scholarly journals Linkage of alterations in systemic iron homeostasis to patients’ outcome in sepsis: a prospective study

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Anna Brandtner ◽  
Piotr Tymoszuk ◽  
Manfred Nairz ◽  
Georg F. Lehner ◽  
Gernot Fritsche ◽  
...  

Abstract Background Sepsis, a dysregulated host response following infection, is associated with massive immune activation and high mortality rates. There is still a need to define further risk factors and laboratory parameters predicting the clinical course. Iron metabolism is regulated by both, the body’s iron status and the immune response. Iron itself is required for erythropoiesis but also for many cellular and metabolic functions. Moreover, iron availability is a critical determinant in infections because it is an essential nutrient for most microbes but also impacts on immune function and intravascular oxidative stress. Herein, we used a prospective study design to investigate the putative impact of serum iron parameters on the outcome of sepsis. Methods Serum markers of iron metabolism were measured in a prospective cohort of 61 patients (37 males, 24 females) with sepsis defined by Sepsis-3 criteria in a medical intensive care unit (ICU) and compared between survivors and non-survivors. Regulation of iron parameters in patients stratified by focus of infection and co-medication as well as association of the markers with sepsis severity scores and survival were investigated with linear and logistic regression corrected for sex and age effects. Results Positive correlations of increased serum iron and ferritin concentrations upon ICU admission with the severity of organ failure (SOFA score) and with mortality were observed. Moreover, high TF-Sat, elevated ferritin and serum iron levels and low transferrin concentrations were associated with reduced survival. A logistic regression model consisting of SOFA and transferrin saturation (SOFA–TF-Sat) had the best predictive power for survival in septic ICU patients. Of note, administration of blood transfusions prior to ICU admission resulted in increased TF-Sat and reduced survival of septic patients. Conclusions Our study could show an important impact of serum iron parameters on the outcome of sepsis. Furthermore, we identified transferrin saturation as a stand-alone predictor of sepsis survival and as a parameter of iron metabolism which may in a combined model improve the prediction power of the SOFA score. Trial registration The study was carried out in accordance with the recommendations of the Declaration of Helsinki on biomedical research. The study was approved by the institutional ethics review board of the Medical University Innsbruck (study AN2013-0006).

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Masood Faghih Dinevari ◽  
Mohammad Hossein Somi ◽  
Elham Sadeghi Majd ◽  
Mahdieh Abbasalizad Farhangi ◽  
Zeinab Nikniaz

Abstract Background There are limited number of studies with controversial findings regarding the association between anemia at admission and coronavirus disease 2019 (COVID-19) outcomes. Therefore, in this research, we aimed to investigate the prospective association between anemia and COVID-19 outcomes in hospitalized patients in Iran. Methods In this prospective study, the data of 1274 consecutive patients hospitalized due to COVID-19 were statistically analyzed. All biomarkers, including hemoglobin and high-sensitivity C-reactive protein (hs-CRP) levels were measured using standard methods. Anemia was defined as a hemoglobin (Hb) concentration of less than 13 g/dL and 12 g/dL in males and females, respectively. Assessing the association between anemia and COVID-19 survival in hospitalized patients was our primary endpoint. Results The mean age of the participants was 64.43 ± 17.16 years, out of whom 615 (48.27%) were anemic subjects. Patients with anemia were significantly older (P = 0.02) and had a higher frequency of cardiovascular diseases, hypertension, kidney disease, diabetes, and cancer (P < 0.05). The frequency of death (anemic: 23.9% vs. nonanemic: 13.8%), ICU admission (anemic: 27.8% vs. nonanemic:14.71%), and ventilator requirement (anemic: 35.93% vs. nonanemic: 20.63%) were significantly higher in anemic patients than in nonanemic patients (P < 0.001). According to the results of regression analysis, after adjusting for significant covariate in the univariable model, anemia was independently associated with mortality (OR: 1.68, 95% CI: 1.10, 2.57, P = 0.01), ventilator requirement (OR: 1.74, 95% CI: 1.19, 2.54, P = 0.004), and the risk of ICU admission (OR: 2.06, 95% CI: 1.46, 2.90, P < 0.001). Conclusion The prevalence of anemia in hospitalized patients with COVID-19 was high and was associated with poor outcomes of COVID-19.


2020 ◽  
Author(s):  
fali zhang ◽  
peng zhao ◽  
zhongming Qian ◽  
mingkang zhong

Abstract BackgroundLPS triggers inflammation response in periphery, whether the infection in CNS induced by LPS ICV injection affected the peripheral iron metabolism was unknown , The current study was to find out whether LPS injected to the brain could regulate hepcidin expression in liver and peripheral iron metabolism. MethodsWide type mice (IL-6+/+) and IL-6-/- mice of 8-week-old were performed on ICV injection with LPS. After 6h, hepcidin expression in liver, as well as serum iron and transferrin saturation was detected and calculated, we also tested the IL-6/JAK2/STAT3 pathway in hepcidin regulation in liver of IL-6 knockout (IL-6-/- mice) and IL-6+/+ mice, AG490 as an inhibitor of JAK2 was used to confirm the effect of IL-6/JAK2/STAT3 pathway on hepcidin expression in liver. ResultsHepcidin mRNA, IL-6 mRNA and protein expression in the liver of IL-6-/- mice was significantly lower than IL-6+/+ mice after LPS administration. IL-6 deficiency abolished the decrease of serum iron, transferrin saturation induced by LPS injection. IL-6 deficiency also abolished the decrease of Fpn1, increase of pSTAT3 and Ft-L protein in liver. AG490 significantly reduced the pSTAT3 protein and abolished the changes of Fpn1 and Ft-L expression induced by LPS in liver. ConclusionThese finding provided further evidence that the effect of central inflammation on the hepatic hepcidin expression and peripheral iron metabolism.


2005 ◽  
Vol 39 (5) ◽  
pp. 387-394 ◽  
Author(s):  
Päivi Maaranen ◽  
Antti Tanskanen ◽  
Kirsi Honkalampi ◽  
Kaisa Haatainen ◽  
Jukka Hintikka ◽  
...  

Objective: This study assessed the prevalence of pathological dissociation in the general population, and the relationship between pathological dissociation and sociodemographic and several psychiatric variables. Method: The stratified population sample consisted of 2001 subjects. The study questionnaires included the Dissociative Experiences Scale, the Dissociative Experiences Scale-Taxon, the Toronto Alexithymia Scale, the Beck Depression Inventory, and sociodemographic background. Results: The prevalence of pathological dissociation (DES-T ≥ 20) was 3.4% in the general population and did not differ significantly between genders. Men scored higher than women in the amnesia subscale, and women in the absorption and imaginative involvement subscale. The relationship between pathological dissociation, alexithymia, depression and suicidality was strong. The likelihood of pathological dissociation was nearly nine-fold higher among depressive subjects, more than seven-fold higher among alexithymic subjects, and more than four-fold higher among suicidal subjects than among the others. Frequent alcohol consumption also associated significantly with pathological dissociation. Conclusions: A significant relationship between pathological dissociation, depression, alexithymia, and suicidality was found in the general population. The importance of these factors should be examined in a prospective study design to determine causality.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9044-9044
Author(s):  
Barbara Kaye Bennett ◽  
Andrew R. Lloyd ◽  
Kate Webber ◽  
Michael Friedlander ◽  
David Goldstein ◽  
...  

9044 Background: Because a cancer diagnosis may be regarded as a potentially traumatic event with untoward consequences, much research has focussed on negative aspects of cancer diagnosis and treatment, emphasising psychological outcomes. A recent paradigm shift recognises that such a psycho-pathological approach discounts the human capacity for resilience "the ability to maintain relatively stable functioning following an aversive life event" (Bonanno GA Curr Direct in Psychol Science 2005 14(3) 135). Predictors of resilience in women who recovered uneventfully from surgical and adjuvant treatment for early stage breast cancer were investigated in a prospective study. Methods: Validated self-report measures of mood, somatic symptoms, temperament, illness attitudes, and social support were completed post-surgery. Clinical, tumor and treatment details were recorded. At end treatment and subsequently at 1, 3, 6, 9 and 12 months, self-report measures of mood and somatic symptoms were completed. Resilience was defined as: no evidence of protracted psychological or somatic distress in the 12 months following treatment completion. Identified resilient and non-resilient groups were compared and predictors sought by logistic regression. Results: Of 218 women evaluated, 106 (49%) were classified as "resilient." They either reported no clinically significant psychological or other distress post-surgery (34%) and 12months following adjuvant treatment or recovered promptly (15%) and remained well. There were no significant differences in age (52 years); marital status; tumor size; treatment; treatment toxicity (nadir hemoglobin and neutrophil count) or mortality at 5 years post treatment (8 confirmed deaths in each group). Logistic regression identified low neuroticism (temperament or personality trait) as the most significant predictor of resilience. Conclusions: These findings suggest that without any intervention almost half the women treated for breast cancer adapt well to diagnosis and treatment. These outcomes warrant further research, to provide further insight into how individuals cope with major illness and to facilitate development of programs to aid those in whom outcomes are protracted.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3354-3354
Author(s):  
Nicola J Svenson ◽  
Russell Patmore ◽  
Heidi J Cox ◽  
James R Bailey ◽  
Stephen Holding

Abstract Introduction Iron deficiency anaemia (IDA) and anaemia of chronic inflammation (AI) are the most prevalent causes of iron related anaemia in subjects with gastrointestinal disorders contributing significantly to morbidity and mortality. Diagnosis of IDA and AI is not always straight forward and currently a combination of several serum parameters (ferritin, transferrin, transferrin saturation, iron and C-reactive protein) is required. Subjects with a mixed aetiology can be difficult to interpret using traditional serum parameters, particularly in the presence of an inflammatory process. Hepcidin (a 25 amino-acid peptide hormone) in conjunction with reticulocyte haemoglobin equivalent (RetHe) has the potential to differentiate IDA from AI and in cases of mixed aetiology replacing the traditional laboratory parameters (serum iron, CRP, transferrin saturation and ferritin). Aim The aim of the study was to evaluate the performance of a commercially available ELISA assay and investigate whether hepcidin and RetHe can differentiate AI from mixed aetiology. Method The study investigated 77 patients with gastrointestinal disorders associated with anaemia in a secondary care setting using a traditional pathway of 6 tests (figure 1): Complete Blood Count (CBC), Reticulocytes, serum ferritin, CRP, transferrin, serum Iron. Hepcidin concentration was measured using a commercially available ELISA method (DRG Diagnostic GmbH, Marburg, Germany), CBC and RetHe using a Sysmex XE-2100 CBC analyser, iron parameters and CRP using Beckman Coulter platforms. Results Hepcidin correlated well with ferritin R2 = 0.79, p<0.0001. The results were compared to traditional parameters with Receiver Operator Curves (ROC) used to determine diagnostic cut off concentrations (table 1). Table 1. Sensitivity and specificity of serum ferritin and serum hepcidin used to determine diagnostic cut off values. Selected cut off values IDA AI Serum ferritin 30.0µg/L Sensitivity 83% Specificity 64% Sensitivity 55% Specificity 75% Serum hepcidin 8ng/mL Sensitivity 73% Specificity 72% Sensitivity 70% Specificity 67% Serum hepcidin 40ng/mL Sensitivity 98% Specificity 32% Sensitivity 25% Specificity 91% Ferritin was unable to distinguish IDA from AI in mixed aetiology situations. This gives rise to a new proposed 2 step pathway (figure 2) using 3 tests: CBC, RetHe and hepcidin differentiating IDA from AI in mixed aetiology cases indicating the cause of the anaemia. The RetHe value can then be used to predict the response to oral iron. Conclusion Serum hepcidin may not yet replace serum ferritin as the preferred iron status marker, but in conjunction with RetHe it may distinguish mixed aetiology subjects. This offers the potential development of a clearer clinical pathway for investigation of difficult subjects, including reduction in the number of tests required during anaemia investigations and shorter diagnosis times. The advantage of hepcidin together with RetHe over traditional iron parameters is both as a real time marker of iron status and an indication of likelihood of response to iron therapy. The patient would benefit from a shorter recovery time, unnecessary testing, reduction in ineffective treatment and overall reduction in costs. Figure 1. Current diagnostic testing pathway using 6 independent tests with serum ferritin used as the primary indicator of iron stores. Figure 1. Current diagnostic testing pathway using 6 independent tests with serum ferritin used as the primary indicator of iron stores. Figure 2. Suggestion of a new 2 step diagnostic testing pathway with serum hepcidin as the primary indicator and reticulocyte haemoglobin equivalent as the predictor of iron deficiency and response to oral iron. Figure 2. Suggestion of a new 2 step diagnostic testing pathway with serum hepcidin as the primary indicator and reticulocyte haemoglobin equivalent as the predictor of iron deficiency and response to oral iron. Disclosures Patmore: Janssen: Honoraria; Gilead: Honoraria.


2018 ◽  
Vol 5 (7) ◽  
pp. 2528
Author(s):  
Mohan Kumar ◽  
Chandan C. S.

Background: Major trauma, major surgery or sepsis include the bulk of Surgical patients who become critically ill. This relates to significant injury of a single organ system or anatomical part, or multiple injuries, often of varying severity, of different body parts good scoring or predicting system essentially clears this confusion. Predicting the patients’ outcome depends on good scoring system. Scoring systems are composed of degrees of organ dysfunction, organ failure or multiple organ failures, and anatomical derangements which eventually contribute to morbidity and mortality. With the help of such evaluation system. A well-performing ICU prognostic model helps to make meaningful comparison of the hospital’s current performance with the past. But present study focuses on mainly on SOFA score. Sequential organ failure assessment score.Methods: Scoring systems in assessing prognosis of critically ill surgical and trauma patients - a prospective study was undertaken at MVJ Medical Hospital and Research Hospital, Bangalore after the approval from Ethics Committee. The study was carried out in the period of November 2016 to September 2017 and 50 patients were included in the study.Results: Studies have shown that in the SOFA scores; cardiovascular, neurological, and respiratory, renal, haematological and hepatic dysfunctions were independent risk factors for mortality.Conclusions: In this study, extensive study of SOFA score was done from day 1 to the last day. The SOFA score on day 1 was high among non-survivors and survivors which was statistically significant (9.33 v/s 6.62, p<0.001). Also, SOFA score showed significant increasing trend in the first week, especially on first 3 days, which signifies progressive organ dysfunction among non-survivors.


2021 ◽  
Author(s):  
Clarice Listik ◽  
Rubens Gisbert Cury ◽  
Sara Carvalho Barbosa Casagrande ◽  
Eduardo Listik ◽  
Debora Arnaut ◽  
...  

Background: DBS is an established treatment option in refractory dystonia, and motor outcomes have been extensively evaluated instead of the usually neglected NMS (e.g., pain). Objective: To describe the non-motor symptoms (NMS) after Deep Brain Stimulation (DBS) surgery for refractory generalized inherited/idiopathic dystonia in a prospective study. Design and setting: A prospective study that evaluated patients in the Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo. Methods: This study evaluated patients before and one year after DBS surgery. We applied the following scales: Burke-Fahn-Marsden Rating Scale (BFMRS), Hospital Anxiety and Depression Scale (HADS), Non-Motor Symptoms Scale for Parkinson’s Disease (NMSS-PD), Parkinson’s Disease Questionnaire-8 (PDQ8) Brief Pain Inventory (BPI), Neuropathic Pain Symptom Inventory (NPSI) and McGill pain questionnaire. Results: 11 patients (38.35 ± 11.30 years) underwent surgery (36.3% women). Motor BFMRS subscore was 64.36 ± 22.94 at baseline and 33.55 ± 17.44 after surgery (p=0.003, 47.9% improvement on motor symptoms). HADS scores remained unchanged. NMSS-PD had a significant change after DBS, from 70.91 ± 59.07 to 37.18 ± 55.05 (p=0.013, 47,5% improvement). Seven patients reported pain before DBS surgery, and after one year, four patients reported chronic pain (i.e., pain improved by 42.28%). BPI’s severity and interference scores were 4.61 ± 2.84 and 4.12 ± 2.67, respectively before surgery, and 2.79 ± 2.31 (0.00–6.25) and 1.12 ± 1.32 (0.00–3.00) after DBS (p=0.043 and p=0.028). NPSI total score was 15.29 ± 13.94 before DBS, and reduced to 2.29 ± 2.98 afterward (p=0.028). McGill’s total score was 9.00 ± 3.32 before DBS, achieving 2.71 ± 2.93 after surgery (p=0.028), mostly driven by the sensory sub-score. Conclusions: We found that DBS improves NMS in dystonia, including chronic pain, anxiety, gastrointestinal symptoms, besides the already established improvement in QoL and motor symptoms.


2003 ◽  
Vol 89 (6) ◽  
pp. 586-593 ◽  
Author(s):  
Domenico Palli ◽  
Franco Berrino ◽  
Paolo Vineis ◽  
Rosario Tumino ◽  
Salvatore Panico ◽  
...  

EPIC-Italy is the Italian section of a larger project known as EPIC (European Prospective Investigation into Cancer and Nutrition), a prospective study on diet and cancer carried out in 10 European countries. In the period 1993-1998, EPIC-Italy completed the recruitment of 47,749 volunteers (15,171 men, 32,578 women, aged 35-65 years) in 4 different areas covered by cancer registries: Varese (12,083 volunteers) and Turin (10,604) in the Northern part of the country; Florence (13,597) and Ragusa (6,403) in Central and Southern Italy, respectively. An associate center in Naples enrolled 5,062 women. Detailed information for each individual volunteer about diet and life-style habits, anthropometric measurements and a blood sample was collected, after signing an informed consent form. A food frequency questionnaire specifically developed for the Italian dietary pattern was tested in a pilot phase. A computerized data base with the dietary and lifestyle information of each participant was completed. Blood samples were processed in the same day of collection, aliquoted (RBC, WBC, serum and plasma) and stored in liquid nitrogen containers. Follow-up procedures were validated and implemented for the identification of newly diagnosed cancer cases. Cancer incidence was related to dietary habits and biochemical markers of food consumption and individual susceptibility in order to test the role of diet-related exposure in the etiology of cancer and its interaction with other environmental or genetic determinants. The comparability of information in a prospective study design is much higher than in other studies. The availability of such a large biological bank linked to individual data on dietary and life-style exposures also provides the unique opportunity of evaluating the role of selected genotypes involved in the metabolism of chemical compounds and DNA repair, potentially related to the risk of cancer, in residents of geographic areas of Italy characterized by specific cancer risk and different dietary patterns. Baseline characteristics of participants are briefly described.


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