Predictive value of iron parameters in neurocritically ill patients.
ABSTRACT: BACKGROUND:Iron, an essential mineral for human body, has the potential to cause toxicity at high levels. Previous studies have shown inconsistent predictive value of iron parameters in critically ill patients. Thus, we aimed to evaluate the performance of iron parameters in outcome prediction of neurocritically ill patients. METHODS:Retrospective data were collected from patients admitted to the neurocritical care unit (NCU) of a tertiary teaching hospital between August 2016 and January 2017. The iron parameters were obtained at NCU admission. Primary endpoints were short-term (30-day) mortality and long-term (6-month) poor outcome, with the latter defined as modified Rankin Scale of 4-6. The predictive value of variables was determined with univariate and multivariate logistic analysis. A further subanalysis was conducted in patients stratified by the level of estimated glomerular filtration rate (eGFR). RESULTS:Of 103 eligible patients, the etiology included stroke (58.2%, N = 60), central nervous system infection (13.6%, N = 14), and other neurologic disorders (28.2%, N = 29). The correlation analysis showed that the increase in ferritin, as well as the reduction in transferrin and total iron-binding capacity, had strong correlation with C-reactive protein, procalcitonin, duration of NCU stay, Acute Physiology and Chronic Health Evaluation II score, and Sequential Organ Failure Assessment score. In a further subanalysis of 75 patients with eGFR ? 60 ml/min/1.73 m2 , twelve (16.0%) patients died within 30 days and 39 (52.0%) patients achieved good follow-up outcome data. In the multivariate logistic regression analysis, we identified baseline ferritin level as an independent predictor of short-term mortality (OR: 1.002; 95% CI: 1.000-1.003; p = 0.008) and long-term functional outcome (OR: 1.002; 95% CI: 1.000-1.004; p = 0.031). CONCLUSIONS:Serum ferritin level at admission could be used as an independent predictor of short-term mortality and long-term functional outcome in neurocritically ill patients with eGFR ? 60 ml/min/1.73 m2 .
Project description:BACKGROUND:Despite the essential functions of the intestinal microbiota in human physiology, little has been reported about the microbiome in neurocritically ill patients. This investigation aimed to evaluate the characteristics of the gut microbiome in neurocritically ill patients and its changes after admission. Furthermore, we investigated whether the characteristics of the gut microbiome at admission were a risk factor for death within 180 days. METHODS:This prospective observational cohort study included neurocritically ill patients admitted to the neurological intensive care unit of a large university-affiliated academic hospital in Guangzhou. Faecal samples were collected within 72 h after admission (before antibiotic treatment) and serially each week. Healthy volunteers were recruited from a community in Guangzhou. The gut microbiome was monitored via 16S rRNA gene sequence analysis, and the associations with the clinical outcome were evaluated by a Cox proportional hazards model. RESULTS:In total, 98 patients and 84 age- and sex-matched healthy subjects were included in the analysis. Compared with healthy subjects, the neurocritically ill patients exhibited significantly different compositions of intestinal microbiota. During hospitalization, the α-diversity and abundance of Ruminococcaceae and Lachnospiraceae decreased significantly over time in patients followed longitudinally. The abundance of Enterobacteriaceae was positively associated with the modified Rankin Scale at discharge. In the multivariate Cox regression analysis, Christensenellaceae and Erysipelotrichaceae were associated with an increased risk of death. The increases in intestinal Enterobacteriales and Enterobacteriaceae during the first week in the neurological intensive care unit were associated with increases of 92% in the risk of 180-day mortality after adjustments. CONCLUSIONS:This analysis of the gut microbiome in 98 neurocritically ill patients indicates that the gut microbiota composition in these patients differs significantly from that in a healthy population and that the magnitude of this dysbiosis increases during hospitalization in a neurological intensive care unit. The gut microbiota characteristics seem to have an impact on patients' 180-day mortality. Gut microbiota analysis could hopefully predict outcome in the future.
Project description:Accumulating evidence suggests that, in critically ill patients, a lower hemoglobin transfusion threshold is safe. However, the optimal hemoglobin level and associated transfusion threshold remain unknown in neurocritically ill patients.We conducted a systematic review of comparative studies (randomized and nonrandomized) to evaluate the effect of hemoglobin levels on mortality, neurologic function, intensive care unit (ICU) and hospital length of stay, duration of mechanical ventilation, and multiple organ failure in adult and pediatric neurocritically ill patients. We searched MEDLINE, The Cochrane Central Register of Controlled Trials, Embase, Web of Knowledge, and Google Scholar. Studies focusing on any neurocritical care conditions were included. Data are presented by using odds ratios for dichotomous outcomes and mean differences for continuous outcomes.Among 4,310 retrieved records, six studies met inclusion criteria (n = 537). Four studies were conducted in traumatic brain injury (TBI), one in subarachnoid hemorrhage (SAH), and one in a mixed population of neurocritically ill patients. The minimal hemoglobin levels or transfusion thresholds ranged from 7 to 10 g/dl in the lower-Hb groups and from 9.3 to 11.5 g/dl in the higher-Hb groups. Three studies had a low risk of bias, and three had a high risk of bias. No effect was observed on mortality, duration of mechanical ventilation, or multiple organ failure. In studies reporting on length of stay (n = 4), one reported a significant shorter ICU stay (mean, -11.4 days (95% confidence interval, -16.1 to -6.7)), and one, a shorter hospital stay (mean, -5.7 days (-10.3 to -1.1)) in the lower-Hb groups, whereas the other two found no significant association.We found insufficient evidence to confirm or refute a difference in effect between lower- and higher-Hb groups in neurocritically ill patients. Considering the lack of evidence regarding long-term neurologic functional outcomes and the high risk of bias of half the studies, no recommendation can be made regarding which hemoglobin level to target and which associated transfusion strategy (restrictive or liberal) to favor in neurocritically ill patients.
Project description:OBJECTIVES:The Society of Critical Care Medicine recommends routine delirium monitoring, based on data in critically ill patients without primary neurologic injury. We sought to answer whether there are valid and reliable tools to monitor delirium in neurocritically ill patients and whether delirium is associated with relevant clinical outcomes (e.g., survival, length of stay, functional independence, cognition) in this population. DATA SOURCES:We systematically reviewed Cumulative Index to Nursing and Allied Health Literature, Web of Science, and PubMed. STUDY SELECTION AND DATA EXTRACTION:Inclusion criteria allowed any study design investigating delirium monitoring in neurocritically ill patients (e.g., neurotrauma, ischemic, and/or hemorrhagic stroke) of any age. We extracted data relevant to delirium tool sensitivity, specificity, negative predictive value, positive predictive value, interrater reliability, and associated clinical outcomes. DATA SYNTHESIS:Among seven prospective cohort studies and a total of 1,173 patients, delirium was assessed in neurocritically patients using validated delirium tools after considering primary neurologic diagnoses and associated complications, finding a pooled prevalence rate of 12-43%. When able to compare against a common reference standard, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the test characteristics showed a sensitivity of 62-76%, specificity of 74-98%, positive predictive value of 63-91%, negative predictive value of 70-94%, and reliability kappa of 0.64-0.94. Among four studies reporting multivariable analyses, delirium in neurocritically patients was associated with increased hospital length of stay (n = 3) and ICU length of stay (n = 1), as well as worse functional independence (n = 1) and cognition (n = 2), but not survival. CONCLUSIONS:These data from studies of neurocritically ill patients demonstrate that patients with primary neurologic diagnoses can meet diagnostic criteria for delirium and that delirious features may predict relevant untoward clinical outcomes. There is a need for ongoing investigations regarding delirium in these complicated neurocritically ill patients.
Project description:BACKGROUND:Iron deficiency is difficult to diagnose in critically ill patients, but may be frequent and may impair recovery. Measurement of hepcidin could help in the diagnosis of iron deficiency. We aim to assess if iron deficiency diagnosed using hepcidin is associated with poorer outcome one year after an intensive care unit stay. METHODS:We used the prospective FROG-ICU, multicentre (n?=?28 ICUs), observational cohort study of critically ill survivors followed up one year after intensive care unit discharge. Iron deficiency was defined as hepcidin <?20 ng/l, ferritin <?100 ng/l or soluble transferrin receptor (sTfR)/log(ferritin) >?0.8, measured in blood drawn at intensive care unit discharge. Main outcomes were one-year all-cause mortality and poor quality of life (defined as a Short Form 36 (SF-36) score below the median). RESULTS:Among the 2087 patients in the FROG-ICU cohort, 1570 were discharged alive and 1161 had a blood sample available at intensive care unit discharge and were included in the analysis. Using hepcidin, 429 (37%) patients had iron deficiency, compared to 72 (6%) using ferritin alone and 151 (13%) using the sTfR/log(ferritin) ratio. Iron deficiency diagnosed according to low hepcidin was an independent predictor of one-year mortality (OR 1.51 (1.10-2.08)) as was high sTfR/log ferritin ratio (OR?=?1.95 (1.27-3.00)), but low ferritin was not. Severe ID, defined as hepcidin <?10 ng/l, was also an independent predictor of poor one-year physical recovery (1.58 (1.01-2.49)). CONCLUSIONS:Iron deficiency, diagnosed using hepcidin, is very frequent at intensive care unit discharge and is associated with increased one-year mortality and poorer physical recovery. Whether iron treatment may improve these outcomes remains to be investigated.
Project description:BACKGROUND:The prevalence, characteristics, and outcomes related to the ventilator-associated event(s) (VAE) in neurocritically ill patients are unknown and examined in this study. METHODS:A retrospective study was performed on neurocritically ill patients at a 413-bed level 1 trauma and stroke center who received three or more days of mechanical ventilation to describe rates of VAE, describe characteristics of patients with VAE, and examine the association of VAE on ventilator days, mortality, length of stay, and discharge to home. RESULTS:Over a 5-year period from 2014 through 2018, 855 neurocritically ill patients requiring mechanical ventilation were identified. A total of 147 VAEs occurred in 130 (15.2%) patients with an overall VAE rate of 13 per 1000 ventilator days and occurred across age, sex, BMI, and admission Glasgow Coma Scores. The average time from the start of ventilation to a VAE was 5 (range 3-48) days after initiation of mechanical ventilation. Using Centers for Disease Control and Prevention definitions, VAEs met criteria for a ventilator-associated condition in 58% of events (n?=?85), infection-related VAE in 22% of events (n?=?33), and possible ventilator-associated pneumonia in 20% of events (n?=?29). A most common trigger for VAE was an increase in positive end-expiratory pressure (84%). Presence of a VAE was associated with an increase in duration of mechanical ventilation (17.4[IQR 20.5] vs. 7.9[8.9] days, p?<?0.001, 95% CI 7.86-13.92), intensive care unit (ICU) length of stay (20.2[1.1] vs. 12.5[0.4] days, p?<?0.001 95% CI 5.3-10.02), but not associated with in-patient mortality (34.1 vs. 31.3%. 95% CI 0.76-1.69) or discharge to home (12.7% vs. 16.3%, 95% 0.47-1.29). CONCLUSIONS:VAE are prevalent in the neurocritically ill. They result in an increased duration of mechanical ventilation and ICU length of stay, but may not be associated with in-hospital mortality or discharge to home.
Project description:AIMS:To develop and validate a novel score for prediction of 3-month functional outcome in neurocritically ill patients. METHODS:The development of the novel score was based on two widely used scores for general critical illnesses (Acute Physiology and Chronic Health Evaluation II, APACHE II; Simplified Acute Physiology Score II, SAPS II) and consideration of the characteristics of neurocritical illness. Data from consecutive patients admitted to neurological ICU (N-ICU) between January 2013 and June 2016 were used for the validation. The modified Rankin Scale (mRS) was used to evaluate 3-month functional outcomes. APACHE II scores, SAPS II scores, and our novel scores at 24 hours and 72 hours in N-ICU were obtained. We compared the prognostic performance of our score with APACHE II and SAPS II. RESULTS:We developed a 44-point scoring system named the INCNS score, and it includes 19 items which were categorized into five parts: inflammation (I), nutrition (N), consciousness (C), neurological function (N), and systemic function (S). We validated the INCNS score with a cohort of 941 N-ICU patients. The 72-hours INCNS score achieved an area under the receiver operating characteristic curve (AUC) of 0.828 (95% CI: 0.802-0.854), and the 24-hours INCNS score achieved an AUC of 0.788 (95% CI: 0.759-0.817). The INCNS score exhibited significantly better discriminative and prognostic performance than APACHE II and SAPS II at both 24 hours and 72 hours in N-ICU. CONCLUSION:We developed an INCNS score with superior predictive power for functional outcome of neurocritically ill patients.
Project description:Anemia occurring as a result of inflammatory processes (anemia of inflammation, AI) has a high prevalence in critically ill patients. Knowledge on changes in iron metabolism during the course of AI is limited, hampering the development of strategies to counteract AI. This case control study aimed to investigate iron metabolism during the development of AI in critically ill patients.Iron metabolism in 30 patients who developed AI during ICU stay was compared with 30 septic patients with a high Hb and 30 non-septic patients with a high Hb. Patients were matched on age and sex. Longitudinally collected plasma samples were analyzed for levels of parameters of iron metabolism. A linear mixed model was used to assess the predictive values of the parameters.In patients with AI, levels of iron, transferrin and transferrin saturation showed an early decrease compared to controls with a high Hb, already prior to the development of anemia. Ferritin, hepcidin and IL-6 levels were increased in AI compared to controls. During AI development, erythroferrone decreased. Differences in iron metabolism between groups were not influenced by APACHE IV score.The results show that in critically ill patients with AI, iron metabolism is already altered prior to the development of anemia. Levels of iron regulators in AI differ from septic controls with a high Hb, irrespective of disease severity. AI is characterized by high levels of hepcidin, ferritin and IL-6 and low levels of iron, transferrin and erythroferrone.
Project description:Association of a high-serum ferritin with poor outcome showed that iron might play a detrimental role in the brain after intracerebral hemorrhage (ICH). Here, we investigated changes in serum iron, ferritin, transferrin (Tf) and ceruloplasmin (CP) in patients with ICH (n?=?100) at day 1 (admission), 3, 7, 14 and 21 and those in control subjects (n?=?75). The hematoma and edema volumes were also determined in ICH-patients on admission and at day 3. The Modified Rankin Scale (mRS) of 59 patients was ?3 (poor outcome) and 41?<?3 (good outcome) at day 90. Serum ferritin was significantly higher and serum iron and Tf markedly lower in patients with poor-outcome than the corresponding values in patients with good-outcome at day 1 to 7 and those in the controls. There was a significant positive correlation between serum ferritin and relative edema volume or ratio at day 1 and 3 and hematoma volume at day 1 (n?=?28), and a negative correlation between serum iron or Tf and hematoma volume at day 1 (n?=?100). We concluded that not only increased serum ferritin but also reduced serum iron and Tf are associated with outcome as well as hematoma volume.
Project description:Patients with high serum ferritin and low transferrin saturation (TSAT) levels could be considered as presenting with dysutilization of iron for erythropoiesis. However, the long-term safety of iron administration in these patients has not been well established. An observational multicenter study was performed over 3 years. In 805 patients undergoing maintenance hemodialysis (MHD), we defined dysutilization of iron for erythropoiesis in patients with lower TSAT (<20%) and higher ferritin (?100 ng/mL) levels. A time-dependent Cox hazard model was used for the evaluation of the association between dysutilization of iron for erythropoiesis and adverse events and survival. Patients with low TSAT levels showed an increased risk of cerebrovascular and cardiovascular disease (CCVD) and death compared to patients with normal or higher TSAT levels. Patients with low ferritin and high TSAT levels had a significantly lower risk of CCVD and death compared with patients with high ferritin and low TSAT levels. Higher TSAT levels were associated with male gender, age, the absence of diabetes, low levels of high-sensitivity CRP, and low ?2 microglobulin levels, but not with intravenous iron administration or ferritin levels. Although patients with low TSAT levels had a significantly higher risk of CCVD or death, high TSAT levels were not linked with iron administration. Patients, who were suspected of dysutilization of iron for erythropoiesis, had a higher risk of CCVD and death. The administration of iron should be performed cautiously for improving TSAT levels, as iron administration could sustain TSAT levels for a short term.
Project description:Human kidney predominant protein, NCU-G1, is a highly conserved protein with an unknown biological function. Initially described as a nuclear protein, it was later shown to be a bona fide lysosomal integral membrane protein. To gain insight into the physiological function of NCU-G1, mice with no detectable expression of this gene were created using a gene-trap strategy, and Ncu-g1(gt/gt) mice were successfully characterized. Lysosomal disorders are mainly caused by lack of or malfunctioning of proteins in the endosomal-lysosomal pathway. The clinical symptoms vary, but often include liver dysfunction. Persistent liver damage activates fibrogenesis and, if unremedied, eventually leads to liver fibrosis/cirrhosis and death. We demonstrate that the disruption of Ncu-g1 results in spontaneous liver fibrosis in mice as the predominant phenotype. Evidence for an increased rate of hepatic cell death, oxidative stress and active fibrogenesis were detected in Ncu-g1(gt/gt) liver. In addition to collagen deposition, microscopic examination of liver sections revealed accumulation of autofluorescent lipofuscin and iron in Ncu-g1(gt/gt) Kupffer cells. Because only a few transgenic mouse models have been identified with chronic liver injury and spontaneous liver fibrosis development, we propose that the Ncu-g1(gt/gt) mouse could be a valuable new tool in the development of novel treatments for the attenuation of fibrosis due to chronic liver damage.