L index de résistance artériel rénal (un marqueur pronostique pour les maladies rénales chroniques ?)

Les maladies rénales chroniques touchent deux à trois millions de Français. Seule une minorité d entre eux évoluera vers l insuffisance rénale chronique terminale. Appréhender les néphropathies les plus sévères et d évolution péjorative par un examen non invasif serait d un intérêt majeur pour les cliniciens. La valeur prédictive de l index de résistance artériel rénal (IR), mesuré par écho-doppler, semble être importante mais reste mal définie. Nous avons réalisé une étude prospective monocentrique dont l objectif principal était de déterminer les paramètres histologiques associés à la valeur de l IR. Les objectifs secondaires étaient de définir les paramètres cliniques et biologiques associés, d évaluer la corrélation de l IR à l évolution de la fonction rénale et de définir un seuil pronostique. Pour cela, l IR a été mesuré par un écho-doppler dans les deux jours précédant la biopsie rénale chez 58 patients de 2006 à 2007. Les données cliniques, biologiques, histologiques et ultrasonographiques ont été collectées prospectivement. La fonction rénale à un an a été recueillie rétrospectivement chez 42 patients. Nous montrons que l IR croît avec les déterminants de la rigidité artérielle (âge, pression pulsée), l extension des lésions d artériosclérose et de fibrose interstitielle et avec la sévérité de l insuffisance rénale. En revanche, il n est corrélé ni à la présence de dépôts hyalins artériolaires ni à l importance de la glomérulosclérose. L IR est associé au pronostic rénal indépendamment de l âge et de la fonction rénale initiale. Un seuil de 0,70, a d excellentes valeurs prédictives négative pour une fibrose interstitielle étendue à plus de 20% du parenchyme, et positive pour une artériosclérose sévère et un déclin de la fonction rénale à un an. Cette étude souligne que l IR constitue un marqueur pronostique non invasif et l intérêt d élargir l utilisation du doppler dans la prise en charge clinique courante des maladies rénales chroniques.Chronic kidney diseases are present in two to three million people in France. Only few of them will develop end stage renal disease. A non invasive exam which could discriminate most severe nephropathies with poor outcome would be of particular interest for clinicians. Predictive value of renal arterial resistive index (RI) seems to be important but remains ill-defined. We realized a prospective monocentric study. The main objective was to determine the histological parameters associated with RI value. Second objectives consisted to define clinical and biological parameters associated with RI, to evaluate correlation between RI and renal outcome and to define a prognostic threshold. In this purpose, RI was measured by echo-doppler in the two days preceedings renal biopsy in 58 patients from 2006 and 2007. Clinical, biological and ultrasonographic data were collected prospectively. Renal function at one year was collected retrospectivey in 42 patients. We showed that RI increases with the determinants of arterial rigidity (age and pulse pressure), the severity of arteriosclerosis and interstitial fibrosis and the importance of renal dysfunction. On the other hand, RI is neither correlated with the presence of hyaline arteriolar deposits nor with glomerulosclerosis. RI is associated with renal prognosis, independently from age and initial glomerular filtration rate. A threshold of 0.70 has excellent negative predictive value for an interstitial fibrosis of more than 20% and excellent positive value for severe arteriosclerosis and decline of renal function at one year. This study underlines that RI is a non invasive prognosis factor and the interest of a current utilization of renal Doppler for the management of chronic kidney diseases.PARIS12-CRETEIL BU Médecine (940282101) / SudocSudocFranceF

Clostridium perfringens related spleen gangrene

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Thrombospondin-1 plays a profibrotic and pro-inflammatory role during ureteric obstruction.

International audienceThrombospondin-1 (TSP-1) is an endogenous activator of transforming growth factor-β (TGF-β), and an anti-angiogenic factor, which may prevent kidney repair. Here we investigated whether TSP-1 is involved in the development of chronic kidney disease using rats with unilateral ureteral obstruction, a well-known model to study renal fibrosis. Obstruction of 10 days duration induced inflammation, tubular cell atrophy, dilation, apoptosis, and proliferation, leading to interstitial fibrosis. TSP-1 expression was increased in parallel to that of collagen III and TGF-β. Relief of the obstruction at day 10 produced a gradual improvement in renal structure and function, the reappearance of peritubular capillaries, and restoration of renal VEGF content over a 7- to 15-day post-relief period. TSP-1 expression decreased in parallel with that of TGF-β1 and collagen III. Mice in which the TSP-1 gene was knocked out displayed less inflammation and had better preservation of renal tissue and the peritubular capillary network compared to wild-type mice. Additional studies showed that the inflammatory effect of TSP-1 was mediated, at least in part, by monocyte chemoattractant protein-1 and activation of the Th17 pathway. Thus, TSP-1 is an important profibrotic and inflammatory mediator of renal disease. Blockade of its action may be a treatment against the development of chronic kidney disease

Exploring the microvascular impact of red blood cell transfusion in intensive care unit patients

International audienceBACKGROUND: Red blood cell (RBC) transfusion is a common treatment for hospitalized patients. However, the effects of RBC transfusion on microvascular function remain controversial.METHODS: In a medical ICU in a tertiary teaching hospital, we prospectively included anemic patients requiring RBC transfusion. Skin microvascular reactivity was measured before and 30 min after RBC transfusion. Plasma was collected to analyze intravascular hemolysis and draw the lipidomic and cytokine profiles.RESULTS: In a cohort of 59 patients, the median age was 66 [55-81] years and SAPS II was 38 [24-48]. After RBC transfusion, endothelium-dependent microvascular reactivity improved in 35 (59%) patients, but worsened in 24 others (41%). Comparing clinical and biological markers revealed that baseline blood leucokyte counts distinguished improving from worsening patients (10.3 [5.7; 19.7] vs. 4.6 [2.1; 7.3] × 109/L; p = 0.001) and correlated with variations of microvascular reactivity (r = 0.36, p = 0.005). Blood platelet count was also higher in improving patients (200 [97; 280] vs 160 [40; 199] × 103/mL, p = 0.03) but did not correlate with variations of microvascular reactivity. We observed no intravascular hemolysis (HbCO, heme, bilirubin, LDH), but recorded a significant increase in RBC microparticle levels specific to improving patients after transfusion (292 [108; 531] vs. 53 [34; 99] MP/μL; p = 0.03). The improvement in microvascular dilation was positively correlated with RBC microparticle levels (R = 0.83, p < 0.001) and conversion of arachidonic acid into vasodilating eicosanoids.CONCLUSIONS: Patients displaying an improved microvascular reactivity after RBC transfusion had high blood leukocyte counts, increased RBC microparticle formation, and enhanced metabolism of arachidonic acid into vasodilating lipids. Our data suggested a contribution of recipient leukocytes to the vascular impact of RBC transfusion

Multicenter Retrospective Study of Invasive Fusariosis in Intensive Care Units, France

Invasive fusariosis can be life-threatening, especially in immunocompromised patients who require intensive care unit (ICU) admission. We conducted a multicenter retrospective study to describe clinical and biologic characteristics, patient outcomes, and factors associated with death and response to antifungal therapy. We identified 55 patients with invasive fusariosis from 16 ICUs in France during 2002­–­­2020. The mortality rate was high (56%). Fusariosis-related pneumonia occurred in 76% of patients, often leading to acute respiratory failure. Factors associated with death included elevated sequential organ failure assessment score at ICU admission or history of allogeneic hematopoietic stem cell transplantation or hematologic malignancies. Neither voriconazole treatment nor disseminated fusariosis were strongly associated with response to therapy. Invasive fusariosis can lead to multiorgan failure and is associated with high mortality rates in ICUs. Clinicians should closely monitor ICU patients with a history of hematologic malignancies or stem cell transplantation because of higher risk for death

Effect of an ICU Diary on Posttraumatic Stress Disorder Symptoms Among Patients Receiving Mechanical Ventilation

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Effects of Standard-Dose Prophylactic, High-Dose Prophylactic, and Therapeutic Anticoagulation in Patients With Hypoxemic COVID-19 Pneumonia The ANTICOVID Randomized Clinical Trial

International audienceIMPORTANCE Given the high risk of thrombosis and anticoagulation-related bleeding in patients with hypoxemic COVID-19 pneumonia, identifying the lowest effective dose of anticoagulation therapy for these patients is imperative. OBJECTIVES To determine whether therapeutic anticoagulation (TA) or high-dose prophylactic anticoagulation (HD-PA) decreases mortality and/or disease duration compared with standard-dose prophylactic anticoagulation (SD-PA), and whether TA outperforms HD-PA; and to compare the net clinical outcomes among the 3 strategies. DESIGN, SETTINGS, AND PARTICIPANTS The ANTICOVID randomized clinical open-label trial included patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram at 23 health centers in France from April 14 to December 13, 2021. Of 339 patients randomized, 334 were included in the primary analysis-114 patients in the SD-PA group, 110 in the HD-PA, and 110 in the TA. At randomization, 90% of the patients were in the intensive care unit. Data analyses were performed from April 13, 2022, to January 3, 2023. INTERVENTIONS Patients were randomly assigned (1:1:1) to receive either SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days. MAIN OUTCOMES AND MEASURES A hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28. Main secondary outcome was net clinical outcome at day 28 (composite of thrombosis, major bleeding, and all-cause death). RESULTS Among the study population of 334 individuals (mean [SD] age, 58.3 [13.0] years; 226 [67.7%] men and 108 [32.3%] women), use of HD-PA and SD-PA had similar probabilities of favorable outcome (47.3% [95%CI, 39.9% to 54.8%] vs 52.7%[95%CI, 45.2%to 60.1%]; P = .48), as did TA compared with SD-PA (50.9% [95%CI, 43.4%to 58.3%] vs 49.1% [95%CI, 41.7%to 56.6%]; P = .82) and TA compared with HD-PA (53.5%[95%CI 45.8% to 60.9%] vs 46.5% [95%CI, 39.1% to 54.2%]; P = .37). Net clinical outcome was met in 29.8% of patients receiving SD-PA (20.2%thrombosis, 2.6%bleeding, 14.0% death), 16.4% receiving HD-PA (5.5%thrombosis, 3.6%bleeding, 11.8%death), and 20.0% receiving TA (5.5% thrombosis, 3.6% bleeding, 12.7%death). Moreover, HD-PA and TA use significantly reduced thrombosis compared with SD-PA (absolute difference, -14.7 [95%CI -6.2 to -23.2] and -14.7 [95%CI -6.2 to -23.2], respectively). Use of HD-PA significantly reduced net clinical outcome compared with SD-PA (absolute difference, -13.5; 95%CI -2.6 to -24.3). CONCLUSIONS AND RELEVANCE This randomized clinical trial found that compared with SD-PA, neither HD-PAnor TAuse improved the primary hierarchical outcome of all-cause mortality or time to clinical improvement in patients with hypoxemicCOVID-19 pneumonia; however, HD-PA resulted in significantly better net clinical outcome by decreasing the risk of de novo thrombosis