TY - JOUR A1 - Grassmann, Felix A1 - Fritsche, Lars G. A1 - Keilhauer, Claudia N. A1 - Heid, Iris M. A1 - Weber, Bernhard H. F. T1 - Modelling the Genetic Risk in Age-Related Macular Degeneration JF - PLoS One N2 - Late-stage age-related macular degeneration (AMD) is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS) for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC) of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05) than patients aged 75 and above (1.45, 95% CI: 1.36-1.54). Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96) for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population) compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population). The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available. KW - AMD KW - complement factor-H KW - grading system KW - United States KW - vitamin C KW - prevalence KW - variants KW - susceptibility KW - association KW - maculopathy KW - variant genotypes KW - genetic loci KW - macular degeneration KW - genetics of disease KW - eyes KW - cased-control studies KW - genotyping KW - human genetics Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131315 VL - 7 IS - 5 ER - TY - JOUR A1 - Eidmann, Annette A1 - Eisert, Marius A1 - Rudert, Maximilian A1 - Stratos, Ioannis T1 - Influence of Vitamin D and C on bone marrow edema syndrome — A scoping review of the literature JF - Journal of Clinical Medicine N2 - Bone marrow edema syndrome (BMES) is a rare disease with a largely unknown etiology. The aim of this scoping review is to systematically evaluate and combine the available evidence about vitamin D and C and BMES. The analysis of the manuscripts was based on country of origin, number of patients, gender, study type, epidemiology, localization, bone mineral density measurements, vitamin status and therapy. Sixty studies were included. The overall number of patients was 823 with a male-to-female ratio of 1.55:1 and a mean age of 40.9 years. Studies were very heterogeneous and of diverging scientific scope with a weak level of evidence. The hip was the most affected joint, followed by the foot and ankle and the knee; 18.3% of patients suffered from multifocal BMES. Sixteen studies reported on vitamin D levels, resulting in a high prevalence of vitamin D deficiency (47%) and insufficiency (17.9%) among BMES patients. Three BME manuscripts were associated with vitamin C deficiency. Current therapeutic interventions include conservative measures (mainly unloading), various osteoactive drugs and iloprost. In summary, data about BMES in association with vitamin status is limited. A causal relationship between vitamin D or vitamin C status, osteopenia, and BMES cannot be determined from the existing literature. KW - lower extremity KW - regional transient osteoporosis KW - bone marrow edema KW - vitamin D KW - vitamin C KW - scoping review Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297356 SN - 2077-0383 VL - 11 IS - 22 ER - TY - JOUR A1 - Dresen, Ellen A1 - Pimiento, Jose M. A1 - Patel, Jayshil J. A1 - Heyland, Daren K. A1 - Rice, Todd W. A1 - Stoppe, Christian T1 - Overview of oxidative stress and the role of micronutrients in critical illness JF - Journal of Parenteral and Enteral Nutrition N2 - Inflammation and oxidative stress represent physiological response mechanisms to different types of stimuli and injury during critical illness. Its proper regulation is fundamental to cellular and organismal survival and are paramount to outcomes and recovery from critical illness. A proper maintenance of the delicate balance between inflammation, oxidative stress, and immune response is crucial for resolution from critical illness with important implications for patient outcome. The extent of inflammation and oxidative stress under normal conditions is limited by the antioxidant defense system of the human body, whereas the antioxidant capacity is commonly significantly compromised, and serum levels of micronutrients and vitamins significantly depleted in patients who are critically ill. Hence, the provision of antioxidants and anti-inflammatory nutrients may help to reduce the extent of oxidative stress and therefore improve clinical outcomes in patients who are critically ill. As existing evidence of the beneficial effects of antioxidant supplementation in patients who are critically ill is still unclear, actual findings about the most promising anti-inflammatory and antioxidative candidates selenium, vitamin C, zinc, and vitamin D will be discussed in this narrative review. The existing evidence provided so far demonstrates that several factors need to be considered to determine the efficacy of an antioxidant supplementation strategy in patients who are critically ill and indicates the need for adequately designed multicenter prospective randomized control trials to evaluate the clinical significance of different types and doses of micronutrients and vitamins in selected groups of patients with different types of critical illness. KW - critical illness KW - vitamins KW - vitamin C KW - inflammation KW - medical nutrition therapy KW - oxidative stress KW - selenium KW - trace elements KW - micronutrients KW - vitamin D KW - zinc Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318186 VL - 47 SP - S38 EP - S49 ER - TY - JOUR A1 - Dresen, Ellen A1 - Lee, Zheng-Yii A1 - Hill, Aileen A1 - Notz, Quirin A1 - Patel, Jayshil J. A1 - Stoppe, Christian T1 - History of scurvy and use of vitamin C in critical illness: A narrative review JF - Nutrition in Clinical Practice N2 - In 1747, an important milestone in the history of clinical research was set, as the Scottish surgeon James Lind conducted the first randomized controlled trial. Lind was interested in scurvy, a severe vitamin C deficiency which caused the death of thousands of British seamen. He found that a dietary intervention with oranges and lemons, which are rich in vitamin C by nature, was effective to recover from scurvy. Because of its antioxidative properties and involvement in many biochemical processes, the essential micronutrient vitamin C plays a key role in the human biology. Moreover, the use of vitamin C in critical illness—a condition also resulting in death of thousands in the 21st century—has gained increasing interest, as it may restore vascular responsiveness to vasoactive agents, ameliorate microcirculatory blood flow, preserve endothelial barriers, augment bacterial defense, and prevent apoptosis. Because of its redox potential and powerful antioxidant capacity, vitamin C represents an inexpensive and safe antioxidant, with the potential to modify the inflammatory cascade and improve clinical outcomes of critically ill patients. This narrative review aims to update and provide an overview on the role of vitamin C in the human biology and in critically ill patients, and to summarize current evidence on the use of vitamin C in diverse populations of critically ill patients, in specific focusing on patients with sepsis and coronavirus disease 2019. KW - antioxidant KW - scurvy KW - sepsis KW - vitamin C KW - critical illness KW - COVID‐19 Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318176 VL - 38 IS - 1 SP - 46 EP - 54 ER -