Efficient treatment of esophageal nutrition bezoars: dissolution outmatches removal-the Zurich approach.

Enteral feed bezoars are difficult to treat and can lead to serious adverse events. There is no standardized treatment approach and various strategies have been suggested. We herein describe three cases of successful dissolutions of feed bezoars consisting of Promote® Fibre Plus with sodium bicarbonate 8.4% in critically ill patients. To provide the rationale for this approach, the effect of sodium bicarbonate 8.4% on enteral feed concretions was studied in vitro. First, Promote® Fibres Plus was incubated with hydrochloric acid with gradually decreasing pH values to establish a pH at which the solution solidifies. The resulting enteral feed concretion was exposed to sodium bicarbonate 8.4% and Coca Cola®. All patients were successfully treated with sodium bicarbonate 8.4% without the need of lengthy or repeat endoscopies. In vitro, Promote® Fibres Plus solidifies when acidified below a pH of 4.6. The resulting enteral feed concretions dissolved when exposed to sodium bicarbonate 8.4%. Incubation with Coca Cola® had no effect. We provide evidence that enteral feed bezoars consisting of Promote® Fibres Plus can be efficiently and safely treated with sodium bicarbonate 8.4% offering a new approach for daily patient care.

Commensal Clostridiales strains mediate effective anti-cancer immune response against solid tumors.

Despite overall success, T cell checkpoint inhibitors for cancer treatment are still only efficient in a minority of patients. Recently, intestinal microbiota was found to critically modulate anti-cancer immunity and therapy response. Here, we identify Clostridiales members of the gut microbiota associated with a lower tumor burden in mouse models of colorectal cancer (CRC). Interestingly, these commensal species are also significantly reduced in CRC patients compared with healthy controls. Oral application of a mix of four Clostridiales strains (CC4) in mice prevented and even successfully treated CRC as stand-alone therapy. This effect depended on intratumoral infiltration and activation of CD8+ T cells. Single application of Roseburia intestinalis or Anaerostipes caccae was even more effective than CC4. In a direct comparison, the CC4 mix supplementation outperformed anti-PD-1 therapy in mouse models of CRC and melanoma. Our findings provide a strong preclinical foundation for exploring gut bacteria as novel stand-alone therapy against solid tumors.

Bilberry-derived anthocyanins prevent IFN-γ-induced pro-inflammatory signalling and cytokine secretion in human THP-1 monocytic cells.

BACKGROUND/AIMS: Anthocyanins are plant-derived dietary components that are highly abundant, for example, in bilberries. We have previously demonstrated that anthocyanins exert anti-inflammatory properties in mouse colitis models and ameliorate disease activity in ulcerative colitis patients. Here, we studied the molecular mechanisms through which anthocyanin-containing bilberry extract (BE) exerts anti-inflammatory effects in human monocytic THP-1 cells. METHODS: THP-1 cells were pre-incubated with BE 20 min prior to TNF-α or IFN-γ (100 ng/ml each) stimulation. Signalling protein activation was studied by Western blotting, mRNA expression by quantitative PCR and cytokine secretion by ELISA. RESULTS: IFN-γ-induced phosphorylation of STAT1 and STAT3 was significantly reduced by BE co-treatment. Consequently, levels of mRNA expression and/or cytokine secretion of MCP-1, IL-6, TNF-α, ICAM-1, and T-bet were lower with BE co-treatment. In contrast, BE enhanced TNF-α-mediated p65-NF-κB phosphorylation but reduced ERK1/2 phosphorylation. BE co-treatment further increased TNF-α-induced mRNA expression and secretion of NF-κB target genes, such as IL-6, IL-8, and MCP-1, while mRNA levels of ICAM-1 were reduced. CONCLUSIONS: BE co-treatment reduced IFN-γ-induced signal protein activation, pro-inflammatory gene expression, and cytokine secretion, whereas it enhanced TNF-α-induced responses. These findings suggest a distinct role for anthocyanins in modulating inflammatory responses that need to be further studied to fully understand anthocyanin-mediated effects.