A dual functional origin of transfer in the ICEclc genomic island of Pseudomonas knackmussii B13.

Genomic islands (GEIs) are large DNA segments, present in most bacterial genomes, that are most likely acquired via horizontal gene transfer. Here, we study the self-transfer system of the integrative and conjugative element ICEclc of Pseudomonas knackmussii B13, which stands model for a larger group of ICE/GEI with syntenic core gene organization. Functional screening revealed that unlike conjugative plasmids and other ICEs ICEclc carries two separate origins of transfer, with different sequence context but containing a similar repeat motif. Conjugation experiments with GFP-labelled ICEclc variants showed that both oriTs are used for transfer and with indistinguishable efficiencies, but that having two oriTs results in an estimated fourfold increase of ICEclc transfer rates in a population compared with having a single oriT. A gene for a relaxase essential for ICEclc transfer was also identified, but in vivo strand exchange assays suggested that the relaxase processes both oriTs in a different manner. This unique dual origin of transfer system might have provided an evolutionary advantage for distribution of ICE, a hypothesis that is supported by the fact that both oriT regions are conserved in several GEIs related to ICEclc.

Proportion of out-of-hospital adult non-traumatic cardiac or respiratory arrest among calls for seizure.

OBJECTIVES: To measure the proportion of adult non-traumatic cardiac or respiratory arrest among calls for seizure to an emergency medical dispatch centre and to record whether known epileptic patients present cardiac or respiratory arrest together with seizure. METHODS: This 2-year prospective observational investigation involved the collection of tape recordings of all incoming calls to the emergency medical dispatch centre, in which an out-of-hospital non-traumatic seizure was the chief complaint in patients >18 years, in addition to the paramedics' records of all patients who presented with respiratory or cardiac arrest. The authors also recorded whether the bystander spontaneously mentioned to the dispatcher that the victim was known to have epilepsy. RESULTS: During the 24-month period, the call centre received 561 incoming calls for an out-of-hospital non-traumatic seizure in an adult. Twelve cases were classified as cardiac or respiratory arrest by paramedics. In one case, the caller spontaneously mentioned that the victim had a history of epilepsy. The proportion of cardiac or respiratory arrest among calls for seizure was 2.1%. CONCLUSION: Although these cases are rare, dispatchers should closely monitor seizure patients with the help of bystanders to exclude an out-of-hospital cardiac or respiratory arrest, in which case the dispatcher can offer telephone cardiopulmonary resuscitation advice until the paramedics arrive. Whenever the activity of the centre allows it and no new incoming call is on hold, this can be achieved by staying on the line with the caller or by calling back. A history of epilepsy should not modify the type of monitoring performed by the dispatcher as those patients may also have an arrest together with seizure.

Symptomatic intracranial hemorrhage after stroke thrombolysis: comparison of prediction scores.

BACKGROUND AND PURPOSE: Several prognostic scores have been developed to predict the risk of symptomatic intracranial hemorrhage (sICH) after ischemic stroke thrombolysis. We compared the performance of these scores in a multicenter cohort. METHODS: We merged prospectively collected data of patients with consecutive ischemic stroke who received intravenous thrombolysis in 7 stroke centers. We identified and evaluated 6 scores that can provide an estimate of the risk of sICH in hyperacute settings: MSS (Multicenter Stroke Survey); HAT (Hemorrhage After Thrombolysis); SEDAN (blood sugar, early infarct signs, [hyper]dense cerebral artery sign, age, NIH Stroke Scale); GRASPS (glucose at presentation, race [Asian], age, sex [male], systolic blood pressure at presentation, and severity of stroke at presentation [NIH Stroke Scale]); SITS (Safe Implementation of Thrombolysis in Stroke); and SPAN (stroke prognostication using age and NIH Stroke Scale)-100 positive index. We included only patients with available variables for all scores. We calculated the area under the receiver operating characteristic curve (AUC-ROC) and also performed logistic regression and the Hosmer-Lemeshow test. RESULTS: The final cohort comprised 3012 eligible patients, of whom 221 (7.3%) had sICH per National Institute of Neurological Disorders and Stroke, 141 (4.7%) per European Cooperative Acute Stroke Study II, and 86 (2.9%) per Safe Implementation of Thrombolysis in Stroke criteria. The performance of the scores assessed with AUC-ROC for predicting European Cooperative Acute Stroke Study II sICH was: MSS, 0.63 (95% confidence interval, 0.58-0.68); HAT, 0.65 (0.60-0.70); SEDAN, 0.70 (0.66-0.73); GRASPS, 0.67 (0.62-0.72); SITS, 0.64 (0.59-0.69); and SPAN-100 positive index, 0.56 (0.50-0.61). SEDAN had significantly higher AUC-ROC values compared with all other scores, except for GRASPS where the difference was nonsignificant. SPAN-100 performed significantly worse compared with other scores. The discriminative ranking of the scores was the same for the National Institute of Neurological Disorders and Stroke, and Safe Implementation of Thrombolysis in Stroke definitions, with SEDAN performing best, GRASPS second, and SPAN-100 worst. CONCLUSIONS: SPAN-100 had the worst predictive power, and SEDAN constantly the highest predictive power. However, none of the scores had better than moderate performance.

Comment prescrire les hormones thyroïdiennes [How to prescribe thyroid hormones]

Thyroid substitution is generally considered easy as well by general practitioners as by specialists, considering that a single hormone levothyroxin is recommended and that laboratory tests are readily available for measurement of free T4 and TSH. However cross sectional studies have shown that about 45% of patients are over-treated and under-treated. This paper summarizes the critical information useful to facilitate a better management of hypothyroid patients by promoting long lasting euthyroidism.

Nosocomial nontyphoidal salmonellosis after antineoplastic chemotherapy: reactivation of asymptomatic colonization?

An increased frequency of nontyphoidal salmonellosis is well established in cancer patients, but it is unclear whether this represents increased susceptibility to exogenous infection or opportunistic, endogenous reactivation of asymptomatic carriage. In a retrospective study, a simple case definition was used to identify the probable presence of reactivation salmonellosis in five cancer patients between 1996 and 2002. Reactivation salmonellosis was defined as the development of nosocomial diarrhea >72 h after admission and following the administration of antineoplastic chemotherapy in an HIV-seronegative cancer patient who was asymptomatic on admission, in the absence of epidemiological evidence of a nosocomial outbreak. Primary salmonellosis associated with unrecognized nosocomial transmission or community acquisition and an unusually prolonged incubation period could not entirely be ruled out. During the same time period, another opportunistic infection, Pneumocystis pneumonia, was diagnosed in six cancer patients. Presumably, asymptomatic intestinal Salmonella colonization was converted to invasive infection by chemotherapy-associated intestinal mucosal damage and altered innate immune mechanisms. According to published guidelines, stool specimens from patients hospitalized for longer than 72 h should be rejected unless the patient is neutropenic or >or=65 years old with significant comorbidity. However, in this study neutropenia was present in only one patient, and four patients were <65 years old. Guidelines should thus be revised in order not to reject stool culture specimens from such patients. In cancer patients, nosocomial salmonellosis can occur as a chemotherapy-triggered opportunistic reactivation infection that may be similar in frequency to Pneumocystis pneumonia.

Dimethylarginines, homocysteine metabolism, and cerebrospinal fluid markers for Alzheimer's disease.

Dimethylarginine and homocysteine metabolism are closely linked and alterations of both were observed in plasma and cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD). CSF parameters of homocysteine metabolism have recently been found to be associated with the CSF level of the AD biomarker phosphorylated tau (ptau) in AD patients. To investigate possible relationships between homocysteine and dimethylarginine metabolism and the AD CSF biomarkers ptau181 and amyloid-β 1-42 (Aβ42), we assessed parameters of homocysteine metabolism (CSF homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), 5-methyltetrahydrofolate (5-MTHF)) and dimethylarginine metabolism (plasma and CSF asymmetric dimethylarginine (ADMA), symmetric dimethylarginine, L-arginine) as well as CSF Aβ42 and ptau181 in 98 controls and 51 AD patients. Multivariate linear regression analyses were performed to assess associations between the considered parameters. SAH concentrations show significant associations to CSF ADMA levels, and CSF ADMA and L-arginine to ptau181, but not to Aβ42 concentrations in AD patients. When including concentrations of homocysteine, 5-MTHF, SAM, and SAH into the analysis, CSF ADMA concentrations independently predicted ptau181 levels in AD patients but homocysteine-related metabolites were associated with ptau181 only when ADMA was removed from the analysis model. These results suggest that CSF ADMA may interact with CNS homocysteine metabolism and may contribute to neurodegeneration and accumulation of phosphorylated tau in AD. Functional and interventional studies are needed to further proof this hypothesis.

Do standard burn mortality formulae work on a population of severely burned children and adults?

Accurate prediction of mortality following burns is useful as an audit tool, and for providing treatment plan and resource allocation criteria. Common burn formulae (Ryan Score, Abbreviated Burn Severity Index (ABSI), classic and revised Baux) have not been compared with the standard Acute Physiology and Chronic Health Evaluation II (APACHEII) or re-validated in a severely (≥20% total burn surface area) burned population. Furthermore, the revised Baux (R-Baux) has been externally validated thoroughly only once and the pediatric Baux (P-Baux) has yet to be. Using 522 severely burned patients, we show that burn formulae (ABSI, Baux, revised Baux) outperform APACHEII among adults (AUROC increase p<0.001 adults; p>0.5 children). The Ryan Score performs well especially among the most at-risk populations (estimated mortality [90% CI] original versus current study: 33% [26-41%] versus 30.18% [24.25-36.86%] for Ryan Score 2; 87% [78-93%] versus 66.48% [51.31-78.87%] for Ryan Score 3). The R-Baux shows accurate discrimination (AUROC 0.908 [0.869-0.947]) and is well-calibrated. However, the ABSI and P-Baux, although showing high measures of discrimination (AUROC 0.826 [0.737-0.916] and 0.848 [0.758-0.938]) in children), exceedingly overestimates mortality, indicating poor calibration. We highlight challenges in designing and employing scores that are applicable to a wide range of populations.

Prognostication of Mortality in Critically Ill Patients With Severe Infections.

BACKGROUND: The purpose of this study was to confirm the prognostic value of pancreatic stone protein (PSP) in patients with severe infections requiring ICU management and to develop and validate a model to enhance mortality prediction by combining severity scores with biomarkers. METHODS: We enrolled prospectively patients with severe sepsis or septic shock in mixed tertiary ICUs in Switzerland (derivation cohort) and Brazil (validation cohort). Severity scores (APACHE [Acute Physiology and Chronic Health Evaluation] II or Simplified Acute Physiology Score [SAPS] II) were combined with biomarkers obtained at the time of diagnosis of sepsis, including C-reactive-protein, procalcitonin (PCT), and PSP. Logistic regression models with the lowest prediction errors were selected to predict in-hospital mortality. RESULTS: Mortality rates of patients with septic shock enrolled in the derivation cohort (103 out of 158) and the validation cohort (53 out of 91) were 37% and 57%, respectively. APACHE II and PSP were significantly higher in dying patients. In the derivation cohort, the models combining either APACHE II, PCT, and PSP (area under the receiver operating characteristic curve [AUC], 0.721; 95% CI, 0.632-0.812) or SAPS II, PCT, and PSP (AUC, 0.710; 95% CI, 0.617-0.802) performed better than each individual biomarker (AUC PCT, 0.534; 95% CI, 0.433-0.636; AUC PSP, 0.665; 95% CI, 0.572-0.758) or severity score (AUC APACHE II, 0.638; 95% CI, 0.543-0.733; AUC SAPS II, 0.598; 95% CI, 0.499-0.698). These models were externally confirmed in the independent validation cohort. CONCLUSIONS: We confirmed the prognostic value of PSP in patients with severe sepsis and septic shock requiring ICU management. A model combining severity scores with PCT and PSP improves mortality prediction in these patients.