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PDF file - 303K, L704N or I941R cis mutation disrupts constitutive dimerization of mutant EGFR (S1); Tyrosine-phosphorylation is abrogated on L704N or I941R compound mutants of dimerization-dependent mutants (S2); Wild-type EGFR, but not Ex20Ins mutant are dependent on asymmetric dimerization for oncogenic transformation (S3); Tyrosine-phosphorylation on dimerization-independent mutants is significantly impaired by introduction of receiver-impairing or activator-impairing mutation (S4); Cell surface expression levels of various EGFR mutants in NIH-3T3 cells (S5); Activities of receiver monomers and activator monomers of wild-type EGFR (S6); Cell surface expression of mutant EGFR in stable cell lines (S7); Differential pharmacological effects of gefitinib and cetuximab against distinct mutant EGFR (S8); Generation and characterization of bitransgenic mice with inducible expression of EGFR Ex20Ins in lung compartments (S9); Cetuximab downregulates tyrosine phosphorylation on mutant EGFR in mouse tumors (S10).

Open long-bone fractures represent a complex injury within the trauma system. Guidelines recommend antibiotics be given within 60 minutes of patient arrival to the emergency department. We sought to measure and improve the timeliness of antibiotic administration at the patient, hospital, and population level within a collaborative quality initiative.Trauma collaborative quality initiative data (January 2017 to December 2020) were analyzed from 34 American College of Surgeons Committee on Trauma verified level 1 and level 2 trauma centers. Inclusion criteria were adult patients (≥16 years), injury severity score ≥5, and open tibia or femur fracture. After the baseline year, hospitals were scored annually on a pay-for-performance metric based on patients receiving antibiotics within 120 minutes of emergency department arrival. Univariate tests examined the differences between baseline and subsequent year(s) performance. A multivariable logistic regression assessed the factors associated with meeting this target time.There were 2,624 patients with an open long-bone fracture. In the baseline year (2017), 76.9% of patients received antibiotics in ≤120 minutes, with a mean time of 57.9 ± 63.3 minutes. After implementing collaborative quality initiative-wide targets, performance significantly improved in subsequent years (2018, 2019, 2020). The collaborative quality initiative achieved their goal of ≥85% of patients receiving antibiotics in ≤120 minutes in 2019 (87.9%) and 2020 (88.5%), with a mean time of 43.3 ± 54.8 minutes (P.05 vs 2017).A pay-for-performance process measure within a statewide trauma collaborative quality initiative improved the timely administration of antibiotics to patients with open fractures. Work remains to align compliance with the guideline target of60 minutes and to identify factors involved in the delay of administration.

Background Emergency general surgery (EGS) encompasses a heterogeneous population of acutely ill patients, and standardized methods for determining disease severity are essential for comparative effectiveness research and quality improvement initiatives. The American Association for the Surgery of Trauma (AAST) has developed a grading system for the anatomic severity of 16 EGS conditions; however, little is known regarding how well these AAST EGS grades can be approximated by diagnosis codes in administrative databases. Methods We identified adults admitted for 16 common EGS conditions in the 2012 to 2017q3 National Inpatient Sample. Disease severity strata were assigned using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes based on AAST EGS anatomic severity grades. We evaluated whether assigned EGS severity (multiple strata or dichotomized into less versus more complex) were associated with in-hospital mortality, complications, length of stay, discharge disposition, and costs. Analyses were adjusted for age, sex, comorbidities, hospital traits, geography, and year. Results We identified 10,886,822 EGS admissions. The number of anatomic severity strata derived from ICD-9/10-CM codes varied by EGS condition and by year. Four conditions mapped to four strata across all years. Two conditions mapped to four strata with ICD-9-CM codes but only two or three strata with ICD-10-CM codes. Others mapped to three or fewer strata. When dichotomized into less versus more complex disease, patients with more complex disease had worse outcomes across all 16 conditions. The addition of multiple strata beyond a binary measure of complex disease, however, showed inconsistent results. Conclusion Classification of common EGS conditions according to anatomic severity is feasible with International Classification of Diseases codes. No condition mapped to five distinct severity grades, and the relationship between increasing grade and outcomes was not consistent across conditions. However, a standardized measure of severity, even if just dichotomized into less versus more complex, can inform ongoing efforts aimed at optimizing outcomes for EGS patients across the nation. Level of evidence Prognostic, level III.