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Transcriptome Profile in Hippocampus During Acute Inflammatory Response to Surgery: Toward Early Stage of PND.

ABSTRACT: Perioperative neurocognitive disorders (PND) are common complications observed in surgical patients, but there are no effective treatments and the detailed mechanisms remain largely unknown. In this study, transcriptome analysis was performed to investigate the hippocampal changes after surgery and underlying molecular mechanisms of PND. Tibial fracture surgery was performed in 3-4 months old C57BL/6J mice to mimic human orthopedic surgery. We demonstrated that memory consolidation of the hippocampal-dependent trace-fear conditioning task was significantly impaired. By using ELISA, a significant elevated IL-6 was observed both in circulating system and central nervous system and peaked at 6 h post-surgery, but transiently returned to baseline thereafter. Hippocampus were collected at 6 h post-surgery then processed for RNA-Seq. A total of 268 genes were screened differentially expressed between the Surgery and Control group, including 170 up-regulated genes and 98 down-regulated genes. By functional enrichment analysis of differently expressed genes, several KEGG pathways involved in inflammatory mediator regulation of TRP channels, neuroactive ligand-receptor interaction and cholinergic synapse were overrepresented. Quantitative real-time PCR confirmed 15 dysregulated genes of interest. These results provide a comprehensive insight into global gene expression changes during the acute presence of hippocampal inflammation and a better understanding on early stage of PND.

SUBMITTER: Xiang X

PROVIDER: S-EPMC6370675 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Transcriptome Profile in Hippocampus During Acute Inflammatory Response to Surgery: Toward Early Stage of PND.

Xiang Xuwu X Yu Yang Y Tang Xiaodong X Chen Manli M Zheng Yueying Y Zhu Shengmei S

Frontiers in immunology 20190205

Perioperative neurocognitive disorders (PND) are common complications observed in surgical patients, but there are no effective treatments and the detailed mechanisms remain largely unknown. In this study, transcriptome analysis was performed to investigate the hippocampal changes after surgery and underlying molecular mechanisms of PND. Tibial fracture surgery was performed in 3-4 months old C57BL/6J mice to mimic human orthopedic surgery. We demonstrated that memory consolidation of the hippoc ...[more]

PMID: 30804943

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Project description:BackgroundPerioperative neurocognitive disorders (PND) are common complications of major surgery among elderly patients, remarkably decreasing patients' life quality. Platelet count has been proved to be an essential factor in inflammation. However, as far as we know, the relationship between platelet count and PND is not clear yet in the orthopedic area. PND could be a long-term disease, which sometimes lasts for several years, and it is meaningful to find a biomarker of PND at the early stage. Thus, we designed this study to find out the association between perioperative platelet count and occurrence of PND, and determine whether preoperative platelet count could be a biomarker of the early stage of PND.MethodsA prospective observational study was performed on the patients who would take total knee arthroplasty or total hip arthroplasty. Their peripheral platelets were counted by blood routine examination 1 day before and 3 days after the surgery. And we assessed their neurocognitive functions 1 day before and 3 days after the surgery. These data were recorded and analyzed to find out the relationship between platelet count and the occurrence of PND.ResultsEventually, 70 patients finished the whole process, and 14 of them developed PND. The median preoperative platelet count in the PND group was significantly higher than that in the non-PND group (239 vs 168 × 10^9/L, p = 0.009). Preoperative platelet count was an independent risk factor for PND (odds ratio = 1.014, 95% confidence interval [CI] 1.000-1.027, P = 0.043) in the logistic multivariable regression, while the area under the curve of the receiver operating characteristic curve of the prediction model was 0.796 (95% CI 0.676-0.916).ConclusionsThe higher preoperative and postoperative level of platelet count in the peripheral blood were associated with the early stage of PND, and preoperative platelet count could be a potential predictor of the early stage of PND in patients undergoing major orthopedic surgeries.Trial registrationChinese Clinical Trial Registry: ChiCTR2000033001 , registration date: 17 May 2020.

Project description:BackgroundThe objective of this study was to describe the perspective of patients with early breast cancer toward research biopsies. The authors hypothesized that more patients at academic sites than at community-based sites would be willing to consider these procedures.MethodsIn total, 198 patients with early stage breast cancer were recruited from 3 academic centers (n = 102) and from 1 community oncology practice (n = 96). The primary objective was to compare the proportion of patients willing to consider donating excess tissue biospecimens from surgery, from a clinically indicated breast biopsy, or from a research purposes-only biopsy (RPOB) between practice types.ResultsMost patients (93% at academic sites, 94% at the community oncology site) said they would consider donating excess tissue from surgery for research. One-half of patients from academic or community sites would consider donating tissue from a clinically indicated breast biopsy. On univariate analysis, significantly fewer patients from academic sites would consider an RPOB (22% at academic sites, 42% at the community site; P = .003); however, this difference was no longer significant on multivariate analysis (P = .96). Longer transportation times and unfavorable prior experiences were associated with less willingness to consider an RPOB on multivariate analysis. Significantly fewer patients from academic sites (14%) than from the community site (35%) would consider a research biopsy in a clinical trial (P = .04). Contributing to scientific knowledge, return of results, and a personal request by their physician were the strongest factors influencing patients' willingness to undergo research biopsies.ConclusionsThe current results rejected the hypothesis that more patients with early breast cancer at academic sites would be willing to donate tissue biospecimens for research compared with those at community oncology sites. These findings identify modifiable factors to consider in biobanking studies and clinical trials.

Project description:Purpose: to evaluate changes in the transcriptome of hippocampal cells during the course of epileptogenesis, from the early events post status epilepticus (SE) to the onset of recurrent spontaneous seizures. Experimental Design: Gene expression profiling was analyzed in hippocampi of rats subjected to the pilocarpine model of epilepsy at different times during the course of epileptogenesis: 3 days post-SE (3D), 7 days post-SE (7D), and immediately (up to 12h) after the first spontaneous seizure (Chronic). All three pilocarpine subgroups had a corresponding age-matched control group (saline-treated rats), from which normal hippocampi samples were obtained at the same experimental time points. Independent microarray hybridizations were carried out for each sample (n = 5, per experimental group) with oligonucleotide microarrays covering 34,000 transcripts representing most of the known and predictive genes of the rat genome (CodeLinkâ¢ Rat Whole Genome Bioarrays, GE Healthcare), following the manufacturerâs protocol. Results: differential expression of almost 1,400 genes was detected during the course of epileptogenesis, from the early events post status epilepticus (SE) to the onset of recurrent spontaneous seizures. Most of these genes are novel and displayed an up-regulation after SE. Noteworthy, a group of 128 genes functioning in neurogenesis, apoptosis, immune response, and intracellular signal transduction was found consistently hyper-expressed throughout epileptogenesis, indicating stable molecular alterations within the hippocampus. Those include modulation of the MAPK, Jak-STAT, PI3K, TGF-beta, and mTOR signaling pathways. Differential expression of genes from the p38 MAPK pathway, mediating inflammation and neurogenesis, was also confirmed by real-time PCR. These findings reveal dynamic molecular changes occurring in the hippocampus that may serve as a starting point for the generation of new hypothesis regarding the underlying mechanisms of epilepsy and for the designing of alternative therapeutic strategies. Keywords: gene expression changes during epileptogenesis. We performed a genome wide analysis of genes differentially expressed during epileptogenesis. Virtually, all possible changes in the rat transcriptome were monitored at distinct time points corresponding to the latent to chronic phase transition of the pilocarpine model of epilepsy, which is probably the most extensively studied chemically inductive model of TLE. Genes identified as being differentially expressed were classified based on their respective biological functions to envisage processes and pathways likely implicated in epileptogenesis, as well as their possible value as targets for therapy. Results were expressed as fold variation, and genes displaying greater than 2-fold changes in transcript abundance and p<0.01 were selected.

Project description:ImportanceValue-based care is increasingly important, with rising health care costs and advances in cancer treatment leading to greater survival for patients with cancer. Regionalization of surgical care for pancreatic cancer has been extensively studied as a strategy to improve perioperative outcomes, but investigation of long-term outcomes relative to health care costs (ie, value) is lacking.ObjectiveTo identify patient and hospital characteristics associated with improved overall survival, decreased costs, and greater value among patients with pancreatic cancer undergoing curative resection.Design, setting, and participantsThis retrospective cohort study identified 2786 patients with stages I to II pancreatic cancer who underwent pancreatic resection at 157 hospitals from January 1, 2004, through December 31, 2012. The study used the California Cancer Registry, which collects data from all California residents newly diagnosed with cancer, linked to the Office of Statewide Health Planning and Development database, which collects administrative data from all California licensed hospitals. Data were analyzed from November 11, 2017, through September 4, 2018.ExposuresPancreatic resection at high-volume and/or National Cancer Institute (NCI)-designated cancer centers.Main outcomes and measuresThe primary outcomes were overall survival, surgical hospitalization costs, and value. High value was defined as the fourth quintile or higher for survival and the second quintile or less for costs. Costs were calculated from charges using cost-charge ratios and adjusted for geographic variation and inflation. Multivariable regression models were used to determine factors associated with overall survival, costs, and high value.ResultsAmong the 2786 patients included (1394 [50.0%] male; mean [SD] age, 67.0 [10.7] years), postoperative chemotherapy (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.64-0.79; P < .001) and high-volume centers (aHR, 0.78; 95% CI, 0.61-0.99; P = .04) were associated with greater overall survival. Higher Elixhauser comorbidity index scores (estimate, 0.006; 95% CI, 0.003-0.008), complications (estimate, 0.22; 95% CI, 0.17-0.27), readmissions (estimate, 0.34; 95% CI, 0.29-0.39), and longer lengths of stay (estimate, 0.03; 95% CI, 0.03-0.04) were associated with higher costs (P < .001), whereas postoperative chemotherapy was associated with lower costs (estimate, -0.06; 95% CI, -0.11 to -0.02; P = .006). National Cancer Institute-designated and high-volume centers were not associated with costs. Although grades III and IV tumors (odds ratio [OR], 0.65; 95% CI, 0.39-0.91; P = .001), T3 category disease (OR, 0.71; 95% CI, 0.46-0.95; P = .005), complications (OR, 0.68; 95% CI, 0.49-0.86; P < .001), readmissions (OR, 0.64; 95% CI, 0.44-0.84; P < .001), and length of stay (OR, 0.82; 95% CI, 0.78-0.85; P < .001) were inversely associated with high-value care, NCI designation (OR, 1.07; 95% CI, 0.66-1.49; P = .74) and high-volume centers (OR, 1.08; 95% CI, 0.54-1.61; P = .07) were not.Conclusions and relevanceIn this study, high-value care was associated with important patient characteristics and postoperative outcomes. However, NCI-designated and high-volume centers were not associated with greater value. These data suggest that targeted measures to enhance value may be needed in these centers.

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Transcriptome Profile in Hippocampus During Acute Inflammatory Response to Surgery: Toward Early Stage of PND.

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Transcriptome Profile in Hippocampus During Acute Inflammatory Response to Surgery: Toward Early Stage of PND.

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