An oral caspase inhibitor as monotherapy or with antibiotics eradicates MRSA skin infections in mice.

Staphylococcus aureus is the leading cause of skin and soft tissue infections. With the emergence of antibiotic-resistant bacteria, there is an unmet clinical need to develop immune-based therapies to treat skin infections. Previously, we have shown pan-caspase inhibition as a potential host-directed immunotherapy against community-acquired methicillin-resistant S aureus (CA-MRSA) and other bacterial skin infections. Here, we evaluated the role of irreversible pan-caspase inhibitor emricasan as a monotherapy and an adjunctive with a standard-of-care antibiotic, doxycycline, as potential host-directed immunotherapies against S. aureus skin infections in vivo. We used the established CA-MRSA strain USA300 on the dorsum of WT C57BL/6J mice and monitored lesion size and bacterial burden noninvasively, and longitudinally over 14 days with in vivo bioluminescence imaging (BLI). Mice in four groups placebo (0.5% carboxymethyl cellulose [CMC] solution), placebo plus doxycycline (100 mg/kg), emricasan (40 mg/kg) plus doxycycline, and emricasan only were treated orally twice daily by oral gavage for 7 days, starting at 4 h after injection of S aureus. When compared with placebo, all three groups, placebo plus doxycycline, emricasan plus doxycycline, and emricasan treated group, exhibited biological effect, with reduction of both the lesion size (*p = .0277, ****p < .0001, ****p < .0001, respectively) and bacterial burden (***p = .003, ****p < .0001, ****p < .0001, respectively). Importantly, the efficacy of emricasan against S. aureus was not due to direct antibacterial activity. Collectively, pan-caspase inhibitor emricasan and emricasan plus doxycycline reduced both the lesion size and bacterial burden in vivo, and emricasan is a potential host-directed immunotherapy against MRSA skin infections in a preclinical mouse model.

Systems-based hematology: highlighting successes and next steps.

Systems-based hematology is dedicated to improving care delivery for patients with blood disorders. First defined by the American Society of Hematology in 2015, the idea of a systems-based hematologist arose from evolving pressures in the health care system and increasing recognition of opportunities to optimize the quality and cost effectiveness of hematologic care. In this review, we begin with a proposed framework to formalize the discussion of the range of initiatives within systems-based hematology. Classification by 2 criteria, project scope and method of intervention, facilitates comparison between initiatives and supports dialogue for future efforts. Next, we present published examples of successful systems-based initiatives in the field of hematology, including efforts to improve stewardship in the diagnosis and management of complex hematologic disorders (eg, heparin-induced thrombocytopenia and thrombophilias), the development of programs to promote appropriate use of hematologic therapies (eg, blood products, inferior vena cava filters, and anticoagulation), changes in care delivery infrastructure to improve access to hematologic expertise (eg, electronic consultation and disorder-specific care pathways), and others. The range of projects illustrates the broad potential for interventions and highlights different metrics used to quantify improvements in care delivery. We conclude with a discussion about future directions for the field of systems-based hematology, including extension to malignant disorders and the need to define, expand, and support career pathways.

MedEdPORTAL: a report on oral health resources for health professions educators.

MedEdPORTAL is a unique web-based peer-reviewed publication venue for clinical health educators sponsored by the Association of American Medical Colleges (AAMC). The open exchange of educational resources promotes professional collaboration across health professions. In 2008, the American Dental Education Association (ADEA) collaborated with AAMC to allow dental educators to use the platform to publish dental curriculum resources. Oral health is integral to general health; hence, collaboration among health care professionals brings enormous value to patient-centered care. The aim of this study was to conduct a current survey of metrics and submission statistics of MedEdPORTAL resources. The data were collected using the MedEdPORTAL search engine and ADEA and AAMC staff. The data collected were categorized and reported in tables and charts. Results showed that at the time of this study there were over 2,000 medical and dental resources available to anyone worldwide. Oral health resources constituted approximately 30 percent of the total resources, which included cross-indexing with information relevant to both medical and dental audiences. There were several types of dental resources available; the most common were the ones focusing on critical thinking. The usage of MedEdPORTAL has been growing, with participation from over 190 countries and 10,000 educational institutions around the world. The findings of this report suggest that MedEdPORTAL is succeeding in its aim to foster global collaborative education, professional education, and educational scholarship. As such, MedEdPORTAL is providing a new forum for collaboration and opens venues for promising future work in professional education.