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  • 1
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    Clinical, serological and genetic predictors of response to immunotherapy in anti-IgLON5 disease
    Oxford University Press (OUP) ; 2023
    In:  Brain Vol. 146, No. 2 ( 2023-02-13), p. 600-611
    Details
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 2 ( 2023-02-13), p. 600-611
    Abstract: Anti-IgLON5 disease is a newly defined clinical entity characterized by a progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune and neurodegenerative diseases were reported. Data on immunotherapy are limited, and its efficacy remains controversial. In this study, we retrospectively investigated an anti-IgLON5 disease cohort with special focus on clinical, serological and genetic predictors of the immunotherapy response and long-term outcome. Patients were recruited from the GENERATE (German Network for Research on Autoimmune Encephalitis) registry. Along with clinical parameters, anti-IgLON5 immunoglobulin (Ig)G in serum and CSF, anti-IgLON5 IgG1-4, IgA and IgM in serum, neurofilament light chain and glial fibrillary acidic protein in serum as well as human leukocyte antigen-genotypes were determined. We identified 53 patients (symptom onset 63.8 ± 10.3 years, female:male 1:1.5). The most frequent initial clinical presentations were bulbar syndrome, hyperkinetic syndrome or isolated sleep disorder [at least one symptom present in 38% (20/53)]. At the time of diagnosis, the majority of patients had a generalized multi-systemic phenotype; nevertheless, 21% (11/53) still had an isolated brainstem syndrome and/ or a characteristic sleep disorder only. About one third of patients [28% (15/53)] reported subacute disease onset and 51% (27/53) relapse-like exacerbations during the disease course. Inflammatory CSF changes were evident in 37% (19/51) and increased blood-CSF-barrier permeability in 46% (21/46). CSF cell count significantly decreased, while serum anti-IgLON5 IgG titre increased with disease duration. The presence of human leukocyte antigen-DRB1*10:01 [55% (24/44)] was associated with higher serum anti-IgLON5 IgG titres. Neurofilament light chain and glial fibrillary acidic protein in serum were substantially increased (71.1 ± 103.9 pg/ml and 126.7 ± 73.3 pg/ml, respectively). First-line immunotherapy of relapse-like acute-to-subacute exacerbation episodes resulted in improvement in 41% (11/27) of patients and early initiation within the first 6 weeks was a predictor for therapy response. Sixty-eight per cent (36/53) of patients were treated with long-term immunotherapy and 75% (27/36) of these experienced no further disease progression (observation period of 20.2 ± 15.4 months). Long-term immunotherapy initiation during the first year after onset and low pre-treatment neurofilament light chain were significant predictors for a better outcome. In conclusion, subacute disease onset and early inflammatory CSF changes support the primary role of autoimmune mechanisms at least at initial stages of anti-IgLON5 disease. Early immunotherapy, prior to advanced neurodegeneration, is associated with a better long-term clinical outcome. Low serum neurofilament light chain at treatment initiation may serve as a potential biomarker of the immunotherapy response.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awac090
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474117-9
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  • 2
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    External quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in primary laboratories in Germany
    Springer Science and Business Media LLC ; 2020
    In:  BMC Infectious Diseases Vol. 20, No. 1 ( 2020-12)
    Details
    In: BMC Infectious Diseases, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2020-12)
    Abstract: Worldwide, an increase in antimicrobial resistance (AMR) of Neisseria gonorrhoeae has been observed. Until now, no protocol for an external quality assessment (EQA) has been available for Germany. The German gonococcal resistance network (GORENET) performed an EQA of primary laboratories in Germany in order to assess quality of antibiotic susceptibility testing, to gain information about laboratory procedures and to assess the impact of these procedures on test results. Methods Laboratories assessed drug susceptibility to cefixime, ceftriaxone, azithromycin, penicillin and ciprofloxacin for five N. gonorrhoeae strains, using their standard laboratory protocols. Minimal inhibitory concentrations (MICs) were compared to World Health Organisation (WHO) consensus results (or, if not available, reference laboratory results), while deviation by +/− one doubling dilution was accepted. Data on laboratory procedures were collected via a standardised questionnaire. Generalized linear models and conditional inference trees (CTREE) were used to assess relationships between laboratory procedures and testing outcomes. Results Twenty-one primary laboratories participated in the EQA in June 2018. 96% of ciprofloxacin MICs were reported within accepted deviations, as well as 88% for cefixime, 85% for ceftriaxone, 79% for penicillin and 70% for azithromycin. The use of interpretation standards and general laboratory procedures like agar base, incubation settings or the use of control strains strongly differed between laboratories. In statistical analysis, incubation time of cultures 〈  24 h was associated with correct measurements. Additionally, a 5% CO 2 concentration was associated with correct results regarding azithromycin compared to 3%. CTREE analysis showed that incubation time, humidity and CO 2 concentration had the greatest influence on the average deviation from consensus results. Conclusions In conclusion, we report the development of a protocol for N. gonorrhoeae antimicrobial susceptibility testing in Germany. While testing results were in accordance with the expected consensus results in 70–96%, depending on the antibiotic agent, laboratory methodology was heterogeneous and may significantly affect the testing quality. We therefore recommend the development of a standard operating procedure (SOP) for N. gonorrhoeae susceptibility testing in Germany.
    Type of Medium: Online Resource
    ISSN: 1471-2334
    URL: Article
    DOI: 10.1186/s12879-020-05234-w
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2041550-3
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  • 3
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    A genome-wide association study in autoimmune neurological syndromes with anti-GAD65 autoantibodies
    Oxford University Press (OUP) ; 2023
    In:  Brain Vol. 146, No. 3 ( 2023-03-01), p. 977-990
    Details
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 3 ( 2023-03-01), p. 977-990
    Abstract: Autoimmune neurological syndromes (AINS) with autoantibodies against the 65 kDa isoform of the glutamic acid decarboxylase (GAD65) present with limbic encephalitis, including temporal lobe seizures or epilepsy, cerebellitis with ataxia, and stiff-person-syndrome or overlap forms. Anti-GAD65 autoantibodies are also detected in autoimmune diabetes mellitus, which has a strong genetic susceptibility conferred by human leukocyte antigen (HLA) and non-HLA genomic regions. We investigated the genetic predisposition in patients with anti-GAD65 AINS. We performed a genome-wide association study (GWAS) and an association analysis of the HLA region in a large German cohort of 1214 individuals. These included 167 patients with anti-GAD65 AINS, recruited by the German Network for Research on Autoimmune Encephalitis (GENERATE), and 1047 individuals without neurological or endocrine disease as population-based controls. Predictions of protein expression changes based on GWAS findings were further explored and validated in the CSF proteome of a virtually independent cohort of 10 patients with GAD65-AINS and 10 controls. Our GWAS identified 16 genome-wide significant (P & lt; 5 × 10−8) loci for the susceptibility to anti-GAD65 AINS. The top variant, rs2535288 [P = 4.42 × 10−16, odds ratio (OR) = 0.26, 95% confidence interval (CI) = 0.187–0.358], localized to an intergenic segment in the middle of the HLA class I region. The great majority of variants in these loci ( & gt;90%) mapped to non-coding regions of the genome. Over 40% of the variants have known regulatory functions on the expression of 48 genes in disease relevant cells and tissues, mainly CD4+ T cells and the cerebral cortex. The annotation of epigenomic marks suggested specificity for neural and immune cells. A network analysis of the implicated protein-coding genes highlighted the role of protein kinase C beta (PRKCB) and identified an enrichment of numerous biological pathways participating in immunity and neural function. Analysis of the classical HLA alleles and haplotypes showed no genome-wide significant associations. The strongest associations were found for the DQA1*03:01-DQB1*03:02-DRB1*04:01HLA haplotype (P = 4.39 × 10−4, OR = 2.5, 95%CI = 1.499–4.157) and DRB1*04:01 allele (P = 8.3 × 10−5, OR = 2.4, 95%CI = 1.548–3.682) identified in our cohort. As predicted, the CSF proteome showed differential levels of five proteins (HLA-A/B, C4A, ATG4D and NEO1) of expression quantitative trait loci genes from our GWAS in the CSF proteome of anti-GAD65 AINS. These findings suggest a strong genetic predisposition with direct functional implications for immunity and neural function in anti-GAD65 AINS, mainly conferred by genomic regions outside the classical HLA alleles.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awac119
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 4
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    Characterization of a universal screening approach for congenital CMV infection based on a highly-sensitive, quantitative, multiplex real-time PCR assay
    Public Library of Science (PLoS) ; 2020
    In:  PLOS ONE Vol. 15, No. 1 ( 2020-1-9), p. e0227143-
    Details
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 15, No. 1 ( 2020-1-9), p. e0227143-
    Type of Medium: Online Resource
    ISSN: 1932-6203
    URL: Article
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    DOI: 10.1371/journal.pone.0227143
    DOI: 10.1371/journal.pone.0227143.g001
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    DOI: 10.1371/journal.pone.0227143.t001
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    DOI: 10.1371/journal.pone.0227143.s001
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    DOI: 10.1371/journal.pone.0227143.s006
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2020
    detail.hit.zdb_id: 2267670-3
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  • 5
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    Rationale and Design of the Hamburg City Health Study
    Springer Science and Business Media LLC ; 2020
    In:  European Journal of Epidemiology Vol. 35, No. 2 ( 2020-02), p. 169-181
    Details
    In: European Journal of Epidemiology, Springer Science and Business Media LLC, Vol. 35, No. 2 ( 2020-02), p. 169-181
    Abstract: The Hamburg City Health Study (HCHS) is a large, prospective, long-term, population-based cohort study and a unique research platform and network to obtain substantial knowledge about several important risk and prognostic factors in major chronic diseases. A random sample of 45,000 participants between 45 and 74 years of age from the general population of Hamburg, Germany, are taking part in an extensive baseline assessment at one dedicated study center. Participants undergo 13 validated and 5 novel examinations primarily targeting major organ system function and structures including extensive imaging examinations. The protocol includes validate self-reports via questionnaires regarding lifestyle and environmental conditions, dietary habits, physical condition and activity, sexual dysfunction, professional life, psychosocial context and burden, quality of life, digital media use, occupational, medical and family history as well as healthcare utilization. The assessment is completed by genomic and proteomic characterization. Beyond the identification of classical risk factors for major chronic diseases and survivorship, the core intention is to gather valid prevalence and incidence, and to develop complex models predicting health outcomes based on a multitude of examination data, imaging, biomarker, psychosocial and behavioral assessments. Participants at risk for coronary artery disease, atrial fibrillation, heart failure, stroke and dementia are invited for a visit to conduct an additional MRI examination of either heart or brain. Endpoint assessment of the overall sample will be completed through repeated follow-up examinations and surveys as well as related individual routine data from involved health and pension insurances. The study is targeting the complex relationship between biologic and psychosocial risk and resilience factors, chronic disease, health care use, survivorship and health as well as favorable and bad prognosis within a unique, large-scale long-term assessment with the perspective of further examinations after 6 years in a representative European metropolitan population.
    Type of Medium: Online Resource
    ISSN: 0393-2990 , 1573-7284
    URL: Article
    DOI: 10.1007/s10654-019-00577-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2004992-4
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  • 6
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    Smaller Than Expected : Effects of Imitative Action Regulation After Experiencing Social Exclusion
    Hogrefe Publishing Group ; 2021
    In:  Experimental Psychology Vol. 68, No. 3 ( 2021-05), p. 137-148
    Details
    In: Experimental Psychology, Hogrefe Publishing Group, Vol. 68, No. 3 ( 2021-05), p. 137-148
    Abstract: Abstract. In two pre-registered studies, we investigated whether processes of imitative action regulation are facilitated after experiencing an episode of social exclusion. We reasoned that imitative action regulation effects should be more pronounced for participants who were socially excluded, providing them with an “automatic means” to socially reconnect with others. Participants played a virtual ball-tossing game to experimentally induce social exclusion or inclusion experiences. Subsequently, pairs of two participants engaged in an observational stimulus–response (SR) binding paradigm modeled after Giesen et al. (2014) : Participants observed color categorization responses in their interaction partner (trial n-1 ) and then executed (in)compatible responses in the subsequent trial (trial n ), with observation and responding occurring in alternation. Stimulus relation (repetition vs. change) from trial n-1 to trial n was orthogonally manipulated. In both studies, stimulus-based retrieval effects of observationally acquired SR bindings were descriptively larger in socially excluded (compared with socially included) participants. However, none of the effects were statistically significant. Even a joint analysis of both experiments did not show the expected modulation. We discuss the implications of our findings for research on social exclusion effects on imitative action regulation processes.
    Type of Medium: Online Resource
    ISSN: 1618-3169 , 2190-5142
    URL: Article
    DOI: 10.1027/1618-3169/a000516
    RVK:
    CL 1000
    Language: English
    Publisher: Hogrefe Publishing Group
    Publication Date: 2021
    detail.hit.zdb_id: 1237835-5
    detail.hit.zdb_id: 2073857-2
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    SSG: 5,2
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  • 7
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    The effect of ageing on fat infiltration of thigh and paraspinal muscles in men
    Springer Science and Business Media LLC ; 2022
    In:  Aging Clinical and Experimental Research Vol. 34, No. 9 ( 2022-05-28), p. 2089-2098
    Details
    In: Aging Clinical and Experimental Research, Springer Science and Business Media LLC, Vol. 34, No. 9 ( 2022-05-28), p. 2089-2098
    Abstract: Myosteatosis, skeletal muscle fat infiltration, is associated with inflammation and fibrosis. The age-related increase of myosteatosis is an important characteristic of sarcopenia and contributes to fragility. Aims To investigate the impact of healthy aging on intermuscular adipose tissue (IMAT) and muscle fat fraction (FF) in the thigh and the paraspinal muscles in males. Methods In 54 healthy males (age 20–70), all active hobby golfers, magnetic resonance imaging was performed to determine volume of IMAT, volume of muscle tissue (MT) and of percentage of FF. Results Between ages 20–70, at the thigh, IMAT/MT volume and MT FF increased annually by 2.9% and 1.3%, respectively. At the psoas IMAT/Psoas volume did not change with age. MT FF increased by 1.5% annually. At the erector spinae IMAT/Erector volume decreased by 0.3% and MT FF increased by 2.8% annually. Discussion With increasing age, in males, thigh muscle atrophied, muscle tissue was partly replaced by adipose tissue and remaining muscle tissue also contained more fat. Similar effects were observed in the erector spinae. The psoas muscle did not atrophy, although MT FF also increased with age. Overall correlations with age were weak to moderate with higher correlations observed in the paraspinal muscles. Conclusions Age-related increases of muscle fat infiltration were observed in the thigh and in the spine. Muscle atrophy did not occur in the psoas. In cross-sectional studies, an adjustment of volumetric parameters by muscle volume is advisable when comparing age-dependent results.
    Type of Medium: Online Resource
    ISSN: 1720-8319
    URL: Article
    DOI: 10.1007/s40520-022-02149-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2119282-0
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  • 8
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    Diagnostics and management of patients with inherited retinal diseases in Germany : Results of a nationwide survey of university and non-university eye departments and specialized practices
    Springer Science and Business Media LLC ; 2023
    In:  Die Ophthalmologie
    Details
    In: Die Ophthalmologie, Springer Science and Business Media LLC
    Abstract: Inherited retinal diseases (IRDs) refer to a heterogeneous group of rare disorders that potentially lead to blindness. Emerging therapeutic options have led to a growing interest in IRDs; however, there are insufficient systematic studies on IRDs in Germany characterizing the demographics and management in clinical practice. Objective To characterize the care for IRD patients in Germany, to assess the applied diagnostics, the use of databases and the implementation of education in ophthalmic genetics. Methods The anonymous online survey (SoSci Survey GmbH) was sent to all German ophthalmology departments listed on the website of the German Ophthalmological Society and to three practices focusing on IRDs. Results The overall response rate was 44.8%. Almost all institutions (93.6%) reported seeing IRD patients, but university and non-university hospitals differed in the number of patients. Databases are used in 60% of universities but only in 5.9% of non-university hospitals. Regarding the number of patients with genetic diagnostics, 53% of the non-university and 12% of the university sites reported that 20% at most of their patients had received a molecular genetic diagnosis. The results of the IRD practices are comparable with the university hospitals. Patients with biallelic RPE65 mutations-associated IRD, potential candidates for treatment with voretigene neparvovec (Luxturna®), were followed in 9/25 participating university departments. Conclusion This survey highlights the deficits in the management of IRD patients. In particular, we found a clear difference between university and non-university hospitals in the rate of patients with known molecular genetic results. Improvements should be initiated in the latter, especially because of existing and emerging therapeutic options.
    Type of Medium: Online Resource
    ISSN: 2731-720X , 2731-7218
    URL: Article
    DOI: 10.1007/s00347-023-01902-9
    Language: German
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 3128800-5
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  • 9
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    Do survey expectations of stock returns reflect risk adjustments?
    Elsevier BV ; 2021
    In:  Journal of Monetary Economics Vol. 117 ( 2021-01), p. 723-740
    Details
    In: Journal of Monetary Economics, Elsevier BV, Vol. 117 ( 2021-01), p. 723-740
    Type of Medium: Online Resource
    ISSN: 0304-3932
    URL: Article
    DOI: 10.1016/j.jmoneco.2020.04.010
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 191155-7
    detail.hit.zdb_id: 1460612-4
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  • 10
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    Linear projection‐based chemical exchange saturation transfer parameter estimation
    Wiley ; 2023
    In:  NMR in Biomedicine Vol. 36, No. 6 ( 2023-06)
    Details
    In: NMR in Biomedicine, Wiley, Vol. 36, No. 6 ( 2023-06)
    Abstract: Isolated evaluation of multiparametric in vivo chemical exchange saturation transfer (CEST) MRI often requires complex computational processing for both correction of B 0 and B 1 inhomogeneity and contrast generation. For that, sufficiently densely sampled Z‐spectra need to be acquired. The list of acquired frequency offsets largely determines the total CEST acquisition time, while potentially representing redundant information. In this work, a linear projection‐based multiparametric CEST evaluation method is introduced that offers fast B 0 and B 1 inhomogeneity correction, contrast generation and feature selection for CEST data, enabling reduction of the overall measurement time. To that end, CEST data acquired at 7 T in six healthy subjects and in one brain tumor patient were conventionally evaluated by interpolation‐based inhomogeneity correction and Lorentzian curve fitting. Linear regression was used to obtain coefficient vectors that directly map uncorrected data to corrected Lorentzian target parameters. L1‐regularization was applied to find subsets of the originally acquired CEST measurements that still allow for such a linear projection mapping. The linear projection method allows fast and interpretable mapping from acquired raw data to contrast parameters of interest, generalizing from healthy subject training data to unseen healthy test data and to the tumor patient dataset. The L1‐regularization method shows that a fraction of the acquired CEST measurements is sufficient to preserve tissue contrasts, offering up to a 2.8‐fold reduction of scan time. Similar observations as for the 7‐T data can be made for data from a clinical 3‐T scanner. Being a fast and interpretable computation step, the proposed method is complementary to neural networks that have recently been employed for similar purposes. The scan time acceleration offered by the L1‐regularization (“CEST‐LASSO”) constitutes a step towards better applicability of multiparametric CEST protocols in a clinical context.
    Type of Medium: Online Resource
    ISSN: 0952-3480 , 1099-1492
    URL: Issue
    URL: Article
    DOI: 10.1002/nbm.v36.6
    DOI: 10.1002/nbm.4697
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2002003-X
    detail.hit.zdb_id: 1000976-0
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