Differential gene expression analysis of peripheral blood leukocytes reveals overexpression of tumor progression-related genes in patients with intra-abdominal infection after surgery for colon cancer: a prospective matched cohort study
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE77167 | GEO | 2017/06/12
SECONDARY ACCESSION(S): PRJNA309650
REPOSITORIES: GEO
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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: Not available
| S-EPMC7808037 | biostudies-literature
Project description:We used unsupervised hierarchical clustering to analyse expression in primary ovarian tumors and associated abdominal deposits. GeneGo pathway analysis of differentially expressed genes between primary tumors and deposits revealed 4 of the top 10 pathways related to cytoskeleton remodeling and cell adhesion. Primary ovarian tumours and matched abdominal deposits were selected for RNA extraction and hybridization on Affymetrix microarrays.
2012-06-14 | E-GEOD-38734 | biostudies-arrayexpress
Project description:Background: Adhesion formation in the peritoneal cavity is the most-common cause of intestinal obstruction. The aim of this study was to analyze the dynamic gene expression patterns in the small bowel of mice featuring surgically-induced intra-abdominal adhesion. Methods: In an experimental study, mRNA was extracted from the small bowels of sham control mice and small bowel-scraping mice following surgically-induced intra-abdominal adhesion at 1, 3, 7, and 14 days post surgery. The mouse cDNA microarray was used to monitor the dynamic changes of the tested genes. Results: We identified 520 genes with a greater than 1.5 fold change across all studied mice groups. Quantitative RT-PCR and immunohistochemical staining certified, respectively, the expression of certain selected genes. The number of apoptotic cells contained within the adhesion tissue increased in a time-dependent manner. The serum concentration of neuropeptide Y was significantly greater for the test mice compared to the controls. Conclusions: Surgical intervention to the small bowel induces an adaptive response of damaged tissue in order to eliminate excessive complement-mediated lysis, prevent oxidative injuries, and enhance cell proliferation. These findings may provide insights into the pathogenesis of complications following adhesion formation and might also help to identify some new target genes for specific diagnostic tools and novel therapeutic strategies. Keywords: Time course study
2006-05-24 | GSE4715 | GEO
Project description:We used unsupervised hierarchical clustering to analyse expression in primary ovarian tumors and associated abdominal deposits. GeneGo pathway analysis of differentially expressed genes between primary tumors and deposits revealed 4 of the top 10 pathways related to cytoskeleton remodeling and cell adhesion.
2012-06-15 | GSE38734 | GEO
Project description:BackgroundIn Italy, surgeons continue to drain the abdominal cavity in more than 50 per cent of patients after colorectal resection. The aim of this study was to evaluate the impact of abdominal drain placement on early adverse events in patients undergoing elective colorectal surgery.MethodsA database was retrospectively analysed through a 1:1 propensity score-matching model including 21 covariates. The primary endpoint was the postoperative duration of stay, and the secondary endpoints were surgical site infections, infectious morbidity rate defined as surgical site infections plus pulmonary infections plus urinary infections, anastomotic leakage, overall morbidity rate, major morbidity rate, reoperation and mortality rates. The results of multiple logistic regression analyses were presented as odds ratios (OR) and 95 per cent c.i.ResultsA total of 6157 patients were analysed to produce two well-balanced groups of 1802 patients: group (A), no abdominal drain(s) and group (B), abdominal drain(s). Group A versus group B showed a significantly lower risk of postoperative duration of stay >6 days (OR 0.60; 95 per cent c.i. 0.51-0.70; P < 0.001). A mean postoperative duration of stay difference of 0.86 days was detected between groups. No difference was recorded between the two groups for all the other endpoints.ConclusionThis study confirms that placement of abdominal drain(s) after elective colorectal surgery is associated with a non-clinically significant longer (0.86 days) postoperative duration of stay but has no impact on any other secondary outcomes, confirming that abdominal drains should not be used routinely in colorectal surgery.
| S-EPMC10763998 | biostudies-literature
Project description:BackgroundAcute high-risk abdominal (AHA) surgery is associated with high mortality, multiple postoperative complications and prolonged hospital stay. Further development of strategies for enhanced recovery programs following AHA surgery is needed. The aim of this study was to describe physical performance and barriers to independent mobilization among patients who received AHA surgery (postoperative days [POD] 1-7).MethodsPatients undergoing AHA surgery were consecutively enrolled from a university hospital in Denmark. In the first postoperative week, all patients were evaluated daily with regards to physical performance, using the Cumulated Ambulation Score (CAS; 0-6 points) to assess basic mobility and the activPAL monitor to assess the 24-hour physical activity level. We recorded barriers to independent mobilization.ResultsFifty patients undergoing AHA surgery (mean age 61.4 ± 17.2 years) were included. Seven patients died within the first postoperative week, and 15 of 43 (35%) patients were still not independently mobilized (CAS < 6) on POD-7, which was associated with pulmonary complications developing (53% v. 14% in those with CAS = 6, p = 0.012). The patients lay or sat for a median of 23.4 hours daily during the first week after AHA surgery, and the main barriers to independent mobilization were fatigue and abdominal pain.ConclusionPatients who receive AHA surgery have very limited physical performance in the first postoperative week. Barriers to independent mobilization are primarily fatigue and abdominal pain. Further studies investigating strategies for early mobilization and barriers to mobilization in the immediate postoperative period after AHA surgery are needed.
| S-EPMC5785288 | biostudies-literature
Project description:ImportanceDelirium is a common postoperative complication for older patients in the ICU. Ketamine, used primarily as an analgesic, has been thought to prevent delirium.ObjectiveDetermine the prevalence and association of delirium with low-dose ketamine use in ICU patients after abdominal surgery.DesignSingle-center, retrospective, propensity-matched cohort study.SettingEight hospital academic medical center.PatientsCohort comprising 1836 patients admitted to the ICU after abdominal surgery between June 23, 2018 and September 1, 2022.Main outcomes and measuresPropensity score matching (PSM) with a 3:1 ratio between no-ketamine use and ketamine use was performed through a greedy algorithm (caliper of 0.005). Outcomes of interest included: delirium (assessed by Confusion Assessment Method-ICU), mean pain score (Numeric Pain Scale or Critical Care Pain Observation Tool score as available), mean opioid consumption (morphine milligram equivalents), length of stay (d), and mortality.ResultsPrevalence of delirium was 47.71% (95% CI, 45.41-50.03%) in the cohort. Of 1836 patients, 120 (6.54%) used low-dose ketamine infusion. After PSM, the prevalence of delirium was 56.02% (95% CI, 51.05-60.91%) in all abdominal surgery patients. The ketamine group had 41% less odds of delirium (odds ratio [OR] = 0.59; 95% CI, 0.37-0.94; p = 0.026) than patients with no-ketamine use. Patients with ketamine use had higher mean pain scores (3.57 ± 2.86 vs. 2.21 ± 2.09, p < 0.001). In the subgroup analysis, patients in the ketamine-use group 60 years old or younger had 64% less odds of delirium (OR = 0.36; 95% CI, 0.13-0.95; p = 0.039). The mean pain scores were higher in the ketamine group for patients 60 years old or older. There was no significant difference in mortality and opioid consumption.Conclusions and relevanceLow-dose ketamine infusion was associated with lower prevalence of delirium in ICU patients following abdominal surgery. Prospective studies should further evaluate ketamine use and delirium.
| S-EPMC10786598 | biostudies-literature
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:Abdominal aortic aneurysm (AAA) is a permanent segmental dilatation of the abdominal aorta, contributing to a high mortality once rupture. We performed RNA-sequencing analysis of abdominal aorta tissues from 14 participants, including seven patients with AAA and seven control individuals.
2023-12-07 | GSE183464 | GEO