Mauser, Martin Ernst2021-11-232021-11-232021https://hdl.handle.net/10539/32056A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Faculty of Health Sciences, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, 2021Background: The gut associated lymphoid tissue (GALT) of the bowel with different lymphocyte subpopulations as an important pillar of the human immune system has never been investigated in the context of trauma; neither the short-term histological trauma induced changes in the GALT, nor its impact on the outcome after trauma surgery. Furthermore, it has never been investigated whether the preexisting altered GALT of HIV-seropositive trauma patients compromises their postoperative course. Methods: This prospective, longitudinal proof-of-concept study included patients who required damage control surgery after abdominal gunshot wounds with small bowel involvement. Bowel specimens were obtained during the index and relook operations, and the T-lymphocytic quantity therein analysed via immunohistochemistry. We investigated how the lymphocyte structure and numbers of the GALT altered, and whether the extent and nature of these changes had an impact on the postoperative outcome with regard to septic and surgical complications. Results: In total, 62 patients were included in the study of which 38 patients were HIV seronegative and 24 were HIV-seropositive. HIV-seropositive patients had a significantly lower quantity of CD4+ T cells in the GALT compared to the HIV seronegative patients (p = 0,0001), which was also associated with a significantly higher rate of septic complications in the postoperative course. The main histological changes between the index and relook specimen was a shift of CD8+ T cells from the lamina propria (LP) into the epithelium and a decrease of T- VI lymphocytes in the LP. The significant increase of the intraepithelial CD8+ T cells was associated with a more extensive enterocyte apoptosis, and correlated significantly, positively with the number of postoperative septic complications. Conclusions: The compromised GALT in HIV-seropositive patients may predispose these patients to postoperative septic complications. Antiretroviral therapy does not result in an adequate immune reconstitution in this tissue. Hence, safe surgery and vigilant postoperative care with early, aggressive diagnostic investigations and a low threshold for relook operations if the postoperative course does not progress as expected, is of paramount importance for these patients. Trauma induces an immune cell-driven impairment of the intestinal epithelium, as well as an increased apoptosis of lymphocytes in the LP which is associated with a worse clinical outcome. The underlying mechanism suggests that a therapeutic approach to minimize apoptosis in the intestine may impact the outcome of severely injured trauma patientsenThesis