The economic burden of the postoperative management in surgically treated trauma patients with peri- and/or intra-articular fractures of the lower extremities: A prospective multicenter cohort study.

OBJECTIVES: To estimate the economic burden expressed in costs and quality of life of the post-surgical treatment of peri­ and/or intra-articular fractures in the lower extremity from a societal perspective. DESIGN: This is a quantitative study as it aims to find averages and generalize results to wider populations. The design is a cost-of-illness and quality of life study focusing on costs (in euros), Activities of Daily Living (ADL) and Quality of Life (Qol) in patients with peri­ and/or intra-articular fractures of the lower extremities. SETTING: Surgically treated trauma patients with peri­ and/or intra-articular fractures of the lower extremities during 26 weeks follow-up. Patients were included from 4 hospitals in the Netherlands. MAIN OUTCOME MEASURES: Costs, ADL and Quality Adjusted Life Years (QALY). METHODS: Cost of illness was estimated through a bottom-up method. The Dutch Eq-5D-5 L questionnaire was used to calculate utilities while Lower Extremity Functional Scale (LEFS) scores were used as a measure of ADL. Non-parametric bootstrapping was used to test for statistical differences in costs. Subgroup analyses were performed to determine the influence of work status and further sensitivity analyses were performed to test the robustness of the results. RESULTS: Total average societal costs were € 9836.96 over six months. Unexpectedly, total societal and healthcare costs were lower for patients with a paid job relative to patients without. Sensitivity analyses showed that our choice of a societal perspective and the EuroQol as our primary utility measurement tool had a significant effect on the outcomes. The ADL at baseline was respectively; 10.4 and at 26 weeks post-surgery treatment 49.5. The QoL was at baseline respectively; 0.3 and at 26 weeks post-surgery treatment 0.7. These findings are indicative of a significantly improved ADL and QoL (p ≤ 0.05) over time. CONCLUSIONS: This study reveal a substantial economic burden in monetary terms and effect on QoL of patients with peri­ and/or intra-articular fractures of the lower extremities during 26 weeks follow-up. REGISTRATION: This study was registered in the Dutch Trial Register (NTR6077). Date of registration: 01-09-2016.

Influence of transferrin glycans on receptor binding and iron-donation.

Human bi-bi-antennary transferrin (Tf) was partially deglycosylated by subsequently incubating with one or more of the following exoglycosidases: neuraminidase, beta-galactosidase or N-Acetyl-beta-D-glucosaminidase. Aglyco-Tf obtained from serum of a patient suffering from the Carbohydrate Deficient Glycoprotein syndrome was isolated. Receptor binding and the Tf and iron uptake capacities of the fully glycosylated-, partially deglycosylated- and aglyco-Tf were compared using the human hepatoma cell line PLC/PRF/5. No difference in binding capacity between the iso-Tf fractions could be demonstrated, however, the Tf and iron uptake capacity of aglyco-Tf was clearly reduced compared with the other Tf fractions.

Isolation, purification and characterization of porcine serum transferrin and hemopexin.

Two techniques are described for the isolation of porcine serum transferrin and hemopexin, respectively, yielding nearly pure proteins (> 99%) as tested with crossed immunoelectrophoresis. Porcine transferrin has an estimated molecular weight of 79 kDa and porcine hemopexin a molecular weight of 62 kDa. Both purified proteins were subjected to amino acid and carbohydrate analyses. Based on carbohydrate and sialic acid analyses, it is proposed that transferrin contains one bi-antennary glycan chain, whereas hemopexin contains two bi-antennary and one tri-antennary glycan chains.

Adaptation of transferrin protein and glycan synthesis.

We report the patterns of variability in transferrin structure in pregnancy, iron deficiency anemia, women using oral contraceptives, nonanaemic rheumatoid arthritis, iron deficient rheumatoid arthritis and anemia of the chronic diseases. Changes in microheterogeneity were assessed by crossed immuno isoelectric focusing of serum transferrin. Intra-individual variation in the control group was minimal. Equally, inter-individual variation in controls and groups with established stable disease was very limited. In pregnancy an increase in transferrin concentration was accompanied by redirection of glycan synthesis to the highly sialylated and highly branched glycans, an effect also shown in women using oral contraceptives. Iron deficiency anemia was accompanied by increased protein core synthesis without the large shifts in the microheterogeneity pattern as seen in pregnancy at similar transferrin concentration. In contrast to this, rheumatoid arthritis was accompanied by decreased protein synthesis while the microheterogeneity pattern shifted significantly towards the highly branched glycans. Interpreted in the respective pathophysiological contexts results show that: (1) N-linked glycosylation of transferrin is a strictly controlled process, both in the physiological states and in disease. (2) Microheterogeneity is determined independently from transferrin protein synthetic rate. (3) Provisionally observed changes in the glycosylation can modulate the biological activity of the glycoprotein and as a result redirect internal iron fluxes. This proposition can be applied to altered iron metabolism in both pregnancy, oral contraceptives and rheumatoid arthritis. Changes are not operative in iron deficiency because qualitatively iron metabolism is not altered in this state.

Effect of phlebotomy on the ferritin iron content in the rat liver as determined morphometrically with the use of electron energy loss spectroscopy.

Phlebotomy of untreated and iron-loaded rats results in a significant decrease in total liver iron. In iron-loaded rats a marked decrease in iron-containing particles is observed ultrastructurally in lysosomes and cytoplasm of hepatic sinusoidal cells but not in parenchymal cells. This remarkable phenomenon was further investigated in a morphometric study, based on element-specific (iron) distribution images made in situ in the parenchymal cell by means of electron energy loss spectroscopy. With the use of this technique it could be shown that in spite of phlebotomy the ferritin iron content of the iron-loaded liver parenchymal cell is not decreased.

Release of iron from endosomes is an early step in the transferrin cycle.

Transferrin bound to K 562 cells at 4 degrees C was internalized quickly on temperature shift to 37 degrees C. Endosomes were isolated according to two different procedures. The endosome fraction was shown to be heterogeneous and consisted of two vesicle populations, differing in density properties and iron content. Iron was partially released from endosomes to the supernatant after 3 and 5 min endocytosis. Isolated endosomes, still capable of internal acidification, did not release iron on incubation with ATP. However, endosomes did release iron on incubation with the iron chelator pyridoxal-isonicotinoyl hydrazone. Gel-filtration of solubilized endosomes demonstrated the presence of the transferrin-transferrin receptor complexes, free transferrin and free low molecular weight iron.

Analysis of iron-binding components in the low molecular weight fraction of rat reticulocyte cytosol.

Rat reticulocytes were incubated with rat 125I-Tf-59Fe under conditions inhibiting heme synthesis. Cytosol, prepared from the reticulocytes, was separated and analysed by gel filtration and Amicon Ultrafiltration. An iron-containing low molecular weight fraction derived from the cytosol was further analysed by HPLC size-exclusion chromatography and HPLC reversed phase chromatography. Conditions inhibiting heme synthesis and uncoupling the oxidative phosphorylations lead to a large increase in the Fe-containing low molecular weight fraction in the cytosol. The components in the low molecular weight fraction have an apparent molecular weight of 5500 Dalton as determined with HPLC size-exclusion chromatography. The low molecular weight fraction contained several iron chelating components like glycin, 1/2 cystine and citrate, but no specific iron-binding proteins, nucleotides or pyrophosphate.

The uptake of iron by reticulocytes. The influence of purification of the ghosts on iron-containing components in the ghost suspension.

1. Rat reticulocytes previously incubated with ((59)Fe, (125)I)-labelled transferrin were hemolysed to yield labelled ghosts. 2. The solubilized ghosts can be fractionated, by gel filtration on Sepharose 2B and 6B, into several (59)Fe- and (125)I-containing compounds, classified as A, B(1) and B(2). 3. These fractions were prepared from ghosts which were obtained at different centrifugation rates and further purified by sucrose density gradient centrifugation in order to obtain membrane compounds purified from mitochondrial and lysosomal impurities. The influence of these purification steps on the appearance and the (59)Fe/(125)I activity of the three components was investigated. 4. The first Sepharose 2B fraction with high molecular mass, greater than 10(6) daltons, is an intracellular product of mitochondrial and lysosomal origin which precipitates with the membrane fractions during the preparation of the ghost. The first Sepharose 6B fraction, B(1), with M(r) approximately 10(6) seems to be a real membrane component. The second Sepharose 6B fraction, B(2), with M(r) approximately 230 000 represents a real membrane receptor transferrin.

Observations on the iron status during pregnancy in rats. Iron transport from mother to fetus.

The objective of the present study was to investigate a transfer of liver iron in rats from mother to fetus during pregnancy. A decrease in maternal liver iron and an increase in fetal liver iron, in groups of 10 rats, have been shown, based on iron analysis and specific activity of 59Fe.