Osteoinductive calcium phosphate with submicron topography as bone graft substitute for maxillary sinus floor augmentation: A translational study.

OBJECTIVES: The aim of this study was the preclinical and clinical evaluation of osteoinductive calcium phosphate with submicron surface topography as a bone graft substitute for maxillary sinus floor augmentation (MSFA). MATERIAL AND METHODS: A preclinical sheep model of MSFA was used to compare a calcium phosphate with submicron needle-shaped topography (BCPN , MagnetOs Granules, Kuros Biosciences BV) to a calcium phosphate with submicron grain-shaped topography (BCPG ) and autologous bone graft (ABG) as controls. Secondly, a 10-patient, prospective, randomized, controlled trial was performed to compare BCPN to ABG in MSFA with two-stage implant placement. RESULTS: The pre-clinical study demonstrated that both BCPN and BCPG were highly biocompatible, supported bony ingrowth with direct bone apposition against the material, and exhibited bone formation as early as 3 weeks post-implantation. However, BCPN demonstrated significantly more bone formation than BCPG at the study endpoint of 12 weeks. Only BCPN reached an equivalent amount of bone formation in the available space and a greater proportion of calcified material (bone + graft material) in the maxillary sinus compared to the "gold standard" ABG after 12 weeks. These results were validated in a small prospective clinical study, in which BCPN was found comparable to ABG in implant stability, bone height, new bone formation in trephine core biopsies, and overall clinical outcome. CONCLUSION: This translational work demonstrates that osteoinductive calcium phosphates are promising bone graft substitutes for MSFA, whereas their bone-forming potential depends on the design of their surface features. Netherlands Trial Register, NL6436.

The influence of Angiostrongylus cantonensis (Nematoda, Metastrongylidae) infection on the aerobic metabolism of Biomphalaria straminea and Biomphalaria tenagophila (Mollusca, Gastropoda).

Angiostrongylus cantonensis is considered the main agent responsible for human eosinophilic meningoencephalitis. This parasite has low specificity for mollusk hosts and it can also use aquatic snails as auxiliary hosts. Studies based on the metabolic profile of Biomphalaria spp. infected by A. cantonensis have been conducted to observe parasite-host interactions. In the present study, the glucose content in the hemolymph and glycogen content in the digestive gland and cephalopedal mass of Biomphalaria tenagophila and Biomphalaria straminea experimentally infected by A. cantonensis were evaluated, along with the activity of LDH. The snails were dissected from 6 to 21days after infection to collect the hemolymph and separate the tissues. Decreases of 96% and 6.4% in the glucose content triggered a transition from aerobic to anaerobic metabolism in the two infected snail species, B. straminea and B. tenagophila, respectively. That finding was confirmed by high-performance liquid chromatography. These results indicate that when infected, these snails are able to change their metabolic profile, suggesting a strategy to maintain their homeostatic balance.

Novel Visual Sensor Coverage and Deployment in Time Aware PTZ Wireless Visual Sensor Networks.

In this paper, we consider the visual sensor deployment algorithm in Pan-Tilt-Zoom (PTZ) Wireless Visual Sensor Networks (WVSNs). With PTZ capability, a sensor's visual coverage can be extended to reduce the number of visual sensors that need to be deployed. The coverage zone of a visual sensor in PTZ WVSN is composed of two regions, a Direct Coverage Region (DCR) and a PTZ Coverage Region (PTZCR). In the PTZCR, a visual sensor needs a mechanical pan-tilt-zoom operation to cover an object. This mechanical operation can take seconds, so the sensor might not be able to adjust the camera in time to capture the visual data. In this paper, for the first time, we study this PTZ time-aware PTZ WVSN deployment problem. We formulate this PTZ time-aware PTZ WVSN deployment problem as an optimization problem where the objective is to minimize the total visual sensor deployment cost so that each area is either covered in the DCR or in the PTZCR while considering the PTZ time constraint. The proposed Time Aware Coverage Zone (TACZ) model successfully captures the PTZ visual sensor coverage in terms of camera focal range, angle span zone coverage and camera PTZ time. Then a novel heuristic, called Time Aware Deployment with PTZ camera (TADPTZ) algorithm, is proposed to solve the problem. From our computational experiments, we found out that TACZ model outperforms the existing M coverage model under all network scenarios. In addition, as compared to the optimal solutions, the TACZ model is scalable and adaptable to the different PTZ time requirements when deploying large PTZ WVSNs.

Analysis of Breath Specimens for Biomarkers of Plasmodium falciparum Infection.

Currently, the majority of diagnoses of malaria rely on a combination of the patient's clinical presentation and the visualization of parasites on a stained blood film. Breath offers an attractive alternative to blood as the basis for simple, noninvasive diagnosis of infectious diseases. In this study, breath samples were collected from individuals during controlled malaria to determine whether specific malaria-associated volatiles could be detected in breath. We identified 9 compounds whose concentrations varied significantly over the course of malaria: carbon dioxide, isoprene, acetone, benzene, cyclohexanone, and 4 thioethers. The latter group, consisting of allyl methyl sulfide, 1-methylthio-propane, (Z)-1-methylthio-1-propene, and (E)-1-methylthio-1-propene, had not previously been associated with any disease or condition. Before the availability of antimalarial drug treatment, there was evidence of concurrent 48-hour cyclical changes in the levels of both thioethers and parasitemia. When thioether concentrations were subjected to a phase shift of 24 hours, a direct correlation between the parasitemia and volatile levels was revealed. Volatile levels declined monotonically approximately 6.5 hours after initial drug treatment, correlating with clearance of parasitemia. No thioethers were detected in in vitro cultures of Plasmodium falciparum. The metabolic origin of the thioethers is not known, but results suggest that interplay between host and parasite metabolic pathways is involved in the production of these thioethers.

A survey on sensor coverage and visual data capturing/processing/transmission in wireless visual sensor networks.

Wireless Visual Sensor Networks (WVSNs) where camera-equipped sensor nodes can capture, process and transmit image/video information have become an important new research area. As compared to the traditional wireless sensor networks (WSNs) that can only transmit scalar information (e.g., temperature), the visual data in WVSNs enable much wider applications, such as visual security surveillance and visual wildlife monitoring. However, as compared to the scalar data in WSNs, visual data is much bigger and more complicated so intelligent schemes are required to capture/process/ transmit visual data in limited resources (hardware capability and bandwidth) WVSNs. WVSNs introduce new multi-disciplinary research opportunities of topics that include visual sensor hardware, image and multimedia capture and processing, wireless communication and networking. In this paper, we survey existing research efforts on the visual sensor hardware, visual sensor coverage/deployment, and visual data capture/ processing/transmission issues in WVSNs. We conclude that WVSN research is still in an early age and there are still many open issues that have not been fully addressed. More new novel multi-disciplinary, cross-layered, distributed and collaborative solutions should be devised to tackle these challenging issues in WVSNs.

Dimethylfumarate: potency prediction and clinical experience.

BACKGROUND: Dimethylfumarate (DMF) was the cause of a major outbreak of allergic contact dermatitis as a consequence of its use as an antifungal agent in leather products, particularly in furniture, with what became known as 'toxic sofa dermatitis'. OBJECTIVES: To determine whether the frequency and severity of reactions to DMF arose as a function of its intrinsic potency and/or the nature and extent of exposure. METHODS: The intrinsic potency of DMF was measured with the standard local lymph node assay (LLNA), with determination of an EC3 value, which is the threshold in the LLNA and serves as an indicator of relative skin-sensitizing potency in humans. RESULTS: The EC3 value for DMF was 0.35% when tested in dimethylformamide as a vehicle, indicating that DMF is a strong, but not an extreme, skin sensitizer in this mouse model. CONCLUSIONS: DMF appears to have a sensitizing potency in the mouse that is very similar to that of formaldehyde, which is also a strong human skin sensitizer. However, the frequency and intensity of allergic contact dermatitis reactions to DMF suggest that it was the prolonged, repeated and occlusive exposure to this chemical over large skin areas, combined with the strong sensitizing potency, that generated the 'perfect storm' conditions that caused the DMF epidemic.

Gut microbiota composition and diversity before, during, and two months after rifamycin-based tuberculosis preventive therapy.

Tuberculosis (TB) preventive therapy (TPT) is an effective strategy to eliminate TB in low-incidence settings. Shorter TPT regimens incorporating the antimicrobial class of rifamycins are designed to improve adherence and completion rates but carry the risk of modifications to the gut microbiota. We enrolled six subjects diagnosed with latent TB infection (LTBI) who accepted to initiate TPT. We also enrolled six healthy volunteers unexposed to the rifamycins. We profiled the gut microbiota using 16S rRNA amplicon sequencing (V1-V2 region) to document the immediate effect of rifamycin-based TPT on the gut microbiota composition and tracked recovery to baseline two months after TPT. Overall, TPT accounted for 17% of the variance in gut microbial community dissimilarity. This rifamycin-based TPT induced dysbiosis was characterized by a depletion of butyrate-producing taxa (Clostridium-XIVa and Roseburia) and expansion of potentially pathogenic taxa within the Firmicutes and Proteobacteria phyla. Recovery of the gut microbial composition was incomplete two months after TPT. Robust clinical studies are necessary to comprehensively catalogue TPT-induced gut microbiota dysbiosis to inform strategies to mitigate potential long-term sequelae of this important TB control intervention.

Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF-α) levels in healthy men.

Total sleep deprivation in humans is associated with increased daytime sleepiness, decreased performance, elevations in inflammatory cytokines, and hormonal/metabolic disturbances. To assess the effects of 40 h of total sleep deprivation (TSD) under constant and well controlled conditions, on plasma levels of TNF-α and its receptor (TNFR1), interleukin-6 (IL-6), cortisol and C-reactive protein (CRP), sleepiness and performance, 12 healthy men (29±3 years) participated in a 5-days sleep deprivation experiment (two control nights followed by a night of sleep loss and one recovery night). Between 0800 and 2300 (i.e. between 25 and 40 h of sleep deprivation), a serial of blood sampling, multiple sleep latency, subjective levels of sleepiness and reaction time tests were completed before (day 2: D2) and after (day 4: D4) one night of sleep loss. We showed that an acute sleep deprivation (i.e. after 34 and 37 h of sleep deprivation) induced a significant increase in TNF-α (P<0.01), but there were no significant changes in TNFR1, IL-6, cortisol and CRP. In conclusion, our study in which constant and controlled experimental conditions were realized with healthy subjects and in absence of psychological or physical stressors, an acute total sleep deprivation (from 34 h) was sufficient to induce secretion of pro-inflammatory cytokine such as TNF-α, a marker more described in chronic sleep restriction or deprivation and as mediators of excessive sleepiness in humans in pathological conditions.

Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding.

Adipose tissue depots originate from distinct precursor cells, are functionally diverse, and modulate disease processes in a depot-specific manner. However, the functional properties of perivascular adipocytes, and their influence on disease of the blood vessel wall, remain to be determined. We show that human coronary perivascular adipocytes exhibit a reduced state of adipocytic differentiation as compared with adipocytes derived from subcutaneous and visceral (perirenal) adipose depots. Secretion of antiinflammatory adiponectin is markedly reduced, whereas that of proinflammatory cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1, is markedly increased in perivascular adipocytes. These depot-specific differences in adipocyte function are demonstrable in both freshly isolated adipose tissues and in vitro-differentiated adipocytes. Murine aortic arch perivascular adipose tissues likewise express lower levels of adipocyte-associated genes as compared with subcutaneous and visceral adipose tissues. Moreover, 2 weeks of high-fat feeding caused further reductions in adipocyte-associated gene expression, while upregulating proinflammatory gene expression, in perivascular adipose tissues. These changes were observed in the absence of macrophage recruitment to the perivascular adipose depot. We conclude that perivascular adipocytes exhibit reduced differentiation and a heightened proinflammatory state, properties that are intrinsic to the adipocytes residing in this depot. Dysfunction of perivascular adipose tissue induced by fat feeding suggests that this unique adipose depot is capable of linking metabolic signals to inflammation in the blood vessel wall.

Two-component polyethylene glycol surgical sealant influence on intraperitoneal infection in a refined rodent model.

OBJECTIVE: This study determined the influence of a 2-component polyethylene glycol surgical sealant (Coseal) as an adhesion prevention device on sepsis-related mortality and/or systemic bacterial translocation to the spleen. STUDY DESIGN: A bacterial inoculum and telemetry probe were implanted in 50 treated and 49 untreated rats. Telemetry probes monitored core-body temperature to determine time of death. Spleens were collected on day 3 for quantitative bacteriology of Escherichia coli and Bacteroides fragilis. RESULTS: Median survival time and mortality of treated rats (37.0 hours, 54.0%) were noninferior to untreated rats (47.5 hours, 55.1%). Median E coli titers in treated rats (2.24 log colony forming units/spleen) were significantly less than untreated rats (4.32 log colony forming units/spleen). B fragilis titers were not different. CONCLUSION: This study demonstrates intraperitoneal administration of a 2-component polyethylene glycol surgical sealant as an adhesion prevention device does not alter time to death or sepsis-related mortality and/or systemic bacterial translocation to the spleen.

Multi-responsive hydrogel structures from patterned droplet networks.

Responsive hydrogels that undergo controlled shape changes in response to a range of stimuli are of interest for microscale soft robotic and biomedical devices. However, these applications require fabrication methods capable of preparing complex, heterogeneous materials. Here we report a new approach for making patterned, multi-material and multi-responsive hydrogels, on a micrometre to millimetre scale. Nanolitre aqueous pre-gel droplets were connected through lipid bilayers in predetermined architectures and photopolymerized to yield continuous hydrogel structures. By using this droplet network technology to pattern domains containing temperature-responsive or non-responsive hydrogels, structures that undergo reversible curling were produced. Through patterning of gold nanoparticle-containing domains into the hydrogels, light-activated shape change was achieved, while domains bearing magnetic particles allowed movement of the structures in a magnetic field. To highlight our technique, we generated a multi-responsive hydrogel that, at one temperature, could be moved through a constriction under a magnetic field and, at a second temperature, could grip and transport a cargo.

The chemical synthesis of discodermolide.

The marine sponge-derived polyketide discodermolide is a potent antimitotic agent that represents a promising natural product lead structure in the treatment of cancer. Discodermolide shares the same microtubule-stabilising mechanism of action as Taxol(®), inhibits the growth of solid tumours in animal models and shows synergy with Taxol. The pronounced cytotoxicity of discodermolide, which is maintained against cancer cell lines that display resistance to Taxol and other drugs, combined with its scarce availability from its natural source, has fuelled significant academic and industrial interest in devising a practical total synthesis as a means of ensuring a sustainable supply for drug development. This chapter surveys the various total syntheses of discodermolide that have been completed over the period 1993-2007, focusing on the strategies employed for introduction of the multiple stereocentres and achieving control over the alkene geometry, along with the various methods used for realising the pivotal fragment couplings to assemble progressively the full carbon skeleton. This dedicated synthetic effort has triumphed in removing the supply problem for discodermolide, providing sufficient material for extensive biological studies and enabling its early stage clinical development, as well as facilitating SAR studies for lead optimisation.

Evaluation of Cell-Mediated Immune Function Using the Cytotoxic T-Lymphocyte Assay.

Evaluation of cell-mediated immunity (CMI) is a significant component in any assessment designed to predict the full range of potential immunotoxic risk underlying health risks. Among measures of CMI, the cytotoxic T-lymphocyte (CTL) response is recognized as perhaps the most relevant functional measure that reflects cell-mediated acquired immune defense against viral infections and cancer. The CTL response against T-dependent antigens requires the cooperation of at least three different major categories of immune cells. These include professional antigen-presenting cells (e.g., dendritic cells), CD4+ T helper lymphocytes, and CD8+ T effector lymphocytes. It is also among the few functional responses dependent on and, hence, capable of evaluating effective antigen presentation via both class I and class II molecules of the major histocompatibility complex (MHC). For this reason, the CTL assay is an excellent candidate for evaluation of potential immunotoxicity. This chapter provides an example of a mouse CTL assay against influenza virus that has been utilized for this purpose.

Host Resistance Assays.

The goal of immunotoxicity testing is to obtain data useful for immunotoxicity safety assessment. Guidance in the performance of immunotoxicity safety evaluations is provided in documents from the US EPA for chemicals and the ICH S8 document for pharmaceuticals. The ICH S8 document outlines a tiered approach that includes (1) standard toxicity studies with associated hematology, immune system organ weights, and histopathology data; (2) functional assays, such as cytotoxic T lymphocyte (CTL) assays, natural killer (NK) cell assays, respiratory burst, phagocytosis, and T-cell-dependent antibody response (TDAR) assays; and (3) host resistance assays. Host resistance assays are considered the gold standard in immunotoxicity testing and provide a critical overview of the extent to which innate, adaptive, and homeostatic regulatory immune functions are integrated to protect the host. Both comprehensive and targeted host resistance assays are available, each with distinct advantages. This chapter serves to provide a general overview of the various assays that may be used, as well as a summary of procedures.

Diurnal variation in expired breath volatiles in malaria-infected and healthy volunteers.

We previously showed that thioether levels in the exhaled breath volatiles of volunteers undergoing controlled human malaria infection (CHMI) with P. falciparum increase as infection progresses. In this study, we show that thioethers have diurnal cyclical increasing patterns and their levels are significantly higher in P. falciparum CHMI volunteers compared to those of healthy volunteers. The synchronized cycle and elevation of thioethers were not present in P. vivax-infection, therefore it is likely that the thioethers are associated with unique factors in the pathology of P. falciparum. Moreover, we found that time-of-day of breath collection is important to accurately predict (98%) P. falciparum-infection. Critically, this was achieved when the disease was asymptomatic and parasitemia was below the level detectable by microscopy. Although these findings are encouraging, they show limitations because of the limited and logistically difficult diagnostic window and its utility to P. falciparum malaria only. We looked for new biomarkers in the breath of P. vivax CHMI volunteers and found that a set of terpenes increase significantly over the course of the malaria infection. The accuracy of predicting P. vivax using breath terpenes was up to 91%. Moreover, some of the terpenes were also found in the breath of P. falciparum CHMI volunteers (accuracy up to 93.5%). The results suggest that terpenes might represent better biomarkers than thioethers to predict malaria as they were not subject to malaria pathogens diurnal changes.

Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic.

Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic, a Society of Toxicology Contemporary Concepts in Toxicology (CCT) workshop was held on March 11, 2017. The meeting was convened to raise awareness of metabolic syndrome and its associated diseases and serve as a melting pot with scientists of multiple disciplines (eg, toxicologists, clinicians, regulators) so as to spur research and understanding of this condition. The criteria for metabolic syndrome include obesity, dyslipidemia (low high-density lipoprotein and/or elevated triglycerides), elevated blood pressure, and alterations in glucose metabolism. It can lead to a greater potential of type 2 diabetes, lipid disorders, cardiovascular disease, hepatic steatosis, and other circulatory disorders. Although there are no approved drugs specifically for this syndrome, many drugs target diseases associated with this syndrome thus potentially increasing the likelihood of drug-drug interactions. There is currently significant research focusing on understanding the key pathways that control metabolism, which would be likely targets of risk factors (eg, exposure to xenobiotics, genetics) and lifestyle factors (eg, microbiome, nutrition, and exercise) that contribute to metabolic syndrome. Understanding these pathways could also lead to the development of pharmaceutical interventions. As individuals with metabolic syndrome have signs similar to that of toxic responses (eg, oxidative stress and inflammation) and organ dysfunction, these alterations should be taken into account in drug development. With the increasing frequency of metabolic syndrome in the general population, the idea of a "normal" individual may need to be redefined. This paper reports on the substance and outcomes of this workshop.

Systematic review of ß blocker, aspirin, and statin in critically ill patients: importance of severity of illness and cardiac troponin.

Non-cardiac critically ill patients with type II myocardial infarction (MI) have a high risk of mortality. There are no evidence-based interventions to mitigate this risk. We systematically reviewed the literature regarding the use of medications known to reduce mortality in patients with cardiac troponin (cTn) elevation due to type I MI (ß blockers, statin, and aspirin) in studies of critically ill patients without Type I MI. All PubMed publications between 1976-2/19/16 were reviewed. Search terms included: ß blocker or aspirin or statin and intensive care unit (ICU) or critically ill or sepsis; 497 primary references were obtained. Inclusion criteria were as follows: (1) study population consisted of critically ill patients in the ICU with non-cardiovascular illnesses, (2) mortality end point, (3) severity of illness (or injury) was measured, and (4) the antiplatelet agent was primarily aspirin. Retrospective investigations, prospective observational studies, meta-analysis, systematic review, and randomized controlled trials were included; case reports were excluded. 25 primary references were obtained. The data were extracted and tabulated using data collection headings as follows: article title, first author/year/reference number, study type/design, population studied, outcome and intervention, and study question addressed. Evidence was not graded as the majority of studies were non-randomized (low-to-moderate quality). 11 studies were found through bibliography reviews for a total of 36 references. In conclusion, ß blockers, statins, and aspirin may play a role in reducing mortality in non-cardiac critically ill patients. Benefit appears to be related to severity of illness, for which cTn may be a marker.

Functional aqueous droplet networks.

Droplet interface bilayers (DIBs), comprising individual lipid bilayers between pairs of aqueous droplets in an oil, are proving to be a useful tool for studying membrane proteins. Recently, attention has turned to the elaboration of networks of aqueous droplets, connected through functionalized interface bilayers, with collective properties unachievable in droplet pairs. Small 2D collections of droplets have been formed into soft biodevices, which can act as electronic components, light-sensors and batteries. A substantial breakthrough has been the development of a droplet printer, which can create patterned 3D droplet networks of hundreds to thousands of connected droplets. The 3D networks can change shape, or carry electrical signals through defined pathways, or express proteins in response to patterned illumination. We envisage using functional 3D droplet networks as autonomous synthetic tissues or coupling them with cells to repair or enhance the properties of living tissues.

Evaluation of 4-methylcyclohexanemethanol (MCHM) in a combined irritancy and Local Lymph Node Assay (LLNA) in mice.

4-Methylcyclohexanemethanol (MCHM) is a flotation reagent used in fine coal beneficiation. On January 9, 2014, crude MCHM, a mixture containing predominantly MCHM, was inadvertently released into the Elk River, a municipal water source that serves about 300,000 people in the Charleston, WV area, resulting in temporary contamination of 15 percent of the state's tap water and causing significant dermal exposure. The current studies were undertaken to determine whether crude MCHM or MCHM has the potential to produce dermal irritancy and/or sensitization. BALB/c female mice were treated daily for 3 consecutive days by direct epicutaneous application of 25 µL of various concentrations of crude MCHM or MCHM to the dorsum of each ear. A mouse ear-swelling test was used to determine irritancy potential and was undertaken in combination with the standardized Local Lymph Node Assay (LLNA) to determine skin sensitizing potential. MCHM was found to produce skin irritation at concentrations above 20% and did not produce sensitization. Crude MCHM also produced irritation, although weaker, and in addition was found to be a weak to moderate skin sensitizer. The results are discussed in terms of potential human health hazard.

Cardiac Troponin Measurement in the Critically Ill: Potential for Guiding Clinical Management.

BACKGROUND: Elevated cardiac troponin (cTn) in the absence of acute coronary syndromes (ACS) is associated with increased mortality in critically ill patients. There are no evidence-based interventions that reduce mortality in this group. OBJECTIVES: We performed a retrospective investigation of the Veterans Administration Inpatient Evaluation Center database to determine whether drugs used in ACS (ß-blockers, aspirin, and statins) are associated with reduced mortality in critically ill patients. METHODS: Thirty-day mortality was determined for non-ACS patients admitted to any Veterans Administration Intensive Care Unit between October 1, 2007, and September 30, 2008, adjusted for severity of illness. Troponin assay values were normalized across institutions. RESULTS: Multivariate analyses for 30-day mortality showed an odds ratio (OR) of 1.82 for patients with high cTn (P < 0.0001, cTn > 10% coefficient of variation) and 1.18 for intermediate cTn (P = 0.0021, cTn between lowest limit detectable and 10% coefficient of variation) compared with patients with no elevation, adjusting for severity of illness (n = 19,979). Logistic regression models showed that patients with no or intermediate elevations of cTn taking statins within 24 hours of cTn measurement had a lower mortality than patients not taking statins (OR, 0.66; 95% confidence interval [95% CI], 0.53-0.82; P = 0.0003), whereas patients with high cTn had a lower mortality if they were taking ß-blockers or aspirin within 24 hours of cTn measurement compared to patients not taking ß-blockers or aspirin (ß-blockers: OR, 0.80; 95% CI, 0.68-0.94; P = 0.0077; aspirin: OR, 0.81;95% CI, 0.69-0.96; P = 0.0134). CONCLUSIONS: This retrospective study confirms an association between elevated troponin and outcomes in critically ill patients without ACS and identifies statins, ß-blockers, and aspirin as potential outcome modifiers in a cTn-dependent manner.