Postmortem dynamic CT-angiography : P30

Purpose: Forensic imaging and especially forensic radiology is a new trend in forensic medicine. More and more forensic institutes set up their own CT-scanner in order to perform postmortem cross-sectional imaging. Due to this trend, a new subspecialty was born: the forensic radiology. To image the vascular system after death, a postmortem CT- angiography can be performed. Methods and materials: In the Institute of Forensic Medicine in Lausanne, a science group has been created with specialists of different medical fields that has set up a new technique of forensic CT-angiography. The method consists in the creation of a postmortem circulation by the use of a modified heart lung machine. As circulating liquid Angiofil, an oily contrast agent, is injected. Results: With the aid of this technique, the whole vascular system of a deceased person can be imaged in detail without autopsy. The circulating contrast allows demonstrating the vascular system when it is under pressure, similarly to living patients. First experiences showed, that vascular pathologies such as cardiac tamponade and aortic dissection can be well demonstrated. Since the oily Angiofil strictly remains in the intravascular space, no artifacts had been observed during the CT-examination and the later performed autopsy. Conclusion: Post-mortem dynamic CT angiography is of great advantage in forensic pathology, because the detailed mapping of the entire vascular system is almost impossible with conventional autopsy tools.

Prescription de statines en prévention primaire: quel score de risque cardiovasculaire faut-il utiliser en Suisse? [Statin prescription in primary prevention: which cardiovascular risk score should be used in Switzerland?]

La prévention primaire des maladies cardiovasculaires par les médecins s'effectue par une prise en charge individualisée des facteurs de risque. L'indication à un traitement par statines se base sur une estimation du risque de survenue d'une maladie cardiovasculaire et sur le taux de LDL-cholestérol. Trois scores de risque sont couramment utilisés: le score PROCAM, le score Framingham, et le SCORE européen. En Suisse, le Groupe Suisse Lipides et Athérosclérose (GSLA) recommande en première instance l'utilisation du score PROCAM avec une adaptation du niveau de risque pour la Suisse. Une enquête a aussi montré que c'est le score le plus utilisé en Suisse. Dans cet article, les particularités de ces scores et leurs applications pratiques en ce qui concerne la prescription de statines en prévention primaire sont discutées. Les conséquences et les bénéfices potentiels de l'application de ces scores en Suisse sont également abordés. [Abstract] Primary prevention of cardiovascular disease by physicians is achieved by management of individual risk factors. The eligibility for treatment with statins is based on both an estimate of the risk of developing cardiovascular disease and the LDL-cholesterol. Three risk scores are commonly used : the PROCAM score, the Framingham score, and the European score. In Switzerland, the Swiss Group Lipids and Atherosclerosis (GSLA) recommends to use the PROCAM score with an adjustment of the level of risk for Switzerland. A survey also showed that PROCAM is the most used in Switzerland. In this article, the differences of these scores and their practical applications regarding the prescription of statins in primary prevention are discussed. The consequences and potential benefits of applying these scores in Switzerland are also discussed.

Glasgow Coma Score für den Patienten mit Schädel-Hirn-Trauma [Glasgow Coma Scale in traumatic brain injury].

Even 30 years after its first publication the Glasgow Coma Scale (GCS) is still used worldwide to describe and assess coma. The GCS consists of three components, the ocular, motor and verbal response to standardized stimulation, and is used as a severity of illness indicator for coma of various origins. The GCS facilitates information transfer and monitoring changes in coma. In addition, it is used as a triage tool in patients with traumatic brain injury. Its prognostic value regarding the outcome after a traumatic brain injury still lacks evidence. One of the main problems is the evaluation of the GCS in sedated, paralysed and/or intubated patients. A multitude of pseudoscores exists but a universal definition has yet to be defined.

A novel method of dynamic culture surface expansion improves mesenchymal stem cell proliferation and phenotype.

Repeated passaging in conventional cell culture reduces pluripotency and proliferation capacity of human mesenchymal stem cells (MSC). We introduce an innovative cell culture method whereby the culture surface is dynamically enlarged during cell proliferation. This approach maintains constantly high cell density while preventing contact inhibition of growth. A highly elastic culture surface was enlarged in steps of 5% over the course of a 20-day culture period to 800% of the initial surface area. Nine weeks of dynamic expansion culture produced 10-fold more MSC compared with conventional culture, with one-third the number of trypsin passages. After 9 weeks, MSC continued to proliferate under dynamic expansion but ceased to grow in conventional culture. Dynamic expansion culture fully retained the multipotent character of MSC, which could be induced to differentiate into adipogenic, chondrogenic, osteogenic, and myogenic lineages. Development of an undesired fibrogenic myofibroblast phenotype was suppressed. Hence, our novel method can rapidly provide the high number of autologous, multipotent, and nonfibrogenic MSC needed for successful regenerative medicine.

Dynamic modulation of CCR7 expression and function on naive T lymphocytes in vivo.

The chemokine receptor CCR7 is critical for the recirculation of naive T cells. It is required for T cell entry into secondary lymphoid organs (SLO) and for T cell motility and retention within these organs. How CCR7 activity is regulated during these processes in vivo is poorly understood. Here we show strong modulation of CCR7 surface expression and occupancy by the two CCR7 ligands, both in vitro and in vivo. In contrast to blood, T cells in SLO had most surface CCR7 occupied with CCL19, presumably leading to continuous signaling and cell motility. Both ligands triggered CCR7 internalization in vivo as shown in Ccl19(-/-) and plt/plt mice. Importantly, CCR7 occupancy and down-regulation led to strongly impaired chemotactic responses, an effect reversible by CCR7 resensitization. Therefore, during their recirculation, T cells cycle between states of free CCR7 with high ligand sensitivity in blood and occupied CCR7 associated with continual signaling and reduced ligand sensitivity within SLO. We propose that these two states of CCR7 are important to allow the various functions CCR7 plays in T cell recirculation.

Conditional manipulation of sex ratios by ant workers: A test of kin selection theory

Variable queen mating frequencies provide a unique opportunity to study the resolution of worker-queen conflict over sex ratio in social Hymenoptera, because the conflict is maximal in colonies headed by a singly mated queen and is weak or nonexistent in colonies headed by a multiply mated queen. In the wood ant Formica exsecta, workers in colonies with a singly mated queen, but not those in colonies with a multiply mated queen, altered the sex ratio of queen-laid eggs by eliminating males to preferentially raise queens. By this conditional response to queen mating frequency, workers enhance their inclusive fitness.

Improving plant functional groups for dynamic models of biodiversity: at the crossroads between functional and community ecology

The pace of on-going climate change calls for reliable plant biodiversity scenarios. Traditional dynamic vegetation models use plant functional types that are summarized to such an extent that they become meaningless for biodiversity scenarios. Hybrid dynamic vegetation models of intermediate complexity (hybrid-DVMs) have recently been developed to address this issue. These models, at the crossroads between phenomenological and process-based models, are able to involve an intermediate number of well-chosen plant functional groups (PFGs). The challenge is to build meaningful PFGs that are representative of plant biodiversity, and consistent with the parameters and processes of hybrid-DVMs. Here, we propose and test a framework based on few selected traits to define a limited number of PFGs, which are both representative of the diversity (functional and taxonomic) of the flora in the Ecrins National Park, and adapted to hybrid-DVMs. This new classification scheme, together with recent advances in vegetation modeling, constitutes a step forward for mechanistic biodiversity modeling.

Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia.

We conducted a genome-wide scan using variance components linkage analysis to localize quantitative-trait loci (QTLs) influencing triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol, and total cholesterol (TC) levels in 3,071 subjects from 459 families with atherogenic dyslipidemia. The most significant evidence for linkage to TG levels was found in a subset of Turkish families at 11q22 [logarithm of the odds ratio (LOD)=3.34] and at 17q12 (LOD=3.44). We performed sequential oligogenic linkage analysis to examine whether multiple QTLs jointly influence TG levels in the Turkish families. These analyses revealed loci at 20q13 that showed strong epistatic effects with 11q22 (conditional LOD=3.15) and at 7q36 that showed strong epistatic effects with 17q12 (conditional LOD=3.21). We also found linkage on the 8p21 region for TG in the entire group of families (LOD=3.08). For HDL-C levels, evidence of linkage was identified on chromosome 15 in the Turkish families (LOD=3.05) and on chromosome 5 in the entire group of families (LOD=2.83). Linkage to QTLs for TC was found at 8p23 in the entire group of families (LOD=4.05) and at 5q13 in a subset of Turkish and Mediterranean families (LOD=3.72). These QTLs provide important clues for the further investigation of genes responsible for these complex lipid phenotypes. These data also indicate that a large proportion of the variance of TG levels in the Turkish population is explained by the interaction of multiple genetic loci.

Objective assessment of image quality in conventional and digital mammography taking into account dynamic range.

The goal of this work is to develop a method to objectively compare the performance of a digital and a screen-film mammography system in terms of image quality. The method takes into account the dynamic range of the image detector, the detection of high and low contrast structures, the visualisation of the images and the observer response. A test object, designed to represent a compressed breast, was constructed from various tissue equivalent materials ranging from purely adipose to purely glandular composition. Different areas within the test object permitted the evaluation of low and high contrast detection, spatial resolution and image noise. All the images (digital and conventional) were captured using a CCD camera to include the visualisation process in the image quality assessment. A mathematical model observer (non-prewhitening matched filter), that calculates the detectability of high and low contrast structures using spatial resolution, noise and contrast, was used to compare the two technologies. Our results show that for a given patient dose, the detection of high and low contrast structures is significantly better for the digital system than for the conventional screen-film system studied. The method of using a test object with a large tissue composition range combined with a camera to compare conventional and digital imaging modalities can be applied to other radiological imaging techniques. In particular it could be used to optimise the process of radiographic reading of soft copy images.

Recommendations for the use of ultrasound in rheumatoid arthritis: literature review and SONAR score experience.

Ultrasound (US) has become a useful tool in the detection of early disease, differential diagnosis, guidance of treatment decisions and treatment monitoring of rheumatoid arthritis (RA). In 2008, the Swiss Sonography in Arthritis and Rheumatism (SONAR) group was established to promote the use of US in inflammatory arthritis in clinical practice. A scoring system was developed and taught to a large number of Swiss rheumatologists who already contributed to the Swiss Clinical Quality Management (SCQM) database, a national patient register. This paper intends to give a Swiss consensus about best clinical practice recommendations for the use of US in RA on the basis of the current literature knowledge and experience with the Swiss SONAR score. Literature research was performed to collect data on current evidence. The results were discussed among specialists of the Swiss university centres and private practice, following a structured procedure. Musculoskelatal US was found to be very helpful in establishing the diagnosis and monitoring the evolution of RA, and to be a reliable tool if used by experienced examiners. It influences treatment decisions such as continuing, intensifying or stepping down therapy. The definite modalities of integrating US into the diagnosis and monitoring of RA treatments will be defined within a few years. There are, however, strong arguments to use US findings as of today in daily clinical care. Some practical recommendations about the use of US in RA, focusing on the diagnosis and the use of the SONAR score, are proposed.

Treatment of ruptured abdominal aortic aneurysm, a permanent challenge or a waste of resources? Prediction of outcome using a multi-organ-dysfunction score.

OBJECTIVES: in a retrospective study, attempts have been made to identify individual organ-dysfunction risk profiles influencing the outcome after surgery for ruptured abdominal aortic aneurysms. METHODS: out of 235 patients undergoing graft replacement for abdominal aortic aneurysms, 57 (53 men, four women, mean age 72 years [s.d. 8.8]) were treated for ruptured aneurysms in a 3-year period. Forty-eight preoperative, 13 intraoperative and 34 postoperative variables were evaluated statistically. A simple multi-organ dysfunction (MOD) score was adopted. RESULTS: the perioperative mortality was 32%. Three patients died intraoperatively, four within 48 h and 11 died later. A significant influence for pre-existing risk factors was identified only for cardiovascular diseases. Multiple linear-regression analysis indicated that a haemoglobin <90 g/l, systolic blood pressure <80 mmHg and ECG signs of ischaemia at admission were highly significant risk factors. The cause of death for patients, who died more than 48 h postoperatively, was mainly MOD. All patients with a MOD score >/=4 died (n=7). These patients required 27% of the intensive-care unit (ICU) days of all patients and 72% of the ICU days of the non-survivors. CONCLUSION: patients with ruptured aortic aneurysms from treatment should not be excluded. However, a physiological scoring system after 48 h appears justifiable in order to decide on the appropriateness of continual ICU support.

Reticulocyte dynamic and hemoglobin variability in hemodialysis patients treated with Darbepoetin alfa and C.E.R.A.: a randomized controlled trial.

BACKGROUND: In a simulation based on a pharmacokinetic model we demonstrated that increasing the erythropoiesis stimulating agents (ESAs) half-life or shortening their administration interval decreases hemoglobin variability. The benefit of reducing the administration interval was however lessened by the variability induced by more frequent dosage adjustments. The purpose of this study was to analyze the reticulocyte and hemoglobin kinetics and variability under different ESAs and administration intervals in a collective of chronic hemodialysis patients. METHODS: The study was designed as an open-label, randomized, four-period cross-over investigation, including 30 patients under chronic hemodialysis at the regional hospital of Locarno (Switzerland) in February 2010 and lasting 2 years. Four subcutaneous treatment strategies (C.E.R.A. every 4 weeks Q4W and every 2 weeks Q2W, Darbepoetin alfa Q4W and Q2W) were compared with each other. The mean square successive difference of hemoglobin, reticulocyte count and ESAs dose was used to quantify variability. We distinguished a short- and a long-term variability based respectively on the weekly and monthly successive difference. RESULTS: No difference was found in the mean values of biological parameters (hemoglobin, reticulocytes, and ferritin) between the 4 strategies. ESAs type did not affect hemoglobin and reticulocyte variability, but C.E.R.A induced a more sustained reticulocytes response over time and increased the risk of hemoglobin overshooting (OR 2.7, p = 0.01). Shortening the administration interval lessened the amplitude of reticulocyte count fluctuations but resulted in more frequent ESAs dose adjustments and in amplified reticulocyte and hemoglobin variability. Q2W administration interval was however more favorable in terms of ESAs dose, allowing a 38% C.E.R.A. dose reduction, and no increase of Darbepoetin alfa. CONCLUSIONS: The reticulocyte dynamic was a more sensitive marker of time instability of the hemoglobin response under ESAs therapy. The ESAs administration interval had a greater impact on hemoglobin variability than the ESAs type. The more protracted reticulocyte response induced by C.E.R.A. could explain both, the observed higher risk of overshoot and the significant increase in efficacy when shortening its administration interval.Trial registrationClinicalTrials.gov NCT01666301.

Application in the STRATHE trial of a score system to compare the efficacy and the tolerability of different therapeutic strategies in the management of hypertension

A score system integrating the evolution of efficacy and tolerability over time was applied to a subpopulation of the STRATHE trial, a trial performed according to a parallel group design, with a double-blind, random allocation to either a fixed-dose combination strategy (perindopril/indapamide 2 mg/0.625 mg, with the possibility to increase the dose to 3 mg/0.935 mg, and 4 mg/1.250 mg if needed, n = 118), a sequential monotherapy approach (atenolol 50 mg, followed by losartan 50 mg and amlodipine 5 mg if needed, n = 108), or a stepped-care strategy (valsartan 40 mg, followed by valsartan 80 mg and valsartan 80 mg+ hydrochlorothiazide 12.5 mg if needed, n = 103). The aim was to lower blood pressure below 140/90 mmHg within a 9-month period. The treatment could be adjusted after 3 and 6 months. Only patients in whom the study protocol was strictly applied were included in this analysis. At completion of the trial the total score averaged 13.1 +/- 70.5 (mean +/- SD) using the fixed-dose combination strategy, compared with -7.2 +/- 81.0 using the sequential monotherapy approach and -17.5 +/- 76.4 using the stepped-care strategy. In conclusion, the use of a score system allows the comparison of antihypertensive therapeutic strategies, taking into account at the same time efficacy and tolerability. In the STRATHE trial the best results were observed with the fixed-dose combination containing low doses of an angiotensin enzyme converting inhibitor (perindopril) and a diuretic (indapamide).