Background & aims: High protein delivery during early critical illness is associated with lower mortality, while energy overfeeding is associated with higher mortality. Protein-to-energy ratios of traditional enteral formulae are sometimes too low to reach protein targets without energy overfeeding. This prospective feasibility study aimed to evaluate the ability of a new enteral formula with a high protein-to-energy ratio to achieve the desired protein target while avoiding energy overfeeding.Methods: Mechanically ventilated non-septic patients received the high protein-to-energy ratio nutrition during the first 4 days of ICU stay (n = 20). Nutritional prescription was 90% of measured energy expenditure. Primary endpoint was the percentage of patients reaching a protein target of ≥1.2 g/kg ideal body weight on day 4. Other endpoints included a comparison of nutritional intake to matched historic controls and the response of plasma amino acid concentrations. Safety endpoints were gastro-intestinal tolerance and plasma urea concentrations. Results: Nineteen (95%) patients reached the protein intake target of ≥1.2 g/kg ideal body weight on day 4, compared to 65% in historic controls (p = 0.024). Mean plasma concentrations of all essential amino acids increased significantly from baseline to day 4. Predefined gastro-intestinal tolerance was good, but unexplained foul smelling diarrhoea occurred in two patients. In one patient plasma urea increased unrelated to acute kidney injury. Conclusions: In selected non-septic patients tolerating enteral nutrition, recommended protein targets can be achieved without energy overfeeding using a new high protein-to-energy ratio enteral nutrition.
MULTIFILE
BACKGROUND: In critical care patients, reaching optimal β-lactam concentrations poses challenges, as infections are caused more often by microorganisms associated with higher MICs, and critically ill patients typically have an unpredictable pharmacokinetic/pharmacodynamic profile. Conventional intermittent dosing frequently yields inadequate drug concentrations, while continuous dosing might result in better target attainment. Few studies address cefotaxime concentrations in this population.OBJECTIVES: To assess total and unbound serum levels of cefotaxime and an active metabolite, desacetylcefotaxime, in critically ill patients treated with either continuously or intermittently dosed cefotaxime.METHODS: Adult critical care patients with indication for treatment with cefotaxime were randomized to treatment with either intermittent dosing (1 g every 6 h) or continuous dosing (4 g/24 h, after a loading dose of 1 g). We defined a preset target of reaching and maintaining a total cefotaxime concentration of 4 mg/L from 1 h after start of treatment. CCMO trial registration number NL50809.042.14, Clinicaltrials.gov NCT02560207.RESULTS: Twenty-nine and 30 patients, respectively, were included in the continuous dosing group and the intermittent dosing group. A total of 642 samples were available for analysis. In the continuous dosing arm, 89.3% met our preset target, compared with 50% in the intermittent dosing arm. Patients not reaching this target had a significantly higher creatinine clearance on the day of admission.CONCLUSIONS: These results support the application of a continuous dosing strategy of β-lactams in critical care patients and the practice of therapeutic drug monitoring in a subset of patients with higher renal clearance and need for prolonged treatment for further optimization, where using total cefotaxime concentrations should suffice.
The angiotensin receptor blocker telmisartan slows progression of kidney disease in patients with type 2 diabetes (T2D), yet many patients remain at high risk for progressive kidney function loss. The underlying mechanisms for this response variation might be attributed to differences in angiotensin-1 receptor occupancy (RO), resulting from individual variation in plasma drug exposure, tissue drug exposure, and receptor availability. Therefore, we first assessed the relationship between plasma telmisartan exposure and urinary-albumin-to-creatinine-ratio (UACR) in 10 patients with T2D and albuminuria (mean age 66 years, median UACR 297 mg/g) after 4 weeks treatment with 80 mg telmisartan once daily. Increasing telmisartan exposure associated with a larger reduction in UACR (Pearson correlation coefficient (PCC) = −0.64, P = 0.046, median change UACR: −40.1%, 95% confidence interval (CI): −22.9 to −77.4%, mean telmisartan area under the curve (AUC) = 2927.1 ng·hour/mL, 95% CI: 723.0 to 6501.6 ng·hour/mL). Subsequently, we assessed the relation among plasma telmisartan exposure, kidney distribution, and angiotensin-1 RO in five patients with T2D (mean age 60 years, median UACR 72 mg/g) in a separate positron emission tomography imaging study with [11C]Telmisartan. Individual plasma telmisartan exposure correlated with telmisartan distribution to the kidneys (PCC = 0.976, P = 0.024). A meaningful RO could be calculated in three patients receiving 120 mg oral telmisartan, and although high exposure seems related to higher RO, with AUC0–last of 31, 840, and 274 ng·hour/mL and corresponding RO values 5.5%, 44%, and 59%, this was not significant (P = 0.64). Together these results indicate, for the first time, a relationship among interindividual differences in plasma exposure, kidney tissue distribution, RO, and ultimately UACR response after telmisartan administration.
Mycelium biocomposites (MBCs) are a fairly new group of materials. MBCs are non-toxic and carbon-neutral cutting-edge circular materials obtained from agricultural residues and fungal mycelium, the vegetative part of fungi. Growing within days without complex processes, they offer versatile and effective solutions for diverse applications thanks to their customizable textures and characteristics achieved through controlled environmental conditions. This project involves a collaboration between MNEXT and First Circular Insulation (FC-I) to tackle challenges in MBC manufacturing, particularly the extended time and energy-intensive nature of the fungal incubation and drying phases. FC-I proposes an innovative deactivation method involving electrical discharges to expedite these processes, currently awaiting patent approval. However, a critical gap in scientific validation prompts the partnership with MNEXT, leveraging their expertise in mycelium research and MBCs. The research project centers on evaluating the efficacy of the innovative mycelium growth deactivation strategy proposed by FC-I. This one-year endeavor permits a thorough investigation, implementation, and validation of potential solutions, specifically targeting issues related to fungal regrowth and the preservation of sustained material properties. The collaboration synergizes academic and industrial expertise, with the dual purpose of achieving immediate project objectives and establishing a foundation for future advancements in mycelium materials.
