Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Severe respiratory syncytial virus (RSV) pneumonia is a leading cause of hospitalization and morbidity in infants and young children. Early identification of severe RSV pneumonia is crucial for timely and effective treatment by pediatricians. Currently, no prediction model exists for identifying severe RSV pneumonia in children. ⋯ This study identified specific biomarkers and developed a diagnostic model for severe RSV pneumonia in children. These findings provide a robust foundation for early identification and treatment of severe RSV pneumonia, offering new insights into its pathogenesis and improving pediatric care.
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The neuronal biomarker NSE correlates with the volume of lung contusion in polytraumatized patients.
Severe injuries caused by accidents, like traumatic brain injury (TBI) or thoracic trauma (TT) continue to be the leading cause of death in younger people with relevant socio-economic impact. Fast and targeted diagnostics is essential for further therapy decisions and prognosis. The following study investigates NSE as a potential biomarker for lung injury after blunt TT. ⋯ A significant NSE release after isolated thoracic trauma peaks on the day of admission. The extent of lung contusion volume (defined as alveolar parenchymal density) correlates with NSE serum concentration. Thus, NSE has predictive value for the extent of pulmonary contusion. However, according to these data, NSE seems to have no diagnostic value as a TBI biomarker in concomitant TT.
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Sepsis, a complex and multifaceted condition, is a common occurrence with serious implications for critically ill patients in the intensive care unit (ICU). The YWHAH gene encodes the 14-3-3n protein, a member of the 14-3-3 protein family. While existing research primarily focuses on the role of 14-3-3n in conditions such as schizophrenia and various cancers, our study revealed that the expression of the YWHAH gene remained relatively stable in both infected individuals and healthy controls. ⋯ In a comprehensive analysis of public single-cell transcriptome databases, the expression of YWHAH was found to be distinctive in cases of sepsis and infection. These findings were corroborated through an in vitro analysis utilizing real-time polymerase chain reaction. This study represents the initial identification of variations in YWHAH gene expression between patients with infection and sepsis, potentially offering insights for the development of early detection and treatment strategies for sepsis.
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Background: Understanding of immune cell phenotypes associated with inflammatory and immunosuppressive host responses in sepsis is imprecise, particularly in low- and middle-income countries, where the global sepsis burden is concentrated. In these settings, elucidation of clinically relevant immunophenotypes is necessary to determine the relevance of emerging therapeutics and refine mechanistic investigations of sepsis immunopathology. Methods: In a prospective cohort of adults hospitalized with suspected sepsis in Uganda (N = 43; median age 46 years [IQR 36-59], 24 [55.8%] living with HIV, 16 [37.2%] deceased at 60 days), we combined high-dimensional flow cytometry with unsupervised machine learning and manual gating to define peripheral immunophenotypes associated with increased risk of 60-day mortality. ⋯ Abundance of T cells expressing inhibitory checkpoint proteins (PD-1, CTLA-4, LAG-3) was similar between patients who died versus those who survived. Conclusions: This is the first study to define high-risk immunophenotypes among adults with sepsis in sub-Saharan Africa, an immunologically distinct region where biologically informed treatment strategies are needed. More broadly, our findings highlight the clinical importance and complexity of myeloid derived suppressor cell expansion during sepsis and support emerging data that suggest a host-protective role for PD-L1 myeloid checkpoints in acute critical illness.
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Sepsis is a life-threatening disease due to a dysregulated host response to infection, with an unknown regulatory mechanism for prognostic necroptosis-related genes (NRGs). Using GEO datasets GSE65682 and GSE134347, we identified six NRG biomarkers ( ATRX , TSC1 , CD40 , BACH2 , BCL2 , and LEF1 ) with survival and diagnostic significance through Kaplan-Meier (KM) and receiver operating characteristic (ROC) analyses. Afterward, the ingenuity pathway analysis (IPA) highlighted enrichment in hepatic fibrosis pathways and BEX2 protein. ⋯ Additionally, DrugBank analysis identified paclitaxel, docetaxel, and rasagiline as potential BCL2-targeting sepsis treatments. Finally, real-time quantitative PCR confirmed ATRX, TSC1, and LEF1 downregulation in sepsis samples, contrasting CD40's increased expression in CTL samples. In conclusion, ATRX , TSC1 , CD40 , BACH2 , BCL2 , and LEF1 may be critical regulatory targets of necroptosis in sepsis, providing a basis for further necroptosis-related studies in sepsis.