Hyponatremia and activation of vasopressin secretion are both independently associated with 30-day mortality: results of a multicenter, observational study.

BACKGROUND: Hyponatremia is a common feature of acute illness and associated with increased mortality. This may be explained by a stress-mediated activation of the vasopressin system with an increase in free-water reabsorption. OBJECTIVES: To investigate whether the association between hyponatremia and mortality could be explained by activation of the vasopressin system. METHODS: We prospectively enrolled adult, medical patients seeking emergency care in three centres in Switzerland, France and the United States. We investigated associations between admission plasma sodium and copeptin, a stable portion of the vasopressin-precursor peptide, with 30-day mortality. We performed uni- and multivariate regression analysis. RESULTS: Of 6962 included patients, 18% had hyponatremia (sodium ≤135 mmol L-1 ), which doubled their risk for mortality compared to patients with normonatremia (8.3% vs. 3.8%). This association was confirmed in a multivariate-adjusted logistic regression analysis [adjusted odds ratio (OR) 1.47, 95% CI 1.12-1.93, P = 0.005]. Vasopressin levels, mirrored by copeptin, were also increased in nonsurvivors and strongly associated with mortality (adjusted OR 3.42, 95% CI 2.76-4.25, P < 0.001). The association between hyponatremia and mortality remained unchanged when adding copeptin levels to the regression model (fully adjusted OR 1.53, 95% CI 1.16-2.00, P = 0.002). CONCLUSION: This prospective study including medical patients upon emergency room admission found hyponatremia as well as an activation of the vasopressin system to be independently associated with mortality. This suggests that stress- and vasopressin-independent mechanisms are responsible for the association of low sodium levels with mortality.

Procalcitonin for clinical decisions on influenza-like illness in emergency department during influenza a(H1N1)2009 pandemic.

PURPOSE: We aimed to determine whether serum procalcitonin (PCT) values could help in identifying flu in patient admitted to the emergency department (ED) with influenza-like illness (ILI) during influenza A(H1N1)2009 pandemic. METHODS: An observational retrospective cohort study was performed in a referral ED for emerging infectious diseases. All patients tested for influenza A(H1N1)2009 by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and procalcitonin between June 2009 and January 2010 were analyzed. PCT was studied for its negative predictive value of bacterial infection. Patients PCT-/RT-PCR + were considered as true positive. RESULTS: On the 80 patients included, 16 were positive for influenza A(H1N1)2009 RT-PCR, all but one of them had low PCT concentrations. Conversely, 19 (30%) of the 64 patients with negative RT-PCR had elevated PCT concentrations. For a PCT threshold <0.25 µg/L, sensitivity was 0.94, specificity 0.30, positive predictive value 0.25 and negative predictive value 0.95 for the diagnosis of flu. CONCLUSION: In the context of an influenza pandemic, serum PCT measurement may be useful for clinical decisions in the ED as most of RT-PCR confirmed patients have low PCT values. Patients with PCT above 0.25 µg/L are unlikely to have a unique diagnosis of flu.

Organization in response to massive afflux of war victims in civilian practice - experimental feedback from the November 2015 Paris terrorist attacks.

The arrival of a large number of war-weapon casualties at a civilian trauma center requires anticipation. A plan defining the management principles and the respective roles of the involved physicians and nurses and their interaction with each other is essential. Uni-directional patient flow associated with adequate numbers of staff physicians and nurses under the leadership of a medical director is essential to prevent the overwhelming of the trauma center. Routine and regular interaction between the pre-hospital medical flow control system and the medical director, on one hand, and between surgical teams and the medical director, on the other, are necessary to know when to apply "damage control" surgical techniques. Based on the feedback of a level 1 trauma center that received 53 victims of the November 13, 2015 terrorist attack in Paris, we present the factors of success, and the stumbling blocks.

The association of admission hyperglycaemia and adverse clinical outcome in medical emergencies: the multinational, prospective, observational TRIAGE study.

AIMS: The clinical relevance of hyperglycaemia in an emergency department population remains incompletely understood. We investigated the association between admission blood glucose levels and adverse clinical outcomes in a large emergency department cohort. METHODS: We prospectively enrolled 7132 adult medical patients seeking emergency department care in three tertiary care hospitals in Switzerland, France and the USA. We used adjusted multivariable logistic regression models to examine the association between admission blood glucose levels and 30-day mortality, as well as adverse clinical course stratified by pre-existing diabetes and principal medical diagnoses. RESULTS: In 6044 people without diabetes (84.7%), severe hyperglycaemia, defined as a glucose level of > 11.1 mmol/l (200 mg/dl), was associated with a doubling in the risk of 30-day mortality [adjusted odds ratio (OR) 1.9; 95% confidence interval (95% CI), 1.1 to 3.3; P = 0.018] and a three-fold increase in the risk of intensive care unit admission (adjusted OR 3.0; 95% CI, 1.9 to 4.9; P < 0.001). These associations were similar among different diagnoses. In the population with diabetes (n = 1088), no association with 30-day mortality was found (adjusted OR 1.0; 95% CI, 0.6 to 1.8; P for interaction = 0.001), whereas the association with intensive care unit admission was weaker (adjusted OR 2.4; 95% CI, 1.5 to 4.1; P for interaction = 0.011). Overall 30-day mortality was higher in those with diabetes than in those without (6.1 vs. 4.4%, P = 0.015). CONCLUSIONS: In this large medical emergency department patient cohort, admission hyperglycaemia was strongly associated with adverse clinical course in people without diabetes. (Clinical Trial Registry No: NCT01768494).

Reproducibility of clinical events adjudications in a trial of venous thromboembolism prevention.

Essentials The reproducibility of Clinical Events Committee (CEC) adjudications is almost unexplored. A random selection of events from a venous thromboembolism trial was blindly re-adjudicated. 'Unexplained sudden deaths' (possible fatal embolism) explained most discordant adjudications. A precise definition for CEC adjudication of this type of events is needed and proposed. SUMMARY: Background When clinical trials use clinical endpoints, establishing independent Clinical Events Committees (CECs) is recommended to homogenize the interpretation of investigators' data. However, the reproducibility of CEC adjudications is almost unexplored. Objectives To assess the reproducibility of CEC adjudications in a trial of venous thromboembolism (VTE) prevention. Methods The PREVENU trial, a multicenter trial of VTE prevention, included 15 351 hospitalized medical patients. The primary endpoint was the composite of symptomatic VTE, major bleeding or unexplained sudden death (interpreted as possible fatal pulmonary embolism [PE]) at 3 months. The CEC comprised a chairman and four pairs of adjudicators. Of 2970 adjudicated clinical events, a random selection of 179 events (121 deaths, 40 bleeding events, and 18 VTE events) was blindly resubmitted to the CEC. Kappa values and their 95% confidence intervals (CIs) were calculated to measure adjudication agreement. Results Overall, 18 of 179 (10.1%, 95% CI 6.5-15.3%) adjudications proved discordant. Agreement for the PREVENU composite primary endpoint was good (kappa = 0.73, 95% CI 0.61-0.85). When analyzed separately, agreements were very good for non-fatal VTE events (1, 95% CI not applicable), moderate for all (fatal and non-fatal) VTE events (0.58, 95% CI 0.34-0.82), good for fatal and non-fatal major bleeding events (0.71, 95% CI 0.55-0.88), and moderate for all fatal events (0.60, 95% CI 0.40-0.81). Unexplained sudden death interpreted as possible fatal PE was responsible for nine of 18 (50%) discordant adjudications. Conclusion The reproducibility of CEC adjudications was good or very good for non-fatal VTE and bleeding events, but insufficient for VTE-related deaths, for which more precise and widely accepted definitions are needed.

Viruses detected by systematic multiplex polymerase chain reaction in adults with suspected community-acquired pneumonia attending emergency departments in France.

UNLABELLED: Infectious agents associated with community-acquired pneumonia (CAP) are under-studied. This study attempted to identify viruses from the upper respiratory tract in adults visiting emergency departments for clinically suspected CAP. Adults with suspected CAP enrolled in the ESCAPED study (impact of computed tomography on CAP diagnosis) had prospective nasopharyngeal (NP) samples studied by multiplex PCR (targeting 15 viruses and four intracellular bacteria). An adjudication committee composed of infectious disease specialists, pneumologists and radiologists blinded to PCR results reviewed patient records, including computed tomography and day 28 follow up, to categorize final diagnostic probability of CAP as definite, probable, possible, or excluded. Among the 254 patients enrolled, 78 (31%) had positive PCR, which detected viruses in 72/254 (28%) and intracellular bacteria in 8 (3%) patients. PCR was positive in 44/125 (35%) patients with definite CAP and 21/83 (25%) patients with excluded CAP. The most frequent organisms were influenza A/B virus in 27 (11%), rhinovirus in 20 (8%), coronavirus in seven (3%), respiratory syncytial virus in seven (3%) and Mycoplasma pneumoniae in eight (3%) of 254 patients. Proportion of rhinovirus was higher in patients with excluded CAP compared with other diagnostic categories (p = 0.01). No such difference was observed for influenza virus. Viruses seem common in adults attending emergency departments with suspected CAP. A concomitant clinical, radiological and biological analysis of the patient's chart can contribute to either confirm their role, or suggest upper respiratory tract infection or shedding. Their imputability and impact in early management of CAP deserve further studies. CLINICAL TRIALS REGISTRATION: NCT01574066.

Biomarkers and infection in the emergency unit.

The emergency unit is one of the main places for acute medical care and therefore, has a pivotal role in determining a diagnosis of bacterial infection and initiating antibiotic therapy. There is an unquestionable and growing interest for infection biomarkers because of the polymorphism of septic state presentations in the emergency unit and the lack of accuracy of available biological tools. The C Reactive protein (CRP) is a biomarker of inflammation, not of infection. CRP is highly sensitive but lacks specificity. Moreover, there are few interventional studies evaluating its true added diagnostic value in the emergency unit, therefore preventing using CRP as a biomarker of infection. Serum procalcitonin (PCT) dosage is more specific for the diagnosis of bacterial infection. PCT levels do not increase or only slightly in non-bacterial inflammatory syndromes. PCT also provides prognostic information and risk stratification assessment in the emergency unit. Moreover, many authors of interventional studies have validated the contribution of PCT in decision taking for antibiotic therapy when suspecting low respiratory tract infection. It is currently the first-line biomarker of infection in the emergency unit. Other biomarkers such as presepsin (sCD14) may be contributive for the diagnosis and prognosis.

Influence of procalcitonin on decision to start antibiotic treatment in patients with a lower respiratory tract infection: insight from the observational multicentric ProREAL surveillance.

Procalcitonin (PCT)-guided antibiotic stewardship is a successful strategy to decrease antibiotic use. We assessed if clinical judgement affected compliance with a PCT-algorithm for antibiotic prescribing in a multicenter surveillance of patients with lower respiratory tract infections (LRTI). Initiation and duration of antibiotic therapy, adherence to a PCT algorithm and outcome were monitored in consecutive adults with LRTI who were enrolled in a prospective observational quality control. We correlated initial clinical judgment of the treating physician with algorithm compliance and assessed the influence of PCT on the final decision to initiate antibiotic therapy. PCT levels correlated with physicians' estimates of the likelihood of bacterial infection (p for trend <0.02). PCT influenced the post-test probability of antibiotic initiation with a greater effect in patients with non-pneumonia LRTI (e.g., for bronchitis: -23 % if PCT ≤ 0.25 µg/L and +31 % if PCT > 0.25 µg/L), in European centers (e.g., in France -22 % if PCT ≤ 0.25 µg/L and +13 % if PCT > 0.25 µg/L) and in centers, which had previous experience with the PCT-algorithm (-16 % if PCT ≤ 0.25 µg/L and +19 % if PCT > 0.25 µg/L). Algorithm non-compliance, i.e. antibiotic prescribing despite low PCT-levels, was independently predicted by the likelihood of a bacterial infection as judged by the treating physician. Compliance was significantly associated with identification of a bacterial etiology (p = 0.01). Compliance with PCT-guided antibiotic stewardship was affected by geographically and culturally-influenced subjective clinical judgment. Initiation of antibiotic therapy was altered by PCT levels. Differential compliance with antibiotic stewardship efforts contributes to geographical differences in antibiotic prescribing habits and potentially influences antibiotic resistance rates.

[Acute airway obstruction mimicking angioedema and revealing spontaneous compressive haematoma of thyroid goitre]. / Détresse respiratoire secondaire à un hématome spontané compressif sur goitre rétrosternal, initialement considérée comme un angiœdème.

Substernal thyroid goitre is the most common cause of superior mediastinal masses. Respiratory symptoms are commonly present, in up to 90% of reported cases. However, these symptoms are rarely acute and life threatening. We report a case of acute airway obstruction, initially misdiagnosed as angioedema, revealing a spontaneous compressive substernal goitre haematoma, in a patient under anticoagulant. This life-threatening complication in patients with goitre and anticoagulant should be known.

Can C-reactive protein, procalcitonin and mid-regional pro-atrial natriuretic peptide measurements guide choice of in-patient or out-patient care in acute pyelonephritis? Biomarkers In Sepsis (BIS) multicentre study.

Whereas C-reactive protein (CRP), procalcitonin (PCT) and mid-regional pro-atrial natriuretic peptide (ANP) may be of use at the bedside in the management of adult patients with infectious disorders, their usefulness has not been established in the setting of acute pyelonephritis. To assess the effectiveness of CRP, PCT and ANP measurements in guiding emergency physicians' decisions whether to admit to hospital patients with acute pyelonephritis, we conducted a multicentre, prospective, observational study in 12 emergency departments in France; 582 consecutive patients were included. The reference standard for admission was defined by experts' advice combined with necessity of admission or death during the 28-day follow-up. Baseline CRP, PCT and ANP were measured and their accuracy in identifying the necessity of admission was analysed using area under curves (AUC) of receiver-operating characteristic (ROC) plots. According to the reference standard, 126 (22%) patients required admission. ANP (AUC 0.75, 95% CI 0.69-0.80) and PCT (AUC 0.75, 95% CI 0.71-0.80) more accurately predicted this than did CRP (AUC 0.69, 95% CI 0.64-0.74). The positive and negative likelihood ratios for each biomarker remained clinically irrelevant whatever the threshold. Our results did not support the use of these markers to help physicians in deciding about admission of patients experiencing acute pyelonephritis in daily practice.

[Increase of serum procalcitonin levels during a neuroleptic malignant syndrome]. / Augmentation de la concentration sérique de la procalcitonine au cours d'un syndrome malin des neuroleptiques.

When fever occurs in a patient treated with a neuroleptic, the diagnosis of a neuroleptic malignant syndrome is difficult to differentiate to that of an infectious event. Among inflammation biomarkers of inflammation, serum procalcitonin levels increase both quickly and specifically during a bacterial infection. We report the first case of a neuroleptic malignant syndrome associated with a significant increase of serum procalcitonin levels, without concomitant septic syndrome. The neuroleptic malignant syndrome might be a non-infectious clinical situation associated with an increased serum procalcitonin concentration.

Procalcitonina: ¿marcador de elección de infección bacteriana en 2007?

La procalcitonina (PCT) es un marcador precoz, sensible pero sobre todo específico de las infecciones bacterianas. Después de haber sido estudiada, principalmente en reanimación, sus indicaciones se ampliaron a los servicios médicos y de urgencias. Los campos de aplicación de la determinación de PCT en Medicina son variados: enfermedad inflamatoria versus complicación infecciosa, infección bacteriana versus infección viral, diagnóstico etiológico de meningitis con examen directo negativo o estado de shock, seguimiento de la eficacia de una terapia con antibióticos. La PCT tiene igualmente un valor pronóstico en el sentido de que su aumento en el curso de una sepsis parece directamente proporcional a la intensidad de la reacción inflamatoria del huésped frente a la agresión microbiana.

[Procalcitonin measurement in adult clinical practice]. / Le dosage de la procalcitonine en pratique clinique chez l'adulte.

PURPOSE: The availability of a sensitive, specific and prognostic marker of bacterial infection is a major issue. More than ten years after the first publication assessing the usefulness of serum procalcitonin dosage (PCT), its exact place in the diagnostic process remained to be defined. The purpose of this review is to point out the indications of PCT measurement in clinical practice in the adult population. RELEVANT DATA: PCT is an early, sensitive but above all specific marker of severe bacterial/parasitic infections. After being studied mostly in critically ill patients, the indications of PCT measurement have been extended to medical and emergency medicine practice, generating cut-off points between 0.2 and 0.6 microg/L. The medical area of application of PCT measurement is varied: discrimination between inflammatory disease and infectious complication or between bacterial/parasitic and viral infection, diagnosis of negative result gram staining meningitis or shock, assessment of antibiotic treatment efficiency. Moreover, PCT measurement provides outcome information in that sepsis-related raised PCT levels seem to be closely related to the magnitude of host systemic inflammatory response to microbial invasion. High PCT levels allow the early identification of patients prone to develop severe sepsis or septic shock. PROSPECTS: After the first published study reporting the usefulness of PCT as a screening biological tool in emergency medicine, future studies will probably refined the place of PCT in such practice fields: decision about inpatient or outpatient management or antibiotics dispensation. Finally, PCT measurement could help physician in screening which septic patients should benefit from sepsis innovative therapeutics.

[Portal thrombosis complicating an acute cytomegalovirus infection in an immunocompetent patient]. / Thrombose portale compliquant une infection à cytomégalovirus aiguë chez un sujet immunocompétent.

INTRODUCTION: The cytomegalovirus (CMV) infection is most often asymptomatic. The grave forms concern the immunocompromised patients. We report a new case pf acute CMV hepatitis complicated with portal thrombosis in an immunocompetent patient. EXEGESIS: A 29 year old man has presented a CMV hepatitis proved by the presence of pp65 protein and the viral DNA in serum. This infection was complicated by a portal thrombosis and the evolution was rapidly favourable under anticoagulant treatment. Eleven cases of major thrombosis complicating acute CMV infection in immunocompetent patients were previously reported in the English and French literature. The absence of local and general cause, the remission without anticoagulation, the elevated risk of thrombosis in both HIV and CMV seropositive patients, and in CMV seropositive renal transplant patients suggest a causal relation. Various pathogenic hypotheses were raised: presence of antiphospholipid antibodies, absent in our case, procoagulant phenotype induction of infected endothelial cells, proliferation induction of smooth cells. CONCLUSION: The acute CMV infection can be considered such as a possible cause of major thrombosis.

AL cardiac amyloidosis and arterial thromboembolic events.

OBJECTIVE: To study the prevalence and characteristics of arterial thromboembolic events (ATEE) in the course of AL amyloidosis. METHODS: We report the case of a non-anticoagulated patient with AL amyloidosis restrictive cardiomyopathy who developed acute lower limb ischaemia. We then prospectively determined the prevalence of ATEE in all patients with AL amyloidosis who were evaluated in our institution for autologous peripheral stem cell transplantation. RESULTS: Nine out of 15 non-anticoagulated patients (60%) developed ATEE: ischaemic stroke (3), transient cerebral ischaemic attack (2), multiple peripheral arterial emboli (1), bilateral iliac artery thrombosis (1), bilateral optic nerve ischaemia (1), and mesenteric ischaemia (1). Haemodynamic stasis seemed to play a leading role in the pathophysiology of ATEE, in that all patients were on sinus rhythm and only one had a thrombus on echocardiography. We identified possible contributing factors to ATEE occurrence: concomitant treatments with oestroprogestogen regimen, thalidomide, granulocyte-macrophage colony-stimulating factor (GM-CSF) and extracellular volume disturbances related to the cytapheresis procedure. CONCLUSION: We report on an unusual frequency of ATEE among patients with AL cardiac amyloidosis. Despite its theoretical risks, anticoagulation should be discussed for patients with amyloid cardiomyopathy.

[Spontaneous hypothermia: a series of ten cases, place of Shapiro's syndrome]. / Hypothermies spontanées: dix observations, place du syndrome de Shapiro.

SUBJECT: Hypothermia (defined as a core temperature lower than 35 degrees C) may result from accidental causes (exposure to cold, drug intoxications), from endocrine disorders (hypothyroidism), or from central or peripheral neurological disease. Among the causes of spontaneous hypothermia, the place of spontaneous periodic hypothermia or Shapiro's syndrome, of which less than 50 cases in children or adults have been reported, remains unclear. METHODS: Case series of spontaneous hypothermia in adults, from a register of the French Society of Internal Medicine (SNFMI). RESULTS: The ten collected cases of spontaneous hypothermia are heterogeneous. In half of the cases, an often ill-labeled psychiatric illness and/or epilepsy and/or anti-psychotic medication were found contributive. Only 5 cases at best seem to conform to the pattern of spontaneous periodic hypothermia or Shapiro's syndrome (in which agenesis of corpus callosum is typically found). In such cases, the episodes of hypothermia start with profuse hyperhidrosis suggesting a paroxystic reset of the hypothalamic thermostat with a lower temperature set point. In none of the cases was found a significant encephalic lesion. None of the treatment trials with anti-epileptics or cyproheptadine were found useful. Spontaneous hypothermia, whether periodic or not, seems to have an unpredictable course, with long periods of remission, and a benign long-term outcome. CONCLUSIONS: Spontaneous hypothermia is a symptom of likely multifactorial etiology. Even in cases conforming to the definition of Shapiro's syndrome, central nervous system anomalies are not unequivocal. No specific treatment for spontaneous hypothermia, whether periodic or not, can be recommended in the current state of knowledge.

Short-term corticosteroids then lamivudine and plasma exchanges to treat hepatitis B virus-related polyarteritis nodosa.

OBJECTIVE: To assess the efficacy and safety of lamivudine, an antiviral agent that strongly inhibits hepatitis B virus (HBV) DNA replication, combined with plasma exchanges after short-term corticosteroids for HBV-related polyartertitis nodosa (PAN). METHODS: Ten patients (8 men, 2 women, mean +/- SD age 50.4 +/- 14.4 years) with previously untreated HBV-related PAN were included in a multicenter, prospective, observational trial. Oral prednisone (1 mg/kg/day) was given for 1 week, then tapered and withdrawn within 1 week. Then, lamivudine (100 mg/day or less in the case of renal insufficiency) was started for a maximum of 6 months. Plasma exchanges were performed simultaneously and scheduled as follows: 3/week for 3 weeks, 2/week for 2 weeks, then 1/week until hepatitis B e antigen (HBeAg) to anti-HBe antibody (HBeAb) seroconversion was obtained or until 2-3 months of clinical recovery was sustained. The primary trial endpoint was clinical recovery from HBV-PAN at 6 months. The secondary endpoint was loss of detectable serum HBeAg and HBV DNA, and HBeAg to HBeAb seroconversion at 9 months. RESULTS: One death, attributed to catheter-related septicemia, was recorded. At 6 months, all 9 survivors had achieved clinical recovery and by 9 months, 6 of 9 (66%) had seroconverted. CONCLUSION: The strategy of short-term steroids followed by lamivudine and plasma exchanges effectively led to recovery from HBV-PAN. Because of its oral administration and good safety profile, lamivudine should henceforth be considered the antiviral agent of choice to treat HBV-related PAN.