Abstract Recent advances have enabled a comprehensive understanding of the genetic architecture of inflammatory bowel disease (IBD) with over 30 identified and replicated disease loci. The ...pathophysiological consequences of disease gene variants in Crohn disease and ulcerative colitis, the two main subentities of IBD, so far are only understood on the single disease gene level, yet complex network analyses linking the individual risk factors into a molecular risk map are still missing. In this review, we will focus on recent pathways and cellular functions that emerged from the genetic studies (e.g. innate immunity, autophagy) and delineate the existence of shared (e.g. IL23R , IL12B ) and unique (e.g. NOD2 for CD) risk factors for the disease subtypes. Ultimately, the defined molecular profiles may identify individuals at risk early in life and may serve as a guidance to administer personalized interventions for causative therapies and/or early targeted prevention strategies. Due to this comparatively advanced level of molecular understanding in the field, IBD may represent precedent also for future developments of individualized genetic medicine in other polygenic disorders in general.
The German government initiated the
Network University Medicine
(NUM) in early 2020 to improve national research activities on the
Severe Acute Respiratory Syndrome Coronavirus 2
(SARS-CoV-2) ...pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the
National Pandemic Cohort Network
(NAPKON). The NAPKON’s goal is creating the most comprehensive
Coronavirus Disease 2019
(COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the
German Centre for Cardiovascular Research.
By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36–62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON’s design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.
Trial registration
https://clinicaltrials.gov/ct2/show/NCT04768998
.
https://clinicaltrials.gov/ct2/show/NCT04747366
.
https://clinicaltrials.gov/ct2/show/NCT04679584
Aims
Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts for up to one-third of all heart failure cases. Since extrinsic and monogenic causes explain ...only a fraction of all cases, common genetic variants are suspected to contribute to the pathogenesis of DCM, its age of onset, and clinical progression. By a large-scale case-control genome-wide association study we aimed here to identify novel genetic risk loci for DCM.
Methods and results
Applying a three-staged study design, we analysed more than 4100 DCM cases and 7600 controls. We identified and successfully replicated multiple single nucleotide polymorphism on chromosome 6p21. In the combined analysis, the most significant association signal was obtained for rs9262636 (P = 4.90 × 10−9) located in HCG22, which could again be replicated in an independent cohort. Taking advantage of expression quantitative trait loci (eQTL) as molecular phenotypes, we identified rs9262636 as an eQTL for several closely located genes encoding class I and class II major histocompatibility complex heavy chain receptors.
Conclusion
The present study reveals a novel genetic susceptibility locus that clearly underlines the role of genetically driven, inflammatory processes in the pathogenesis of idiopathic DCM.
Purpose We characterized the profile of Crohn's disease (CD) or ulcerative colitis (UC) biologic-naïve patients (starting a new therapy with vedolizumab or TNFalpha-antagonists), their baseline ...disease activity predictors, and their perception of the quality of life (HRQoL). Methods The VEDO.sub.IBD-Study is a real-world study on the effectiveness of vedolizumab vs other biologics as induction and maintenance therapy for CD and UC. A total of 627 CD and 546 UC patients were enrolled from IBD-experienced centers across Germany. In both biologic-naïve vedolizumab (n=397) and anti-TNF (n=359) patients, CD and UC disease severity and HRQoL predictors were analyzed with logistic regression. The results were reported as odds ratio (OR) and 95% confidence interval (CI). Results When compared to biologic-naïve anti-TNF patients, a first biological therapy with vedolizumab was considered for older CD patients, with a less complicated though longer disease course, and with a history of comorbidities. No differences in (unmet) needs were observed among patients with UC. The presence of extra-intestinal manifestations in biologic-naïve anti-TNF patients with CD (OR (95% CI): 3.83 (1.69-8.68)) and, in both biologic-naïve groups of patients with UC, stool frequency (2.00 (1.25-3.19); 1.82 (1.10-3.02), respectively) and rectal bleeding (2.24 (1.20-4.18); 1.92 (1.19-3.11), respectively) emerged as the most important predictors of disease severity, which in turn were also significantly associated with a worse HRQoL. Conclusion This study highlights the existence of unmet medical needs of patients with CD or UC, for whom a new biological therapy is planned as part of the VEDO.sub.IBD-Study, which considerably impacts their HRQoL.
Abstract
Background
Ulcerative proctitis is a common and often highly symptomatic form of inflammatory bowel disease. We performed a systematic review to assess the efficacy of different therapies in ...the management of patients with ulcerative proctitis.
Methods
We identified randomized controlled trials in adults with ulcerative proctitis treated with oral or topical therapies for induction of response or remission, or prevention of relapse.
Results
A total of 32 randomized controlled trials were included 27 induction/2839 participants, five maintenance/334 participants. Follow-up varied from 3 to 8 weeks for induction, and from 6 to 24 months for maintenance of remission. 5-Aminosalicylic acid 5-ASA suppository was the most frequently evaluated treatment 14/32, 43.7%, followed by steroid enema 7/32, 21.9%. Topical 5-ASA demonstrated effectiveness for induction of clinical response or remission and prevention of relapse in several studies. Combined topical steroids and 5-ASA was more effective than topical 5-ASA or topical steroids alone to induce response 100% of patients for combination vs 70% for beclomethasone alone and 76% for 5-ASA alone. One observational study suggested azathioprine may be effective in patients with ulcerative proctitis. Only two cohort studies evaluated the efficacy of tumour necrosis factor inhibitors in ulcerative proctitis. Small molecules, anti-integrins and anti-interleukin therapies have not been evaluated in isolated ulcerative proctitis.
Conclusion
The role of topical 5-ASA as a treatment for ulcerative proctitis has been confirmed in this systematic literature review, for induction and maintenance of remission. Future trials are needed to investigate the efficacy of more recent and upcoming drug classes in patients with ulcerative proctitis.
Hydrogel sensors are well suited to measuring the concentration of substances in liquids, and, because the hydrogel is biocompatible, they are ideal for medical use. Hydrogels change their volume in ...response to stimuli. The larger the hydrogel, the more pronounced the measurement signal. However, a larger volume also leads to slower swelling due to the longer diffusion paths. One method of determining the degree of swelling is to measure the swelling pressure using a piezoresistive pressure sensor. With current approaches, measurement times of several minutes can be achieved. By exploiting the bimorph effect, we were able to reduce the thickness of the hydrogel and, thus, reduce the response time of the entire sensor to less than 1 min. The aim of this paper is now to show how a sensor with short response times can be designed and manufactured and, in particular, how to find a suitable hydrogel composition, how to appropriately structure the hydrogel layer and how a robust adhesion of the hydrogel to the sensor chip can be achieved. As a result, we were able to show that such hydrogel sensors with response times of just a few seconds are possible.
