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.
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.
Project description:To explore serum proteins associated with postoperative pulmonary infection in children with CHD, a total of 98 serum samples collected from the 23 patients before and after surgery were subjected to proteomic analysis
Project description:Adhesions are fibrotic scars that form between abdominal organs following surgery or infection, and may cause bowel obstruction, chronic pain, or infertility. Adhesions occur post-operatively in 50-90% of all open abdominal operations and as such, represent an enormous clinical problem impacting hundreds of millions of patients worldwide. Our understanding of the biology of adhesion formation is very limited, which explains why there are essentially no available treatments that prevent adhesions. In this study, we systemically analyzed abdominal adhesions in mouse and human tissues gene expression using bulk- and sc-RNA-seq technologies to characterize the fibroblasts responsible for this devastating pathology.
Project description:Perioperative neurocognitive disorder (PNDs) can commonly occur after major surgery in at risk patients and its occurrence increases medical healthcare burdens and even mortality. Accumulating evidence points to neuroinflammation being pivotal to the pathogenesis of these conditions. The complement cascade contributes to neuroinflammatory responses in the central nervous system (CNS) and complement C3 has been implicated in the manifestation of cognitive deficits in several neurological conditions. Neurotoxic reactive astrocytes function differently to their non-activated counterparts and release complement components in response to pathological triggers. We observed previously that surgery induces a rapid rise and then fall in cytokines but a more sustained glial activation response that coincided with postoperative cognitive impairment. In this study, we explored the relationship between the expression of complement C3, glial activation, and cognitive deficits. Using a murine model of surgery, we characterized the transcriptional profiles of hippocampal astrocytes after surgery and examined the effects of C3 suppression on the neuroinflammatory response and cognitive performance. There was a delayed but sustained rise in hippocampal C3 of astrocytic in origin after surgery which corresponded with the onset of cognitive decline. Furthermore, the A1 or the neurotoxic phenotype predominated in this postoperative astrocytic activation, and these cells have a distinct transcriptional profile including C3 upregulation. Suppression of C3 inhibited synaptic phagocytosis by microglia and attenuated postoperative cognitive impairment. Therefore, C3 from reactive astrocytes appear central to the development of cognitive dysfunction associated with postoperative neuroinflammation.
Project description:We investigated the individual phenotypic predisposition to developing uncomplicated infection or sepsis in a large cohort of non-infected patients undergoing major elective surgery. Whole blood RNA sequencing analysis was performed on preoperative samples taken from 267 patients. These comprised patients who developed postoperative infection with (n=77) or without (n=49) sepsis, non-infectious systemic inflammatory response (n=31), or an uncomplicated postoperative course (n=110). Machine learning classification models built on preoperative transcriptomic signatures predicted postoperative outcomes including sepsis.
Project description:The aim was to investigate the effect of postoperative intra-abdominal infection on the gene expression patterns of peripheral blood leukocytes (PBL) after surgery for colorectal cancer
Project description:Rationale: Adhesion formation is a frequent complication after abdominal surgery. Adhesion formation might be reduced by laparoscopic surgery, however sound evidence is lacking. Colorectal surgery would be a good clinical model to investigate adhesion formation between open and laparoscopic surgery because of the adhesion formation propensity of colorectal surgery. However, a randomized controlled study to provide direct evidence is unlikely because of large numbers of patients needed for such a trial and the difficulty to check for adhesion formation at second surgery. Therefore we investigate adhesion formation after laparoscopic and open colorectal surgery for malignancy at liver surgery for metastases.
Objective: The aim of our study is to compare the incidence of adhesions after laparoscopic versus open surgery for colorectal malignancies during liver resection for colorectal metastases.
Study design: The study is designed as a prospective observational cohort study.
Study population: All consecutive, adult patients undergoing laparotomy or laparoscopy for intended liver resection or radio frequency ablation for liver metastases of a colorectal malignancy in whom inspection of the middle and lower abdomen is possible to map adhesions.
Main study parameters/endpoints:
* Primary endpoint is incidence of adhesions to the ventral abdominal wall around the site of the original incision.
* Secondary endpoints are episodes of bowel obstruction between index surgery and liver surgery; total incidence of adhesions; extent of adhesions; Zühlke classification of adhesions; performance of adhesiolysis; duration of adhesiolysis; peroperative complications: enterotomy, seromuscular injury, inadvertent organ injury during adhesiolysis; postoperative complications: delayed diagnosed perforation, SAE’s.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: This study is an observational study. The existence of adhesions will be assessed during laparotomy or laparoscopy for the treatment of liver metastases. The laparotomy is indicated for medical treatment and should not be enlarged solely for the assessment of adhesions nor will the operating time be influenced for this purpose.
Adhesions and peroperative complications have to be scored by the operating surgeon during or directly after surgery. The postoperative complications have to be scored during the postoperative course by the doctors on the ward. These assessments do not interfere with the treatment of the patients.
Project description:This study is an analysis of the Bern perioperative Biobank, a prospective cohort of adults who underwent cardiac surgery with the use of cardiopulmonary bypass at Bern University Hospital between January and December 2019. Blood samples were taken at induction of anaesthesia and on postoperative day one.