[Curriculum "patient safety" for undergraduate medical students at the department of surgery, University of Greifswald]. / Curriculum "Patientensicherheit" im Blockpraktikum Chirurgie an der Universität Greifswald.

BACKGROUND: Risk reducing measures like the surgical checklist have been proven to reduce effectively adverse events and improve patient safety and teamwork among surgical staff members. Nevertheless, many physicians still refuse to use even simple safety tools like the WHO checklist. A progress in patient safety can only be achieved by changing the operating proceedings and mentality of medical students. This is best performed by teaching patient safety already very early in the medical education. METHOD: The present study demonstrates the implementation and evaluation of the curriculum "patient safety" for undergraduate medical students in the 4th year of medical school at the Department of Surgery, University of Greifswald. 141 students evaluated a total of six lectures from April to October 2011. RESULTS: The results indicate that young medical students show great enthusiasm in safety matters and are willing to adopt the principles. Especially the importance of the issue and the didactic design were evaluated as being very high. CONCLUSION: The curriculum "patient safety" as part of the training program in medical school is a powerful and effective educational tool that is able to raise the student's awareness of patient safety affairs. Thereby it is crucial to start early within medical education during the phase of socialisation. We recommend the general implementation of a patient safety curriculum in medical school.

Surgical trauma and postoperative immune dysfunction.

BACKGROUND: In postoperative sepsis, mortality is increased due to the surgically induced immune dysfunction. Further causes of this traumatic effect on the immune system include burn injuries and polytrauma, as well as endogenous traumata like stroke. Several animal models have been defined to analyse the characteristics of trauma-induced immune suppression. This article will correlate our results from animal studies and clinical observations with the recent literature on postoperative immune suppression. METHODS: The previously described model of surgically induced immune dysfunction (SID) was performed in mice by laparotomy and manipulation of the small intestine in the antegrade direction. Blood samples were collected 6 and 72 h following SID to analyse the white blood cell count and corticosterone levels. To assess the postoperative immune status in humans, we analysed expression of HLA-DR on monocytes of 118 patients by flow cytometry prior to and 24, 48 and 72 h after surgery. RESULTS: The postoperative immune suppression in our SID model is characterised by lymphocytopenia and significantly increased corticosterone levels in mice dependent on the degree of surgical trauma. This is comparable to the postoperative situation in humans: major and especially long-lasting surgery results in a significantly reduced expression of HLA-DR on circulating monocytes. Previous studies describe a similar situation following burn injury and endogenous trauma, i.e. stroke. CONCLUSIONS: We suggest the completion of our previously published sepsis classification due to the immune status at the onset of sepsis: type A as the spontaneously acquired sepsis and type B as sepsis in trauma-induced pre-existing immune suppression.

[Thoracic aortic interventions]. / Intervention an der thorakalen Aorta.

The treatment of thoracic aortic diseases has undergone a paradigm shift due to the introduction and further development of interventional techniques in recent years. Thoracic endovascular aortic repair (TEVAR) of the descending aorta has significantly lower mortality and complication rates compared to open repair. Meanwhile this endovascular approach is the first option for the treatment of the majority of thoracic aortic diseases.

Postoperative immune suppression in visceral surgery: characterisation of an intestinal mouse model.

BACKGROUND: Postoperatively acquired immune dysfunction is associated with a higher mortality rate in case of septic complications. As details of this severe clinical problem are still unknown, animal models are essential to characterise the mechanisms involved. METHODS: Mice were laparotomised and the small intestine was pressed smoothly in antegrade direction. For extension of trauma, the intestine was manipulated three times consecutively. Following this, the ex vivo cytokine release of splenocytes was determined. The degree of surgical trauma was analysed by detection of HMGB1 and IL-6 in serum and by neutrophil staining in the muscularis mucosae. RESULTS: We adapted the previously described animal model of intestinal manipulation to provide a model of surgically induced immune dysfunction. Following intestinal manipulation, the mice showed elevated serum levels of HMGB1 and IL-6 and increased infiltration of granulocytes into the muscularis mucosae. Ex vivo cytokine release by splenocytes was suppressed in the postoperative period. The degree of suppression correlated with the extent of surgical trauma. CONCLUSIONS: In this study, we describe a surgically induced immune dysfunction animal model, in which a significant surgical trauma is followed by an immune dysfunction. This model may be ideal for the characterisation of the postoperative immune dysfunction syndrome.

Stimulation of TLR7 prior to polymicrobial sepsis improves the immune control of the inflammatory response in adult mice.

OBJECTIVE: The role of Toll-like receptor 7 (TLR7), so far regarded as a receptor for viral RNA, was evaluated in a murine sepsis model. MATERIAL: We used the colon ascendens stent peritonitis model (CASP) in female C57B/6 mice. R-848 (1.5 µg/g body weight) was injected intravenously prior to sepsis induction. METHODS: We determined levels of cytokines by CBA detection kit. Different cell populations were isolated from the spleen by magnetic cell separation and the expression of TLR7 was visualized by immunofluorescence staining. Bacterial load of organs was quantified by incubating suspensions on agar in colony forming units. RESULTS: R-848 application per se led to elevated cytokine levels in serum, spleen and peritoneal cavity. Expression of TLR7 on splenocytes was upregulated following CASP. Bacterial clearance in polymicrobial sepsis was significantly increased in spleen and peritoneum of mice pre-treated with the TLR7-agonist. Cytokine release was regulated in the peritoneum and spleen. Furthermore, apoptosis in thymus and spleen during polymicrobial sepsis was significantly decreased following TLR7 agonist application. CONCLUSIONS: TLR7 seems to be essential for pathogen defence not only in viral but also in bacterial infections. Pharmacological stimulation of this receptor prior to induction of sepsis improves the host's capacity to cope with pathogens.

[Surgical trauma and postoperative immunosuppression]. / Operatives Trauma und postoperative Immunsuppression.

Abdominal surgery is regularly followed by immune dysfunction that can last for several days. In case of septic complications during this period, there is imminent danger of mortality due to reduced immune function. This fact leads to classification of sepsis in regard to its genesis: spontaneously acquired sepsis type A is distinguishable from sepsis type B, which is acquired postoperatively. The main difference between these types is the immunologic condition at the time point of sepsis development. Postoperative immune dysfunction can be described by several parameters, i.e. reduction of HLA-DR expression on monocytes and increased apoptosis of T lymphocytes. A direct correlation exists between magnitude of immune dysfunction and complexity of the previous surgical trauma. For the first time it is now possible to study this phenomenon of postoperative immune dysfunction by use of an adequate animal model. Intestinal manipulation in mice fulfils the necessary criteria to serve as a model of surgically induced immune dysfunction.

Detrimental role for CD4+ T lymphocytes in murine diffuse peritonitis due to inhibition of local bacterial elimination.

BACKGROUND: Abdominal sepsis due to intestinal leakage of endogenous gut bacteria is a life-threatening condition. In healthy individuals, T lymphocytes have essential functions in balancing the immune response to the commensal gut flora. AIM: To determine how T lymphocytes shape the process of diffuse faecal peritonitis. METHODS: In colon ascendens stent peritonitis (CASP), a clinically relevant mouse model of diffuse peritonitis, the kinetics of systemic T cell activation were investigated by assessment of activation markers. CD4(+) T cells were then depleted with monoclonal antibodies, and survival, bacterial dissemination and cytokine concentrations were measured. T cell receptor signalling was blocked with tacrolimus. RESULTS: In diffuse peritonitis, CD4(+) T cells, both Foxp3(-) and Foxp3(+), became systemically involved within hours and upregulated CTLA-4 and other activation markers. Depletion of the CD4(+) T cells enhanced local bacterial clearance from the peritoneal cavity, reduced bacterial dissemination and improved survival. This was accompanied by increased immigration of granulocytes and macrophages into the peritoneum, indicating that CD4(+) T cells inhibit the local innate immune response. Blockade of T cell receptor (TCR) signalling by tacrolimus did not influence the survival in this peritonitis model, showing that the inhibitory effects of the CD4(+) T lymphocytes were independent of TCR-mediated antigen recognition. CONCLUSION: In diffuse peritonitis caused by commensal gut bacteria the CD4(+) T lymphocytes exert a net negative effect on the local anti-bacterial defence, and thereby contribute to bacterial dissemination and poor outcome.

[Special aspects of abdominal sepsis]. / Besonderheiten der abdominellen Sepsis.

Abdominal sepsis remains a major cause of perioperative morbidity and mortality in surgical intensive care units. It must be considered a life-threatening condition and requires multidisciplinary coordination of intensive care. Apart from the local abdominal infection (peritonitis), abdominal sepsis is defined by extraperitoneal systemic reactions potentially leading to septic shock and death in the further course. Early and radical focus sanitation as well as aggressive systemic antimicrobial therapy remain the causal therapy strategies of abdominal sepsis.