No abstract

After use, surgical instruments are sent to a Sterile Processing Department (SPD) or facility to be cleaned, reorganized, maintained, sterilized and stored for eventual re-use. Though essential for safe, efficient and cost-effective surgical delivery, the functions, trade-offs and outcomes within SPDs have rarely been studied. Patient safety incident (PSI) reports are the most ubiquitous form of safety data collected within acute care environments and are often used to report issues in the SPD. Using the work systems analysis perspective we developed in previous work, we created a framework for areas where system failures might occur and manually evaluated PSI reports to investigate a period of possible system strain. We identify the assembly stage as a potentially significant contributor to system strain in the SPD and suggest that several issues related to sterile processing may be interconnected with an aim to assist decisionmakers and healthcare team members in SPD system management.

Congenital heart disease (CHD) is the most common birth defect worldwide; however, underlying mechanisms remain unknown. Loss-of-function mutations in PTPN11, the gene encoding the protein tyrosine phosphatase SHP2, are implicated in CHD and cause Noonan Syndrome with Multiple Lentigines (NSML). NSML presents with multiple cardiac defects, including hypertrophy. Here, we found that the NSML-associated adult-onset cardiac hypertrophy stems from aberrant signaling originating from developing endocardium. Embryonic NSML hearts showed diminished trabeculation and valvular hyperplasia, defects recapitulated in endocardial-, but not myocardial- or neural crest-, specific NSML mice. NSML hearts also developed ventricular septal defects, a phenotype reproduced only in myocardial-specific NSML hearts, suggesting NSML mutations have both cell autonomous and non-autonomous functions in cardiac development. Importantly, endocardial-specific expression of NSML was sufficient to induce adult-onset cardiac hypertrophy. Mechanistically, we observed aberrant AKT activity in NSML embryos, with decreased downstream FOXP1/FGF and NOTCH1/EPHB2 signaling, two pathways necessary for reciprocal crosstalk between developing endocardium and myocardium. Taken together, our data provide the first functional and disease-based evidence to suggest that critical mechanisms exist to control endocardial-myocardial crosstalk, the aberrant regulation of which may lead to CHD and adult-onset cardiac disease.