The EGS Grading Scale For Skin And Soft Tissue Infections Is Predictive Of Poor Outcomes : A Multicenter Validation Study

Introduction: 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

Reduced Sox9 Function Promotes Heart Valve Calcification Phenotypes In Vivo

RATIONALE: Calcification of heart valve structures is the most common form of valvular disease and is characterized by the appearance of bone-like phenotypes within affected structures. Despite the clinical significance, the underlying etiology of disease onset and progression is largely unknown and valve replacement remains the most effective treatment. The SRY-related transcription factor Sox9 is expressed in developing and mature heart valves, and its function is required for expression of cartilage-associated proteins, similar to its role in chondrogenesis. In addition to cartilage-associated defects, mice with reduced sox9 function develop skeletal bone prematurely, however the ability of sox9 deficiency to promote ectopic osteogenic phenotypes in heart valves has not been examined. OBJECTIVE: This study aims to determine the role of Sox9 in maintaining connective tissue homeostasis in mature heart valves using in vivo and in vitro approaches. METHODS AND RESULTS: Using histological and molecular analyses we report that Sox9(fl/+);Col2a1-cre mice develop calcific lesions in heart valve leaflets from 3 months of age associated with increased expression of bone-related genes and activation of inflammation and matrix remodeling processes. Consistently, ectopic calcification is also observed following direct knockdown of Sox9 in heart valves in vitro. Further, we show that retinoic acid treatment in mature heart valves is sufficient to promote calcific processes in vitro, which can be attenuated by Sox9 overexpression. CONCLUSIONS: This study provides insights into the molecular mechanisms of heart valve calcification and identifies reduced Sox9 function as a potential genetic basis for calcific valvular disease

The EGS Grading Scale For Skin And Soft Tissue Infections Is Predictive Of Poor Outcomes

IntroductionOver the last 5 years, the American Association for the Surgery of Trauma has developed grading scales for emergency general surgery (EGS) diseases. In a previous 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 (STIs).MethodsThis multi-institutional trial encompassed 12 centers. Data collected included demographic variables, disease characteristics, and outcomes such as mortality, overall complications, and 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.Results1170 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 Laboratory Risk Indicator for Necrotizing Fasciitis 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.ConclusionThis 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.Level of evidencePrognostic/Epidemiologic retrospective multicenter trial, level III