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World Journal of Gastroenterology Oct 2022Estimation of the functional reserve of the remnant liver is important to reduce morbidity and mortality. (Review)
Review
BACKGROUND
Estimation of the functional reserve of the remnant liver is important to reduce morbidity and mortality.
AIM
To estimate the functional reserve of the remnant liver in patients with hepatocellular carcinoma (HCC).
METHODS
We reviewed the medical records of 199 patients who underwent resection of HCC. Hepatic clearance of the remnant liver was calculated using fusion images of Tc-labelled galactosyl-human serum albumin liver scintigraphy and computed tomography. Posthepatectomy liver failure (PHLF) was classified according to the International Study Group of Liver Surgery. Complications was classified according to Clavien-Dindo classification. We analyzed by the risk factors for PHLF, morbidity and mortality with multivariate analysis.
RESULTS
Twenty-seven (30%) patients had major complications and 23 (12%) developed PHLF. The incidence of major complications increased with increasing albumin-bilirubin (ALBI) grade. The area under the curve values for hepatic clearance of the remnant liver, liver to heart-plus-liver radioactivity at 15 min (LHL15), and ALBI score predicting PHLF were 0.868, 0.629, and 0.655, respectively. The area under the curve for hepatic clearance of the remnant liver, LHL15, and ALBI score predicting major complications were 0.758, 0.594, and 0.647, respectively. The risk factors for PHLF and major complications were hepatic clearance of the remnant liver and intraoperative bleeding.
CONCLUSION
The measurement of hepatic clearance may predict PHLF and major complications for patients undergoing resection of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Hepatectomy; Liver Neoplasms; Retrospective Studies; Liver Failure; Bilirubin; Albumins; Postoperative Complications
PubMed: 36304091
DOI: 10.3748/wjg.v28.i38.5614 -
Kidney360 Jun 2023
Topics: Adult; Humans; Nephrosis, Lipoid; Chronic Disease; Recurrence; Albumins
PubMed: 37384885
DOI: 10.34067/KID.0000000000000169 -
Journal of Clinical Pharmacology Feb 2021Treatment of patients with biologics such as infliximab may trigger development of antidrug antibodies, which are associated with faster drug clearance, reduced... (Randomized Controlled Trial)
Randomized Controlled Trial
Treatment of patients with biologics such as infliximab may trigger development of antidrug antibodies, which are associated with faster drug clearance, reduced treatment efficacy, and increased risk of infusion-related reactions. The aim of this study was to identify predictors of baseline infliximab clearance and early antidrug antibody formation. Pharmacokinetic and pharmacokinetic/pharmacodynamic models for infliximab were developed using 21 178 observations from 859 patients from the PLANETRA (ClinicalTrials.gov identifier: NCT01217086) and PLANETAS (NCT01220518) studies in rheumatoid arthritis and ankylosing spondylitis, respectively, to address the specified aims. Infliximab pharmacokinetics were well described by a 2-compartment model with linear mean estimated baseline clearance of 0.26 L/day. Alongside increased body weight, serum C-reactive protein, and antidrug antibody concentrations and decreased serum albumin, elevated serum glucose levels predicted higher clearance. In patients with rheumatoid arthritis, baseline infliximab clearance and body weight were the only identified predictors of early antidrug antibody detection. The odds ratio for antidrug antibody detection for each 0.1 L/day increase in baseline infliximab clearance was 1.78 (95% confidence interval, 1.50-2.12); for each 10-kg increase in body weight, this was 1.19 (1.06-1.33). Here we describe increased serum glucose levels as a novel independent predictor of baseline infliximab clearance. Estimates of baseline infliximab clearance should be incorporated to guide dosing modifications and/or antidrug antibody prophylaxis in clinical practice.
Topics: Adolescent; Adult; Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Blood Glucose; Body Weight; C-Reactive Protein; Double-Blind Method; Female; Humans; Infliximab; Male; Metabolic Clearance Rate; Middle Aged; Serum Albumin; Spondylitis, Ankylosing; Young Adult
PubMed: 32905628
DOI: 10.1002/jcph.1732 -
Journal of Clinical Pharmacology Jan 2023Patritumab deruxtecan is an antibody-drug conjugate consisting of a fully human monoclonal antibody against human epidermal growth factor receptor 3 (HER3) attached to...
Patritumab deruxtecan is an antibody-drug conjugate consisting of a fully human monoclonal antibody against human epidermal growth factor receptor 3 (HER3) attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. As part of the pharmacometric analysis informing dose selection for later-stage development, population pharmacokinetics (PK) analysis of patritumab deruxtecan was conducted with pooled serum PK data from patients with HER3-expressing solid tumors (from 3 phase 1/2 studies in breast, lung, and colorectal cancer; N = 425) treated over the dose range of 1.6 to 8.0 mg/kg intravenously every 3 weeks. Population PK modeling for deruxtecan (DXd)-conjugated antibody (representing patritumab deruxtecan) and unconjugated MAAA-1181a (DXd, payload) was carried out sequentially. DXd-conjugated antibody PK was described using a 2-compartment model with parallel linear and nonlinear clearance. Unconjugated DXd PK was described using a 1-compartment model with linear clearance and release of DXd as a first-order, time-dependent function of the level of DXd-conjugated antibody in the central compartment. Preliminary covariate evaluation was conducted for prespecified covariates of pharmacological plausibility and clinical interest. The final model retained weight (on linear clearance and central volume) and albumin level, sex, and tumor type (on linear clearance) for DXd-conjugated antibody, and weight (on release rate constant) and hepatic function (on clearance) for unconjugated DXd. Effects of these covariates on the exposure metrics were generally mild and did not require dose adjustment for subpopulations in subsequent development. Further PK characterization for patritumab deruxtecan will evolve with emerging data.
Topics: Humans; Antibodies, Monoclonal, Humanized; Camptothecin; Immunoconjugates; Neoplasms; Trastuzumab; Receptor, ErbB-2
PubMed: 36053771
DOI: 10.1002/jcph.2137 -
International Journal of Molecular... Jan 2023A hallmark of acute respiratory distress syndrome (ARDS) is an accumulation of protein-rich alveolar edema that impairs gas exchange and leads to worse outcomes. Thus,...
A hallmark of acute respiratory distress syndrome (ARDS) is an accumulation of protein-rich alveolar edema that impairs gas exchange and leads to worse outcomes. Thus, understanding the mechanisms of alveolar albumin clearance is of high clinical relevance. Here, we investigated the mechanisms of the cellular albumin uptake in a three-dimensional culture of precision-cut lung slices (PCLS). We found that up to 60% of PCLS cells incorporated labeled albumin in a time- and concentration-dependent manner, whereas virtually no uptake of labeled dextran was observed. Of note, at a low temperature (4 °C), saturating albumin receptors with unlabeled albumin and an inhibition of clathrin-mediated endocytosis markedly decreased the endocytic uptake of the labeled protein, implicating a receptor-driven internalization process. Importantly, uptake rates of albumin were comparable in alveolar epithelial type I (ATI) and type II (ATII) cells, as assessed in PCLS from a SftpcCre: tdTomato mouse strain (defined as EpCAMCD31CD45tdTomatoSPCT1α for ATI and EpCAMCD31CD45tdTomatoSPCT1α for ATII cells). Once internalized, albumin was found in the early and recycling endosomes of the alveolar epithelium as well as in endothelial, mesenchymal, and hematopoietic cell populations, which might indicate transcytosis of the protein. In summary, we characterize albumin uptake in alveolar epithelial cells in the complex setting of PCLS. These findings may open new possibilities for pulmonary drug delivery that may improve the outcomes for patients with respiratory failure.
Topics: Mice; Animals; Alveolar Epithelial Cells; Epithelial Cell Adhesion Molecule; Clathrin; Lung; Epithelial Cells; Serum Albumin; Pulmonary Alveoli
PubMed: 36768968
DOI: 10.3390/ijms24032644 -
Annals of Gastroenterological Surgery Nov 2023Liver resection is an effective therapeutic option for patients with hepatocellular carcinoma. However, posthepatectomy liver failure (PHLF) remains a major cause of... (Review)
Review
Liver resection is an effective therapeutic option for patients with hepatocellular carcinoma. However, posthepatectomy liver failure (PHLF) remains a major cause of hepatectomy-related mortality, and the accurate prediction of PHLF based on preoperative assessment of liver functional reserve is a critical issue. The definition of PHLF proposed by the International Study Group for Liver Surgery has gained acceptance as a standard grading criterion. Liver function can be estimated using a variety of parameters, including routine blood biochemical examinations, clinical scoring systems, dynamic liver function tests, liver stiffness and fibrosis markers, and imaging studies. The Child-Pugh score and model for end-stage liver disease scores are conventionally used for estimating liver decompensation, although the alternatively developed albumin-bilirubin score shows superior performance for predicting hepatic dysfunction. Indocyanine green clearance, a dynamic liver function test mostly used in Japan and other Asian countries, serves as a quantitative estimation of liver function reserve and helps determine indications for surgical procedures according to the estimated risk of PHLF. In an attempt to improve predictive accuracy, specific evaluation of liver fibrosis and portal hypertension has gained popularity, including liver stiffness measurements using ultrasonography or magnetic resonance elastography, as well as noninvasive fibrosis markers. Imaging modalities, including Tc-99m-labeled galactosyl serum albumin scintigraphy and gadolinium-enhanced magnetic resonance imaging, are used for preoperative evaluation in combination with liver volume. This review aims to provide an overview of the usefulness of current options for the preoperative assessment of liver function in predicting PHLF.
PubMed: 37927928
DOI: 10.1002/ags3.12692 -
Scientific Reports Jul 2022The aim of this study was to evaluate the prognostic value of the Lactate to Albumin (L/A) ratio compared to that of lactate and lactate clearance in predicting outcomes... (Comparative Study)
Comparative Study Observational Study
Comparison of lactate/albumin ratio to lactate and lactate clearance for predicting outcomes in patients with septic shock admitted to intensive care unit: an observational study.
The aim of this study was to evaluate the prognostic value of the Lactate to Albumin (L/A) ratio compared to that of lactate and lactate clearance in predicting outcomes in patients with septic shock. This was a multi-center observational study of adult patients with septic shock, who admitted to intensive care units (ICUs) at Shohada and Imam Reza Hospitals, Tabriz, Iran, between Sept 2018 and Jan 2021. The area under the curve (AUC) of receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were used to explore associations of the L/A ratio, lactate and lactate clearance on the primary (mortality) and secondary outcomes [ICU length of stay (LOS), duration of mechanical ventilation (MV), need of renal replacement therapy (RRT) and duration of using vasopressors] at baseline, 6 h and 24 h of septic shock recognition. Best performing predictive value for mortality were related to lactate clearance at 24 h, L/A ratio at 6 h and lactate levels at 24 h with (AUC 0.963, 95% CI 0.918-0.987, P < 0.001), (AUC 0.917, 95% CI 0.861-0.956, P < 0.001), and (AUC 0.904, 95% CI 0.845-0.946, P < 0.001), respectively. Generally, the lactate clearance at 24 h had better prognostic performance for mortality and duration of using vasopressor. However, the L/A ratio had better prognostic performance than serum lactate and lactate clearance for RRT, ICU LOS and MV duration.
Topics: Adult; Albumins; Humans; Intensive Care Units; Lactic Acid; Prognosis; ROC Curve; Retrospective Studies; Shock, Septic
PubMed: 35906231
DOI: 10.1038/s41598-022-14764-z -
Peritoneal Dialysis International :... Jul 2022Transport of serum proteins from the circulation to peritoneal dialysate in peritoneal dialysis patients mainly focused on total protein. Individual proteins have hardly... (Review)
Review
Transport of serum proteins from the circulation to peritoneal dialysate in peritoneal dialysis patients mainly focused on total protein. Individual proteins have hardly been studied. We determined serum and effluent concentrations of four individual proteins with a wide molecular weight range routinely in the standardised peritoneal permeability analysis performed yearly in all participating patients. These include β-microglobulin, albumin, immunoglobulin G and α-macroglobulin. The dependency of transport of these proteins on their molecular weight and diffusion coefficient led to the development of the peritoneal protein restriction coefficient (PPRC), which is the slope of the relation between the peritoneal clearances of these proteins and their free diffusion coefficients in water, when plotted on a double logarithmic scale. The higher the PPRC, the more size restriction to transport. In this review, we discuss the results obtained on the PPRC under various conditions, such as effects of various osmotic agents, vasoactive drugs, peritonitis and the hydrostatic pressure gradient. Long-term follow-up of patients shows an increase of the PPRC, the possible causes of which are discussed. Venous vasculopathy of the peritoneal microcirculation is the most likely explanation.
Topics: Biological Transport; Dialysis Solutions; Humans; Peritoneal Dialysis; Peritoneum; Permeability; Protein Transport
PubMed: 35102776
DOI: 10.1177/08968608221075102 -
International Journal of Molecular... Dec 2022The care of systemic amyloidosis has improved dramatically due to improved awareness, accurate diagnostic tools, the development of powerful prognostic and companion... (Review)
Review
The care of systemic amyloidosis has improved dramatically due to improved awareness, accurate diagnostic tools, the development of powerful prognostic and companion biomarkers, and a continuous flow of innovative drugs, which translated into the blooming of phase 2/3 interventional studies for light chain (AL) and transthyretin (ATTR) amyloidosis. The unprecedented availability of effective drugs ignited great interest across various medical specialties, particularly among cardiologists who are now recognizing cardiac amyloidosis at an extraordinary pace. In all amyloidosis referral centers, we are observing a substantial increase in the prevalence of wild-type transthyretin (ATTRwt) cardiomyopathy, which is now becoming the most common form of cardiac amyloidosis. This review focuses on the oral drugs that have been recently introduced for the treatment of ATTR cardiac amyloidosis, for their ease of use in the clinic. They include both old repurposed drugs or fit-for-purpose designed compounds which bind and stabilize the TTR tetramer, thus reducing the formation of new amyloid fibrils, such as tafamidis, diflunisal, and acoramidis, as well as fibril disruptors which have the potential to promote the clearance of amyloid deposits, such as doxycycline. The development of novel therapies is based on the advances in the understanding of the molecular events underlying amyloid cardiomyopathy.
Topics: Humans; Amyloid Neuropathies, Familial; Prealbumin; Diflunisal; Cardiomyopathies; Amyloid
PubMed: 36555787
DOI: 10.3390/ijms232416145 -
Frontiers in Pharmacology 2022To develop a population pharmacokinetic (PopPK) model describing unbound teicoplanin concentrations in Chinese adult patients and perform Monte Carlo simulations to...
To develop a population pharmacokinetic (PopPK) model describing unbound teicoplanin concentrations in Chinese adult patients and perform Monte Carlo simulations to optimize the dosing regimens. The raw data for PopPK analysis in this study were collected from Chinese adult patients. A PopPK model of unbound teicoplanin was developed and Monte Carlo simulations were used to optimize the dosing regimens. The trough concentrations of unbound teicoplanin were targeted at 0.75 mg/L and 1.13 mg/L for most infection induced by Gram-positive bacteria and endocarditis or severe infections, respectively. A total of 103 teicoplanin unbound concentrations were collected from 72 Chinese adult patients. A one-compartment pharmacokinetic model with first-order elimination was established. The typical values of clearance and the volume of distribution were 11.7 L/h and 811 L, respectively. The clearance and volume of distribution of unbound teicoplanin were positively correlated with estimated glomerular filtration rate (eGFR) and serum albumin concentrations, respectively. Dosing simulation results showed that standard dosing regimens were unable to meet the treatment needs of all patients, and the dosing regimen need optimize based on eGFR and serum albumin concentrations. The high eGFR and serum albumin concentration were associated with reduced probability of achieving target unbound trough concentrations. We successfully characterized the pharmacokinetics of unbound teicoplanin in Chinese adult patients. Importantly, we further highlight the importance of guiding dosing through unbound drugs. To achieve safe and effective treatment, the dosing regimens need to be adjusted according to eGFR and serum albumin concentrations.
PubMed: 36506535
DOI: 10.3389/fphar.2022.1045895