Evaluation of the impact of an enhanced recovery after surgery (ERAS) programme on the quality of recovery in patients undergoing a scheduled hysterectomy: a prospective single-centre before-after study protocol (RAACHYS study).

INTRODUCTION: The enhanced recovery after surgery (ERAS) programmes following hysterectomies have been studied since 2010, and their positive effects on clinical or economic criteria are now well established. However, the benefits on health outcomes, especially rapid recovery after surgery from patients' perspective is lacking in literature, leading to develop scores supporting person-centred and value-based care such as patient-reported outcome measures. The aim of this study is to assess the impact of an ERAS programme on patients' well-being after undergoing hysterectomy. METHODS AND ANALYSIS: This is an observational, prospective single-centre before-after clinical trial. 148 patients are recruited and allocated into two groups, before and after ERAS programme implementation, respectively. The ERAS programme consists in optimising factors dealing with early rehabilitation, such as preoperative patient education, multimodal pain management, early postoperative fluid taken and mobilisation. A self-questionnaire quality of recovery-15 (QoR-15) on the preoperative day 1 (D-1), postoperative day 0 evening (D0) and the postoperative day 1 (D+1) is completed by patients. Patients scheduled to undergo hysterectomy, aged 18 years and above, whose physical status are classified as American Society of Anesthesiologists score 1-3 and who are able to return home after being discharged from hospital and contact their physician or the medical department if necessary are recruited for this study. The total duration of inclusion is 36 months. The primary outcome is the difference in QoR-15 scores measured on D+1 which will be compared between the 'before' and the 'after' group, using multiple linear regression model. ETHICS AND DISSEMINATION: Approval was obtained from the Ethical Committee (Paris, France). Subjects are actually being recruited after giving their oral agreement or non-objection to participate in this clinical trial and following the oral and written information given by the anaesthesiologist practitioner.Trial registration number: ClinicalTrials.gov: NCT04268576 (Pre-result).

Identification of the preoperative and perioperative factors that predict postoperative endothelial cell density after Descemet membrane endothelial keratoplasty: A retrospective cohort study.

Low postoperative endothelial-cell density (ECD) plays a key role in graft failure after Descemet-membrane endothelial keratoplasty (DMEK). Identifying pre/perioperative factors that predict postoperative ECD could help improve DMEK outcomes. This retrospective study was conducted with consecutive adult patients with Fuchs-endothelial corneal dystrophy who underwent DMEK in 2015-2019 and were followed for 12 months. Patients underwent concomitant cataract surgery (triple-DMEK) or had previously undergone cataract surgery (pseudophakic-DMEK). Multivariate analyses assessed whether: patient age/sex; graft-donor age; preoperative ECD, mean keratometry, or visual acuity; triple DMEK; surgery duration; surgical difficulties; and need for rebubbling predicted 6- or 12-month ECD in the whole cohort or in subgroups with high/low ECD at 6 or 12 months. The subgroups were generated with the clinically relevant threshold of 1000 cells/mm2. Surgeries were defined as difficult if any part was not standard. In total, 103 eyes (95 patients; average age, 71 years; 62% women) were included. Eighteen eyes involved difficult surgery (14 difficult graft preparation or unfolding cases and four others). Regardless of how the study group was defined, the only pre/perioperative variable that associated significantly with 6- and 12-month ECD was difficult surgery (p = 0.01, 0.02, 0.05, and 0.0009). Difficult surgery also associated with longer surgery duration (p = 0.002). Difficult-surgery subgroup analysis showed that difficult graft dissection associated with lower postoperative ECD (p = 0.03). This association may reflect endothelial cell loss due to excessive graft handling and/or an intrinsic unhealthiness of the endothelial cells in the graft that conferred unwanted physical properties onto the graft that complicated its preparation/unfolding.

Comparative effect of sodium butyrate and sodium propionate on proliferation, cell cycle and apoptosis in human breast cancer cells MCF-7.

INTRODUCTION: Short-chain fatty acids (SCFAs) are ubiquitous lipids produced as a result of bacterial fermentation of dietary fiber. While their role in colorectal cancer is well known, the effect of SCFAs in breast cancer is poorly defined. OBJECTIVE: To understand the various effects of SCFAs on breast carcinogenesis, we investigated the effect of sodium butyrate (NaB) and sodium propionate (NaP) in MCF-7 cell line. MATERIALS AND METHODS: Cells were incubated with different concentrations of NaB or NaP for 24, 48, 72 or 96 h. Cell proliferation was assayed using MTT kit. Cell cycle was performed using propidium iodide staining then analyzed with a flow cytometer. Apoptosis was assessed by Hoechst technique and cell-cycle sub-G1 phase. RESULTS: NaB and NaP inhibited MCF-7 cell proliferation in a dose-dependent manner with respective IC50 of 1.26 mM and 4.5 mM, thus indicating that NaB is more potent than NaP. Low and medium levels of both SCFAs induced morphology changes which are characteristic of a differentiated phenotype. Flow cytometry analysis revealed a blockage in G1 growth phase. Interestingly, removing NaB or NaP from culture media after few days of treatment showed a reversible effect on cell morphology and proliferation where cells reentered the cycle after 24 h of drug wash-out. Finally, treatment with medium levels of these molecules induced low MCF-7 apoptosis, while higher doses led to massive apoptosis. CONCLUSION: Our results show that SCFAs may be considered as an interesting inhibitor for breast cancer progression.

No evidence for oxidative stress in the cerebellar tissues or cells of juvenile male mice exposed via lactation to the 6 non-dioxin-like PCBs at levels below the regulatory safe limits for humans.

The developing central nervous system is particularly vulnerable to environmental contaminants such as non-dioxin-like polychlorinated biphenyls (NDL-PCBs). This study investigated the potential oxidative effects in mice pups exposed via lactation to the sum of the six indicator NDL-PCBs (∑6 NDL-PCBs) at 0, 1, 10 and 100 ng/kg per 14 days, constituting levels below the guidance values fixed by French food safety agencies for humans at 10 ng/kg body weight per day. For this purpose, the oxidative status was assessed by flow cytometry via dichloro-dihydro-fluorescein diacetate in the cerebellum of juvenile male offspring mice during brain growth spurt [postnatal day (PND) 14]. No significant differences were found in the levels of reactive oxygen species in the cerebellar neurons or glial cells (astrocytes, oligodendrocytes and microglia) of lactationally exposed male mice at PND 14 (p>0.05). Concordantly, oxidative-stress related gene expression was measured by qPCR for catalase, copper zinc superoxide dismutase 1, glyoxalase 1, glutathione peroxidase 1, and glutathione reductase 1, in the cerebellum at PND 14 appeared unaffected, as also verified at the protein level by immunoblots. Moreover, transcriptomic data from our previous work have not shown differences in the mRNA expressions of genes belonging to GO terms involved in oxidative stress in neurons of male mice exposed to ∑6 NDL-PCBs compared to controls; except for glyoxalase 1 which was downregulated in neurons isolated from exposed group compared to controls. Our findings suggest that lactational exposure to NDL-PCBs at environmental relevant concentrations may not cause significant oxidative effect on juvenile cerebellum.

Lactational exposure of mice to low levels of non-dioxin-like polychlorinated biphenyls increases susceptibility to neuronal stress at a mature age.

Lactational exposure to low levels of the sum of the six indicator polychlorinated biphenyls (Σ6 NDL-PCBs, 10ng/kg/day) is known to lead to persistent anxious behavior in young and adult offspring mice at postnatal days 40 and 160, respectively. At more advanced life stages, we evaluated the effects on the mouse brain of neuronal stress induced by the synaptotoxic amyloid-beta (Aß) peptide. Perinatal exposure of lactating mice to Σ6 NDL-PCBs did not affect short-term memory performances of their offspring male mice aged 14 months as compared to control PCB-naive mice. However, following intracerebroventricular injection of soluble Aß oligomers, significant impairments in long-term memory were detected in the mice that had been lactationally treated with Σ6 NDL-PCBs. In addition, immunoblot analyses of the synaptosomal fraction of hippocampal tissues from treated mice revealed a lower expression of the synaptic proteins synaptophysin and PSD-95. Though preliminary, our findings suggest for the first time that early exposure to low levels of NDL-PCBs induce late neuronal vulnerability to amyloid stress. Additional experiments are needed to confirm whether early environmental influences are involved in the etiology of brain aging and cognitive decline.

Lactational exposure to low levels of the six indicator non-dioxin-like polychlorinated biphenyls induces DNA damage and repression of neuronal activity, in juvenile male mice.

Previously, we evaluated the effects of lactational exposure to a representative mixture of the six indicator non-dioxin-like polychlorinated biphenyls (∑6 NDL-PCBs) at low levels on the neurobiological changes and developmental/behavioral performances in mice. In this study, we analyzed the global gene expression profile in cerebellar neurons isolated from male mice presenting the most significant induction of anxiety-like behavior in our previous study (10 ng/kg ∑6 NDL-PCBs). Our results revealed changes in the expression of 16658 genes in the neurons of the exposed mice. Among these, 693 upregulated [fold change (FC)>2; p<0.05] and 665 downregulated (FC<2; p<0.05) genes were statistically linked to gene ontology terms (GO). Overexpressed genes belonged to GO terms involved with the cell cycle, DNA replication, cell cycle checkpoint, response to DNA damage stimulus, regulation of RNA biosynthetic processes, and microtubule cytoskeleton organization. Downregulated genes belonged to terms involved with the transmission of nerve impulses, projection neurons, synapse hands, cell junctions, and regulation of RNA biosynthetic processes. Using qPCR, we quantified gene expression related to DNA damage and validated the transcriptomic study, as a significant overexpression of Atm-Atr Bard1, Brca2, Fancd2, Figf, Mycn, p53 and Rad51 was observed between groups (p<0.001). Finally, using immunoblots we determined the expression level of six selected proteins. We found that changes in the protein expression of Atm Brca1, p53, Kcnma1, Npy4r and Scn1a was significant between exposed and control groups (p<0.05), indicating that the expression pattern of these proteins agreed with the expression pattern of their genes by qPCR, further validating our transcriptomic findings. In conclusion, our study showed that early life exposure of male mice to a low level of ∑6 NDL-PCBs induced p53-dependent responses to cellular stress and a decrease in the expression of proteins involved in the generation, conduction, and transmission of electrical signals in neurons.

Neurodevelopmental and behavioral toxicity via lactational exposure to the sum of six indicator non-dioxin-like-polychlorinated biphenyls (∑6 NDL-PCBs) in mice.

In this study, the neurobehavioral toxicity of lactational exposure to a representative mixture of the six indicator non-dioxin-like-polychlorinated biphenyls (∑6 NDL-PCBs 28, 52, 101, 138, 153 and 180) found in contaminated fish matrices were assessed in neonatal (postnatal day 0) to adult (postnatal day 275) mice. Thus, a battery of developmental, behavioral and cognitive tests was performed. The performance of mice whose mothers were orally exposed to ∑6 NDL-PCBs at environmental doses of 1 ng/kg, 10 ng/kg or 100 ng/kg was compared to that of mice whose mothers were orally exposed to vehicle. Our results showed that neonatal offspring mice exposed to ∑6 NDL-PCBs through lactation exhibited significantly longer turning reflexes on postnatal days 7 and 9 (p=0.001, p=0.002, respectively) at 100 ng/kg and showed a reduction in their general activity at 1 ng/kg (p=0.002) and 10 ng/kg (p=0.001) compared to controls. However, these developmental alterations were sex-dependent; only the female reflexes and male locomotor activity were affected. These disturbances were transient, and they disappeared with age. In addition, the males' visuomotor integration was also altered at the doses of 1 ng/kg (p=0.02) and 100 ng/kg (p=0.004), as revealed by the WESPOC test. Nevertheless, lactational exposure to ∑6 NDL-PCBs (1-100 ng/kg) resulted in persistent disturbances despite a long post-weaning period; the exposed mice exhibited anxious behavior that was detected at more progressive life stages, i.e., at postnatal days 40 and 160, using an elevated plus maze and the light/dark choice test, respectively. This persistent anxious behavior could be related to the overexpression of RyR3 in the cerebellum via the disruption of calcium signaling in the neurons. We found no differences in the offspring mice with regard to their cognitive function and mood or mRNA neurotransmitter receptor gene expression in several brain areas, including 5-HT(1A), MOR1 and GABA(Aα1), suggesting the absence of adverse effects of postnatal exposure to ∑6 NDL-PCBs under these conditions. Therefore, our results suggest that regular consumption of contaminated fish matrices by lactating women could be detrimental to the neurodevelopment of their newborns.