Coagulation factor 2 receptor (F2R), also well-known as a protease-activated receptor 1 (PAR1), is the first known thrombin receptor and plays a critical role in transmitting thrombin-mediated activation of intracellular signaling in many types of cells. It has been known that bacterial infections lead to activation of coagulation systems, and recent studies suggest that PAR1 may be critically involved not only in mediating bacteria-induced detrimental coagulation, but also in innate immune and inflammatory responses. Community-acquired pneumonia, which is frequently caused by Streptococcus pneumoniae (S. pneumoniae), is characterized as an intra-alveolar coagulation and an interstitial neutrophilic inflammation. Recently, the role of PAR1 in regulating pneumococcal infections has been proposed. However, the role of PAR1 in pneumococcal infections has not been clearly understood yet. In this review, recent findings on the role of PAR1 in pneumococcal infections and possible underlying molecular mechanisms by which S. pneumoniae regulates PAR1-mediated immune and inflammatory responses will be discussed.
Bacterial Infections ; Blood Coagulation Factors* ; Inflammation ; Negotiating ; Neutrophils ; Pneumococcal Infections* ; Pneumonia ; Receptor, PAR-1 ; Receptors, Thrombin ; Streptococcus pneumoniae

Streptococcus pneumoniae (S. pneumoniae, also known as pneumococcus) infections are major causes of death worldwide. Despite the development and use of effective antibiotics, high, early mortality due to pneumococcal infections has not been decreased for the last few decades. Recent study found a deadly hemorrhagic acute lung injury (ALI) as a major cause of death at the early stage of severe pneumococcal infections. Interleukin (IL)-1beta was known to play critical roles not only for the development of ALI but also resolution of it. The role of IL-1beta on the pathogenesis of pneumococcal ALI, however, has not been well understood yet. This study aims to investigate the role of IL-1beta on the development of pneumococcal ALI and subsequent death. IL-1beta expression was upregulated in the lungs of pneumococcal ALI in wild-type (WT) mice, but not in the plasma. Despite an increased expression of pulmonary IL-1beta, no inflammatory cell infiltration into airway has been observed. Upregulation of IL-1beta expression was indeed dependent on pneumococcal cytoplasmic toxin pneumolysin and its cell surface receptor Toll-like receptor 4. Deficiency of IL-1R1, a cell surface receptor of IL-1beta, resulted in a markedly reduced hemorrhagic pulmonary edema and early death in pneumococcal ALI. Finally, IL-1beta neutralization in WT mice protects against pulmonary hemorrhagic edema and death. These data suggest that pulmonary expression of IL-1beta exacerbates pneumolysin-induced ALI and death by promoting alveolar hemorrhagic edema.
Acute Lung Injury* ; Animals ; Anti-Bacterial Agents ; Cause of Death ; Cytoplasm ; Edema ; Interleukin-1beta* ; Interleukins ; Lung ; Mice ; Mortality ; Plasma ; Pneumococcal Infections ; Pneumonia ; Pulmonary Edema ; Streptococcus pneumoniae ; Toll-Like Receptor 4 ; Up-Regulation

Background: This study aimed to validate the Geriatric Trauma Outcome Score (GTOS) for predicting mortality associated with trauma in older Korean adults and compare the GTOS with the Trauma and Injury Severity Score (TRISS). Methods: This study included patients aged ≥65 years who visited the Chungbuk National University Hospital Regional Trauma Center between January 2016 and December 2022. We used receiver operating characteristic curves and calibration plots to assess the discrimination and calibration of the scoring systems. Results: Among 3,053 patients, the median age was 77 years, and the mortality rate was 5.2%. The overall GTOS-predicted mortality and 1–TRISS were 5.4% (interquartile range [IQR], 3.7–9.5) and 4.7% (IQR, 4.7–4.7), respectively. The areas under the curves (AUCs) of 1–TRISS and GTOS for the total population were 0.763 (95% confidence interval [CI], 0.719–0.806) and 0.794 (95% CI, 0.755–0.833), respectively. In the Glasgow Coma Scale (GCS) ≤12 group, the in-hospital mortality rate was 27.5% (79 deaths). The GTOS-predicted mortality and 1–TRISS in this group were 18.6% (IQR, 7.5–34.7) and 26.9% (IQR, 11.9–73.1), respectively. The AUCs of 1–TRISS and GTOS for the total population were 0.800 (95% CI, 0.776–0.854) and 0.744 (95% CI, 0.685–0.804), respectively. Conclusion The GTOS and TRISS demonstrated comparable accuracy in predicting mortality, while the GTOS offered the advantage of simpler calculations. However, the GTOS tended to underestimate mortality in patients with GCS ≤12; thus, its application requires care in such cases.

Background: This study aimed to validate the Geriatric Trauma Outcome Score (GTOS) for predicting mortality associated with trauma in older Korean adults and compare the GTOS with the Trauma and Injury Severity Score (TRISS). Methods: This study included patients aged ≥65 years who visited the Chungbuk National University Hospital Regional Trauma Center between January 2016 and December 2022. We used receiver operating characteristic curves and calibration plots to assess the discrimination and calibration of the scoring systems. Results: Among 3,053 patients, the median age was 77 years, and the mortality rate was 5.2%. The overall GTOS-predicted mortality and 1–TRISS were 5.4% (interquartile range [IQR], 3.7–9.5) and 4.7% (IQR, 4.7–4.7), respectively. The areas under the curves (AUCs) of 1–TRISS and GTOS for the total population were 0.763 (95% confidence interval [CI], 0.719–0.806) and 0.794 (95% CI, 0.755–0.833), respectively. In the Glasgow Coma Scale (GCS) ≤12 group, the in-hospital mortality rate was 27.5% (79 deaths). The GTOS-predicted mortality and 1–TRISS in this group were 18.6% (IQR, 7.5–34.7) and 26.9% (IQR, 11.9–73.1), respectively. The AUCs of 1–TRISS and GTOS for the total population were 0.800 (95% CI, 0.776–0.854) and 0.744 (95% CI, 0.685–0.804), respectively. Conclusion The GTOS and TRISS demonstrated comparable accuracy in predicting mortality, while the GTOS offered the advantage of simpler calculations. However, the GTOS tended to underestimate mortality in patients with GCS ≤12; thus, its application requires care in such cases.

Background: This study aimed to validate the Geriatric Trauma Outcome Score (GTOS) for predicting mortality associated with trauma in older Korean adults and compare the GTOS with the Trauma and Injury Severity Score (TRISS). Methods: This study included patients aged ≥65 years who visited the Chungbuk National University Hospital Regional Trauma Center between January 2016 and December 2022. We used receiver operating characteristic curves and calibration plots to assess the discrimination and calibration of the scoring systems. Results: Among 3,053 patients, the median age was 77 years, and the mortality rate was 5.2%. The overall GTOS-predicted mortality and 1–TRISS were 5.4% (interquartile range [IQR], 3.7–9.5) and 4.7% (IQR, 4.7–4.7), respectively. The areas under the curves (AUCs) of 1–TRISS and GTOS for the total population were 0.763 (95% confidence interval [CI], 0.719–0.806) and 0.794 (95% CI, 0.755–0.833), respectively. In the Glasgow Coma Scale (GCS) ≤12 group, the in-hospital mortality rate was 27.5% (79 deaths). The GTOS-predicted mortality and 1–TRISS in this group were 18.6% (IQR, 7.5–34.7) and 26.9% (IQR, 11.9–73.1), respectively. The AUCs of 1–TRISS and GTOS for the total population were 0.800 (95% CI, 0.776–0.854) and 0.744 (95% CI, 0.685–0.804), respectively. Conclusion The GTOS and TRISS demonstrated comparable accuracy in predicting mortality, while the GTOS offered the advantage of simpler calculations. However, the GTOS tended to underestimate mortality in patients with GCS ≤12; thus, its application requires care in such cases.