[Heparin-induced thrombocytopenia type II (HIT II) : A medical-economic view]. / Die heparininduzierte Thrombozytopenie (HIT II) : Eine medizinökonomische Betrachtung.

BACKGROUND: In the context of inpatient and increasingly ambulatory thrombosis prophylaxis, heparins have been recognised as standard therapy for decades. In addition to the therapeutic benefit, therapy with heparins also entails the risk of undesirable side effects, such as bleeding and thrombocytopenia. Heparin-induced thrombocytopenia (HIT II) is deemed a serious side effect. AIM: In the following work, HIT II is subjected to a medico-economic consideration (treatment, pharmaceuticals, subsequent costs due to possible complications) and, with regard to a possible HIT II prophylaxis, aspects of increasingly respected patient safety are also considered. METHODS: In the context of a literature search the active ingredients argatroban and danaparoid, which are approved for HIT II treatment, were evaluated. RESULTS: HIT II - especially in combination with thromboembolic complications - represents a medical-economic burden for the hospital. Although this is only an orientation guide, it shows that HIT II syndrome is not adequately cost-covered by the G­DRG system. An early thrombosis prophylaxis with argatroban/danaparoid for HIT II risk patients should therefore be taken into account for medical-related as well as patient safety-relevant aspects. According to experience, the pharmaceutical supply for these medically needed products (anticoagulants) should be ensured for reasons of patient safety. CONCLUSION: The risk of an immunological response to heparin therapy is known. Within the context of increased patient safety, thrombosis prophylaxis should be issued with a risk-adjusted prophylaxis.

[Patient Satisfaction as a Measure of Quality of Patient Care - Comparison between a University Hospital and a General Hospital]. / Patientenzufriedenheit als Maßeinheit im Qualitätsmanagement ­ ein Vergleich zwischen einem Universitätsklinikum und einem Krankenhaus der Regelversorgung.

Objective: The aim of the study was to compare the satisfaction of patients of a general hospital with a university hospital. A patient satisfaction index was calculated based on the assessed levels of satisfaction. In general, higher satisfaction could lead to increased competitiveness and improved cost efficiency for achieving profitability. Methods: The authors developed and administered a questionnaire on distinct parameters presumed to reflect the quality of the hospital stay to patients of a university hospital (University Hospital of Bonn, UKB, 1 224 beds) and a general hospital (Johanniterkrankenhaus, Bonn, JKH, 364 beds). Data were collected anonymously. Patient satisfaction and the relative importance of each parameter were assessed. The quotient of both parameters yields the patient satisfaction index (PZI). In order to account for possible differences in patient demands, statistical analysis was performed. Results: The demands and wishes, satisfaction and importance of the retrieved parameters did not differ significantly between the patients of the hospitals in any of aspects assessed (information, participation, contact and comfort during the hospital-stay). The study showed that communication and the contact to physicians and nurses was significantly more important for the patients than comfort (each p<0.001). The highest PZI were found in the categories entertainment (UKB 1.02; JKH 1.25) and contact to the nursing personnel (PZI UKB 0.94; PZI JKH 0.96). The standard of medical-technical care (UKB 0.93; JKH 0.95) was also highly ranked by patients of both hospitals. Needs for improvement related especially to the communication of errors (UKB 0.33; JKH 0.31). Discussion: Surveillance of patient wishes and criticism may result in a more patient-oriented care on a daily basis. Scrutinizing the resources employed may lead to more efficient use of resources and personnel and thus help cut costs and improve the attractiveness of hospitals.

Preoperative patient assessment: Identifying patients at high risk.

Postoperative mortality remains alarmingly high with a mortality rate ranging between 0.4% and 4%. A small subgroup of multimorbid and/or elderly patients undergoing different surgical procedures naturally confers the highest risk of complications and perioperative death. Therefore, preoperative assessment should identify these high-risk patients and stratify them to individualized monitoring and treatment throughout all phases of perioperative care. A "tailored" perioperative approach might help further reduce perioperative morbidity and mortality. This article aims to elucidate individual morbidity-specific risks. It further suggests approaches to detect patients at the risk of perioperative complications.

Regulation of p53 under hypoxic and inflammatory conditions in periodontium.

OBJECTIVES: Different studies suggest that inflammation as well as hypoxia leads to an increase of p53 protein levels. However, the implication of p53 during oral inflammatory processes is still unknown. The aim of this study was therefore to investigate the effect of hypoxia and inflammation on p53 regulation in human periodontium in vitro and in vivo. MATERIALS AND METHODS: Under hypoxic and normoxic conditions, human primary periodontal ligament (PDL) fibroblasts (n = 9) were stimulated with lipopolysaccharides (LPS) from Porphyromonas gingivalis (P.g.), a periodontal pathogenic bacterium. After different time points, cell viability was tested; p53 gene expression, protein synthesis, and activation were measured using quantitative RT-PCR, immunoblotting, and immunofluorescence. Moreover, healthy and inflamed periodontal tissues were obtained from 12 donors to analyze p53 protein in oral inflammatory diseases by immunohistochemistry. RESULTS: LPS-P.g. and hypoxia initially induced a significant upregulation of p53 mRNA expression and p53 protein levels. Nuclear translocation of p53 after inflammatory stimulation supported these findings. Hypoxia first enhanced p53 levels, but after 24 h of incubation, protein levels decreased, which was accompanied by an improvement of PDL cell viability. Immunohistochemistry revealed an elevation of p53 immunoreactivity in accordance to the progression of periodontal inflammation. CONCLUSIONS: Our data indicate that p53 plays a pivotal role in PDL cell homeostasis and seems to be upregulated in oral inflammatory diseases. CLINICAL RELEVANCE: Upregulation of p53 may promote the destruction of periodontal integrity. A possible relationship with carcinogenesis may be discussed.

[Characteristics of Focal Degenerative Cartilage Lesions in the Knee Joint. A Radiologic, Spectroscopic, Histological and Biochemical Study]. / Eigenschaften fokaler degenerativer Knorpelschäden am Kniegelenk. Eine radiologische, spektroskopische histologische und biochemische Untersuchung.

OBJECTIVE: The aim of this study was to perform a macroscopic, spectroscopic and biochemical/histological examination of the defect margins of grade IIIb cartilage lesions in the patella, the medial femoral condyle, the corresponding articular surface and the remaining cartilage surfaces of the knee joint. Our null hypothesis was that there would be no difference in characteristics between the cartilage surrounding the defect, the corresponding articular surface and the remaining articular surfaces of the knee joint on the one hand and the cartilage within the defect on the other. METHOD: The study included ten patients treated for focal cartilage lesions (ICRS classification grade IIIb) by autologous cartilage transplantation (ACT). All patients underwent a preoperative magnetic resonance imaging scan (1, 5 T). The articular cartilage lesions were classified pursuant to the recommendations of the International Cartilage Repair Society (ICRS). During the arthroscopic procedure, spectroscopic examinations were performed to measure the degree of cartilage degeneration in a total of 14 defined areas including the defect itself and the region of the defect margins. Biopsies for a histological and biochemical examination (collagen II, glycosaminoglycan, DNA) were taken from the centre of the defect and the defect margins that seemed to be intact on macroscopic examination. RESULTS: All knee joints had focal grade IIIb cartilage lesions with an intact margin and an intact corresponding articular surface. The readings obtained on spectroscopic examination both in the defect, the apparently intact margins, the corresponding articular surface and all other examined areas of the knee suggested that severe degenerative changes had already occurred in the cartilage. The histological and biochemical examinations of the residual cartilage in the centre of the defect and the apparently intact margins revealed no significant differences. CONCLUSIONS: Focal cartilage lesions frequently occur in the main weight-bearing zones of the patella and the medial femoral condyle. If they are the result of degenerative changes in the knee joint, the residual cartilage in the defect does not differ from the cartilage of the defect margins, the corresponding articular surface and the other cartilage surfaces. This leads to the conclusion that focal cartilage defects seen in degenerative joint damage are only one aspect of general joint degeneration.

[Perioperative risk and mortality after major surgery]. / Perioperatives Risiko und Letalität nach großen chirurgischen Eingriffen.

Although anesthesia-associated mortality has been significantly reduced down to 0.00068-0.00082% over the last decades, recent studies have revealed a high perioperative mortality of 0.8- 4%. Apart from anesthesia and surgery-induced major complications, perioperative mortality is primarily negatively influenced by individual patient comorbidities. These risk factors predispose for acute critical incidents (e.g., myocardial infarction); however, the majority of fatal complications are a result of slowly progressing conditions, particularly infections or the sequelae of systemic inflammation. This implicates a broad window of opportunity for the detection and treatment of slow-onset complications to improve the perioperative outcome. The term "failure to rescue" (FTR), i.e., the proportion of patients who die from major complications compared to the number of all patients with complications, has been introduced as a valid indicator for the quality of perioperative care. Growing evidence has already shown that FTR is an underestimated factor in perioperative medicine accounting for or at least being involved in the development of postoperative mortality. While the incidence of severe postoperative complications amazingly does not show much variation between hospitals, FTR shows significant differences implying a major potential for improvement. With 14 million surgical procedures per year in Germany, a postoperative mortality of approximately 1% and an avoidable FTR rate of 40% mean that there are an estimated 60,000 preventable deaths per year. Hence, in the future it will be imperative to (1) identify patients at risk, (2) to prevent the development of postoperative complications with the use of adequate adjunctive therapeutic strategies, (3) to establish surveillance and monitoring systems for the early detection of postoperative complications and (4) to treat postoperative complications efficiently and in time when they arise.

Epidemiology of the high-risk population: perioperative risk and mortality after surgery.

PURPOSE OF REVIEW: This review will provide an overview of actual data concerning perioperative risk. Furthermore, strategies to prevent, detect and treat perioperative complications will be discussed. RECENT FINDINGS: Perioperative in-hospital mortality rate of 0.4-4% has not improved over the last years possibly resulting in one to several million deaths during or immediately after surgery each year worldwide. Perioperative complications and mortality are determined not only by the type of surgery but also by preexisting comorbidities of the patient. However, most potentially lethal complications have a slow onset like surgical site infections, pneumonia and sepsis. Therefore, a time window of opportunity might exist to detect and treat these complications as well as to improve outcome. In this context, failure to rescue (FTR) has been introduced as an indicator for the quality of perioperative care. There is growing evidence that FTR is a relevant phenomenon in perioperative medicine, possibly accounting for almost half of postoperative mortality. SUMMARY: It is imperative to reliably identify patients at risk for postoperative complications and to implement strategies into clinical practice allowing for prevention, early detection and effective treatment of complications. By bundling best practice concepts in all phases of perioperative care, patient outcome will be effectively improved.

[Anesthesia in children and adolescents with congenital heart defects]. / Anästhesie bei Kindern und Jugendlichen nach angeborenen Herzfehlern.

The incidence of congenital heart defects (CHD) has remained constant over many years; however, due to improved therapeutic options an increasing number of children and adolescents even with complex heart defects now reach adulthood. The increasing prevalence of adults with persisting or surgically corrected CHD as well as age-dependent non-cardiac comorbidities will increase the need for medical and non-cardiac surgical treatment in this population. Although elective medical care for these patients should be reserved for highly specialized centers, emergency treatment might become necessary in a non-specialized hospital setting as well. Due to the variety and complexity of CHD it is difficult to provide standardized guidelines for the anesthetic management. The treatment of patients with complex CHD requires a profound understanding of the underlying CHD and the current state of the hemodynamics by the anesthesiologist. Furthermore, typical comorbidities, such as chronic heart failure, altered coagulation and arrhythmia also have to be taken into account to ensure successful perioperative treatment. Especially in patients with shunt lesions or passive pulmonary blood flow the anesthetic management often substantially affects the hemodynamics and may be the starting point of severe decompensation. Awareness of anesthesia-induced changes of pulmonary and/or systemic vascular resistance as well as of preload alterations are the basis for successful anesthetic management. Finally, a multidisciplinary approach including cardiologists and radiologists in the planning is absolutely essential to achieve an optimal postoperative result for the patient.

Hypoxia and P. gingivalis synergistically induce HIF-1 and NF-κB activation in PDL cells and periodontal diseases.

Periodontitis is characterized by deep periodontal pockets favoring the proliferation of anaerobic bacteria like Porphyromonas gingivalis (P. gingivalis), a periodontal pathogen frequently observed in patients suffering from periodontal inflammation. Therefore, the aim of the present study was to investigate the signaling pathways activated by lipopolysaccharide (LPS) of P. gingivalis (LPS-PG) and hypoxia in periodontal ligament (PDL) cells. The relevant transcription factors nuclear factor-kappa B (NF-κB) and hypoxia inducible factor-1 (HIF-1) were determined. In addition, we analyzed the expression of interleukin- (IL-) 1ß, matrix metalloproteinase-1 (MMP-1), and vascular endothelial growth factor (VEGF) in PDL cells on mRNA and protein level. This was accomplished by immunohistochemistry of healthy and inflamed periodontal tissues. We detected time-dependent additive effects of LPS-PG and hypoxia on NF-κB and HIF-1α activation in PDL cells followed by an upregulation of IL-1ß, MMP-1, and VEGF expression. Immunohistochemistry performed on tissue samples of gingivitis and periodontitis displayed an increase of NF-κB, HIF-1, and VEGF immunoreactivity in accordance with disease progression validating the importance of the in vitro results. To conclude, the present study underlines the significance of NF-κB and HIF-1α and their target genes VEGF, IL-1ß, and MMP-1 in P. gingivalis and hypoxia induced periodontal inflammatory processes.

Antibiotic consumption after implementation of a procalcitonin-guided antimicrobial stewardship programme in surgical patients admitted to an intensive care unit: a retrospective before-and-after analysis.

PURPOSE: To analyse antibiotic use density (AD)--World Health Organization defined daily doses/1,000 patient-days--before and after implementation of a local antimicrobial stewardship programme (ASP) in conjunction with a procalcitonin (PCT)-guided protocol in a surgical intensive care unit (ICU). METHODS: In this retrospective observational study, data on 2,422 ICU patients between 2010 and 2012 were analysed. In 2011, an ASP in conjunction with a PCT protocol had been introduced into clinical practice. In a multivariate analysis, hospital mortality, length of stay (LOS) in hospital and ICU LOS were adjusted for effects from effective cost weight, gender, and age. AD and changes in the use of antibiotic classes were analysed. RESULTS: AD decreased from 1,005.0 in 2010 to 791.9 in 2012 which is a total reduction of 21.2%. Consumption of aminoglycosides, cephalosporins and quinolones showed a marked reduction, whereas the use of penicillins did not change significantly. The multivariate models revealed no relevant changes in mortality rate, ICU LOS and hospital LOS. CONCLUSIONS: Implementation of an ASP in conjunction with a PCT protocol in 2011 was associated with a marked decrease in total AD and led to a significant change in the spectrum of antibiotics. Clinical outcomes appeared to remain unchanged over the study period.

LPS from P. gingivalis and hypoxia increases oxidative stress in periodontal ligament fibroblasts and contributes to periodontitis.

Oxidative stress is characterized by an accumulation of reactive oxygen species (ROS) and plays a key role in the progression of inflammatory diseases. We hypothesize that hypoxic and inflammatory events induce oxidative stress in the periodontal ligament (PDL) by activating NOX4. Human primary PDL fibroblasts were stimulated with lipopolysaccharide from Porphyromonas gingivalis (LPS-PG), a periodontal pathogen bacterium under normoxic and hypoxic conditions. By quantitative PCR, immunoblot, immunostaining, and a specific ROS assay we determined the amount of NOX4, ROS, and several redox systems. Healthy and inflamed periodontal tissues were collected to evaluate NOX4 and redox systems by immunohistochemistry. We found significantly increased NOX4 levels after hypoxic or inflammatory stimulation in PDL cells (P < 0.001) which was even more pronounced after combination of the stimuli. This was accompanied by a significant upregulation of ROS and catalase (P < 0.001). However, prolonged incubation with both stimuli induced a reduction of catalase indicating a collapse of the protective machinery favoring ROS increase and the progression of inflammatory oral diseases. Analysis of inflamed tissues confirmed our hypothesis. In conclusion, we demonstrated that the interplay of NOX4 and redox systems is crucial for ROS formation which plays a pivotal role during oral diseases.

[Rare complication after endoscopic discectomy]. / Seltene Komplikation der endoskopischen Nukleotomie.

Surgical treatment of the lumbar spine is a standard procedure in orthopedic and neurosurgery. After endoscopic discectomy an otherwise healthy patient developed massive dyspnea in combination with severe abdominal pain. Sonography revealed a large volume of free fluid in the abdominal cavity which proved to be surgical irrigation solution after computed tomography (CT) guided puncture. After insertion of a drainage channel fluid could be removed and the patient was transferred to a peripheral ward after a 24 h monitoring period. This review reports on the complications and anesthetic characteristics of percutaneous spinal interventions and presents differential diagnoses of postoperative dyspnea.

Pre-conditioning with synthetic CpG-oligonucleotides attenuates myocardial ischemia/reperfusion injury via IL-10 up-regulation.

The aim of the study was to investigate whether pre-conditioning with CpG-oligodeoxynucleotides (CpG-ODN) may change cardiac ischemia/reperfusion (I/R)-dependent inflammation and modulates infarct size and cardiac performance. WT and TLR9-deficient mice were pre-treated with 1668-, 1612- and H154-thioate or D-Gal as control. Priming with 1668-thioate significantly induced inflammatory mediators in the serum and a concomitant increase of immune cells in the blood and spleen of WT mice. Furthermore, it induced myocardial pattern recognition receptors and pro-inflammatory cytokines peaking 2 h after priming and a continuous increase of IL-10. 16 h after pre-conditioning, myocardial ischemia was induced for 1 h. Infarct size determined after 24 h of I/R was reduced by 75 % due to pre-conditioning with 1668-thioate but not in the other groups. During reperfusion, cytokine expression in 1668-thioate primed mice increased further with IL-10 exceeding the other mediators by far. These changes were observed neither in animals pre-treated with 1612- or H154-thioate nor in TLR9-deficient mice. The 1668-thioate-dependent increase of IL-10 was further supported by results of a micro-array analysis 3 h after begin of reperfusion. Block of IL-10 signaling increased I/R size and prevented influence of priming. In the group pre-treated with 1668-thioate, cardiac function was preserved 24 h, 14 days and 28 days after I/R, whereas animals without pre-conditioning exhibited impaired heart function 24 h and 14 days after I/R. The excessive 1668-thioate-dependent IL-10 up-regulation during pre-conditioning and after I/R seems to be the key factor for reducing infarct size and improving cardiac function. This is in agreement with the finding that IL-10 block prevents cardioprotection by pre-conditioning.

In vivo TLR9 inhibition attenuates CpG-induced myocardial dysfunction.

The involvement of toll-like receptor 9 (TLR9), a receptor for bacterial DNA, in septic cardiac depression has not been clarified in vivo. Thus, the aim of the study was to test possible TLR9 inhibitors (H154-thioate, IRS954-thioate, and chloroquine) for their ability to protect the cardiovascular system in a murine model of CpG oligodeoxynucleotide- (ODN-) dependent systemic inflammation. Sepsis was induced by i.p. application of the TLR9 agonist 1668-thioate in C57BL/6 wild type (WT) and TLR9-deficient (TLR9-D) mice. Thirty minutes after stimulation TLR9 antagonists were applied i.v. Survival was monitored up to 18 h after stimulation. Cardiac mRNA expression of inflammatory mediators was analyzed 2 h and 6 h after stimulation with 1668-thioate and hemodynamic parameters were monitored at the later time point. Stimulation with 1668-thioate induced a severe sepsis-like state with significant drop of body temperature and significantly increased mortality in WT animals. Additionally, there was a time-dependent increase of inflammatory mediators in the heart accompanied by development of septic heart failure. These effects were not observed in TLR9-D mice. Inhibition of TLR9 by the suppressive ODN H154-thioate significantly ameliorated cardiac inflammation, preserved cardiac function, and improved survival. This suppressive ODN was the most efficient inhibitor of the tested substances.

[Evaluation of cartilage degeneration by near infrared spectroscopy (NIRS): methodical description and systematic literature review]. / Bestimmung des Degenerationsgrads am hyalinen Gelenkknorpel durch Nah-Infrarot-Spektroskopie (NIRS): Methodenbeschreibung und Literaturübersicht.

Damage to hyaline cartilage is the most important pathophysiological tool in the development of osteoarthritis. Cartilage lesions are the most frequent pathological findings during arthroscopic operations. Arthroscopies as well as magnetic resonance tomography are gold standards for detection of cartilage lesions. But the arthroscopic evaluation of cartilage lesions is descriptive and subjective only. The surgeon is able to differentiate between intact cartilage surface, softening, superficial or deep fissure or flake and finally a complete defect. In routine arthroscopy the grading mostly is made by use of different scores [e.g. ICRS (International Cartilage Repair Society), Outerbridge, Insall, Jäger-Wirth or others]. Because the arthroscopic evaluation is subjective the reliability of this method is poor. Spectroscopic methods are established for evaluation of different tissue diseases in different indications. NIRS (near infrared spectroscopy) has become an important method for medical diagnostics in the last years. NIR is very energy-rich and suitable for glass fibre transport without relevant reduction. Insofar this technology may be ideal for endoscopic procedures. Our systematic literature review reveals that NIRS is a sufficient method for an objective diagnosis of cartilage lesions. In the current work we demonstrate an NIRS-based device for intraoperative, real-time cartilage evaluation. Furthermore, we discuss the possible clinical consequences from such measurements.

[Cardiopulmonary bypass in cardiac surgery]. / Kardiopulmonaler bypass in der herzchirurgie.

Cardiopulmonary bypass (CPB) is a standard procedure in cardiac surgery; however, apart from its therapeutic options a CPB might also initiate systemic and organ-specific complications, such as heart failure, renal and pulmonary dysfunction, impaired coagulation as well as neurological and cognitive dysfunction. The immunological response to the extracorporeal circulation generates systemic inflammation which often meets the definition of systemic inflammatory response syndrome (SIRS). The main inducers of SIRS are contact of blood with the artificial surfaces of the CPB, mechanical stress which affects the blood components and the extensive surgical trauma. Hence, a number of technical and surgical developments aim at reduction of the inflammatory response caused by the CPB. By reason of surgical demands, the majority of cardiothoracic procedures still depend on the use of CPB; however, there is an on-going development of new techniques trying to reduce the surgical trauma and the negative consequences of CPB. Here, minimized systems with biocompatible surfaces have been shown to be effective in attenuating the inflammatory response to CPB. Alternative procedures such as off-pump surgery may help to avoid CPB-associated complications but due to specific limitations will not replace conventional bypass surgery.

[Student evaluation of anesthesiological teaching: steering instrument of a continuous improvement process]. / Studentische Evaluation der anästhesiologischen Lehre : Steuerinstrument eines kontinuierlichen Verbesserungsprozesses.

BACKGROUND: The amendment to the higher education act ("Hochschulrahmengesetz") of 1998 postulates an evaluation of teaching for quality assurance. Hence, in the winter semester of 2004 the University Medical Center of Bonn introduced a semester questionnaire for students to evaluate the quality of teaching (EVALON). This evaluation is designed to be an objective benchmarking tool which is used for the distribution of university funds. It is also a steering instrument for direct improvement of teaching in clinical subjects. The aim of this study was to investigate, whether EVALON improved the quality of teaching between 2006 and 2010 and whether the department of anesthesiology improved its ranking in comparison with the other participating institutes. MATERIALS AND METHODS: Data from the EVALON questionnaire from the years 2006-2010 were analyzed for improvements in the quality of teaching in anesthesiology. This study focused on three essential contents of the EVALON questionnaire (structural content and organizational procedure of lectures and seminars, course presentation), which were used for the generation of a ranking list of all participating medical institutes and departments. On the basis of these results, 12.5% of the funding was assigned for educational purposes. RESULTS: There was an average return rate of the questionnaires of 74.5%. A significant increase in the overall assessment score of 43.4% could be observed from 5.3 in the summer semester of 2006 to 7.6 in the winter semester of 2009/10. The evaluation score for the department of anesthesiology concerning structural content of seminars and lectures increased by 79% from 4.8 in 2006 to 8.6 in 2010. The quality of organizational procedure was evaluated with a score of 4.9 in 2006 and improved by 74% to 8.5 in 2010. The course presentation skills of the teachers as evaluated by EVALON improved by 61% from a score of 5.2 in 2006 to 8.4 in 2010. In comparison with all other participating medical institutes the department of anesthesiology improved its ranking from position 36 in the winter semester 2006 to position 2 in the summer semester 2010. CONCLUSIONS: The reorganization of teaching anesthesiology, directly controlled by the results of EVALON improved the ranking of the department of anesthesiology. There was also a concomitant increase of the performance-oriented allocation of funds assigned to the department of anesthesiology based on the EVALON results.

[Traumatic tricuspid valve insufficiency with right-to-left shunt: bridging using extracorporeal venovenous membrane oxygenation]. / Traumatische Trikuspidalklappeninsuffizienz mit Rechts-links-Shunt: "Bridging" mithilfe der extrakorporalen venovenösen Membranoxygenierung.

The case of a young male motor vehicle driver is reported who suffered multiple trauma in a car accident with pulmonary and cardiac contusions. In the course of severe pneumonia and traumatic tricuspid valve insufficiency a right-to-left shunt with refractory hypoxemia developed across a pre-existing atrial septal defect (ASD). The patient could be successfully treated by the combination of extracorporeal membrane oxygenation for bridging, interventional ASD occlusion and in the long-term by operative reconstruction of the tricuspid valve.

Systemically administered ligands of Toll-like receptor 2, -4, and -9 induce distinct inflammatory responses in the murine lung.

OBJECTIVE: To determine whether systemically administered TLR ligands differentially modulate pulmonary inflammation. METHODS: Equipotent doses of LPS (20 mg/kg), CpG-ODN (1668-thioat 1 nmol/g), or LTA (15 mg/kg) were determined via TNF activity assay. C57BL/6 mice were challenged intraperitoneally. Pulmonary NFκB activation (2 h) and gene expression/activity of key inflammatory mediators (4 h) were monitored. RESULTS: All TLR ligands induced NFκB. LPS increased the expression of TLR2, 6, and the cytokines IL-1αß, TNF-α, IL-6, and IL-12p35/p40, CpG-ODN raised TLR6, TNF-α, and IL12p40. LTA had no effect. Additionally, LPS increased the chemokines MIP-1α/ß, MIP-2, TCA-3, eotaxin, and IP-10, while CpG-ODN and LTA did not. Myeloperoxidase activity was highest after LPS stimulation. MMP1, 3, 8, and 9 were upregulated by LPS, MMP2, 8 by CpG-ODN and MMP2 and 9 by LTA. TIMPs were induced only by LPS. MMP-2/-9 induction correlated with their zymographic activities. CONCLUSION: Pulmonary susceptibility to systemic inflammation was highest after LPS, intermediate after CpG-ODN, and lowest after LTA challenge.

Antagonism of lipopolysaccharide-induced blood pressure attenuation and vascular contractility.

OBJECTIVE: Aim was to assess whether lipopolysaccharide (LPS)-induced decrease of total peripheral resistance depends on Toll-like receptor (TLR)4 signaling and whether it is sensitive to NO-synthase or TLR4 antagonists. METHODS AND RESULTS: C3H/HeN mice (control), expressing a functional, and C3H/HeJ mice, expressing a nonfunctional TLR4, were compared. LPS (20 mg/kg) was injected i.p. 6 hours before hemodynamic measurements. L-NAME and SMT, inhibitors of NO production, and Eritoran, a TLR4 antagonist, were tested for their impact on vascular contractility. Aortic rings were incubated for 6 hours with or without LPS (1 microg/mL), or with LPS+Eritoran (2 microg/mL) and their phenylephrine-induced contractility was measured using a myograph. The expression of cytokines in aortic tissue was examined by real-time polymerase chain reaction. In control mice LPS induced a significant decrease of blood pressure and an increase of heart rate, whereas C3H/HeJ remained unaffected. LPS induced an increase of cytokine expression and a depression of vascular contractility only in control mice but not in C3H/HeJ. L-NAME and SMT increased contractility in all rings and restored LPS-dependent depression of contractility. Eritoran prevented LPS-induced loss of contractility. CONCLUSIONS: LPS upregulates cytokine expression via TLR4 and induces attenuation of smooth muscle contractility which can be effectively antagonized.