Persistent hyperglycemia at 24-48 h in acute hyperglycemic stroke patients is not associated with a worse functional outcome.

BACKGROUND: Recently, it was shown that the relation between admission glucose and functional outcome after ischemic stroke is described by a J-shaped curve, with a glucose range of 3.7-7.3 mmol/l associated with a favorable outcome. We tested the hypothesis that persistence of hyperglycemia above this threshold at 24-48 h after stroke onset impairs 3-month functional outcome. METHODS: We analyzed all patients with glucose >7.3 mmol/l on admission from the Acute STroke Registry and Analysis of Lausanne (ASTRAL). Patients were divided into two groups according to their subacute glucose level at 24-48 h after last well-being time (group 1: ≤7.3 mmol/l, group 2: >7.3 mmol/l). A favorable functional outcome was defined as a modified Rankin Score (mRS) ≤2 at 3 months. A multiple logistic regression analysis of multiple demographic, clinical, laboratory and neuroimaging covariates was performed to assess predictors of an unfavorable outcome. RESULTS: A total of 1,984 patients with ischemic stroke were admitted between January 1, 2003 and October 20, 2009, within 24 h after last well-being time. In the 421 patients (21.2%) with admission glucose >7.3 mmol/l, the proportion of patients with a favorable outcome was not statistically significantly different between the two groups (59.2 vs. 48.7%, respectively). In multiple logistic regression analysis, unfavorable outcome was significantly associated with age (odds ratio, OR: 1.06, 95% confidence interval, 95% CI: 1.03-1.08 for every 10-year increase), National Institute of Health Stroke Score, NIHSS score, on admission (OR: 1.16, 95% CI: 1.11-1.21), prehospital mRS (OR: 12.63, 95% CI: 2.61-61.10 for patients with score >0), antidiabetic drug usage (OR: 0.36, 95% CI: 0.15-0.86) and glucose on admission (OR: 1.16, 95% CI: 1.02-1.31 for every 1 mmol/l increase). No association was found between persistent hyperglycemia at 24-28 h and outcome in either diabetics or nondiabetics. CONCLUSIONS: In ischemic stroke patients with acute hyperglycemia, persistent hyperglycemia (>7.3 mmol/l) at 24-48 h after stroke onset is not associated with a worse functional outcome at 3 months whether the patient was previously diabetic or not.

The vasodilatory effect of juxta-arteriolar microinjection of endothelinA receptor inhibitor in healthy and acute branch retinal vein occlusion minipig retinas.

Purpose. To investigate the effect of the endothelin(A) receptor inhibitor BQ-123 on the retinal arteriolar vasculature in minipig retinas in normal eyes and eyes with acute branch retinal vein occlusion (BRVO). Methods. Seven healthy eyes of seven minipigs and six eyes of six minipigs with experimental BRVO were evaluated under systemic anesthesia. An intravitreal juxta-arteriolar microinjection of 30 microL BQ-123 0.61 microg/mL (pH 7.4) was performed in all but one eye from each group, into which the physiologic saline vehicle alone was injected. Vessel-diameter changes were measured with a retinal vessel analyzer. Results. In healthy minipig retinas (n = 6), arteriolar diameter (+/-SD) increased 6.19% +/- 3.55% (P < 0.05), 25.98% +/- 2.37% (P < 0.001), 23.65% +/- 1.2% (P < 0.001), and 16.84% +/- 1.95% (P < 0.001), at 1, 5, 10, and 15 minutes, respectively, after BQ-123 microinjection. Two hours after experimental BRVO (n = 5), the retinal arteriolar diameter had decreased (13.07% +/- 5.7%; P < 0.01). One, 5, 10, and 15 minutes after BQ-123 microinjection, retinal arteriolar diameter had increased by 7.14% +/- 3.3% (P < 0.01), 26.74% +/- 7.63% (P < 0.001), 23.67% +/- 6.4% (P < 0.001), and 16.09% +/- 3.41% (P < 0.001), respectively. Vehicle only injection had no vasoactive effect on physiologic or BRVO retinas. Conclusions. A significant increase in retinal arteriolar diameter was demonstrated after juxta-arteriolar BQ-123 microinjection in healthy and in acute BRVO minipig retinas. The results suggest a role for endothelin-1 in maintaining retinal basal arteriolar tone. Reversing the BRVO-related vasoconstriction by juxta-arteriolar BQ-123 microinjection could bring a new perspective to the management of BRVO.

Obesity in long-term survivors of childhood acute lymphoblastic leukemia

Rapport de synthèse : Le traitement des leucémies aiguës chez l'enfant représente un des succès de la médecine moderne avec des taux de guérison avoisinant les 80% ce qui implique la nécessité de suivre les effets secondaires à long terme des traitements chez cette population de patients. Récemment plusieurs études internationales ont relevé une prévalence plus importante de surpoids et d'obésité chez les enfants traités pour une leucémie aiguë. L'origine de ce processus reste incertaine :aux effets secondaires bien connus et décrits des traitements (stéroïdes et radiothérapie) semblent s'ajouter des facteurs génétiques, familiaux (age, BMI au diagnostic, BMI parents et fratrie), environnementaux. L'objectif de ce travail est d'estimer la prévalence et les facteurs de risque pour le surpoids et l'obésité chez les enfants traités et guéris d'une leucémie aiguë en Suisse romande et de comparer ces résultats à ceux d'études internationales. Pour répondre à ces questions nous avons inclus 54 patients (40 de Lausanne et 14 de Genève) traités pour une leucémie aiguë. Seuls les enfants à 5 ans de leur première rémission clinique, sans atteinte du système nerveux central, testiculaire ou médullaire et traités par chimiothérapie seule sont retenus. Leur poids, taille sont enregistrés durant les phases précises de traitement (au diagnostic, à la rémission, fin de consolidation, milieumaintenance et en fin de traitement) puis annuellement jusqu'à 12 ans post fin de traitement. Le BMI (kg/ml) et sa déviation standard BMI-SDS (spécifique pour Page et le sexe) pour les patients et leurs parents sont calculés selon les valeurs internationales (IOTF) respectivement BMI-SDS >1.645 (p<0.05) pour le surpoids et> 1.96 (p<0.025) pour l'obésité. Les résultats de ce travail confirment une prévalence double de surpoids (30% versus 17%) et quadruple d'obésité (18% versus 4%) au sein de la population d'enfants traités pour une leucémie aiguë comparées à la population suisse standard. Les facteurs de risque impliqués sont le BMI initial au diagnostic et le BMI maternel contrairement à Page, sexe, stéroïdes et au BMI paternel. Ces données confirment une prévalence significative d'enfants en surpoids/obèses au sein de cette population avec des résultats similaires à ceux retrouvés dans des études internationales récentes. Les facteurs de risque identifiés semblent plutôt liés à l'environnement familial qu'aux traitements. Ces constatations pourraient être le résultat d'interactions complexes entre "le background génétique", les facteurs environnementaux, les habitudes socioculturelles (activité physique, status nutritionnel) paramètres non évalués dans cette revue. Des études plus larges, prospectives sont nécessaires pour clarifier les rôles des différents facteurs de risque et de leurs interactions ;celles-ci devraient inclure des données génétiques (LEPR), taux de leptine, activité physique et le status nutritionnel. Enfin, l'identification des patients à risque est cruciale afin de prévenir les effets secondaires cardio-vasculaires, métaboliques bien connus liés au surpoids et à l'obésité.

Goodpasture's disease presenting with acute renal failure

A 15-year-old boy was admitted for vomiting, diarrhea, fatigue, crampy abdominal pain and oliguria. A renal failure was diagnosed (creatinine 2523 μmol/, urea 53,1 mmol/l) with severe aregenerative anemia (80 g/l), metabolic acidosis, hyperkalemia, elevated inflammatory markers and normal platelet count. A nephrotic proteinuria was noticed (350 g/mol). Patient's creatinine was normal 4 months before. The diagnosis of rapidly progressive glomerulonephritis was suspected. C3 and C4 were normal, ANA and ANCA were negative; anti-glomerular basement membrane antibody (anti-GBM) was positive (1/320) which lead to the diagnosis of Goodpasture's disease. Chest X-ray showed bilateral hilar infiltration and CT-scan revealed multiple alveolar haemorrhages, confirmed by broncho-alveolar lavage. Renal ultrasound showed swollen and hyperechogenous kidneys with loss of corticomedullary differentiation. Renal biopsy revealed a global extracapillary necrotising glomerulonephritis, with IgG lining the membrane at immunofluorescence. The patient was treated with continuous venovenous hemodia- filtration, plasmapheresis and immunosuppressive therapy (cyclophosphamid and corticoids) which lead to normalisation of anti-GBM level and favourable respiratory evolution with no sequelae. The renal evolution was unfavourable and the patient developed end stage renal disease and was treated with haemodialysis. Goodpasture's disease is an autoimmune process in which anti-GBM are produced against collagen IV present in the kidneys and pulmonary alveolae, resulting in acute or rapidly progressive glomerulonephritis and altering the pulmonary alveolae. It is a rare disease concerning mostly infants and young adults. Clinical presentation consists in an acute renal failure with proteinuria. Pulmonary symptoms (60-70% of the total cases) are dyspnea, cough, and haemoptysis. Diagnosis is made with the dosage of immunological anti-GBM and with renal biopsy. Factors of poor prognosis are initial oliguria, alteration of >50% of the glomerulus, very high creatinine or need of dialysis. Anti-GBM dosage is used for follow up. Patients are treated with immunosuppressive therapy for 6 to 9 months and plasmapheresis. Few recurrences are seen. Goodpasture's disease should be evoqued whenever a young patient is seen with glomerulonephritis, especially if pulmonary abnormalities are present. The disease requires an aggressive treatment in order to prevent respiratory and kidney failure.

Acute hepatitis A in a young returning traveler from Kenya despite immunization before departure.

Aluminum-adsorbed hepatitis A vaccines are known to be highly efficient. We present here the case of a patient who was immunized against hepatitis A before leaving for Kenya and who contracted an acute symptomatic hepatitis A during travel.

Economics of dialysis dependence following renal replacement therapy for critically ill acute kidney injury patients.

BACKGROUND: The obective of this study was to perform a cost-effectiveness analysis comparing intermittent with continuous renal replacement therapy (IRRT versus CRRT) as initial therapy for acute kidney injury (AKI) in the intensive care unit (ICU). METHODS: Assuming some patients would potentially be eligible for either modality, we modeled life year gained, the quality-adjusted life years (QALYs) and healthcare costs for a cohort of 1000 IRRT patients and a cohort of 1000 CRRT patients. We used a 1-year, 5-year and a lifetime horizon. A Markov model with two health states for AKI survivors was designed: dialysis dependence and dialysis independence. We applied Weibull regression from published estimates to fit survival curves for CRRT and IRRT patients and to fit the proportion of dialysis dependence among CRRT and IRRT survivors. We then applied a risk ratio reported in a large retrospective cohort study to the fitted CRRT estimates in order to determine the proportion of dialysis dependence for IRRT survivors. We conducted sensitivity analyses based on a range of differences for daily implementation cost between CRRT and IRRT (base case: CRRT day $632 more expensive than IRRT day; range from $200 to $1000) and a range of risk ratios for dialysis dependence for CRRT as compared with IRRT (from 0.65 to 0.95; base case: 0.80). RESULTS: Continuous renal replacement therapy was associated with a marginally greater gain in QALY as compared with IRRT (1.093 versus 1.078). Despite higher upfront costs for CRRT in the ICU ($4046 for CRRT versus $1423 for IRRT in average), the 5-year total cost including the cost of dialysis dependence was lower for CRRT ($37 780 for CRRT versus $39 448 for IRRT on average). The base case incremental cost-effectiveness analysis showed that CRRT dominated IRRT. This dominance was confirmed by extensive sensitivity analysis. CONCLUSIONS: Initial CRRT is cost-effective compared with initial IRRT by reducing the rate of long-term dialysis dependence among critically ill AKI survivors.

Home versus in-hospital treatment of outpatients with acute deep venous thrombosis of the lower limbs.

BACKGROUND: Some physicians are still concerned about the safety of treatment at home of patients with acute deep venous thrombosis (DVT). METHODS: We used data from the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry to compare the outcomes in consecutive outpatients with acute lower limb DVT according to initial treatment at home or in the hospital. A propensity score-matching analysis was carried out with a logistic regression model. RESULTS: As of December 2012, 13,493 patients had been enrolled. Of these, 4456 (31%) were treated at home. Patients treated at home were more likely to be male and younger and to weigh more; they were less likely than those treated in the hospital to have chronic heart failure, lung disease, renal insufficiency, anemia, recent bleeding, immobilization, or cancer. During the first week of anticoagulation, 27 patients (0.20%) suffered pulmonary embolism (PE), 12 (0.09%) recurrent DVT, and 51 (0.38%) major bleeding; 80 (0.59%) died. When only patients treated at home were considered, 12 (0.27%) had PE, 4 (0.09%) had recurrent DVT, 6 (0.13%) bled, and 4 (0.09%) died (no fatal PE, 3 fatal bleeds). After propensity analysis, patients treated at home had a similar rate of venous thromboembolism recurrences and a lower rate of major bleeding (odds ratio, 0.4; 95% confidence interval, 0.1-1.0) or death (odds ratio, 0.2; 95% confidence interval, 0.1-0.7) within the first week compared with those treated in the hospital. CONCLUSIONS: In outpatients with DVT, home treatment was associated with a better outcome than treatment in the hospital. These data may help safely treat more DVT patients at home.

α₁-Adrenergic receptors contribute to the acute effects of 3,4-methylenedioxymethamphetamine in humans.

Preclinical studies implicate a role for α₁-noradrenergic receptors in the effects of psychostimulants, including 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). The present study evaluated the effects of the α₁-noradrenergic receptor antagonist doxazosin on the acute pharmacodynamic and pharmacokinetic response to MDMA in 16 healthy subjects. Doxazosin (8 mg/d) or placebo was administered for 3 days before MDMA (125 mg) or placebo using a randomized, double-blind, placebo-controlled, 4-session, crossover design. Doxazosin reduced MDMA-induced elevations in blood pressure, body temperature, and moderately attenuated positive mood but enhanced tachycardia associated with MDMA. The results indicate that α₁-adrenergic receptors contribute to the acute cardiostimulant and to a minor extent possibly also to the thermogenic and euphoric effects of MDMA in humans.

Recommendations on percutaneous coronary intervention for the reperfusion of acute ST elevation myocardial infarction

Little information is currently available from the various societies of cardiology on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Since primary PCI is the main method of reperfusion in AMI in many centres, and since of all cardiac emergencies AMI represents the most urgent situation for PCI, recommendations based on scientific evidence and expert experience would be useful for centres practising primary PCI, or those looking to establish a primary PCI programme. To this aim, a task force for primary PCI in AMI was formed to develop a set of recommendations to complement and assist clinical judgment. This paper represents the product of their recommendations.