Inferior Vena Cava Volume Is an Independent Predictor of Massive Transfusion in Patients With Trauma.

OBJECTIVES: Early adequate resuscitation of patients with trauma is crucial in preventing shock and early mortality. Thus, we aimed to determine the performance of the inferior vena cava (IVC) volume and other risk factors and scores in predicting massive transfusion and mortality. METHODS: We included all patients with trauma who underwent computed tomography (CT) scan of the torso, which included the abdominal area, in our emergency department (ED) from January 2014 to January 2017. We calculated the 3-dimensional IVC volume from the left renal vein to the IVC bifurcation. The primary outcome was the performance of IVC volume in predicting massive transfusion, and the secondary outcome was the performance of IVC volume in predicting 24-hour and 30-day in-hospital mortality. RESULTS: Among the 236 patients with trauma, 7.6% received massive transfusions. The IVC volume and revised trauma score (RTS) were independent predictors of massive transfusion (adjusted odds ratio [OR]: 0.79 vs 1.86, 95% confidence interval [CI], 0.71-0.89 vs 1.4-2.47, respectively). Both parameters showed the good area under the curve (AUC) for the prediction of massive transfusion (adjusted AUC: 0.83 and 0.82, 95% CI, 0.74-0.92 vs 0.72-0.93, respectively). Patients with a large IVC volume (fourth quartile) were less likely to receive massive transfusion than those with a small IVC volume (first quartile, ≥28.29 mL: 0% vs <15.08 mL: 20.3%, OR: 0.13, 95% CI, 0.03-0.66). CONCLUSIONS: The volume of IVC measured on CT scan and RTS are independent predictors of massive transfusion in patients with trauma in the ED.

Effectiveness of Treatments and Diagnostic Tools and Declining Mortality in Patients With Severe Sepsis: A 12-Year Population-Based Cohort Study.

Sepsis is a major cause of morbidity and mortality worldwide. With the advance of medical care, the mortality of sepsis has decreased in the past decades. Many treatments and diagnostic tools still lack supporting evidence. We conducted a retrospective population-based cohort study with propensity score matched subcohorts based on a prospectively collected national longitudinal health insurance database in Taiwan. Severe sepsis-associated hospital admissions from 2000 to 2011 based on International Classification of Diseases, Ninth Revision, Clinical Modification codes of infections and acute organ dysfunction were identified. To compare the effectiveness of treatment and diagnostic tool, propensity scores were generated to match the comparable control groups. During the 12-year period, 33 375 patients and 50 465 hospitalizations of severe sepsis were identified. The age-standardized 28-day in-hospital mortality decreased significantly from 21% in 2008 to 15% in 2011 with increasingly implemented treatment and diagnostic tool. After propensity score matching, procalcitonin (odds ratio [OR]: 0.70, 95% confidence interval [95% CI]: 0.61-0.81) and lactate testing (OR: 0.90, 95% CI: 0.84-0.97, respectively), transfusion of packed red blood cell (OR: 0.60, 95% CI: 0.52-0.69), albumin (OR: 0.72, 95% CI: 0.55-0.93), balanced crystalloid (OR: 0.29, 95% CI: 0.20-0.41), and use of dopamine (OR: 0.44, 95% CI: 0.39-0.49) were found to be significantly associated with lower mortality rate. However, inconsistent findings need to be further validated.

Development and validation of a parsimonious and pragmatic CHARM score to predict mortality in patients with suspected sepsis.

BACKGROUND: We aimed to derive and validate a parsimonious and pragmatic clinical prediction rule using the concepts of Predisposition, Infection, Response, and Organ Dysfunction to predict in-hospital mortality; and to compare it with other prediction rules, as well as with conventional biomarkers for evaluating the mortality risk of patients with suspected sepsis in the emergency department (ED). METHODS: We conducted a pragmatic cohort study with consecutive ED patients aged 18 or older with documented diagnostic codes of infection and two sets of blood culture ordered by physicians between 2010 and 2012 in a tertiary teaching hospital. RESULTS: 7011 and 12,110 patients were included in the derivation cohort and the validation cohort for the final analysis. There were 479 deaths (7%) in the derivation cohort and 1145 deaths (9%) in the validation cohort. Independent predictors of death were absence of Chills (odds ratio: 2.28, 95% confidence interval: 1.75-2.97), Hypothermia (2.12, 1.57-2.85), Anemia (2.45, 1.97-3.04), wide Red cell Distribution Width (RDW) (3.27, 2.63-4.05) and history of Malignancy (2.00, 1.63-2.46). This novel clinical prediction rule (CHARM) performed well for stratifying patients into mortality risk groups (sensitivity: 99.4%, negative predictive value 99.7%, receiver operating characteristic area 0.77). The CHARM score also outperformed the other scores or biomarkers such as PIRO, SIRS, MEDS, CURB-65, C-reactive protein, procalcitonin and lactate (all p<.05). CONCLUSIONS: In patients with suspected sepsis, this parsimonious and pragmatic model could be utilized to stratify the mortality risk of patients in the early stage of sepsis.

Transfusion of Red Blood Cells to Patients with Sepsis.

Sepsis is one of the major causes of death worldwide, and is the host response to infection which renders our organs malfunctioning. Insufficient tissue perfusion and oxygen delivery have been implicated in the pathogenesis of sepsis-related organ dysfunction, making transfusion of packed red blood cells (pRBCs) a reasonable treatment modality. However, clinical trials have generated controversial results. Even the notion that transfused pRBCs increase the oxygen-carrying capacity of blood has been challenged. Meanwhile, during sepsis, the ability of our tissues to utilize oxygen may also be reduced, and the increased blood concentrations of lactate may be the results of strong inflammation and excessive catecholamine release, rather than impaired cell respiration. Leukodepleted pRBCs more consistently demonstrated improvement in microcirculation, and the increase in blood viscosity brought about by pRBC transfusion helps maintain functional capillary density. A restrictive strategy of pRBC transfusion is recommended in treating septic patients.

IL-5 induces suspended eosinophils to undergo unique global reorganization associated with priming.

The experiments described herein define a unique program of polarization of suspended human eosinophils stimulated with IL-5 family cytokines. We found that eosinophil granules and the nucleus move in opposite directions to form, respectively, a granular compartment and the nucleopod, a specialized uropod occupied by the nucleus and covered with adhesion receptors, including P-selectin glycoprotein ligand-1, CD44, and activated αMß2 integrin. Ligated IL-5 family receptors localize specifically at the tip of the nucleopod in proximity to downstream signaling partners Janus tyrosine kinase 2, signal transducer and activator of transcription-1 and -5, and extracellular signal-regulated kinase. Microscopy and effects of cytochalasin B and nocodazole indicate that remodeling of filamentous actin and reorientation of the microtubule network are required for eosinophil polarization and nucleopod formation. IL-5 induces persistent polarization and extracellular signal-regulated kinase redistribution that are associated with eosinophil priming, a robust response on subsequent stimulation with N-formyl-methionyl-leucyl-phenylalanine. Global reorganization of cytoskeleton, organelles, adhesion receptors, and signaling molecules likely facilitates vascular arrest, extravasation, migration, granule release, and survival of eosinophils entering inflamed tissues from the bloodstream.

Semaphorin 7A is expressed on airway eosinophils and upregulated by IL-5 family cytokines.

Semaphorin 7A (sema7a) plays a major role in TGF-ß1-induced lung fibrosis. Based on the accumulating evidence that eosinophils contribute to fibrosis/remodeling in the airway, we hypothesized that airway eosinophils may be a significant source of sema7a. In vivo, sema7a was expressed on the surface of circulating eosinophils and upregulated on bronchoalveolar lavage eosinophils obtained after segmental bronchoprovocation with allergen. Based on mRNA levels in unfractionated and isolated bronchoalveolar cells, eosinophils are the predominant source of sema7a. In vitro, among the members of the IL-5-family cytokines, sema7a protein on the surface of blood eosinophils was increased more by IL-3 than by GM-CSF or IL-5. Cytokine-induced expression of cell surface sema7a required translation of newly synthesized protein. Finally, a recombinant sema7a induced alpha-smooth muscle actin production in human bronchial fibroblasts. semaphorin 7A is a potentially important modulator of eosinophil profibrotic functions in the airway remodeling of patients with chronic asthma.

Development and External Validation of Clinical Features-based Machine Learning Models for Predicting COVID-19 in the Emergency Department.

Introduction: Timely diagnosis of patients affected by an emerging infectious disease plays a crucial role in treating patients and avoiding disease spread. In prior research, we developed an approach by using machine learning (ML) algorithms to predict serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on clinical features of patients visiting an emergency department (ED) during the early coronavirus 2019 (COVID-19) pandemic. In this study, we aimed to externally validate this approach within a distinct ED population. Methods: To create our training/validation cohort (model development) we collected data retrospectively from suspected COVID-19 patients at a US ED from February 23-May 12, 2020. Another dataset was collected as an external validation (testing) cohort from an ED in another country from May 12-June 15, 2021. Clinical features including patient demographics and triage information were used to train and test the models. The primary outcome was the confirmed diagnosis of COVID-19, defined as a positive reverse transcription polymerase chain reaction test result for SARS-CoV-2. We employed three different ML algorithms, including gradient boosting, random forest, and extra trees classifiers, to construct the predictive model. The predictive performances were evaluated with the area under the receiver operating characteristic curve (AUC) in the testing cohort. Results: In total, 580 and 946 ED patients were included in the training and testing cohorts, respectively. Of them, 98 (16.9%) and 180 (19.0%) were diagnosed with COVID-19. All the constructed ML models showed acceptable discrimination, as indicated by the AUC. Among them, random forest (0.785, 95% confidence interval [CI] 0.747-0.822) performed better than gradient boosting (0.774, 95% CI 0.739-0.811) and extra trees classifier (0.72, 95% CI 0.677-0.762). There was no significant difference between the constructed models. Conclusion: Our study validates the use of ML for predicting COVID-19 in the ED and demonstrates its potential for predicting emerging infectious diseases based on models built by clinical features with temporal and spatial heterogeneity. This approach holds promise for scenarios where effective diagnostic tools for an emerging infectious disease may be lacking in the future.

Platelet activation, P-selectin, and eosinophil ß1-integrin activation in asthma.

RATIONALE: Eosinophil ß1-integrin activation correlates inversely with FEV1 and directly with eosinophil-bound P-selectin in subjects with nonsevere allergic asthma. OBJECTIVES: Determine the relationships between ß1-integrin activation and pulmonary function or eosinophil-bound P-selectin in subjects with asthma of varying severity and discern the source of eosinophil-bound P-selectin. METHODS: Blood was assayed by flow cytometry for P-selectin and activated ß1-integrin on eosinophils and platelets. Plasma was analyzed with ELISA for soluble P-selectin, platelet factor 4, and thrombospondin-1. MEASUREMENTS AND MAIN RESULTS: Activated ß1-integrin correlated with eosinophil-bound P-selectin among all subjects with asthma even though activated ß1-integrin was higher in subjects with nonsevere asthma than severe asthma. Activated ß1-integrin correlated inversely with FEV1 corrected for FVC only in younger subjects with nonsevere asthma. Paradoxically, platelet surface P-selectin, a platelet activation marker, was low in subjects with severe asthma, whereas plasma platelet factor 4, a second platelet activation marker, was high. Correlations indicated that P-selectin-positive platelets complexed to eosinophils are the major source of the eosinophil-bound P-selectin associated with ß1-integrin activation. After whole-lung antigen challenge of subjects with nonsevere asthma, a model of asthma exacerbation known to cause platelet activation, circulating eosinophils bearing P-selectin and activated ß1-integrin disappeared. CONCLUSIONS: The relationship between eosinophil ß1-integrin activation and pulmonary function was replicated only for younger subjects with nonsevere asthma. However, we infer that platelet activation and binding of activated platelets to eosinophils followed by P-selectin-mediated eosinophil ß1-integrin activation occur in both nonsevere and severe asthma with rapid movement of platelet-eosinophil complexes into the lung in more severe disease.

Applying symptom dynamics to accurately predict influenza virus infection: An international multicenter influenza-like illness surveillance study.

BACKGROUND: Public health organizations have recommended various definitions of influenza-like illnesses under the assumption that the symptoms do not change during influenza virus infection. To explore the relationship between symptoms and influenza over time, we analyzed a dataset from an international multicenter prospective emergency department (ED)-based influenza-like illness cohort study. METHODS: We recruited patients in the US and Taiwan between 2015 and 2020 with: (1) flu-like symptoms (fever and cough, headache, or sore throat), (2) absence of any of the respiratory infection symptoms, or (3) positive laboratory test results for influenza from the current ED visit. We evaluated the association between the symptoms and influenza virus infection on different days of illness. The association was evaluated among different subgroups, including different study countries, influenza subtypes, and only patients with influenza. RESULTS: Among the 2471 recruited patients, 45.7% tested positive for influenza virus. Cough was the most predictive symptom throughout the week (odds ratios [OR]: 7.08-11.15). In general, all symptoms were more predictive during the first 2 days (OR: 1.55-10.28). Upper respiratory symptoms, such as sore throat and productive cough, and general symptoms, such as body ache and fatigue, were more predictive in the first half of the week (OR: 1.51-3.25). Lower respiratory symptoms, such as shortness of breath and wheezing, were more predictive in the second half of the week (OR: 1.52-2.52). Similar trends were observed for most symptoms in the different subgroups. CONCLUSIONS: The time course is an important factor to be considered when evaluating the symptoms of influenza virus infection.

Diagnostic accuracy of clinical signs and symptoms of COVID-19: A systematic review and meta-analysis to investigate the different estimates in a different stage of the pandemic outbreak.

Background: The coronavirus (COVID-19) pandemic caused enormous adverse socioeconomic impacts worldwide. Evidence suggests that the diagnostic accuracy of clinical features of COVID-19 may vary among different populations. Methods: We conducted a systematic review and meta-analysis of studies from PubMed, Embase, Cochrane Library, Google Scholar, and the WHO Global Health Library for studies evaluating the accuracy of clinical features to predict and prognosticate COVID-19. We used the National Institutes of Health Quality Assessment Tool to evaluate the risk of bias, and the random-effects approach to obtain pooled prevalence, sensitivity, specificity, and likelihood ratios. Results: Among the 189 included studies (53 659 patients), fever, cough, diarrhoea, dyspnoea, and fatigue were the most reported predictors. In the later stage of the pandemic, the sensitivity in predicting COVID-19 of fever and cough decreased, while the sensitivity of other symptoms, including sputum production, sore throat, myalgia, fatigue, dyspnoea, headache, and diarrhoea, increased. A combination of fever, cough, fatigue, hypertension, and diabetes mellitus increases the odds of having a COVID-19 diagnosis in patients with a positive test (positive likelihood ratio (PLR) = 3.06)) and decreases the odds in those with a negative test (negative likelihood ratio (NLR) = 0.59)). A combination of fever, cough, sputum production, myalgia, fatigue, and dyspnea had a PLR = 10.44 and an NLR = 0.16 in predicting severe COVID-19. Further updating the umbrella review (1092 studies, including 3 342 969 patients) revealed the different prevalence of symptoms in different stages of the pandemic. Conclusions: Understanding the possible different distributions of predictors is essential for screening for potential COVID-19 infection and severe outcomes. Understanding that the prevalence of symptoms may change with time is important to developing a prediction model.

Current Evidence and Limitation of Biomarkers for Detecting Sepsis and Systemic Infection.

Sepsis was recently redefined as a life-threatening disease involving organ dysfunction caused by a dysregulated host response to infection. Biomarkers play an important role in early detection, diagnosis, and prognostication. We reviewed six promising biomarkers for detecting sepsis and systemic infection, including C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), CD64, presepsin, and sTREM-1. Among the recent studies, we found the following risks of bias: only a few studies adopted the random or consecutive sampling strategy; extensive case-control analysis, which worsened the over-estimated performance; most of the studies used post hoc cutoff values; and heterogeneity with respect to the inclusion criteria, small sample sizes, and different quantitative synthesis methods applied in meta-analyses. We recommend that CD64 and presepsin should be considered as the most promising biomarkers for diagnosing sepsis. Future studies should enroll a larger sample size with a cohort rather than a case-control study design. A random or consecutive study design with a pre-specified laboratory threshold, consistent sampling timing, and an updated definition of sepsis will also increase the reliability of the studies. Further investigations of appropriate specimens, testing assays, and cutoff levels for specific biomarkers are also warranted.

Xanthine oxidoreductase and neurological sequelae of carbon monoxide poisoning.

Neurological sequelae (NS) is a common complication of carbon monoxide (CO) poisoning and structural alterations of myelin basic protein have been proven to initiate immunological reactions leading to NS. To determine whether xanthine oxidoreductase (XOR) participates in the pathophysiology of CO-mediated NS, we examined myelin basic protein in CO poisoned XOR-depleted rats and performed radial maze studies to evaluate the alteration of cognitive function. Carbon monoxide poisoned XOR-depleted rats did not exhibit myelin basic protein alterations or impaired cognitive function, both found in CO poisoned control rats. These results indicate that XOR is essential to the pathological cascade of CO-mediated NS.

The number of displaced rib fractures is more predictive for complications in chest trauma patients.

BACKGROUND: Traumatic rib fractures can cause chest complications that need further treatment and hospitalization. We hypothesized that an increase in the number of displaced rib fractures will be accompanied by an increase in chest complications. METHODS: We retrospectively reviewed the trauma registry between January 2013 and May 2015 in a teaching hospital in northeastern Taiwan. Patients admitted with chest trauma and rib fractures without concomitant severe brain, splenic, pelvic or liver injuries were included. The demographic data, such as gender, age, the index of coexistence disease, alcohol consumption, trauma mechanisms were analyzed as potential predictors of pulmonary complications. Pulmonary complications were defined as pneumothorax, hemothorax, flail chest, pulmonary contusion, and pneumonia. RESULTS: In the 29 months of the study period, a total of 3151 trauma patients were admitted to our hospital. Among them, 174 patients were enrolled for final analysis. The most common trauma mechanism was road traffic accidents (58.6%), mainly motorbike accidents (n = 70, 40.2%). Three or more displaced rib fractures had higher specificity for predicting complications, compared to three or more total rib fractures (95.5% vs 59.1%). Adjusting the severity of chest trauma using TTSS and Ribscore by multivariable logistic regression analysis, we found that three or more rib fractures or any displaced rib fracture was the most significant predictor for developing pulmonary complication (aOR: 5.49 95% CI: 1.82-16.55). Furthermore, there were 18/57 (31.6%) patients with fewer than three ribs fractures developed pulmonary complications. In these 18 patients, only five patients had delayed onset complications and four of them had at least one displaced rib fracture. DISCUSSION: In this retrospective cohort study, we found that the number of displaced or total rib fractures, bilateral rib fractures, and rib fractures in more than two areas were associated with the more chest complications. Furthermore, three or more rib fracture or any displacement were found to be the most sensitive risk factor for chest complications, independent of other risk factors or severity index. CONCLUSION: The number of displaced rib fractures could be a strong predictor for developing pulmonary complications. For patients with fewer than three rib fractures without rib displacement and initial lung or other organ injuries, outpatient management could be safe and efficient.

Comparison of diagnostic accuracy in sepsis between presepsin, procalcitonin, and C-reactive protein: a systematic review and meta-analysis.

BACKGROUND: The soluble cluster of differentiation 14 (or presepsin) is a free fragment of glycoprotein expressed on monocytes and macrophages. Although many studies have been conducted recently, the diagnostic performance of presepsin for sepsis remains debated. We performed a systematic review and meta-analysis of the available literature to assess the accuracy of presepsin for the diagnosis of sepsis in adult patients and compared the performance between presepsin, C-reactive protein (CRP), and procalcitonin (PCT). METHODS: A comprehensive systemic search was conducted in PubMed, EMBASE, and Google Scholar for studies that evaluated the diagnostic accuracy of presepsin for sepsis until January 2017. The hierarchical summary receiver operating characteristic method was used to pool individual sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the receiver operating characteristic curve (AUC). RESULTS: Eighteen studies, comprising 3470 patients, met our inclusion criteria. The pooled diagnosis sensitivity and specificity of presepsin for sepsis were 0.84 (95% CI 0.80-0.87) and 0.76 (95% CI 0.67-0.82), respectively. Furthermore, the pooled DOR, PLR, NLR, and AUC were 16 (95% CI 10-25), 3.4 (95% CI 2.5-4.6), 0.22 (95% CI 0.17-0.27), and 0.88 (95% CI 0.85-0.90), respectively. Significant heterogeneity was found in both sensitivities (Cochrane Q = 137.43, p < 0.001, I 2 = 87.63%) and specificities (Cochrane Q = 180.76, p < 0.001, I 2 = 90.60%). Additionally, we found no significant difference between presepsin and PCT (AUC 0.87 vs. 0.86) or CRP (AUC 0.85 vs. 0.85). However, for studies conducted in ICU, the pooled sensitivity of presepsin was found to be higher than PCT (0.88, 95% CI 0.82-0.92 vs. 0.75, 95% CI 0.68-0.81), while the pooled specificity of presepsin was lower than PCT (0.58, 95% CI 0.42-0.73 vs. 0.75, 95% CI 0.65-0.83). CONCLUSION: Based on the results of our meta-analysis, presepsin is a promising marker for diagnosis of sepsis as PCT or CRP, but its results should be interpreted more carefully and cautiously since too few studies were included and those studies had high heterogeneity between them. In addition, continuing re-evaluation during the course of sepsis is advisable.

Systemic inflammatory response syndrome is more associated with bacteremia in elderly patients with suspected sepsis in emergency departments.

Early diagnosis of bacteremia for patients with suspected sepsis is 1 way to improve prognosis of sepsis. Systemic inflammatory response syndrome (SIRS) has long been utilized as a screening tool to detect bacteremia by front-line healthcare providers. The value of SIRS to predict bacteremia in elderly patients (≥65 years) with suspected sepsis has not yet been examined in emergency departments (EDs).We aimed to evaluate the performance of SIRS components in predicting bacteremia among elderly patients in EDs.We retrospectively evaluated patients with suspected sepsis and 2 sets of blood culture collected within 4 hours after admitting to ED in a tertiary teaching hospital between 2010 and 2012. Patients were categorized into 3-year age groups: young (18-64 years), young-old (65-74 years), and old patients (≥75 years). Vital signs and Glasgow Coma Scale with verbal response obtained at the triage, comorbidities, sites of infection, blood cultures, and laboratory results were retrieved via the electronic medical records.A total of 20,192 patients were included in our study. Among them, 9862 (48.9%) were the elderly patients (young-old and old patients), 2656 (13.2%) developed bacteremia. Among patients with bacteremia, we found the elderly patients had higher SIRS performance (adjusted odds ratio [aOR]: 2.40, 95% confidence interval [CI]: 1.90-3.03 in the young-old and aOR: 2.66, 95% CI: 2.19-3.23 in the old). Fever at the triage was most predictive of bacteremia, especially in the elderly patients (aOR: 2.19, 95% CI: 1.81-2.65 in the young-old and aOR: 2.27, 95% CI: 1.95-2.63 in the old), and tachypnea was not predictive of bacteremia among the elderly patients (all P > 0.2).The performance of SIRS to predict bacteremia was more suitable for elderly patients in EDs observed in this study. The elderly patients presented with more fever and less tachypnea when they had bacteremia.

Intravascular neutrophil activation due to carbon monoxide poisoning.

RATIONALE: We hypothesized that platelet-neutrophil interactions occur as a result of acute carbon monoxide (CO) poisoning, and subsequent neutrophil activation triggers events that cause neurologic sequelae. OBJECTIVES: To identify platelet-neutrophil interactions and neutrophil activation in patients and in animal models, and to establish the association between these intravascular events and changes linked to CO-mediated neurologic sequelae in an animal model. MEASUREMENTS AND MAIN RESULTS: Blood was obtained from 50 consecutive patients. Abnormalities were variable depending on the carboxyhemoglobin level at study admission and duration of CO exposure. Platelet-neutrophil aggregates were detected and plasma myeloperoxidase (MPO) concentration was significantly elevated in those with confirmed CO poisoning. Among patients exposed to CO for over 3 h, flow cytometry scans of neutrophils revealed increased surface expression of CD18 and, in some groups, MPO on the cell surface. Animal models revealed consistent evidence of platelet-neutrophil aggregates, neutrophil activation and surface MPO, and plasma MPO elevation. MPO was deposited along the brain vascular lining and colocalized with nitrotyrosine. CO poisoning caused abnormalities in the charge pattern of myelin basic protein (MBP), changes linked to adaptive immunologic responses responsible for neurologic sequelae in this model. Changes did not occur in thrombocytopenic rats, those receiving tirofiban to inhibit platelet-neutrophil interactions, or those receiving L-nitroarginine methyl ester to inhibit nitric oxide synthesis. Alterations in MBP did not occur in CO-poisoned knockout mice lacking MPO. CONCLUSIONS: Acute CO poisoning causes intravascular neutrophil activation due to interactions with platelets. MPO liberated by neutrophils mediates perivascular oxidative stress, which is linked to immune-mediated neurologic sequelae.

Cardiac toxicity caused by Achyranthes aspera.

A 57-y-old man took over 1000 ml of a decoction made from Acyranthes aspera and was found unconscious in his bathroom. Hypotension and bradycardia were noted. The patient recovered 4 d later after dopamine and supportive care. There was no further cardiac abnormalities noted in serial cardiac examinations. We suggest that Achyranthes aspera causes a dose-related transient cardiovascular toxicity.