BackgroundNormocaloric vs. calorie-restricted feeding in Intensive Care Unit (ICU) patients with refeeding hypophosphatemia (RH) is associated with increased mortality rates. Until now, only total... Show moreBackgroundNormocaloric vs. calorie-restricted feeding in Intensive Care Unit (ICU) patients with refeeding hypophosphatemia (RH) is associated with increased mortality rates. Until now, only total energy provision has been studied. Data on individual macronutrients (proteins, lipids, and carbohydrates) and clinical outcomes are lacking. This study evaluates associations between macronutrient intake among RH patients during the first week of ICU admission and clinical outcomes.MethodsA single-centre retrospective observational cohort study was conducted among prolonged mechanically ventilated RH ICU patients. The primary outcome was the association of separate macronutrient intakes during the first week of ICU admission with 6-month mortality, adjusted for relevant variables. Other parameters included ICU-, hospital- and 3-month mortality, mechanical ventilation duration and length of ICU and hospital stay. Macronutrient intakes were subsequently analyzed during day 1–3 and day 4–7 of ICU admission.ResultsIn total, 178 RH patients were included. Six-month all-cause mortality was 29.8%. Higher protein intake during days 1–3 of ICU admission (>0.71 g/kg∗day; HR 2.224, 95%CI 1.261–3.923, p = 0.006), higher age (HR 1.040, 95%CI 1.015–1.066, p = 0.002) and higher APACHE II scores on ICU admission (HR 1.086, 95%CI 1.034–1.140, p = 0.001) were associated with increased 6-month mortality. No differences in other outcomes were observed.ConclusionHigh protein - not carbohydrate or lipid - intake during the first three days of ICU admission in patients with RH is associated with increased 6-month mortality, but not short-term outcomes. We hypothesize a time-dependent and dose–response relationship between protein intake and mortality in refeeding hypophosphatemia ICU patients, although additional (randomized controlled) studies are needed to confirm this hypothesis. Show less
O'Flynn, J.; Kotimaa, J.; Faber-Krol, R.; Koekkoek, K.; Klar-Mohamad, N.; Koudijs, A.; ... ; Kooten, C. van 2018
The phagocyte NAPDH-oxidase complex consists of several phagocyte oxidase (phox) proteins, generating reactive oxygen species (ROS) upon activation. ROS are involved in the defense against... Show moreThe phagocyte NAPDH-oxidase complex consists of several phagocyte oxidase (phox) proteins, generating reactive oxygen species (ROS) upon activation. ROS are involved in the defense against microorganisms and also in immune regulation. Defective ROS formation leads to chronic granulomatous disease (CGD) with increased incidence of autoimmunity and disturbed resolution of inflammation. Because regulatory T cells (Tregs) suppress autoimmune T-cell responses and are crucial in down-regulating immune responses, we hypothesized that ROS deficiency may lead to decreased Treg induction. Previously, we showed that in p47(phox)-mutated mice, reconstitution of macrophages (Mph) with ROS-producing capacity was sufficient to protect the mice from arthritis. Now, we present evidence that Mph-derived ROS induce Tregs. In vitro, we showed that Mph ROS-dependently induce Treg, using an NADPH-oxidase inhibitor. This finding was confirmed genetically: rat or human CGD Mph with mutated p47(phox) or gp91(phox) displayed hampered Treg induction and T-cell suppression. However, basal Treg numbers in these subjects were comparable to those in controls, indicating a role for ROS in induction of peripheral Tregs. Induction of allogeneic delayed-type hypersensitivity with p47(phox)-mutated Mph confirmed the importance of Mph-derived ROS in Treg induction in vivo. We conclude that NAPDH oxidase activity in Mph is important for the induction of Tregs to regulate T cell-mediated inflammation. Show less
Gelderman, K.A.; Kraaij, M.D.; Kooij, S.W. van der; Koekkoek, K.; Wang, J.; Holmdahl, R.; Kooten, C. van 2010
