Understanding of how the human organism functions has preoccupied researchers in medicine for a very long time. While most of the mechanisms are well understood and detailed thoroughly, medicine has yet much to discover. Iron (Fe), Copper (Cu), and Zinc (Zn) are elements on which organisms, ranging from simple bacteria all the way to complex ones such as mammals, rely on these divalent ions. Compounded by the continuously evolving biotechnologies, these ions are still relevant today. This review article aims at recapping the mechanisms involved in Fe, Cu, and Zn homeostasis. By applying the knowledge and expanding on future research areas, this article aims to shine new light of existing illness. Thanks to the expanding field of nanotechnology, genetic disorders such as hemochromatosis and thalassemia can be managed today. Nanoparticles (NPs) improve delivery of ions and confer targeting capabilities, with the potential for use in treatment and diagnosis. Iron deficiency, cancer, and sepsis are persisting major issues. While targeted delivery using Fe NPs can be used as food fortifiers, chemotherapeutic agents against cancer cells and microbes have been developed using both Fe and Cu NPs. A fast and accurate means of diagnosis is a major impacting factor on outcome of patients, especially when critically ill. Good quality imaging and bed side diagnostic tools are possible using NPs, which may positively impact outcome.

Purpose: To describe the correlation between clinically measured hyomental distance ratio (HMDR_clin) and the ultrasound measurement (HMDR_echo) in patients with and without morbid obesity and to compare their diagnostic accuracy for difficult airway prediction. Methods: HMDR_clin and HMDR_echo were recorded the day before surgery in 160 consecutive consenting patients. Laryngoscopy was performed by a skilled anesthesiologist, with grades III and IV Cormack–Lehane being considered difficult views of the glottis. Linear regression was used to assess the correlation between HMDR_clin and HDMR_echo and receiver operating curve analysis was used to compare the performance of the two for predicting difficult airway. Results: The linear correlation between HMDR_clin and HDMR_echo in patients without morbid obesity had a Pearson coefficient of 0.494, while for patients with morbid obesity this was 0.14. A slightly higher area under the curve for HMDR_echo was oberved: 0.64 (5%CI 0.56–0.71) versus 0.52 (95%CI, 0.44–0.60) (p = 0.34). Conclusion: The association between HMDR_clin and HDMR_echo is moderate in patients without morbid obesity, but negligible in morbidly obese patients. These might be explained by difficulties in palpating anatomical structures of the airway.

Inflammation in COVID-19 produces intracellular iron overload with low circulating iron available for metabolic processes. The accumulated intracellular iron generates reactive species of oxygen and results in ferroptosis, a non-programmed cell death. Since no organ is spared, iron dysmetabolism increases the mortality and morbidity. Hepcidin and the mediator interleukin 6 are believed to play a role in the process. Our aim is to evaluate the predictive values of serologic iron and inflammatory parameters in COVID-19 critically ill patients. Hence, 24 patients were included. Hepcidin and interleukin 6, along with routine blood parameters, were determined and outcomes, such as death, multiple organ damage (MOD), anemia, and need for transfusions, were assessed. The results of this pilot study indicate that iron metabolism parameters individually, as well as models consisting of multiple laboratory and clinical variables, may predict the outcomes. Further larger studies are needed to validate the results of this pilot stud. However, this paper identifies a new direction for research.

High-throughput proteomic analysis could offer new insights into the pathogenesis of systemic sclerosis (SSc) and reveal non-invasive biomarkers for diagnosis and severity. This study aimed to assess the protein signature of patients with SSc compared to that of healthy volunteers, decipher various disease endotypes using circulating proteins, and determine the diagnostic performance of significantly expressed plasma analytes. We performed targeted proteomic profiling in a cohort of fifteen patients with SSc and eighteen controls using the Olink^® (Olink Bioscience, Uppsala, Sweden)Target 96 Inflammation Panels. Seventeen upregulated proteins involved in angiogenesis, innate immunity, and co-stimulatory pathways discriminated between patients with SSc and healthy controls (HCs) and further classified them into two clusters, a low-inflammatory and a high-inflammatory endotype. Younger age, shorter disease duration, and lack of reflux esophagitis characterized patients in the low-inflammatory endotype. TNF, CXCL9, TNFRSF9, and CXCL10 positively correlated with disease progression, while the four-protein panel comprising TNF, CXCL9, CXCL10, and CX3CL1 showed high diagnostic performance. Collectively, this study identified a distinct inflammatory signature in patients with SSc that reflects a persistent T helper type 1 (Th 1) immune response irrespective of disease duration, while the multi-protein panel might improve early diagnosis in SSc.

Chronic immune activation in systemic sclerosis is supported by the production of a plethora of cytokines with proven regulatory activities of the immune responses. This study aimed to explore PBMCs’ cytokine profiles in SSc patients versus controls, as well as to investigate the balance between pro- and anti-inflammatory cytokines in association with disease duration. PBMCs were isolated from 18 SSc patients and 17 controls and further subjected to in vitro stimulation with lipopolysaccharide and heat-killed Candida albicans. Cytokine production was measured after 24 h and 7 days, respectively, using ELISA kits for interleukin (IL)-1β, IL-1 receptor antagonist (IL-1Ra), IL-6, tumor necrosis factor (TNF), IL-10, IL-17, and interferon-gamma (IFN-gamma). IL-1 β, IL-6, and TNF levels were increased in SSc patients compared with healthy volunteers irrespective of the stimulus used. IL-1Ra and Il-17 concentrations were not statistically different between groups, even though a trend toward higher levels in patients compared with their matched controls was also observed. Most cytokines demonstrated a stable course with disease progression, except for IL-10 levels, which declined over time. In conclusion, the results of this pilot study reveal that in patients with SSc a persistently enhanced immune response is established and maintained regardless of stimulus or disease duration.

COVID-19 produces cytokine-mediated persistent inflammation and is associated with elevated iron stores and low circulating iron. It is believed that central to the pathophysiological mechanism is interleukin 6 and hepcidin. A state of iron overload, termed hyperferritinemia, and inflammatory anemia take place. Both conditions are linked to a worse result in critically ill patients. Blocking the interleukin 6—hepcidin pathway with Tocilizumab could present favorable outcomes. The aim of this study was to evaluate if Tocilizumab influences survival, the occurrence of sepsis, anemia and transfusions in critically ill patients suffering from COVID-19. This prospective observational study focused on levels of interleukin 6, hepcidin and blood iron parameters in patients treated with Tocilizumab. Data were compared before and after therapy as well as between treated and control groups. Results indicate that there is no difference in terms of survival nor in the rate of anemia or sepsis occurrence. Hepcidin was elevated and anemia ensued after treatment, which could indicate alternative pathways. In conclusion, when the classic interleukin 6—hepcidin pathway is blocked, inflammation seems to use alternative routes. Further understanding of these pathways is required and new pharmacological therapies need to be developed to treat persistent inflammation.