The association between intraoperative fluid management and perioperative allogenic blood transfusion during adolescent idiopathic scoliosis surgery.

INTRODUCTION: Bleeding and transfusion remain important concerns during surgical correction of scoliosis even when multiple conservative strategies, such as preoperative recombinant erythropoietin and/or antifibrinolytic agents, are used. The current work aimed to determine the impact of other potential risk factors, especially the volume of intraoperative fluid intake, on the perioperative risk of allogenic transfusion during surgical correction of adolescent idiopathic scoliosis. METHODS: This prospective study included all cases of adolescent idiopathic scoliosis operated in a single center during 2 years (2018-2020). Predictors analyzed were as follows: body mass index, preoperative hemoglobin concentration, thoracoplasty, preoperative halo-gravity, volume of intraoperative crystalloid administration, use of esophageal Doppler (for goal-directed fluid therapy), and duration of surgery. Statistical analyses were performed using a multivariable logistic regression model. RESULTS: Two hundred patients were included in the analysis. Multivariable analysis found: an increased volume of intraoperative crystalloid administration as a significant predictor of allogenic blood transfusion. Receiving operator characteristics analysis found the model exhibiting an area under the curve of 0.85 (95% confidence interval: 0.75-0.95). Optimizing stroke volume using esophageal Doppler was associated with a decrease in intraoperative crystalloid intake. CONCLUSION: These results indicate a statistical association between the increase in crystalloid intake and the risk of allogenic blood transfusion during surgical correction of adolescent idiopathic scoliosis. Controlled studies are needed to address the causative relation between intraoperative fluid intake and the risk of allogenic transfusion.

Tumor Lysis Syndrome and AKI: Beyond Crystal Mechanisms.

BACKGROUND: The pathophysiology of AKI during tumor lysis syndrome (TLS) is not well understood due to the paucity of data. We aimed to decipher crystal-dependent and crystal-independent mechanisms of TLS-induced AKI. METHODS: Crystalluria, plasma cytokine levels, and extracellular histones levels were measured in two cohorts of patients with TLS. We developed a model of TLS in syngeneic mice with acute myeloid leukemia, and analyzed ultrastructural changes in kidneys and endothelial permeability using intravital confocal microscopy. In parallel, we studied the endothelial toxicity of extracellular histones in vitro. RESULTS: The study provides the first evidence that previously described crystal-dependent mechanisms are insufficient to explain TLS-induced AKI. Extracellular histones that are released in huge amounts during TLS caused profound endothelial alterations in the mouse model. The mechanisms of histone-mediated damage implicates endothelial cell activation mediated by Toll-like receptor 4. Heparin inhibits extracellular histones and mitigates endothelial dysfunction during TLS. CONCLUSION: This study sheds new light on the pathophysiology of TLS-induced AKI and suggests that extracellular histones may constitute a novel target for therapeutic intervention in TLS when endothelial dysfunction occurs.

Intraoperative cerebral oxygen saturation and neurological outcomes following surgical management of necrotizing enterocolitis: Predictive factors of neurological complications following neonatal necrotizing enterocolitis: Predictive factors of neurological complications following neonatal necrotizing enterocolitis.

BACKGROUND: The goal of the present study was to investigate intraoperative factors associated with major neurological complications at 1 year following surgery for necrotizing enterocolitis. MATERIAL AND METHODS: The study consisted of a retrospective review of medical charts of patients operated for over one calendar year in one institution. Data collected included demographic data, cardiac resuscitation at birth, Bell classification, antibiotics usage, time of day of surgery, surgical technique, surgical duration, type of ventilation, intraoperative vasoactive agents, and albumin use, nadir cerebral saturation, the decrease in cerebral saturation from baseline, the time period when cerebral saturation was at least 20% below baseline, and the mean arterial pressure at nadir cerebral saturation. Reported follow-up complications were assessed during formal neonatologist consultation and additional imaging exploration as needed. Analyses included descriptive statistics, and univariable and multivariable statistics. RESULTS: The study included 32 patients with no prior clinical neurological complications, of which 25 had normal cerebral imaging. Severe neurological complications occurred in nine patients at 1 year: Intraventricular hemorrhage (N = 2) and Periventricular leukomalacia (N = 7). However, preoperative cerebral imaging was lacking in seven patients. Consequently, the observed neurological complications at 1 year might be present before the surgery. Multivariable analysis found the decrease in cerebral saturation ≥36% from baseline as the only factor associated with the occurrence of those complications. CONCLUSION: Intraoperative decrease of cerebral oxygen saturation below ≥36% from baseline is associated with severe neurological complications in neonates undergoing surgery for necrotizing enterocolitis.

Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation.

OBJECTIVES: Sepsis is defined as the host's inflammatory response to a life-threatening infection. The endothelium is implicated in immunoregulation during sepsis. Macrolides have been proposed to display immunomodulatory properties. The goal of this study was to analyze whether macrolides can exert immunomodulation of endothelial cells (ECs) in an experimental model of sepsis. METHODS: Human ECs were stimulated by proinflammatory cytokines and lipopolysaccharide before exposure to macrolides. ECs phenotypes were analyzed by flow cytometry. Cocultures of ECs and peripheral blood mononuclear cells (PBMCs) were performed to study the ECs ability to alter T-cell viability and differentiation in the presence of macrolides. Soluble factor production was assessed. RESULTS: ECs act as non-professional antigen presenting cells and expressed human leukocyte antigen (HLA) antigens, the adhesion molecules CD54, CD106, and the coinhibitory molecule CD274 after septic stimulation. Incubation with macrolides induced a significant decrease of HLA class I and HLA class II HLA-DR on septic-stimulated ECs, but did not alter either CD54, CD106, nor CD274 expression. Interleukin-6 (IL-6) and IL-8 production by stimulated ECs were unaltered by incubation with macrolides, whereas Clarithromycin exposure significantly decreased IL-6 gene expression. In cocultures of septic ECs with PBMCs, neither the proportion of CD4 + , CD8 + T nor their viability was altered by macrolides. T-helper lymphocyte subsets Th1, Th17, and Treg polarization by stimulated ECs were unaltered by macrolides. CONCLUSION: This study reports phenotypic and gene expression changes in septic-stimulated ECs exposed to macrolides, without resulting in altered immunogenicity of ECs in co-cultures with PBMCs. In vivo studies may help to further understand the impact of macrolide therapy on ECs immune homeostasis during sepsis.

Immune Consequences of Endothelial Cells' Activation and Dysfunction During Sepsis.

The vascular endothelium provides a direct interface between circulating blood cells and parenchymal cells. Thus, it has a key role in vasomotor tone regulation, primary hemostasis, vascular barrier, and immunity. In the case of systemic inflammation, endothelial cell (EC) activation initiates a powerful innate immune response to eliminate the pathogen. In some specific conditions, ECs may also contribute to the activation of adaptive immunity and the recruitment of antigen-specific lymphocytes. However, the loss of EC functions or an exaggerated activation of ECs during sepsis can lead to multiorgan failure.