.

How intrauterine growth restriction due to nutritional stress changes the function of key proteins in brain serotonin metabolism during development.

This review aimed to describe and comment on how experimental intrauterine nutritional stress in animals produced some changes in tryptophan-5-hydroxylases (TPH) 1 and 2 in the brain and other key proteins such as plasma albumin, and how the intrauterine nutritional stress could produce long-lasting alterations in serotonin function in the brain of human infants.

El objetivo de esta revisión es describir y comentar cómo el estrés nutricional intrauterino experimental en animales produjo algunos cambios en las triptófano-5-hidroxilasas 1 y 2 en el cerebro y en otras proteínas clave, como la albúmina plasmática, y de qué manera el estrés nutricional intrauterino podría producir alteraciones duraderas en la función de la serotonina en el cerebro de lactantes.

Platelet adhesion in type 2 diabetes: impact of plasma albumin and mean platelet volume.

BACKGROUND: Altered mean platelet volume (MPV) and plasma albumin has been reported in type 2 diabetes (T2D). MPV is suggested to predict cardiovascular risk but there is a lack of evidence for associations between MPV and platelet adhesion. Plasma albumin and magnesium are other factors reported to influence thrombotic risk. The objectives of this study were to assess the association between platelet adhesion and plasma factors with a potential role to affect platelet activation. METHODS: Blood was collected from 60 T2D patients and 60 healthy controls. Platelet adhesion to different protein surfaces induced by various soluble activators were measured in microplates. MPV, albumin and magnesium were analysed together with additional routine tests. RESULTS: Despite normal levels, plasma albumin significantly correlated with adhesion of T2D platelets but not with controls. There was a significant association between MPV and platelet adhesion in both groups, but association was smaller in T2D. Levels of glucose, HbA1c or magnesium did not correlate with platelet adhesion. CONCLUSIONS: Plasma albumin was associated with platelet adhesion in T2D suggesting that albumin may be a factor to consider upon cardiovascular risk assessment. MPV was more associated with the level of platelet adhesion in healthy individuals than in well-controlled T2D patients.

Intravascular albumin loss is strongly associated with plasma volume withdrawal in dialysis patients.

INTRODUCTION: Low circulating albumin closely predicts mortality in end-stage renal disease (ESRD) patients. The cause(s) of hypoalbuminemia (hALB) in ESRD patients remains to be elucidated. The aim of the present study was to determine the role of plasma volume (PV) withdrawal in the reduction of total circulating albumin and essential blood solutes induced by hemodialysis (HD). METHODS: PV determined with high-precision automated carbon monoxide-rebreathing, total circulating as well as concentration of plasma albumin and electrolytes were assessed prior to and after 4-hour HD in 10 ESRD patients. FINDINGS: Baseline PV ranged from 3.5 to 6.2 l. After HD, PV was decreased by 689 ± 566 mL (-16%) (P = 0.004). Total circulating albumin was largely reduced after HD (170.8 ± 35.1 vs. 146.1 ± 48.9 g, P = 0.008), while albumin concentration was unaltered. According to a strong linear relationship (r = 0.91, P < 0.001), one-third of total circulating albumin is lost from the intravascular compartment for every liter of PV removed. Similar results were found regarding Na+ and Ca2+ electrolytes. DISCUSSION: Total circulating albumin, but not albumin concentration, is substantially reduced by HD in proportion to the amount of PV removed from the circulation. This study highlights the potential contributing role of PV withdrawal to hALB in ESRD patients.

Real World Evidence on Second-Line Palliative Chemotherapy in Advanced Pancreatic Cancer.

Background: The outcome and tolerability of palliative second line chemotherapy for advanced pancreatic cancer (APC) in real life patients are largely unknown. Prognostic parameters for risk stratification and treatment guidance are lacking. Materials and Methods: A population based multicenter retrospective cohort study was conducted, covering all APC patients who received palliative second-line chemotherapy between 2011 and 2018 at any cancer center in the South East Region of Sweden. Primary outcome was overall survival after second-line therapy (OS2). Time to treatment failure after second-line therapy (TTF2), hematological toxicity, and unplanned hospitalizations were key secondary outcomes. A number of baseline potentially prognostic parameters were assessed. Results: A total of 509 patients received first-line palliative chemotherapy, and of these 167 (33%) received at least one dose of second-line therapy and formed the final study population. Median OS2 was 5.2 months (95% CI = 4.7-5.7) and median TTF2 was 1.9 months (1.5-2.2). OS2 and TTF2 were similar regardless regimen, including comparison of the two most common regimens (fluoropyrimidine monotherapy vs. fluoropyrimidine/oxaliplatin doublet). Multivariate analysis revealed that normal plasma albumin (≥35) and serum CA-19-9 above median (>1,550) were independent predictors for OS2 (HR = 0.21, p < 0.001 and HR = 2.03, p = 0.009) and TTF2 (HR = 0.22, p < 0.001 and HR = 2.03, p = 0.01), while ECOG performance status >1 was predictive for TTF2 (HR = 2.05, p = 0.032). Grade 3-4 hematological toxicity was registered in 17 patients (10%). 50 (30%) had at least one event of hospitalization. Conclusion: The real world outcome of second line palliative chemotherapy for refractory APC remains dismal. Baseline plasma albumin, serum CA-19-9, and performance status emerge as key prognostic factors, and should be further studied as tools for individualized treatment decisions.

Contributing factors to the plasma albumin level at diagnosis of hematological malignancy.

OBJECTIVES: Many factors contribute to the plasma albumin (PA) level. We aimed to quantify different factors' relative contribution to the PA level when diagnosing hematological malignancy (HM). METHODS: The study was a population-based registry study including patients with HM in a Danish region. We applied multivariate linear regression analyses with C-reactive protein (CRP), WHO performance score (WHO-PS), age, sex, comorbidity, and HM type as exposures and the PA level on the day of the HM diagnosis (DX) as the outcome. The relative contribution of each exposure was determined as a percentage of the models' coefficient of determination (R2). RESULTS: In total, 2528 patients with HM had PA measured on DX. In the model comprising all exposures, CRP contributed with 65.8% to the R2 of 0.389 whereas 3 variables (CRP, WHO-PS, HM type) together contributed with 96.1%. When CRP was excluded from the model, R2 declined to 0.215 and the WHO-PS contributed with 96%. Other models, including separate analyses for each HM type, corroborated these results, except in myeloma patients where WHO-PS contributed with 61.1% to the R2 of 0.234. CONCLUSION: The inflammation biomarker CRP was the main predictor of the PA level on DX. The WHO-PS also contributed to the PA level on DX whereas the remaining factors (HM type, age, sex, and comorbidity) were of much less importance.

[Clinical effects of concentrated growth factor combined with plasma albumin gel in treating facial depressed scar].

Objective: To explore the clinical effects of concentrated growth factor (CGF) combined with plasma albumin gel (PAG) in treating facial depressed scar. Methods: From January 2018 to June 2019, 14 patients in the First Affiliated Hospital of Zhengzhou University and 10 patients in Henan NO.3 Provincial People's Hospital with facial depressed scar who met the inclusion criteria were admitted, and their clinical data were retrospectively analyzed by the method of case-control study. Based on the method of treatment, 8 patients (4 males and 4 females) aged 28.50 (25.50, 31.50) years were enrolled in CGF alone group, 8 patients (3 males and 5 females) aged 32.00 (28.50, 35.00) years were enrolled in PAG alone group, and 8 patients (5 males and 3 females) aged 33.50 (29.00, 35.75) years were enrolled in CGF+ PAG group. Suitable amount of CGF, PAG, and CGF+ PAG (mixed at a ratio of 1.0∶1.0-1.0∶1.5) prepared from autologous blood were injected subcutaneously via a single or multiple entrance (s) into the depressed scar of patients in CGF alone, PAG alone, and CGF+ PAG groups respectively to fill up the concavity, once every 4 weeks for a total of 3 times. Before the first treatment (hereinafter referred to as before treatment) and 3 months after the last treatment (hereinafter referred to as after treatment), the Goodman & Baron Acne Scar Grading System was used for scar grading, and the difference was calculated; the Anxiety Self-Rating Scale was used to score anxiety, and the difference was calculated. The Visual Analogue Score was used to score pain immediately after the first treatment. By one, two, and three months after treatment, the patients' satisfaction to scar treatment was scored, and the Global Aesthetic Improvement Scale was used to score the scar improvement. Adverse reaction of patients after treatment was monitored. Data were statistically analyzed with Fisher's exact probability test, Kruskal-Wallis H test, Mann-Whitney U test, Bonferroni correction, and Wilcoxon signed rank sum test. Results: (1) The scars of patients in the three groups were all graded 4.00 (4.00, 4.00) before treatment (χ(2)<0.001, P>0.05). By three months after treatment, compared with 2.00 (1.25, 2.00) of CGF alone group, the scar grades of patients in PAG alone group and CGF+ PAG group (3.00 (2.00, 3.00) and 1.00 (1.00, 1.00), respectively) had no significant change (Z=2.199, 2.003, P>0.05). The scar grade of patients in CGF+ PAG group was significantly lower than that in PAG alone group (Z=3.229, P<0.01). Compared with those before treatment, the scar grades of patients in CGF alone group, PAG alone group, and CGF+ PAG group were significantly reduced three months after treatment (Z=2.588, 2.598, 2.640, P<0.05 or P<0.01). The difference in scar grade before and after the treatment was significantly higher in CGF+ PAG group than in PAG alone group (Z=3.229, P<0.01). (2) The anxiety scores of patients in the three groups were similar before treatment and 3 months after (χ(2)=2.551, 2.768, P>0.05). Compared with those before treatment, the anxiety scores of patients in CGF alone group, PAG alone group, and CGF+ PAG group were significantly reduced three months after treatment (Z=2.395, 2.527, 2.533, P<0.05). The differences in anxiety score before and after the treatment were similar among the three groups (χ(2)=1.796, P>0.05). (3) The pain scores of patients in the three groups were similar immediately after the first treatment (χ(2)=0.400, P>0.05). (4) By one and two month (s) after treatment, the patients' satisfaction scores to scar treatment in the three groups were similar (χ(2)=2.688, 5.989, P>0.05). By three months after treatment, the patients' satisfaction score to scar treatment in CGF+ PAG group was significantly higher than that in PAG alone group (Z=2.922, P<0.01). Compared with those one month after treatment within the same group, the patients' satisfaction scores to scar treatment in CGF alone group, PAG alone group, and CGF+ PAG group were significantly increased two and three months after treatment (Z=1.121, 2.392, 2.000, 2.828, 2.449, 2.598, P<0.05 or P<0.01). Compared with those two months after treatment within the same group, the patients' satisfaction scores to scar treatment in CGF alone group, PAG alone group, and CGF+ PAG group were significantly increased three months after treatment (Z=2.271, 2.000, 2.646, P<0.05 or P<0.01). (5) One month after treatment, the scar improvement scores of patients in the three groups were similar (χ(2)=4.438, P>0.05). Two months after treatment, the scar improvement scores of patients in CGF alone group and CGF+ PAG group were 2.00 (2.00, 2.75) and 2.00 (2.00, 2.00) points, respectively, which were significantly higher than 1.00 (1.00, 1.00) point of PAG alone group (Z=3.303, 3.771, P<0.01). Three months after treatment, the scar improvement score of patients in CGF+ PAG group was 3.00 (3.00, 3.00) points, which was significantly higher than 2.00 (2.00, 2.75) points of CGF alone group and 1.00 (1.00, 2.00) points of PAG alone group (Z=2.450, 3.427, P<0.05 or P<0.01). Compared with those one month after treatment within the same group, the scar improvement scores of patients were significantly higher in CGF alone group and CGF+ PAG group two and three months after treatment and in PAG alone group three months after treatment (Z=2.828, 2.828, 2.530, 2.640, 2.121, P<0.05 or P<0.01). Compared with that two months after treatment within the same group, the scar improvement score of patients in CGF+ PAG group was significantly higher three months after treatment (Z=2.449, P<0.05). (6) After injection, all patients in the three groups had slight redness and swelling at the needle prick point and no other adverse reactions. Conclusions: CGF combined with PAG can reduce the scar grading, anxiety of patients, and enhance patients' satisfaction and scar improvement in the treatment of patients with facial depressed scar. The combined CGF+ PAG injection, without significant adverse reactions, is better than single component injection and is worthy of clinical application.

Cerebrospinal Fluid/Plasma Albumin Ratio as a Biomarker for Blood-Brain Barrier Impairment Across Neurodegenerative Dementias.

BACKGROUND: Previous studies have shown an association between disruption of the blood-brain-barrier (BBB) and dementias of different etiologies. The protein concentration of cerebrospinal fluid (CSF) can be used as an indirect measurement for the permeability of the BBB using the CSF/plasma albumin quotient (Q-Alb) or total CSF protein. OBJECTIVE: In the current study, we wanted to investigate Q-Alb and CSF protein concentration in dementias of different etiologies and the possible confounding factors. METHODS: A total of 510 patients and healthy controls were included in the current study. The patients were diagnosed with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), vascular dementia (VaD), or frontotemporal dementia (FTD). RESULTS: We found that Q-Alb was significantly different between the groups (p = 0.002, F = 3.874). Patients with DLB and VaD showed the largest Q-Alb. Although not significant for CSF total protein, we found the same overall pattern for DLB and VaD. When examining confounding factors, we found a positive association with age and a lower Fazekas score in DLB as compared to VaD. CONCLUSION: These results suggest that Q-Alb can contribute to our understanding of the pathophysiological mechanisms in DLB, and Q-Alb may serve as a supplementary diagnostic marker. Furthermore, we found a positive association with age, which may be due to differences in vascular co-morbidities. In addition, in patients with DLB, the increased Q-Alb is not due to vascular lesions. Studies are needed to validate the possible diagnostic value of Q-Alb in a larger cohort.