Is serum albumin a pivotal biomarker in anticipating acute pancreatitis outcomes?

This study aimed to assess the significance of serum albumin levels within 24 h of patient admission in correlation with the incidence of outcomes and mortality in patients diagnosed with acute pancreatitis. A retrospective study was conducted over a 5-year period, from January 2018 to December 2023, at the Mohammed VI University Hospital in Oujda, Morocco. The study included 371 patients diagnosed with acute pancreatitis. Hypoalbuminemia (≤ 30 g/L) was observed in 124 patients (33.4% of cases), and these patients had a higher mean age compared to those with normal albumin levels (P = 0.003). Hypoalbuminemia was significantly associated with persistent Systemic Inflammatory Response Syndrome (SIRS) (70.8% vs. 29.2%, P = 0.000), a higher BISAP score (66.7% vs. 33.3%, P = 0.000), and a higher CTSI score (51.7% vs. 48.3%, P = 0.000). Hypoalbuminemia was also associated with the presence of pleural effusion (P = 0.000). The mortality in the sample was 4.6%, and it was significantly associated with hypoalbuminemia (76.5%, P = 0.000). In conclusion, serum albumin levels within 24 h of patient admission appear to be a significant prognostic biomarker in acute pancreatitis, particularly in anticipating persistent organ failure and mortality.

The Effect of Nutritional Status in the Treatment of Periprosthetic Joint Infections in Total Hip Arthroplasty.

BACKGROUND: Periprosthetic joint infections (PJIs) continue to be a complication that plagues arthroplasty. Albumin is a surrogate marker for nutrition as well as chronic inflammation, and hypoalbuminemia increases the risk of complications in arthroplasty. Patients with PJI are at increased risk for malnutrition and complications. This study's objective was to analyze patients who underwent treatment of PJI following total hip arthroplasty and investigate the outcome with regards to albumin levels. METHODS: Overall, 48 patients who underwent surgery for a total hip PJI at 1 institution were reviewed. Albumin and C-reactive protein were recorded preoperatively and 2 to 3 weeks postoperatively. Treatment failure was determined by further surgical treatment for PJI or repeat infection, as determined by Musculoskeletal Infection Society guidelines. RESULTS: A debridement, antibiotics, and implant retention procedure was performed in 39 patients, and explant with the placement of an antibiotic spacer was performed in 9. Preoperative mean albumin levels were significantly decreased in patients who failed to clear their infection compared to patients who remained infection-free (2.5 versus 3.3, P < .001). Postoperative albumin levels decreased in this same population (2.6 versus 3.8, P < .001). C-reactive protein was elevated in patients who failed to clear their infection preoperatively (19.9 versus 7.5, P < .001) and postoperatively (7.0 versus 1.7, P < .001). The average time to repeat surgical treatment for their PJI was 9 months CONCLUSIONS: Lower albumin levels are observed in patients with PJI who failed to remain infection-free after surgery. Albumin is a surrogate marker for nutrition, and low albumin is associated with poor immune function. Hypoalbuminemia is found with chronic inflammation as well as malnutrition. Nutritional reserves are diverted to the acute inflammatory response during an infection, which can lead to a deficient state. Further research may develop treatments to alter this modifiable risk factor. LEVEL OF EVIDENCE: Level 4.

[Research progress on detection techniques for effective albumin concentration].

Hypoalbuminemia is one of the important clinical features of decompensated cirrhosis. As the disease progresses, not only does the total albumin concentration decrease, but so does the proportion of albumin that remains structurally and functionally intact. The structural and functional integrity of albumin is essential for its normal physiological role in the body. This led to the concept of "effective albumin concentration," which may be much lower than the total albumin concentration routinely measured clinically in patients with advanced cirrhosis. Liquid chromatography-tandem mass spectrometry, and electron paramagnetic resonance (EMR) are emerging technologies for effective albumin concentration detection, showing promising clinical application prospects, but research in patients with cirrhosis is still in the preliminary stage. Therefore, this article will comprehensively summarize the latest research on the aspects of effective albumin detection methods, liquid chromatography-tandem mass spectrometry, and electron paramagnetic resonance, as well as their applications.

Hypoalbuminemia in patients following their recovery from severe coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) is caused by a contagious virus that has spread to more than 200 countries, territories, and regions. Thousands of studies to date have examined all aspects of this disease, yet little is known about the postrecovery status of patients, especially in the long term. Here, we examined erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum albumin biomarkers in patients with a history of severe and mild-to-moderate COVID-19 following their recovery. In patients with severe COVID-19 serum albumin had a strong negative correlation with both ESR and CRP levels (R2 = - 0.861 and R2 = - 0.711), respectively. Also, there was a positive correlation between ESR and CRP level (R2 = 0.85) in the same group. However, there was no correlation between these biomarkers among mild-to-moderate COVID-19 patients. In addition, no correlation was recorded between the severe and mild-to-moderate COVID-19 groups. This finding highlights the sustained elevation of ESR and CRP level and reduced serum albumin level that may persist postrecovery in patients with a history of severe COVID-19.

Treatment patterns and outcomes of older patients with mantle cell lymphoma in an Asian population.

BACKGROUND: Significant progress has been made in the treatment outcomes of mantle cell lymphoma (MCL) since the introduction of cytarabine and rituximab in modern regimens. However, older patients may not readily tolerate these agents nor derive benefit. We investigated the impact of age on treatment patterns and clinical outcomes of MCL patients in an Asian population. METHODS: A retrospective study was conducted on patients (n = 66) diagnosed with MCL at the National Cancer Centre Singapore between 1998 and 2018. The median follow-up duration was 40 months. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. RESULTS: The median age of the cohort was 59 years (range, 26-84), with a male predominance (73%). The majority (86%) had advanced stage 3-4 disease at diagnosis. Compared with younger patients, older patients aged ≥60 years (n = 32; 48.5%) presented more frequently with B-symptoms (75% vs 38%, p = 0.0028), anaemia (75% vs 35%, p = 0.0013), and carried higher prognostic risk scores (sMIPI high risk 84% vs 56%, p = 0.016). Non-cytarabine-based induction chemotherapy was more commonly administered in older patients (76% vs 32%, p = 0.0012). The 5-year overall survival (OS) and progression-free survival (PFS) was 68 and 25% respectively. In a multivariable model, older age (HR 3.42, 95%CI 1.48-7.92, p = 0.004) and anemia (HR 2.56, 95%CI 1.10-5.96, p = 0.029) were independently associated with poorer OS while older age (HR 2.24, 95%CI 1.21-4.14, p = 0.010) and hypoalbuminemia (HR 2.20, 95%CI 1.17-4.13, p = 0.014) were independently associated with poorer PFS. In an exploratory analysis, maintenance rituximab following induction chemotherapy improved PFS in younger patients, with median PFS of 131 months and 45 months with or without maintenance therapy respectively (HR 0.39, 95%CI 0.16-0.93, p = 0.035). In contrast, no survival benefit was observed in older patients. CONCLUSIONS: We demonstrated in our analysis that older patients with MCL may harbor adverse clinical features and may not derive benefit from maintenance rituximab, highlighting the need for further research in this area of need.

Population Pharmacokinetic Analysis and Dosing Optimization Based on Unbound Daptomycin Concentration and Cystatin C in Nonobese Elderly Patients with Hypoalbuminemia and Chronic Kidney Disease.

PURPOSE: This study evaluated the population pharmacokinetics of daptomycin in nonobese elderly patients with hypoalbuminemia and chronic kidney disease (CKD) using the glomerular filtration rate estimated from cystatin C (eGFRcys) and estimated its optimal dose. METHODS: We performed population pharmacokinetic analysis of the unbound concentrations of daptomycin. The probability of target attainment of 90% for achieving an area under the concentration-time curve of unbound daptomycin at steady state/ minimum inhibitory concentration ratio of ≥66.6 was stochastically simulated. RESULTS: In the population pharmacokinetic analysis of 25 patients aged ≥65 years, the two-compartment model using eGFRcys and age as covariates of clearance in central compartment of unbound daptomycin were optimal. The unbound fraction rate (fu) was 0.05-0.14. According to the Monte Carlo simulation, the optimal doses for patients with eGFRcys of 20-60 mL/min and aged 65-95 years were calculated as 200-500 mg q24h. CONCLUSION: These results suggest that establishing the dose using total concentrations may result in under- or overestimation caused by alterations in fu. The optimal dose for nonobese elderly patients with hypoalbuminemia and CKD depends on eGFRcys and age, and a standard dose may be insufficient for some patients.

Tolerability of Highly Protein Bound Targeted Oral Oncolytic Drugs in Patients With Hypoalbuminemia: A Retrospective Analysis.

BACKGROUND: Hypoalbuminemia is commonly observed in cancer patients. Given the pharmacokinetic interactions between serum proteins and protein bound medications, administration of highly protein bound targeted oral oncolytic drugs may result in elevated unbound drug levels and decreased tolerability in those with hypoalbuminemia. OBJECTIVE: To describe the impact of hypoalbuminemia on oral oncolytic drug tolerability. METHODS: A retrospective study was conducted of adult patients receiving treatment with targeted oral oncolytic drugs with ≥95% protein binding. The primary end point of this study was to compare time to discontinuation resulting from documented toxicity in those with and without hypoalbuminemia. RESULTS: The study included 143 patients receiving 16 targeted oral oncolytic drugs (42% with hypoalbuminemia, 58% without hypoalbuminemia). Adverse events were common, with similar incidence among patients with and without hypoalbuminemia (73% vs 76%, respectively; P = 0.727). Median time to therapy discontinuation resulting from documented toxicity was significantly shorter in those with hypoalbuminemia (22 months vs not reached; P = 0.003). Cox regression demonstrated that hypoalbuminemia was the only significant risk factor for shorter time to discontinuation resulting from documented adverse effects (hazard ratio = 3.0; 95% CI = 1.15-8.0; P = 0.025). CONCLUSION AND RELEVANCE: This represents the first report of the impact of hypoalbuminemia on tolerability of highly protein bound oral oncolytic drugs, demonstrating that patients with hypoalbuminemia may be at increased risk for early discontinuation resulting from toxicity. Given the importance of maintaining dose intensity in patients receiving oncolytic therapy, albumin levels should be monitored throughout treatment and supportive care maximized in those developing hypoalbuminemia.

A randomized trial of albumin infusion to prevent intradialytic hypotension in hospitalized hypoalbuminemic patients.

BACKGROUND: Intradialytic hypotension (IDH) is a frequent complication of intermittent hemodialysis (IHD), occurring from 15 to 50% of ambulatory sessions, and is more frequent among hospitalized patients with hypoalbuminemia. IDH limits adequate fluid removal and increases the risk for vascular access thrombosis, early hemodialysis (HD) termination, and mortality. Albumin infusion before and during therapy has been used for treating IDH with the varying results. We evaluated the efficacy of albumin infusion in preventing IDH during IHD in hypoalbuminemic inpatients. METHODS: A randomized, crossover trial was performed in 65 AKI or ESKD patients with hypoalbuminemia (albumin < 3 g/dl) who required HD during hospitalization. Patients were randomized to receive 100 ml of either 0.9%sodium chloride or 25% albumin intravenously at the initiation of each dialysis. These two solutions were alternated for up to six sessions. Patients' vital signs and ultrafiltration removal rate were recorded every 15 to 30 min during dialysis. IDH was assessed by different definitions reported in the literature. All symptoms associated with a noted hypotensive event as well as interventions during the dialysis were recorded. RESULTS: Sixty-five patients were submitted to 249 sessions; the mean age was 58 ([Formula: see text] 12), and 46 (70%) were male with a mean weight of 76 ([Formula: see text] 18) kg. The presence of IDH was lower during albumin sessions based on all definitions. The hypotension risk was significantly decreased based on the Kidney Disease Outcomes Quality Initiative definition; (15% with NS vs. 7% with albumin, p = 0.002). The lowest intradialytic SBP was significantly worse in patients who received 0.9% sodium chloride than albumin (NS 83 vs. albumin 90 mmHg, p = 0.035). Overall ultrafiltration rate was significantly higher in the albumin therapies [NS - 8.25 ml/kg/h (- 11.18 5.80) vs. 8.27 ml/kg/h (- 12.22 to 5.53) with albumin, p = 0.011]. CONCLUSION: In hypoalbuminemic patients who need HD, albumin administration before the dialysis results in fewer episodes of hypotension and improves fluid removal. Albumin infusion may be of benefit to improve the safety of HD and achievement of fluid balance in these high-risk patients. ClinicalTrials.gov Identifier: NCT04522635.

Independent and joint effects of high-sensitivity c-reactive protein and hypoalbuminemia on long-term all-cause mortality among coronary artery disease: a prospective and multicenter cohort study.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) plays an important role in hypoalbuminemia as a representative of inflammation, which is closely associated with poor prognosis among patients with coronary artery disease (CAD). The present study aimed to evaluate the independent and joint effects of high hs-CRP levels and hypoalbuminemia on long-term mortality among CAD patients. METHODS: A total of 1449 CAD patients were included from a prospective, multicenter, observational cohort study (REICIN, NCT01402232) of patients referred for coronary angiography (CAG). The primary endpoint was long-term all-cause death. RESULTS: During a median follow-up of 2.9 (2.0-3.0) years, a total of 107 (7.4%) patients died. The long-term mortality was higher among CAD patients with high hs-CRP levels (> 3 mg/L) than those with the low hs-CRP levels (≤ 3 mg/L; 10.7% versus 4.1%; hazard ratio [HR] 2.49; 95% confidence interval [CI] 1.48-4.17). Similarly, CAD patients with hypoalbuminemia had higher mortality than those without hypoalbuminemia (12.2% versus 4.9%; HR 1.93; 95% CI 1.20-3.08). When hs-CRP and albumin were combined, CAD patients with high hs-CRP levels (> 3 mg/L) and with hypoalbuminemia were at the highest risk of death compared with their reference group (hs-CRP ≤ 3 mg/L and albumin > 35 g/L; HR 3.79; 95% CI 1.91-7.52). CONCLUSIONS: High hs-CRP levels and hypoalbuminemia were independently and jointly associated with long-term mortality among CAD patients. Patients with high hs-CRP levels and hypoalbuminemia had the highest risk of long-term mortality compared with other groups.

Evaluation of early unplanned readmissions and predisposing factors in an oncology clinic.

BACKGROUND: Unplanned readmission in the first 30 days after discharge is an important medical problem, although the data on cancer patients is limited. So we planned to evaluate the rates and causes of early readmissions and the predisposing factors. METHODS: Patients hospitalized in Hacettepe University Oncology services between August 2018 and July 2019 were included. The demographic features, tumor stages, regular drugs, last laboratory parameters before discharge, and readmissions in the first 30 days after discharge were recorded. The predisposing features were evaluated with univariate and multivariate analyses. RESULTS: A total of 562 hospitalizations were included. The mean age of the patients was 58.5 ± 14.5 years. Almost 2/3 of the hospitalizations were due to symptom palliation and infections. Eighty-three percent of the patients had advanced disease, and over 60% had an ECOG score of 2 and above. In the first 30 days after discharge, 127 patients were readmitted (22.6%). Advanced stage disease, presence of polypharmacy (5 or more regular drugs), hospitalization setting (emergency department (ED) vs. outpatient clinic), and hypoalbuminemia (< 3 gr/dL) were associated with a statistically significant increase in the risk of readmission. Among these factors, advanced-stage disease (HR: 2.847, 95% CI: 1.375-5.895), hospitalization from ED (HR: 1.832, 95% CI: 1.208-2.777), and polypharmacy (HR: 1.782, 95% CI: 1.173-2.706) remained significant in multivariate analyses. CONCLUSIONS: In this study, 22% of cancer patients had early readmissions. The readmission risk increased in patients with advanced disease, hospitalization from ED, and polypharmacy. The optimal post-discharge plan may reduce readmissions in all oncology patients, with priority for these patient groups.

Low serum albumin levels and in-hospital outcomes in patients with ST segment elevation myocardial infarction.

BACKGROUND AND AIMS: Low serum albumin (SA) is associated with an increased risk of long-term adverse events (AEs) among patients with chronic coronary syndromes. Its prognostic role in patients with ST-elevation myocardial infarction (STEMI) is less clear. To investigate the association between low SA and in-hospital AEs in STEMI patients. METHODS AND RESULTS: Multicenter retrospective cohort study of 220 STEMI patients undergoing primary percutaneous coronary intervention within 12 h from the onset of symptoms. Hypoalbuminemia was defined by serum SA <35 g/L. SA. In-hospital AEs were defined as cardiogenic shock, resuscitated cardiac arrest and death. Median SA was 38 (IQR 35.4-41.0) g/L and 37 (16.8%) patients showed hypoalbuminemia (<35 g/L) on admission. Patients with hypoalbuminemia were older, more frequently women and diabetics, prior CAD and HF. Furthermore, they showed lower hemoglobin levels and impaired renal function. At multivariable logistic regression analysis, diabetes (odds ratio [OR]:4.59, 95% confidence interval [CI] 1.71-12.28, p = 0.002) and haemoglobin (OR:0.52, 95%CI 0.37-0.72, p < 0.001) were associated with low SA. In a subgroup of 132 patients, SA inversely correlated with D-Dimer (rS -0.308, p < 0.001). Globally, twenty-eight (14.6%) AEs were recorded. Hypoalbuminemia (OR:3.43, 95%CI 1.30-9.07, p = 0.013), high-sensitive (HS)-Troponin peak above median (OR:5.41, 95%CI 1.99-14.7, p = 0.001), C-reactive protein (CRP) peak above median (OR:6.03, 95%CI 2.02-18.00, p = 0.001), and in-hospital infection (OR:3.61, 95%CI 1.21-10.80, p = 0.022) were associated with AEs. CONCLUSION: Low SA levels are associated with worse in-hospital AEs in STEMI patients, irrespective of HS-troponin and CRP plasma levels. Our findings suggest that low SA may contribute to the pro-thrombotic phenotype of these patients.

Hypoalbuminemia is Associated with Mortality in Patients Undergoing Lower Extremity Amputation.

BACKGROUND: Poor nutritional status is common among patients undergoing lower extremity amputation (LEA). In this study, the association between preoperative hypoalbuminemia, a marker for malnutrition, and postoperative mortality in patients undergoing LEA was explored. METHODS: Data on patients undergoing LEA between 2005 and 2017 were retrospectively analyzed from the prospectively collected American College of Surgeons National Surgical Quality Improvement Program database. Patients were divided into clinically relevant categories based on their serum albumin level (<2.5, 2.5-3.39, ≥3.4 g/dl) and were further stratified according to amputation level. Operative death was compared across groups and multivariable logistic regression was performed to estimate risk-adjusted odds ratio (AOR). RESULTS: In 35,383 patients, the rate of 30-day postoperative mortality was 7.6% (n = 2693). Mortality rate was highest in patients with very low albumin levels (11%) as compared to low (6.8%) and normal levels (3.9%). On multivariable analysis, lower albumin levels emerged as a risk-adjusted independent predictor of mortality. After risk-adjustment, patients with very low albumin levels (AOR [95% CI]: 2.25 [1.969-2.56], P < 0.001) and low albumin levels (AOR [95% CI]: 1.42 [1.239-1.616], P < 0.001) had higher odds of mortality when compared to patients with normal albumin levels. On sensitivity analysis, a similar trend was seen in patients undergoing above knee amputation but not in patients undergoing minor amputations. CONCLUSIONS: In patients undergoing major LEA, hypoalbuminemia is associated with an increased risk of postoperative mortality in a dose response manner, specifically in above knee amputations. Monitoring and optimizing patients' nutritional status before surgery, when possible, may be warranted and should be further explored.

Clinical characteristics of cardiovascular patients with extremely low levels of high-density lipoprotein cholesterol.

BACKGROUND: Extremely low levels of high-density lipoprotein cholesterol (HDL-C) are related to high cardiovascular mortality. The underlying mechanism is not well known. This research aims to study the clinical characteristics of cardiovascular patients with extremely low levels of HDL-C. METHODS: All cardiovascular patients in a single Chinese cardiology center that were admitted from January to December 2019 were reviewed. The clinical characteristics of those with HDL-C<20 mg/dL were investigated. RESULTS: A total of 20,655 individuals were enrolled. Of these, 52.17 % were males, and the average age was 58.20 ± 12.98 years old. The prevalence of HDL-C<20 mg/dL was 0.47 % for all patients (N=98) and 1.05 % for inpatients. Of those with HDL-C<20 mg/dL, 88.8 % were inpatients, and 77.6 % were males. Their average age was 60.7 ± 15.1 years. Compared with matched patients with normal HDL-C, systemic inflammation (OR= 5.556, 95% CI 2.798-11.030), hypoalbuminemia (OR=5.714, 95% CI 2.702-12.085), hyperuricemia (OR=5.156, 95% CI 2.560-10.386), low T3 syndrome (OR=4.278, 95% CI 1.627-11.245), anemia (OR=3.577, 95% CI 1.680-7.617), diabetes (OR=3.534, 95% CI 1.693-7.376) and hypertriglyceridemia (OR=2.493, 95% CI 1.264-4.918) were identified as adverse concomitant factors of extremely low HDL-C. HDL-C levels were inversely correlated with the total risk scores in patients with HDL-C<20 mg/dL (r=-0.381, P<0.001) and more significantly correlated in patients with HDL-C<15 mg/dL (r=-0.511, P=0.004). CONCLUSIONS: Extremely low levels of HDL-C tend to occur more frequently in males, older individuals and inpatients. For cardiovascular patients, extremely low levels of HDL-C are usually due to the presence of multiple adverse factors with relatively severe conditions. This could explain the high cardiovascular mortality of individuals with extremely low levels of HDL-C.

Preoperative malnutrition in patients with colorectal cancer.

Preoperative malnutrition in patients with colorectal cancer is associated with several postoperative consequences and poorer prognosis. Currently, there is a lack of a universal screening tool to assess nutritional status, and intervention to treat preoperative malnutrition is often neglected. This review summarizes and compares preoperative screening and interventional tools to help providers optimize malnourished patients with colorectal cancer for surgery. We found that nutritional screenings, such as the Subjectibe Global Assessment, Patient-Generated Subjective Global Assessment, Prognostic Nutritional Index, Nutrition Risk Index, Malnutrition Universal Screening Tool, Nutrition Risk Screening 2002, Nutrition Risk Score, serum albumin, and prealbumin, have all effectively predicted postoperative outcome. Physicians should consider which of these tools best fits their needs based on the their mode of assessment, efficiency, and specified parameters. Additionally, preoperative nutritional support, such as trimodal prehabilitation, modified peripheral parenteral nutrition, and N-3 fatty acid and arginine supplementation, which have also benefited patients postoperatively, ought to be implemented appropriately according to their ease of execution. Given the high prevalence of preoperative malnutrition in patients undergoing surgery for colorectal cancer, it is essential that health care providers assess and treat this malnutrition to reduce postoperative complications and length of hospital stay, and to improve prognosis to augment a patient's quality of care.La malnutrition préopératoire chez les patients atteints d'un cancer colorectal est associée à plusieurs complications postopératoires et à un pronostic plus sombre. Il n'existe actuellement aucun outil universel d'évaluation du statut nutritionnel, et les mesures visant à corriger la malnutrition préopératoire font souvent défaut. La présente revue résume et compare les outils de dépistage et d'intervention préopératoires pour aider les professionnels à améliorer l'état des patients dénutris qui doivent subir une chirurgie pour le cancer colorectal. Nous avons constaté que le dépistage nutritionnel à l'aide de questionnaires tels que l'Évaluation globale subjective, l'Index nutritionnel pronostique, l'Outil universel de dépistage de la malnutrition, NRS 2002 (Nutrition Risk Screening 2002), l'évaluation du risque nutritionnel, et le dosage de l'albumine et de la préalbumine sériques, a permis de prédire avec justesse l'issue de la chirurgie. Les médecins devraient vérifier lequel de ces outils est le mieux adapté à leurs besoins selon leur modalité d'évaluation, leur efficience et autres paramètres spécifiques. Également, un soutien nutritionnel préopératoire, comme la préadaptation trimodale, la nutrition parentérale périphérique modifiée et les suppléments d'acides gras N-3 et d'arginine, qui ont aussi donné des résultats postopératoires favorables, devrait être appliqué selon sa facilité d'administration. Étant donné la forte prévalence de la malnutrition préopératoire chez les patients soumis à une chirurgie pour cancer colorectal, les professionnels de la santé se doivent d'évaluer et de corriger la malnutrition afin de prévenir les complications postopératoires, d'abréger la durée du séjour hospitalier, et d'améliorer ainsi le pronostic et la qualité des soins.

Prediction of Serum-Free and Cerebrospinal Fluid Valproic Acid Levels in Patients With Hypoalbuminemia After Craniotomy.

BACKGROUND: In patients with hypoalbuminemia after craniotomy, total serum concentrations of valproic acid (VPA) may provide poor clinical insights, owing to saturated protein binding and increased unbound fractions. However, very few clinical laboratories routinely analyze free concentrations of the drug. The aim of this study was to develop a model to predict serum-free and cerebrospinal fluid (CSF) levels of VPA based on its total concentration and to investigate the model's applicability. METHODS: Total serum and CSF concentrations of VPA in 79 patients were measured using a validated immunoassay between January 2015 and December 2015. The demographic, clinical, and laboratory information of patients were retrieved from medical records. A multiple linear regression analysis was adopted to determine the potential variations and establish the functional relationship between CSF concentration and significant clinical factors. RESULTS: Based on the stepwise multiple linear regression analysis performed using the natural logarithm of the concentration of VPA in the CSF as the dependent variable, serum concentrations of VPA (X1, ß' = 0.844), serum albumin concentration (X2, ß' = -0.393), and CSF protein concentration (X3, ß' = 0.098) were identified as the 3 variables that significantly predicted the dependent variable: (Equation is included in full-text article.), with a coefficient of determination (R) of 0.874. As the CSF protein level is often unavailable, the model was redefined to include 2 variables-serum concentrations of VPA (X1, ß' = 0.840) and serum albumin concentration (X2, ß' = -0.359): (Equation is included in full-text article.), with R = 0.813. CONCLUSIONS: Based on total VPA and serum albumin concentrations, we developed a model to predict serum-free and CSF levels of VPA. This model is useful for correcting dose adjustment in patients with hypoalbuminemia after craniotomy.

A prediction model of contrast-associated acute kidney injury in patients with hypoalbuminemia undergoing coronary angiography.

BACKGROUND: Risk stratification is recommended as the key step to prevent contrast-associated acute kidney injury (CA-AKI) among at-risk patients following coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). Patients with hypoalbuminemia are prone to CA-AKI and do not have their own risk stratification tool. Therefore, this study developed and validated a new model for predicting CA-AKI among hypoalbuminemia patients CAG/PCI. METHODS: 1272 patients with hypoalbuminemia receiving CAG/PCI were enrolled and randomly allocated (2:1 ratio) into the development cohort (n = 848) and the validation cohort (n = 424). CA-AKI was defined as an increase of ≥0.3 mg/dL or 50% in serum creatinine (SCr) compared to baseline in the 48 to 72 h after CAG/PCI. A prediction model was established with independent predictors according to stepwise logistic regression, showing as a nomogram. The discrimination of the new model was evaluated by the area under the curve (AUC) and was compared to the classic Mehran CA-AKI model. The Hosmer-Lemeshow test was conducted to assess the calibration of our model. RESULTS: Overall, 8.4% (71/848) patients of the development group and 11.2% (48/424) patients of the validation group experienced CA-AKI. A new nomogram included estimated glomerular filtration rate (eGFR), serum albumin (ALB), age and the use of intra-aortic balloon pump (IABP); showed better predictive ability than the Mehran score (C-index 0.756 vs. 0.693, p = 0.02); and had good calibration (Hosmer-Lemeshow test p = 0.187). CONCLUSIONS: We developed a simple model for predicting CA-AKI among patients with hypoalbuminemia undergoing CAG/PCI, but our findings need validating externally. TRIAL REGISTRATION: http://www.ClinicalTrials.gov NCT01400295 , retrospectively registered 21 July 2011.

Serum albumin, cardiometabolic and other adverse outcomes: systematic review and meta-analyses of 48 published observational cohort studies involving 1,492,237 participants.

Objectives. A general body of evidence suggests that low serum albumin might be associated with increased risk of adverse cardiometabolic outcomes, but findings are divergent. We aimed to quantify associations of serum albumin with the risk of type 2 diabetes (T2D), cardiovascular disease (CVD), all-cause mortality, and other adverse outcomes using a systematic review and meta-analyses of published observational cohort studies. Design. MEDLINE, Embase, Web of Science, and manual search of relevant bibliographies were systematically searched to January 2020. Relative risks (RRs) with 95% confidence intervals (CIs) comparing top versus bottom thirds of serum albumin levels were pooled. Results. Fifty-four articles based on 48 unique observational cohort studies comprising of 1,492,237 participants were eligible. Multivariable adjusted RRs (95% CIs) comparing the top vs bottom third of serum albumin levels were: 1.03 (0.86-1.22) for T2D; 0.60 (0.53-0.67) for CVD; 0.74 (0.66-0.84) for coronary heart disease (CHD); 0.57 (0.36-0.91) for CHD death; 0.76 (0.65-0.87) for myocardial infarction; 0.66 (0.55-0.77) for all-cause mortality; 0.71 (0.61-0.83) for venous thromboembolism; 0.65 (0.48-0.88) for cancer mortality; and 0.62 (0.46-0.84) for fracture. Heterogeneity between contributing studies of T2D was partly explained by sample sizes of studies (p for meta-regression = .035). Conclusions. Elevated levels of serum albumin are associated with reduced risk of vascular outcomes, all-cause mortality, certain cancers, and fracture. Inconsistent findings for T2D may be attributed to selective reporting by studies. Further research is needed to assess any potential causal relevance to these findings and the role of serum albumin concentrations in disease prevention.Systematic review registration: PROSPERO 2019: CRD42019125869.

Antifungal prophylaxis with posaconazole tablet and oral suspension in patients with haematologic malignancy: Therapeutic drug monitoring, efficacy and risk factors for the suboptimal level.

BACKGROUND: Posaconazole is used to prevent invasive fungal infections (IFIs) in patients with haematologic malignancy. In this study, we compared plasma posaconazole concentrations (PPCs) and the incidence of breakthrough IFIs between patients with haematologic malignancy receiving posaconazole oral suspension vs tablet. METHODS: We retrospectively collected data on adult patients with haematologic malignancies who received posaconazole prophylaxis during chemotherapy from April 2014 through May 2018. A total of 242 cases with PPCs, 88 in the oral suspension group and 154 in the tablet group, were included in this study. RESULTS: Patients receiving tablets achieved a significantly higher mean PPC than did those on oral suspension (1.631 ± 0.878 µg/mL in the tablet group vs. 0.879 ± 0.585 µg/mL in the oral suspension group). One hundred and thirty-seven of 154 patients (89.0%) receiving tablets had PPCs of 0.7 µg/mL or more, while only 41 of 88 patients (46.6%) receiving oral suspension attained an optimal level (P < .001). The incidence of breakthrough IFIs was significantly higher in the oral suspension group compared with in the tablet group (14.8% of oral suspension vs. 4.5% of tablet; P = .005). In the analysis including patients receiving posaconazole tablets, hypoalbuminemia (< 3.5 g/dL) was found to be a risk factor associated with suboptimal levels (odds ratio: 8.872; 95% confidence interval: 3.011 - 26.141; P < .001). CONCLUSIONS: Suboptimal PPCs in the tablet group were less common than those in the oral suspension group. Therapeutic drug monitoring may be still necessary even in patients receiving posaconazole tablets, especially in those with hypoalbuminemia.

Quantification of total and unbound cefuroxime in plasma by ultra-performance liquid chromatography tandem mass spectrometry in a cohort of critically ill patients with hypoalbuminemia and renal failure.

BACKGROUND: Pharmacokinetic studies of cefuroxime by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) have been limited to measurements of total concentrations. Here, we developed a robust method for quantifying total and unbound cefuroxime concentrations using UPLC-MS/MS and ultrafiltration in critically ill patients with hypoalbuminemia and renal failure. METHODS: Method validation included accuracy, linearity, precision, repeatability, recovery, and limit of quantification (LOQ). Feasibility of the method was performed on samples obtained from randomly selected intensive care unit (ICU) patients. Total and unbound cefuroxime concentrations were quantified using UPLC-MS/MS. Sampling times were categorized as trough (180-1 min prior to administration), peak (10-30 min after administration), mid (30-360 min after administration), and continuous (sampling during administration). Pharmacokinetic/pharmacodynamic (PK/PD) targets were unbound cefuroxime concentrations above 4 times the minimum inhibitory concentration (32 mg/L). RESULTS: Intra-assay and inter-assay precision was <3%. Recovery was 99.7%-100.3%, and LOQ was 0.1 mg/L. We included 11 patients (median age 72 years (range 54-77). Median albumin serum concentrations and eGFR were 19 g/L (range 11-40 g/L) and 48 mL/min/1.73 m2 (range 7-115 mL/min/1.73 m2 ), respectively. Median trough and mid concentrations of total cefuroxime were 22.27 mg/L (range 5.42-54.03 mg/L) and 71.49 mg/L (range 53.87-73.86 mg/L), and median unbound fraction was 75.42% (range 27.36%-99.75%). Median unbound cefuroxime concentrations were 11.94 mg/L (range 3.85-32.39 mg/L) (trough) and 55.62 mg/L (range 10.03-62.62 mg/L) (mid). CONCLUSION: The method is precise and accurate according to ISO 15189 and within the clinical range of cefuroxime (0.5-100 mg/L). The method was applied in ICU patients and is suitable for TDM on unbound cefuroxime concentrations.

Thigh sarcopenia and hypoalbuminemia predict impaired overall survival after infrainguinal revascularization in patients with critical limb ischemia.

OBJECTIVE: This study was performed to determine whether thigh sarcopenia can serve as a clinically relevant predictor of postoperative complications and overall survival after revascularization in patients with critical limb ischemia. METHODS: Patients who underwent preoperative computed tomography followed by infrainguinal revascularization from 2006 to 2015 were retrospectively analyzed. An axial computed tomography image was obtained at the midpoint of a line extending from the superior border of the patella to the greater trochanter of the femur. The thigh muscle area and bone area were measured. Thigh sarcopenia was defined as thigh muscle area/thigh bone area of <9. RESULTS: We included 117 patients with critical limb ischemia who underwent infrainguinal revascularization. The overall survival rates at two years were 86.5% and 55.1% in the thigh sarcopenia (-) and (+) groups, respectively (p < 0.01). The multivariate analysis showed that thigh sarcopenia (hazard ratio, 2.64; 95% confidence interval, 1.11-6.70; p = 0.03), cerebrovascular disease (hazard ratio, 3.18; 95% confidence interval, 1.31-7.36; p = 0.01), and serum albumin level (1 g/dL per increments) (hazard ratio, 0.41; 95% confidence interval, 0.21-0.81; p = 0.01) were the risk factors for overall survival two years after revascularization. CONCLUSION: Thigh sarcopenia is a risk factor for two-year overall survival in patients with critical limb ischemia after infrainguinal revascularization.