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1.
Science ; 371(6534)2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33707237

RESUMO

Antiphospholipid antibodies (aPLs) cause severe autoimmune disease characterized by vascular pathologies and pregnancy complications. Here, we identify endosomal lysobisphosphatidic acid (LBPA) presented by the CD1d-like endothelial protein C receptor (EPCR) as a pathogenic cell surface antigen recognized by aPLs for induction of thrombosis and endosomal inflammatory signaling. The engagement of aPLs with EPCR-LBPA expressed on innate immune cells sustains interferon- and toll-like receptor 7-dependent B1a cell expansion and autoantibody production. Specific pharmacological interruption of EPCR-LBPA signaling attenuates major aPL-elicited pathologies and the development of autoimmunity in a mouse model of systemic lupus erythematosus. Thus, aPLs recognize a single cell surface lipid-protein receptor complex to perpetuate a self-amplifying autoimmune signaling loop dependent on the cooperation with the innate immune complement and coagulation pathways.


Assuntos
Apresentação do Antígeno , Autoimunidade , Coagulação Sanguínea/imunologia , Receptor de Proteína C Endotelial/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Lisofosfolipídeos/imunologia , Monoglicerídeos/imunologia , Animais , Anticorpos Antifosfolipídeos/biossíntese , Autoanticorpos/biossíntese , Modelos Animais de Doenças , Perda do Embrião/imunologia , Endossomos/imunologia , Receptor de Proteína C Endotelial/genética , Humanos , Imunidade Inata , Lúpus Eritematoso Sistêmico/sangue , Camundongos , Camundongos Mutantes , Esfingomielina Fosfodiesterase/metabolismo , Trombose/imunologia , Receptor 7 Toll-Like/imunologia
2.
J. optom. (Internet) ; 14(1): 50-57, ene.-mar. 2021. tab, graf
Artigo em Espanhol | IBECS-Express | IBECS | ID: ibc-ET6-1896

RESUMO

PURPOSE: Low birth weight (BW) individuals have an increased risk for myopic refractive error. However, it is unclear which ocular geometric alterations lead to an increase in myopic refractive error. This study aims to evaluate the impact of ocular biometry in interaction with BW on refractive error. METHODS: Participants of the prospective, observational, population-based Gutenberg Health Study (GHS) with self-reported BW aged 40-80 years and objective refraction and optical biometry were included. Linear regression analyses were conducted to evaluate associations between spherical equivalent with corneal power, anterior chamber depth, lens thickness and axial length and its interaction with BW adjusted for age and sex. Low BW was defined as BW < 2500 g and normal BW between 2500-4000 g. RESULTS: Overall, 5123 participants were included. Linear regression showed an interaction of axial length (B = 0.009/100 g, p = 0.002) with BW on spherical equivalent while corneal power, anterior chamber depth and lens thickness revealed no interaction with BW on refractive error. Furthermore, linear regression analysis revealed, that axial length explains 58% of variance of spherical equivalent in low BW subjects, and 54% in normal BW subjects. In contrast, corneal power explained 1% of variance of spherical equivalent in both groups. CONCLUSIONS: Our results indicate that axial length variation explains the majority of variance in refractive error, while steeper corneal shape has no conclusive effects on refractive error. Low BW is not linked to effects of steeper corneal shape on myopic refractive error, while the effect of axial length on myopia is fractionally enlarged in those subjects


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3.
Cardiovasc Res ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33724298

RESUMO

AIMS: Evidence suggests that peripheral vascular function is related to cardiovascular disease (CVD) and mortality. We evaluated the associations of noninvasive measures of flow-mediated dilatation and peripheral arterial tonometry with incident CVD and mortality. METHODS AND RESULTS: In a post-hoc analysis of the community-based Gutenberg Health Study, median age 55 years (25th/75th percentile 46/65) and 49.5% women, we measured brachial artery flow-mediated dilatation (N = 12,599) and fingertip peripheral arterial tonometry (N = 11,125). After a follow-up of up to 11.7 years, we observed 595 incident CVD events, 106 cardiac deaths, and 860 deaths in total. Survival curves showed decreased event-free survival with higher mean brachial artery diameter and baseline pulse amplitude and better survival with higher mean flow-mediated dilatation and peripheral arterial tonometry ratio (all Plog rank<0.05). In multivariable-adjusted Cox regression analyses only baseline pulse amplitude was inversely related to mortality ((hazard ratio) per standard deviation increase, 0.86, 95% confidence interval, 0.79-0.94; P = 0.0009). After exclusion of individuals with prevalent cardiovascular disease the association was no longer statistically significant in multivariable-adjusted models (hazard ratio 0.91, 95% confidence interval 0.81-1.02; P = 0.11). None of the vascular variables substantially increased the C-index of a model comprising clinical risk factors. CONCLUSIONS: In our cohort, noninvasive measures of peripheral vascular structure and function did not reveal clinically relevant associations with incident cardiovascular disease or mortality. Whether determination of pulse amplitude by peripheral arterial tonometry improves clinical decision-making in primary prevention needs to be demonstrated. TRANSLATIONAL PERSPECTIVE: In our large middle-aged community cohort with more than 15,000 individuals, median age 55 years (25th/75th percentile 46/65), 49.5% women noninvasively measured peripheral vascular function using flow-mediated dilation after upper arm occlusion or fingertip peripheral arterial tonometry was not relevantly associated with incident cardiovascular disease or mortality in multivariable-adjusted analyses. An interaction of the association of peripheral arterial tonometry with mortality by prevalent cardiovascular disease was observed. Routine measurement of flow-mediated dilation or peripheral arterial tonometry in our community cohort to screen for high risk of cardiovascular disease or mortality was not effective.

4.
JAMA Cardiol ; 6(4): 448-456, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33533883

RESUMO

Importance: Global longitudinal strain (GLS) is an emerging echocardiographic biomarker of cardiac function in heart failure (HF). Evidence from large-scale studies comprehensively investigating GLS for its association with clinical phenotypes and mortality in asymptomatic and symptomatic chronic HF is limited. Objective: To assess the factors associated with GLS and its prognostic value in patients with chronic HF. Design, Setting, and Participants: The observational, prospective MyoVasc cohort study enrolled 3289 individuals with asymptomatic to symptomatic HF between January 17, 2013, and April 27, 2018. The median follow-up was 3.2 years (interquartile range, 2.0-4.0 years). Participants with stages A to D HF according to American Heart Association (AHA) criteria were examined at a dedicated study center. Echocardiography was performed with GLS measurement by independent reviewers. Data were analyzed from September 2, 2019, to January 15, 2020. Main Outcomes and Measures: All-cause and cardiac mortality were recorded by structured follow-up and validated via death certificates. Results: In the study sample, data on GLS were available on 2440 individuals, of whom 2186 (mean [SD] age, 65.0 [10.5] years; 1418 [64.9%] men) were classified as having AHA HF stages A to D. Mean (SD) GLS worsened across AHA stages from stage A (n = 434; -19.44 [3.15%]) to stage B (n = 629; -18.01 [3.46%]) to stages C/D (n = 1123; -15.52 [4.64%]). Age (ß = -0.27; 95% CI, -0.47 to -0.067; per decade, P = .009), female sex (ß = -1.2; 95% CI, -1.6 to -0.77; per decade, P < .001), obesity (ß = 0.64; 95% CI, 0.25-1.0; P = .001), atrial fibrillation (ß = 1.2; 95% CI, 0.69-1.6; P < .001), myocardial infarction (ß = 1.5; 95% CI, 1.00-2.1; P < .001), and estimated glomerular filtration rate (ß = -0.53; 95% CI, -0.73 to -0.32; per SD, P < .001) were independently associated with GLS in multivariable regression analysis. Global longitudinal strain was associated with the severity of HF as reflected by N-terminal prohormone B-type natriuretic protein (NT-proBNP) levels after additionally adjusting for cardiac structure and function (P < .001). During follow-up, GLS was associated with all-cause mortality (hazard ratio [HR] per SD, 1.55; 95% CI, 1.19-2.01; P < .001) and cardiac death (HR per SD, 2.32; 95% CI, 1.57-3.42; P < .001) independent of image quality, observer variability, clinical profile, HF medications, NYHA class, and cardiac structure and function. After further adjustment for the NT-proBNP level, GLS remained associated with cardiac death (HR per SD, 1.60; 95% CI, 1.07-2.41; P = .02) but not all-cause mortality (HR per SD, 1.26; 95% CI, 0.95-1.66; P = .11). Conclusions and Relevance: In patients with chronic HF, GLS was associated with clinical and cardiac status, reflected neurohormonal activation, and was associated with cardiac mortality independent of clinical and cardiac status. These findings suggest that GLS may serve as a useful tool to improve risk stratification in patients with HF.

5.
Blood ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33529319

RESUMO

Patients with isolated pulmonary embolism (PE) have a distinct clinical profile from those with deep vein thrombosis (DVT)-associated PE, with more pulmonary conditions and atherosclerosis. These findings suggest a distinct molecular pathophysiology and the potential involvement of alternative pathways in isolated PE. To test this hypothesis, data from 532 individuals from the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism (GMP-VTE) Project, a multi-center prospective cohort study with extensive biobanking, were analyzed. Targeted, high-throughput proteomics, machine learning, and bioinformatic methods were applied to contrast the acute-phase plasma proteomes of isolated PE patients (n=96) against those of patients with DVT-associated PE (n=276) or isolated DVT (n=160). This resulted in the identification of shared molecular processes between PE phenotypes, as well as an isolated PE-specific protein signature. Shared processes included upregulation of inflammation, response to oxidative stress, and the loss of pulmonary surfactant. The isolated PE-specific signature consisted of five proteins: interferon-γ (IFNG), glial cell line-derived neurotrophic growth factor (GDNF), polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), peptidyl arginine deiminase type-2 (PADI2) and interleukin-15 receptor subunit α (IL-15Rα). These proteins were orthogonally validated using cis protein quantitative trait loci (cis pQTLs). External replication in an independent population-based cohort (n=5,778) further validated the proteomic results, and showed that they were prognostic for incident primary isolated PE in individuals without history of VTE (median time to event: 2.9 years, interquartile range: 1.6 - 4.2 years), supporting their possible involvement in the early pathogenesis. This study has identified molecular overlaps and differences between VTE phenotypes. In particular, the results implicate non-canonical pathways more commonly associated with respiratory and atherosclerotic disease in the acute pathophysiology of isolated PE.

6.
J Am Heart Assoc ; 10(5): e015609, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33624513

RESUMO

Background Vascular alterations induced by antineoplastic treatment might be considered as a possible underlying mechanism of increased cardiovascular sequelae in childhood cancer survivors (CCSs). We aimed to evaluate arterial stiffness among long-term CCSs and to compare the data against a population-based sample. Methods and Results Arterial stiffness was assessed by digital photoplethysmography (stiffness index; m/s) among 1002 participants of the CVSS (Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer) study, diagnosed with neoplasia (1980-1990) before an age of 15 years. A population-based sample from the GHS (Gutenberg Health Study) (n=5252) was investigated for comparison. All subjects underwent a comprehensive, standardized clinical examination in the same study center. CCSs had higher stiffness index (ß=0.66 m/s; 95% CI, 0.51-0.80 m/s) in multivariable linear regression analysis after adjustment for cardiovascular risk factors compared with the population sample of comparable age range. Stiffer vessels were found among CCSs also in absence of arterial hypertension (ß=0.66; 95% CI, 0.50-0.81) or history of chemotherapy/radiotherapy (ß=0.56; 95% CI, 0.16-0.96) in fully adjusted models. Moreover, stiffness index differed by tumor entity, with highest values in bone and renal tumors. Almost 5.2-fold higher prevalence of stiffness index values exceeding age-specific, population-based reference limits was observed among CCSs compared with GHS participants. Conclusions This is the first study demonstrating increased arterial stiffness among long-term CCSs. The data suggest that vascular compliance might differ in survivors of childhood cancer from the established development concept for arterial stiffness in the population; cancer growth and antineoplastic treatment might be relevant determinants of the pathobiological features. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02181049.

7.
Sci Rep ; 11(1): 2271, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33500534

RESUMO

Depression has been associated with increased inflammation. However, only few large-scale, prospective studies have evaluated whether inflammation leads to new cases of depression and whether this association can be found in men and women. Longitudinal data of N = 10,357 adult participants with no evidence of depression at baseline (based on Patient Health Questionnaire (PHQ-9), lifetime diagnoses, and current antidepressant medication) were evaluated for depression 5 years later. Multivariate logistic regression models were used to predict the onset of depression based on C-reactive protein (CRP) and white blood cell count (WBC). We used interaction terms and separate analyses in men and women to investigate gender-dependent associations. Based on both markers, inflammation was predictive of new cases of depression 5 years later, even when adjusting for sociodemographic, physical health, health behavior variables, and baseline depression symptoms. As established by interaction terms and separate analyses, inflammatory markers were predictive of depression in men, but not in women. Additional predictors of new onset of depression were younger age, loneliness, smoking (only in men), cancer and less alcohol consumption (only in women). The study indicates gender differences in the etiology of depressive disorders within the community, with a greater role of physical factors in men.

8.
Sci Rep ; 11(1): 2577, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510343

RESUMO

To evaluate the cost-saving of a specialized, eHealth-based management service (CS) in comparison to regular medical care (RMC) for the management of patients receiving oral anticoagulation (OAC) therapy. Costs of hospitalization were derived via diagnosis-related groups which comprise diagnoses (ICD-10) and operation and procedure classification system (OPS), which resulted in OAC-related (i.e. bleeding/ thromboembolic events) and non-OAC-related costs for both cohorts. Cost for anticoagulation management comprised INR-testing, personnel, and technical support. In total, 705 patients were managed by CS and 1490 patients received RMC. The number of hospital stays was significantly lower in the CS cohort compared to RMC (CS: 23.4/100 py; RMC: 68.7/100 py); with the most pronounced difference in OAC-related admissions (CS: 2.8/100 py; RMC: 13.3/100 py). Total costs for anticoagulation management amounted to 101 EUR/py in RMC and 311 EUR/py in CS, whereas hospitalization costs were 3261 [IQR 2857-3689] EUR/py in RMC and 683 [504-874] EUR/py in CS. This resulted in an overall cost saving 2368 EUR/py favoring the CS. The lower frequency of adverse events in anticoagulated patients managed by the telemedicine-based CS compared to RMC translated into a substantial cost-saving, despite higher costs for the specialized management of patients.Trial registration: ClinicalTrials.gov, unique identifier NCT01809015, March 8, 2013.

9.
Z Psychosom Med Psychother ; 66(4): 355-375, 2020 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-33284063

RESUMO

Psychosomatic medicine in the Gutenberg Health Study (GHS) - research questions, measurement instruments, selected results Goal: Main questions from the Gutenberg Health Study (GHS) related to psychosomatic medicine are presented: (1) Prevalence and incidence of mental illnesses, (2) Sex-specific risk- and protective factors for mental health, (3) Interplay between psychological and somatic diseases and (4) methodical-psychometric developments. Methods: The GHS is an ongoing, prospective and interdisciplinary cohort study in Mainz. The comprehensive examinations include psychological characteristics and clinical and laboratory tests. 15010 respondents were selected in the baseline study from 2007 until 2012 and re-examined after 2.5 years and 5 years. Results: Of the first 5000 respondents in the baseline study 413 women (8.7 %) and 276 men (5.8 %) indicated depressive symptoms (PHQ-9 > = 10). After five years, half of the participants with depressive symptoms at baseline also indicated depressive symptoms five years later. Risk factors for men were a lack of social support, for women smoking and Type D personality. The proportion of new cases of depression at follow-up was 4.4 %. Risk factors were symptoms of anxiety, Type D, smoking and comorbid cancer. Protective were age and social support. Findings on the association of physical and mental disorders and their behavioral and biological links (atherosclerosis, inflammation) are presented. Conclusions: Prospective assessment of biological, psychological and social parameters offers the possibility to study their interplay in the development of mental and somatic illnesses.

10.
PLoS One ; 15(12): e0243487, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33315883

RESUMO

Targeted proteomics utilizing antibody-based proximity extension assays provides sensitive and highly specific quantifications of plasma protein levels. Multivariate analysis of this data is hampered by frequent missing values (random or left censored), calling for imputation approaches. While appropriate missing-value imputation methods exist, benchmarks of their performance in targeted proteomics data are lacking. Here, we assessed the performance of two methods for imputation of values missing completely at random, the previously top-benchmarked 'missForest' and the recently published 'GSimp' method. Evaluation was accomplished by comparing imputed with remeasured relative concentrations of 91 inflammation related circulating proteins in 86 samples from a cohort of 645 patients with venous thromboembolism. The median Pearson correlation between imputed and remeasured protein expression values was 69.0% for missForest and 71.6% for GSimp (p = 5.8e-4). Imputation with missForest resulted in stronger reduction of variance compared to GSimp (median relative variance of 25.3% vs. 68.6%, p = 2.4e-16) and undesired larger bias in downstream analyses. Irrespective of the imputation method used, the 91 imputed proteins revealed large variations in imputation accuracy, driven by differences in signal to noise ratio and information overlap between proteins. In summary, GSimp outperformed missForest, while both methods show good overall imputation accuracy with large variations between proteins.


Assuntos
Proteômica/métodos , Adulto , Idoso , Algoritmos , Viés , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/normas , Feminino , Humanos , Interleucina-6/sangue , Interleucina-6/normas , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Proteômica/normas , Controle de Qualidade , Tromboembolia Venosa/metabolismo , Tromboembolia Venosa/patologia
11.
Ophthalmologica ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33197918

RESUMO

PURPOSE: To investigate the incidence of retinal detachment in the German population and assess potential risk factors. METHODS: The Gutenberg Health Study is a population-based cohort study in Mainz, Germany including subjects (n=15.010) with an age range from 35 to 74 years at baseline. Participants underwent a comprehensive ophthalmologic examination including distant-corrected visual acuity, refraction and slit-lamp examination at baseline. A computer-assisted telephone interview was conducted after 2.5 and 5 years. The 5-year cumulative incidence of retinal detachment was computed for the study sample and stratified on age decades. Risk factors were analyzed using logistic regression including age, sex, spherical equivalent, pseudophakia and prior laser retinal therapy. RESULTS: 13.416 participants (age 52.2 ±10.7 years, 48.8% female) were included in this analysis. 28 subjects had a retinal detachment in one eye, no subject had a retinal detachment in both eyes. The 5-year cumulative incidence of retinal detachment was 0.21% (95%-confidence interval: 0.14 - 0.31%), the incidence rate was 42/100.000 person-years. Risk factors were male sex (OR= 4.16, p=0.004), pseudophakia (OR=3.93, p=0.045) and myopia (OR=1.31 per diopter myopia, p<0.0001), but not prior retinal laser therapy or age. CONCLUSION: The incidence of retinal detachment in Germany at age 35 to 74 years is comparable to estimates from neighboring European countries. Risk factors are male sex, pseudophakia and myopia.

12.
J Clin Med ; 9(10)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066188

RESUMO

Venous thromboembolism (VTE) is a life-threatening disease with risk of recurrence. Oral anticoagulation (OAC) with vitamin K antagonists (VKA) is effective to prevent thromboembolic recurrence. We aimed to investigate the quality of OAC of VTE patients in regular medical care (RMC) compared to a telemedicine-based coagulation service (CS). The thrombEVAL study (NCT01809015) is a prospective, multi-center study to investigate OAC treatment (recruitment: January 2011-March 2013). Patients were evaluated using clinical visits, computer-assisted personal interviews, self-reported data and laboratory measurements according to standard operating procedures. Overall, 360 patients with VTE from RMC and 254 from CS were included. Time in therapeutic range (TTR) was higher in CS compared to RMC (76.9% (interquartile range [IQR] 63.2-87.1%) vs. 69.5% (52.3-85.6%), p < 0.001). Crude rate of thromboembolic events (rate ratio [RR] 11.33 (95% confidence interval [CI] 1.85-465.26), p = 0.0015), clinically relevant bleeding (RR 6.80 (2.52-25.76), p < 0.001), hospitalizations (RR 2.54 (1.94-3.39), p < 0.001) and mortality under OAC (RR 5.89 (2.40-18.75), p < 0.001) were consistently higher in RMC compared with CS. Patients in RMC had higher risk for primary outcome (clinically relevant bleedings, thromboembolic events and mortality, hazard ratio [HR] 5.39 (95%CI 2.81-10.33), p < 0.0001), mortality (HR 5.54 (2.22-13.84), p = 0.00025), thromboembolic events (HR 6.41 (1.51-27.24), p = 0.012), clinically relevant bleeding (HR 5.31 (1.89-14.89), p = 0.0015) and hospitalization (HR 1.84 (1.34-2.55), p = 0.0002). Benefits of CS care were still observed after adjusting for comorbidities and TTR. In conclusion, anticoagulation quality and outcome of VTE patients undergoing VKA treatment was significantly better in CS than in RMC. Patients treated in CS had lower rates of adverse events, hospitalizations and lower mortality. CS was prognostically relevant, beyond providing advantages of improved international ratio (INR) monitoring.

13.
J Thromb Haemost ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33073460

RESUMO

BACKGROUND: Severe prekallikrein deficiency (PK deficiency) is an autosomal-recessive condition thought to be very rare. Recently we reported that the previously unnoticed variant c.451dupT, p.Ser151Phefs*34 in KLKB1, which is listed in databases aggregating genome data, causes PK deficiency and is common in Africans according to gnomAD (allele frequency 1.43%). PATIENTS/METHODS: The most common African (c.451dupT) and European (c.1643G>A, p.Cys548Tyr) PK deficiency causing KLKB1 variants were analyzed in two population-based collectives of 300 Nigerian and 300 German subjects. Genome databases were evaluated for variant frequencies and ethnicity of the subjects. The geographic origin of PK-deficient cases due to 451dupT was assessed. RESULTS: Two of five patients with PK deficiency caused by homozygous 451dupT were African, one African American, one from Oman, and one of unknown origin. The frequency of 451dupT was 1.17% in the Nigerian collective (7/600 alleles); none had Cys548Tyr. Subjects with 451dupT were found among different Nigerian ethnicities. Both variants were absent in the European collective. Database research was compatible with these findings, even though mainly data of African Americans (451dupT: 1.12%-1.78%) was accessible. A relevant number of non-American Africans are included only in the 1000Genomes collective: 451dupT frequency was 1.29% in native Africans and 1.56% in African Caribbeans. CONCLUSIONS: This study underlines the higher prevalence of PK deficiency among people with African descent compared to Europeans. In order to avoid delay of necessary surgical procedures in patients of African origin, diagnostic algorithms for isolated, unexplained, activated partial thromboplastin time prolongation in these subjects should include PK deficiency screening.

14.
J Optom ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32980297

RESUMO

PURPOSE: Low birth weight (BW) individuals have an increased risk for myopic refractive error. However, it is unclear which ocular geometric alterations lead to an increase in myopic refractive error. This study aims to evaluate the impact of ocular biometry in interaction with BW on refractive error. METHODS: Participants of the prospective, observational, population-based Gutenberg Health Study (GHS) with self-reported BW aged 40-80 years and objective refraction and optical biometry were included. Linear regression analyses were conducted to evaluate associations between spherical equivalent with corneal power, anterior chamber depth, lens thickness and axial length and its interaction with BW adjusted for age and sex. Low BW was defined as BW<2500 g and normal BW between 2500-4000 g. RESULTS: Overall, 5123 participants were included. Linear regression showed an interaction of axial length (B = 0.009/100 g, p = 0.002) with BW on spherical equivalent while corneal power, anterior chamber depth and lens thickness revealed no interaction with BW on refractive error. Furthermore, linear regression analysis revealed, that axial length explains 58% of variance of spherical equivalent in low BW subjects, and 54% in normal BW subjects. In contrast, corneal power explained 1% of variance of spherical equivalent in both groups. CONCLUSIONS: Our results indicate that axial length variation explains the majority of variance in refractive error, while steeper corneal shape has no conclusive effects on refractive error. Low BW is not linked to effects of steeper corneal shape on myopic refractive error, while the effect of axial length on myopia is fractionally enlarged in those subjects.

16.
Ophthalmic Epidemiol ; : 1-9, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32990141

RESUMO

PURPOSE: This study investigates the relationship between diabetic retinopathy (DR) and birth weight (BW) in diabetic subjects sampled from the general population. METHODS: The Gutenberg Health Study (GHS) is a population-based, observational cohort study in participants aged from 35 to 74 years. Criteria for diabetes diagnosis were HbA1c ≥6.5% at study entry, a doctor-diagnosis of diabetes, or diabetes medication. The presence of DR was determined by evaluating fundus photographs. BW was assessed by self-reports. GHS participants were divided into three different BW groups (low: <2500 g; normal: 2500-4000 g; high:>4000 g). Logistic regression analysis was conducted as uni- and multivariable analysis with adjustment for age and sex. Effect mediators were separately investigated. RESULTS: A total of 1,124 GHS participants (7.5% of the cohort) had diabetes at study entry. Of these, 402 subjects (35.8%) had gradable fundus photographs, reported BW data and were included into this study. Overall, 91/402 subjects (23%) had DR. With regard to BW groups, DR was descriptively more frequent in subjects with low (28.1% [95%-CI: 14.4-47.0%; n = 32]) and high BW (30.8% [95%-CI: 19.1-45.3%; n = 52]) compared to normal BW (20.8% [95%-CI: 16.5-25.7%; n = 318]). Both high and low BW were associated with DR in multivariable analysis (high: OR = 1.68, p = .037; low: OR = 1.81, p = .05). The BW effect was mediated by duration of diabetes in both BW groups and by arterial hypertension in the low BW group. CONCLUSION: Low and high BW in persons with diabetes is related to higher risk of diabetic retinopathy. Longer duration of diabetes and higher prevalence of arterial hypertension are factors in these subjects explaining the elevated risk.

17.
Transl Vis Sci Technol ; 9(9): 35, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32884859

RESUMO

Purpose: To investigate the retinal nerve fiber layer profile measured by optical coherence tomography and its relation to refractive error and axial length. Methods: The Gutenberg Health Study is a population-based study in Mainz, Germany. At the five-year follow-up examination, participants underwent optical coherence tomography, objective refraction and biometry. Peripapillary retinal nerve fiber layer (pRNFL) was segmented using proprietary software. The pRNFL profiles were compared between different refraction groups and the angle between the maxima, i.e., the peaks of pRNFL thickness in the upper and lower hemisphere (angle between the maxima of pRNFL thickness [AMR]) was computed. Multivariable linear regression analysis was carried out to determine associations of pRNFL profile (AMR) including age, sex, optic disc size, and axial length in model 1 and spherical equivalent in model 2. Results: A total of 5387 participants were included. AMR was 145.3° ± 23.4° in right eyes and 151.8° ± 26.7° in left eyes and the pRNFL profile was significant different in the upper hemisphere. The AMR decreased with increasing axial length by -5.86°/mm (95% confidence interval [CI]: [-6.44; -5.29], P < 0.001), female sex (-7.61°; 95% CI: [-8.71; -6.51], P < 0.001) and increased with higher age (0.08°/year; 95% CI: [0.03; 0.14], P = 0.002) and larger optic disc size (2.29°/mm2; 95% CI: [1.18; 3.41], P < 0.001). In phakic eyes, AMR increased with hyperopic refractive error by 2.60°/diopters (dpt) (95% CI: [2.33; 2.88], P < 0.001). Conclusions: The pRNFL profiles are related to individual ocular and systemic parameters. Translational Relevance: Biometric parameters should be considered when pRNFL profiles are interpreted in diagnostics, i.e., in glaucoma.

18.
EBioMedicine ; 60: 102978, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32920367

RESUMO

BACKGROUND: The pathogenesis of arterial and venous thrombosis is in large part interlaced. How much platelet phenotype relates to acute venous thromboembolism (VTE) independent of the underlying cardiovascular profile is presently poorly investigated. METHODS: Platelet count and mean platelet volume (MPV), platelet aggregation in whole blood and platelet rich plasma (PRP), platelet-dependent thrombin generation (TG) and platelet surface activation markers were measured under standardized conditions. Machine learning was applied to identify the most relevant characteristics associated with VTE from a large array (N = 58) of clinical and platelet-related variables. FINDINGS: VTE cases (N = 159) presented with lower platelet count and MPV vs controls (N = 140). Whole blood aggregation showed shorter collagen/Epinephrine closure times in cases, particularly within acetylsalicylic acid (ASA) users. Within ASA users, higher PRP aggregation after adenosine diphosphate (ADP), epinephrine, collagen and arachidonic acid was observed in cases vs controls. Within non-ASA and/or subjects on anticoagulants, cases presented with lower aggregation after ADP and collagen vs controls. Lower platelet-dependent TG, higher CD63 on resting and lower PAC-1 expression after collagen/ADP in-vitro stimulated platelets further characterized VTE cases vs controls, independent of therapy. Lasso regression analysis identified 26 variables associated with VTE of which 69% were platelet-related. INTERPRETATION: Comprehensive phenotyping of platelet function identified a large proportion of low responders to ASA in VTE cases. Lower platelet-dependent TG and lower platelet reactivity after ex-vivo stimulation characterized the "platelet exhausted syndrome" in cases. Finally, from a large array of covariates including clinical risk factors, platelet biomarkers comprised 69% of all selected variables differentiating VTE cases vs controls. FUNDING: German Federal Ministry of Education and Research, CTH-Mainz and Bayer AG.

19.
Thromb Haemost ; 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32877953

RESUMO

OBJECTIVE: Tissue factor pathway inhibitor (TFPI) is a potent anticoagulant protein in the extrinsic coagulation pathway. In the present study, we aim to identify the cardiovascular determinants for total TFPI activity and its association with cardiovascular disease (CVD) and total mortality. METHODS: Total TFPI activity was assessed in a selection of the population-based Gutenberg Health Study (n = 5,000). Statistical analysis was performed to identify the determinants for total TFPI activity as well as the associations with CVD and mortality. RESULTS: Multivariable linear regression analysis identified smoking (ß 0.095 [0.054-0.136]) as a positive determinant for total TFPI activity, while diabetes (ß -0.072 [-0.134 to -0.009]), obesity (ß -0.063 [-0.101 to -0.024]), and history of coronary artery disease (CAD) were negatively associated with total TFPI activity, independent of age, sex, and the remaining cardiovascular risk factors. After adjustment for lipoprotein levels, the association between total TFPI activity levels and obesity and CAD was lost. The analysis additionally revealed a strong positive association between total TFPI activity levels and low-density lipoprotein (ß 0.221 [0.204-0.237]). The Cox regression models revealed that a higher total TFPI activity, above 97.5th percentile of the reference group, was associated with an increased mortality risk (hazard ratio = 2.58 [95% confidence interval: 1.49-4.47]), independent of age, sex, and cardiovascular risk profile. CONCLUSION: In the Gutenberg Health Study population-based cohort, the highest percentage of total TFPI correlated with an increased mortality risk. While elevated TFPI may reflect endothelial cell activation, the associations between total TFPI activity and obesity and CAD, points to additional mechanistic interactions.

20.
J Ophthalmol ; 2020: 8386160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802490

RESUMO

Purpose: Retinal vein occlusion (RVO) is the second most common retinal vascular disease and a major cause of visual impairment. In this study, we aimed to observe whether RVO cases have different antibody profiles as a new potential risk factor and whether a conversion of retinal vein occlusion (RVO) to neovascular glaucoma (NVG), one of the major complications, is occurring within a 5-year timeframe. Methods: We performed a nested case-control study (1 : 4) within the Gutenberg Health Study (GHS), a population-based, prospective cohort study in the Rhine-Main Region of Germany including 15,010 participants. RVO subjects (n = 59) were identified by grading of fundus photographs. Optic nerves of RVO subjects and age- and sex-matched controls (n = 229) at baseline and their follow-up examination after 5 years were analyzed for glaucomatous alterations. Of all RVO subjects and controls, serum autoantibody profiles were measured using in-house manufactured antigen-antibody microarrays. Results: Of the 59 RVO patients, 3 patients (5%) showed glaucomatous optic disc alterations at baseline, whereas no new glaucoma case was detected at 5-year follow-up. Four of the autoantibodies measured (against dermcidin, neurotrophin-3, superoxide dismutase 1, and signal recognition particle 14 kDa protein) were significantly increased in the serum of RVO patients (p < 0.001). Multivariable conditional logistic regression analysis showed that 3 of these 4 antibodies were independent of cardiovascular risk factors. Conclusions: We found several autoantibodies associated with RVO, targeting proteins and structures possibly involved in RVO pathogenesis.

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