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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Observational Study
Blood Interleukin-6 Levels Predict Multiple Organ Dysfunction in Critically Ill Patients.
Predicting multiple organ dysfunction (MOD) in the late phase of critical illnesses is essential. Cytokines are considered biomarkers that can predict clinical outcomes; however, their predictive value for late-phase MOD is unknown. This study aimed to identify the biomarker with the highest predictive value for late-phase MOD. ⋯ Of the measured biomarkers, blood IL-6 levels had the highest predictive value for MOD on days 3 and 7. Blood IL-6 levels predict early- and late-phase MOD in critically ill patients.
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It was reported that carbon monoxide-releasing molecule-3 (CORM-3) administration immediately after hemorrhagic shock and resuscitation (HSR) ameliorates the HSR-induced acute lung injury (ALI); however, the specific mechanism of the protective effects against HSR-induced ALI remains unclear. ⋯ We identified the protective effects of CORM-3 against HSR-induced ALI. The mechanism might be related to the inhibition of p38MAPK signaling pathway in lung macrophages.
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Decompensation is a major prehospital threat to survival from trauma/hemorrhage shock (T/HS) after controlling bleeding. We recently showed higher than expected mortality from a combat-relevant rat model of T/HS (27 mL/kg hemorrhage) with tourniquet (TQ) and permissive hypotensive resuscitation (PHR) with Plasmalyte. Mortality and fluid requirements were reduced by resuscitation with 25% albumin presaturated with oleic acid (OA-sat) compared with fatty-acid -free albumin or Plasmalyte. ⋯ Decompensation was due to vascular decompensation rather than loss of cardiac performance. Albumin concentration was lower in decompensating groups, suggesting decreased stressed volume, which may explain the association of low albumin on admission with poor outcomes after trauma. Our findings suggest that acute decompensation may be common after trauma and severe hemorrhage treated with TQ and PHR and OA-sat albumin may benefit early survival and reduce transfusion volume by improving venous constriction and preventing decompensation.
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Sepsis-induced immunosuppression involves both innate and adaptive immunity and is associated with the increased expression of checkpoint inhibitors, such as programmed cell-death protein 1 (PD-1). The expression of PD-1 is associated with poor outcomes in septic patients, and in models of sepsis, blocking PD-1 or its ligands with antibodies increased survival and alleviated immune suppression. While inhibitory antibodies are effective, they can lead to immune-related adverse events (irAEs), in part due to continual blockade of the PD-1 pathway, resulting in hyperactivation of the immune response. ⋯ Altered survival was associated with improved macrophage phagocytic activity and T-cell production of interferon-γ. Further, myeloperoxidase levels and esterase-positive cells were significantly reduced in LD01-treated mice. Taken together, these data establish that LD01 modulates host immunity and is a viable therapeutic candidate for alleviating immunosuppression that characterizes sepsis and other infectious diseases.