Abstract Background In inflammatory bowel disease (IBD), symptoms of depression and fatigue overlap to great extent, making it difficult for medical practitioners to differentiate between these symptoms and provide patients with proper treatment options. In this study, we prospectively monitored multiple factors including mood, sleep, physical and psychological wellbeing, quality of life and stress perception, and explored the effects of these factors on symptoms of depression and fatigue in IBD. Our aim was to define specific combinations of symptoms helping to better distinguish between depression and fatigue in IBD populations. Methods Sixteen patients with IBD provided daily indices of sleep duration and quality as well as ratings of depressive symptoms, fatigue, stress perception, mood and IBD-related symptoms 6 times per day for 7 consecutive days of ecological momentary assessment (EMA) monitoring. Additionally, participants were provided with a series of questionnaires, stool samples were collected, as well as ambulatory physiological monitoring was performed. Multiple linear regression analyses were computed to explore how these specific factors can predict depression and fatigue in IBD. Network analyses were applied to identify and analyse distinct patterns of statistical associations related to depression and fatigue in IBD. Results Self-reported sleep quality (pFDR = .034) and feelings of sadness (pFDR = .045) significantly predicted symptoms of depression in IBD, while fatigue could only be predicted by poor sleep quality (pFDR = .030). Network analyses revealed two distinct patterns: symptoms of depression were associated with less positive (pFDR = .024) and more negative affect (pFDR = .012), as well as stronger feelings of tiredness (pFDR = .014) in daily life. Fatigue was characterized by an inability of feeling relaxed (pFDR = .002), more severe tiredness (pFDR = .013) and exhaustion (pFDR = .022). Conclusion Our preliminary results indicate that depressive symptoms are associated with the experience of negative emotions in daily life, which could affect patients‘ motivation to engage in activities and social interactions and thus, resulting in a stronger perception of tiredness. In contrast, the manifestation of fatigue in IBD is characterised by a stronger perception of tiredness and exhaustion, but not with the experience of negative affect. Additionally to the improvement of patient’s sleep quality, treatment of depressive symptoms should focus on fostering daily activities linked to positive emotions, while relaxation techniques and regular amount of moderate exercise can be a good treatment option for fatigued patients, if these associations could be found in larger studies as well.

Abstract Background Due to the relapsing course of inflammatory bowel diseases (IBD) with varying disease activity and symptom burden, patients tend to monitor symptoms and bodily sensations to recognize early signs of relapses. Interoception is the ability to perceive and evaluate internal processes of the body. Visceral hypervigilance (VH) describes anxiety and increased attention towards gastrointestinal symptoms. It has been shown to be associated with psychologic comorbidities and reduced quality of life in patients with IBD1, but the factors causing VH are still unknown. In this study we explored whether changes in interoceptive abilities (accuracy, I-acc; sensibility, I-sens and awareness, I-aw) are associated with VH. Methods Adults with IBD (n=34) performed a heartbeat tracking task (Schandry, 1981) for assessment of I-acc and completed questionnaires to assess VH (Visceral Sensitivity Index, VSI) and I-sens. Correlations between I-acc and I-sens were used for an approximation of I-aw. Associations were examined using t-tests and Pearson correlation. Results A preliminary examination of the current sample (recruitment is ongoing) showed no significant association between VH and I-acc (r=-0.041; p=0.817) or I-sens (r=0.236; p=0.178). Comparison of a low VH (VSI<20) vs high VH (VSI>40) group showed no significant differences in I-acc or I-sens (VSI<20: n=11; VSI>40: n=9; I-sens: t= -1,183; p= 0,126; I-acc: t= 0,47; p=0,322). Moreover I-aw was not significantly different between a high VH and a low VH group (z=0.218, p=0.828). I-acc and I-sens correlated positively (r=0.374 p = 0.018). VH was strongly correlated with symptoms of anxiety (r=0.659, p<0.001) and depression (r=0.618; p<0.001), but I-acc was not significantly associated with symptoms of anxiety and depression (anxiety r=0.188 p=0.328; depression r=0.067, p=0.729). I-sens was associated with symptoms of anxiety (r= 0.371, p = 0.048), but not with symptoms of depression (r=0.32, p=0.091). Conclusion Our preliminary results suggest no associations between VH and objective or subjective interoceptive abilities in patients with IBD. This may be owed to the small sample size with only few patients showing high or low VH. Moreover - even though previous data showed a relationship between perception of cardiac and gastrointestinal signals, and both communicate via the vagal nerve 2-3 - heart-beat tracking may not be the optimal task to measure interoception in patients with IBD. VH and interoception should be examined in larger IBD samples that include individuals with a higher symptom burden. Future studies may also explore further possibilities to assess interoception in IBD patients. References 1.Thomann AK, Knödler LL, Karthikeyan S, et al. The Interplay of Biopsychosocial Factors and Quality of Life in Inflammatory Bowel Diseases: A Network Analysis. J Clin Gastroenterol. 2023;57(1):57-65. Published 2023 Jan 1. doi:10.1097/MCG.0000000000001625 2.Herbert BM, Muth ER, Pollatos O, Herbert C. Interoception across modalities: on the relationship between cardiac awareness and the sensitivity for gastric functions. PLoS One. 2012;7(5):e36646. doi:10.1371/journal.pone.0036646 3.Whitehead WE, Drescher VM. Perception of gastric contractions and self-control of gastric motility. Psychophysiology. 1980;17(6):552-558. doi:10.1111/j.1469-8986.1980.tb02296.x

Background Neoadjuvant chemotherapy is an option for patients with locally advanced rectal cancer at low risk for local recurrence. This randomized phase II trial investigated whether the addition of aflibercept to modified FOLFOX6 (mFOLFOX6) could improve the rates of centrally confirmed pathological complete remissions (pCR) and (disease-free) survival in magnetic resonance imaging (MRI)-staged cT3 rectal cancer. Patients and methods Patients with rectal cancer fulfilling the following criteria were included: lower border of tumor >5 cm and <16 cm from anal verge; circumferential resection margin >2 mm and T3-tumor with a maximum infiltration of 10 mm, as determined by MRI. Patients were randomized 1 : 2 to six cycles mFOLFOX6 ± aflibercept. Surgery was scheduled 4 weeks after chemotherapy. Primary endpoint was the rate of centrally confirmed pCR. The study was designed to detect an improvement of pCR from 10% to 27% (power 80%, type I error 20%). Results A total of 119 randomized patients started treatment (39 patients mFOLFOX6, arm A, and 80 mFOLFOX + aflibercept, arm B). The incidence of all grade adverse events was similar in both arms, however, adverse events grade ≥3 were more than twice as high in the experimental arm due to hypertension. Surgical complications were comparable. Aflibercept did not improve the pCR rate (arm A 26% versus arm B 19%, P = 0.47) and more patients in arm B had node positivity. With a median follow-up of 40.1 months, the 4-year disease-free survival was 83% in arm A and 85% in arm B (P = 0.82). Only two patients in arm A and one patient in arm B developed local recurrence. Conclusions In patients with locally advanced rectal cancer and MRI-defined low risk of local recurrence, neoadjuvant mFOLFOX6 + aflibercept was feasible and did not compromise surgery. Survival data were favorable in both arms, but pCR rates were not increased by the addition of aflibercept.

Many open questions remain about the microbes in the stomach, an environment long considered inhospitable. Our understanding of the gastric environment has been revolutionized over the last four decades by the identification of Helicobacter pylori (H. pylori). Despite significant advances, we are still unraveling the complex interactions within this ecosystem and identifying new microbial players in the acidic environment. In this review, we summarize the annual knowledge on the gastric microbiota published from 2023 to 2024, providing a comprehensive overview of the latest findings. Recent data shed light on the dynamics of the microbiome in the healthy state, as well as after H. pylori eradication and antibiotic resistance. Research on the microbiome in gastric cancer is revealing information about microbiota transitions during cancer progression and the potential role of the microbiome in assessing disease phenotype. The evidence surrounding Fusobacterium nucleatum (F. nucleatum) provides strong support for its clinical impact, although other bacteria and viruses also contribute. We look forward to further developments in this area, particularly in translating knowledge into clinical practice to improve the diagnosis and treatment of gastric diseases.

Einleitung: Therapeutische Antikörper gegen den inhibitorischen Immuncheckpoint “programmed-cell-death-1” (PD1) erzielen klinische Wirksamkeit nur in einer kleinen Subgruppe von Patienten mit immunologisch aktivem, mikrosatelliten-instabilen (MSI) kolorektalen Karzinom (KRK), nicht aber in der Mehrheit der mikrosatelliten-stabilen (MSS) Tumore. Zudem führen Mutationen in onkogenen Treibergenen u.a. KRAS zu einer Hochregulation von PD1 und einem immunsuppressiven Mikromilieu, welches eine effektive Behandlung verhindert.