The soil‐borne obligate pathogen Plasmodiophora brassicae causes clubroot disease in species of Brassicaceae, including Arabidopsis thaliana. The host–pathogen interaction was studied with respect to the age of the plant at the time point of inoculation and to different infection pressures in order to establish a standardization of infection parameters and evaluation of disease extent for A. thaliana lines. Spore number per root weight, root and shoot weight of inoculated and non‐inoculated plants as well as infection rate and disease index (DI) were analysed and correlated. The disease extent of different lines was comparable as measured by the relation of root weight of inoculated and non‐inoculated plants (Ri/Rni index) and the DI. Most of the 71 screened A. thaliana lines turned out to be susceptible. However, the mutant lines tu8, tu3, det1‐1, and rhd3‐1 showed a certain degree of tolerance under specific culture conditions. The reactions of rhd3‐1 indicate that hypertrophy is a prerequisite for maturation of the pathogen. The reactions of the tu3 and tu8 mutants indicate a role of indole glucosinolates and indole‐3‐acetonitrile/IAA in development of clubroot disease.

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Summary Background Advanced fibrosis has been established as the most important predictor of overall mortality in patients with non‐alcoholic fatty liver disease (NAFLD). In contrast to cirrhosis, advanced, non‐cirrhotic NAFLD is difficult to identify and data from Germany are lacking. Aim To identify clinical factors associated with advanced, non‐cirrhotic fibrosis. Methods Patients were recruited in the prospectively enrolling European NAFLD Registry. Clinical characteristics and the performance of non‐invasive surrogate scores compared with vibration‐controlled transient elastography are reported. Results Two hundred and sixty‐one patients with non‐cirrhotic NAFLD on liver biopsy (mean age 51 years, equal sex distribution) were included. The prevalence of stage 3 fibrosis on liver biopsy was 15.7%. These patients were significantly older (57 vs 50 years, P < 0.01), had a higher body mass index (32.3 vs 30.5, P < 0.05), and more frequent arterial hypertension (78% vs 50%, P = 0.001) and type 2 diabetes (61% vs 24.1%, P < 0.001). On multivariate logistic regression, diabetes (OR = 4.68, 95% CI 2.17‐10.10) and hypertension (OR = 2.91, 95% CI 1.12‐7.18) were independent predictors of advanced fibrosis. Comedication included metformin in 50% and insulin in 33% of patients with diabetes. Despite the presence of cardiovascular risk factors, the use of statins was low. Liver stiffness measurement identified advanced fibrosis with an AUROC of 0.81 (95% CI 0.72‐0.91). The performance of NAFLD fibrosis score, Fibrosis‐4, and AST to platelet ratio index were lower with AUCs of 0.74, 0.71, and 0.67, respectively. Conclusions The prevalence of metabolic comorbidities in a German population with non‐cirrhotic biopsy‐proven NAFLD is high. While the examined scores exhibit an acceptable specificity, liver stiffness measurement appeared to be superior to blood‐based non‐invasive surrogate scores in ruling out advanced fibrosis.

Nonalcoholic fatty liver disease (NAFLD), depression, and anxiety disorders are frequent diseases, and data on mutual influence are inconsistent. The aim of this study was to explore the incidence of depression and anxiety in a large primary care cohort in Germany and to study the impact of NAFLD over a 10‐year time frame. Patients with NAFLD diagnosed between 2010 and 2015 were matched to a cohort without NAFLD controlling for age, sex, physician, index year, and Charlson comorbidity index. The primary outcome of the study was the incidence of depression, anxiety, and first prescription of antidepressant drugs. We compared 19,871 patients with NAFLD to 19,871 matched controls. Within 10 years of the index date, 21.2% of patients with NAFLD and 18.2% of controls were diagnosed with depression (P < 0.001). On regression analysis, the hazard ratio (HR) for incidence of depression was 1.21 (P < 0.001). This association was similar for the endpoint of the first prescription of antidepressant drugs (HR, 1.21; P < 0.001). Anxiety disorders were diagnosed in 7.9% of patients with NAFLD and 6.5% of controls during the observation time (P = 0.003). The HR for incidence of anxiety was 1.23 (P < 0.001). This association remained significant in women (P < 0.001), while there was only a trend in men (HR, 1.15; 95% confidence interval, 0.99‐1.34; P < 0.067). The risk of developing anxiety disorders was higher in younger patients. Conclusion: NAFLD constitutes an independent risk factor for emerging depression and anxiety even after controlling for confounding comorbidities.

Covert HE was associated with impaired HRQoL and sleep quality. MHE and HE1 affected both outcomes to a comparable extent supporting the use of CHE as a clinically useful term for patients with both entities of HE in clinical practice.

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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 a 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 titer increased with disease duration. The presence of human leukocyte antigen-DRB1*10:01 (55% [24/44]) was associated with higher serum anti-IgLON5 IgG titers. 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 six weeks was a predictor for therapy response. Sixty-eight percent (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.

Summary Background Systemic inflammation is a driving force for the development of hepatic encephalopathy and recent studies demonstrated that elevated Interleukin‐6 (IL‐6) serum levels are associated with the presence of minimal hepatic encephalopathy in patients with liver cirrhosis. Aim To test the hypothesis that IL‐6 is a suitable marker to identify patients with liver cirrhosis at high risk for the development of overt hepatic encephalopathy. Methods 201 patients were included into this prospective cohort study and were followed for a mean time of 322 days. Covert hepatic encephalopathy was diagnosed according to the West‐Haven criteria (hepatic encephalopathy grade 1) and with the portosystemic encephalopathy (PSE) test. Results The cumulative incidence of overt hepatic encephalopathy was higher in patients with IL‐6 levels above the median of 9 pg/mL than in patients with IL‐6 levels at or below the median (35.6% vs 1.9%, P < .001). After adjustment for covert hepatic encephalopathy, history of overt hepatic encephalopathy, C‐reactive protein (CRP) and model for end‐stage liver disease (MELD), IL‐6 levels above the median remained independently associated with the development of overt hepatic encephalopathy. The predictive performance of IL‐6 regarding the development of overt hepatic encephalopathy during the next 180 days (AUROC, 0.931) was numerically higher than that of MELD (AUROC, 0.841) or CRP (AUROC, 0.835). In patients without prior overt hepatic encephalopathy, the predictive performance of IL‐6 (AUROC, 0.966) was even significantly higher than that of MELD (AUROC 0.843) or CRP (AUROC 0.850). The ideal cut‐off for IL‐6 in this setting was 23.5 pg/mL with a sensitivity and specificity of 89.3% and 89.5% respectively. Conclusion IL‐6 serum levels are closely linked to the development of overt hepatic encephalopathy in patients with liver cirrhosis.