Ontology highlight
ABSTRACT:
PROVIDER: PRJNA859507 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20277500_1.fastq.gz | Fastqsanger.gz | |||
| SRR20277500_2.fastq.gz | Fastqsanger.gz | |||
| SRR20277501_1.fastq.gz | Fastqsanger.gz | |||
| SRR20277501_2.fastq.gz | Fastqsanger.gz | |||
| SRR20277502_1.fastq.gz | Fastqsanger.gz |
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Project description:Rationale
Nosocomial infections are a major healthcare challenge, developing in over 20% of patients aged 45 or over undergoing major-abdominal surgery, with postoperative pneumonia associated with an almost five-fold increase in 30-day mortality.
Objectives
To describe immune-pathways and gene-networks altered following major-abdominal surgery and identify transcriptomic patterns associated with postoperative pneumonia.
Methods and Measurements
From a prospective consecutive cohort (n=150) undergoing major-abdominal surgery whole-blood RNA was collected preoperatively and at three time-points postoperatively (2-6, 24 and 48hrs). Twelve patients diagnosed with postoperative pneumonia and 27 matched patients remaining infection-free were identified for analysis with RNA-sequencing.
Main Results
Compared to preoperative sampling, 3,639 genes were upregulated and 5,043 downregulated at 2-6hrs. Pathway-analysis demonstrated innate-immune activation with neutrophil-degranulation and Toll-like-receptor signalling upregulation alongside adaptive-immune suppression. Cell-type deconvolution of preoperative RNA-sequencing revealed elevated S100A8/9-high neutrophils alongside reduced naïve CD4 T-cells in those later developing pneumonia. Preoperatively, a gene-signature characteristic of neutrophil-degranulation was associated with postoperative pneumonia acquisition (P=0.00092). A previously reported Sepsis Response Signature (SRSq) score, reflecting neutrophil-dysfunction and a more dysregulated host response, at 48hrs postoperatively, differed between patients subsequently developing pneumonia and those remaining infection-free (P=0.045). Analysis of the novel neutrophil gene-signature and SRSq scores in independent major-abdominal surgery and polytrauma cohorts indicated good predictive performance in identifying patients suffering later infection.
Conclusions
Major-abdominal surgery acutely upregulates innate-immune pathways while simultaneously suppressing adaptive-immune pathways. This is more prominent in patients developing postoperative pneumonia. Preoperative transcriptomic signatures characteristic of neutrophil-degranulation and postoperative SRSq scores may be useful predictors of subsequent pneumonia risk.
| EGAS00001007229 | EGA
Project description:Abdominal adhesions form in response to peritoneal trauma that can occur during surgery. Postoperative adhesions, which develop in approximately 50-85% of patients who have undergone abdominal surgery, often result in severe complications, including intestinal obstruction, female infertility, chronic pain, and contraindication of surgery for future abdominal illnesses such as cancer. Here, we investigated the cell source of collagen production in postoperative adhesions and explored molecular mechanisms of adhesion using microarray.
2018-12-07 | GSE123413 | GEO
Project description:Cardiovascular disease is the leading cause of death worldwide and patients with severe symptoms undergo cardiac surgery. Even after uncomplicated surgeries, some patients experience postoperative complications such as lung injury. We hypothesized that the procedure elicits metabolic activity that can be related to the disease progression, which is commonly observed two-three days postoperatively. More than 700 blood samples were collected from 50 patients at nine time points pre-, intra-, and postoperatively. Dramatic metabolite shifts were observed during and immediately after the intervention. Prolonged surgical stress was linked to an augmented anaerobic environment. Time series analysis showed shifts in purine-, nicotinic acid-, tyrosine-, hyaluronic acid-, ketone-, fatty acid, and lipid metabolism. A characteristic ‘metabolic biosignature’ was identified correlating with the risk of developing postoperative complications two days before the first clinical signs of lung injury. Hence, this study demonstrates the link between intra- and postoperative time-dependent metabolite changes and later postoperative outcome. In addition, the results indicate that metabotyping patients’ journeys early, during or just after the end of surgery, may have potential impact in hospitals for the early diagnosis of postoperative lung injury, and for the monitoring of therapeutics targeting disease progression.
2020-05-15 | MTBLS881 | MetaboLights
Project description:Dynamic changes of muscle insulin sensitivity after metabolic surgery
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Project description:Cardiac surgery and cardiopulmonary bypass induce a substantial immune and inflammatory response, the overactivation of which is associated with significant complications. Longitudinal DNA methylation profiling allows the potential to identify changes in gene regulatory mechanisms that are secondary to surgery and to identify molecular processes that predict and/or cause postoperative complications. In this study, we measure DNA methylation in preoperative and postoperative whole blood samples from 96 patients undergoing cardiac surgery on cardiopulmonary bypass. We identify several loci with statistically significant postoperative changes in methylation. Additionally, two of these loci are associated with new-onset postoperative atrial fibrillation, a significant complication after cardiac surgery. This research establishes that there are statistically significant changes in DNA methylation that occur immediately after cardiac surgery and that these acute alterations in DNA methylation have the granularity to identify processes associated with major postoperative complications.
2023-01-09 | GSE215937 | GEO
Project description:Objective: Roux-en-Y gastric bypass surgery (RYGB) is among the most effective therapies for obesity and type 2 diabetes (T2D), and intestinal adaptation is a proposed mechanism for these effects. We hypothesized that intestinal adaptation precedes and relates to metabolic improvement in humans after RYGB. Methods: This was a prospective, longitudinal first-in-human study of gene expression (GE) in Roux limb (RL) collected surgically/endoscopically from 19 patients with and without diabetes. GE was determined by microarray across 6 postoperative months, including at an early postoperative (1 month 15 days) timepoint. Results: RL GE demonstrated tissue remodeling and metabolic reprogramming, including increased glucose and amino acid utilization. RL GE signatures were established early, before maximal clinical response, and persisted. Distinct GE fingerprints predicted concurrent and future improvements in HbA1c and in weight. Human RL exhibits GE changes characterized by anabolic growth and shift in metabolic substrate utilization. Paradoxically, anabolic growth in RL appears to contribute to the catabolic state elicited by RYGB. Conclusions: These data support a role for a direct effect of intestinal energy metabolism to contribute to the beneficial clinical effects of RYGB, suggesting that related pathways might be potential targets of therapeutic interest for patients with obesity with or without T2D.
2024-11-09 | GSE281144 | GEO
Project description:Dynamic changes of muscle insulin sensitivity after metabolic surgery II
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Project description:Dynamic changes of muscle insulin sensitivity after metabolic surgery IV
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Project description:Dynamic changes of muscle insulin sensitivity after metabolic surgery I
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