A systematic review of high-fibre dietary therapy in diverticular disease

The exact pathogenesis of diverticular disease of the sigmoid colon is not well established. However, the hypothesis that a low-fibre diet may result in diverticulosis and a high-fibre diet will prevent symptoms or complications of diverticular disease is widely accepted. The aim of this review is to assess whether a high-fibre diet can improve symptoms and/or prevent complications of diverticular disease of the sigmoid colon and/or prevent recurrent diverticulitis after a primary episode. Clinical studies were eligible for inclusion if they assessed the treatment of diverticular disease or the prevention of recurrent diverticulitis with a high-fibre diet. The following exclusion criteria were used for study selection: studies without comparison of the patient group with a control group. No studies concerning prevention of recurrent diverticulitis with a high-fibre diet met our inclusion criteria. Three randomised controlled trials (RCT) and one case-control study were included in this systematic review. One RCT of moderate quality showed no difference in the primary endpoints. A second RCT of moderate quality and the case-control study found a significant difference in favour of a high-fibre diet in the treatment of symptomatic diverticular disease. The third RCT of moderate quality found a significant difference in favour of methylcellulose (fibre supplement). This study also showed a placebo effect. High-quality evidence for a high-fibre diet in the treatment of diverticular disease is lacking, and most recommendations are based on inconsistent level 2 and mostly level 3 evidence. Nevertheless, high-fibre diet is still recommended in several guideline

Pentoxifylline as a therapeutic option for pre-eclampsia: a study on its placental effects

Background and Purpose Recently pentoxifylline, a non-selective phosphodiesterase inhibitor and adenosine receptor antagonist, has attracted much interest for the treatment of the increased vascular resistance and endothelial dysfunction in pre-eclampsia. We therefore investigated the placental transfer, vascular effects and anti-inflammatory actions of pentoxifylline in healthy and pre-eclamptic human placentas. Experimental Approach The placental transfer and metabolism of pentoxifylline were studied using ex vivo placenta perfusion experiments. In wire myography experiments with chorionic plate arteries, pentoxifyllines vasodilator properties were investigated, focusing on the cGMP and cAMP pathways and adenosine receptors. Its effects on inflammatory factors were also studied in placental explants. Key Results Pentoxifylline transferred from the maternal to foetal circulation, reaching identical concentrations. The placenta metabolized pentoxifylline into its active metabolite lisofylline (M1), which was released into both circulations. In healthy placentas, pentoxifylline potentiated cAMP- and cGMP-induced vasodilation, as well as causing vasodilation by adenosine A(1) antagonism and via NO synthase and PKG. Pentoxifylline also reduced inflammatory factors secretion. In pre-eclamptic placentas, we observed that its vasodilator capacity was preserved, however not via NO-PKG but likely through adenosine signalling. Pentoxifylline neither potentiated vasodilation through cAMP and cGMP, nor suppressed the release of inflammatory factors from these placentas. Conclusion and Implications Pentoxifylline is transferred across and metabolized by the placenta. Its beneficial effects on the NO pathway and inflammation are not retained in pre-eclampsia, limiting its application in this disease, although it could be useful for other placenta-related disorders. Future studies might focus on selective A(1) receptor antagonists as a new treatment for pre-eclampsia

Serum cytokine levels are associated with tumor progression during FOLFIRINOX chemotherapy and overall survival in pancreatic cancer patients

Background: Biomarkers predicting treatment response may be used to stratify patients with pancreatic ductal adenocarcinoma (PDAC) for available therapies. The aim of this study was to evaluate the association of circulating cytokines with FOLFIRINOX response and with overall survival (OS). Methods: Serum samples were collected before start and after the first cycle of FOLFIRINOX from patients with PDAC (n=83) of all disease stages. Overall, 34 circulating cytokines were analyzed with a multiplex immunoassay. In addition, changes in peripheral blood immune cell counts were determined by flow cytometry to correlate with differences in cytokine levels. Chemotherapy response was determined by CT scans with the RECIST 1.1 criteria, as disease control (n=64) or progressive disease (n=19) within eight cycles of FOLFIRINOX. Results: Patients with high serum IL-1RA concentrations after one cycle of chemotherapy were less likely to have tumor progression during FOLFIRINOX (OR 0.25, P=0.040). Increase of circulating IL-1RA concentrations correlated with increase of total, classical (CD14+CD16-), and non-classical monocytes (CD14-CD16+), and dendritic cells. In multivariable cox regression, including the variables chemotherapy response outcome and baseline CA19-9 level, serum concentrations of IL-7 (HR 2.14, P=0.010), IL-18 (HR 2.00, P=0.020), and MIP-1β (HR 0.51, P=0.025) after one cycle of FOLFIRINOX showed correlations with OS. Conclusions: Circulating IL-1RA, IL-7, IL-18, and MIP-1β concentrations are biomarkers associated with FOLFIRINOX response in PDAC patients, suggesting an important role for specific immune cells in chemotherapy response and PDAC progression. Cytokine-based treatment might improve patient outcome and should be evaluated in future studies