scholarly journals Association of Brain Iron Overload With Brain Edema and Brain Atrophy After Intracerebral Hemorrhage

2020 ◽  
Vol 11 ◽  
Author(s):  
Ran Liu ◽  
Haoran Zhang ◽  
Shuangjuan Cheng ◽  
Yuyao Sun ◽  
Haijiao Li ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Iron Overload ◽  
Brain Edema ◽  
Brain Atrophy ◽  
Contralateral Side ◽  
Iron Deposition ◽  
Ipsilateral Side ◽  
Observational Cohort ◽  
3.0 T

Objective: This study evaluated iron overload after intracerebral hemorrhage (ICH) using ESWAN sequences.Methods: This single-center prospective observational cohort study enrolled supratentorial ICH patients. MRI was obtained with a 3.0-T scanner at day 1, day 14, day 30, and follow-up (300 days or later). R2* mapping was generated based on the ESWAN. R2* value of the ipsilateral side represented iron deposition, and the R2* value of the contralateral side served as control. R2* value was adjusted by volume and used to assess total iron overload. Brain edema was measured on T2 FLAIR-weighted images. Brain atrophy was calculated as the contralateral hemisphere volume minus the injured hemisphere volume.Results: Twnety-seven patients with a spontaneous supratentorial ICH were included in this analysis. The ipsilateral R2* value was 40.27 ± 11.62, 41.92 ± 13.56, and 60.89 ± 14.09 at days 1, 14, and 30, respectively. The R2* value was significantly higher in the ICH side than the contralateral side (p < 0.01). Increased R2* value was seen on day 30 compared to day 14 (p < 0.01). The R2* value showed logistic decay with the distance to the hematoma margin (p < 0.01). Brain edema at day 14 and brain atrophy at follow-up correlated with R2* value adjusted by volume at day 14 (p < 0.01).Conclusions: After ICH, the iron deposition in the perihematomal region was progressively increased during the first month. R2* value adjusted by volume predicted acute brain edema and chronic brain atrophy.

Intracerebral Hematoma, Perihemorrhagic Edema and Urinary Excreted Cysteinyl Leukotrienes Correlation Study

2014 ◽  
Vol 68 (2) ◽  
pp. 85-88
Author(s):  
Natalija Dolnenec-Baneva ◽  
Dijana Nikodijevic ◽  
Gordana Kiteva-Trenchevska ◽  
Igor Petrov ◽  
Dragana Petrovska-Cvetkovska ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Edema ◽  
Correlation Study ◽  
Intracerebral Hematoma ◽  
Moderate Correlation ◽  
Hematoma Volume ◽  
Cysteinyl Leukotrienes ◽  
Edema Volume ◽  
Perihemorrhagic Edema

AbstractIntroduction.Several mechanisms in formation of perihemorrhagic edema are activated after contact of brain tissue-extravasated blood in intracerebral hemorrhage. Cysteinyl leukotrienes (cysLT) (C4, D4, E4) are included in this process as significant edema factors and they determine the neurological deficit and outcome. The study aim was a 5-day follow-up (admission/3 day/5 day) of urinary cysLT, hematoma volume, edema volume values and their correlation in patients after spontaneous, primary supratentorial intracerebral hemorrhage.Methods.An enzyme immunoassay was used for urinary cysLT measured in 62 patients and 80 healthy controls. Hematoma and edema volumes were visualized and measured by computed tomography and mathematically calculated with a special spheroid shape formula (V=AxBxC/2).Results.CysLT of hemorrhagic patients (1842.20±1413.2, 1181.54±906.2, 982.30±774.2pg/ml/mg creatinine) were significantly excreted (p<0.01). Brain edema (12.86±13.5, 22.38±21.1, 28.45±29.4cm3) was significantly increased (p<0.01). Hematoma volume values (13.05±14.5, 13.13±14.7, 12.99±14.7cm3) were not significant (p>0.05). A high correlation (multiple regression) between cysLT, hematoma and edema was found on the 3rdday (R=0.6) and a moderate correlation at admission (R=0.3) and on the 5thday (R=0.3).Conclusion.In our 5-day follow-up study a significant cysLT brain synthesis and significant brain edema progression versus constant hematoma volume values in hemorrhagic patients was found. A high correlation between cysLT, hematoma and edema volume was found on the 3rdday, a moderate correlation on admission and on the 5thday, which means that high cysLT and hematoma values were associated with high/moderate edema values.

scholarly journals Minocycline-Induced Attenuation of Iron Overload and Brain Injury After Experimental Intracerebral Hemorrhage

Stroke ◽  
2011 ◽  
Vol 42 (12) ◽  
pp. 3587-3593 ◽  
Author(s):  
Fan Zhao ◽  
Ya Hua ◽  
Yangdong He ◽  
Richard F. Keep ◽  
Guohua Xi
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Iron Overload ◽  
Brain Edema ◽  
Neuronal Death ◽  
Iron Chelator ◽  
Total Iron ◽  
Brain Iron

Background and Purpose— Brain iron overload plays a detrimental role in brain injury after intracerebral hemorrhage (ICH). A recent study found that minocycline acts as an iron chelator and reduces iron-induced neuronal death in vitro. The present study investigated if minocycline reduces iron overload after ICH and iron-induced brain injury in vivo. Methods— This study was divided into 4 parts: (1) rats with different sizes of ICH were euthanized 3 days later for serum total iron and brain edema determination; (2) rats had an ICH treated with minocycline or vehicle. Serum iron, brain iron, and brain iron handling proteins were measured; (3) rats had an intracaudate injection of saline, iron, iron+minocycline, or iron+macrophage/microglia inhibitory factor and were used for brain edema and neuronal death measurements; and (4) rats had an intracaudate injection of iron and were treated with minocycline. The brains were used for edema measurement. Results— After ICH, serum total iron and brain nonheme iron increased and these changes were reduced by minocycline treatment. Minocycline also reduced ICH-induced upregulation of brain iron handling proteins and neuronal death. Intracaudate injection of iron caused brain edema, blood–brain barrier leakage, and brain cell death, all of which were significantly reduced by coinjection with minocycline. Conclusions— The current study found that minocycline reduces iron overload after ICH and iron-induced brain injury. It is also well known minocycline is an inhibitor of microglial activation. Minocycline may be very useful for patients with ICH because both iron accumulation and microglia activation contribute to brain damage after ICH.

Changes In Pituitary Iron and Volume with Deferasirox In Transfusional Iron Overload

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5161-5161
Author(s):  
Leila Noetzli ◽  
Aleya Hyderi ◽  
Ashok Panigrahy ◽  
Susan Carson ◽  
Thomas D. Coates ◽  
...  
Keyword(s):  
Iron Overload ◽  
Anterior Pituitary ◽  
Research Funding ◽  
Somatic Growth ◽  
Small Sample ◽  
Iron Deposition ◽  
Z Score ◽  
Z Scores ◽  
One Year

Abstract Abstract 5161 Introduction: The relationship between organ iron overload and clinical toxicity in chronically transfused patients is not completely understood. Given that hypogonadotropic hypogonadism (HH) is the most common endocrine problem in chronically transfused patients, it is important to qualify the effects of pituitary iron overload. MRI can image preclinical pituitary iron deposition, similar to its use in the heart, liver and pancreas. Increased pituitary R2, a surrogate for iron, and decreased pituitary volume predict clinical and biochemical HH in iron overloaded adults 1,2. However, data regarding pituitary iron deposition and its effect on pituitary growth in the pediatric population is lacking. In addition, the effect of chelation therapy on pituitary iron and volume over time is unknown. We present first year results from a two year observational trial of changes in pituitary R2 and volume in response to deferasirox therapy in patients with transfusional siderosis. Methods: We report 16 chronically-transfused patients with Thalassemia Major and one patient with Diamond Blackfan Anemia studied over a one year period. All patients were on deferasirox for at least 6 months prior to start of study; drug dosing was determined by the patient's physician and was independent of the research study. The average age at the final exam was 14.1 ± 5.2 years (range: 5.1–24.6 years). All studies were performed on a 1.5 T Philips Achieva. Anterior pituitary R2 was assessed in the sagittal and coronal planes using multiple spin echoes from 15 to 120 ms. Pituitary volume was assessed using a 3D spoiled gradient echo sequence with 1 mm3 isotropic voxels. Pituitary R2 was calculated by pixelwise monoexponential fit, with median values used to represent the overall gland R2; boundaries were confirmed by a board-certified neuroradiologist. Normative data for pituitary iron and volume was drawn from another study in 100 normal volunteers. Patient height, pituitary R2, and pituitary volume were all expressed as age corrected Z-scores. MRI estimates of hepatic iron concentration (HIC), cardiac iron (T2*), and pancreatic iron (R2*) were obtained as clinical standard of care. All statistics were performed using JMP5.1 (SAS, Cary, NC). Results: Patients were mild to moderately iron overloaded with HIC of 6.7 ± 6.9 mg/g dry weight, cardiac T2* of 31.3 ± 7.8 ms, and pancreas R2* of 117.2 ± 128.7 Hz at the beginning of the study. These results were not yet available for the one year follow up. Ferritin values were available for 16/17 of the patients at both baseline (1346.9 ± 1479.5 ng/mL) and year one visits (1102.2 ± 1074.0 ng/mL, p=0.24). Change in ferritin did not correlate with change in pituitary R2. Median sagittal measurements of pituitary R2 were 13.7 ± 1.9 Hz (baseline) and 13.4 ± 1.7 Hz (year one). An improvement was seen in average Z-score for patient height and in average Z-score for anterior pituitary volume. There was no correlation between the change in Z-score for height and the change in Z-score for pituitary volume. Figure 1 summarizes the average Z-scores for height, pituitary volume, and pituitary R2 at baseline and at year one; p-values reflect paired statistics. Discussion: The present data suggest that deferasirox monotherapy stabilizes pituitary iron levels and facilitates normal pituitary and somatic growth in children and young adults. Although reductions in pituitary R2 Z-score did not reach statistical significance, the favorable glandular and somatic growth responses suggest that deferasirox is successfully detoxifying glandular iron. Although encouraging, these data are limited by small sample size and short follow-up; two-year data will provide more robust estimates of treatment efficacy and predictors of response. References 1. Argyropoulou MI, Metafratzi Z, et al. AJR Am J Roentgenol. 2000;175:1567-1569. 2. Argyropoulou MI, Kiortsis DN, et al. Neuroradiology. 2001;43:1056-1058. Disclosures: Coates: Novartis: Research Funding, Speakers Bureau. Wood:Novartis: Consultancy, Research Funding, Symposia speaker.

scholarly journals Hemochromatosis mutations, dementia and brain iron deposition: a prospective cohort study

2020 ◽  
Author(s):  
David Melzer ◽  
Janice L Atkins ◽  
Luke C Pilling ◽  
Christine J Heales ◽  
Sharon Savage ◽  
...  
Keyword(s):  
Iron Overload ◽  
Gray Matter ◽  
Brain Mri ◽  
Iron Deposition ◽  
European Ancestry ◽  
Brain Iron ◽  
Incident Dementia ◽  
Gray Matter Volumes ◽  
Brain Iron Deposition

ABSTRACTImportanceBrain iron deposition is common in dementia, but its causal significance is uncertain. The HFE p.C282Y homozygous mutation in European ancestry populations can lead to iron overload and hemochromatosis, mainly in males. Data on brain outcomes in homozygotes are scarce.ObjectiveTo estimate HFE variant associations with MRI features plus incident dementia diagnoses during follow-up in a large community based cohort.DesignUK Biobank cohort with follow-up in routine hospitalization records (mean 8.8 years). MRI imaging available on a participant subset scanned 2014 to 2018.SettingCommunity cohort participants across England, Wales and Scotland.ParticipantsEuropean ancestry participants (n=451,186) aged 40 to 70 years at baseline, including 2,890 p.C282Y homozygotes (predominantly without baseline haemochromatosis diagnoses). MRI scanning on 9,464 males and 10,475 females, including 40 male and 75 female p.C282Y homozygotes.ExposureHFE C282Y and H63D genetic variantsMain outcome and measuresBrain MRI site specific T2* measures (lower values associated with iron deposition) and gray matter volumes. Incident dementia diagnoses during follow-up.ResultsMale p.C282Y homozygotes had lower T2* measures in several brain areas including the thalamus (beta = -1.04 standard deviations, 95% CI -1.33 to -0.76, multiple testing adjusted p-value=4.9*10-10), putamen and hippocampus, compared to those without HFE mutations. Male homozygotes also had smaller gray matter volumes in the putamen (beta -0.80 sd, 95%CI -1.12 to - 0.47, adjusted p=2.2*10-4) and ventral striatum.Diagnoses of incident dementia (Hazard Ratio HR=2.27; 95% CI 1.36 to 3.80, p=0.002) were more common in p.C282Y homozygous men, as were delirium diagnoses (HR=2.04, CI 1.09 to 3.82, p=0.03), but there was no association with Stroke.In p.C282Y homozygote females and p.C282Y/H63D heterozygotes, MRI associations were less marked.Conclusion and RelevanceIn a community sample, men with the HFE p.C282Y homozygote genotype had more brain iron deposition, smaller specific gray matter volumes, and increased incidence of dementia. As iron overload in hemochromatosis is treatable, early intervention may prevent or limit related brain pathology in male HFE p.C282Y homozygotes.Key PointsQuestionIs the hemochromatosis HFE p.C282Y homozygous variant in men associated with brain MRI features and incident dementia?FindingsOn MRI, p.C282Y homozygote males had evidence of more iron deposition in areas including the thalamus, putamen and hippocampus, plus smaller putamen gray matter volumes, compared to men without HFE mutations. In 451,186 UK Biobank participants during the mean 8.8 year follow-up, incident dementia diagnoses were more than twice as common in the 1,294 homozygous men.MeaningAs iron overload in hemochromatosis is treatable, early intervention may prevent or limit related brain pathology in male HFE p.C282Y homozygotes.

Abstract 2156: Minocycline-induced Attenuation Of Iron Overload And Brain Injury Following Experimental Intracerebral Hemorrhage

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Fan Zhao ◽  
Ya Hua ◽  
Richard F Keep ◽  
Guohua Xi
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Iron Overload ◽  
Brain Edema ◽  
Blood Brain Barrier ◽  
Neuronal Death ◽  
Total Iron ◽  
Brain Barrier ◽  
Brain Iron ◽  
Blood Brain

Background and Purpose: Brain iron overload plays a detrimental role in brain injury after intracerebral hemorrhage (ICH). A recent study found that minocycline acts as an iron chelator and reduces iron-induced neuronal death in vitro. The present study investigated if minocycline reduces iron overload after ICH and iron-induced brain injury in vivo. Methods: This study was divided into three parts. (1) Male Sprague-Dawley rats with different sizes of ICH were euthanized 3 days later for serum total iron and brain edema determination. (2) Rats had an ICH treated with minocycline or vehicle. Rats were euthanized 1, 3 and 7 days later for serum iron, brain iron, and brain iron handling protein measurements. (3) Rats had a 50µl intracaudate injection of either saline, FeCl2, FeCl2+minocycline or FeCl2+macrophage/microglia inhibitory factor and were euthanized at one day later for measurements of brain edema, blood-brain barrier disruption and neuronal death. Results: After ICH, serum total iron and brain non-heme iron increased and these changes were reduced by minocycline treatment (e.g. serum total iron at day 3: 158±36 vs. 245±22 µg/dL in the vehicle-treated group, p<0.01). Minocycline also reduced ICH-induced upregulation of brain iron handling proteins and neuronal death. Intracaudate injection of iron caused brain edema, blood-brain barrier leakage and brain cell death, all of which were significantly reduced by co-injection with minocycline (p<0.05). Conclusions: The current study found that minocycline reduces iron overload after ICH and iron-induced brain injury. It is also well known minocycline is an inhibitor of microglial activation. Minocycline may be very useful for ICH patients because both iron accumulation and microglia activation contribute to brain damage following ICH.

scholarly journals Toll-like receptor 4 (TLR4) expression is correlated with T2* iron deposition in response to doxorubicin treatment: cardiotoxicity risk assessment

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Nelu-Mihai Trofenciuc ◽  
Aurora Diana Bordejevic ◽  
Mirela Cleopatra Tomescu ◽  
Lucian Petrescu ◽  
Simina Crisan ◽  
...  
Keyword(s):  
Iron Overload ◽  
Elevated Serum ◽  
Left Ventricular ◽  
Iron Deposition ◽  
Serum Transferrin ◽  
Antitumor Antibiotic ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Baseline Serum

Abstract Although doxorubicin (Dox) is an effective antitumor antibiotic in the anthracycline class, it often induces the undesirable side effect of cardiomyopathy leading to congestive heart failure, which limits its clinical use. The primary goal of this study is to evaluate a reliable translational method for Dox-induced cardiotoxicity (CTX) screening, aiming to identify a high-risk population and to discover new strategies to predict and investigate this phenomenon. Early identification of the presence of iron deposits and genetic and environmental triggers that predispose individuals to increased risk of Dox-induced CTX (e.g., overexpression of Toll-like receptor 4 (TLR4)) will enable the early implementation of countermeasure therapy, which will improve the patient’s chance of survival. Our cohort consisted of 25 consecutive patients with pathologically confirmed cancer undergoing Dox chemotherapy and 12 control patients. The following parameters were measured: serum TLR4 (baseline), serum transferrin (baseline and 6-week follow-up) and iron deposition (baseline and 6-week follow-up). The average number of gene expression units was 0.121 for TLR4 (range 0.051–0.801). We subsequently correlated serum TLR4 levels in our cohort with myocardial iron overload using the cardiac magnetic resonance (CMR) T2* technique, the ventricular function (% ejection fraction, %EF) and serum transferrin levels. There is a strong negative linear relationship between serum TLR4 and CMR T2* values (r =  − 0.9106, ****P < 0.0001). There is also a linear correlation (either positive or negative) with EF and transferrin; no established relationship related to the sex of the patients was found. Patients with elevated serum TLR4 at baseline also exhibited an increase in serum transferrin levels and Dox-induced left ventricular dysfunction with a decreased EF (< 50%); this phenomenon was observed in 7 of 25 patients (28%) at the 6-week follow-up. There were no significant differences or correlations based on sex. We concluded that there is a direct relationship between Dox-induced CTX (indicated by elevated serum TLR4) and the times (ms) for T2* (decreases in which correspond to immediate and rapid iron overload).

scholarly journals Prevalence and Course of IgA and IgG Antibodies against SARS-CoV-2 in Healthcare Workers during the First Wave of the COVID-19 Outbreak in Germany: Interim Results from an Ongoing Observational Cohort Study

Healthcare ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 498
Author(s):  
Mark Reinwald ◽  
Peter Markus Deckert ◽  
Oliver Ritter ◽  
Henrike Andresen ◽  
Andreas G. Schreyer ◽  
...  
Keyword(s):  
Cohort Study ◽  
Healthcare Workers ◽  
Significant Proportion ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Observational Cohort Study ◽  
Igg Antibodies ◽  
University Hospitals ◽  
Observational Cohort

(1) Background: Healthcare workers (HCWs) are prone to intensified exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the ongoing pandemic. We prospectively analyzed the prevalence of antibodies against SARS-CoV-2 in HCWs at baseline and follow up with regard to clinical signs and symptoms in two university hospitals in Brandenburg, Germany. (2) Methods: Screening for anti-SARS-CoV-2 IgA and IgG antibodies was offered to HCWs at baseline and follow up two months thereafter in two hospitals of Brandenburg Medical School during the first wave of the COVID-19 pandemic in Germany in an ongoing observational cohort study. Medical history and signs and symptoms were recorded by questionnaires and analyzed. (3) Results: Baseline seroprevalence of anti-SARS-CoV-2 IgA was 11.7% and increased to 15% at follow up, whereas IgG seropositivity was 2.1% at baseline and 2.2% at follow up. The rate of asymptomatic seropositive cases was 39.5%. Symptoms were not associated with general seropositivity for anti-SARS-CoV-2; however, class switch from IgA to IgG was associated with increased symptom burden. (4) Conclusions: The seroprevalence of antibodies against SARS-CoV-2 was low in HCWs but higher compared to population data and increased over time. Screening for antibodies detected a significant proportion of seropositive participants cases without symptoms.

scholarly journals 99. Effectiveness of Antibiotic Prophylaxis Among Patients Undergoing Elective Transurethral Resection of the Prostate in the Era of Antibiotic Resistance

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S179-S180
Author(s):  
Thana Khawcharoenporn ◽  
Pimjira Kanoktipakorn
Keyword(s):  
Antibiotic Resistance ◽  
Antibiotic Prophylaxis ◽  
Transurethral Resection ◽  
Tertiary Care ◽  
Multidrug Resistant ◽  
Prophylactic Antibiotics ◽  
Care Hospital ◽  
Extended Spectrum Beta Lactamase ◽  
Observational Cohort

Abstract Background Data existing on effectiveness of antibiotic prophylaxis (AP) for transurethral resection of the prostate (TURP) are limited in the era of antibiotic resistance. Methods A 4-year prospective observational cohort study was conducted among patients undergoing TURP in an academic tertiary-care hospital during 2016–2019. Patients were excluded if pre-operative (pre-op) urine cultures were not sent or grew mixed (&gt;2) organisms, or they had pre-op urinary tract infection (UTI) or lost follow-up after TURP. Appropriateness of AP was defined as 1) correct dosing and duration and narrowest spectrum according to the hospital AP guidelines and local epidemiology and 2) being active against uropathogens isolated from the pre-op culture. Primary outcome was the rate of UTI within 30 days post TURP compared between appropriate antibiotic prophylaxis (AAP) and inappropriate antibiotic prophylaxis (IAP) groups. Results 342 patients were screened and 61 were excluded. Of the 281 patients included, 139 (49%) received AAP and 142 (51%) received IAP. The reasons for IAP were prescribing too broad-spectrum antibiotics (57%), inactive antibiotics (41%) and incorrect dosing (2%). Pre-op urine cultures were no growth in 148 patients (53%). Among the 133 positive urine cultures with 144 isolates, Escherichia coli (52%) was the most commonly isolated. Thirty-one percent of these 144 isolates produced extended-spectrum beta-lactamase (ESBL) and 23 (16%) isolates were multidrug-resistant. The resistant rates of Enterobacteriaceae were 73% for ciprofloxacin, 65% for TMP-SMX and 46% for ceftriaxone. The two most commonly prescribed prophylactic antibiotics were ceftriaxone (51%) and ciprofloxacin (34%). The rate of UTI within 30 days post-TURP was significantly higher in IAP group compared to AAP group (47% vs 27%; P&lt; 0.001). Prescribing inactive prophylactic antibiotics was the independent factor associated with 30-day post-TURP UTI (adjusted odds ratio 2.88; P=0.001). Conclusion Appropriate antibiotic prophylaxis significantly reduced UTI within 30 days of elective TURP. Obtaining pre-op urine culture and prescribing an active prophylactic agent are critical for preventing post-TURP UTI in the era of antibiotic resistance. Disclosures All Authors: No reported disclosures

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