Effectiveness of oral versus intravenous tranexamic acid in primary total hip and knee arthroplasty: a randomised, non-inferiority trial.

BACKGROUND: Tranexamic acid (TXA) reduces rates of blood transfusion for total hip arthroplasty (THA) and total knee arthroplasty (TKA). Although the use of oral TXA rather than intravenous (i.v.) TXA might improve safety and reduce cost, it is not clear whether oral administration is as effective. METHODS: This noninferiority trial randomly assigned consecutive patients undergoing primary THA or TKA under neuraxial anaesthesia to either one preoperative dose of oral TXA or one preoperative dose of i.v. TXA. The primary outcome was calculated blood loss on postoperative day 1. Secondary outcomes were transfusions and complications within 30 days of surgery. RESULTS: Four hundred participants were randomised (200 THA and 200 TKA). The final analysis included 196 THA patients (98 oral, 98 i.v.) and 191 TKA patients (93 oral, 98 i.v.). Oral TXA was non-inferior to i.v. TXA in terms of calculated blood loss for both THA (effect size=-18.2 ml; 95% confidence interval [CI], -113 to 76.3; P<0.001) and TKA (effect size=-79.7 ml; 95% CI, -178.9 to 19.6; P<0.001). One patient in the i.v. TXA group received a postoperative transfusion. Complication rates were similar between the two groups (5/191 [2.6%] oral vs 5/196 [2.6%] i.v.; P=1.00). CONCLUSIONS: Oral TXA can be administered in the preoperative setting before THA or TKA and performs similarly to i.v. TXA with respect to blood loss and transfusion rates. Switching from i.v. to oral TXA in this setting has the potential to improve patient safety and decrease costs.

A Novel Analytical Approach to Assessing Sorption of Trace Organic Compounds into Micro- and Nanoplastic Particles.

Assessing the sorption of trace organic compounds (TOrCs) into micro- and nanoplastic particles has traditionally been performed using an aqueous phase analysis or solvent extractions from the particle. Using thermal extraction/desorption-gas chromatography/mass spectrometry (TD-Pyr-GC/MS) offers a possibility to analyze the TOrCs directly from the particle without a long sample preparation. In this study, a combination of two analytical methods is demonstrated. First, the aqueous phase is quantified for TOrC concentrations using Gerstel Twister® and TD-GC/MS. Subsequently, the TOrCs on the particles are analyzed. Different polymer types and sizes (polymethyl methacrylate (PMMA), 48 µm; polyethylene (PE), 48 µm; polystyrene (PS), 41 µm; and PS, 78 nm) were analyzed for three selected TOrCs (phenanthrene, triclosan, and α-cypermethrin). The results revealed that, over a period of 48 h, the highest and fastest sorption occurred for PS 78 nm particles. This was confirmed with a theoretical calculation of the particle surface area. It was also shown for the first time that direct quantification of TOrCs from PS 78 nm nanoparticles is possible. Furthermore, in a mixed solute solution, the three selected TOrCs were sorbed onto the particles simultaneously.

The Perioperative Use of Benzodiazepines for Major Orthopedic Surgery in the United States.

BACKGROUND: Despite numerous indications for perioperative benzodiazepine use, associated risks may be exacerbated in elderly and comorbid patients. In the absence of national utilization data, we aimed to describe utilization patterns using national claims data from total hip/knee arthroplasty patients (THA/TKA), an increasingly older and vulnerable surgical population. METHODS: We included data on 1,863,996 TKAs and 985,471 THAs (Premier Healthcare claims data, 2006-2019). Benzodiazepine utilization (stratified by long- and short-acting agents) was assessed by patient- and health care characteristics, and analgesic regimens. Given the large sample size, standardized differences instead of P values were utilized to signify meaningful differences between groups (defined by value >0.1). RESULTS: Among 1,863,996 TKA and 985,471 THA patients, the utilization rate of benzodiazepines was 80.5% and 76.1%, respectively. In TKA, 72.6% received short-acting benzodiazepines, while 7.9% received long-acting benzodiazepines, utilization rates 68.4% and 7.7% in THA, respectively. Benzodiazepine use was particularly more frequent among younger patients (median age [interquartile range {IQR}]: 66 [60-73]/64 [57-71] among short/long-acting compared to 69 [61-76] among nonusers), White patients (80.6%/85.4% short/long-acting versus 75.7% among nonusers), commercial insurance (36.5%/34.0% short/long-acting versus 29.1% among nonusers), patients receiving neuraxial anesthesia (56.9%/56.5% short/long-acting versus 51.5% among nonusers), small- and medium-sized (≤500 beds) hospitals (68.5% in nonusers, and 74% and 76.7% in short- and long-acting benzodiazepines), and those in the Midwest (24.6%/25.4% short/long-acting versus 16% among nonusers) in TKA; all standardized differences ≥0.1. Similar patterns were observed in THA except for race and comorbidity burden. Notably, among patients with benzodiazepine use, in-hospital postoperative opioid administration (measured in oral morphine equivalents [OMEs]) was substantially higher. This was even more pronounced in patients who received long-acting agents (median OME with no benzodiazepines utilization 192 [IQR, 83-345] vs 256 [IQR, 153-431] with short-acting, and 329 [IQR, 195-540] with long-acting benzodiazepine administration). Benzodiazepine use was also more frequent in patients receiving multimodal analgesia (concurrently 2 or more analgesic modes) and regional anesthesia. Trend analysis showed a persistent high utilization rate of benzodiazepines over the last 14 years. CONCLUSIONS: Based on a representative sample, 4 of 5 patients undergoing major orthopedic surgery in the United States receive benzodiazepines perioperatively, despite concerns for delirium and delayed postoperative neurocognitive recovery. Notably, benzodiazepine utilization was coupled with substantially increased opioid use, which may project implications for perioperative pain management.

Organic Contaminants and Interactions with Micro- and Nano-Plastics in the Aqueous Environment: Review of Analytical Methods.

Micro- and nanoplastic particles are increasingly seen not only as contaminants themselves, but also as potential vectors for trace organic chemicals (TOrCs) that might sorb onto these particles. An analysis of the sorbed TOrCs can either be performed directly from the particle or TOrCs can be extracted from the particle with a solvent. Another possibility is to analyze the remaining concentration in the aqueous phase by a differential approach. In this review, the focus is on analytical methods that are suitable for identifying and quantifying sorbed TOrCs on micro- and nano-plastics. Specific gas chromatography (GC), liquid chromatography (LC) and ultraviolet-visible spectroscopy (UV-VIS) methods are considered. The respective advantages of each method are explained in detail. In addition, influencing factors for sorption in the first place are being discussed including particle size and shape (especially micro and nanoparticles) and the type of polymer, as well as methods for determining sorption kinetics. Since the particles are not present in the environment in a virgin state, the influence of aging on sorption is also considered.

Systematic Development of a Simultaneous Determination of Plastic Particle Identity and Adsorbed Organic Compounds by Thermodesorption-Pyrolysis GC/MS (TD-Pyr-GC/MS).

Micro-, submicro- and nanoplastic particles are increasingly regarded as vectors for trace organic chemicals. In order to determine adsorbed trace organic chemicals on polymers, it has usually been necessary to carry out complex extraction steps. With the help of a newly designed thermal desorption pyrolysis gas chromatography mass spectrometry (TD-Pyr-GC/MS) method, it is possible to identify adsorbed trace organic chemicals on micro-, submicro- and nanoparticles as well as the particle short chain polymers in one analytical setup without any transfers. This ensures a high sample throughput for the qualitative analysis of trace substances and polymer type. Since the measuring time per sample is only 2 h, a high sample throughput is possible. It is one of the few analytical methods which can be used also for the investigation of nanoplastic particles. Initially adsorbed substances are desorbed from the particle by thermal desorption (TD); subsequently, the polymer is fragmented by pyrolysis (PYR). Both particle treatment techniques are directly coupled with the same GC-MS system analyzing desorbed molecules and pyrolysis products, respectively. In this study, we developed a systematic and optimized method for this application. For method development, the trace organic chemicals phenanthrene, α-cypermethrin and triclosan were tested on reference polymers polystyrene (PS), polymethyl methacrylate (PMMA) and polyethylene (PE). Well-defined particle fractions were used, including polystyrene (sub)micro- (41 and 40 µm) and nanoparticles (78 nm) as well as 48-µm sized PE and PMMA particles, respectively. The sorption of phenanthrene (PMMA << PS 40 µm < 41 µm < PE < PS 78 nm) and α-cypermethrin (PS 41 µm < PS 40 µm < PE < PMMA < PS 78 nm) to the particles was strongly polymer-dependent. Triclosan adsorbed only on PE and on the nanoparticles of PS (PE < PS78).

Characteristics of Neuropsychiatric Mobile Health Trials: Cross-Sectional Analysis of Studies Registered on ClinicalTrials.gov.

BACKGROUND: The development of mobile health (mHealth) technologies is progressing at a faster pace than that of the science to evaluate their validity and efficacy. Under the International Committee of Journal Medical Editors (ICMJE) guidelines, clinical trials that prospectively assign people to interventions should be registered with a database before the initiation of the study. OBJECTIVE: The aim of this study was to better understand the smartphone mHealth trials for high-burden neuropsychiatric conditions registered on ClinicalTrials.gov through November 2018, including the number, types, and characteristics of the studies being conducted; the frequency and timing of any outcome changes; and the reporting of results. METHODS: We conducted a systematic search of ClinicalTrials.gov for the top 10 most disabling neuropsychiatric conditions and prespecified terms related to mHealth. According to the 2016 World Health Organization Global Burden of Disease Study, the top 10 most disabling neuropsychiatric conditions are (1) stroke, (2) migraine, (3) major depressive disorder, (4) Alzheimer disease and other dementias, (5) anxiety disorders, (6) alcohol use disorders, (7) opioid use disorders, (8) epilepsy, (9) schizophrenia, and (10) other mental and substance use disorders. There were no date, location, or status restrictions. RESULTS: Our search identified 135 studies. A total of 28.9% (39/135) of studies evaluated interventions for major depressive disorder, 14.1% (19/135) of studies evaluated interventions for alcohol use disorders, 12.6% (17/135) of studies evaluated interventions for stroke, 11.1% (15/135) of studies evaluated interventions for schizophrenia, 8.1% (11/135) of studies evaluated interventions for anxiety disorders, 8.1% (11/135) of studies evaluated interventions for other mental and substance use disorders, 7.4% (10/135) of studies evaluated interventions for opioid use disorders, 3.7% (5/135) of studies evaluated interventions for Alzheimer disease or other dementias, 3.0% (4/135) of studies evaluated interventions for epilepsy, and 3.0% (4/135) of studies evaluated interventions for migraine. The studies were first registered in 2008; more than half of the studies were registered from 2016 to 2018. A total of 18.5% (25/135) of trials had results reported in some publicly accessible location. Across all the studies, the mean estimated enrollment (reported by the study) was 1078, although the median was only 100. In addition, across all the studies, the actual reported enrollment was lower, with a mean of 249 and a median of 80. Only about a quarter of the studies (35/135, 25.9%) were funded by the National Institutes of Health. CONCLUSIONS: Despite the increasing use of health-based technologies, this analysis of ClinicalTrials.gov suggests that only a few apps for high-burden neuropsychiatric conditions are being clinically evaluated in trials.

UV-C Irradiation of Rolled Fillets of Ham Inoculated with Yersinia enterocolitica and Brochothrix thermosphacta.

Bacteria on ready-to-eat meat may cause diseases and lead to faster deterioration of the product. In this study, ready-to-eat sliced ham samples were inoculated with Yersinia enterocolitica or Brochothrix thermosphacta and treated with ultraviolet (UV) light. The initial effect of a UV-C irradiation was investigated with doses of 408, 2040, 4080, and 6120 mJ/cm2 and the effect after 0, 7, and 14 days of refrigerated storage with doses of 408 and 4080 mJ/cm2. Furthermore, inoculated ham samples were stored under light and dark conditions after the UV-C treatment to investigate the effect of photoreactivation. To assess the ham quality the parameters color and antioxidant capacity were analyzed during storage. UV-C light reduced Yersinia enterocolitica and Brochothrix thermosphacta counts by up to 1.11 log10 and 0.79 log10 colony forming units/g, respectively, during storage. No photoreactivation of the bacteria was observed. Furthermore, significantly lower a* and higher b* values after 7 and 14 days of storage and a significantly higher antioxidant capacity on day 0 after treatment with 4080 mJ/cm2 were detected. However, there were no other significant differences between treated and untreated samples. Hence, a UV-C treatment can reduce microbial surface contamination of ready-to-eat sliced ham without causing considerable quality changes.

Modulation of PAH toxicity on the freshwater organism G. roeseli by microparticles.

Polycyclic aromatic hydrocarbons are widespread and environmentally persistent chemicals that readily bind to particles in air, soil and sediment. Plastic particles, which are also an ubiquitous global contamination problem, may thus modulate their environmental fate and ecotoxicity. First, the acute aqueous toxicity of phenanthrene in adult Gammarus roeseli was determined with a LC50 of 471 µg/L after 24 h and 441 µg/L after 48 h. Second, considering lethal and sublethal endpoints, effects of phenanthrene concentration on G. roeseli were assessed in relation to the presence of anthropogenic and natural particles. The exposure of gammarids in presence of either particle type with phenanthrene resulted after 24 and 48 h in reduced effect size. Particle exposure alone did not result in any effects. The observed reduction of phenanthrene toxicity by polyamide contradicts the discussion of microplastics acting as a vector or synergistically. Especially, no difference in modulation by plastic particles and naturally occurring sediment particles was measured. These findings can most likely be explained by the similar adsorption of phenanthrene to both particle types resulting in reduced bioavailability.

Inactivation of Yersinia enterocolitica and Brochothrix thermosphacta on pork by UV-C irradiation.

Ultraviolet (UV) irradiation has gained interest as a decontamination method for food for several years. This study investigated how UV-C affected the microbial load of pork, inoculated with Yersinia (Y.) enterocolitica and Brochothrix (B.) thermosphacta. The initial effect as well as the effect after 1, 7 and 14 days of storage were investigated. Additionally, the meat quality parameters color, pH value, myoglobin redox form percentages and antioxidant capacity were analyzed. During storage, the bacterial load on pork was significantly reduced up to 1.2 log10 using doses of 408 or 2040 mJ/cm2. In contrast to this, in vitro experiments with bacterial suspensions showed that calculated UV doses of 16.16 and 19.30 mJ/cm2 resulted in a 3.0 log10 reduction of Y. enterocolitica and B. thermosphacta, respectively. The analyzed meat quality parameters were not influenced by UV-C treatment. Hence, UV-C light can reduce microbial surface contamination without negatively affecting meat quality.

Low concordance between surgical and radiological assessment of degree of resection and treatment-related hypothalamic damage: results of KRANIOPHARYNGEOM 2007.

BACKGROUND: Assessment of presurgical hypothalamic involvement (psHI) and treatment-related hypothalamic damage (trHD) is relevant for the decision on risk-adapted treatment and rehabilitation strategies in craniopharyngioma. PATIENTS AND METHODS: 129 surgical reports of childhood-onset craniopharyngioma patients recruited 2007-2014 in KRANIOPHARYNGEOM 2007 were analyzed. Data on psHI were available based on surgeon's (63%), reference neuroradiologist's (95%), and local radiologist's (23%) assessment. The surgical degree of resection (DoR) was assessed by neurosurgeon (95%), reference neuroradiologist (73%), and local radiologist (61%). TrHD was assessed by neurosurgeon (33%), by reference neuroradiologist (95%), and by local radiologist (2%). Neurosurgical center size was categorized based on patient load. RESULTS: Surgical assessments on psHI (n = 78), DoR (n = 89) and trHD (n = 42) as documented in surgical reports could be compared with the assessment of respective parameters by reference neuroradiologist. Differences with regard to DoR (p = 0.0001) and trHD (p < 0.0001) were detectable between surgeon's and reference neuroradiologist's assessment, whereas psHI was assessed similarly. Concordance for DoR and trHD was observed in 48 and 62%, respectively. Surgeons estimated a higher rate of complete resections and a lower rate of trHD. Neuroradiological reference assessment of trHD had higher predictive value for hypothalamic sequelae then surgical assessment. Observed differences were not related to neurosurgical center size. CONCLUSIONS: Observed differences between surgical and neuroradiological estimation of risk factors in craniopharyngioma support the necessity of neuroradiological reference review to assure standards of quality. This could be established by central internet-based neuroradiological review in KRANIOPHARYNGEOM 2007. Standardization of surgical reports including specific assessment of tumor/damage location is recommended.

First experiences with neuropsychological effects of oxytocin administration in childhood-onset craniopharyngioma.

PURPOSE: The hypothalamic hormone oxytocin plays a major role in regulation of behavior and body composition. Quality of survival is frequently impaired in childhood craniopharyngioma patients due to sequelae such as behavioral deficits and severe obesity caused by tumor or treatment-related hypothalamic lesions. METHODS: In our pilot cross-sectional study, we analyzed emotion recognition abilities and oxytocin concentrations in saliva and urine before and after single nasal administration of 24 IU oxytocin in 10 craniopharyngioma patients. Four craniopharyngioma presented with grade I lesions (limited to anterior hypothalamic areas) and 6 craniopharyngioma with grade II lesions (involving mammillary bodies and posterior hypothalamic areas). Emotional tasks were assessed before and after administration of oxytocin using the Geneva multimodal emotion portrayals corpus and the Multidimensional Mood Questionnaire. RESULTS: All patients presented with detectable levels of oxytocin before administration. Nasal administration of oxytocin was well-tolerated and resulted in increased oxytocin concentrations in saliva and urine. After oxytocin administration, craniopharyngioma patients with postsurgical lesions limited to the anterior hypothalamus area showed improvements in emotional identifications compared to craniopharyngioma patients with lesions of anterior and posterior hypothalamic areas. Focusing on correct assignments to positive and negative emotion categories, craniopharyngioma patients improved assignment to negative emotions. CONCLUSIONS: Oxytocin might have positive effects on emotion perception in craniopharyngioma patients with specific lesions of the anterior hypothalamic area. Further studies on larger cohorts are warranted.

Nuchal Skinfold Thickness: A Novel Parameter for Assessment of Body Composition in Childhood Craniopharyngioma.

CONTEXT: Hypothalamic obesity, cardiovascular disease (CVD), and relapse/progression have a major impact on prognosis in childhood-onset craniopharyngioma (CP). We analyzed nuchal skinfold thickness (NST) on magnetic resonance imaging performed for follow-up monitoring as a novel parameter for body composition (BC) and CVD in CP. OBJECTIVE: The objective of the study was to identify the association of NST with body mass index (BMI), waist to height ratio (WHtR), functional capacity, and blood pressure (BP) in CP and controls. DESIGN: This was a cross-sectional and longitudinal prospective study in CP patients. SETTING: The study was conducted at HIT-Endo, KRANIOPHARYNGEOM 2000/2007. PATIENTS: Participants included 94 CP patients and 75 controls. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: Association of NST with BC and BP in 43 CP and 43 controls was measured. RESULTS: NST correlated with BMI SD score (SDS; r = 0.78; P < .001; n = 169) and WHtR (r = 0.85; P < .001; n = 86) in the total cohort and CP patients (NST-BMI SDS: r = 0.77, P < .001, n = 94); NST-WHtR: r = 0.835, P < .001, n=43) and controls (NST-BMI SDS: r = 0.792, P < .001, n = 75; NST-WHtR: r = 0.671, P < .001, n = 43). In CP, systolic BP correlated with NST (r = 0.575, P < .001), BMI SDS (r = 0.434, P = .004), and WHtR (r = 0.386, P = .011). Similar results were observed for diastolic BP in CP. In multivariate analyses, NST had a predictive value for hypertension in postpubertal CP and controls (odds ratio 6.98, 95% confidence interval [1.65, 29.5], P = .008). During a longitudinal follow-up, changes in NST correlated with changes in BMI SDS (P < .001) and WHtR (P = .01) but not with changes in BP and functional capacity. CONCLUSIONS: Because monitoring of magnetic resonance imaging and BC is essential for follow-up in CP, NST could serve as a novel and clinically relevant parameter for longitudinal assessment of BC and CVD risk in CP.

Oxytocin in survivors of childhood-onset craniopharyngioma.

Quality of survival of childhood-onset craniopharyngioma patients is frequently impaired by hypothalamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits. Oxytocin, a peptide hormone produced in the hypothalamus and secreted by posterior pituitary gland, plays a major role in regulation of behavior and body composition. In a cross-sectional study, oxytocin saliva concentrations were analyzed in 34 long-term craniopharyngioma survivors with and without hypothalamic involvement or treatment-related damage, recruited in the German Childhood Craniopharyngioma Registry, and in 73 healthy controls, attending the Craniopharyngioma Support Group Meeting 2014. Oxytocin was measured in saliva of craniopharyngioma patients and controls before and after standardized breakfast and associations with gender, body mass index, hypothalamic involvement, diabetes insipidus, and irradiation were analyzed. Patients with preoperative hypothalamic involvement showed similar oxytocin levels compared to patients without hypothalamic involvement and controls. However, patients with surgical hypothalamic lesions grade 1 (anterior hypothalamic area) presented with lower levels (p = 0.017) of oxytocin under fasting condition compared to patients with surgical lesion of posterior hypothalamic areas (grade 2) and patients without hypothalamic lesions (grade 0). Craniopharyngioma patients' changes in oxytocin levels before and after breakfast correlated (p = 0.02) with their body mass index. Craniopharyngioma patients continue to secrete oxytocin, especially when anterior hypothalamic areas are not involved or damaged, but oxytocin shows less variation due to nutrition. Oxytocin supplementation should be explored as a therapeutic option in craniopharyngioma patients with hypothalamic obesity and/or behavioral pathologies due to lesions of specific anterior hypothalamic areas. Clinical trial number: KRANIOPHARYNGEOM 2000/2007(NCT00258453; NCT01272622).

Fusiform dilatation of the internal carotid artery in childhood-onset craniopharyngioma: multicenter study on incidence and long-term outcome.

PURPOSE: Fusiform dilatations of the internal carotid artery (FDCA) represent a vascular complication following surgery for suprasellar tumors in children. Incidence rate and long-term prognosis of FDCA in terms of survival rates, vascular complications, and quality of survival are unknown for patients with childhood-onset craniopharyngioma. METHODS: Magnetic resonance imaging (MRI) results of 583 patients with childhood-onset craniopharyngioma, recruited from 2001 to 2015 in the German Childhood Craniopharyngioma Registry, were reviewed for FDCA. Risk factors for FDCA and long-term outcome after FDCA were analyzed. RESULTS: Fourteen of 583 patients (2.4 %) developed FDCA based on reference assessment of MRI. FDCA occurred ipsilateral to the surgical approach and was not related to degree of resection, hypothalamic involvement, or irradiation. The median time interval between first detection of FDCA and initial surgery was 0.79 years (range 0.01-5.56 years). During a median follow-up of 6.47 years (range 1.2-21.9 years) after first detection of FDCA, no bleeding or cerebrovascular events were observed in any patient. Irradiation was not related to FDCA. Survival rates and functional capacity were similar in patients with and without FDCA. Clinically the FDCA was unapparent in all cases and not treated. CONCLUSION: FDCA is a rare complication related to surgical treatment of childhood-onset craniopharyngioma without major impact on prognosis and clinical course of the disease. CLINICAL TRIAL NUMBER: KRANIOPHARYNGEOM 2000-NCT00258453; KRANIOPHARYNGEOM 2007-NCT01272622.

Anti-platelet drugs and outcome in severe infection: clinical impact and underlying mechanisms.

Platelet activation contributes to microvascular thrombosis and organ failure in systemic inflammation. We tested the hypothesis whether anti-platelet drugs might favourably affect outcome in patients at risk for organ failure as well as in a mouse model of endotoxin shock. Two hundred twenty-four consecutive patients who were admitted for community acquired pneumonia over a time period of 5 years to a University Hospital were enrolled; about 20% of whom received anti-platelet drugs (acetylsalicylic acid, thienopyridines) for secondary prevention of cardiovascular disease. Patients with anti-platelet drugs were about 12 years old but did not differ in SOFA score and routine laboratory parameters at admission. Logistic regression and 2 x 2 table analysis in age-matched subgroups indicated that anti-platelet drugs may reduce the need of intensive care treatment (odds ratio (OR) 0.32 [95% confidential interval: 0.10-1.00] and 0.19 [0.04-0.87], respectively). In age-matched subgroups, the use of anti-platelet drugs was also associated with a shorter stay in hospital (13.9 +/- 6.2 vs. 18.2 +/- 10.2 days; p < 0.02). In the animal model Balb/c mice were pre-treated with clopidogrel (added to drinking water) for 4 days prior to intraperitoneal (i.p.) administration of endotoxin (lipopolsaccharide (LPS) from Escherichia coli 0111:B4). Within the first 48 hours after LPS there were no differences between clopidogrel and control animals (n = 26 each) in macro-haemodynamics. However, clopidogrel abolished the LPS-induced drop in platelet count and reduced fibrin deposition in lung tissue. Using DNA microarray technology, we could show that clopidogrel suppressed endotoxin-induced up-regulation of inflammation-relevant genes, including arachidonate-5-lipoxygenase activating protein and leukotriene B4 receptor 1. According to our data a possible benefit of anti-platelet drugs in patients on risk for systemic inflammation and organ failure should be tested in a prospective trial.