Body Evaluation and Body Ownership in Patients with Inflammatory Bowel Disease: the Role of Interoceptive Sensibility and Childhood Maltreatment.

Objective: Inflammatory bowel diseases (IBD) are accompanied by symptoms that can vastly affect patients' representations of their bodies. The aim of this study was to investigate alterations in body evaluation and body ownership in IBD and their link to interoceptive sensibility, gastrointestinal-specific anxiety, and history of childhood maltreatment.

Methods: Body evaluation and ownership was assessed in 41 clinically remitted patients with IBD and 44 healthy controls (HC) using a topographical self-report method.

Associations Between Brain Morphology, Inflammatory Markers, and Symptoms of Fatigue, Depression, or Anxiety in Active and Remitted Crohn's Disease.

Background: Fatigue and psychosocial impairments are highly prevalent in IBD, particularly during active disease. Disturbed brain-gut interactions may contribute to these symptoms. This study examined associations between brain structure, faecal calprotectin, and symptoms of fatigue, depression, and anxiety in persons with Crohn's disease [CD] in different disease states.

Validation of the German version of the Short Health Scale - a brief, valid and reliable instrument to assess health-related quality of life in German-speaking patients with inflammatory bowel diseases.

Background: Health-related quality of life (hrQoL) may be the most important patient-reported outcome for patients with chronic disorders. The Short Health Scale (SHS) is a brief four-item instrument to assess hrQoL in patients with bowel disorders. This study examined the validity, reliability and sensitivity of the German translation of the SHS in a cohort of outpatients with inflammatory bowel diseases (IBD).

Label-free high-throughput screening via acoustic ejection mass spectrometry put into practice.

Acoustic droplet ejection-open port interface-mass spectrometry (ADE-OPI-MS) is a novel label-free analytical technique, promising to become a versatile readout for high-throughput screening (HTS) applications. The recent introduction of ADE-OPI-MS devices to the laboratory equipment market, paired with their compatibility with laboratory automation platforms, should facilitate the adoption of this technology by a broader community. Towards this goal, instrument robustness in the context of HTS campaigns - where up to millions of samples in complex matrices are tested in a short time frame - represents a major challenge, which explains the absence of detailed literature reports on this subject.

BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy.

Objective: Obesity and its associated comorbidities represent a global health challenge with a need for well-tolerated, effective, and mechanistically diverse pharmaceutical interventions. Oxyntomodulin is a gut peptide that activates the glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R) and reduces bodyweight by increasing energy expenditure and reducing energy intake in humans. Here we describe the pharmacological profile of the novel glucagon receptor (GCGR)/GLP-1 receptor (GLP-1R) dual agonist BI 456906.

Questions to consider when caring for patients with ulcerative colitis.

Although the management of patients with ulcerative colitis (UC) is well defined by national and international guidelines, there are many debates and open questions related to daily care of UC patients. Here, we aimed to review topics with high clinical relevance including therapy algorithms, potential biomarkers for disease prognosis and response to therapy, the role of interventions targeting the gut microbiota, insights from head-to-head trials, novel UC medications, exit strategies, the impact of COVID19 on UC, care of patients with acute severe disease, cancer screening, and the role of surgery.

Differential analyte derivatization enables unbiased MALDI-TOF-based high-throughput screening: A proof-of-concept study for the discovery of catechol-o-methyltransferase inhibitors.

Recent advances in label-free high-throughput screening via matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) offer unprecedented opportunities for the identification of novel chemical starting points in target-based drug discovery. A clear advantage of the technology is the possibility for label-free, direct quantification of analytes with high precision and robustness. Here we have expanded the range of analytes and biology that can be addressed via MALDI-TOF HTS, by developing a method based on post-reaction pyrylium-based derivatization to detect 3-methoxytyramine, the physiological enzyme product of the catechol-O-methyltransferase (COMT) enzyme.

Is It a Gut Feeling? Bodily Sensations Associated With the Experience of Valence and Arousal in Patients With Inflammatory Bowel Disease.

Background: Previous studies have shown dysfunctional emotion processing in patients with inflammatory bowel diseases (IBD), characterized by a hypersensitivity to negative emotions and a hyposensitivity to positive emotions. Models of emotion processing emphasize the importance of bodily sensations to the experience of emotions. Since there have been no studies on whether emotion-associated bodily sensations are changed in IBD, we investigated the experience of bodily sensations related to valence and arousal, together with their links to emotional awareness, as one domain of interoceptive sensibility relevant to emotion processing.

A case series of severe breakthrough infections observed in nine patients with COVID-19 in a southwestern German university hospital.

Purpose: Vaccination is the key element for protection against COVID-19. Increased vaccination breakthroughs raise the question of whether additional prevention is necessary in case of individual risk factors for a severe course with hospitalization or death despite vaccination.

Methods: Since July 13, 2021, there is an extended reporting requirement by German law.

Association of ileocolic pedicle division with postoperative complications after restorative proctocolectomy and ileal pouch-anal anastomosis for ulcerative colitis.

Background: When performing a restorative proctocolectomy (RPC) with an ileal pouch-anal anastomosis (IPAA), it is common practice to divide the ileocolic artery (ICA) if the patient has a tumor or dysplasia, or in order to gain sufficient length to secure a tension-free anastomosis. However, it is unclear whether there is an association between division of the ICA and the rate of postoperative complications.

Methods: We retrospectively analysed all patients with ulcerative colitis who underwent RPC and IPAA in our department between January 2010 and December 2016.

The Interplay of Biopsychosocial Factors and Quality of Life in Inflammatory Bowel Diseases: A Network Analysis.

Goal: The aim of this study was to investigate the network of biopsychosocial factors and quality of life (QoL) in persons with inflammatory bowel diseases (IBDs) and explore the influence of psychological factors on the course of the disease.

Background: QoL of persons with IBD depends on disease activity but also on numerous interacting psychosocial factors. The influence of psychosocial factors on the disease course in controversially discussed.

Acoustic Ejection Mass Spectrometry: A Fully Automatable Technology for High-Throughput Screening in Drug Discovery.

Acoustic droplet ejection (ADE)-open port interface (OPI)-mass spectrometry (MS) has recently been introduced as a versatile analytical method that combines fast and contactless acoustic sampling with sensitive and accurate electrospray ionization (ESI)-MS-based analyte detection. The potential of the technology to provide label-free measurements in subsecond analytical cycle times makes it an attractive option for high-throughput screening (HTS). Here, we report the first implementation of ADE-OPI-MS in a fully automated HTS environment, based on the example of a biochemical assay aiming at the identification of small-molecule inhibitors of the cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthase (cGAS).

Multidimensional Assessment of Interoceptive Abilities, Emotion Processing and the Role of Early Life Stress in Inflammatory Bowel Diseases.

Perception of internal bodily sensations includes three dissociable processes: interoceptive accuracy, interoceptive sensibility, and interoceptive awareness. Interoceptive abilities play a crucial role in emotion processing and impairments of these processes have been reported in several psychiatric disorders. Studies investigating interoceptive abilities and their role in emotional experience in individuals with somatic disorders such as inflammatory bowel diseases (IBD) are sparse.

Exploring joint patterns of brain structure and function in inflammatory bowel diseases using multimodal data fusion.

Background: A growing number of neuroimaging studies suggest distinct neural changes in inflammatory bowel diseases (IBDs). Whether such changes may show similar spatial patterns across distinct neural features within and between specific IBD is unclear. To address this question, we used multivariate multimodal data fusion analysis to investigate structure/function modulation in remitted patients with Crohn's disease (CD) and ulcerative colitis (UC).

MALDI-TOF-Based Affinity Selection Mass Spectrometry for Automated Screening of Protein-Ligand Interactions at High Throughput.

Demonstration of in vitro target engagement for small-molecule ligands by measuring binding to a molecular target is an established approach in early drug discovery and a pivotal step in high-throughput screening (HTS)-based compound triaging. We describe the setup, evaluation, and application of a ligand binding assay platform combining automated affinity selection (AS)-based sample preparation and label-free matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis. The platform enables mass spectrometry (MS)-based HTS for small-molecule target interactions from single-compound incubation mixtures and is embedded into a regular assay automation environment.

The Innate Immune Response to Infection Induces Erythropoietin-Dependent Replenishment of the Dendritic Cell Compartment.

Dendritic cells (DC) play a key role in the adaptive immune response due to their ability to present antigens and stimulate naïve T cells. Many bacteria and viruses can efficiently target DC, resulting in impairment of their immunostimulatory function or elimination. Hence, the DC compartment requires replenishment following infection to ensure continued operational readiness of the adaptive immune system.

Ultrahigh-Throughput ESI-MS: Sampling Pushed to Six Samples per Second by Acoustic Ejection Mass Spectrometry.

We present an acoustic ejection mass spectrometry (AEMS) setup for contactless electrospray ionization mass spectrometry (ESI-MS)-based sample injection at a sampling rate faster than current ESI and matrix-assisted laser desorption ionization (MALDI) techniques. For the direct transfer of samples out of 384-well plates into a modified ESI source, an open port interface (OPI) was combined with a modified acoustic droplet ejection (ADE) system. AEMS has the potential to eliminate bottlenecks known from classical MS approaches, such as speed, reproducibility, carryover, ion suppression, as well as sample preparation and consumption.

Ustekinumab Inhibits T Follicular Helper Cell Differentiation in Patients With Crohn's Disease.

Background & Aims: The pathogenesis of chronic inflammatory bowel diseases (Crohn's disease [CD] and ulcerative colitis) involves dysregulated TH1 and TH17 cell responses, which can be targeted therapeutically by the monoclonal antibody Ustekinumab directed against the joint p40 subunit of IL-12 and IL-23. These cytokines may also regulate the differentiation of T follicular helper (TFH) cells, which promote B cell function in germinal centers. However, the role of TFH cells in CD pathogenesis and impact of Ustekinumab therapy on TFH cell fate in patients are poorly defined.

Tofacitinib in Treatment-Refractory Moderate to Severe Ulcerative Colitis: Real-World Experience from a Retrospective Multicenter Observational Study.

(1) Background: Tofacitinib is approved in Europe for the treatment of adults with moderately to severely active ulcerative colitis since 2018. Real-world efficacy and safety data are currently scarce. (2) Methods: We performed a retrospective multicenter study at three German tertiary outpatient clinics for inflammatory bowel diseases and included all patients who started tofacitinib therapy between August 2018 and March 2020.

Review article: bugs, inflammation and mood-a microbiota-based approach to psychiatric symptoms in inflammatory bowel diseases.

Background: Psychiatric co-morbidities including depression and anxiety are common in inflammatory bowel diseases (IBD). Emerging evidence suggests that interactions between the gut microbiota and brain may play a role in the pathogenesis of psychiatric symptoms in IBD.

Aim: To review the literature on microbiota-brain-gut interactions in gut inflammation, psychosocial stress and mental disorders and to discuss the putative mediating role of gut microbiota in the development of psychiatric symptoms or co-morbidities in IBD.

MITIGATE-NeoBOMB1, a Phase I/IIa Study to Evaluate Safety, Pharmacokinetics, and Preliminary Imaging of Ga-NeoBOMB1, a Gastrin-Releasing Peptide Receptor Antagonist, in GIST Patients.

Gastrin-releasing peptide receptors (GRPRs) are potential molecular imaging targets in a variety of tumors. Recently, a Ga-labeled antagonist to GRPRs, NeoBOMB1, was developed for PET. We report on the outcome of a phase I/IIa clinical trial (EudraCT 2016-002053-38) within the EU-FP7 project Closed-loop Molecular Environment for Minimally Invasive Treatment of Patients with Metastatic Gastrointestinal Stromal Tumors ('MITIGATE') (grant agreement no.

Ustekinumab serum concentrations are associated with clinical outcomes in Crohn's disease - a regional multi-center pilot study.

Background And Aim:  The role of therapeutic drug monitoring (TDM) in ustekinumab (UST) therapy for Crohn's disease (CD) has not been established, as only few studies have analyzed the relationship between UST serum concentrations and clinical outcome. In this pilot study, we retrospectively examined the potential of UST-concentrations (cUST) 8 weeks after induction (cUSTw8) to predict clinical response at week 16.

Methods:  Serum samples and clinical data from patients (n = 72) with moderate to severely active CD who received intravenous induction with UST were retrospectively analyzed.

Reducing Perioperative Risks of Surgery in Crohn's Disease.

Background: Approximately one-third of all patients suffering from Crohn's disease (CD) undergo surgery within the first 10 years after diagnosis and another 20% will have a second operation in the 10 years after their first operation. Surgery will remain an essential part of managing CD and therefore it is crucial to prevent perioperative complications by optimizing perioperative management.

Methods: We reviewed the current literature on managing immunomodulating therapy, nutritional support, and thromboembolic prophylaxis in the perioperative situation.