Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial.

PURPOSE: In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population. METHODS: Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the concomitant phase of chemotherapy. RESULTS: HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was similar between treatment arms (CCNU/TMZ 11.5; TMZ 13 days). Chemotherapy was more often discontinued due to HAE in CCNU/TMZ than in TMZ (19.7 vs. 6.3%, p = 0.036). The occurrence of HAE was not associated with survival differences (p = 0.76). Regression analysis confirmed older age (OR 1.08) and female sex (OR 2.47), but not treatment arm, as predictors of HAE. CONCLUSION: Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures. TRIAL REGISTRATION: NCT01149109.

Protocolised thromboelastometric-guided haemostatic management in patients with traumatic brain injury: a pilot study.

Coagulopathy in patients with traumatic brain injury is associated with an increase in morbidity and mortality. Although timely and aggressive treatment of coagulopathy is of paramount importance, excessive transfusion of blood products has been linked with poor long-term outcomes in patients with traumatic brain injury. A point-of-care thromboelastometric-guided algorithm could assist in creating a more individually tailored approach to each patient. The aim of this study was to evaluate the feasibility of implementing a thromboelastometric-guided algorithm in centres that were formerly naïve to thromboelastometry. Hence, we developed such an algorithm and provided training to four centres across Europe to direct the haemostatic management of patients with severe traumatic brain injury. The primary outcome was adherence to the algorithm and timing of the availability of relevant results. Thirty-two patients were included in the study. Complete adherence to the algorithm was observed in 20 out of 32 cases. The availability of thromboelastometric results after hospital admission was reported significantly earlier than conventional coagulation tests (median (IQR [range]) 33 (20-40 [14-250]) min vs. 71 (51-101 [32-290]) min; p = 0.037). Although only 5 out of 32 patients had abnormalities of conventional coagulation tests, 21 out of 32 patients had a coagulopathic baseline thromboelastometric trace. Implementing a thromboelastometric-guided algorithm for the haemostatic therapy of traumatic brain injury is feasible in centres formerly naïve to this technology and may lead to more rapid and precise coagulation management. Further large-scale studies are warranted to confirm the results of this pilot trial and evaluate clinical outcomes.

Norepinephrine modulates osteoarthritic chondrocyte metabolism and inflammatory responses.

OBJECTIVE: Norepinephrine (NE) was measured in synovial fluid of trauma patients and sympathetic nerve fibers were detected in healthy and osteoarthritic (OA) joint tissues indicating that cartilage pathophysiology might be influenced by sympathetic neurotransmitters. The aim of this study was to elucidate the mostly unknown role of NE in OA chondrocyte metabolism and inflammatory responses. METHODS: Articular cartilage was received after total knee replacement surgery from OA patients. Expression of adrenergic receptors (AR) and tyrosine hydroxylase (TH) was tested with end point polymerase chain reaction (PCR) and immunohistochemistry. 3-dimensional (3D) cell cultures were employed to analyze effects of NE on chondrocyte cell metabolism and the expression of interleukins (ILs), matrix metalloproteases (MMPs), tissue inhibitor of metalloproteases (TIMPs), glycosaminoglycan (GAG) and collagen II under non- and inflammatory conditions. Chondrocyte monolayer cultures were used to specify AR subtypes, to analyze cell cycle distribution and to determine catecholamines in cell culture supernatants. RESULTS: AR subtypes and TH were detected in chondrocytes, whereas NE was not released in measurable amounts. 10(-6) M NE reversed IL-1ß induced changes in IL-8, MMP-13, GAG and collagen II expression/production indicating for ß-AR signaling. Additionally, NE caused cell cycle slow down and decreased proliferation via ß-AR signaling. 10(-8) M NE increased the number of proliferating cells and induced apoptosis via α1-AR signaling. CONCLUSIONS: NE affects chondrocytes from OA cartilage regarding inflammatory response and its cell metabolism in a dose dependent manner. The sympathetic nervous system (SNS) may have a dual function in OA pathology with preserving a stable chondrocyte phenotype via ß-AR signaling and OA pathogenesis accelerating effects via α-AR signaling.

In vitro effects of different sources of fibrinogen supplementation on clot initiation and stability in a model of dilutional coagulopathy.

OBJECTIVES: To analyse which fibrinogen source may improve coagulation using an in vitro 33% dilutional coagulopathy model. BACKGROUND: Uncritical volume resuscitation in the context of trauma haemorrhage contributes to the iatrogenic arm of the acute trauma-induced coagulopathy through dilution and depletion of coagulation factors, with fibrinogen reaching critical levels first. MATERIALS AND METHODS: By using an experimental model of 33% dilutional coagulopathy, we have analysed which fibrinogen source may exert superior effects on improving haemocoagulative capacities and correcting depleted fibrinogen levels. As fibrinogen sources, we supplemented (i) fresh frozen plasma (FFP), (ii) fibrinogen concentrate low-dose (Fiblow ) and (iii) fibrinogen concentrate high-dose (Fibhigh ), the latter both in the presence and absence of additional FXIII. RESULTS: The dilution was associated with decreased haemoglobin and haematocrit levels. Fibrinogen supplementation with fibrinogen-containing formulations led to increased fibrinogen levels (FFP: 172·2 ± 17·4 mg dL-1 ; Fiblow : 211·5 ± 20·61 mg dL-1 ; Fibhigh : 255·8 ± 21·4 mg dL-1 ) than in a diluted-only sample (155·5 ± 19·7 mg dL-1 ). Extrinsically activated assay with tissue factor (EXTEM) clot formation times, α-angles and maximum clot firmness significantly improved in the groups of Fiblow + FXIII (79 ± 12·2 s; 74·3 ± 2·4°; 62 ± 2·3 mm), Fibhigh (70·8 ± 10·6 s; 76·2 ± 2·7°; 64·3 ± 2·3 mm) and Fibhigh + FXIII (69·8 ± 11·5 s; 77·5 ± 2·7°; 64·33 ± 2·5 mm) compared with the dilution groups (104·2 ± 19 s; 69·7 ± 2·9°; 56·5 ± 3·1 mm). In contrast, rotational thromboelastometric trace (ROTEM) measures of samples supplemented with FFP largely remained unchanged. CONCLUSION: Fibrinogen concentrates corrected and improved haemodilution-induced changes in blood clotting in vitro. High-dose fibrinogen supplementation was associated with correction and improvement in clot dynamics and stability.

[Surgical Therapy and Prognostic Factors for Carcinoma of Vater's Papilla]. / Chirurgische Therapie und prognostische Faktoren des Papillenkarzinoms.

BACKGROUND: Carcinoma of ampulla of Vater are rare tumours of the GI-tract with an improved prognosis compared to other periampullary tumours. Analysis of survival and prognostic factors are limited due to the low incidence of the carcinoma. The intention of this study in patients with papillary carcinoma was to evaluate short- and long-term survival and to identify prognostic factors for pancreatectomy and reconstruction using pancreatogastrostomy as treatment of carcinoma of Vater's ampulla. PATIENTS AND METHODS: Between 1989 and 2008 76 patients with a carcinoma of the ampulla of Vater were treated by oncological resection followed by pancreatogastrostomy. Various factors such as demographics, perioperative factors, histopathological findings as well as short- and long-term survival were evaluated retrospectively. Data were analysed statistically using Kaplan-Meier estimates of survival with log-rank test and uni- and multivariate analysis with Cox regression. RESULTS: The overall 5-year survival was 46 %, the 10-year survival 26 % for resected patients. By univariate analysis we could demonstrate that lymph node metastasis is the only predictor for outcome. In the multivariate analysis, age, sex, grading and especially lymph node status were a significant predictor for the survival of patients. CONCLUSION: In the current patient cohort lymph node status was the most important independent predictor of outcome after resection of carcinoma of Vater's papilla.

[Implementation of the Perioperative WHO Safety Checklist at a Maximum Care Hospital - A Retrospective Analysis]. / Implementierung der perioperativen WHO-Sicherheitscheckliste an einem Klinikum der Maximalversorgung - eine retrospektive Analyse.

BACKGROUND: In recent years there has been a significant increase of surgical procedures worldwide. Perioperative complication occurred in approximately 10 %, mortality was about 0.5 %. Half of these adverse events were considered to have been preventable. With the introduction of a perioperative checklist by the WHO in 2008, a significant reduction of morbidity and mortality could be achieved. The aim of this study was to investigate the success of the implementation process of the checklist at a maximum care hospital over a three-year period and to expose and analyse any occurring issues. PATIENTS AND METHODS: At various time points (introduction phase, five months, one year and three years after implementation) a total of 358 operations was investigated. First the presence and the handling of the checklist were investigated followed by an analysis of possible influencing factors on the processing. To examine a potential perioperative malpractice, three typical perioperative errors known from the literature on patient safety were analysed. RESULTS: The presence of the checklist improved significantly during the study. With the exception of the first column (signed by ward nurse) the checklist was processed more often among the participants (anaesthesia nurse, anaesthesia physician, surgeon) over the time. However the "sign out" column edited by the surgeon at the end of the operation fell below expectations. In addition to the duration after implementation the level of experience of the surgeon was a relevant factor for a properly completed checklist. During the study a malpractice was found in two cases, a checklist could not be detected. CONCLUSION: Within the study we could demonstrate the difficulties of introducing a surgical checklist at a maximum care hospital. Therefore involved nursing or medical staff must be aware of the usefulness of the checklist and should be motivated to use it. In addition, periodical lectures, training courses and role modelling of nursing and medical staff are required. The objective must be to establish the checklist into daily routine as it is a simple and efficient tool to reduce perioperative morbidity and mortality.

[Posthepatectomy Liver Failure in Extended Liver Resections: An Overview Based on a Retrospective Single-Centre Analysis]. / Postoperatives Leberversagen nach erweiterten Leberresektionen - eine Übersicht, gestützt durch eine retrospektive Single-Center-Analyse.

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the most serious complications after major liver resections and an important factor in terms of perioperative morbidity and mortality. Despite many advances in the understanding and grading of PHLF, the definitions found in literature are very heterogeneous, which complicates the identification of high-risk patients. In this study we analysed the results of extended liver resections and potential risk factors for PHLF based on patient data derived from our tertiary referral centre. The aim of the study was to gain an overview of the essential aspects in the prevention of PHLF combined with key intraoperative issues and postoperative treatment strategies. METHODS: We analysed data from 202 patients who underwent extended elective liver resections at our centre between April 1989 and September 2009 (135 right hemihepatectomies, 39 left hemihepatectomies, 28 right trisectionectomies). According to Balzan's "50/50 criteria", PHLF was defined as prothrombin time (PT) < 50 % combined with serum bilirubin (SB) > 50 micromol/L on postoperative day (POD) 5 or as death due to primary or secondary liver failure. RESULTS: Thirty-day mortality and overall in-hospital mortality were 4.95 and 8.91 %, respectively. Twenty-eight (14 %) patients developed PHLF and 16 (57 %) patients died. Compared to patients with normal postoperative liver function, several significant pre- and intraoperative factors for PHLF were identified, e.g. primary malignant liver tumour (p < 0.001), extended liver resection (p < 0.001), time of surgery (p < 0.001) and intraoperative transfusion of packed RBC (p < 0.02) or FFP (p < 0.001). CONCLUSION: Although progress has been made in hepatobiliary surgery, PHLF remains a serious complication, especially after extended liver resections. Careful, optimised preoperative risk stratification is required to identify patients at risk for PHLF.

[Brain stem infarction, temporal headache, and elevated inflammatory parameters in a 74-year-old man]. / Hirnstamminfarkt, temporaler Kopfschmerz und erhöhte Entzündungsparameter bei einem 74-jährigen Patienten.

We report the case of a 74 year old man with a brain stem infarction, temporal headache and elevated inflammatory parameters. Giant cell arteritis with involvement of the temporal and vertebral arteries was proven by histology, duplex sonography and MRI. Although intensive immunosuppressive therapy was started, the patient developed two brain infarcts within 6 months. Initially, C­reactive protein and erythrocyte sedimentation rate were significantly elevated, but normalized over time. Involvement of the vertebral artery in giant cell arteritis is thought to be rare; steroid refractory courses are very rare. Brain stem infarction might be the consequence.

[A 58-year-old patient with temporal headache, jaw claudication and B symptoms]. / Ein 58-jähriger Patient mit temporalen Kopfschmerzen, Kauclaudicatio und B-Symptomatik.

CASE REPORT: We report the case of a patient with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with involvement of the temporal artery, presenting with clinical manifestations of giant cell arteritis and temporal arteritis, such as temporal headache, jaw claudication, weight loss, night sweats and increased inflammatory parameters. The ultrasound scan showed a typical halo sign of the temporal artery. DIAGNOSTICS: In the case of further atypical organ symptoms, e.g. hematuria and proteinuria, detailed differential diagnostic investigations are essential to clarify the situation. Histological findings from the affected organs play a decisive role. CONCLUSION: An involvement of the temporal artery due to ANCA-associated vasculitis is extremely rare and may mimic giant cell arteritis. The exact diagnosis of ANCA-associated vasculitis is, however, important because this leads to a different approach concerning therapy and prognosis.

Bevacizumab treatment in malignant meningioma with additional radiation necrosis. An MRI diffusion and perfusion case study.

BACKGROUND AND PURPOSE: Recently two retrospective cohort studies report efficacy of bevacizumab in patients with recurrent atypical and anaplastic meningioma. Another successful therapeutic option of bevacizumab seems to be treatment of cerebral radiation necrosis. However, the antiangiogenic effects in MRI diffusion and perfusion in meningiomas have not been previously described in detail. The objective of this research was to evaluate the clinical and MR imaging effects of bevacizumab in a malignant meningioma patient harboring additional cerebral radiation necrosis. CASE PRESENTATION: We report the case of an 80-year-old woman who underwent bevacizumab therapy (5 mg/kg every 2 weeks for 2 months) for treatment of a symptomatic radiation necrosis in malignant meningiomatosis of World Health Organization (WHO) grade III. The patient was closely monitored with MRI including diffusion and perfusion studies. Upon bevacizumab therapy, the clinical situation was well stabilized over a period of 4 months until the patient unfortunately died due to pneumonia/septicemia probably unrelated to bevacizumab therapy. Consecutive MRI demonstrated 4 important aspects: (1) considerable decrease of the contrast medium (CM)-enhanced radiation necrosis, (2) mixed response with respect to the meningiomatosis with stable and predominantly growing tumor lesions, (3) a new diffusion-weighted imaging (DWI) lesion in a CM-enhanced tumor as described in gliomas, which we did not interpret as a response to bevacizumab therapy, and (4) new thrombembolic infarcts, which are a known side-effect of bevacizumab treatment. CONCLUSION: Bevacizumab is effective in the treatment of radiation necrosis. We could not confirm the potential antitumor effect of bevacizumab in this patient. However, we could describe several new radiographic effects of bevacizumab therapy in malignant meningioma.

Learning To Fold Proteins Using Energy Landscape Theory.

This review is a tutorial for scientists interested in the problem of protein structure prediction, particularly those interested in using coarse-grained molecular dynamics models that are optimized using lessons learned from the energy landscape theory of protein folding. We also present a review of the results of the AMH/AMC/AMW/AWSEM family of coarse-grained molecular dynamics protein folding models to illustrate the points covered in the first part of the article. Accurate coarse-grained structure prediction models can be used to investigate a wide range of conceptual and mechanistic issues outside of protein structure prediction; specifically, the paper concludes by reviewing how AWSEM has in recent years been able to elucidate questions related to the unusual kinetic behavior of artificially designed proteins, multidomain protein misfolding, and the initial stages of protein aggregation.

Ifosfamide, carboplatin and etoposide in recurrent malignant glioma.

After failure of temozolomide, there is no established standard salvage chemotherapy for patients with recurrent glioblastoma (GBM). Two phase II trials combining ifosfamide, carboplatin and etoposide chemotherapy (ICE) showed favorable results. We therefore applied the ICE protocol to 13 patients (10 GBM, 3 anaplastic astrocytomas). Partial or complete remissions were not observed. None of the 13 patients survived progression-free for 6 months. Our retrospective analysis suggests that the ICE regimen is not effective in patients with recurrent high-grade glioma if applied at second or third relapse.

Meloxicam, a COX-2 inhibitor, ameliorates ischemia/reperfusion injury in non-heart-beating donor livers.

BACKGROUND/AIMS: Chronic organ donor shortage has led to the consideration to expand the donor pool with livers from non-heart-beating donors (NHBD), although a higher risk of graft dys- or nonfunction is associated with these livers. We examined the effects of selective cyclooxygenase-2 (COX-2) inhibition on hepatic warm ischemia (WI) reperfusion (I/R) injury of NHBD. METHODS: Male Wistar rats were used as donors and meloxicam (5 mg/kg body weight) was administered into the preservation solution. Livers were excised after 60 min of WI in situ, flushed and preserved for 24 h at 4°C. Reperfusion was carried out in vitro at a constant flow for 45 min. During reperfusion (5, 15, 30 and 45 min), enzyme release of alanine aminotransferase and glutamate lactate dehydrogenase were measured as well as portal venous pressure, bile production and oxygen consumption. The production of malondialdehyde was quantified and TUNEL staining was performed. Quantitative PCR analyzed COX-2 mRNA. COX-2 immunohistochemistry and TxB(2) detection completed the measurements. RESULTS: Meloxicam treatment led to better functional recovery concerning liver enzyme release, vascular resistance and metabolic activity over time in all animals. Oxidative stress and apoptosis were considerably reduced. CONCLUSION: Cold storage using meloxicam resulted in significantly better integrity and function of livers retrieved from NHBD. Selective COX-2 inhibition is a new therapeutic approach achieving improved preservation of grafts from NHBD.

Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial.

PURPOSE: Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs). METHODS: This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI). RESULTS: Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76-1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54-1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84-5.34). CONCLUSION: There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols.

Deceptive and Nondeceptive Placebos to Reduce Pain: An Experimental Study in Healthy Individuals.

OBJECTIVES: Recent research has shown that placebos can be effective even if they are openly prescribed to participants. Yet, it is unclear how such "open-label placebos" (OLPs) compare to deceptive placebo (DP) and what the mechanisms of actions are. In this study, we therefore compared 2 versions of OLP to DP and no treatment (NT). MATERIALS AND METHODS: Using a standard heat pain paradigm, 117 healthy volunteers underwent a baseline and a posttreatment pain assessment. With the exception of NT, all groups received an inert placebo cream after the first assessment. OLP was administered by either evoking positive expectancies or by raising hope for placebo analgesia, thus distinguishing for the first time conceptually between expectancy and hope in experimental pain research. The primary outcome was pre-post change in pain tolerance. RESULTS: Increase in pain tolerance was larger in the 3 treatment groups compared with NT, whereas the treatment groups did not differ from each other. Further results showed that participants receiving DP reported a large reduction of subjective pain intensity and unpleasantness, whereas no such reduction was found for the 2 OLP groups. The 2 OLP versions did not differ in terms of their analgesic effects. DISCUSSION: The study provided evidence for traditional placebo analgesia on the basis of deception. For OLP, we found that OLP indeed increased pain tolerance; however, participants receiving OLP were reluctant to report any subjective analgesic effects. Combined with previous studies, the present findings suggest that the effects of OLP are weaker in healthy volunteers than in clinical samples.

[The history of thymus surgery]. / Die Geschichte der Thymuschirurgie.

Thymus surgery was initially dominated by the erroneous interpretation of the organs' pathogenicity and associated thymus diseases. Misleadingly, the thymus gland was made responsible for dyspnoea in children and a transcervical ektropexia was performed in a child suffering from dyspnoea in 1896. After F. Sauerbruch's thymectomy in a patient with myasthenia gravis syndrome (MG), A. Blalock established thymectomy in the 1940s for the treatment of MG. At the same time, the drug treatment initiated by M.B. Walker increased in significance. Despite progress in surgical techniques and the molecular understanding of MG pathogenesis, randomized controlled trials, which would increase the evidence for surgical access and indications for surgery compared to immunosuppressive treatment in MG, are lacking.

[Port stapling for simplified port implantation in laparoscopic adjustable gastric banding]. / Port-Stapling zur Erleichterung der Portimplantation bei der laparoskopischen Magenbandoperation.

BACKGROUND: The purpose of this study was to evaluate the applicability of a port stapling device to simplify and improve port implantation in laparoscopic adjustable gastric banding (LAGB). METHODS: From November 2005 to September 2006, a prospective study was conducted on 23 consecutive patients who underwent LAGB with Swedish adjustable gastric banding. Patients were randomized to either conventional titanium-port implantation or port stapling using the "Velocity" device. RESULTS: No differences in age, body weight, body mass index, fascia depth or incision length were reported between the groups. Port implantation time was significantly less using port stapling (90+/-24 s) compared to conventional port implantation (521+/-138 s). Port related complaints postoperatively and at follow-up were equal in both groups. CONCLUSIONS: Port stapling is an excellent tool to facilitate port implantation, particularly in massively obese patients with a thick abdominal wall.

Practice management of acute trauma haemorrhage and haemostatic disorders across German trauma centres.

PURPOSE: Early detection and management of trauma haemorrhage and coagulopathy have been associated with improved outcomes. We assessed infrastructure, logistics and management practice of trauma-associated haemorrhage and coagulopathy across German trauma centres. METHODS: A web-based survey of 20 questions was developed using the open source survey application LimeSurvey®. It was disseminated among surgeons and anaesthetists in Germany. RESULTS: 145 Questionnaires were returned of which 106 were completed and analysed. Two-thirds of the respondents declared they worked in level I trauma centres. Only 61 % followed a treatment algorithm. Over 90 % used standard laboratory and coagulation tests for decision-making. 56.6 % declared they additionally used extended coagulation assays (TEG/ROTEM). Packed red blood cells, fresh frozen plasma, platelet concentrates, prothrombin complex concentrates, tranexamic acid, calcium, fibrinogen and vitamin K were used by more than 85 % of the respondents for the initial treatment. In all hospitals, irrespective of care level, the first blood product was administered in less than 30 min upon patient arrival (49 % <15 min, 48.1 % <30 min). New oral anticoagulants (NOACs) were identified as an increasing problem in today`s trauma care (>95 %) and 65 % of the respondents necessitated reliable tests for early risk stratification. 57.6 % necessitated interdisciplinary training programs to improve clinical skills. CONCLUSIONS: There is variation in the local infrastructure, logistics and management of trauma haemorrhage and coagulopathy across German trauma centres. More than one-third of the respondents declare they do not consistently follow a treatment algorithm. NOACs are considered as an increasing problem in acute trauma care.

The coeliac aneurysm: a rare cause of abdominal pain.

Visceral artery aneurysms (VAA) represent 0.1-0.2% of all vascular aneurysms. For VAA's etiology, congenital or arteriosclerotic factors, media defects, infections, vasculitis and trauma are discussed. Ultrasound, CT scan and magnetic resonance imaging underline the diagnosis of VAA. The low perioperative morbidity and mortality and the excellent surgical longterm results justify the prophylactic therapy also from asymptomatic VAA because the mortality of ruptured VAA is close to 100%. The radiological interventional treatment is indicated for only selected patients whereas an advantage is not verified yet.

Therapy of leptomeningeal metastasis in solid tumors.

Leptomeningeal metastasis (LM), i.e. the seeding of tumor cells to the cerebrospinal fluid (CSF) and the leptomeninges, is a devastating and mostly late-stage complication of various solid tumors. Clinical signs and symptoms may include cranial nerve palsies, radicular symptoms, signs of increased intracranial pressure such as headache, nausea and vomiting, and cognitive dysfunction. In cases of suspected LM, the highest diagnostic sensitivity is provided by the combination of CSF cytology and contrast-enhanced MRI (cranial as well as complete spine). The therapeutic spectrum includes radiotherapy of the clinically involved region as well as systemic and intrathecal chemotherapy. The choice of treatment modalities depends on the type of LM (non-adherent tumor cells in the CSF vs. nodular contrast-enhancing tumor growth), additional systemic involvement (uncontrolled vs. controlled systemic disease) and additional involvement of the CNS parenchyma (LM as the only CNS involvement vs. LM+parenchymal CNS metastases). Larger contrast-enhancing nodular LM or symptomatic lesions of the spine may be treated with radiotherapy. In case of uncontrolled systemic disease, the treatment regimen should include systemic chemotherapy. The choice of systemic treatment should take into account the histology of the primary tumor. Intrathecal chemotherapy is most important in cases of LM of the non-adherent type. There are three substances for routine use for intrathecal chemotherapy: methotrexate, cytarabine, and thiotepa. Liposomal cytarabine shows advantages in terms of longer injection intervals, a sufficient distribution in the entire subarachnoid space after lumbar administration and improved quality-of-life. The role of new agents (e.g. rituximab and trastuzumab) for intrathecal therapy is still unclear.