Refine
Has Fulltext
- yes (3)
Is part of the Bibliography
- yes (3)
Document Type
- Journal article (3)
Language
- English (3)
Keywords
- AOM/DSS (1)
- JAK inhibitor (1)
- NPWT (1)
- Toxikologie (1)
- VAC (1)
- abdominal compartment syndrome (1)
- abdominal trauma (1)
- anti-inflammatory cytokines (1)
- burst abdomen (1)
- chronic IBD model (1)
Purpose
Definitive fascial closure is an essential treatment objective after open abdomen treatment and mitigates morbidity and mortality. There is a paucity of evidence on factors that promote or prevent definitive fascial closure.
Methods
A multi-center multivariable analysis of data from the Open Abdomen Route of the European Hernia Society included all cases between 1 May 2015 and 31 December 2019. Different treatment elements, i.e. the use of a visceral protective layer, negative-pressure wound therapy and dynamic closure techniques, as well as patient characteristics were included in the multivariable analysis. The study was registered in the International Clinical Trials Registry Platform via the German Registry for Clinical Trials (DRK00021719).
Results
Data were included from 630 patients from eleven surgical departments in six European countries. Indications for OAT were peritonitis (46%), abdominal compartment syndrome (20.5%), burst abdomen (11.3%), abdominal trauma (9%), and other conditions (13.2%). The overall definitive fascial closure rate was 57.5% in the intention-to-treat analysis and 71% in the per-protocol analysis. The multivariable analysis showed a positive correlation of negative-pressure wound therapy (odds ratio: 2.496, p < 0.001) and dynamic closure techniques (odds ratio: 2.687, p < 0.001) with fascial closure and a negative correlation of intra-abdominal contamination (odds ratio: 0.630, p = 0.029) and the number of surgical procedures before OAT (odds ratio: 0.740, p = 0.005) with DFC.
Conclusion
The clinical course and prognosis of open abdomen treatment can significantly be improved by the use of treatment elements such as negative-pressure wound therapy and dynamic closure techniques, which are associated with definitive fascial closure.
Delayed and limited administration of the JAKinib tofacitinib mitigates chronic DSS-induced colitis
(2023)
In inflammatory bowel disease, dysregulated T cells express pro-inflammatory cytokines. Using a chronic azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis model resembling ulcerative colitis, we evaluated whether and when treatment with the Janus kinase (JAK) inhibitor tofacitinib could be curative. Comparing the treatment with two and three cycles of tofacitinib medication in drinking water – intermittently with DSS induction – revealed that two cycles were not only sufficient but also superior over the 3-x regimen. The two cycles of the 2-x protocol paralleled the second and third cycles of the longer protocol. T cells were less able to express interferon gamma (IFN-γ) and the serum levels of IFN-γ, interleukin (IL)-2, IL-6, IL-17, and tumor necrosis factor (TNF) were significantly reduced in sera, while those of IL-10 and IL-22 increased under the 2-x protocol. Likewise, the frequency and effector phenotype of regulatory T cells (Tregs) increased. This was accompanied by normal weight gain, controlled clinical scores, and restored stool consistency. The general and histologic appearance of the colons revealed healing and tissue intactness. Importantly, two phases of tofacitinib medication completely prevented AOM-incited pseudopolyps and the hyper-proliferation of epithelia, which was in contrast to the 3-x regimen. This implies that the initial IBD-induced cytokine expression is not necessarily harmful as long as inflammatory signaling can later be suppressed and that time-restricted treatment allows for anti-inflammatory and tissue-healing cytokine activities.