IL-1R Type 1-Deficient Mice Demonstrate an Impaired Host Immune Response against Cutaneous Vaccinia Virus Infection.

The IL-1 superfamily of cytokines and receptors has been studied extensively. However, the specific roles of IL-1 elements in host immunity to cutaneous viral infection remain elusive. In this study, we applied vaccinia virus (VACV) by scarification to IL-1R1 knockout mice (IL-1R1-/-) and found that these mice developed markedly larger lesions with higher viral genome copies in skin than did wild-type mice. The phenotype of infected IL-1R1-/- mice was similar to eczema vaccinatum, a severe side effect of VACV vaccination that may develop in humans with atopic dermatitis. Interestingly, the impaired cutaneous response of IL-1R1-/- mice did not reflect a systemic immune deficiency, because immunized IL-1R1-/- mice survived subsequent lethal VACV intranasal challenge, or defects of T cell activation or T cell homing to the site of inoculation. Histologic evaluation revealed that VACV infection and replication after scarification were limited to the epidermal layer of wild-type mice, whereas lack of IL-1R1 permitted extension of VACV infection into dermal layers of the skin. We explored the etiology of this discrepancy and determined that IL-1R1-/- mice contained significantly more macrophages and monocyte-derived dendritic cells in the dermis after VACV scarification. These cells were vulnerable to VACV infection and may augment the transmission of virus to adjacent skin, thus leading to larger skin lesions and satellite lesions in IL-1R1-/- mice. These results suggest new therapeutic strategies for treatment of eczema vaccinatum and inform assessment of risks in patients receiving IL-1 blocking Abs for treatment of chronic inflammatory disorders.

Muscle herniation as a cause of superficial lumps on the legs of a healthy teenager.

Muscular hernias, focal protrusions of muscle through fascial weaknesses, are uncommon in pediatric patients. When diagnosed, they are usually found on the legs from protrusions of tibialis anterior muscle in young male athletes. Here, we present a case of a healthy 16-year-old boy who developed asymptomatic nodules on the bilateral feet and lateral lower legs, which were confirmed by ultrasound to be focal muscle herniations. Our case highlights a rare example of bilateral muscle herniation in a pediatric patient and the utility of ultrasound as a diagnostic modality for this uncommon condition.

Angioedema After Squaric Acid Treatment in a 6-Year-Old Girl.

Alopecia areata (AA) involves the immune-related destruction of hair follicles, resulting in patches of complete hair loss, most often on the scalp. The topical sensitizer squaric acid dibutylester (SADBE) is a popular treatment option given its low side-effect profile, hair regrowth potential, and lack of cross-reactivity with other chemicals. We describe a unique case of a 6-year-old girl who developed angioedema after SADBE treatment for AA.

How we used a patient visit tracker tool to advance experiential learning in systems-based practice and quality improvement in a medical student clinic.

Poorly designed healthcare systems increase costs and preventable medical errors. To address these issues, systems-based practice (SBP) education provides future physicians with the tools to identify systemic errors and implement quality improvement (QI) initiatives to enhance the delivery of cost-effective, safe and multi-disciplinary care. Although SBP education is being implemented in residency programs and is mandated by the Accreditation Council for Graduate Medical Education (ACGME) as one of its core competencies, it has largely not been integrated into undergraduate medical education. We propose that Medical Student-Faculty Collaborative Clinics (MSFCCs) may be the ideal environment in which to train medical students in SBPs and QI initiatives, as they allow students to play pivotal roles in project development, administration, and management. Here we describe a process of experiential learning that was developed within a newly established MSFCC, which challenged students to identify inefficiencies, implement interventions, and track the results. After identifying bottlenecks in clinic operations, our students designed a patient visit tracker tool to monitor clinic flow and implemented solutions to decrease patient visit times. Our model allowed students to drive their own active learning in a practical clinical setting, providing early and unique training in crucial QI skills.

Reduced-Intensity Conditioning Regimens, Prior Chronic Lymphocytic Leukemia, and Graft-Versus-Host Disease Are Associated with Higher Rates of Skin Cancer after Allogeneic Hematopoietic Stem Cell Transplantation.

To assess incidence and risk factors for skin cancer associated with allogeneic hematopoietic stem cell transplantation, we evaluated 1,974 adult allogeneic hematopoietic stem cell transplantation patients from Beth Israel Deaconess Medical Center and Dana-Farber Cancer Institute who received transplants between January 1995 and July 2013 for hematologic malignancy and survived at least 100 days. Median age was 51.1 years, and median follow-up time was 3 years. Overall, 119 patients had 221 skin cancers. The incidences of squamous cell carcinomas (incidence rate ratio = 9.8; 95% confidence interval = 7.7-12.3), basal cell carcinomas (incidence rate ratio = 2.5; 95% confidence interval = 1.9-3.2), and melanoma (standardized incidence ratio = 3.3; 95% confidence interval = 1.7-5.9) were elevated in our cohort. In multivariable models, risk factors for squamous cell carcinomas were increased age (P < 0.0001), chronic lymphocytic leukemia (P = 0.02), and chronic graft-versus-host disease (P = 0.0002). Risk factors for basal cell carcinomas were chronic lymphocytic leukemia (P = 0.003), reduced-intensity conditioning (P = 0.02), acute graft-versus-host disease (P = 0.03), and chronic graft-versus-host disease (P = 0.003). To our knowledge, previously unreported risk factors in this contemporary cohort include prior CLL for squamous cell carcinoma and basal cell carcinoma and reduced-intensity conditioning for basal cell carcinoma. This study also supports chronic graft-versus-host disease as a risk factor for nonmelanoma skin cancer, particularly squamous cell carcinoma.

Rethinking the Educator Portfolio: An Innovative Criteria-Based Model.

PROBLEM: Academic medical centers struggle to achieve parity in advancement and promotions between educators and discovery-oriented researchers in part because of narrow definitions of scholarship, lack of clear criteria for measuring excellence, and barriers to making educational contributions available for peer review. Despite recent progress in expanding scholarship definitions and identifying excellence criteria, these advances are not integrated into educator portfolio (EP) templates or curriculum vitae platforms. APPROACH: From 2013 to 2015, a working group from the Academy of Medical Educators (AME) at the University of California, San Francisco (UCSF) designed a streamlined, criteria-based EP (EP 2.0) template highlighting faculty members' recent activities in education and setting rigorous evaluation methods to enable educational scholarship to be objectively evaluated for academic advancement, AME membership, and professional development. OUTCOMES: The EP 2.0 template was integrated into the AME application, resulting in high overall satisfaction among candidates and the selection committee and positive feedback on the template's transparency, ease of use, and streamlined format. In 2016, the EP 2.0 template was integrated into the campus-wide curriculum vitae platform and academic advancement system. NEXT STEPS: The authors plan to increase awareness of the EP 2.0 template by educating promotions committees and faculty at UCSF and partnering with other institutions to disseminate it for use. They also plan to study the impact of the template on supporting educators by making their important scholarly contributions available for peer review, providing guidance for professional development, and decreasing disparities in promotions.

Medical education in the United States: do residents feel prepared?

BACKGROUND: Medical schools face a growing challenge in providing a comprehensive educational experience. Students must graduate with not only the medical knowledge but also the requisite skills to care for patients and serve as physicians-in-training. OBJECTIVE: To assess whether residents felt prepared by their medical school training. METHOD: We developed a questionnaire to assess resident attitudes towards various aspects of their medical school training and electronically distributed it among 107 United States training institutions. RESULTS: A total of 2287 residents responded. Overall, a majority (53.8 %) agreed that 'medical school prepared me well to be a resident.' Most residents felt very well or mostly prepared in medical knowledge and clinical skills such as collecting a history (92.3 %), presenting a physical exam (86.1 %), or pathophysiology (81.6 %), but not for applied medical and psychosocial practices including end-of-life care (41.7 %), dealing with a patient death (46.3 %), and considering cost-effective care (28.7 %). Additionally, many residents reported feeling underprepared for time and fatigue management, debt, and medical-legal issues. CONCLUSIONS: Medical school graduates generally feel well prepared for residency. However, they may be less prepared to face important psychosocial, cultural and professional issues. Ultimately, a greater emphasis on skills and psychosocial experience may yield graduates who feel better prepared for today's residency challenges.

In vivo screening for secreted proteins that modulate glucose handling identifies interleukin-6 family members as potent hypoglycemic agents.

Diabetes is a disease of abnormal glucose homeostasis characterized by chronic hyperglycemia and a broad array of consequent organ damage. Because normal glucose homeostasis is maintained by a complex interaction between behavior (feeding and physical activity) and metabolic activity that is modulated by inter-organ signaling through secreted factors, disease modeling in vitro is necessarily limited. In contrast, in vivo studies allow complex metabolic phenotypes to be studied but present a barrier to high throughput studies. Here we present the development of a novel in vivo screening platform that addresses this primary limitation of in vivo experimentation. Our platform leverages the large secretory capacity of the liver and the hepatocyte transfection technique of hydrodynamic tail vein injection to achieve supraphysiologic blood levels of secreted proteins. To date, the utility of hydrodynamic transfection has been limited by the deleterious impact of the variable transfection efficiency inherent to this technique. We overcome this constraint by co-transfection of a secreted luciferase cDNA whose product can be easily monitored in the blood of a living animal and used as a surrogate marker for transfection efficiency and gene expression levels. To demonstrate the utility of our strategy, we screened 248 secreted proteins for the ability to enhance glucose tolerance. Surprisingly, interleukin-6 and several of its family members but not other well-recognized insulin sensitizing agents were identified as potent hypoglycemic factors. We propose this experimental system as a powerful and flexible in vivo screening platform for identifying genes that modulate complex behavioral and metabolic phenotypes.