Rationale Muscle mass maintenance is largely regulated by the postprandial rise in muscle protein synthesis rates. It remains unclear whether postprandial protein handling differs between women and men. Methods Healthy men (43±3 y; BMI: 23.4±0.4 kg/m²; n=12) and women (46±2 y; BMI: 21.3±0.5 kg/m²; n=12) received primed continuous infusions of L-[ring-²H₅]-phenylalanine and L-[ring-3,5-²H₂]-tyrosine and ingested 25 g intrinsically L-[1-¹³C]-phenylalanine-labeled whey protein. Blood samples and muscle biopsies were collected to assess dietary protein digestion and amino acid absorption kinetics as well as basal and postprandial myofibrillar protein synthesis rates. Results Plasma phenylalanine and leucine concentrations rapidly increased following protein ingestion (both P<0.001), with no differences between middle-aged women and men (Time×Sex P=0.307 and 0.529, respectively). The fraction of dietary protein-derived phenylalanine that appeared in the circulation over the 5 h postprandial period averaged 56±1 and 53±1% in the women and men, respectively (P=0.145). Myofibrillar protein synthesis rates increased (Time P=0.010) from 0.035±0.004 and 0.030±0.002 %/h in the post-absorptive state (t-test P=0.319) to 0.045±0.002 and 0.034±0.002 %/h in the 5 h postprandial phase in middle-aged women and men, respectively, with higher postprandial myofibrillar protein synthesis rates in women compared with men (t-test P=0.005). Middle-aged women showed a greater increase in myofibrillar protein synthesis rates during the early (0-2 h) postprandial period when compared with men (Time×Sex P=0.001). Conclusions There are no differences in post-absorptive myofibrillar protein synthesis rates between middle-aged women and men. The myofibrillar protein synthetic response to the ingestion of 25 g whey protein is greater in women when compared with men.

Measuring calprotectin concentration in stool is increasingly important in monitoring disease activity and treatment response in inflammatory bowel disease. This study evaluates the impact of preanalytical storage conditions on reliability of calprotectin testing using 5 different calprotectin immunoassays. Aliquots of homogenized fresh fecal samples in untreated or extracted form were stored at room temperature or 4°C. Calprotectin concentration was measured day 0 to 4 and 8. Five different immunoassays and accompanying extraction buffers were used (CALiaGold, Phadia EliA, Bühlmann fCal turbo, ELISA Bühlmann, Inova Quanta Flash). Repeated measurements of change from baseline calprotectin levels over time were analyzed using a mixed model analysis. Calprotectin concentrations declined over time under all preanalytical conditions with all assays, except for extracted feces stored at 4°C. The rate of decline was greatest in untreated stool kept at room temperature, reaching significant difference from baseline already after 1 day (P < 0.001). In extracted feces kept at room temperature, significant difference from baseline was reached after 2 days, and in untreated feces at 4°C, after 4 days. However, the results differed significantly between assays. After 4 days of storage at room temperature, the mean calprotectin decline from baseline differed between 30% and 60%, dependent on the assay used. Fecal calprotectin concentration in stool samples declines over time, and the rate of decline is greater at higher temperatures. In extracted feces stored at 4°C, calprotectin is most stable. It is assay-dependent how long extracted feces stored at 4°C give reliable test results.

This study aimed to determine whether published pharmacokinetic (PK) models can adequately predict the PK profile of imatinib in a new indication, such as coronavirus disease 2019 (COVID‐19). Total (bound + unbound) and unbound imatinib plasma concentrations obtained from 134 patients with COVID‐19 participating in the CounterCovid study and from an historical dataset of 20 patients with gastrointestinal stromal tumor (GIST) and 85 patients with chronic myeloid leukemia (CML) were compared. Total imatinib area under the concentration time curve (AUC), maximum concentration (C_max) and trough concentration (C_trough) were 2.32‐fold (95% confidence interval [CI] 1.34–3.29), 2.31‐fold (95% CI 1.33–3.29), and 2.32‐fold (95% CI 1.11–3.53) lower, respectively, for patients with CML/GIST compared with patients with COVID‐19, whereas unbound concentrations were comparable among groups. Inclusion of alpha1‐acid glycoprotein (AAG) concentrations measured in patients with COVID‐19 into a previously published model developed to predict free imatinib concentrations in patients with GIST using total imatinib and plasma AAG concentration measurements (AAG‐PK‐Model) gave an estimated mean (SD) prediction error (PE) of −20% (31%) for total and −7.0% (56%) for unbound concentrations. Further covariate modeling with this combined dataset showed that in addition to AAG; age, bodyweight, albumin, CRP, and intensive care unit admission were predictive of total imatinib oral clearance. In conclusion, high total and unaltered unbound concentrations of imatinib in COVID‐19 compared to CML/GIST were a result of variability in acute phase proteins. This is a textbook example of how failure to take into account differences in plasma protein binding and the unbound fraction when interpreting PK of highly protein bound drugs, such as imatinib, could lead to selection of a dose with suboptimal efficacy in patients with COVID‐19.

Thromboelastometry plays a key role in many transfusion algorithms. ROTEM® Sigma is the fully automated successor of ROTEM® Delta. Compatibility with current ROTEM® Delta-based algorithms remains uncertain. This study compares ROTEM® Delta with ROTEM® Sigma in patients undergoing thoracic aortic surgery. Three ROTEM® measurements in duplicate (one Delta and one Sigma) per patient were performed during aortic surgery. The primary outcome was the percentage of patients who would have received a different haemostatic intervention after protamine reversal based on the institutional ROTEM®-guided transfusion algorithm ('deviation'). A 10% deviation was deemed acceptable. Secondary outcomes were differences in numerical values assessed by Passing-Bablok regressions, Bland-Altman plots, and correlations with conventional coagulation tests. Of 111 patients, 102 had matched post-protamine ROTEM® measurements. There were 43 algorithm deviations. Most deviations (29) were attributable to conflicting advice on CT EXTEM-based plasma or prothrombin complex concentrate (PCC) administration; in 25 patients, Delta results advised the administration of plasma or PCC, whereas Sigma did not, and vice versa in four patients. Deviations on additional protamine, fibrinogen concentrate, or platelet administration were acceptable. All numerical ROTEM® variables examined passed the criteria for equivalence, except for A10 FIBTEM at baseline and A10 EXTEM in heparinised and post-protamine samples, which would not have led to clinical consequences. Correlations with conventional coagulation tests were similar or better for Sigma compared with Delta. ROTEM® Sigma can be used with existing ROTEM-guided transfusion algorithms in cardiothoracic surgery except for the advice for administration of plasma or PCC. Netherlands trial register NL8273.

Micronutrient deficiencies can develop in critically ill patients, arising from factors such as decreased intake, increased losses, drug interactions, and hypermetabolism. These deficiencies may compromise important immune functions, with potential implications for patient outcomes. Alternatively, micronutrient blood levels may become low due to inflammation-driven redistribution rather than consumption. This explorative pilot study investigates blood micronutrient concentrations during the first three weeks of ICU stay in critically ill COVID-19 patients and evaluates the impact of additional micronutrient administration. Moreover, associations between inflammation, disease severity, and micronutrient status were explored. We measured weekly concentrations of vitamins A, B6, D, and E; iron; zinc; copper; selenium; and CRP as a marker of inflammation state and the SOFA score indicating disease severity in 20 critically ill COVID-19 patients during three weeks of ICU stay. Half of the patients received additional (intravenous) micronutrient administration. Data were analyzed with linear mixed models and Pearson’s correlation coefficient. High deficiency rates of vitamins A, B6, and D; zinc; and selenium (50–100%) were found at ICU admission, along with low iron status. After three weeks, vitamins B6 and D deficiencies persisted, and iron status remained low. Plasma levels of vitamins A and E, zinc, and selenium improved. No significant differences in micronutrient levels were found between patient groups. Negative correlations were identified between the CRP level and levels of vitamins A and E, iron, transferrin, zinc, and selenium. SOFA scores negatively correlated with vitamin D and selenium levels. Our findings reveal high micronutrient deficiency rates at ICU admission. Additional micronutrient administration did not enhance levels or expedite their increase. Spontaneous increases in vitamins A and E, zinc, and selenium levels were associated with inflammation resolution, suggesting that observed low levels may be attributed, at least in part, to redistribution rather than true deficiencies.

Background: Home use of a buffer-containing extraction device for fecal calprotectin determination can bypass the labor-intensive extraction procedure and potentially prevent degradation at room temperature.Methods: In this prospective cross-sectional observational study, 2 CALiaGold tubes (extraction device) and one native tube were filled from the same bowel movement by patients with inflammatory bowel disease. Afterwards patients completed a questionnaire including whether they preferred the extraction device or the normal sampling method. All tubes were sent to the laboratory and when they arrived, 2 more CALiaGold tubes were filled at the laboratory from the native sample. The fecal calprotectin concentrations in all tubes were measured by a particle-enhanced turbidimetric immunoassay.Results: Fifty-three patients were included in the study. Fecal calprotectin levels were significantly higher in samples extracted by the patient compared to the analyst-performed extractions. When patients were divided into 3 groups (i.e., fecal calprotectin levels 200 µg/g) a substantial concordance was found (Cohen kappa 0.654). Patients sampling imprecision was higher (P < 0.018, median CV 16%) compared to the analyst. Most patients preferred this extraction device.Conclusions: Patient-performed fecal calprotectin extraction seems a realistic alternative sampling method and is preferred by most patients.