The Role of Biomarkers for Starting Antifungals in the Intensive Care Unit

Invasive candidiasis is associated with high mortality rates (35% to 60%), similar to the range reported for septic shock. The most common types include candidemia, frequently observed in immunocompromised patients, and noncandidemic systemic candidiasis, which constitutes the majority of cases in critically ill patients. However, they are difficult to prove and a definite diagnosis usually occurs late in the course of the disease, thus contributing to their bad prognosis. Early empirical treatment improves the prognosis and currently relies on the positive predictive value (PPV) of risk-assessment strategies (colonization index, Candida score, predictive rules) based on combinations of risk factors, but it may have also largely contributed to the overuse of antifungal agents in critically ill patients. In this context, non- culture-based diagnostic methods, including specific and nonspecific biomarkers, may significantly improve the diagnosis of invasive candidiasis. Candida DNA and mannan antigen/antimannan antibodies are of limited interest for the diagnosis of invasive candidiasis as they fail to identify noncandidemic systemic candidiasis, despite early positivity in candidemic patients. The utility of 1,3-beta-D-glucan (b-D-glucan), a panfungal cell wall antigen, has been demonstrated for the diagnosis of fungal infections in immunocompromised patients. Preliminary data suggest that it is also detectable early in critically ill patients developing noncandidemic systemic candidiasis. To take advantage of the high negative predictive value of risk-assessment strategies and the early increase in specific fungal biomarkers in high-risk patients, we propose a practical 2-step approach to improve the selection of patients susceptible to benefit from empirical antifungal treatment.

Mesure de l'impact de l'implication des proches aidants de patients hospitalises dans une unité de soins psychiatriques aigus sur eux-mêmes

Le but de cette étude est de mesurer ainsi que de qualifier l'impact de l'implication des proches aidants de patients hospitalisés dans des unités de soins psychiatriques aigus sur eux-mêmes. Le cadre conceptuel utilisé est celui du fardeau des familles de Schene (1990). Il différencie les parties objectives et subjectives du fardeau familial. La récolte de données a été réalisée à l'aide de l'Involvement Evaluation Questionnaire (IEQ). Les résultats de cette étude montrent que les proches aidants souffrent d'un niveau d'inquiétude élevé, 3.8 sur une échelle de Likert à 5 questions, ainsi que d'un niveau de tension à 2.44 sur une échelle de Likert à 5 questions. Des associations ont été trouvées. L'augmentation de la durée du trouble diminue l'inquiétude, avec une valeur ρ de 0.048. Le fait d'être habitué à la situation a également un impact en diminuant la tension, avec une valeur ρ de 0.002. Plus on est « habitué à la situation », avec une valeur ρ de -0.021, moins le proche est inquiet par rapport à la situation du patient. Ainsi que, plus le patient est jeune, plus le proche aidant ressent de tension, avec une valeur ρ de 0.008. Ces résultats, peu généralisables au vu du petit échantillon (n=24), pourraient toutefois impliquer une réflexion approfondie sur l'accueil, la place et le soutien des proches aidants de patients souffrants de troubles psychiatriques hospitalisés dans une unité de soins aigus de la part des infirmières.

Alzheimer's disease-like APP processing in wild-type mice identifies synaptic defects as initial steps of disease progression.

BACKGROUND: Alzheimer's disease (AD) is the most frequent form of dementia in the elderly and no effective treatment is currently available. The mechanisms triggering AD onset and progression are still imperfectly dissected. We aimed at deciphering the modifications occurring in vivo during the very early stages of AD, before the development of amyloid deposits, neurofibrillary tangles, neuronal death and inflammation. Most current AD models based on Amyloid Precursor Protein (APP) overproduction beginning from in utero, to rapidly reproduce the histological and behavioral features of the disease within a few months, are not appropriate to study the early steps of AD development. As a means to mimic in vivo amyloid APP processing closer to the human situation in AD, we used an adeno-associated virus (AAV)-based transfer of human mutant APP and Presenilin 1 (PS1) genes to the hippocampi of two-month-old C57Bl/6 J mice to express human APP, without significant overexpression and to specifically induce its amyloid processing. RESULTS: The human APP, βCTF and Aβ42/40 ratio were similar to those in hippocampal tissues from AD patients. Three months after injection the murine Tau protein was hyperphosphorylated and rapid synaptic failure occurred characterized by decreased levels of both PSD-95 and metabolites related to neuromodulation, on proton magnetic resonance spectroscopy ((1)H-MRS). Astrocytic GLT-1 transporter levels were lower and the tonic glutamatergic current was stronger on electrophysiological recordings of CA1 hippocampal region, revealing the overstimulation of extrasynaptic N-methyl D-aspartate receptor (NMDAR) which precedes the loss of long-term potentiation (LTP). These modifications were associated with early behavioral impairments in the Open-field, Y-maze and Morris Mater Maze tasks. CONCLUSIONS: Altogether, this demonstrates that an AD-like APP processing, yielding to levels of APP, βCTF and Aβ42/Aβ40 ratio similar to those observed in AD patients, are sufficient to rapidly trigger early steps of the amyloidogenic and Tau pathways in vivo. With this strategy, we identified a sequence of early events likely to account for disease onset and described a model that may facilitate efforts to decipher the factors triggering AD and to evaluate early neuroprotective strategies.

Cranial computed tomography findings in patients admitted to the emergency unit of Hospital Universitário Cajuru

Objective To identify and analyze the prevalence of cranial computed tomography findings in patients admitted to the emergency unit of Hospital Universitário Cajuru. Materials and Methods Cross-sectional study analyzing 200 consecutive non contrast-enhanced cranial computed tomography reports of patients admitted to the emergency unit of Hospital Universitário Cajuru. Results Alterations were observed in 76.5% of the patients. Among them, the following findings were most frequently observed: extracranial soft tissue swelling (22%), bone fracture (16.5%), subarachnoid hemorrhage (15%), nonspecific hypodensity (14.5%), paranasal sinuses opacification (11.5%), diffuse cerebral edema (10.5%), subdural hematoma (9.5%), cerebral contusion (8.5%), hydrocephalus (8%), retractable hypodensity /gliosis/ encephalomalacia (8%). Conclusion The authors recognize that the most common findings in emergency departments reported in the literature are similar to the ones described in the present study. This information is important for professionals to recognize the main changes to be identified at cranial computed tomography, and for future planning and hospital screening aiming at achieving efficiency and improvement in services.

Le pool ou unité commune de personnel soignant

L'unité commune de personnel soignant ou pool infirmier du CHUV est un service de professionnels qualifiés, disponibles et capables de remplacer les défections du personnel régulier ou renforcer les effectifs lors de surcharge de travail occasionnel. [Table des matières] 1. Le pool: perspective historique: Origine du travail intérimaire; Le travail intérimaire en Suisse et son développement; Genèse du Pool; Développement du Pool. 2. Problématique du Pool : Perspective conceptuelle et théorique. L'hôpital, modèle d'organisation pris entre deux logiques; Marché-hiérarchie: théorie des coûts de transactions; La coordination collective des actions individuelles apport de l'économie des conventions. Concept de flexibilité. Connaissance tacite et explicite. 3. Le terrain d'observation. Annexes: Questionnaire des poolistes et résumé des commentaires; etc.

Different Storing and Processing Conditions of Human Lymphocytes do not Alter P-Glycoprotein Rhodamine 123 Efflux.

P-glycoprotein (Pgp), a protein codified by Multi Drug Resistance (MDR1) gene, has a detoxifying function and might influence the toxicity and pharmacokinetics and pharmacodynamics of drugs. Sampling strategies to improve Pgp studies could be useful to optimize the sensitivity and the reproducibility of efflux assays. This study aimed to compare Pgp expression and efflux activity by measuring Rhodamine123 (Rh123) retention in lymphocytes stored under different conditions, in order to evaluate the potential utility of any of the storing conditions in Pgp functionality. Our results show no change in protein expression of Pgp by confocal studies and Western blotting, nor changes at the mRNA level (qRT-PCR). No differences in Rh123 efflux by Pgp activity assays were found between fresh and frozen lymphocytes after 24 hours of blood extraction, using either of the two Pgp specific inhibitors (VP and PSC833). Different working conditions in the 24 hours post blood extraction do not affect Rh123 efflux. These results allow standardization of Pgp activity measurement in different individuals with different timing of blood sampling and in different geographic areas. _______________