Higher Serum Iron Levels Research Articles

The causal relationships between iron status and sarcopenia in Europeans: a bidirectional two-sample Mendelian randomization study.

Previous studies have indicated potential associations between metals, lifestyle factors, and sarcopenia. However, the specific causal relationships between iron status, lifestyle factors, and sarcopenia remain unclear. Therefore, we conducted a bidirectional two-sample Mendelian Randomization (MR) approach to investigate these relationships. The exposure variables included iron status, living alone, coffee intake, alcohol taken with meals, and moderate physical activity, while the outcome variable was sarcopenia, assessed by grip strength in both hands and usual walking pace. We employed the Weighted Median (WM), the Inverse Variance-Weighted (IVW), and other MR methods to explore these problems for analysis. Simultaneously, we conducted a bidirectional MR analysis to assess whether sarcopenia has a reverse causal relationship with internal iron status. In our present research, we found serum iron (P = 0.033), ferritin (P = 0.001), transferrin saturation (P = 0.029) and coffee intake (P = 0.002) revealed a negative trend for sarcopenia, living alone (P = 0.022) and alcohol taken with meal (P = 0.006) showed a opposite trend for sarcopenia. Whereas sarcopenia showed negative trend for ferritin (P = 0.041) and transferrin saturation (P = 0.043), showed the opposite trend for transferrin (P = 0.021). Our study suggested that higher serum iron levels might reduce the risk of sarcopenia. Moreover, living alone and alcohol consumption might increase the sarcopenia risk, while coffee intake and moderate physical activity could reduce the sarcopenia risk.

#2938 The association between serum iron biomarkers and health-related quality of life in patients undergoing dialysis

Abstract Background and Aims Anemia is a very common complication of chronic kidney disease, affecting most patients undergoing dialysis. Iron deficiency, one of the causes of anemia, is generally a second consideration in the management of anemia. Nephrologists mainly focus on the correction of hemoglobin, often prescribing iron therapy for this indication only. However, iron has important physiological functions besides erythropoiesis. Conversely, iron overload can lead to oxidative stress and cellular damage. Therefore, nephrologists have been cautious to prescribe iron therapy to patients with already high serum iron levels. This caution has been underscored by studies linking higher levels of iron to increased mortality. Unfortunately, evidence is lacking regarding the impact of iron on important patient-reported outcomes like health-related quality of life (HRQoL). Therefore, the aim of this study is to explore the association between serum iron biomarkers, health-related quality of life (HRQoL) and the presence of anemia-related symptoms over a one-year period in patients undergoing dialysis. Method Data were obtained from the multicenter, prospective, observational Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO). Adult patients new to dialysis were included, and had a baseline and follow-up assessments at 3, 6 and 12 months, with measurements of serum iron biomarkers ferritin and transferrin saturation (TSAT). HRQoL, encompassing physical and mental HRQoL, was measured using the validated 12-item Short Form Health Survey (SF12, summary scores ranging from 0 to 100). The presence of anemia-related symptoms: fatigue, shortness of breath, restless legs and muscle cramps were assessed using the Dialysis Symptom Index. Patients were categorized into 4 groups depending on their ferritin levels (μg/L): <200, 200–500 (reference), >500–700 and >700, and into 3 groups depending on their TSAT levels (%) at baseline: <20, 20–39 (reference), and ≥40. Longitudinal analyses were conducted using sequential conditional mean models to adjust for time-independent and time-varying confounding. All analyses captured the overall association over a one-year follow-up. Results We included 1069 patients, of whom 76% started hemodialysis, the median age was 68, 66% were male, and 32% were receiving iron therapy. Over a one-year follow-up, patients with ferritin <200 μg/L had similar physical HRQoL (MD=0.5 ; 95% CI –2.4 to 3.3 ) and mental HRQoL (MD=0.04 ; 95% CI -2.0 - 2.0) compared to the reference group with ferritin between 200–500 μg/L. Patients with ferritin between 501–700 μg/L also had a similar physical and mental HRQoL mental HRQoL compared to those with ferritin between 200-500 μg/L. This was also found for patients with ferritin above 700 μg/L (Fig. 1). Similarly, patients with TSAT levels below 20% and patients with TSAT levels ≥40% had comparable physical and mental HRQoL compared the reference group of patients with a TSAT between 20-39% (Fig. 2). For the secondary objectives, we found no significant differences in the anemia-related symptoms fatigue, shortness of breath, restless legs, or muscle cramps between patients with various levels of ferritin nor between the various TSAT groups. Conclusion We found that dialysis patients with higher or lower levels of ferritin or TSAT did not have a significantly different physical or mental HRQoL over a one year-follow up after starting dialysis. Similarly, no significant differences were found in the presence of fatigue, shortness of breath, restless legs, and muscle cramps between patients with these higher or lower levels of serum iron markers. And although iron levels do have impact on clinical outcomes such as mortality, these results suggest that they do not influence patient reported outcomes such as physical and mental HRQoL.

1153 Many Reasons for Restless Legs, Not to Rest

Abstract Introduction Restless leg syndrome (RLS) involves an urge to move the legs that is exacerbated by rest, relieved by movement, and most prominent in the evening. While RLS is commonly associated with low ferritin, here we present a complex case in a patient requiring phlebotomy for symptom control related to elevated ferritin levels. Report of case(s) A 52 year-old male presented with uncontrolled RLS diagnosed 12 years prior. Sleep history included obstructive sleep apnea (OSA) on CPAP and hypersomnolence. Diagnostic polysomnogram was notable for an AHI 36.4 events/hr with associated hypoxia. Ferritin was 374ng/mL. He presented to our clinic on melatonin and wearing socks with bars of soap atop his feet. On exam, he was obese and plethoric with significant hypersomnolence despite excellent CPAP compliance. He was previously treated unsuccessfully with a combination of phenobarbital, trazodone, and ropinirole, which exacerbated his hypersomnia. He drank 4-5 liters (L) of soda daily. In the 5 years after initial presentation, he went through periods of total cessation to drinking up to 12L a day. He eventually developed uncontrolled diabetes, hypertension, hyperlipidemia, and NASH with advanced fibrosis. He was referred to Hematology and underwent therapeutic phlebotomy every 2-4 months. He was found to have HFE-C282Y Heterozygous mutation and NASH fibrosis without iron overload on MRI. His RLS was eventually controlled with a combination of pramipexole 1.5 mg, gabapentin 1800 mg, alprazolam 0.5 mg along with therapeutic phlebotomy to maintain a ferritin level less than 250 ng/mL. His hypersomnia was managed with amphetamine-dextroamphetamine. Conclusion RLS has been associated with high serum ferritin, iron, and saturation transferrin index levels with a low transferrin level due to impaired mobilization of stored iron. Iron deposits can be seen on MRI in the globus pallidus, dentate, red nuclei and substantia nigra. In this patient, soda cessation would help improve his diabetes, thereby decreasing chronic inflammation and lowering ferritin levels. Chronic liver disease, HFE C282Y mutations, and hypoxia from OSA can also contribute to increased ferritin levels. Abstaining from caffeine can likewise improve symptoms of RLS as caffeine is known to heighten proprioceptive awareness and increase neuromuscular reactivity which may include myoclonus. Support (if any)

Hemojuvelin-mediated hepcidin induction requires both bone morphogenetic protein type I receptors ALK2 and ALK3

AbstractHemojuvelin (HJV) is a glycosylphosphatidylinositol-anchored protein of the repulsive guidance molecule family acting as a bone morphogenetic protein (BMP) coreceptor to induce the hepatic iron regulatory protein hepcidin. Hepcidin causes ubiquitination and degradation of the sole known iron exporter ferroportin, thereby limiting iron availability. The detailed signaling mechanism of HJV in vivo has yet to be investigated. In the current manuscript, we used an established model of adeno-associated virus (AAV)-mediated liver-specific overexpression of HJV in murine models of hepatocyte-specific deficiency of the BMP type I receptors Alk2 or Alk3. In control mice, HJV overexpression increased hepatic Hamp messenger RNA (mRNA) levels, soluble HJV (sHJV), splenic iron content (SIC), as well as phosphorylated small mothers against decapentaplegic protein (pSMAD1/5/8) levels. In contrast, in Alk2fl/fl;Alb-Cre and Alk3fl/fl;Alb-Cre mice, which present with moderate and severe iron overload, respectively, the administration of AAV-HJV induced HJV and sHJV. However, it did not rescue the iron overload phenotypes of those mice. Serum iron levels were induced in Alk2fl/fl;Alb-Cre mice after HJV overexpression. In phosphate-buffered saline–injected Alk3fl/fl;Alb-Cre mice, serum iron levels and the expression of duodenal ferroportin remained high, whereas Hamp mRNA levels were decreased to 1% to 5% of the levels detected in controls. This was reduced even further by AAV-HJV overexpression. SIC remained low in mice with hepatocyte-specific Alk2 or Alk3 deficiency, reflecting disturbed iron homeostasis with high serum iron levels and transferrin saturation and an inability to induce hepcidin by HJV overexpression. The data indicate that ALK2 and ALK3 are both required in vivo for the HJV-mediated induction of hepcidin.

Serum Iron Levels, Dietary Iron Intake, and Supplement Use in Relation to Metabolic Syndrome in Adolescents: A Cross-Sectional Study.

The objective of this study was to investigate the potential associations between serum iron levels, dietary iron intake, and iron supplementation, and the prevalence of metabolic syndrome (MetS) in adolescents A cross-sectional analysis was conducted, utilizing data from adolescents participating in the 2003-2018 cycle of the National Health and Nutrition Examination Survey (NHANES). Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) pertaining to serum iron, dietary iron, and iron supplementation were derived through multivariate logistic regression models. Additionally, a restricted cubic spline (RCS) regression model was applied to explore the nonlinear relationship between dietary iron and serum iron concerning MetS. The study encompassed 4858 American adolescents aged 12 to 19, among whom 413 (8.5%) manifested MetS. The study cohort exhibited an average age of 15.52years, comprising 2551 males (52.51%) and 2307 females (47.49%). Relative to individuals in the lowest serum iron quartile, those in the highest quartile for serum iron (OR = 0.33, 95% CI 0.21-0.50), the highest quartile for dietary iron (OR = 0.53, 95% CI 0.32-0.89), and those utilizing iron supplements (OR = 0.61, 95% CI 0.37-0.99) evinced a diminished prevalence of MetS, even post adjustment for potential confounding variables. A non-linear relationship was discerned between serum iron and MetS, exhibiting a statistically significant negative correlation when serum iron concentrations exceeded the inflection point (serum iron = 8.66µmol/L, P for nonlinear < 0.001). This investigation reveals that higher levels of serum iron, increased dietary iron intake, and the use of iron supplements are linked to a lower prevalence of MetS in US adolescents. These findings suggest that dietary modifications could play a role in promoting the health of adolescents.

COVID associated mucormycosis: various trends, effects of treatment and sequelae

Background: With second wave of covid-19 pandemic rapid rise in cases of covid associated mucormycosis (CAM) was detected. The primary reason that appears to be facilitating Mucorales spores to germinate in people with COVID-19 is an ideal environment of low oxygen, high blood glucose, acidic medium (metabolic acidosis, diabetic ketoacidosis [DKA], high serum iron levels. Aim of this study is to evaluate the extent of disease, its causative factors, various associations and effect of treatment. Methods: This is a prospective study done on 180 patients. Detailed history and diagnostic nasal endoscopic guided biopsies were taken and sent for histopathological and microbial examination. Computed tomography (CT) and MRI of paranasal sinus, orbit, skull base and brain were done. The data collected was entered in Microsoft excel and analyzed data was presented in form of frequency and percentage shown by bar chart and pie charts. Results: The average age of the patients was 50.53 ± 11.280 years. Majority of patients were male (73.3%). Mean duration of onset was 19.28±11.482 days. The most common presenting symptom was headache( 90%). 98.9% (N=178) patients were diabetics, 52.2% patients were known diabetics, newly diagnosed diabetics were 41.7%. 73.90% patients had history of steroid intake. 39 patients were certified dead with overall 21.7% mortality rate. Conclusions: Increase in mucormycosis in Indian context appears to be an unholy intersection of trinity of COVID-19, Diabetes mellitus and corticosteroid. High suspicion, early diagnosis and rigorous management is the key to favourable prognosis.

Low ceruloplasmin levels exacerbate retinal degeneration in a hereditary hemochromatosis model.

In a previous report, a 39-year-old patient with high serum iron levels from hereditary hemochromatosis (HH) was diagnosed with a form of retinal degeneration called bull's eye maculopathy. This is atypical for patients with HH, so it was theorized that the low serum levels of ferroxidase ceruloplasmin (CP) of this patient coupled with the high iron levels led to the retinal degeneration. CP, by oxidizing iron from its ferrous to ferric form, helps prevent the oxidative damage caused by ferrous iron. To test this, a hepcidin knockout (KO) mouse model of HH was combined with Cp KO to test whether the combination would lead to more severe retinal degeneration. Monthly in vivo retinal images were acquired and, after 11 months, mice were euthanized for further analyses. Both heterozygous and homozygous Cp KO increased the rate and severity of retinal degeneration. These results demonstrate the protective role of CP, which is most likely owing to its ferroxidase activity. The findings suggest that CP levels may influence the severity of retinal degeneration, especially in individuals with high serum iron.

Correlation of T-regulatory Cells and Iron Status in β-Thalassemia Major Patients.

Background The increased risk of infections in transfusion-dependent β-thalassemia major (TDT) patients is mainly due to underlying immune dysfunction; however, its cause is largely unidentified. There is sufficientevidence to suggest immune changes due to iron deficiency; however, similar studies demonstrating the effects of iron excess on immune cells in these cases are limited. Aim and objectives To analyze the correlation between T-regulatory cells and iron stores in β-thalassemia major patients. Methods In this study, 20 β-thalassemia major cases and 20 healthy controls were studied for complete hemogram, iron profile, and flow cytometric immunophenotyping for CD3+, CD4+, CD8+, and T-regulatory cells markers (CD4+CD25+ and CD4+CD25+FOXP3+). Result Significantly higher levels of serum iron, ferritin, transferrin saturation, and CD4+ cell percentage were observed in cases than in controls. In 70% of cases with serum ferritin cut-off levels of less than 1000 µg/L, the T-regulatory cell marker CD4+CD25+ and serum ferritin revealed a significant moderate positive correlation (p=0.031, r=0.627). These same 70%cases also demonstrated a moderately significant positive correlation between serum iron and absolute lymphocyte count (r=0.529, p=0.042). Conclusion The results suggest that serum ferritin in excess amounts can increase T-regulatory cells, which may further alter the immune status of TDT patients; however, the absence of such a correlation in cases with serum ferritin of more than 1000 µg/L remains unanswered. It is important to understand immune system alterations as this will help provide new modalities for managing thalassemia patients in the form of immunoregulatory therapies.

A pilot study to evaluate clinical factors associated with iron and ferritin elevations during pediatric extracorporeal membrane oxygenation.

Introduction: Elevations in serum ferritin and serum iron occur during pediatric extracorporeal membrane oxygenation (ECMO). Previous reports attribute the elevation to frequent red blood cell transfusions and/or hemolysis. Chronic transfusion can cause iron deposition in tissues leading to multisystem organ dysfunction. This study aims identify clinical factors associated with elevated ferritin and iron in pediatric ECMO patients, along with post-decannulation magnetic resonance imaging (MRI) assessment of iron deposition in liver and brain.Methods: Prospective, pilot study, using descriptive statistics to investigate potential associations between patient characteristics, serum ferritin and iron levels, and post-decannulation hepatic and basal ganglia iron deposition.Results: In this study, nine patients (100%) had elevated serum ferritin levels during ECMO. High ferritin levels were more common with veno-arterial than with veno-venous cannulation (p = 0.026) and were also associated with high plasma free hemoglobin levels (p < 0.001). Five patients presented with elevated serum iron levels. High serum iron levels were associated with higher daily (p = 0.016) and cumulative transfusion volumes (p = 0.013) as well ECMO duration beyond 7days. MRI scans were performed on three patients with no evidence of abnormal iron deposition detected in the liver or brain.Conclusions: This pilot study shows that during pediatric ECMO, elevations in serum ferritin and serum iron occur and those elevations may be related to the cannulation modality, ECMO duration, amount of hemolysis, and volume of red blood cell transfusions. Further investigation is warranted to fully understand the implications of elevated serum iron and ferritin in pediatric ECMO.

Predictive value of ferroptosis-related biomarkers for diabetic kidney disease: a prospective observational study

AimsTo explore the predictive value of ferroptosis-related (FR) biomarkers for diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM).MethodsThis prospective observational study enrolled patients with T2DM at the Second Hospital of Jilin University between December 2021 and March 2022. DKD was measured by the urinary albumin-to-creatinine ratio. Receiver operating characteristic curve (ROC) analysis was performed to assess the predictive value of ferroptosis-related biomarkers for DKD.The risk factors for massive proteinuria were performed by multivariable logistic regression analysis.ResultsFinally, 118 patients (53.0 ± 12.2 years, 76 males) were enrolled, 52 of them without DKD (had normal proteinuria), while 66 with DKD. (Forty-one had microproteinuria, and 25 had massive proteinuria.) FR biomarkers, including acyl-CoA synthase long chain family member 4 (ACSL4), malondialdehyde (MDA), and reactive oxygen species (ROS), were significantly higher in the massive proteinuria group than in the other groups, while glutathione peroxidase 4 (GPX4) was significantly lower (all P < 0.05). The area under the ROC of the combination of GPX4, ACSL4, MDA, and ROS for predicting DKD was 0.804 (P < 0.001). Additionally, multivariate logistic regression analysis showed that the course of disease and ferritin levels were independent risk factors for massive proteinuria, while high serum iron, transferrin, and GPX4 levels were independent protective factors for massive proteinuria in patients with T2DM (all P < 0.05).ConclusionsThe GPX4, ACSL4, MDA, and ROS combination might have a good predictive value for DKD. Additionally, the course of disease, ferritin levels, serum iron, transferrin, and GPX4 were independently associated with massive proteinuria.

DRIVERS OF HYPERFERREMIA IN CHILDREN LIVING ON RADIOLOGICALLY CONTAMINATED TERRITORIES AFTER THE CHNPP ACCIDENT IN UKRAINE.

assessment of clinical-hematological and metabolic-biochemical parameters of the of bone tissue and hormonal regulation depending on the serum iron content and radiation dose values in children living on radiologically contaminated territories after the ChNPP accident in Ukraine. Children (n = 271) living on radiologically contaminated territories (RCT) of Ukraine were involved in the study. Three study groups were formed according to the serum iron level (SIL), namely group I with SIL 10.0-22.0 μmol/l (n = 92), group II with SIL 23.0-34.0 μmol/l (n = 144), and group III with SIL above 35.0 μmol/l (n = 35). Diseases in the family tree, bodyweight at birth, complaints on osalgia, bone fractures, jaw anomalies, dental caries, and obesity were accounted. Morphometric parameters of erythrocytes and hemogram elements were analyzed. Creatinine, alkaline phosphatase, calcium, total protein, iron, cholesterol, bilirubin, and transaminases were assayed in blood serum. The urine content of the 19 free amino acids, serum content of the free thyroxine (FT4), pituitary thyroid-stimulating hormone (TSH), and cortisol were assayed both with bone tissue density. Individual radiation doses were calculated. In 12.9 % of cases the SIL was > 35.0 μmol/l. Relatives with endocrine diseases were often present in the family tree of children with SIL > 23.0 μmol/l. There were increased urine content of the free amino acids (p < 0.05) and signs of protein degradation under high SIL. Contents of amino acids involved in collagen synthesis and antioxidant status (alanine, serine, glutamine, aspartic acid) and iron metabolism (arginine, leucine) were assayed at the highest levels (p < 0.05). Urinary levels of valine, lysine, and methionine, which are associated with iron metabolism, were decreased (p < 0.05). An inverse correlation (rs = -0.58; p < 0.01) was established between the serum TSH and cortisol levels regardless of the SIL. Serum TSH level directly correlated with urine content of amino acids involved in collagen synthesis. An inverse correlation (rs = -0.55; p < 0.001) was established between the serum TSH level and urine content of tyrosine that is essential for the thyroid hormone (triiodothyronine and thyroxine) synthesis.Cortisol was found having a negative effect on protein synthesis. Inverse correlation was established between the serum cortisol level and urine content of the free amino acids essential for collagen synthesis. There was no dependence of the average radiation dose values on the SIL. An inverse correlation was determined between the patient's radiation dose and SIL > 35.0 μmol/l (rs = -0.29; p < 0.05). The increased SIL in children living on RCT may occur due to both a genetic predisposition and the acquired factors driving protein and mineral metabolism of bone and their hormonal regulation.

Association of Biochemical Anemic Markers in STEMI and NSTEMI Patients – A Retrospective Study

Body iron stores and its significant association with the increased risk of cardiac disease was first time reported by the National Health and Nutrition Examination Survey. There are several molecular mechanisms and discrete pathways involved in developing Myocardial Infarction (MI) as a result of increased body iron store. Various studies showed that there lies a significant association between serum iron and serum ferritin with the MI, but to the best of our knowledge studies have not focused on the difference in their levels in STEMI and NSTEMI patients. Hence, the aim of the study is to associate the levels of iron and ferritin with STEMI and NSTEMI patients and the objective of the study is to investigate and associate the iron, ferritin and lipid profile parameters among STEMI and NSTEMI patients. The cross-sectional study recruited 75 individuals who lie in the age group of 25-55 years. The participants were divided into three groups with 25 participants in STEMI, 25 in NSTEMI (based on the ECG findings and cardiologist findings) and 25 healthy participants who are age and sex-matched as controls. The blood sample was obtained from the participants and analysed for the following biochemical parameters: CK - MB, iron, ferritin, and lipid profile. The data was analysed using SPSS software and represented as mean and SD. One-way ANOVA, Pearson’s correlation and odds calculation were carried out. For all statistical test p value &lt;0.05 were considered as significant. It is found that serum iron and ferritin were significantly elevated in STEMI individuals compared to NSTEMI and controls. But the lipid profile levels were increased in NSTEMI individuals. It is found that individuals with increased levels of iron and ferritin are at high risk of developing STEMI and NSTEMI compared with controls. Iron and ferritin were significantly elevated in STEMI individuals compared to NSTEMI individuals. In NSTEMI group lipid profile levels were increased and is associated with ferritin levels compared to STEMI group. Independent to the type of MI, individuals with high levels of serum iron and ferritin are at higher risk of developing myocardial infarction.&#x0D;

Evaluating risk factors for catheter-related infections in hemodialysis patients

Introduction: Catheter-related infection in the patients with end-stage renal disease (ESRD) is one of the leading causes of death. Identifying risk factors for infection, including patients’ iron profile, plays an important role in preventing this complication. Objectives: In this study, we aimed to determine the risk factors of catheter-related infections among the ESRD patients in Qazvin, Iran. Patients and Methods: In this observational study, 41 patients with hemodialysis venous catheter-related infection (case group) and 42 patients without catheter-related infection ( control group) in Qazvin educational and medical centers were studied. The definition of functional iron deficiency anemia included ferritin &lt;500 ng/mL and serum iron/total iron-binding capacity (TIBC) &lt;30%. The laboratory evaluation method was based on enzyme-linked immunosorbent assay method. Definition of catheter-related infection in this study consisted of two positive results of the three cultures from blue and red catheter lines and blood at the same time with the same microorganism. Results: In studying iron parameters, a significant difference between serum iron levels and transferrin saturation in the two groups was detected (P values of 0.0016 and 0.003, respectively). Both parameters were higher in the control group. The most common microorganism causing the infection was Staphylococcus aureus (43.9%) and most of the catheters used were of temporary internal jugular vein types. The most important risk factors in the incidence of catheter infection were diabetes mellitus (OR = 5.059) and high serum iron levels (OR = 1.053). Decreased transferrin saturation levels reduced the risk of infection (OR = 0.825). Conclusion: There was a relationship between iron profile and diabetes mellitus and the increased risk of catheter-related infections. To prevent infection, patients with ESRD undergoing hemodialysis with venous catheters, blood sugar and serum iron levels need to be monitored carefully and iron overdose should be prevented in these patients.

Mucormycosis – A prosthodontists perspective

Mucormycosis, an opportunistic fungal infection commonly associated with diabetes, is now intermittent as a result of co-infection with COVID-19 and steroid use, affecting the nose and paranasal sinuses of the head and neck region, with high mortality and morbidity. It is also more common in diabetic ketoacidosis, neutropenia, cancer, organ transplantation, and/or high serum iron levels, burns, acquired immunodeficiency syndrome, indiscriminate usage of steroids, lymphoma, leukemia, poor metabolic status etc. The most common treatment protocol for such conditions is aggressive surgical debridement, which includes resection of involved maxillofacial structures such as the maxilla, orbit, and/or nose.Rehabilitation of such large maxillofacial defects is a Prosthodontic challenge, with many problems encountered such as lack of retention due to dislodging forces exerted by scarred postsurgical soft tissues, lack of bony base, lost structures of the posterior palatal seal area, multiple defect sites, and compromised medical status due to comorbidities, which also affects the defect's healing rate.For patients to survive, early diagnosis and treatment are frequently required. The clinical manifestations, etiopathogenesis, and management of the dreaded fungal infection known as mucormycosis in the head and neck region will be reviewed in this paper.

Association Between the Serum Iron and Acute Cognitive Impairment After Stroke: A Cross-Sectional Study.

Complications such as cognitive impairment are common in stroke victims. The goal of this study was to see if there was a link between blood iron levels and post-stroke cognitive impairment (PSCI) within 2weeks after stroke. A total of 313 patients with ischemic stroke were recruited and separated into two groups: PSCI (n = 202) and non-PSCI (n = 111). The Mini-mental state examination scale was used to evaluate the cognitive status within 2weeks after stroke (acute phase). The serum iron levels were divided into 4 layers: Q1 ≤ 11.7μmol/L, Q2 11.8-15.1μmol/, Q3 15.2-19.3μmol/L, Q4 ≥ 19.4μmol/L, respectively. The connection between serum iron and PSCI was then investigated further using binary logistic regression, which was adjusted for confounders. The difference in serum iron levels between the PSCI and non-PSCI group was initially conducted by the Mann-Whitney test, and a significant difference was found (14.5 (11.0-17.8) vs. 16.9 (13.7-21.8), p < .001), with no confounders being adjusted. After adjusting for confounding factors, the binary regression analysis showed that the Q4 layer showed the lowest risk of PSCI, with the Q1 layer being the reference. (odds ratio (OR) = 0.297, 95% confidence interval (CI) = 0.136-0.649, p = 0.002). A decreased risk of early-onset PSCI was linked to high serum iron levels. Low serum iron levels were found to be a risk factor for acute cognitive impairment following stroke, which could help physicians identify and take intervention measures early to reduce the risk of cognitive impairment after stroke.

Iron and Ferritin as novel screening markers of Acute Myocardial Infarction

Introduction: Cardiovascular disease is a public health problem globally. In India, the prevalence of Acute Myocardial Infarction (AMI) was 6.43%. Several causes lead to AMI, among which excess serum Iron and Ferritin is responsible for an increase in the generation of free radicals, thus accelerate atherogenesis through oxidation of Low-density lipoprotein – cholesterol (LDL-C). Assess serum Iron and Ferritin status and compare them with the cardic marker (CK-MB) among patients with AMI. Methods: The study was performed in a tertiary care centre in TamilNadu, India. This casecontrol study was conducted on 25 patients diagnosed with AMI and 25 age and sex-matched healthy participants as control group. Iron, Ferritin, CK-MB and lipid profile parameters were analyzed in serum samples of the participants. Result: The mean levels of serum Iron, Ferritin, CK-MB and lipid profile parameters were increased significantly among the cases when compared to the control group. CK-MB had a strong positive correlation with serum Iron and Ferritin. Serum Iron and Ferritin also had a positive correlation with total cholesterol and LDL-C, and a negative correlation with Highdensity lipoprotein – cholesterol. The odds of developing AMI in those with serum Iron &gt;51.5µg/dl and Ferritin &gt;137ng/dl were 36 and 61.7 times at higher risk respectively. Conclusion: Higher levels of serum Iron and Ferritin seem to be stronger risk factors for AMI, and shall be considered as early screening cardiac markers for AMI.

SARS-CoV-2 Infects Red Blood Cell Progenitors and Dysregulates Hemoglobin and Iron Metabolism

BackgroundSARS-CoV-2 infection causes acute respiratory distress, which may progress to multiorgan failure and death. Severe COVID-19 disease is accompanied by reduced erythrocyte turnover, low hemoglobin levels along with increased total bilirubin and ferritin serum concentrations. Moreover, expansion of erythroid progenitors in peripheral blood together with hypoxia, anemia, and coagulopathies highly correlates with severity and mortality. We demonstrate that SARS-CoV-2 directly infects erythroid precursor cells, impairs hemoglobin homeostasis and aggravates COVID-19 disease.MethodsErythroid precursor cells derived from peripheral CD34+ blood stem cells of healthy donors were infected in vitro with SARS-CoV-2 alpha variant and differentiated into red blood cells (RBCs). Hemoglobin and iron metabolism in hospitalized COVID-19 patients and controls were analyzed in plasma-depleted whole blood samples. Raman trapping spectroscopy rapidly identified diseased cells.ResultsRBC precursors express ACE2 receptor and CD147 at day 5 of differentiation, which makes them susceptible to SARS-CoV-2 infection. qPCR analysis of differentiated RBCs revealed increased HAMP mRNA expression levels, encoding for hepcidin, which inhibits iron uptake. COVID-19 patients showed impaired hemoglobin biosynthesis, enhanced formation of zinc-protoporphyrine IX, heme-CO2, and CO-hemoglobin as well as degradation of Fe-heme. Moreover, significant iron dysmetablolism with high serum ferritin and low serum iron and transferrin levels occurred, explaining disturbances of oxygen-binding capacity in severely ill COVID-19 patients.ConclusionsOur data identify RBC precursors as a direct target of SARS-CoV-2 and suggest that SARS-CoV-2 induced dysregulation in hemoglobin- and iron-metabolism contributes to the severe systemic course of COVID-19. This opens the door for new diagnostic and therapeutic strategies.Graphical

The TXNIP/Trx-1/GPX4 pathway promotes ferroptosis in hippocampal neurons after hypoxia-ischemia in neonatal rats

To observe the change in ferroptosis in hippocampal neurons after hypoxia-ischemia (HI) in neonatal rats and investigate the related mechanism based on the TXNIP/Trx-1/GPX4 signaling pathway. Healthy neonatal Sprague-Dawley rats, aged 7 days, were randomly divided into three groups: sham-operation (n=30), hypoxic-ischemic brain damage (HIBD) (n=30) and siRNA (TXNIP siRNA) (n=12). The classic Rice-Vannucci method was used to establish a neonatal rat model of HIBD. At 6 hours, 24 hours, 72 hours, and 7 days after modeling, Western blot was used to measure the protein expression of GPX4 in the hippocampal tissue at the injured side; at 24 hours after modeling, laser speckle imaging combined with hematoxylin-eosin staining was used to determine whether the model was established successfully; NeuN/GPX4 and GFAP/GPX4 immunofluorescence staining combined with Western blot and other methods was used to measure the protein expression of GPX4 and the signal molecules TXNIP and Trx-1 in the hippocampal tissue at the injured side; the kits for determining the content of serum iron and tissue iron were used to measure the change in iron content; quantitative real-time PCR was used to measure the mRNA expression of TXNIP, Trx-1, and GPX4. At 6 hours, 24 hours, 72 hours, and 7 days after modeling, the HIBD group had a significantly lower protein expression level of GPX4 than the sham-operation group (P<0.05). At 24 hours after modeling, the HIBD group had a significantly lower cerebral blood flow of the injured side than the sham-operation group (P<0.05), with loose and disordered arrangement and irregular morphology of hippocampal CA1 neurons at the injured side. Compared with the sham-operation group, the HIBD group had a significantly higher number of TXNIP+ cells and significantly lower numbers of Trx-1+ cells and NeuN+GPX4+/NeuN+ cells in the hippocampal CA1 region at the injured side (P<0.05), with almost no GFAP+GPX4+ cells in the hippocampal CA1 region. Compared with the sham-operation group, the HIBD group and the siRNA group had significantly higher levels of serum iron and tissue iron in the hippocampus at the injured side (P<0.05). Compared with the HIBD group, the siRNA group had significantly lower levels of serum iron and tissue iron in the hippocampus at the injured side (P<0.05). The HIBD group and the siRNA group had significantly higher mRNA and protein expression levels of TXNIP than the sham-operation group (P<0.05), and the siRNA group had significantly lower expression levels than the HIBD group (P<0.05). The HIBD group and the siRNA group had significantly lower mRNA and protein expression levels of Trx-1 and GPX4 in the hippocampus at the injured side than the sham-operation group (P<0.05), and the siRNA group had significantly higher expression levels than the HIBD group (P<0.05). HI induces ferroptosis of hippocampal neurons in neonatal rats by activating the TXNIP/Trx-1/GPX4 pathway, thereby resulting in HIBD.

MUCORMYCOSIS IN COVID 19- 2ND WAVE : CLINICAL PROFILE IN CENTRAL INDIA

A sudden surge of Rhino-Orbito-Cerebral Mucormycosis (ROCM) was observed following second wave of Covid-19 in India. Diabetes mellites (DM) , steroids, hypoxia, hyperglycemia ,metabolic acidosis or Diabetic ketoacidosis, high serum iron levels, zinc supplementation, immunosuppression along with other risk factors have been found to facilitate fungal germination. Patients diagnosed with ROCM, a total of 273, were included in the study. Detailed history was noted and assessment was done. Male:Female ratio was 2.59:1. Most common presenting age group was 31 to 50 yrs (51.65%). The commonest presenting symptom was nasal obstruction (58.97%) followed by ipsilateral facial swelling (53.11%). Palatal ulceration, blood stained nasal discharge ,orbital swelling, diminution or loss of vision, headache, loosening of teeth were among other presentations. Common associated comorbidity was diabetes(84.61%), hypertension (HTN) , anemia, immunocompromised state etc. History of associated past covid infection was seen in 75.52% while 18.68% had coexisting mucor with covid. History of steroid use was in 86.81%, O2 administration by mask in 64.10%, ventilatory support in 5.12 % and tablet zinc intake in 86.45%. Covid-19 along with DM, HTN, anemia, steroid therapy and oxygen therapy are the risk factors for ROCM. Thus regular blood sugar monitoring , judicious use of corticosteroids, maintaining hygiene of mask and circuit during oxygen therapy is recommended while treating covid.

Causal Effects of Genetically Predicted Iron Status on Sepsis: A Two-Sample Bidirectional Mendelian Randomization Study.

Background/Aim: Several observational studies showed a significant association between elevated iron status biomarkers levels and sepsis with the unclear direction of causality. A two-sample bidirectional mendelian randomization (MR) study was designed to identify the causal direction between seven iron status traits and sepsis.Methods: Seven iron status traits were studied, including serum iron, ferritin, transferrin saturation, transferrin, hemoglobin, erythrocyte count, and reticulocyte count. MR analysis was first performed to estimate the causal effect of iron status on the risk of sepsis and then performed in the opposite direction. The multiplicative random-effects and fixed-effects inverse-variance weighted, weighted median-based method and MR-Egger were applied. MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran's Q statistic methods were used to assess heterogeneity and pleiotropy.Results: Genetically predicted high levels of serum iron (OR = 1.21, 95%CI = 1.13–1.29, p = 3.16 × 10−4), ferritin (OR = 1.32, 95%CI = 1.07–1.62, p =0.009) and transferrin saturation (OR = 1.14, 95%CI = 1.06–1.23, p = 5.43 × 10−4) were associated with an increased risk of sepsis. No significant causal relationships between sepsis and other four iron status biomarkers were observed.Conclusions: This present bidirectional MR analysis suggested the causal association of the high iron status with sepsis susceptibility, while the reverse causality hypothesis did not hold. The levels of transferrin, hemoglobin, erythrocytes, and reticulocytes were not significantly associated with sepsis. Further studies will be required to confirm the potential clinical value of such a prevention and treatment strategy.