The combination of kidney function variables with cell cycle arrest biomarkers identifies distinct subphenotypes of sepsis-associated acute kidney injury: a analysis (the PHENAKI study).

Background: The severity and course of sepsis-associated acute kidney injury (SA-AKI) are correlated with the mortality rate. Early detection of SA-AKI subphenotypes might facilitate the rapid provision of individualized care.

Patients And Methods: In this analysis of a multicenter prospective study, we combined conventional kidney function variables with serial measurements of urine (tissue inhibitor of metalloproteinase-2 [TIMP-2])* (insulin-like growth factor-binding protein [IGFBP7]) at 0, 6, 12, and 24 h) and then using an unsupervised hierarchical clustering of principal components (HCPC) approach to identify different phenotypes of SA-AKI.

Correction to: Urine cell cycle arrest biomarkers distinguish poorly between transient and persistent AKI in early septic shock: a prospective, multicenter study.

An amendment to this paper has been published and can be accessed via the original article.

Urine cell cycle arrest biomarkers distinguish poorly between transient and persistent AKI in early septic shock: a prospective, multicenter study.

Background: The urine biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been validated for predicting and stratifying AKI. In this study, we analyzed the utility of these biomarkers for distinguishing between transient and persistent AKI in the early phase of septic shock.

Methods: We performed a prospective, multicenter study in 11 French ICUs.

Respiratory Variability of Pulmonary Velocity-Time Integral As a New Gauge of Fluid Responsiveness For Mechanically Ventilated Patients in the ICU.

Objectives: To evaluate reliability and feasibility of the respiratory variability of pulmonary velocity-time integral as a new dynamic marker of fluid responsiveness in mechanically ventilated patients.

Design: Prospective observational study.

Setting: Medical-surgical ICU of a general hospital.

Value and determinants of the mean systemic filling pressure in critically ill patients.

Mean systemic filling pressure (Pmsf) is a major determinant of venous return. Its value is unknown in critically ill patients (ICU). Our objectives were to report Pmsf in critically ill patients and to look for its clinical determinants, if any.

Therapeutic hypothermia after nonshockable cardiac arrest: the HYPERION multicenter, randomized, controlled, assessor-blinded, superiority trial.

Background: Meta-analyses of nonrandomized studies have provided conflicting data on therapeutic hypothermia, or targeted temperature management (TTM), at 33°C in patients successfully resuscitated after nonshockable cardiac arrest. Nevertheless, the latest recommendations issued by the International Liaison Committee on Resuscitation and by the European Resuscitation Council recommend therapeutic hypothermia. New data are available on the adverse effects of therapeutic hypothermia, notably infectious complications.

Prospective assessment of a score for assessing basic critical-care transthoracic echocardiography skills in ventilated critically ill patients.

Background: We studied a score for assessing basic transthoracic echocardiography (TTE) skills exhibited by residents who examined critically ill patients receiving mechanical ventilation.

Methods: We conducted a prospective study in the 16 residents who worked in our medical-surgical ICU between 1 May 2008 and 1 November 2009. The residents received theoretical teaching (two hours) then performed supervised TTEs during their six-month rotation.

Pulse pressure variations to guide fluid therapy in donors: a multicentric echocardiographic observational study.

Purpose: Preload responsiveness parameters could be useful in the hemodynamic management of septic shock.

Methods: A multicentric prospective echocardiographic observational study was conducted from March 2009 to August 2011. Clinically brain-dead subjects were included.

Echocardiography: a help in the weaning process.

Introduction: To evaluate the ability of transthoracic echocardiography (TTE) to detect the effects of spontaneous breathing trial (SBT) on central hemodynamics and to identify indices predictive of cardiac-related weaning failure.

Methods: TTE was performed just before and at the end of a 30-min SBT in 117 patients fulfilling weaning criteria. Maximal velocities of mitral E and A waves, deceleration time of E wave (DTE), maximal velocity of E' wave (tissue Doppler at the lateral mitral annulus), and left ventricular (LV) stroke volume were measured.

Reversal of refractory septic shock with drotrecogin alpha (activated).

Objective: We previously reported that early continuous veno-venous hemodiafiltration (CVVHDF) enables rapid identification of a subgroup of patients with "refractory" septic shock and a 100% risk of death. The objective of this study was to investigate whether early administration of drotrecogin alpha (activated) (DrotAA) to this selected subgroup of septic patients at extremely high risk of death would significantly improve prognosis.

Method: Prospective observational study in a medical intensive-care unit of a University Hospital.

Acute aortic dissection detected by contrast echocardiography.

We describe the case of a man with acute aortic dissection detected by contrast transthoracic echocardiography. Conventional echocardiography was not contributory. To our knowledge, this is the first report of the usefulness of contrast echocardiography in ascending aortic dissection at bedside.

Actual incidence of global left ventricular hypokinesia in adult septic shock.

Rationale And Objective: To evaluate the actual incidence of global left ventricular hypokinesia in septic shock.

Method: All mechanically ventilated patients treated for an episode of septic shock in our unit were studied by transesophageal echocardiography, at least once a day, during the first 3 days of hemodynamic support. In patients who recovered, echocardiography was repeated after weaning from vasoactive agents.

Hemodynamic effects of passive leg raising: an echocardiographic study in patients with shock.

Objectives: To determine the effects of passive leg raising (PLR) on hemodynamics and on cardiac function according to the preload dependency defined by the superior vena cava collapsibility index (DeltaSVC).

Results: Forty patients with shock, sedated and mechanically ventilated, were included. Transesophageal echocardiography was performed.

Prone positioning unloads the right ventricle in severe ARDS.

Background: Despite airway pressure limitation, acute cor pulmonale persists in a minority of ARDS patients. Insufficient airway pressure limitation, hypercapnia, or both may be responsible. Because prone positioning (PP) has been shown to be a safe way to reduce airway pressure and to improve alveolar ventilation, we decided to assess its effect on right ventricular (RV) pressure overload in ARDS patients.

Validation of a skills assessment scoring system for transesophageal echocardiographic monitoring of hemodynamics.

Objective: Transesophageal echocardiography (TEE) is increasingly used in hemodynamic monitoring in the intensive care unit. This paper describes and validates a scoring system for assessing competence in TEE performed by intensivists for this indication.

Design: Prospective study over an 18-month period.

Efficacy of therapeutic hypothermia after out-of-hospital cardiac arrest due to ventricular fibrillation.

Aim Of The Study: We investigated implementation and efficacy of mild therapeutic hypothermia in the treatment of out-of-hospital cardiac arrest due to ventricular fibrillation.

Materials And Methods: Two periods were compared, an historical one (36 patients) between 2000 and 2002 where therapeutic hypothermia was never used, and a recent period (32 patients) between 2003 and 2005 where therapeutic hypothermia (32-34 degrees C) was implemented prospectively in our unit. Cooling was obtained by simply using wet cloths and ice packs.

Genes required for osmoregulation and apical secretion in Caenorhabditis elegans.

Few studies have investigated whether or not there is an interdependence between osmoregulation and vesicular trafficking. We previously showed that in Caenorhabditis elegans che-14 mutations affect osmoregulation, cuticle secretion, and sensory organ development. We report the identification of seven lethal mutations displaying che-14-like phenotypes, which define four new genes, rdy-1-rdy-4 (rod-like larval lethality and dye-filling defective).

[Fluvastatin affects HLA class I expression on endothelial cells].

Originally designed to target elevated lipids, the "traditional" cause of atherosclerosis, statins might also confer vascular benefit by directly or indirectly modulating both the inflammatory and immune responses. Statins have been shown to downregulate MHC class II and CD40 expression on activated endothelial cells (EC). In this study, we investigate the potential effect of statins on MHC class I expression and regulation in response to IFNgamma.

[Circulatory failures].

To treat circulatory failures and recognize their mechanisms, we need to understand circulatory physiology. What determines systemic venous return? How does the right ventricle feed the pulmonary circulation? Where is the left ventricular preload reserve located? Four types of circulatory failure are conventionally recognized: hypovolemic, obstructive, vasoplegic and cardiogenic. One or more of these mechanisms may account for circulatory failure in septic shock.

The binding affinity of double-stranded RNA motifs to HIV-1 Tat protein affects transactivation and the neutralizing capacity of anti-Tat antibodies elicited after intranasal immunization.

In this study we examined the hypothesis that the binding affinity of two double-stranded (ds) RNA motifs to HIV-1 Tat protein might affect transactivation and the type of anti-Tat immune responses. Using surface plasmon resonance technology we demonstrated the capacity of the poly(A):poly(U) (pA:pU) motif to bind with high affinity to a totally synthetic Tat protein and to inhibit more efficiently the Tat/transactivation response element (TAR) RNA interaction as compared to the poly(I):poly(C) (pI:pC) motif. Furthermore, the pA:pU motif was tenfold more effective in inhibiting Tat-driven transactivation than the pI:pC motif.

Tat-neutralizing versus Tat-protecting antibodies in rhesus macaques vaccinated with Tat peptides.

The human immunodeficiency virus (HIV) regulatory protein Tat represents an attractive target for developing vaccine strategies. Both humoral and cellular responses against Tat might reduce disease progression by interfering with the deleterious functions of extracellularly secreted protein and by reducing viral replication. We have immunized Rhesus macaques intramuscularly and intranasally with a cocktail of three Tat peptides encompassing residues 1-20, 1-61 and 44-61 administrated in the presence of Montanide ISA 720 as adjuvant.

Important B-cell epitopes for neutralization of human immunodeficiency virus type 1 Tat in serum samples of humans and different animal species immunized with Tat protein or peptides.

The Tat regulatory protein of human immunodeficiency virus type 1 (HIV-1) is secreted by infected cells and plays a key role in viral pathogenesis and replication. Tat protein has been proposed as a target antigen for vaccine design since anti-Tat antibodies may interfere with virus spread and disease progression. The aim of this study was to analyse the serum antibody response of mice, rabbits, macaques and humans immunized with recombinant Tat, synthetic Tat, Tat toxoid or Tat peptides and to examine the biological properties of these antibodies in terms of Tat-induced transactivation and HIV-1 replication.

Specificity and effect on apoptosis of Tat antibodies from vaccinated and SHIV-infected rhesus macaques and HIV-infected individuals.

Recent contributions have demonstrated that actively secreted Tat protein plays an important functional role in human immunodeficiency virus-1 (HIV-1) infection and that Tat antibodies might interfere with disease progression by blocking the protein extracellularly. In this context we have studied the recognition of several Tat mutants as well as various synthetic Tat fragments by anti-Tat monoclonal antibodies and by IgG antibodies from a large collection of slow and fast-progressor infected individuals. We have also tested the sera from simian/human immunodeficiency virus (SHIV)-infected macaques with these Tat peptides.