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Key Words: adrenal, ACTH, cortisol, critical illness

Patients hospitalized with decompensated cirrhosis and a serum albumin level of less than 30 g per liter were randomly assigned to daily albumin infusions to raise the albumin level to 30 g per liter or higher or to standard care. Albumin infusions did not reduce the incidences of infection, kidney dysfunction, and death. More serious adverse events occurred in the albumin group.

In patients with severe sepsis, albumin replacement in addition to crystalloid administration conferred no benefit, as compared with crystalloids alone, with respect to mortality at 28 or 90 days. Post hoc analysis suggested a possible benefit in patients with septic shock. For decades, human albumin has been administered to patients to provide adequate oncotic pressure and intravascular volume. 1 In 1998, however, a report from the Cochrane Injuries Group Albumin Reviewers indicated that the administration of albumin may be potentially harmful in critically ill patients, as compared with the administration of crystalloid solutions. 2 Subsequent meta-analyses reported contradictory findings. 3 , 4 To clarify this issue, a large, double-blind, randomized trial (the Saline versus Albumin Fluid Evaluation [SAFE] study) 5 was conducted, in which 4% albumin solution was compared with normal saline as fluid replacement in critically ill patients, with results indicating that albumin administration was . . .

BackgroundDespite inadequate supply and potential contamination risk, human plasma has remained the only source for human serum albumin (pHSA) intravenous administration since the 1940s.ObjectiveWe sought to establish the safety and efficacy of OsrHSA, a recombinant HSA from bioengineered Oryza sativa (rice).DesignIn this multicentre, randomised, double-blind and positive-controlled study, patients with decompensated liver cirrhosis and serum albumin ≤30 g/L were recruited from 22 centres in China. The patients were randomly assigned to OsrHSA or pHSA (4:1) to once-daily intravenous injection (10 g or 20 g) until their serum albumin level reached 35 g/L, for a maximum of 2 weeks, with 2 weeks of follow-up. The primary outcome was the proportion of patients to reach a serum albumin level of 35 g/L (non-inferiority margin <−0.20). Outcomes were evaluated in patients who received the study drug and had at least one post-baseline serum albumin value (full analysis set, FAS). Safety was evaluated in all patients who received the study drug.ResultsBetween 22 March 2021 and 2 June 2022, 220 patients received OsrHSA (n=175) or pHSA (n=45). 216 patients were included in the FAS (OsrHSA, n=171; pHSA, n=45). Primary outcome of OsrHSA (130/171, 76%) was non-inferior to pHSA (34/45, 75.6%) (difference=0.5%; lower limit of 97.5% CI=−0.119). There was no significant difference between all secondary outcomes of OsrHSA and pHSA. There were no drug-related serious adverse events.ConclusionsRice-derived HSA is non-inferior to plasma-derived HSA in efficacy and safety. This finding should be confirmed in phase 3 trial.Trial registration number NCT04835480.

We studied osteogenesis induction after implantation of porous cryogenically structured 3D scaffolds based on chitosan, alginate, and serum albumin and containing a bioregulator from bovine serum into in vivo modeled experimental bone defect in rats. It was shown that such 3D-matrices are effective as osteoconductors due to their effect on osteoblast precursors. All types of bioregulator-loaded 3D materials promote active bone repair, which manifested in restoration of the dense bone tissue, formation of the bone marrow, and the recovery of osteons on day 14 after surgery. In animals receiving implantation of control 3D scaffolds without the bioregulator, the formation of dense fibrous tissue and spongy bone was observed by this term.

Background Aneurysmal subarachnoid hemorrhage (aSAH) is a dreadful acute neurological condition with an overwhelmingly high rate of associated morbidities and mortality. Despite leaping advancement in neurosurgical techniques and imaging modalities, there is no substantiative improvement in the overall prognosis for aSAH. Cerebral vasospasm remains the predominant cause of associated morbidities. Human albumin has been used in different neurological conditions, including head trauma, intracerebral hemorrhages, and ischemic strokes, with favorable outcomes. However, its beneficial use in aSAH has not been sufficiently explored until recently a published systematic review by our team. In view of the scarcity of published data and lack of robust evidence, our group has designed the first-ever RCT to compare the use of human albumin-enhanced fluid management versus standard fluid therapy with crystalloids in patients with aSAH. Methods This single-center open-label, prospective, parallel group randomized control trial will be conducted at Hamad General Hospital, Doha, Qatar, from August 2024 to July 2027. A sample size of 84 (42 in each arm) has been calculated to be sufficient to detect a clinically significant difference in the modified Rankin scale good score between two groups (human-albumin induced volume expansion therapy versus crystalloid only) for fluid management in aneurysmal subarachnoid hemorrhage patients. The primary outcome will be based on a dichotomized modified Rankin scale [good grades (0–2) and poor grades (3–6)], while the secondary outcome will include symptomatic vasospasm, transcranial Doppler velocities, and Pulse index Contour Cardiac Output (PiCCO) parameters. Discussion The trial aims to provide firsthand evidence on the beneficial use of human albumin to achieve an optimal fluid management regime to explore its potential role in improving clinical outcomes in patients with aSAH. Trial registration ClinicalTrials.gov NCT06548477. Registered on August 9, 2024. https://clinicaltrials.gov/search?term=NCT06548477 .

Background Fluid loading with crystalloids is the conventional treatment of major hemorrhage but might tend to create fluid overload. We studied hemodynamic profiles of fluid replacement therapies during major surgical hemorrhage and compared the ability of pulse pressure variation (PPV), plethysmographic variation index (PVI), cardiac output (CO) and Guyton´s approach to detect hypovolemia. Methods In this single center randomized controlled trial, fluid replacement therapy to treat hemorrhage in 42 patients was randomized to consist of either 5% albumin (12 mL/kg) or 20% albumin (3 mL/kg) over 30 min, both completed by Ringer lactate replacing blood loss in a 1:1 ratio, or Ringer solution alone in a 3:1 ratio. Measurements included CO, PPV, PVI, arterial and central venous pressures, heart rate (HR) and subsequent calculation of Guyton´s physiological parameters. CO was measured by an esophageal Doppler probe. Results The Ringer-only fluid program resulted in slight hypovolemia (mean, 313 mL), decreased mean arterial pressure (MAP), increased HR, PPV values and vasopressor requirement. The 5% and 20% albumin programs were more effective in filling the vascular system, as evidenced by higher mean circulatory filling pressure and unchanged or decreased PPV over the 5 h observation period. The 20% albumin increased the systemic vascular resistance and the resistance to venous return. Receiver operating characteristics curves indicated that hypovolemia > 500 mL could only be accurately detected by PPV when 5% albumin was used, that PVI was reliable when Ringer was infused, and that CO indicated the hypovolemia when 20% albumin was administered. Conclusions The trends in PPV, PVI, and CO reflected the changes in intravascular volume, but how well they indicated hypovolemia > 500 mL may differ depending on the choice of infusion fluid. Identifying hypovolemia using non-invasive hemodynamic monitors remains challenging and associated with low predictive values. Trial registration number: NCT05391607, May 26, 2022.

Understanding the interaction between pharmaceuticals and serum proteins is crucial for optimizing therapeutic strategies, especially in patients with coexisting chronic diseases. The primary goal of this study was to assess the potential changes in binding affinity and competition between glipizide (GLP, a second-generation sulfonylurea hypoglycemic drug) and losartan (LOS, a medication commonly prescribed for hypertension, particularly for patients with concurrent diabetes) with non-glycated (HSA) and glycated (gHSAGLC, gHSAFRC) human serum albumin using multiple spectroscopic techniques (fluorescence, UV-visible absorption, and circular dichroism spectroscopy). The results indicated that FRC is a more effective glycation agent for HSA than GLC, significantly altering the albumin structure and affecting the microenvironment around critical amino acid residues, Trp-214 and Tyr. These modifications reduce the binding affinity of LOS and GLP to gHSAGLC and gHSAFRC, compared to HSA, resulting in less stable drug–protein complexes. The study revealed that LOS and GLP interact nonspecifically with the hydrophobic regions of the albumin surface in both binary (ligand–albumin) and ternary systems (ligand–albumin–ligandconst) and specifically saturate the binding sites within the protein molecule. Furthermore, the presence of an additional drug (GLP in the LOS–albumin complex or LOS in the GLP–albumin complex) complicates the interactions, likely leading to competitive binding or displacement of the initially bound drug in both non-glycated and glycated albumins. Analysis of the CD spectra suggests mutual interactions between GLP and LOS, underscoring the importance of closely monitoring patients co-administered these drugs, to ensure optimal therapeutic efficacy and safety.

Background This phase I/II study aimed to determine the maximum tolerated dose (MTD) of nanoparticle albumin-bound paclitaxel ( nab ® -paclitaxel) plus cisplatin as treatment for metastatic nasopharyngeal carcinoma (NPC). Methods Patients were enrolled into 1 of 3 dose cohorts, each with 21-day treatment cycles: 1) intravenous (IV) nab -paclitaxel 260 mg/m 2 on day 1; 2) IV nab -paclitaxel 140 mg/m 2 on days 1 and 8; 3) IV nab -paclitaxel 100 mg/m 2 on days 1, 8, and 15. All patients received IV cisplatin 75 mg/m 2 on day 1. Treatment continued for 4–6 cycles, or until progression or unacceptable toxicity. If more than one-third of the patients in a cohort experienced a dose-limiting toxicity (DLT), the dose used in the previous cohort would be designated the MTD. Secreted protein acidic and rich in cysteine (SPARC) expression was detected by immunohistochemistry staining. Results Sixty-nine patients were enrolled, of whom 64 and 67 were eligible for efficacy and safety analysis, respectively. Two DLTs occurred in cohort 1 (grade 4 febrile neutropenia, grade 3 myalgia), none occurred in cohort 2, and 2 occurred in cohort 3 (both grade 3 fatigue). The MTD was not reached. Partial responses were achieved by 42 patients, 15 had stable disease, and 7 had progressive disease, giving an overall response rate of 66 %. Median progression-free survival was 9 months (95 % CI, 6–12 months). Grade ≥ 3 adverse events were mainly hematologic. There was no significant difference between the 3 cohorts with respect to efficacy or safety. Biomarker analyses indicated that stromal, rather than tumoral, SPARC may predict the response to nab-paclitaxel in NPC. Conclusions Our findings suggest that nab -paclitaxel plus cisplatin is a highly active regimen with moderate toxicity for the treatment of metastatic NPC, which warrants further investigation in a phase III study. Trial registrations ClinicalTrials.gov ID: NCT01735409 . The trial was registered on November 20th, 2012.