Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Immunothrombosis has emerged as a potential mechanistic link underlying the development and progression of acute respiratory distress syndrome (ARDS), but understanding its specific profile in patients, both locally and systemically, is limited. The objective of this study was to characterize and compare the immunothrombotic signatures in patients diagnosed with pneumonia-related ARDS (p-ARDS) at both the pulmonary and systemic levels and to evaluate their clinical relevance. The study included 23 consecutive patients diagnosed with p-ARDS admitted to the intensive care unit at a tertiary university hospital from July 2022 to May 2023, alongside 40 concurrently hospitalized patients with common pneumonia as controls. ⋯ These observations were maintained after adjustment for severity of illness (Acute Physiology and Chronic Health Evaluation II scores). In terms of clinical relevance, inflammatory biomarkers (interleukin [IL]-6, IL-8) in BALF were found to correlate with PaO2/FiO2 ratio, while serum levels of a disintegrin and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS-13) and thrombomodulin showed associations with Sequential Organ Failure Assessment and Disseminated Intravascular Coagulation scores. In conclusion, this preliminary investigation identified compartment-specific variations in the immunothrombotic signature between patients with p-ARDS and those with pneumonia alone, with inflammatory responses predominantly localized in the alveolar compartments and coagulation/endothelial injury biomarkers more pronounced in peripheral blood.
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In this retrospective cohort study, we investigated the prognostic value of sarcopenia evaluated by Computed Tomography (CT)-based indices for adverse hospitalization outcomes in patients with acute infections. We analyzed data from 225 patients admitted to the hospital for acute infections between 2019 and 2020. Patients who had undergone an abdominal CT scan either up to 1 month before or within the first 3 days of hospitalization were included. ⋯ Notably, patients with both low SMI and pMD exhibited the poorest hospitalization outcomes: aOR for 1-year mortality 5.015 (95% CI 1.767-14.23, p = 0.002), and prolonged length of stay aOR 3.197, (95% CI 1.159-8.821, p = 0.025). CT-based muscle indices serve as independent prognostic factors in medical patients admitted with acute infection. Incorporating radiological assessments of sarcopenia into routine care for hospitalized patients with acute infection may enable risk stratification and early intervention in reversible conditions.
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Infection with Borrelia burgdorferi can spread and cause central nervous system involvement, known as neuroborreliosis. Microglia phagocytose bacteria, mediate inflammation, and elicit an immune response toward the spirochete. Like other tissue macrophages, microglia can polarize into two different modulatory phenotypes, M1 and M2. ⋯ A decrease of iNOS at 4 h of infection suggests a diminished production of reactive nitrogen species that are a critical component of innate defense against infection. Increased iNOS and simultaneously decreased expression of CX3CR1 at 24 h, may suggest initiation of neuroprotective regulation of microglia recruitment to neuroinflammation. The dynamics of major inflammatory cytokines appear to be important in the microglial response to B. burgdorferi and should be further studied as these could become therapeutic targets in neuroborreliosis.
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The occurrence of sepsis-associated acute kidney injury (SA-AKI) predicts a worse prognosis. We aimed to assess the impact of acetaminophen use on short-term mortality in patients with SA-AKI. A total of 6563 patients diagnosed with SA-AKI from the 2008 to 2019 Medical Information Mart for Intensive Care IV (MIMIC-IV) database were enrolled in this retrospective cohort study. ⋯ The PSM analysis demonstrated that acetaminophen use was still related to a reduced risk of 30-day mortality and in-hospital mortality. Subgroup analysis showed that the relationships between acetaminophen and 30-day mortality and in-hospital mortality were consistent across subgroups (p < 0.05). The use of acetaminophen has an association with lower short-term mortality in patients with SA-AKI.
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Cisplatin (DDP) resistance represents a pivotal contributing factor to chemotherapy failure and adverse patient outcomes in gastric cancer (GC). The objective of the present study was to investigate the roles and underlying mechanisms of myocyte enhancer factor 2A (MEF2A) in DDP resistance in GC. GC cell line AGS and MKN-45 cells were applied to construct DDP-resistant cells. ⋯ Mechanistically, MEF2A acts as a transcriptional activator of NFKBIA, which led to the reduction of phosphorylation of p65 and cytoplasmic retention. Moreover, MEF2A overexpression promoted the sensitivity of GC cells to DDP and tumor growth, whereas these effects were partially reversed by NFKBIA silence. Collectively, MEF2A mitigated the DDP resistance in GC cells by modulatory actions on the NFKBIA/NF-κB signaling, shedding light on MEF2A/NFKBIA might be a promising intervention target for improving DDP resistance in GC.