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Item The EGS Grading Scale For Skin And Soft Tissue Infections Is Predictive Of Poor Outcomes : A Multicenter Validation Study(Lippincott, Williams & Wilkins, 2020-04-01) Savage, Stephanie A.; Li, Shi Wen; Utter, Garth H.; Cox, Jessica A.; Wydo, Salina M.; Cahill, Kevin; Sarani, Babak; Holzmacher, Jeremy; Duane, Therese M.; Gandhi, Rajesh R.; Zielinski, Martin D.; Ray-Zack, Mohamed; Tierney, Joshua; Chapin, Trinette; Murphy, Patrick B.; Vogt, Kelly N.; Schroeppel, Thomas J.; Callaghan, Emma; Kobayashi, Leslie; Coimbra, Raul; Schuster, Kevin M.; Gillaspie, Devin; Timsina, Lava; Louis, Alvancin; Crandall, Marie; Medicine, School of MedicineIntroduction: Over the last five years, the American Association for the Surgery of Trauma (AAST) has developed grading scales for Emergency General Surgery (EGS) diseases. In a prior validation study using diverticulitis, the grading scales were predictive of complications and length of stay. As EGS encompasses diverse diseases, the purpose of this study was to validate the grading scale concept against a different disease process with a higher associated mortality. We hypothesized that the grading scale would be predictive of complications, length of stay and mortality in skin and soft tissue infections (STI). Methods: This multi-institutional trial encompassed 12 centers. Data collected included demographic variables, disease characteristics and outcomes such as mortality, overall complications, hospital and ICU length of stay. The EGS scale for STI was used to grade each infection and two surgeons graded each case to evaluate inter-rater reliability. Results: 1170 patients were included in this study. Inter-rater reliability was moderate (kappa coefficient 0.472-0.642, with 64-76% agreement). Higher grades (IV and V) corresponded to significantly higher LRINEC scores when compared with lower EGS grades. Patients with grade IV and V STI had significantly increased odds of all complications, as well as ICU and overall length of stay. These associations remained significant in logistic regression controlling for age, gender, comorbidities, mental status and hospital-level volume. Grade V disease was significantly associated with mortality as well. Conclusion: This validation effort demonstrates that Grade IV and V STI are significantly predictive of complications, hospital length of stay and mortality. Though predictive ability does not improve linearly with STI grade, this is consistent with the clinical disease process, in which lower grades represent cellulitis and abscess and higher grades are invasive infections. This second validation study confirms the EGS grading scale as predictive, and easily used, in disparate disease processes.Item Two Acinetobacter baumannii Isolates Obtained From a Fatal Necrotizing Fasciitis Infection Display Distinct Genomic and Phenotypic Characteristics in Comparison to Type Strains(Frontiers Media, 2021-04-12) Grier, Jennifer T.; Arivett, Brock A.; Ramírez, Maria; Chosed, Renee J.; Bigner, Jessica A.; Ohneck, Emily J.; Metz, Maeva L.; Wood, Cecily R.; Arce, Sergio; Tartaro, Andrea; Relich, Ryan F.; Actis, Luis A.; Fiester, Steven E.; Pathology and Laboratory Medicine, School of MedicineAcinetobacter baumannii has been recognized as a critical pathogen that causes severe infections worldwide not only because of the emergence of extensively drug-resistant (XDR) derivatives, but also because of its ability to persist in medical environments and colonize compromised patients. While there are numerous reports describing the mechanisms by which this pathogen acquires resistance genes, little is known regarding A. baumannii's virulence functions associated with rare manifestations of infection such as necrotizing fasciitis, making the determination and implementation of alternative therapeutic targets problematic. To address this knowledge gap, this report describes the analysis of the NFAb-1 and NFAb-2 XDR isolates, which were obtained at two time points during a fatal case of necrotizing fasciitis, at the genomic and functional levels. The comparative genomic analysis of these isolates with the ATCC 19606T and ATCC 17978 strains showed that the NFAb-1 and NFAb-2 isolates are genetically different from each other as well as different from the ATCC 19606T and ATCC 17978 clinical isolates. These genomic differences could be reflected in phenotypic differences observed in these NFAb isolates. Biofilm, cell viability and flow cytometry assays indicate that all tested strains caused significant decreases in A549 human alveolar epithelial cell viability with ATCC 17978, NFAb-1 and NFAb-2 producing significantly less biofilm and significantly more hemolysis and capacity for intracellular invasion than ATCC 19606T. NFAb-1 and NFAb-2 also demonstrated negligible surface motility but significant twitching motility compared to ATCC 19606T and ATCC 17978, likely due to the presence of pili exceeding 2 µm in length, which are significantly longer and different from those previously described in the ATCC 19606T and ATCC 17978 strains. Interestingly, infection with cells of the NFAb-1 isolate, which were obtained from a premortem blood sample, lead to significantly higher mortality rates than NFAb-2 bacteria, which were obtained from postmortem tissue samples, when tested using the Galleria mellonella in vivo infection model. These observations suggest potential changes in the virulence phenotype of the A. baumannii necrotizing fasciitis isolates over the course of infection by mechanisms and cell processes that remain to be identified.