[Surgical History Taking and Clinical Examination: Establishing a Standardised System by Means of a Nation-Wide Academic Teaching Project]. / Chirurgische Anamneseerhebung und klinische Untersuchung: Etablierung eines Standards an der Universitätsmedizin Greifswald mithilfe eines deutschlandweiten universitären Lehrprojekts.

Background: History taking and systematic clinical examination are central techniques of physicians. Medicine in general and surgery in particular frequently require immediate decisions and start of therapies. So far, a standardised surgical system for history taking and clinical examination in teaching has been lacking at our faculty. A consensus of all medical faculties on a standardised system could be a tool to improve the medical teaching and education at our teaching institutions. Methods: The established Anglo-Saxonian system of history taking and clinical examination was adapted to our own clinical needs. Thereafter, this system was sent out to all chairmen of general and visceral surgery departments in German University Hospitals asking for evaluation and improvements. We adapted the system according to the chairmen's comments and suggestions. Since winter semester 2011 this system has been integrated into the clinical course of history taking and examination. It is compulsory for all 5th semester students (first clinical year/graduate course) at the Universitätsmedizin Greifswald. In addition, a video was produced demonstrating all major techniques of clinical examination. This video is available for all students on a password blocked site of the World Wide Web. Results: Altogether, 89 % of all contacted chairmen returned their comments and suggestions for improvements. After implementation of the new system, positive evaluations of students increased significantly from 63.5 to 77.0 % in general and abdominal surgery (p < 0.0001) and from 76.4 to 83.5 % in vascular and thoracic surgery (p < 0.0001). Conclusions: The presented system is a standardised tool of history taking and clinical examination applicable for students as well as qualified surgeons in daily routine work. It has been approved by the majority of the departments of surgery of all German university hospitals. Furthermore, it can be applied by other medical specialties, in particular, internal medicine. Furthermore, the standardisation of history taking and clinical examination can contribute to improve patients' safety as well as medical documentation. Also, the standardisation will be a sound basis for expert medical opinions in legal actions. Finally, it has improved the value of medical education at our medical faculty and could form the basis for the development of national medical standards.

[Principles of Teaching in Surgery - State of the Art]. / Was muss der Chirurg über Aus- und Weiterbildung in der Chirurgie wissen?

Ten to 15 years ago the number of applications for a surgical residency position was very much larger than the positions available. Today, this situation has clearly reversed itself as indicated through a noticeable deficit in recruits. The decision to become a surgeon has become more uncommon. This can be blamed upon not only the demotivatingly viewed "work-life imbalance" associated with being a surgeon, but also on the basically non-inspiring training process during medical school. Due to the fact that university educators/instructors are not fundamentally trained teachers, they often fail in their capacity to convey their extensive knowledge to medical students and potentially future surgical residents. The quality of primary as well as postgraduate training is an important central factor in the effort to once again restore the attractive image of surgery within the realm of the medical disciplines. This paper presents an overview of the basic modern training concepts by which every surgeon should be able to effectively convey knowledge and practical skills. Furthermore, this work should inspire a more intensive interest in clinical graduate and postgraduate education. Due to the hand in hand relationship, this manuscript does not differentiate between student teaching and postgraduate training.

Green light-induced apoptosis in cancer cells by a tetrapyridyl ruthenium prodrug offering two trans coordination sites.

In this work, two new photopharmacological ruthenium prodrugs are described that can be activated by green light. They are based on the tetrapyridyl biqbpy ligand (6,6'-bis[N-(isoquinolyl)-1-amino]-2,2'-bipyridine), which coordinates to the basal plane of the metal centre and leaves two trans coordination sites for the binding of monodentate sulphur ligands. Due to the distortion of the coordination sphere these trans ligands are photosubstituted by water upon green light irradiation. In vitro cytotoxicity data on A431 and A549 cancer cell lines shows an up to 22-fold increase in cytotoxicity after green light irradiation (520 nm, 75 J cm-2), compared to the dark control. Optical microscopy cell imaging and flow cytometry indicate that the cancer cells die via apoptosis. Meanwhile, very low singlet oxygen quantum yields (∼1-2%) and cell-free DNA binding studies conclude that light-induced cell death is not caused by a photodynamic effect, but instead by the changes induced in the coordination sphere of the metal by light, which modifies how the metal complexes bind to biomolecules.

Absolute protein quantification of clinically relevant cytochrome P450 enzymes and UDP-glucuronosyltransferases by mass spectrometry-based targeted proteomics.

Cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGT) are major determinants in the pharmacokinetics of most drugs on the market. To investigate their impact on intestinal and hepatic drug metabolism, we developed and validated quantification methods for nine CYP (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5) and four UGT enzymes (UGT1A1, UGT1A3, UGT2B7 and UGT2B15) that have been shown to be of clinical relevance in human drug metabolism. Protein quantification was performed by targeted proteomics using liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based determination of enzyme specific peptides after tryptic digestion using in each case stable isotope labelled peptides as internal standard. The chromatography of the respective peptides was performed with gradient elution using a reversed phase (C18) column (Ascentis(®) Express Peptide ES-C18, 100mm×2.1mm, 2.7µm) and 0.1% formic acid (FA) as well as acetonitrile with 0.1% FA as mobile phases at a flow rate of 300µl/min. The MS/MS detection of all peptides was done simultaneously with a scheduled multiple reaction monitoring (MRM) method in the positive mode by monitoring in each case three mass transitions per proteospecific peptide and the internal standard. The assays were validated according to current bioanalytical guidelines with respect to specificity, linearity (0.25-50nM), within-day and between-day accuracy and precision, digestion efficiency as well as stability. Finally, the developed method was successfully applied to determine the CYP and UGT protein amount in human liver and intestinal microsomes. The method was shown to possess sufficient specificity, sensitivity, accuracy, precision and stability to quantify clinically relevant human CYP and UGT enzymes.

LC-MS/MS-based quantification of clinically relevant intestinal uptake and efflux transporter proteins.

Multidrug transporter proteins are crucial determinants in the pharmacokinetics of many drugs. To evaluate their impact on intestinal drug absorption, we developed and validated quantification methods for 10 uptake transporters (OATP1A2, OATP2B1, PEPT1, ASBT, OCT1, OCT3) and efflux transporters (ABCB1, ABCC2, ABCC3, ABCG2) that have been reported to be expressed and to be of clinical relevance in the human intestine. Quantification was performed by targeted liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based quantification of proteospecific peptides after tryptic digestion using stable isotope labeled internal standard peptides. The chromatography of the respective peptides was performed by gradient elution using a reversed phase (C18) column (Kinetex(®), 100 × 3.0 mm, 2.6 µm) and 0.1% formic acid (FA) and acetonitrile with 0.1% FA as mobile phases at a flow rate of 0.5 ml/min. The MS/MS detection was done in the positive multiple reaction monitoring (MRM) mode by monitoring in each case three mass transitions for the transporter-derived peptides and the internal standard peptides. The assays were validated with respect to specificity, linearity (0.1-25 nM), within-day and between-day accuracy and precision as well as stability according to current bioanalytical guidelines. Finally, the developed methods were used to determine the transporter protein content in human intestinal tissue (jejunum and ileum). The methods were shown to possess sufficient specificity, sensitivity, accuracy, precision and stability to measure transporter proteins in the human intestine.

[Therapy of pancreatic pseudocysts: endoscopy versus surgery]. / Therapie von Pankreaspseudozysten : Endoskopie vs. Chirurgie.

Pancreatic pseudocysts are frequent complications following acute and chronic pancreatitis as well as abdominal trauma. They originate from enzymatic and/or necrotizing processes within the organ involving the surrounding tissues through inflammatory processes following pancreatic ductal lesion(s). Pseudocysts require definitive treatment if they become symptomatic, progressive, larger than 5 cm after a period of more than 6 weeks and/or have complications. Cystic neoplasms must be excluded before treatment. Endoscopic interventions are commonly accepted first line approaches. Should these fail or not be feasible surgical procedures have been well established and show comparable results. In summary, pancreatic pseudocysts require a reliable diagnostic approach with a multidisciplinary professional management involving gastroenterologists and surgeons.

[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.

[Introduction of operating room checklists as a part of clinical risk management: are there hard facts on complication prevention available?]. / Einführung von Operationschecklisten als Teil des Risikomanagements : Sind harte Daten zur Komplikationsvermeidung verfügbar?

For approximately the past 10 years the aspects of quality and risk management have spread widely not only into the realm of hospitals but also into overall general medicine, which is viewed by many physicians as a paradigmatic change. The required use of the WHO operating room (OR) checklist has in the meantime become routine procedure in many hospitals but with varying degrees of acceptance. Current data reaffirm the positive effect of the checklist in lowering complication and mortality rates. This effect can be directly traced to a higher level for safety culture in the OR.

[Introduction of operating room checklists as a part of clinical risk management : are there hard facts on complication prevention available?]. / Einführung von Operationschecklisten als Teil des Risikomanagements : Sind harte Daten zur Komplikationsvermeidung verfügbar?

For approximately the past 10 years the aspects of quality and risk management have spread widely not only into the realm of hospitals but also into overall general medicine, which is viewed by many physicians as a paradigmatic change. The required use of the WHO operating room (OR) checklist has in the meantime become routine procedure in many hospitals but with varying degrees of acceptance. Current data reaffirm the positive effect of the checklist in lowering complication and mortality rates. This effect can be directly traced to a higher level for safety culture in the OR.

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.

[Modular postgraduate training in surgery - a national concept with future]. / Modulare Weiterbildung in der Chirurgie - ein nationales Konzept mit Zukunft.

BACKGROUND: The quality of postgraduate training is an important motivating factor for the career decisions of young doctors and has an impact on the satisfaction of postgraduate trainees. In Germany, we still lack a postgraduate training programme in surgery that defines the competency profile at the time of certification. This article describes the development of a national modular competency-based core curriculum for postgraduate surgery training as well as first experience and evaluation data from the initial period of implementation. METHODS: The curriculum was developed in a group of highly motivated surgeons according to the "Kern-cycle", a conceptual framework for curriculum development in medicine, and includs considerations from the "CanMEDS"-competency framework for physicians. The curriculum follows a "blended learning" concept with modular attendance courses and associated preparatory online courses. The didactics follows the principles of adult learning and are characterised by learner-centred, self-directed learning processes in small groups with feedback. The initial implementation phase was accompanied by a detailed evaluation of the general concept as well as the quality of content and didactics of the attendance courses. RESULTS: Seven of the planned 12 attendance courses have been designed, 6 courses have been implemented2q1. Altogether 562 participants from hospitals of all levels of patient care took part in the attendance courses, some of them in several courses. The gender distribution was almost balanced with a slight female surplus. The majority of participants were supported by their clinics through exemption from clinical work or financial sponsoring. 80 % of the participants completed the evaluation of the attendance courses. The data show a high degree of participant satisfaction with the content and didactic concept of the courses, as well as with the surrounding conditions and the commitment of the trainers. CONCLUSIONS: The evaluation data on the attendance courses implemented reveal a high acceptance among participants concerning the overall concept of the modular postgraduate training programme as well as the support of the programme by surgeons responsible for postgraduate training.

[Consequences drawn from the evaluation of logbook-based surgical training for final year students]. / Konsequenzen aus der Evaluation eines chirurgischen PJ-Logbuchs.

BACKGROUND: The current training programme for final year medical students does not meet the requirements of surgery and is obviously not able to encourage young physicians to become surgeons. After finishing the surgical trimester, the motivation to become a doctor decreases considerably more strongly than after any other specialty during the final year programme. This emphasises the urgent need for a consequent redesign involving modern educational programmes. METHOD: The present article represents a systematic analysis of 70 logbooks used by final year medical students, which accompanied them during the surgical trimester from August 2008 to December 2009 at the Department of Surgery at the University of Greifswald, Germany. This analysis was subsequently compared to an evaluation of the same students as to how valuable the logbook was for their surgical education by means of an anonymous questionnaire. RESULTS: The results indicate that the general quality of education during the surgical trimester was evaluated to be high, but that the use of a logbook in the current mode did not contribute to enhance medical/surgical training programmes. Although most of the requested examinations and procedures were carried out by at least 70 % of the students, less than half of them had the impression that the use of this specific logbook improved their education. The students ask for a more intense interaction with the tutor/mentor and request differentiated discussions about their personal stronger and weaker spots, as well as more bedside teaching, e. g., the terms of training ward rounds with the consultant surgeon. Besides, they demand more supervised practical skill training in contrast to the often commonly practiced "learning by doing". CONCLUSION: The logbook is a powerful and effective educational tool able to structure and examine medical training and skills. But the present evaluation of the surgical logbook indicates that there is a need to adapt the current version to student's and institution's requirements. Otherwise it will only be seen as a purely labour intensive obligation, which will consequently lead to frustration and will not enrich the surgical training programme within the final year of medical school.

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.

[Quality and quality assurance of teaching in surgery - recommendations from a workshop of the surgical cooperative for quality assurance]. / Qualität und Qualitätssicherung der Lehre in der Chirurgie - Empfehlungen aus einem Workshop der Chirurgischen Arbeitsgemeinschaft für Qualitätssicherung.

The shortage of surgeons in the operative disciplines field has in recent years further increased. The training of a surgeon and the required lifestyle combined with the work-life balance of the surgeons are perceived as being less attractive, so that young doctors after finishing medical school rarely decide for surgical careers. Changes in the social environment outside of our clinics has resulted in a decline of the social prestige. The modified structural preconditions require a rethinking of the training processes for studying and working conditions in surgery. The quality of surgical education is therefore a cornerstone for the future development of our subject and is directly linked to the training and junior development. The CAQ meeting in Greifswald in February 2009, has focused on the teaching in surgery and developed together with medical students of different faculties solutions for the three major problem factors: teaching, training and junior development. The students are demanding clear guidelines regarding the required theoretical and practical knowledge in the form of catalogues or learning logs. The absence of intrinsic commitment to an excellent teaching and role model is due to the ongoing conflict between patient care and teaching. Because in teaching usually neither the quantity nor the quality will be systematically registered and no sanctions promote the lesson, so that the training is always considered as a last resort. One approach could be a scoring system for teaching that reflect the quantity and quality of teaching in points. The practical year needs to be reformed, since over 25% of the students spend their surgery part abroad, because they are afraid to be considered as cheap labour. Especially at this point, the lecturer is asked to reform the education of students during the practical year and to strengthen the role model for young academic teachers.