Development and validation of a clinico-biological score to predict outcomes in patients with drowning-associated cardiac arrest.

BACKGROUND: While several scoring systems have been developed to predict short-term outcome in out-of-hospital cardiac arrest patients, there is currently no dedicated prognostic tool for drowning-associated cardiac arrest (DACA) patients. METHODS: Patients experiencing DACA from two retrospective multicenter cohorts of drowning patients were included in the present study. Among the patients from the development cohort, risk-factors for day-28 mortality were assessed by logistic regression. A prediction score was conceived and assessed in patients from the validation cohort. RESULTS: Among the 103 included patients from the development cohort, the day-28 mortality rate reached 51% (53/103). Identified independent early risk-factors for day-28 mortality included cardiopulmonary resuscitation duration longer than 20 min (OR 6.40 [95% CI 1.88-23.32]; p = 0.003), temperature at Intensive Care Unit admission <34 °C (OR 8.84 [95% CI 2.66-32.92]; p < 0.001), need for invasive mechanical ventilation (OR 6.83 [95% CI 1.47-40.87]; p = 0.02) and lactate concentration > 7 mmol/L (OR 3.56 [95% CI 1.01-13.07]; p = 0.04). The Area Under the ROC Curve (AUC) of the developed score based on those variables reached 0.91 (95% CI, 0.86-0.97). The optimal cut-off for predicting poor outcomes was 4 points with a sensitivity of 92% (95% CI, 82-98%), a specificity of 82% (95% CI, 67-91%), a positive predictive value (PPV) of 84% (95% CI, 72-95%) and a negative predictive value (NPV) of 91% (95% CI, 79-96%). The assessment of this score on the validation cohort of 81 patients exhibited an AUC of 0.82. Using the same 4 points threshold, sensitivity, specificity, PPV and NPV values of the validation cohort were: 81%, 67%, 72% and 77%, respectively. CONCLUSION: In patients suffering from drowning induced initial cardiac arrest admitted to ICU with a DACA score ≥ 4, the likelihood of survival at day-28 is significantly lower. Prospective validation of the DACA score and assessment of its usefulness are warranted in the future.

Time to source control and outcome in community-acquired intra-abdominal infections: The multicentre observational PERICOM study.

BACKGROUND: Optimal management of community-acquired intra-abdominal infections (IAI) requires timely surgical source control and adequate anti-infective treatment. OBJECTIVE: To describe the initial management of community-acquired IAI admitted to the emergency department and assess the association between the length of time to either diagnosis or therapeutic procedures and patient outcomes. DESIGN: A prospective, multicentre, observational study. SETTING: Thirteen teaching hospitals in France between April 2018 and February 2019. PATIENTS: Two hundred and five patients aged at least 18 years diagnosed with community-acquired IAI. MAIN OUTCOME MEASURES: The primary outcome was hospital length of stay. The secondary outcome was hospital mortality. RESULTS: Patients had a mean age of 56 (± 21) years and a median [interquartile] SAPS II of 26 [17 to 34]. Among the study cohort, 18% were postoperatively transferred to intensive care unit and 7% had died by day 28. Median [IQR] time to imaging, antibiotic therapy and surgery were 4 [2 to 6], 7.5 [4 to 12.5] and 9 [5.5 to 17] hours, respectively. The length of time to surgical source control [0.99, 95% confidence interval (CI), 0.98 to 0.99], SOFA greater than 2 [0.36 (95% CI, 0.26 to 0.651)], age greater than 60 years [0.65 (95% CI, 0.45 to 0.94)], generalized peritonitis [0.7 (95% CI, 0.56 to 0.89)] and laparotomy surgery [0.657 (95% CI, 0.42 to 0.78)] were associated with longer hospital length of stay. The duration of time to surgical source control [1.02 (95% CI, 1.01 to 1.04)], generalized peritonitis [2.41 (95% CI, 1.27 to 4.61)], and SOFA score greater than 2 [6.14 (95% CI, 1.40 to 26.88)] were identified as independent risk factors for 28-day mortality. CONCLUSION: This multicentre observational study revealed that the time to surgical source control, patient severity and generalized peritonitis were identified as independent risk factors for increased hospital LOS and mortality in community-acquired IAI. Organisational strategies to reduce the time to surgical management of intra-abdominal infections should be further evaluated. STUDY REGISTRATION: ClinicalTrials.gov on 1 April 2018, NCT03544203.

CD169 and CD64 could help differentiate bacterial from CoVID-19 or other viral infections in the Emergency Department.

The identification of a bacterial, viral, or even noninfectious cause is essential in the management of febrile syndrome in the emergency department (ED), especially in epidemic contexts such as flu or CoVID-19. The aim was to assess discriminative performances of two biomarkers, CD64 on neutrophils (nCD64) and CD169 on monocytes (mCD169), using a new flow cytometry procedure, in patients presenting with fever to the ED during epidemics. Eighty five adult patients presenting with potential infection were included during the 2019 flu season in the ED of La Timone Hospital. They were divided into four diagnostic outcomes according to their clinical records: no-infection, bacterial infection, viral infection and co-infection. Seventy six patients with confirmed SARS-CoV-2 infection were also compared to 48 healthy volunteers. For the first cohort, 38 (45%) patients were diagnosed with bacterial infections, 11 (13%) with viral infections and 29 (34%) with co-infections. mCD169 was elevated in patients with viral infections, with a majority of Flu A virus or Respiratory Syncytial Virus, while nCD64 was elevated in subjects with bacterial infections, with a majority of Streptococcus pneumoniae and Escherichia coli. nCD64 and mCD169 showed 90% and 80% sensitivity, and 78% and 91% specificity, respectively, for identifying patients with bacterial or viral infections. When studied in a second cohort, mCD169 was elevated in 95% of patients with SARS-CoV-2 infections and remained at normal level in 100% of healthy volunteers. nCD64 and mCD169 have potential for accurately distinguishing bacterial and acute viral infections. Combined in an easy and rapid flow cytometry procedure, they constitute a potential improvement for infection management in the ED, and could even help for triage of patients during emerging epidemics.

Pneumothorax diagnosis with lung sliding quantification by speckle tracking: A prospective multicentric observational study.

INTRODUCTION: Lung ultrasound is commonly used for the diagnosis of pneumothorax. However, recognition of pleural sliding is subjective and can be difficult for novice. The primary objective was to compare a novices physician's performance in diagnosing pneumothorax from ultrasound (US) scans either with visual evaluation or with maximum longitudinal pleural strain (MLPS). The secondary objective was to compare the diagnostic relevance of US with visual evaluation or MLPS to diagnose pneumothorax with an intermediately experienced and an expert physician. METHODS: We conducted a prospective, observational study in two emergency department and two intensive care unit, between February 2019 and June 2020. We included 99 adult patients with suspected pneumothorax, who received a chest computed tomography (CT). Three physicians with different experience of interpreting US scans (a novice physician, an intermediately experienced physician, and an expert) analyzed the US scans of 99 patients with suspected pneumothorax (50 (51%) with confirmed pneumothorax), which were confirmed by CT scan. RESULTS: With a threshold of 5%, the MLPS sensitivity was 94% (95% CI [83%; 98%]), and the specificity was 100% (95% CI [93%; 100%]). The novice physician had an area under the curve (AUC) with visual analysis of 0.75 (95% CI [0.67; 0.83]) vs 0.86 (95% CI [0.79; 0.94]) with MLPS (p = 0.04). The intermediate physician's AUC for diagnosing pneumothorax with visual analysis was 0.93 (95% CI [0.88; 0.99]) vs 1.00 (95% CI [1.00; 1.00]) with MLPS (p < 0.01) and for the expert physician it was 0.98 (95% CI [0.95;1.00]) vs 0.97 (95% CI [0.93; 1.00]), respectively (p = 0.69). CONCLUSION: In our study, speckle tracking analysis improved the accuracy of US for the novice and the intermediate but not the expert sonographer in the diagnosis of pneumothorax.

Outbreak of pneumococcal pneumonia among shipyard workers in Marseille, France, January to February 2020.

We report the third outbreak of pneumococcal pneumonia within one year among workers in European shipyards. During January and February 2020, 37 cases of pneumonia were identified in a shipyard in Marseille, south-eastern France. Outbreak control measures were implemented, including a mass vaccination campaign with 23-valent pneumococcal polysaccharide vaccine targeting all shipyard workers. Given the high mobility of shipyard workers, coordinated responses between European public health institutes are necessary to avoid further outbreaks.

Adenosine plasma level in patients with paroxysmal or persistent atrial fibrillation and normal heart during ablation procedure and/or cardioversion.

The mechanism of atrial fibrillation (AF) in patients with normal heart remains unclear. While exogenous adenosine can trigger AF, nothing is known about the behavior of endogenous adenosine plasma level (APL) at the onset of AF and during ablation procedure. Ninety-one patients (68 with paroxysmal AF: 40 males, 66 ± 16 years; 23 with persistent AF: 14 males, 69 ± 11 years) and 18 controls were included. Among paroxysmal patients: i) medical therapy alone was performed in 45 cases and ablation procedure in 23. AF was spontaneously resolutive in 6 cases; ii) 23 underwent ablation procedure and blood was collected simultaneously in a brachial vein and in the left atrium; 17 were spontaneously in sinus rhythm while 6 were in sinus rhythm after direct current cardioversion. Among persistent patients: i) in 17 patients, blood samples were collected in a brachial vein before and after direct current cardioversion; ii) in 6 patients, blood samples were collected simultaneously in a brachial vein and in left atrium before and after cardioversion during ablation procedure. CV-APL was higher in patients with persistent AF vs patients with paroxysmal AF (median [range]: 0.9[0.6-1.1] vs 0.7[0.4-1.1] µM; p < 0.001). In patients with paroxysmal AF, LA-APL increased during the AF episode (0.95[0.85-1.4] vs 2.7[1.5-7] µM; p = 0.03) and normalized in sinus rhythm after DCCV. In patients with persistent AF, LA-APL was higher than CV-APL (1.2[0.7-1.8] vs 0.9[0.6-1.1] µM; p < 0.001), and both normalized in sinus rhythm (CV-APL: 0.8[0.6-1.1] vs 0.75[0.4-1] µM; p = 0.03), (LA-APL: 1.95[1.3-3] vs 1[0.5-1.15] µM; p = 0.03). The occurrence of AF is associated with a strong increase of APL in the atrium. The cause of this increase needs further investigations.

From Expert Protocols to Standardized Management of Infectious Diseases.

We report here 4 examples of management of infectious diseases (IDs) at the University Hospital Institute Méditerranée Infection in Marseille, France, to illustrate the value of expert protocols feeding standardized management of IDs. First, we describe our experience on Q fever and Tropheryma whipplei infection management based on in vitro data and clinical outcome. Second, we describe our management-based approach for the treatment of infective endocarditis, leading to a strong reduction of mortality rate. Third, we report our use of fecal microbiota transplantation to face severe Clostridium difficile infections and to perform decolonization of patients colonized by emerging highly resistant bacteria. Finally, we present the standardized management of the main acute infections in patients admitted in the emergency department, promoting antibiotics by oral route, checking compliance with the protocol, and avoiding the unnecessary use of intravenous and urinary tract catheters. Overall, the standardization of the management is the keystone to reduce both mortality and morbidity related to IDs.

Effects of acute respiratory and metabolic acidosis on diaphragm muscle obtained from rats.

BACKGROUND: Acute respiratory acidosis is associated with alterations in diaphragm performance. The authors compared the effects of respiratory acidosis and metabolic acidosis in the rat diaphragm in vitro. METHODS: Diaphragmatic strips were stimulated in vitro, and mechanical and energetic variables were measured, cross-bridge kinetics calculated, and the effects of fatigue evaluated. An extracellular pH of 7.00 was obtained by increasing carbon dioxide tension (from 25 to 104 mmHg) in the respiratory acidosis group (n = 12) or lowering bicarbonate concentration (from 24.5 to 5.5 mM) in the metabolic acidosis group (n = 12) and the results compared with a control group (n = 12, pH = 7.40) after 20-min exposure. RESULTS: Respiratory acidosis induced a significant decrease in maximum shortening velocity (-33%, P < 0.001), active isometric force (-36%, P < 0.001), and peak power output (-59%, P < 0.001), slowed relaxation, and decreased the number of cross-bridges (-35%, P < 0.001) but not the force per cross-bridge, and impaired recovery from fatigue. Respiratory acidosis impaired more relaxation than contraction, as shown by impairment in contraction-relaxation coupling under isotonic (-26%, P < 0.001) or isometric (-44%, P < 0.001) conditions. In contrast, no significant differences in diaphragmatic contraction, relaxation, or contraction-relaxation coupling were observed in the metabolic acidosis group. CONCLUSIONS: In rat diaphragm, acute (20 min) respiratory acidosis induced a marked decrease in the diaphragm contractility, which was not observed in metabolic acidosis.

Impact of a computerized decision support system on compliance with guidelines on antibiotics prescribed for urinary tract infections in emergency departments: a multicentre prospective before-and-after controlled interventional study.

OBJECTIVES: Urinary tract infections (UTIs) are one of the leading reasons for antibiotic prescriptions in emergency departments (EDs), with half of these antibiotics being inappropriately prescribed. Our objective was to assess the impact of a computerized decision support system (CDSS) on compliance with guidelines on empirical antibiotic prescriptions (antibiotic and duration) for UTIs in EDs. METHODS: A multicentre prospective before-and-after controlled interventional study was conducted from 19 March to 28 October 2012. All adults diagnosed with community-acquired UTIs (cystitis, pyelonephritis or prostatitis) at three French EDs were included. The antibiotic therapy was considered compliant with guidelines if the antibiotic and the duration prescribed were in accordance with the national guidelines. Data were collected using electronic medical records. Paired tests were used when comparing periods within each ED and global analyses used multivariate logistic mixed models. RESULTS: Nine hundred and twelve patients were included during the 30 week study period. The CDSS was used in 59% of cases (182/307). The CDSS intervention improved the compliance of antibiotic prescriptions in only one ED in a bivariate analysis (absolute increase +20%, P = 0.007). The choice of the antibiotic was improved in multivariate analyses but only when the CDSS was used [OR = 1.94 (95% CI 1.13-3.32)]. The CDSS also changed the initial diagnosis in 23% of cases, in all three EDs. CONCLUSIONS: The CDSS only partially improved compliance with guidelines on antibiotic prescriptions in UTIs.

Undercorrection of hypernatremia is frequent and associated with mortality.

BACKGROUND: About 1% of patients admitted to the Emergency Department (ED) have hypernatremia, a condition associated with a mortality rate of 20 to 60%. Management recommendations originate from intensive care unit studies, in which patients and medical diseases differ from those in ED. METHODS: We retrospectively studied clinical characteristics, treatments, and outcomes of severely hypernatremic patients in the ED and risk factors associated with death occurrence during hospitalization. RESULTS: During 2010, 85 cases of severe hypernatremia ≥ 150 mmol/l were admitted to ED. Hypernatremia occurred in frail patients: mean age 79.7 years, 55% institutionalized, 28% with dementia.Twenty four percent of patients died during hospitalization. Male gender and low mean blood pressure (MBP) were independently associated with death, as well as slow natremia correction speed, but not the severity of hyperosmolarity at admission. Infusion solute was inappropriate for 45% of patients with MBP <70 mmHg who received hypotonic solutes and 22% of patients with MBP ≥ 70 mmHg who received isotonic solutes or were not perfused. CONCLUSIONS: This is the first study assessing outcome of hypernatremic patients in the ED according to the treatment provided. It appears that not only a too quick, but also a too slow correction speed is associated with an increased risk of death regardless of initial natremia. Medical management of hypernatremic patients must be improved regarding evaluation and treatment.

Can the use of whole-body CT be reduced in cases of kinetic-based polytrauma patients without a clinical severity criterion? A bi-center retrospective study.

OBJECTIVE: To identify clinical and biological criteria predictive of significant traumatic injury in only kinetic-based polytrauma patients without clinical severity criteria. To propose a decisional algorithm to assist the emergency doctor in deciding whether or not to perform a WBCT in the above population. METHODS: Retrospective bi-center study. 1270 patients with high velocity trauma without clinical severity criteria, for whom a WBCT was performed in 2017, were included. Patients with hemodynamic, respiratory or neurological severity criterion or those requiring pre-hospital resuscitation measures were excluded. Our primary endpoint was the identification of a significant lesion, i.e. any lesion that led to hospitalization > 24 h for monitoring or medico-surgical treatment. Data collected were age, sex, mechanism of injury, Glasgow Coma Scale score, number of symptomatic body regions, blood alcohol level, and neutrophil count. RESULTS: Multivariate analysis found independent predictors of significant injury: fall > 5 m (OR: 14.36; CI: 2.3-283.4; p = 0.017), Glasgow score = 13 or 14 (OR: 4.40; CI:1.30-18.52; p = 0.027), presence of 2 symptomatic body regions (OR: 10.21; CI: 4.66-23.72; p = 0.05), positive blood alcohol level (OR: 2.81; CI: 1.13-7.33; p = 0.029) and neutrophilic leukocytosis (OR: 8.76; CI: 3.94-21.27; p = 0.01). A composite clinico-biological endpoint predictive of the absence of significant lesion was identified using a Classification and Regression Tree: number of symptomatic regions < 2, absence of Neutrophilic leukocytosis and negative blood alcohol concentration. CONCLUSION: A simple triage algorithm was created with the objective of identifying, in high velocity trauma without clinical severity criteria, those without significant traumatic injury.

A pig model for blunt chest trauma: no pulmonary edema in the early phase.

OBJECTIVE: Chest trauma remains a leading cause of trauma-death. Since lung contusion is one of the most important lesions implicated, the aim of this experimental study was to evaluate the cardiorespiratory consequences of an isolated lung contusion model. METHODS: Twenty-eight anesthetized pigs were studied during four hours. We induced a right lung contusion with five bolt shots (70 joules each) using a 22-caliber charge in twenty of them. Eight others pigs constituted the control group. The trauma consequences were assessed by histology, measurements of arterial oxygenation, plasma cytokines, pressure-volume mechanics, hemodynamic monitoring using the PiCCO system and a pulmonary artery catheter. The extra-vascular lung water was measured using the gravimetric method. RESULTS: Histology confirmed an isolated right lung contusion without cardiac injury. Compared to baseline values, the trauma group was characterized by a decrease in cardiac index (3.3 ± 0.8 vs 3.9 ± 1.2 l/min/m(2); P < .05) and mean arterial pressure (80 ± 21 vs 95 ± 16 mmHg; P < .05) without preload or afterload modification. Oxygenation (PaO2/FiO2: 349 ± 87 vs 440 ± 75; P < .05) and static compliance (26.3 ± 7.4 vs 30.3 ± 7.8 ml/cmH2O; P < .05) were also impaired during two hours compared to baseline. No edema was noticed in either group whatever the lung considered. All measured cytokines were below the detection threshold. CONCLUSIONS: An isolated right lung contusion is associated with rapid but transient cardiorespiratory impairments. Despite the large extent of the lung contusion, no pulmonary edema appeared during the period studied.

Crew and patient safety in ambulances: results of a personnel survey and experimental side impact crash test.

INTRODUCTION: Ambulance drivers often travel under stressful conditions at high speed while using vehicles with poor high-speed maneuverability. The occupant safety of ambulance vehicles has not yet been addressed by the automotive safety paradigm; particularly for the rear patient compartment. This study had two objectives: (1) to assess by survey the French Emergency Medical Services (EMS) to determine the layout of the vehicle most often used and the EMS personnel's behavior during transport; and (2) to conduct a crash test to analyze the injuries which may affect EMS personnel and patients in the rear patient compartment. METHOD: Firstly, a survey was distributed to the 50 largest metropolitan French EMS programs. Secondly, a crash test was performed with a Mobile Intensive Care Unit (MICU) in conditions closest to reality. RESULTS: Forty-nine of the 50 biggest metropolitan French EMS programs responded to the survey. This represents 108 French MICUs. During the last three years, 12 of 49 EMS programs (24%) identified at least one accident with an MICU, and six of these 12 (50%) suffered at least one death in those accidents. A crash test using a typical French EMS MICU showed that after impact of a collision, the ambulance was moved more than five meters with major consequences for all passengers. A study-approved human cadaver placed in the position of a potential patient was partially thrown from the stretcher with a head impact. The accelerometric reaction of the anthropomorphic manikin head was measured at 48G. CONCLUSION: The crash test demonstrated a lack of safety for EMS personnel and patients in the rear compartment. It would be preferable if each piece of medical equipment were provided with a quick release system resistant to three-dimensional 10G forces. The kinetic changes undergone by the "patient" substitute on the stretcher would probably have an effect of causing injury pathology. This study highlights the need for more research and development in this area.

Impact of the implementation of a trauma system on compliance with evidence-based clinical management guidelines in penetrating thoracic trauma.

PURPOSE: Since 2014, a trauma system (TS) for the Provence-Alpes-Cote-d'Azur (PACA) region has been set up with protocols based on the European guidelines for the management of bleeding trauma patients. The present study aims to assess compliance with protocols in penetrating thoracic trauma on admission to a level I trauma centre and to determine whether compliance impacts morbidity and mortality. METHODS: This multicentric pre-post study included all penetrating thoracic trauma patients referred to Marseille area level I centres between January 2009 and December 2019. On the basis of the European guidelines, eight objectively measurable recommendations concerning the in-hospital trauma care for the first 24 h were analysed. Per-patient and per-criterion compliance rates and their impact on morbidity and mortality were evaluated before and after TS implementation. RESULTS: A total of 426 patients were included. No differences between the two groups (before and after 2014) were reported for demographics or injury severity. The median (interquartile range) per-patient compliance rate increased from 67% [0.50; 0.75] to 75% [0.67; 1.0] (p < 0.01) after implementation of a TS. The 30-day morbidity-mortality was, respectively, of 17% (30/173) and 13% (32/253) (p = 0.18) before and after TS implementation. A low per-patient compliance rate was associated with an increase in the 30-day morbidity-mortality rate (p < 0.01). Severity score-adjusted per-patient compliance rates were associated with decreased 30-day morbidity-mortality (odds ratio [IC 95%] = 0.98 [0.97; 0.99] p = 0.01). CONCLUSION: Implementation of a TS was associated with better compliance to European recommendations and better outcomes for severe trauma patients. These findings should encourage strict adherence to European trauma protocols to ensure the best patient outcomes.

Acute mesenteric ischemia: which predictive factors of delayed diagnosis at emergency unit?

PURPOSE: Acute mesenteric ischemia (AMI) is frequently diagnosed late, leading to a poor prognosis. Our aims were to identify predictive factors of delayed diagnosis and to analyze the outcomes of patients with AMI admitted in emergency units. METHODS: All the patients with AMI (2015-2020), in two Emergency units, were retrospectively included. Two groups were defined according to the time of diagnosis between the arrival at emergency unit and the CT scan: ≤ 6 h (early), > 6 h (delayed). RESULTS: 119 patients (mean age = 71 ± 7 years) were included. The patients with a delayed diagnosis (n = 33, 28%) were significantly associated with atypical presentation, including lower rates of abdominal pain (73 vs 89%, p = 0.003), abdominal tenderness (33 vs 43%, p = 0.03), and plasma lactate (4 ± 2 vs 6 ± 7 mmol/l, p = 0.03) when compared with early diagnosis. After multivariate analysis, the absence of abdominal pain was the only independent predictive factor of delayed diagnosis (Odd Ratio = 0.17; 95% CI = 0.03-0.88, p = 0.03). Patients with delayed diagnosis tended to be associated to lower rates of revascularization (9 vs 17%, p = 0.4), higher rates of major surgical morbidity (90 vs 57%, p = 0.1), longer length of stay (16 ± 23 vs 13 ± 15 days, p = 0.4) and, at the end of follow-up, higher rate of short small bowel syndrome (18 vs 7%, p = 0.095). CONCLUSION: AMI is a challenge for emergency physicians. History of patient, physical exam, biological data are not sufficient to diagnose AMI. New biomarkers, and awareness of emergency physicians should improve and accelerate the diagnosis of AMI.

Adenosinergic System and Neuroendocrine Syncope: What Is the Link?

Although very common, the precise mechanisms that explain the symptomatology of neuroendocrine syncope (NES) remain poorly understood. This disease, which can be very incapacitating, manifests itself as a drop in blood pressure secondary to vasodilation and/or extreme slowing of heart rate. As studies continue, the involvement of the adenosinergic system is becoming increasingly evident. Adenosine, which is an ATP derivative, may be involved in a large number of cases. Adenosine acts on G protein-coupled receptors with seven transmembrane domains. A1 and A2A adenosine receptor dysfunction seem to be particularly implicated since the activation leads to severe bradycardia or vasodilation, respectively, two cardinal symptoms of NES. This mini-review aims to shed light on the links between dysfunction of the adenosinergic system and NHS. In particular, signal transduction pathways through the modulation of cAMP production and ion channels in relation to effects on the cardiovascular system are addressed. A better understanding of these mechanisms could guide the pharmacological development of new therapeutic approaches.

Fall in oxygen tension of culture medium stimulates the adenosinergic signalling of a human T cell line.

We examined the short-course expression of various parameters involved in the adenosinergic signalling of a human T cell line during in vitro decrease of the medium culture oxygen tension mimicking in vivo hypoxia. Fall of 92 mmHg in oxygen tension of culture medium induced in CEM, a CD4+ human T cell line, a continuous production of hypoxia-inducing factor-1α with a plateau value at 9 h, a rapid increase in adenosine production peaking at 3 h and a decrease in adenosine deaminase peaking at 6 h. The adenosine A(2A) receptor (A(2A)R) protein level of CEM cells was enhanced with a peak at 6 h. Intracellular 3',5'-cyclic adenosine monophosphate accumulated in CEM cells with a maximal level at 9 h. These results show that a human-cultured T cells line can upregulate its own adenosine production and A(2A)R expression during exposure to acute hypoxia. Hypoxia-increased stimulation of the adenosinergic signalling of T cells may have immunosuppressive properties and, consequently, A(2A)R agonists may have therapeutic relevance.

Association of mechanical chest compression and prehospital thrombolysis.

Pulmonary embolism (PE) is a common cause of sudden death; the use of prehospital thrombolysis is currently a last-resort option and requires a prolonged cardiopulmonary resuscitation (CPR). Novel mechanical devices have recently been introduced that provides automatic mechanical chest compression (AMCC) according to the guidelines and continually without decrease efficiency throughout prolonged resuscitation. A 54 year-old woman with a history of breast cancer experienced sudden chest pain and severe dyspnea. A mobile intensive care unit was dispatched to her home. During physical examination, she suddenly collapsed with pulseless electrical activity as the initial rhythm. Prehospital thrombolysis during CPR combined with use of AMCC was performed based on a strongly suspected diagnosis of massive PE. After 75 minutes of effective CPR, return of spontaneous circulation was attained. After admission to an intensive care unit, computed tomographic scan confirmed bilateral PE. The patient was discharged 3 weeks after CPR in good neurologic condition. To our knowledge, this is the first case describing combined use of thrombolysis and AMCC in out-ofhospital cardiac arrest. However, for the time being, prehospital thrombolysis in CPR continues to be a measure that should only be performed on a case-by-case basis based on informed decision. Further studies are needed to evaluate the efficacy and safety of AMCC with thrombolysis and thus prolonged CPR.

Safety, Pharmacokinetic, and Pharmacodynamic Study of a Sublingual Formula for the Treatment of Vasovagal Syncope.

BACKGROUND: Vasovagal syncope is a common cause of syncope which, if recurrent, can have multiple negative consequences such as injury and occupational disability. Various medications can be used to decrease the recurrence of vasovagal syncope but there are no drugs that can be used by patients to interrupt a perceived vasovagal episode. METHODS: A phase I study was performed to evaluate the tolerability and safety of a gel formulation containing capsaicin (1 mg), phenylephrine HCL (PE) and caffeine citrate (200 mg) (CPC) in normal adult volunteers. Secondary objectives were to characterize the pharmacokinetics (PK) of the CPC formulation and the highest dose of PE needed to achieve a target increase in systolic BP of at least 40 mmHg. After receiving the first dose, a second dose of the CPC mixture was administered at 2 h. Suboptimal changes in systolic blood pressure (SBP) were noted at PE doses of 0.6, 1.2, and 1.8 mg, therefore a second cohort was studied at PE doses of 10, 20, and 30 mg. Blood samples were collected in rapid sequence and were assayed for all three drugs. RESULTS: A total of 17 subjects received the drug with no serious adverse effects reported. All doses were well tolerated, although the capsaicin content usually caused expected temporary oral and gastric discomfort. One subject did not complete the study because of a vasovagal reaction that was associated with the frequent blood sampling. There was a 5-25 min lag in the appearance of measurable blood concentrations of capsaicin and phenylephrine. Most subjects had baseline caffeine concentrations from dietary use, with a gradual increase noted after 15 min consistent with GI absorption. Although the intended criterion of a 40 mmHg increase in SBP was not reached, a clinically significant increase in BP for at least 15 min was noted in the six subjects who received the highest dose of PE (30 mg), with a gradual decline over the next 2 h. CONCLUSION: The ternary mixture of capsaicin, phenylephrine, and caffeine was well tolerated when administered as two sublingual/oral doses over a 2-h period.

Survival and Factors Associated with Survival with Extracorporeal Life Support During Cardiac Arrest: A Systematic Review and Meta-Analysis.

The survival rate after cardiac arrest (CA) remains low. The utilization of extracorporeal life support is proposed to improve management. However, this resource-intensive tool is associated with complications and must be used in selected patients. We performed a meta-analysis to determine predictive factors of survival. Among the 81 studies included, involving 9256 patients, survival was 26.2% at discharge and 20.4% with a good neurologic outcome. Meta-regressions identified an association between survival at discharge and lower lactate values, intrahospital CA, and lower cardio pulmonary resuscitation (CPR) duration. After adjustment for age, intrahospital CA, and mean CPR duration, an initial shockable rhythm was the only remaining factor associated with survival to discharge (ß = 0.02, 95% CI: 0.007-0.02; p = 0.0004).