Angela Horvath

Background: Postoperative delirium is a serious complication in intensive care units (ICUs), particularly following cardiac surgery. It is associated with circadian rhythm disruption, sleep disturbances and adverse outcomes. ICU environments often lack natural time cues, which may exacerbate circadian misalignment and increase delirium risk. Aim: The primary aim of the study was the evaluation of the implementation of two chronotherapeutic ICU interventions regarding recruitment, implementability and safety. Its secondary aim was to descriptively assess postoperative delirium across intervention groups. Study Design: This randomized feasibility study was conducted in a tertiary cardiac surgery ICU in Austria. Adult patients undergoing elective cardiac surgery were allocated to one of three groups: (1) forest environment, (2) light exposure or (3) standard ICU care. Interventions were applied for 12 h daily. Delirium was assessed at three postoperative time points using the confusion assessment method for the ICU (CAM‐ICU) and intensive care delirium screening checklist (ICDSC). Results: This study was conducted between March 2020 and 2025. Seventy‐seven patients were enrolled, and 64 remained in the final analytical cohort. Interventions were delivered within routine care. Patients and ICU staff did not report intervention‐related concerns. Implementation challenges included ICU restructuring, patient transfers due to COVID‐19 and deviations from randomized allocation because of operational constraints. No intervention‐related adverse events occurred. Delirium assessments were limited at several time points because of sedation, early ICU discharge or transfer. Across all groups, postoperative delirium was detected in 5 of 130 CAM‐ICU completed assessments (3.8%) and 8 of 115 ICDSC completed assessments (6.9%), precluding inferential group comparisons. Conclusions: Chronotherapeutic environmental interventions were feasible and safe in ICU care. Feasibility results highlighted challenges related to ICU logistics, sedation‐related assessment limitations and pandemic‐related disruptions. The unexpectedly low delirium incidence limited conclusions regarding intervention efficacy. Future trials should include larger high‐risk populations and prospectively defined feasibility outcomes. Relevance to Clinical Practice: Optimized ICU environments, including noise reduction and light management, may support delirium prevention. Chronotherapeutic environmental interventions are feasible additions to routine ICU care.

Background Microplastics (MPs) have been found in human tissues, indicating widespread exposure, but little is known about their excretion and influencing factors. We investigated MP-like particles in human urine and potential differences related to menstrual cycle status in women. Methods Urine samples from 30 healthy adults (15 women, 15 men) were collected twice, with female samples timed for menstruation and non-menstruation, and male samples at random. Samples were purified (hydrogen peroxide), stained (Nile-Red), filtered (3 mm gold coated membrane), scanned (FITC fluorescence) and examined for MP-like particles (manual counted and categorised). Participants completed a questionnaire, statistical analyses explored links between exposure factors and particle counts. Results 30 volunteers provided 2 urine samples; 59 samples could be collected, of which 53 were evaluable. MP-like particles were detected in 48 samples, counts varied across individuals and timepoints (up to 15 particles/mL). No significant difference was observed between sexes, though a trend toward lower counts during menstruation was noted (p = 0.076). In explanatory modelling, self-reported period pad use, composite-packaged drink consumption, coffee preparation method, intimate shaving habits, and sea-salt intake emerged as potential explanatory factors for particle concentrations. Conclusion MP-like particles were detectable in the majority of urine samples analysed using a Nile Red/DAPI fluorescence microscopy workflow. Considerable variability in particle concentrations was observed between individuals and across sampling timepoints. Several questionnaire-derived variables emerged in exploratory analyses; however, given the limited sample size, and the absence of polymer-specific particle identification, these findings should be viewed as exploratory signals needing further confirmation.

INTRODUCTION: Cirrhosis is associated with microbiome alterations beyond the gut, including skin, saliva, and serum. This study investigated the urinary microbiome in patients with cirrhosis, who have an increased risk of urinary tract infections. METHODS: Midstream urine from 137 patients was analyzed by 16S rRNA sequencing; 68 patients with cirrhosis and 32 noncirrhotic controls met inclusion criteria. RESULTS: Patients with cirrhosis showed significantly reduced alpha-diversity. The urinary microbiome of controls was enriched in Streptococcus species. DISCUSSION: Reduced microbial diversity and lower Streptococcus abundance in patients with cirrhosis might help to explain their heightened susceptibility to urinary tract infections.

Liver cirrhosis is a complex condition characterized by oxidative stress, inflammation, and metabolic dysfunction, contributing to systemic complications and high mortality. High-density lipoprotein (HDL), particularly its small subclasses, is known for its antioxidant, anti-inflammatory, and cholesterol efflux capacities. This study examined changes in HDL subclass distribution and composition in cirrhosis and assessed their prognostic relevance for mortality. We analyzed HDL profiles using nuclear magnetic resonance spectroscopy in patients with compensated (n = 205) and decompensated (n = 158) cirrhosis, compared to healthy controls (n = 16). Across all HDL subclasses in cirrhotic patients, cholesterol content was decreased, and triglyceride levels were elevated. In particular, compensated cirrhosis was associated with a marked reduction in small and extra-small HDL particles, while large HDL levels remained unchanged. This reduction was even more pronounced in decompensated disease. Small HDL particle levels were inversely correlated with oxidative stress markers and liver dysfunction and independently predicted 12-month mortality in patients with compensated cirrhosis, even after adjusting for MELD score. In conclusion, our findings highlight a substantial depletion of small and extra-small HDL particles as a key feature of cirrhosis, linked to oxidative stress and mortality in the compensated stage.

Major depression (MD) significantly impacts individual well-being and society. The vagus nerve plays a pivotal role in the gut-brain axis, facilitating bidirectional communication between these systems. Recent meta-analyses suggest potential antidepressant effects of probiotics, although their mechanisms remain unclear. This study aimed to assess the impact of a multi-species probiotic (OMNi-BiOTiC® STRESS Repair) on vagus nerve function in 43 MD patients and 43 healthy controls (HC). Participants received either probiotics or placebo twice daily. Serum and stool samples were collected at baseline, 7 days, 28 days, and 3 months. Vagus nerve (VN) function was evaluated using 24-hour electrocardiography (ECG) for heart rate variability (HRV), alongside stool microbiome analysis via 16S rRNA sequencing. After 3 months, MD patients receiving probiotics demonstrated significantly improved morning VN function compared to HC. MD participants who were in the probiotic group showed a significant increase in Christensellales, particularly Akkermansia muciniphila along with improved sleep parameters (use of sleep medication, sleep latency) as measured by the Pittsburgh Sleep Quality Inventory (PSI). This study highlights potential physiological benefits of probiotics in MD, potentially mediated through VN stimulation. Understanding these mechanisms could lead to novel therapeutic approaches for MD management.

Background/Objectives: Neoadjuvant chemotherapy (NAC) followed by radical gastrectomy is the current standard approach for locally advanced gastric cancer (GC) in the West. Both NAC and gastrectomy can significantly influence the gut microbiome, potentially leading to clinically significant changes. However, no longitudinal studies to date support this hypothesis. This study investigates gut microbiome changes throughout GC treatment, including NAC and gastrectomy. Methods: This longitudinal observational study included GC patients undergoing NAC followed by gastrectomy. Fecal microbiome composition, intestinal inflammation (fecal calprotectin), and gut permeability (LBP, sCD14) markers were investigated at baseline, after NAC, and after gastrectomy. Results: A total of 38 patients were included in the study. The results showed that NAC did not affect the gut microbiome composition at the phylum level. In contrast, radical gastrectomy led to an increased abundance of Bacteroidetes and Proteobacteria and a decreased abundance of Firmicutes and Actinobacteria. Furthermore, NAC alone did not impact alpha or beta diversity, while a combination of NAC and gastrectomy significantly influenced both. After gastrectomy, the gut microbiome composition analysis also revealed enrichment of oralization-associated bacterial species such as Escherichia-Shigella, Streptococcus equinus, uncultured Streptococcus species, and species from the Enterobacteriaceae family. Intestinal inflammation and gut permeability markers did not significantly change throughout the treatment. Conclusions: The radical treatment of advanced GC with NAC and radical surgery has long-term effects on the gut microbiome, characterized by gut microbiome oralization. These sustained alterations primarily stem from the radical gastrectomy rather than the NAC. Since previous studies have linked oralization-associated dysbiosis to various gastrointestinal symptoms, this study highlights the gut microbiome as a potential therapeutic target to enhance the quality of life in long-term survivors following gastrectomy.

Human diseases are multifaceted, starting with alterations at the cellular level, damaging organs and their functions, and disturbing interactions and immune responses. In vitro systems offer clarity and standardisation, which are crucial for effectively modelling disease. These models aim not to replicate every disease aspect but to dissect specific ones with precision. Controlled environments allow researchers to isolate key variables, eliminate confounding factors and elucidate disease mechanisms more clearly. Technological progress has rapidly advanced model systems. Initially, 2D cell culture models explored fundamental cell interactions. The transition to 3D cell cultures and organoids enabled more life-like tissue architecture and enhanced intercellular interactions. Advanced bioreactor-based devices now recreate the physicochemical environments of specific organs, simulating features like perfusion and the gastrointestinal tract’s mucus layer, enhancing physiological relevance. These systems have been simplified and adapted for high-throughput research, marking significant progress. This review focuses on in vitro systems for modelling gastrointestinal tract cancer and the side effects of cancer treatment. While cell cultures and in vivo models are invaluable, our main emphasis is on bioreactor-based in vitro modelling systems that include the gut microbiome.

Pediatric short bowel syndrome (SBS) is a rare condition characterized by a massive loss of the small intestine, leading to the inability to meet nutritional requirements without the use of parenteral or enteral supplementation. SBS causes profound alterations in the intestinal microbiome and metabolome. The aim of this study was a detailed assessment of the intestinal microbiome and metabolome in a murine model of SBS. We performed a 60% proximal small bowel resection versus a sham operation in C57BL/6 mice. Four weeks postoperatively, the microbial communities of different intestinal segments (jejunum, ileum, colon) and stool were assessed by 16S rRNA gene sequencing. Bile acids in serum and stool and volatile organic compounds (VOCs) in the fecal headspace were assessed using LC-MS and GC-MS techniques. The α-diversity of the different intestinal segments did not significantly differ between the two groups. β-diversity significantly differed between sham and SBS mice. While in the jejunum, Faecalibaculum was significantly increased in SBS animals, a significant reduction in Lactobacillus and Sporosarcina was detected in the ileum of SBS mice. In the colon of SBS mice, a significant decrease in Ruminococcaceae and a significant increase in Proteobacteria such as Faecalibaculum and Escherichia-Shigella were found. Serum levels of deoxycholic, taurocholic and taurochenodeoxycholic acids were significantly higher in the SBS group. Of the 29 VOCs tested, hexane, isoflurane and pentane were significantly higher in the SBS group, and pyrrole was significantly lower. We were able to show that SBS causes shifts in the murine intestinal microbiome and metabolome including serum BAs and fecal VOCs.

Cancer therapy is often associated with severe side effects such as drug induced weight loss, also known as chemotherapy-induced cachexia. The aim of this study was to investigate the effects of a multispecies probiotic (OMNi-BiOTiC^® 10 AAD) in a chemotherapy mouse model. A total of 24 male BALB/c mice were gavage-fed with the probiotic formulation or water, once a day for 3 weeks. In the third week, the mice received intraperitoneal cyclophosphamide. At euthanasia, the organs were dissected, and serum was sampled for cytokine analysis. Tight junction components, myosin light chain kinase, mucins, and apoptosis markers were detected in the ileum and colon using histological analyses and qRT-PCR. Lipolysis was analyzed by enzymatic activity assay, Western blotting analyses, and qRT-PCR in WAT. The fecal microbiome was measured with 16S-rRNA gene sequencing from stool samples, and fecal volatile organic compounds analysis was performed using gas chromatography/mass spectrometry. The probiotic-fed mice exhibited significantly less body weight loss and adipose tissue wasting associated with a reduced CGI58 mediated lipolysis. They showed significantly fewer pro-inflammatory cytokines and lower gut permeability compared to animals fed without the probiotic. The colons of the probiotic-fed animals showed lower inflammation scores and less goblet cell loss. qRT-PCR revealed no differences in regards to tight junction components, mucins, or apoptosis markers. No differences in microbiome alpha diversity, but differences in beta diversity, were observed between the treatment groups. Taxonomic analysis showed that the probiotic group had a lower relative abundance of Odoribacter and Ruminococcus-UCG014 and a higher abundance of Desulfovibrio. VOC analysis yielded no significant differences. The results of this study indicate that oral administration of the multispecies probiotic OMNi-BiOTiC^® 10 AAD could mitigate cyclophosphamide-induced chemotherapy side effects.

Background & Aims: On a global scale, liver cirrhosis is attributable to ~1 million deaths per year. This systemic disease comes along with diverse sequelae, including microbiota alterations, increased gut permeability and translocation of microbial components into the systemic circulation. Alongside the extensively studied influence of bacterial translocation and its host–pathogen interactions, far less is known about the role and impact of fungal components once having crossed the intestinal barrier.Methods: Including 70 patients with different aetiologies of liver cirrhosis, we investigated the relationship between fungal translocation, measured by 1,3‐β‐D‐glucan (BDG), and biomarkers of gut integrity, inflammation and severity/outcome of liver disease.Results: Patients with cirrhosis Child–Pugh class (CPC)‐B were more likely to have positive serum BDG (aOR 5.4, 95% CI 1.2–25.2) compared to patients with cirrhosis CPC‐A. BDG showed a moderate positive correlation with several markers of inflammation (sCD206, sCD163, Interleukin 8, interferon‐gamma‐induced protein). Mortality differed significantly between patients with positive versus negative BDG (log‐rank test, p = 0.015). The multivariable Cox regression model yielded an aHR of 6.8 (95% CI 1.8–26.3).Discussion: We observed trends for increased fungal translocation depending on the severity of liver cirrhosis, an association of BDG with an inflammatory environment and the adverse effects of BDG on disease outcome. In order to gain more in‐depth knowledge about (fungal‐)dysbiosis and its detrimental consequences in the setting of liver cirrhosis, these trends need to be studied in more detail including prospective sequential testing in larger cohorts together with mycobiome analyses. This will further elucidate complex host–pathogen interactions and potentially introduce points of application for therapeutic interventions.