Under Armour - Use of personal protective equipment for simulated CPR of COVID-19 patients: an observational study.

BACKGROUND: Personal protective equipment (PPE) protects healthcare workers and patients. Data on guideline compliance on how to dress (donning) or remove (doffing) PPE and the assistance among multiple participants (buddying) are limited. This study assesses the quality of donning, doffing, and buddying of PPE in a simulated medical emergency. METHOD: Physicians handling a simulated cardiac arrest of a COVID-19 patient. Adjacent to the victim, PPE was available. The appropriateness of PPE choice was assessed by using video recordings, with each individual participant being analyzed from the beginning of the simulation scenario from two perspectives regarding the selection of items during donning and doffing, hygiene aspects, time, and team support (buddying). The primary outcome was the number of participants being appropriately protected, defined as both wearing (a) all PPE items provided, and (b) all PPE items correctly at the time of first patient contact (FPC). Secondary outcomes included the timing of participants being appropriately protected. Statistical analysis was performed using SPSS (version 28). Mann-Whitney test, chi-square test, and linear regression analysis were performed as appropriate. RESULTS: At first patient contact 21% (91/437) were correctly protected. One or more incorrect PPE items were found in 4% (19/437), whereas 61% (265/437) wore one or more PPE items incorrectly. In 14% (62/437), one or more PPE items were missing. The time interval between donning start and FPC was 66 (55-78) sec. Time to FPC was longer in correctly than in incorrectly protected participants 77 (66-87) vs. 64 (54-75) sec; p < 0.001) and decreased by 7 ± 2 s per PPE item omitted (P = 0.002). Correct doffing was observed in 192/345 (56%), while buddying occurred in 120 participants (27%), indicating that they either assisted other participants in some manner (verbally or physically) or received assistance themselves. CONCLUSIONS: Our findings imply a need for education in correct and timely PPE donning and doffing. Donning PPE as intended delayed FPC. This and the influence of buddying needs further investigation (German study register number DRKS00023184).

Distinguishing in-hospital and out-of-hospital status epilepticus: clinical implications from a 10-year cohort study.

BACKGROUND AND PURPOSE: The aim was to determine differences of clinical, treatment and outcome characteristics between patients with in-hospital and out-of-hospital status epilepticus (SE). METHODS: From 2005 to 2014, clinical data were assessed in adults with SE treated in an academic medical care centre. Clinical characteristics, treatment and outcomes were compared between patients with in-hospital and out-of-hospital SE. RESULTS: Amongst 352 patients, 213 were admitted with SE and 139 developed in-hospital SE. Patients with in-hospital SE had more acute/fatal aetiologies (60% vs. 35%, P < 0.001), fewer previous seizures (33% vs. 50%, P = 0.002), a higher median Charlson Comorbidity Index (3 vs. 2, P < 0.001), longer median SE duration (1 vs. 0.5 days, P = 0.001), more refractory SE (52% vs. 39%, P = 0.022), less return to functional baseline (38% vs. 54%, P = 0.006) and increased mortality (29% vs. 19%, P = 0.001). Whilst in multivariable analyses an increasing Status Epilepticus Severity Score (STESS) was an independent predictor for death in both groups, increased Charlson Comorbidity Index and treatment refractory SE were associated with death only in patients with in-hospital SE. Continuous anaesthesia for refractory SE was associated with increased mortality only in patients with out-of-hospital SE. The area under the receiver operating curve was 0.717 for prediction of death by STESS in patients with in-hospital SE and 0.811 in patients with out-of-hospital SE. CONCLUSIONS: Patients with in-hospital SE had more fatal aetiologies and comorbidities, refractory SE, less return to functional baseline, and increased mortality compared to patients with out-of-hospital SE. Whilst the STESS was a robust predictor for death in both groups, the association between continuous anaesthesia and death was limited to out-of-hospital SE.

Impact of MALDI-TOF-MS-based identification directly from positive blood cultures on patient management: a controlled clinical trial.

OBJECTIVES: Rapid identification of pathogens directly from positive blood cultures (BC) in combination with an antimicrobial stewardship programme (ASP) is associated with improved antibiotic treatment and outcomes, but the effect of each individual intervention is less clear. The current study investigated the impact of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) versus conventional identification on antibiotic management in a setting with a well-established ASP and low resistance rates. METHODS: In this single-centre open label, controlled clinical trial 425 patients with positive BCs were allocated by weekday during a 1-year period to either MALDI-TOF directly from positive BCs or conventional processing. ASP was identical throughout the study period. The primary outcome was duration of intravenous antimicrobial therapy and was analysed in an intention-to-treat approach. RESULTS: In all, 368 patients were analysed (MALDI-TOF n = 168; conventional n = 200) with similar baseline characteristics. Mean duration of intravenous antimicrobial therapy (12.9 versus 13.2 days, p 0.9) and length of stay (16.1 versus 17.9 days, p 0.3) were comparable. In the clinically significant bloodstream infection subgroup (n = 242) mean time from Gram-stain to active treatment was significantly shorter (3.7 versus 6.7 h, p 0.003). Admission to the intensive care unit after bloodstream infection onset was less frequent in the MALDI-TOF group (23.1 versus 37.2%, p 0.02). CONCLUSIONS: Rapid identification of contaminated BCs (n = 126) resulted in a shorter duration of intravenous antimicrobial therapy (mean 4.8 versus 7.5 days, p 0.04). Rapid identification using MALDI-TOF directly from positive BCs did not impact on duration of intravenous antimicrobial therapy, but provided fast and reliable microbiological results and may improve treatment quality in the setting of an established ASP.

Early predictors of refractory status epilepticus: an international two-center study.

BACKGROUND AND PURPOSE: Status epilepticus (SE) refractory to first- and second-line antiepileptic drugs carries high mortality. Little is known on early prediction of refractory SE (RSE)­an essential tool for planning appropriate therapy. Our aim was to identify and validate independent early RSE predictors in adults. METHODS: Clinical and laboratory data on consecutive intensive care unit patients with SE from two academic care centers (a derivation data set from a Swiss center and a validation data set from a US center) were assessed. Multivariable analysis was performed with the derivation set to identify RSE predictors at SE onset. Their external validity was evaluated with an independent validation set. Measures of calibration and discrimination were assessed. RESULTS: In all, 302 patients were analyzed (138 with and 164 without RSE), 171 in the derivation data set and 131 in the validation data set. Acute SE etiology, coma/stupor and serum albumin <35 g/l at SE onset were independent predictors for RSE in the derivation data set [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.01-4.07; OR 4.83, 95% CI 2.42-9.68; OR 2.45, 95% CI 1.16-5.16]. The prediction model showed good measures of calibration (Hosmer-Lemesow goodness-of-fit test P = 0.99) and discrimination (area under the receiver operating characteristic curve 0.8) on the derivation data set­results that were similar in the validation data set (Hosmer-Lemeshow P = 0.24; area under the receiver operating characteristic curve 0.73). CONCLUSIONS: This study confirms the independent prognostic value of readily available parameters for early RSE prediction. Prospective studies are needed to identify additional robust predictors, which could be added to the proposed model for further optimization towards a reliable prediction scoring system.

Effect of n-3 fatty acids on markers of brain injury and incidence of sepsis-associated delirium in septic patients.

BACKGROUND: Data regarding immunomodulatory effects of parenteral n-3 fatty acids in sepsis are conflicting. In this study, the effect of administration of parenteral n-3 fatty acids on markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients was investigated. METHODS: Fifty patients with sepsis were randomized to receive either 2 ml/kg/day of a lipid emulsion containing highly refined fish oil (equivalent to n-3 fatty acids 0.12 mg/kg/day) during 7 days after admission to the intensive care unit or standard treatment. Markers of brain injury and inflammatory mediators were measured on days 1, 2, 3 and 7. Assessment for sepsis-associated delirium was performed daily. The primary outcome was the difference in S-100ß from baseline to peak level between both the intervention and the control group, compared by t-test. Changes of all markers over time were explored in both groups, fitting a generalized estimating equations model. RESULTS: Mean difference in change of S-100ß from baseline to peak level was 0.34 (95% CI: -0.18-0.85) between the intervention and control group, respectively (P = 0.19). We found no difference in plasma levels of S-100ß, neuron-specific enolase, interleukin (IL)-6, IL-8, IL-10, and C-reactive protein between groups over time. Incidence of sepsis-associated delirium was 75% in the intervention and 71% in the control groups (risk difference 4%, 95% CI -24-31%, P = 0.796). CONCLUSION: Administration of n-3 fatty acids did not affect markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients.

[Patients in intensive care after a suicide attempt with legal drugs - risk profile and course]. / Patienten mit Intensivpflichtigen Medikamentösen Suizidversuchen - Risikoprofil und Verlauf.

Little is known about the risk profile and the further history of patients who attempted suicide by severe medicinal intoxication.All patients residing in Basel (n = 190) admitted to the intensive care unit between 01/01/1998 and 12/31/2001 because of a suicide attempt with legal drugs were investigated regarding psychopathology and sociodemographic features. Also, until the end of 2005, further suicide attempts as well as potential cases of death were followed up.All 190 patients had psychiatric disorders. Compared to the general population, female sex, single status, low educational level, unemployment and invalidity were found significantly more often. Until the end of 2005 almost half of 118 patients followed up in our outpatient department committed further suicide attempts. 28 patients died, 6 of these by suicide.These patients should preferably not be prescribed medication with a low therapeutic range and they should receive intensive follow-up care.

Midregional pro-atrial natriuretic peptide and procalcitonin improve survival prediction in VAP.

Ventilator-associated pneumonia (VAP) affects mortality, morbidity and cost of critical care. Reliable risk estimation might improve end-of-life decisions, resource allocation and outcome. Several scoring systems for survival prediction have been established and optimised over the last decades. Recently, new biomarkers have gained interest in the prognostic field. We assessed whether midregional pro-atrial natriuretic peptide (MR-proANP) and procalcitonin (PCT) improve the predictive value of the Simplified Acute Physiologic Score (SAPS) II and Sequential Related Organ Failure Assessment (SOFA) in VAP. Specified end-points of a prospective multinational trial including 101 patients with VAP were analysed. Death <28 days after VAP onset was the primary end-point. MR-proANP and PCT were elevated at the onset of VAP in nonsurvivors compared with survivors (p = 0.003 and p = 0.017, respectively) and their slope of decline differed significantly (p = 0.018 and p = 0.039, respectively). Patients with the highest MR-proANP quartile at VAP onset were at increased risk for death (log rank p = 0.013). In a logistic regression model, MR-proANP was identified as the best predictor of survival. Adding MR-proANP and PCT to SAPS II and SOFA improved their predictive properties (area under the curve 0.895 and 0.880). We conclude that the combination of two biomarkers, MR-proANP and PCT, improve survival prediction of clinical severity scores in VAP.

Human factors in resuscitation: Lessons learned from simulator studies.

Medical algorithms, technical skills, and repeated training are the classical cornerstones for successful cardiopulmonary resuscitation (CPR). Increasing evidence suggests that human factors, including team interaction, communication, and leadership, also influence the performance of CPR. Guidelines, however, do not yet include these human factors, partly because of the difficulties of their measurement in real-life cardiac arrest. Recently, clinical studies of cardiac arrest scenarios with high-fidelity video-assisted simulations have provided opportunities to better delineate the influence of human factors on resuscitation team performance. This review focuses on evidence from simulator studies that focus on human factors and their influence on the performance of resuscitation teams. Similar to studies in real patients, simulated cardiac arrest scenarios revealed many unnecessary interruptions of CPR as well as significant delays in defibrillation. These studies also showed that human factors play a major role in these shortcomings and that the medical performance depends on the quality of leadership and team-structuring. Moreover, simulated video-taped medical emergencies revealed that a substantial part of information transfer during communication is erroneous. Understanding the impact of human factors on the performance of a complex medical intervention like resuscitation requires detailed, second-by-second, analysis of factors involving the patient, resuscitative equipment such as the defibrillator, and all team members. Thus, high-fidelity simulator studies provide an important research method in this challenging field.

A novel directed evolution method to enhance cell-type specificity of adeno-associated virus vectors.

Clinical application of viral vectors is often hampered by the lack of selectivity of viral particles for the targeted tissue. This drawback decreases the efficiency of gene delivery and raises safety concerns. We successfully established a novel in vitro evolution protocol to engineer adeno-associated virus vectors with increased selectivity for designated target cells. Subjecting a peptide-display library of AAV capsids to negative selection cycles on human primary fibroblasts and to positive selection cycles on a human melanoma cell line, we isolated several variants with up to 3.7-fold increased specificity for malignant cells in comparison to fibroblasts and other cell types. These mutants can be used to achieve high levels of gene transfer to target cells reducing undesired transduction of neighbouring tissues.

Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study.

In patients with ventilator-associated pneumonia (VAP), guidelines recommend antibiotic therapy adjustment according to microbiology results after 72 h. Circulating procalcitonin levels may provide evidence that facilitates the reduction of antibiotic therapy. In a multicentre, randomised, controlled trial, 101 patients with VAP were assigned to an antibiotic discontinuation strategy according to guidelines (control group) or to serum procalcitonin concentrations (procalcitonin group) with an antibiotic regimen selected by the treating physician. The primary end-point was antibiotic-free days alive assessed 28 days after VAP onset and analysed on an intent-to-treat basis. Procalcitonin determination significantly increased the number of antibiotic free-days alive 28 days after VAP onset (13 (2-21) days versus 9.5 (1.5-17) days). This translated into a reduction in the overall duration of antibiotic therapy of 27% in the procalcitonin group (p = 0.038). After adjustment for age, microbiology and centre effect, the rate of antibiotic discontinuation on day 28 remained higher in the procalcitonin group compared with patients treated according to guidelines (hazard rate 1.6, 95% CI 1.02-2.71). The number of mechanical ventilation-free days alive, intensive care unit-free days alive, length of hospital stay and mortality rate on day 28 for the two groups were similar. Serum procalcitonin reduces antibiotic therapy exposure in patients with ventilator associated pneumonia.

Intracranial pressure in patients with sepsis.

INTRODUCTION: In sepsis the brain is frequently affected although there is no infection of the CNS (septic encephalopathy). One possible cause of septic encephalopathy is failure of the blood-brain barrier. Brain edema has been documented in animal models of sepsis. Aggressive fluid resuscitation in the early course of sepsis improves survival and is standard practice. We hypothesized that aggressive fluid administration will increase intracranial pressure (ICP) and may cause critical reductions in cerebral perfusion pressure (CPP). MATERIALS AND METHODS: Patients with sepsis were investigated daily on up to four consecutive days in the intensive care unit. Mean arterial blood pressure (MAP) and blood flow velocity in the middle cerebral artery were monitored for one hour each day. ICP was calculated non-invasively from MAP and flow velocity data. S-100beta was determined daily. FINDINGS: Fifty-two measurements were performed in 16 patients. ICP could be determined in 45 measurements in 15 patients. Seven patients had an ICP > 15 mmHg and 11 patients had a CPP < 60 mmHg on at least 1 day. We found no significant correlation between ICP and fluid administration, but low CPP was significantly correlated with elevated S-100beta (r = -0.47, p = 0.001). CONCLUSIONS: Further research is needed to determine the role of ICP/CPP monitoring in patients with sepsis.

Legionella bozemanii, an elusive agent of fatal cavitary pneumonia.

A 67-year-old patient died of Legionella bozemanii pneumonia with negative urinary antigen and negative serology. Cystic lesions in pneumonia of unknown origin should lead to the differential diagnosis of L. bozemanii infections.

Unnecessary interruptions of cardiac massage during simulated cardiac arrests.

BACKGROUND AND OBJECTIVE: Cardiopulmonary resuscitation should not be interrupted until the return of spontaneous circulation or the decision to withhold further treatment. There are no data on how consistent in-hospital cardiopulmonary resuscitation is performed. Accordingly, the aim of the present study was to identify length and type of unnecessary interruptions in simulated cardiac arrests. METHODS: The study was carried out in a patient simulator. A scenario of cardiac arrest due to ventricular fibrillation was used. Resuscitation teams consisted of three nurses, a resident and a staff physician. Using videotapes recorded during simulations, the activities of the teams were coded in 5-s intervals. Unnecessary interruptions were defined as any interruptions in cardiac massage of 10 s or more that were not caused by defibrillation or endotracheal intubation. RESULTS: Twelve teams were studied. The total time of possible cardiac massage was 414 +/- 125 s. In each team at least one unnecessary interruption occurred (range 1-5). Interruptions mounted up to 65 +/- 40 s (range 20-155) or 16 +/- 10% (range 5-41) of the total time of possible cardiac massage. Failure to swiftly resume cardiac massage after an unsuccessful defibrillation accounted for 14 of 39 episodes and for 44 +/- 40% of the time of unnecessary interruptions. The debriefings revealed that participants had generally not noticed the unnecessary interruptions during the simulation. CONCLUSIONS: The present study identified a significant amount of unnecessary interruptions in cardiac massage. These interruptions were not noticed by the health-care workers involved.

Life-threatening orolingual angioedema during thrombolysis in acute ischemic stroke.

BACKGROUND: Orolingual angioedema can occur during thrombolysis with alteplase in stroke patients. However, data about its frequency, severity and the significance of concurrent use of angiotensin-converting-enzyme inhibitors (ACEi) are sparse. OBJECTIVE: (1), to alert to the potentially life-threatening complication of orolingual angioedema. (2), to present CT-scans of the tongue which exclude lingual hematoma. (3), to estimate the frequency of orolingual angioedema. (4), to evaluate the risk associated with the concurrent use of ACEi. METHODS: Single center, databank-based observational study on 120 consecutive patients with i. v. alteplase for acute stroke. Meta-analysis of all stroke studies on alteplase-associated angioedema, which provided detailed information about the use of ACE-inhibitors. Across studies, the Peto odds ratio of orolingual angioedema for "concurrent use of ACEi" was calculated. RESULTS: Orolingual angioedema occurred in 2 of 120 patients (1.7%, 95% CI 0.2-5.9 %). Angioedema was mild in one, but rapidly progressive in another patient. Impending asphyxia prompted immediate intubation. CT showed orolingual swelling but no bleeding. One of 19 (5%) patients taking ACEi had orolingual angioedema, compared to 1 of 101 (1%) patients without ACEi. Medline search identified one further study about the occurrence of alteplase-associated angioedema in stroke patients stratified to the use of ACEi. Peto odds ratio of 37 (95 % CI 8-171) indicated an increased risk of alteplasetriggered angioedema for patients with ACEi (p <0.001). CONCLUSION: Orolingual angioedema is a potentially life-threatening complication of alteplase treatment in stroke patients, especially in those with ACEi. Orolingual hematoma as differential diagnosis can be excluded by CT-scan.

Burden of illness imposed by severe sepsis in Switzerland.

OBJECTIVE: This study aims to determine the burden of illness imposed by severe sepsis in Switzerland by evaluating the direct and indirect patient-related costs for critically ill patients with severe sepsis. METHODS: In order to estimate the direct costs a retrospective analysis was undertaken using records from 61 adult patients treated in three intensive care units (ICUs) in three different University hospitals in Switzerland, in 2001. Resource use was determined by a bottom up approach and valued using centre-specific unit costs for medication, nutrition, blood products, disposables and official tariffs for laboratory and microbiology analysis, diagnostic services, and clinical procedures. By adding centre-specific personnel and basic bed (hotel) costs total direct costs in the ICU were calculated. Indirect costs resulting from unfitness for work, early retirement, and premature death were calculated using official Swiss statistics for the years 1998-2000. RESULTS: The mean total direct costs for a severely septic patient are CHF 41,790 (+/- 33,222 CHF) or CHF 3244 (+/- 757 CHF) per day. Nonsurvivors cause significantly higher costs than survivors (CHF 45,956 vs. CHF 37,759, p <0.001). The total intensive care costs in Switzerland due to severe sepsis amount to CHF 146-355 million. Indirect costs were estimated to range from CHF 347 to 844 million (predominantly due to premature death). Consequently the burden of illness of severe sepsis can be estimated to range from CHF 493 to 1199 million per year in Switzerland (1 CHF = 0.662 Euro in 2001). CONCLUSION: Patients suffering from severe sepsis in Switzerland have a high mortality rate and spend a prolonged time in the ICU, leading to high direct and indirect costs. Particularly productivity losses due to premature death represent a considerable burden to the Swiss society.

Adverse cardiac events in ICU patients with presumptive antidepressant overdose.

BACKGROUND: Antidepressants account for most poison-related admissions to intensive care units. In selected patients with confirmed cyclic antidepressant intoxication a QRS interval <0.1 s in the ECG limb leads during the first six hours excludes adverse cardiac events. However, the incidence of cardiac events and the value of ECG criteria have never been assessed prospectively on patients with presumed antidepressant overdose. AIM: To assess ingested drugs, adverse cardiac events, and ECG findings in ICU patients with a presumptive diagnosis of antidepressant overdose. METHODS: 103 consecutive patients with a presumptive diagnosis of antidepressant overdose were enrolled and prospectively followed. Outcome criteria were arrhythmias, mortality, and duration of the ICU stay. RESULTS: Mixed intoxication was identified in 66 (64%) patients. Tricyclic antidepressants were found in 88 (85%), and serotonin-reuptake inhibitors in 25 (24%) patients. Mean APACHE II score was 9.5 (SD +/- 6.0). Arrhythmias affected 15 (15%) and cardiopulmonary resuscitation was performed on 4 (4%) patients. Three patients (3%) died in the ICU. Median duration of the ICU stay was 1 day (12 hours to 6 days). Adverse cardiac events affected patients with normal and prolonged QRS interval at study entry. CONCLUSIONS: Mixed intoxication is present in most ICU patients with suspected antidepressant overdose. There is a considerable risk for adverse cardiac events, even in the presence of normal ECG recordings within the first six hours after hospital admission.

[Pain management in surgical wards. Quality and solutions for improvement in the early postoperative period]. / Schmerzmanagement auf chirurgischen Bettenstationen. Qualität und Optimierbarkeit frühpostoperativer Schmerzbetreuung.

INTRODUCTION: Following guidelines pain levels should not exceed a score of 3 on the visual analog scale (VAS 1-10). We were interested in the actual surgical pain management of the postoperative period and the potential influences of a nurse-controlled intravenous morphine administration (NCA) on its quality. METHODS: Interventional study: interview of patients and nursing staff and examination of records concerning pain treatment following surgery. RESULTS: The interviews were conducted with 110 patients before and 125 patients after the intervention program. Before the intervention, one-half of the patients noted that they were never asked about their pain intensity within the first 24 h after surgery. Only 42% of the records showed at least one VAS documentation. Every fourth individual experienced a pain intensity > 3 without having received a supplementary pain medication. Following the morphine intervention program, documentation of pain scores increased significantly (72%; p < 0.0001) and more patients were familiar with the VAS (64% vs 46%; p < 0.0004). Median maximum as well as actual pain at the time of the interview decreased by one point (VAS). The percentage of patients whose supplementary pain prescription was totally used showed a significant increase (p = 0.035). Following morphine administration, no single individual complained about an undue waiting time in comparison to 15% of patients previously. Even though the morphine intervention project caused more work for the nursing staff, 75% of the personnel were convinced that the procedure was worth this investment. CONCLUSION: This data revealed a relevant deficiency of surgical pain management. Already basic instructions on pain management can significantly improve this treatment. Assigning additional authority to the nursing staff, such as a nurse-based intravenous opioid administration, can significantly raise the motivation of the personnel as well as the satisfaction of the patients involved.

[Diagnosis and risk stratification of acute coronary syndrome in general practice and in the hospital]. / Diagnostik und Risikostratifizierung des akuten Koronarsyndroms beim Hausarzt und im Spital.

Acute coronary syndromes usually present as acute chest pain but a manifestation with atypical symptoms or entirely without symptoms makes rapid diagnosis of this potentially lethal syndrome difficult and may lead to delay of the appropriate therapy. The role of the practitioner in this situation is complex since early exclusion of an acute coronary syndrome may be very difficult with the means available in a private practice; on the other hand the early hours which are critical for early therapy may be lost in a private practice. In the early phase of an acute coronary syndrome, diagnoses and risk stratification are based primarily on history, clinical presentation, ECG and biological markers. In the hospital, the time course of these parameters, functional tests for diagnosis and risk stratification as well as determination of left ventricular function and coronary angiography have additional relevance. Recent developments are the availability of highly sensitive and specific biological markers (Troponins), the new classification in acute coronary syndrome with and without ST-elevation and the identification of inflammatory processes in the coronary artery, which have added importantly to our understanding of the acute coronary syndrome. The availability of very early therapy and the possibilities of telemedicine have the potential to influence the pre-hospital diagnostic strategy and management of acute coronary syndromes.

Lethal autoimmune myocarditis in interferon-gamma receptor-deficient mice: enhanced disease severity by impaired inducible nitric oxide synthase induction.

BACKGROUND: Interferon-gamma (IFN-gamma) is an essential cytokine in the regulation of inflammatory responses in autoimmune diseases. Little is known about its role in inflammatory heart disease. METHODS AND RESULTS: We showed that IFN-gamma receptor-deficient mice (IFN-gammaR(-/-)) on a BALB/c background immunized with a peptide derived from cardiac alpha-myosin heavy chain develop severe myocarditis with high mortality. Although myocarditis subsided in wild-type mice after 3 weeks, IFN-gammaR(-/-) mice showed persistent disease. The persistent inflammation was accompanied by vigorous in vitro CD4 T-cell responses and impaired inducible nitric oxide synthase expression, together with evidence of impaired nitric oxide production in IFN-gammaR(-/-) hearts. Treatment of wild-type mice with the nitric oxide synthetase inhibitor N:-nitro-l-arginine-methyl-ester enhanced in vitro CD4 T-cell proliferation and prevented healing of myocarditis. CONCLUSIONS: Our data provide evidence that IFN-gamma protects mice from lethal autoimmune myocarditis by inducing the expression of inducible nitric oxide synthase followed by the downregulation of T-cell responses.