Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19

: Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n = 110) and MIS-C (n = 76), along with pediatric healthy controls (pHCs; n = 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-κB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy

Accuracy of the WSES classification system for pelvic ring disruptions: an international validation study

Abstract Background In 2017, a novel classification for pelvic injuries was established by the World Society of Emergency Surgery (WSES). We validated its effectiveness using nationwide real-world data. The roles of associated vascular injury and open fracture in this system were also evaluated. Methods Patients with pelvic fractures in the National Trauma Data Bank 2015 dataset were retrospectively studied. First, the mortality rates were compared by WSES classification. Second, independent predictors of mortality were evaluated using a multivariate logistic regression model. Patients with and without associated vascular injuries and the same hemodynamic and pelvic ring stability statuses were compared. Patients with associated vascular injuries were compared to the proportion of nonsurvivors and survivors with unstable pelvic ring injuries. Third, the outcomes were compared between patients with open pelvic fracture and closed pelvic fracture in the mild, moderate and severe WSES classes. Results During the 12-month study period, 44,163 blunt pelvic fracture patients were included. The mortality rates were 1.8%, 3.8% and 10.6% for the mild, moderate and severe WSES classes, respectively (p &lt; 0.001). MLR analysis showed that unstable pelvic ring injury did not significantly affect mortality (p = 0.549), whereas open pelvic fracture and associated vascular injury were independent predictors of mortality (odds of mortality: open pelvic fracture 1.630, p &lt; 0.001; associated vascular injury 1.602, p &lt; 0.001). Patients with associated vascular injuries showed that there was no significant difference in the proportion of patients with unstable pelvic ring injuries between survivors and nonsurvivors (37.2% vs. 32.7%, p = 0.323). In all three classes, patients with open pelvic fractures had significantly higher mortality rates and infection rates than patients with closed fractures (mortality rates: minor 3.5% vs. 1.8%, p = 0.009, moderate 11.2% vs. 3.3%, p &lt; 0.001, severe 23.8% vs. 9.8%, p &lt; 0.001; infection rates: minor 3.3% vs. 0.7%, p &lt; 0.001, moderate 6.7% vs. 2.1%, p &lt; 0.001, severe 7.9% vs. 2.8%, p &lt; 0.001). Conclusions Based on this nationwide study, the WSES guideline provides an accurate and reproducible classification of pelvic fractures. It is recommended that open/closed fractures and associated vascular injuries be evaluated as supplements of the WSES classification. </jats:sec

The application of the WSES classification system for open pelvic fractures—validation and supplement from a nationwide data bank

Abstract Background Open pelvic fractures are rare but complex injuries. Concomitant external and internal hemorrhage and wound infection-related sepsis result in a high mortality rate and treatment challenges. Here, we validated the World Society Emergency Society (WSES) classification system for pelvic injuries in open pelvic fractures, which are quite different from closed fractures, using the National Trauma Data Bank (NTDB). Methods Open pelvic fracture patients in the NTDB 2015 dataset were retrospectively queried. The mortality rates associated with WSES minor, moderate and severe injuries were compared. A multivariate logistic regression model (MLR) was used to evaluate independent factors of mortality. Patients with and without sepsis were compared. The performance of the WSES classification in the prediction of mortality was evaluated by determining the discrimination and calibration. Results A total of 830 open pelvic fracture patients were studied. The mortality rates of the mild, moderate and severe WSES classes were 3.5%, 11.2% and 23.8%, respectively (p &lt; 0.001). The MLR analysis showed that the presence of sepsis was an independent factor of mortality (odds of mortality 9.740, p &lt; 0.001). Compared with patients without sepsis, those with sepsis had significantly higher mortality rates in all WSES classes (minor: 40.0% vs. 3.1%, p &lt; 0.001; moderate: 50.0% vs. 9.1%, p &lt; 0.001; severe: 66.7% vs. 22.2%, p &lt; 0.001). The receiver operating characteristic (ROC) curve showed an acceptable discrimination of the WSES classification alone for evaluating the mortality of open pelvic fracture patients [area under curve (AUC) = 0.717]. Improved discrimination with an increased AUC was observed using the WSES classification plus sepsis (AUC = 0.767). Conclusions The WSES guidelines can be applied to evaluate patients with open pelvic fracture with accurate evaluation of outcomes. The presence of sepsis is recommended as a supplement to the WSES classification for open pelvic fractures. </jats:sec