Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways.

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKß independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.

4-Octyl itaconate reduces influenza A replication by targeting the nuclear export protein CRM1.

IMPORTANCE: Itaconate derivates, as well as the naturally produced metabolite, have been proposed as antivirals against influenza virus. Here, the mechanism behind the antiviral effects of exogenous 4-octyl itaconate (4-OI), a derivative of itaconate, against the influenza A virus replication is demonstrated. The data indicate that 4-OI targets the cysteine at position 528 of the CRM1 protein, resulting in inhibition of the nuclear export of viral ribonucleoprotein complexes in a similar manner as previously described for other selective inhibitors of nuclear export. These results postulate a mechanism not observed before for this immuno-metabolite derivative. This knowledge is helpful for the development of derivatives of 4-OI as potential antiviral and anti-inflammatory therapeutics.

Dimethyl fumarate and 4-octyl itaconate are anticoagulants that suppress Tissue Factor in macrophages via inhibition of Type I Interferon.

Excessive inflammation-associated coagulation is a feature of infectious diseases, occurring in such conditions as bacterial sepsis and COVID-19. It can lead to disseminated intravascular coagulation, one of the leading causes of mortality worldwide. Recently, type I interferon (IFN) signaling has been shown to be required for tissue factor (TF; gene name F3) release from macrophages, a critical initiator of coagulation, providing an important mechanistic link between innate immunity and coagulation. The mechanism of release involves type I IFN-induced caspase-11 which promotes macrophage pyroptosis. Here we find that F3 is a type I IFN-stimulated gene. Furthermore, F3 induction by lipopolysaccharide (LPS) is inhibited by the anti-inflammatory agents dimethyl fumarate (DMF) and 4-octyl itaconate (4-OI). Mechanistically, inhibition of F3 by DMF and 4-OI involves suppression of Ifnb1 expression. Additionally, they block type I IFN- and caspase-11-mediated macrophage pyroptosis, and subsequent TF release. Thereby, DMF and 4-OI inhibit TF-dependent thrombin generation. In vivo, DMF and 4-OI suppress TF-dependent thrombin generation, pulmonary thromboinflammation, and lethality induced by LPS, E. coli, and S. aureus, with 4-OI additionally attenuating inflammation-associated coagulation in a model of SARS-CoV-2 infection. Our results identify the clinically approved drug DMF and the pre-clinical tool compound 4-OI as anticoagulants that inhibit TF-mediated coagulopathy via inhibition of the macrophage type I IFN-TF axis.

Social competence improves the performance of biomimetic robots leading live fish.

Collective motion is commonly modeled with static interaction rules between agents. Substantial empirical evidence indicates, however, that animals may adapt their interaction rules depending on a variety of factors and social contexts. Here, we hypothesized that leadership performance is linked to the leader's responsiveness to the follower's actions and we predicted that a leader is followed longer if it adapts to the follower's avoidance movements. We tested this prediction with live guppies that interacted with a biomimetic robotic fish programmed to act as a 'socially competent' leader. Fish that were avoiding the robot were approached more carefully in future approaches. In two separate experiments we then asked how the leadership performance of the socially competent robot leader differed to that of a robot leader that either approached all fish in the same, non-responsive, way or one that did change its approach behavior randomly, irrespective of the fish's actions. We found that (1) behavioral variability itself appears attractive and that socially competent robots are better leaders which (2) require fewer approach attempts to (3) elicit longer average following behavior than non-competent agents. This work provides evidence that social responsiveness to avoidance reactions plays a role in the social dynamics of guppies. We showcase how social responsiveness can be modeled and tested directly embedded in a living animal model using adaptive, interactive robots.

Polyamine metabolism is a central determinant of helper T cell lineage fidelity.

Polyamine synthesis represents one of the most profound metabolic changes during T cell activation, but the biological implications of this are scarcely known. Here, we show that polyamine metabolism is a fundamental process governing the ability of CD4+ helper T cells (TH) to polarize into different functional fates. Deficiency in ornithine decarboxylase, a crucial enzyme for polyamine synthesis, results in a severe failure of CD4+ T cells to adopt correct subset specification, underscored by ectopic expression of multiple cytokines and lineage-defining transcription factors across TH cell subsets. Polyamines control TH differentiation by providing substrates for deoxyhypusine synthase, which synthesizes the amino acid hypusine, and mice in which T cells are deficient for hypusine develop severe intestinal inflammatory disease. Polyamine-hypusine deficiency caused widespread epigenetic remodeling driven by alterations in histone acetylation and a re-wired tricarboxylic acid (TCA) cycle. Thus, polyamine metabolism is critical for maintaining the epigenome to focus TH cell subset fidelity.

Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatinum in patients with HER2-negative breast cancer and homologous recombination deficiency (GeparOLA study).

BACKGROUND: The efficacy and toxicity of olaparib as combination therapy in early breast cancer (BC) patients with homologous recombinant deficiency (HRD) [score high and/or germline (g) or tumour (t) BRCA1/2 mutation] is not well described. GeparOLA (ClinicalTrials.gov, NCT02789332) investigated olaparib in combination with paclitaxel in HER2-negative early BC with HRD. PATIENTS AND METHODS: Patients with untreated primary HER2-negative cT2-cT4a-d or cT1c with either cN+ or pNSLN+ or cT1c and triple-negative breast cancer (TNBC) or cT1c and Ki-67>20% BC with HRD were randomised either to paclitaxel (P) 80 mg/m2 weekly plus olaparib (O) 100 mg twice daily for 12 weeks or P plus carboplatinum (Cb) area under the curve 2 weekly for 12 weeks, both followed by epirubicin/cyclophosphamide (EC). Stratification factors were hormone receptor (HR) status (HR+ versus HR-) and age (<40 versus ≥40 years). The primary endpoint was pathological complete response (pCR; ypT0/is ypN0). A two-sided one-group χ2-test was planned to exclude a pCR rate of ≤55% in the PO-EC arm. Secondary end points were other pCR definitions, breast conservation rate, clinical/imaging response, tolerability and safety. RESULTS: A total of 107 patients were randomised between September 2016 and July 2018; 106 (PO N = 69; PCb N = 37) started treatment. Median age was 47.0 years (range 25.0-71.0); 36.2% had cT1, 61.0% cT2, 2.9% cT3, and 31.8% cN-positive tumours; grade 3 tumours: 86.8%; Ki-67>20%: 89.6%; TNBC: 72.6%; confirmed gBRCA1/2 mutation: 56.2%. The pCR rate with PO was 55.1% [90% confidence interval (CI) 44.5% to 65.3%] versus PCb 48.6% (90% CI 34.3% to 63.2%). Analysis for the stratified subgroups showed higher pCR rates with PO in the cohorts of patients <40 years and HR+ patients. CONCLUSION: GeparOLA could not exclude a pCR rate of ≤55% in the PO arm. PO was significantly better tolerated and the combination merits further evaluation.

Bridging the gap - a new role for STAT3 in TLR4-mediated metabolic reprogramming.

Balic et al. describe a new role for STAT3 in TLR4 signalling in macrophages, linking LPS mediated activation of this innate immune receptor to phosphorylation of mitochondrial STAT3, resulting in distinct metabolic reprogramming.

Metabolite Transporters as Regulators of Immunity.

In the past decade, the rise of immunometabolism has fundamentally reshaped the face of immunology. As the functions and properties of many (immuno)metabolites have now been well described, their exchange among cells and their environment have only recently sparked the interest of immunologists. While many metabolites bind specific receptors to induce signaling cascades, some are actively exchanged between cells to communicate, or induce metabolic reprograming. In this review, we give an overview about how active metabolite transport impacts immune cell function and shapes immunological responses. We present some examples of how specific transporters feed into metabolic pathways and initiate intracellular signaling events in immune cells. In particular, we focus on the role of metabolite transporters in the activation and effector functions of T cells and macrophages, as prototype adaptive and innate immune cell populations.

Guppies Prefer to Follow Large (Robot) Leaders Irrespective of Own Size.

Body size is often assumed to determine how successfully an individual can lead others with larger individuals being better leaders than smaller ones. But even if larger individuals are more readily followed, body size often correlates with specific behavioral patterns and it is thus unclear whether larger individuals are more often followed than smaller ones because of their size or because they behave in a certain way. To control for behavioral differences among differentially-sized leaders, we used biomimetic robotic fish (Robofish) of different sizes. Live guppies (Poecilia reticulata) are known to interact with Robofish in a similar way as with live conspecifics. Consequently, Robofish may serve as a conspecific-like leader that provides standardized behaviors irrespective of its size. We asked whether larger Robofish leaders are preferentially followed and whether the preferences of followers depend on own body size or risk-taking behavior ("boldness"). We found that live female guppies followed larger Robofish leaders in closer proximity than smaller ones and this pattern was independent of the followers' own body size as well as risk-taking behavior. Our study shows a "bigger is better" pattern in leadership that is independent of behavioral differences among differentially-sized leaders, followers' own size and risk-taking behavior.

Trimethylamine-N-oxide is elevated in the acute phase after ischaemic stroke and decreases within the first days.

BACKGROUND AND PURPOSE: Trimethylamine-N-oxide (TMAO) is a biomarker of the gut microbiome and correlates with the risk of cardiovascular diseases. However, conflicting data exist on the specific role of TMAO in ischaemic stroke patients. We aimed to analyze the time course of TMAO levels in stroke patients compared with controls. METHODS: In this prospective, case-control study, patients suffering from ischaemic stroke (onset <24 h) and control patients with less than two cardiovascular risk factors were enrolled. Plasma TMAO levels were analyzed on admission, after 48 h and after 3 months. The primary endpoint was the difference in TMAO levels on admission between stroke patients and controls. RESULTS: A total of 196 patients with ischaemic stroke and 100 controls were included between February 2018 and April 2019. Plasma TMAO levels on admission were significantly higher in stroke patients than in controls [median value 4.09 (2.87-6.49) vs. 3.16 (2.08-5.16) µmol/L, P = 0.001]. There was a significant decrease in TMAO levels in stroke patients after 48 h [median at 48 h, 3.49 (2.30-5.39) µmol/L, P = 0.027]. TMAO levels increased again 3 months after stroke [median 4.23 (2.92-8.13) µmol/L, P = 0.047]. In controls, TMAO levels did not change between admission and after 48 h [median at 48 h, 3.14 (1.63-4.61) µmol/L, P = 0.11]. An inverse correlation between TMAO values and kidney function was found (Spearman rho -0.334, P < 0.001). CONCLUSIONS: Our study emphasizes the importance of the time course of TMAO levels after ischaemic stroke. Future studies should define the time point of TMAO analysis, preferably in the acute phase (<24 h).

Colour Doppler sonography in the preoperative assessment of the vascular pedicle from the anterolateral thigh flap: proposal for a mathematical formula to predict pedicle length.

INTRODUCTION: The anterolateral thigh flap (ALT) is one of the most commonly used grafts in head and neck reconstructive surgery. In this type of surgery, it is essential that the vascular pedicle be long enough to ensure proper vascular anastomosis. However, it is difficult to accurately estimate the pedicle length preoperatively. In this context, the current study had two aims: (1) to assess the value of colour Doppler sonography (CDS) in the preoperative assessment of the vascular pedicle and (2) to develop a mathematical model to predict the length of the vascular pedicle based on the ultrasound findings. MATERIALS AND METHODS: Retrospective review of patients who underwent primary surgery for head and neck cancer followed by ALT flap reconstruction at our institution from 2014 to 2018. All patients underwent CDS prior to surgical excision of the flap. RESULTS: Preoperative CDS was useful to identify the location of the vascular perforators, to estimate the pedicle length, and to identify the vascularization variant. Using the proposed mathematical formula, the estimated minimum pedicle length and actual length agreed in 73.9% of cases, increasing to 84.1% when a 5 mm margin of error was allowed. Moreover, preoperative ultrasound accurately distinguished the two anatomical variants of the ALT vasculature in nearly all cases (97.1%). CONCLUSION: This study confirms the value of preoperative colour Doppler sonography for ALT flap reconstruction. The proposed mathematical model provides a highly accurate method of preoperatively assessing the length of the vascular pedicle, which may be of value in head and neck surgery.

Insights into the Social Behavior of Surface and Cave-Dwelling Fish (Poecilia mexicana) in Light and Darkness through the Use of a Biomimetic Robot.

Biomimetic robots (BRs) are becoming more common in behavioral research and, if they are accepted as conspecifics, allow for new forms of experimental manipulations of social interactions. Nevertheless, it is often not clear which cues emanating from a BR are actually used as communicative signals and how species or populations with different sensory makeups react to specific types of BRs. We herein present results from experiments using two populations of livebearing fishes that differ in their sensory capabilities. In the South of Mexico, surface-dwelling mollies (Poecilia mexicana) successfully invaded caves and adapted to dark conditions. While almost without pigment, these cave mollies possess smaller but still functional eyes. Although previous studies found cave mollies to show reduced shoaling preferences with conspecifics in light compared to surface mollies, it is assumed that they possess specialized adaptations to maintain some kind of sociality also in their dark habitats. By testing surface- and cave-dwelling mollies with RoboFish, a BR made for use in laboratory experiments with guppies and sticklebacks, we asked to what extent visual and non-visual cues play a role in their social behavior. Both cave- and surface-dwelling mollies followed the BR as well as a live companion when tested in light. However, when tested in darkness, only surface-dwelling fish were attracted by a live conspecific, whereas cave-dwelling fish were not. Neither cave- nor surface-dwelling mollies were attracted to RoboFish in darkness. This is the first study to use BRs for the investigation of social behavior in mollies and to compare responses to BRs both in light and darkness. As our RoboFish is accepted as conspecific by both used populations of the Atlantic molly only under light conditions but not in darkness, we argue that our replica is providing mostly visual cues.

[The concept of small volume resuscitation for preclinical trauma management. Experiences in the Air Rescue Service]. / Das Konzept der "small volume resuscitation" im Rahmen des präklinischen Traumamanagements. Erfahrungen im Luftrettungsdienst

BACKGROUND: Prompt hemorrhage control and adequate fluid resuscitation are the key components of early trauma care. However, the optimal resuscitation strategy remains controversial. In this context the small volume resuscitation (SVR) concept with hypertonic-hyperoncotic solutions is a new strategy. PATIENTS AND METHODS: This was a retrospective study in the Helicopter Emergency Medical Service over a 5-year period. Included were all major trauma victims if they were candidates for SVR (initially 4 ml HyperHaes/kg body weight, followed by conventional fluid resuscitation with crystalloids and colloids). Demographic data, type and cause of injury and injury severity score (ISS) were recorded and the amount of fluid volume and the hemodynamic profile were analyzed. Negative side-effects as well as sodium chloride serum levels on hospital admission were recorded. RESULTS: A total of 342 trauma victims (male 70.2%, mean age 39.0 ± 18.8 years, ISS 31.6 ± 16.9, ISS>16, 81.6%) underwent prehospital SVR. A blunt trauma mechanism was predominant (96.8%) and the leading cause of injury was motor vehicle accidents (61.5%) and motorcycle accidents (22.3%). Multiple trauma and polytrauma were noted in 87.4% of the cases. Predominant was traumatic brain injury (73.1%) as well as chest injury (73.1%) followed by limb injury (69.9%) and abdominal/pelvic trauma (45.0%). Within the whole study group in addition to 250 ml HyperHaes, mean volumes of 1214 ± 679 ml lactated Ringers and 1288 ± 954 ml hydroxethylstarch were infused during the prehospital treatment phase. There were no statistically significant differences in the amount of crystalloids and colloids infused regarding the subgroups multisystem trauma (ISS>16), severe traumatic brain injury (GCS<9) and entrapment trauma compared to the total study group. In patients with an initial systolic blood pressure (SBP) >80 mmHg significantly less colloids (1035 ± 659 ml vs. 1288 ± 954 ml, p<0.006) were infused, whereas in patients with an initial SBP ≤ 80 mmHg significantly more colloids were infused (1609 ± 1159 ml vs. 1288 ± 954 ml, p<0.002). There was a statistically significant increase in systolic as well as diastolic blood pressure at all times of blood pressure measurement during prehospital treatment after bolus infusion of HyperHaes within the whole study group. The same applies to the subgroups multisystem trauma, severe traumatic brain injury and entrapment trauma. Minor negative side-effects were observed in 4 cases (1.2%). The mean serum sodium chloride profile on hospital admission was 146.9 ± 5.0 mmol/l, the base excess (BE) was -5.7 ± 5.3 mmol/l) and the pH was 7.3 ± 0.1. CONCLUSION: The concept of small volume resuscitation provides early and effective hemodynamic control. Clinical side-effects associated with bolus infusion of hypertonic-hyperoncotic solutions are rare.

[Extended medical quality management exemplified by the tracer diagnosis multiple trauma. Pilot study in the air rescue service]. / Erweitertes medizinisches Qualitätsmanagement am Beispiel der "Tracer"-Diagnose "Polytrauma". Pilotstudie aus dem Bereich des Luftrettungsdienstes.

BACKGROUND: Adequate prehospital and inhospital primary care is a decisive factor in the successful treatment of multiple trauma patients. For optimization of treatment algorithms the implementation of a medical quality management is of utmost importance. The aim of this study was to extend quality management by including data on process quality. METHODS: A retrospective study of primary rescue missions of the Helicopter Emergency Medical Service (HEMS) Christoph 22 in Ulm over a period of 2.5 years was performed. In a detailed analysis of filter criteria, in which relevant deviations from the recommendations (not fulfilled in > 10% of the cases) occurred, process data was included (vital data, measurements and events). RESULTS: In the study population (n = 298, males 71.8%, mean age 39.8 ± 21.8 years) 2 filter criteria were identified in which relevant deviations where observed: time management where prehospital treatment time ≤ 60 min in 36% of the cases was not fulfilled and circulatory management where the systolic blood pressure, detected with Riva-Rocci method (RR(sys)) ≥ 120 mmHg on hospital admission in patients with severe head trauma was not fulfilled in 45% of the cases. In patients with deviations in time management, prehospital treatment time was prolonged (75.6 ± 18.3 min versus 50.5 ± 6.7 min; p < 0.01) caused by a prolonged on scene attendance time (34.1 ± 22.1 min versus 20.6 ± 9.2 min; p < 0.01) and transport time (17.3 ± 9.4 min versus 13.3 ± 4.8 min; p < 0.01). In entrapment trauma prehospital treatment time was expanded (44% versus 10%; p < 0.01). Patients in whom circulatory management deviations were observed were more often in shock on arrival at the scene (RR(sys) ≤ 90 mmHg: 60% versus 30%; p < 0.01), more often hypoxemic [pulse oximeter oxygen saturation (S(p)O(2)) ≤ 90%: 36% versus 19%; p < 0.05] and more often sustained a trauma to the chest as well as to chest and abdomen/pelvis (69% versus 52% and 42% versus 28%, respectively; p < 0.05). Furthermore, the infusion volume of colloids was higher (1241 ± 810 ml versus 753 ± 359 ml; p < 0.05) and the combined usage of small volume resuscitation and catecholamines was more often necessary (42% versus 25%; p < 0.05). CONCLUSIONS: Including process data of prehospital mission data recording facilitates an extended medical quality management.

Dissection of mitogenic and neurodegenerative actions of cystine and glutamate in malignant gliomas.

Malignant glioma represents one of the most aggressive and lethal human neoplasias. A hallmark of gliomas is their rapid proliferation and destruction of vital brain tissue, a process in which excessive glutamate release by glioma cells takes center stage. Pharmacologic antagonism with glutamate signaling through ionotropic glutamate receptors attenuates glioma progression in vivo, indicating that glutamate release by glioma cells is a prerequisite for rapid glioma growth. Glutamate has been suggested to promote glioma cell proliferation in an autocrine or paracrine manner, in particular by activation of the (RS)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrate (AMPA) subtype of glutamate receptors. Here, we dissect the effects of glutamate secretion on glioma progression. Glioma cells release glutamate through the amino-acid antiporter system X(c)(-), a process that is mechanistically linked with cystine incorporation. We show that disrupting glutamate secretion by interfering with the system X(c)(-) activity attenuates glioma cell proliferation solely cystine dependently, whereas glutamate itself does not augment glioma cell growth in vitro. Neither AMPA receptor agonism nor antagonism affects glioma growth in vitro. On a molecular level, AMPA insensitivity is concordant with a pronounced transcriptional downregulation of AMPA receptor subunits or overexpression of the fully edited GluR2 subunit, both of which block receptor activity. Strikingly, AMPA receptor inhibition in tumor-implanted brain slices resulted in markedly reduced tumor progression associated with alleviated neuronal cell death, suggesting that the ability of glutamate to promote glioma progression strictly requires the tumor microenvironment. Concerning a potential pharmacotherapy, targeting system X(c)(-) activity disrupts two major pathophysiological properties of glioma cells, that is, the induction of excitotoxic neuronal cell death and incorporation of cystine required for rapid proliferation.

[Primary documentation quality for paper-assisted digital mission data documentation. Initial results from the air rescue service]. / Primäre Dokumentationsqualität bei papiergestützter digitaler Einsatzdokumentation. Erste Ergebnisse aus dem Luftrettungsdienst.

BACKGROUND: With the assistance of digital pen and paper technology in the field of prehospital data reporting, it seems to be possible to fulfill the requirements of "documentation" as well as the requirements of "quality management". The aim of this study was to determine the "primary documentation quality" (PDQ) of a data reporting system based on digital pen and paper technology (so-called DINO) within a helicopter emergency medical service (HEMS) over a 6-month period. RESULTS: The PDQ is defined as the proportion of prehospital documented data, which is primarily recorded correctly by the data reporting system. For the national uniform core dataset (so-called MIND2) the PDQ was 96.7%, for "checkbox" and "numeric data fields" the PDQ was 99.8% and 93.6%, respectively and for "vital data" the PDQ was 96.7% [heart rate (HF), measurement of blood pressure] and 84.1% [peripheral oxygen saturation (S(p)O2), end tidal carbon dioxide concentration (etCO2), oxygen administration (O2)]. For "measurements" the PDQ was 96.9% (time stamps) and 86.9% (time frames), for "drugs" the PDQ was 43.6% (drug name) and 69.8% (drug dosage) and for"placement of infusion" 42% (infusion name) and 85.3% (infusion time), respectively. The average time for the "verification process" after mission completion was 1.5+/-0.4 min/mission. CONCLUSIONS: The "primary documentation quality" of prehospital mission data reporting with the assistance of a digital pen and paper based documentation system (DINO) has been shown to completely fulfill the requirements of rapid and safe data documentation in actual missions, even at this early stage of development.

[Paper-assisted digital Mission documentation in air rescue services. Quality management in preclinical emergency medicine]. / Papiergestützte digitale Einsatzdokumentation im Luftrettungsdienst. Qualitätsmanagement in der präklinischen Notfallmedizin.

BACKGROUND: Recording of adequate mission data is of utmost importance in prehospital emergency medicine. For this, a nationwide uniform core dataset for prehospital data reporting, the so-called MIND 2, was introduced. With this procedure adequate information about structure and outcome quality, but only little information about process quality, can be obtained. Regarding the quality of data recording, primarily computer-based techniques are superior to other techniques. Against this background, the aim of this study was to develop a documentation system, which sets new standards regarding documentation dataset and documentation quality. RESULTS: A primarily computer-based documentation system based on the "digital paper" technology was achieved. This technology allows conventional data entry via a (digital) pen and documentation on conventional paper. As the core-dataset MIND 2 was realized - furthermore, the measurements performed during prehospital management as well as data on vital signs (blood pressure, heart frequency, S(a)O(2), p(et)CO(2) etc.) were included into routine data recording. Integration of this documentation system into an already existing medical quality management system was achieved via a defined interface. Testing of this new system over a 3-month period at the helicopter emergency medical service (HEMS) "Christoph 22" showed a high degree of functionality and stability of the system. Serious problems, especially a total break-down of the whole system, were not observed during the study period. CONCLUSIONS: The new data recording concept, which is based on the "digital paper" technology, has proven to be completely satisfactory with respect to functionality and documentation quality during the test period.

[Intraosseous puncture in preclinical emergency medicine. Ten years experience in air rescue service]. / Die intraossäre Punktion in der präklinischen Notfallmedizin. 10-jährige Erfahrungen im Luftrettungsdienst.

INTRODUCTION: The intraosseous puncture (IO) is a fast and safe alternative to the puncture of peripheral veins in emergency situations in children < or =6 years of age. The purpose of this paper is to summarize 10 years of experience on the prehospital use of the IO method by the Helicopter Emergency Medical Service (HEMS) "Christoph 22", Ulm. MATERIALS AND METHODS: This was a retrospective study from 1 January 1996 to 31 December 2005. RESULTS: Out of a total of 9,549 missions, the proportion of children was 11.1%. In 27 children (4.2% of the children < or =6 years of age) an IO puncture was performed. Patients of the IO group were younger (1.0 vs. 3.7 years of age; p<0.001) and showed a higher degree of injury severity (NACA 6 vs. 4; p<0.001) compared to the total children group. In all children of the IO group (100%), the intraosseous puncture was the method of first choice to obtain access to the vascular system by the HEMS team. In 96.4% of these cases (26/27), the first IO puncture attempt was successful - in one child, a second puncture attempt was necessary. A standardized puncture technique was performed using the proximal tibia. The time required for successful placement of the IO infusion line was 60 s or less in all cases. In 37% of the cases (10/27) the IO infusion line was used for induction of general anaesthesia; dosage and onset of administered drugs were described as being equivalent to a peripheral infusion line. In all cases, the IO needle was replaced in-hospital within 2 h by a central or peripheral iv line. No complications were observed. CONCLUSIONS: The IO infusion technique is a simple, fast and safe alternative method for emergency access to the vascular system in children < or =6 years of age in the prehospital setting.