Fibroblast growth factor 23 in acute burn patients: Novel insights from an intact-form assay.

INTRODUCTION: Fibroblast growth factor 23 (FGF23) is a key regulator in phosphate and vitamin D metabolism When measured with c-terminal assay, it has been shown to be increased following burn. Progress in understanding FGF23 physiology has emphasized the importance of assessing the intact form of FGF23. METHODS: The present cohort study is a complementary analysis of a previously published work. Patients >18 years, admitted within 24h after injury with burn surface area (BSA) >10% were included. C-terminal (c-term) and intact (i) FGF23 assay were performed at admission and every week during 4 weeks of follow-up. Inflammation and iron status were assessed at the same time points. RESULTS: Twenty patients were initially included and 12 were followed until day 28. The c-term FGF23 tended to gradually increase during the 4 weeks of follow-up while iFGF23 was quite stable into normal ranges. Iron status showed a typical inflammatory profile. C-term FGF23 was significantly positively correlated with c-reactive protein (CRP) and negatively correlated with iron levels. iFGF23 was not correlated with CRP or iron. CONCLUSION: FGF23 status following burn is characterized by a dissociation between c-term FGF23 and iFGF23. The hypothesis of an increased cleavage may be raised. Respective role of inflammation and iron levels in such deregulation need to be specified. Both c-term and intact assays should be performed in further studies aiming to increase knowledge on FGF23 regulation and effects in burn patients.

Vitamin D status after a high dose of cholecalciferol in healthy and burn subjects.

BACKGROUND: Burn patients are at risk of vitamin D (VD) deficiency and may benefit from its pleiotropic effects as soon as acute phase. Aim of this observational study was to assess effects of a cholecalciferol (VD3) bolus on VD status in adult burn patients (Group B, GB) after admission, compared to healthy subjects (Group H, GH). METHODS: Both groups received an oral dose of 100,000 IU VD3. Blood samples were collected before (D0) and 7 days (D7) after bolus to measure 250H-D, 1,25(OH)2-D, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). Albumin (ALB) and VD binding protein (DBP) were measured and used to calculate free 25OH-D level. Data were expressed as median (min-max) or proportions. RESULTS: A total of 49 subjects were included: 29 in GH and 20 in GB. At D0, prevalence of VD deficiency was higher in GB: 25OH-D was 21.5 (10.1-46.3) ng/ml in GH vs 11 (1.8-31.4) ng/ml in GB. DBP and ALB were lower in GB. At D7, DBP was stable in both groups while ALB decreased in GB. 25OH-D increased by 66.6 (13.5-260.3)% in GH. In GB, changes in 25OH-D extended from -36.7% to 333.3% with a median increase of 33.1%. Similar changes were observed in each group for free 25OH-D. High FGF23 levels were observed in GB. CONCLUSIONS: This study highlighted the differences in VD status and in response to a high dose VD3 in burn patients when compared to healthy patients. Pitfalls in VD status assessment are numerous during acute burn care: 25OH-D measurement needs cautious interpretation and interest of free 25OH-D is still questionable. They should not prevent burn patients to receive VD supplements during acute care. Higher doses than general recommendations should probably be considered.

Effects of cholecalciferol supplementation and optimized calcium intakes on vitamin D status, muscle strength and bone health: a one-year pilot randomized controlled trial in adults with severe burns.

OBJECTIVE: Burn patients are at risk of hypovitaminosis D and osteopenia or sarcopenia. Vitamin D pleiotropic effects may influence bone and muscle health. The aim of this pilot study was to assess effects of a cholecalciferol (VD3) supplementation and an optimized calcium (Ca) regimen on vitamin D (VD) status, bone and muscle health during sequelar stage of burn injury. DESIGN: Monocentric randomized controlled trial. METHODS: Fifteen adults with thermal burns dating from 2 to 5 years were randomized into two groups. For 12 months, they either received a quarterly IM injection of 200,000IU VD3 and daily oral Ca (Group D) or placebo (Group P). VD status and bone remodeling markers were assessed every 3 months. Knee muscle strength and bone mineral density were, respectively, assessed using isokinetic dynamometry and dual X-ray absorptiometry at initiation (M0) and completion (M12) of the protocol. RESULTS: Of all the patients, 66% presented with VD deficiency and 53% (with 3 men <40y) were considered osteopenic at inclusion. After one year, calcidiol levels significantly increased in Group D to reach 40 (37-61)ng/ml. No significant change in bone health was observed in both groups while Group D significantly improved quadriceps strength when tested at high velocity. CONCLUSIONS: This VD3 supplementation was safe and efficient to correct hypovitaminosis D in burn adults. When combined with optimized Ca intakes, it demonstrated positive effects on muscle health but not on bone health. A high prevalence of hypovitaminosis D and osteopenia in these patients, as well as their wide range of muscle performances, seem to be worrying when considering rehabilitation and quality of life.

Effect of cholecalciferol recommended daily allowances on vitamin D status and fibroblast growth factor-23: an observational study in acute burn patients.

OBJECTIVE: Burn patients are at risk of hypovitaminosis D. Optimal vitamin D (VD) intakes are not defined in burn nutrition guidelines and studies mostly focused on ergocalciferol (VD2) supplementation in burn children. Aim of our study was to describe adult burns VD status, to measure effects of our cholecalciferol (VD3) supplementation on VD metabolism during acute burn care, and to assess correlation between FGF23 and C-reactive protein (CRP). DESIGN: Cohort study. METHODS: From March 2012 to January 2013, patients >18 years, admitted within 24 h after injury with burn surface area (BSA) ≥10% were included. Patients daily received VD3 from oral or enteral nutrition (400-600 IU) and from oral or intravenous multivitamin complex (200-220 IU). Serum levels of 25(OH)-D, 1-25(OH)2-D, 3rd generation PTH, C-terminal FGF23, total calcium, phosphate, albumin and CRP were measured at admission (D0) and every week during 4 weeks of follow-up. Data are expressed as percentage or median (min-max). Paired data were compared using Wilcoxon test. Correlation between CRP and FGF23 was assessed using nonparametric Spearman test. A p value <0.05 was considered to be statistically significant. RESULTS: We initially included 24 patients. Median age and BSA were, respectively, 46 [19-86] years and 15 [10-85]%. At D0, 75% presented a VD insufficiency (25(OH)-D 21-29 ng/ml) and 17% presented a deficiency (25(OH)-D ≤20 ng/ml). We followed 12 patients until day 28: 25(OH)-D was unchanged while 1-25(OH)2-D and FGF23 decreased without reaching significance. We observed a significant positive correlation between FGF23 and CRP (r=0.59, 95% CI: 0.22-0.82, p=0.0032). CONCLUSIONS: Most of our adult burns presented hypovitaminosis D regardless of age. Nutrition supplemented with low dose of VD3 (intakes reaching recommended daily allowances) was insufficient to correct 25(OH)-D level. Moreover, an interesting correlation between CRP and FGF23 was found.

Liver transplantation in Jehovah's witnesses.

For religious reasons, Jehovah's witnesses refuse transfusion of blood products (red cells, platelets, plasma), but may accept organ transplantation. The authors developed a multidisciplinary protocol for liver transplantation in Jehovah's witnesses. In a 6-year period, nine Jehovah's witness patients were listed for liver transplantation. They received preoperative erythropoietin therapy, with iron and folic acid that allowed significant haematocrit increase. Two patients underwent partial spleen embolization to increase platelet count. Seven patients underwent cadaveric whole liver transplantation, and two right lobe living-related liver transplantation, using continuous circuit cell saving system and high dose aprotinin. No patient received any blood product during the surgical procedure. One patient suffering from deep anaemia after living-related liver transplantation was transfused as required by his family, but died from aspergillus infection. One 6-year-old child was transfused against her parent's will. The authors demonstrated that it is possible to increase haematocrit and platelet levels in cirrhotic patients awaiting liver transplantation. They were able to reduce intraoperative need for blood products, allowing liver transplantation in prepared Jehovah's witness patients. This experience may be beneficial for non-Jehovah's witness liver transplant recipients.

Auditory processing in severely brain injured patients: differences between the minimally conscious state and the persistent vegetative state.

BACKGROUND: The minimally conscious state (MCS) is a recently defined clinical condition; it differs from the persistent vegetative state (PVS) by the presence of inconsistent, but clearly discernible, behavioral evidence of consciousness. OBJECTIVE: To study auditory processing among patients who are in an MCS, patients who are in a PVS, and healthy control subjects. METHODS: By means of (15)O-radiolabeled water-positron emission tomography, we measured changes in regional cerebral blood flow induced by auditory click stimuli in 5 patients in an MCS, 15 patients in a PVS, and 18 healthy controls. RESULTS: In both patients in an MCS and the healthy controls, auditory stimulation activated bilateral superior temporal gyri (Brodmann areas 41, 42, and 22). In patients in a PVS, the activation was restricted to Brodmann areas 41 and 42 bilaterally. We also showed that, compared with patients in a PVS, patients in an MCS demonstrated a stronger functional connectivity between the secondary auditory cortex and temporal and prefrontal association cortices. CONCLUSIONS: Although assumptions about the level of consciousness in severely brain injured patients are difficult to make, our findings suggest that the cerebral activity observed in patients in an MCS is more likely to lead to higher-order integrative processes, thought to be necessary for the gain of conscious auditory perception.

Brain function in the vegetative state.

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However, this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction.