Prophylactic Intra-Uterine β-Cyclodextrin Administration during Intra-Uterine Ureaplasma parvum Infection Partly Prevents Liver Inflammation without Interfering with the Enterohepatic Circulation of the Fetal Sheep

Chorioamnionitis can lead to inflammation and injury of the liver and gut, thereby predisposing patients to adverse outcomes such as necrotizing enterocolitis (NEC). In addition, intestinal bile acids (BAs) accumulation is causally linked to NEC development. Plant sterols are a promising intervention to prevent NEC development, considering their anti-inflammatory properties in the liver. Therefore, we investigated whether an intra-amniotic (IA) Ureaplasma parvum (UP) infection affected the liver and enterohepatic circulation (EHC) and evaluated whether an IA administered plant sterol mixture dissolved in β-cyclodextrin exerted prophylactic effects. An ovine chorioamnionitis model was used in which liver inflammation and the EHC were assessed following IA UP exposure in the presence or absence of IA prophylactic plant sterols (a mixture of β-sitosterol and campesterol dissolved in β-cyclodextrin (carrier)) or carrier alone. IA UP exposure caused an inflammatory reaction in the liver, histologically seen as clustered and conflated hepatic erythropoiesis in the parenchyma, which was partially prevented by IA administration of sterol + β-cyclodextrin, or β-cyclodextrin alone. In addition, IA administration of β-cyclodextrin prior to UP caused changes in the expression of several hepatic BAs transporters, without causing alterations in other aspects of the EHC. Thereby, the addition of plant sterols to the carrier β-cyclodextrin did not have additional effects

Chronic intra-uterine Ureaplasma parvum infection induces injury of the enteric nervous system in ovine fetuses

Background: Chorioamnionitis, inflammation of the fetal membranes during pregnancy, is often caused by intra-amniotic (IA) infection with single or multiple microbes. Chorioamnionitis can be either acute or chronic, and is associated with adverse postnatal outcomes of the intestine, including necrotizing enterocolitis (NEC). Neonates with NEC have structural and functional damage to the intestinal mucosa and the enteric nervous system (ENS), with loss of enteric neurons and glial cells. Yet, the impact of acute, chronic or repetitive antenatal inflammatory stimuli on the development of the intestinal mucosa and ENS has not been studied. The aim of this study is therefore to investigate the effect of acute, chronic and repetitive microbial exposure on the intestinal mucosa, submucosa and ENS in premature lambs. Materials and Methods: A sheep model of pregnancy was used in which the ileal mucosa, submucosa and ENS were assessed following IA exposure to lipopolysaccharide (LPS) for 2 or 7 days (acute), Ureaplasma parvum (UP) for 42 days (chronic) or repetitive microbial exposure (42 days UP with 2 or 7 days LPS). Results: IA LPS exposure for 7 days or IA UP exposure for 42 days caused intestinal injury and inflammation in the mucosal and submucosal layer of the gut. Repetitive microbial exposure did not further aggravate injury of the terminal ileum. Chronic IA UP exposure caused significant structural ENS alterations characterized by loss of PGP9.5 and S100β immunoreactivity whereas these changes were not found after re-exposure of chronic UP-exposed fetuses to LPS for 2 or 7 days. Conclusion: The in utero loss of PGP9.5 and S100β immunoreactivity following chronic UP exposure corresponds with intestinal changes in neonates with NEC, and may therefore form a novel mechanistic explanation for the association of chorioamnionitis and NEC

Perinatal inflammation and adverse outcomes of the intestine and liver

A major cause of preterm birth is infection of the amniotic membranes during pregnancy. This thesis investigated whether such an infection has adverse effects on the intestine and liver of the premature, in a laboratory model. The research demonstrated that infection of the amniotic membranes can induce intestinal inflammation, which coincided with damage of the gastrointestinal nerve system, especially when an infection is induced early in pregnancy. Moreover, it was found that shortly after such an infection, an inflammatory reaction occurred in the liver, which contributed to an overall immune response of the fetus. It is known that preterm birth and amniotic infection increase the risk of developing necrotizing enterocolitis, one of the most severe neonatal gastrointestinal emergencies. The results described in this thesis suggest that the onset of this disease may already have its origin in the womb. Lastly, a potential intervention was described that can reduce the inflammatory response in the liver

Reducing seroma formation and its sequelae after mastectomy by closure of the dead space:The interim analysis of a multi-center, double-blind randomized controlled trial (SAM trial)

Objective: The main objective of this double-blind randomized controlled trial (RCT) was to assess seroma formation and its sequelae in patients undergoing mastectomy. Patients were randomized into one of three groups in which different wound closure techniques were applied: 1) conventional wound closure without flap fixation (CON) 2) flap fixation using sutures (FF-S) and 3) flap fixation using an adhesive tissue glue (FF-G). Background: Seroma formation is still a bothersome complication after mastectomy. Flap fixation seems promising in reducing seroma formation. Various flap fixation techniques remain to be analyzed, including long-term outcome measures. Methods: This trial was conducted in three different hospitals between June 2014 and November 2016. Patients were allocated to one of three groups. The primary outcome was the number of seroma needle aspirations. Secondary outcomes were (surgical site) infections, number of outpatient clinic visits, shoulder function, postoperative pain, patient-reported cosmesis and skin dimpling. Results: A total of 187 patients were randomly assigned to CON (n = 61), FF-S (n = 64) and FF-G (n = 62). The number of seroma aspirations was significantly higher in CON when compared to both flap fixation groups (p = 0.032), with no difference between FF-S and FF-G. Secondary outcomes showed no statistical differences between all groups. The higher number of outpatient clinic visits in CON was considered to be of clinical importance (CON = 27 (44.3%), FF-S = 19 (30.6%) and FF-G = 21 (34.4%)). Conclusions: Mastectomy followed by flap fixation with either sutures or adhesive tissue glue reduces the number of seroma aspirations when compared to simple wound closure. (C) 2019 Elsevier Ltd. All rights reserved