Curated Collections for Clinician Educators: Five Key Papers on Graduated Responsibility in Residency Education.

Introduction The Accreditation Council for Graduate Medical Education calls graduated responsibility "one of the core tenets of American graduate medical education." However, there is no clear set of resources for programs to implement a system of progressively increasing responsibilities for trainees. This project aimed to identify a set of high-yield papers on graduated responsibility for junior faculty members. Methods A study group of Academic Life in Emergency Medicine Faculty Incubator participants identified relevant literature on graduated responsibility via a comprehensive literature search and a call to the online medical education community; 59 total papers were identified. The most relevant and applicable were selected by the study group via a three-round modified Delphi process. Results Five key articles for junior faculty interested in implementing more robust graduated responsibility at their residency training program were selected and described here. Summaries of key points, along with considerations for faculty developers and relevance to junior faculty, are presented for each article. Conclusions The articles presented here provide a solid theoretical and practical basis for junior faculty to explore graduated responsibility. The five articles presented here provide the junior faculty with a toolkit to examine and improve their systems for assigning responsibilities in a graded fashion at their own institutions.

The early acute phase response after burn injury in mice.

In the hours immediately after burn injury, the body enters into an acute phase reaction characterized, in part, by the augmentation of cytokine and acute phase protein production. This reaction has been poorly characterized in the 24 hours immediately after injury. To better understand the early acute phase response, 8- to 10-week-old BALB/C female mice were subjected to a 15% total body surface area (TBSA). Hepatic levels of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 were monitored. In addition, the circulating level of serum amyloid A, an acute phase protein, also was measured at the same time points. Tumor necrosis factor-alpha levels peaked 2 hours after burn injury, whereas interleukin-1beta had a biphasic response, increasing 2 hours after injury and again at 12 hours. Interleukin-6 and serum amyloid A were not increased until 12 hours after injury and began to decline at 24 hours. These results demonstrate that within the liver, the acute phase response after burn injury initially involves tumor necrosis factor-alpha and interleukin-1beta, whereas interleukin-6 is not involved until later and that systemic serum amyloid A levels are not increased until interleukin-6 is also increased.

Acute ethanol exposure impairs angiogenesis and the proliferative phase of wound healing.

Acute ethanol exposure represents an increased risk factor for morbidity and mortality associated with surgical or traumatic injury. Despite clinical observations suggesting that ethanol exposure before injury alters tissue repair processes, little direct evidence about the mechanism by which ethanol affects the wound healing process is available. In this study, excisional wounds from female BALB/c mice with or without circulating ethanol levels of 100 mg/dl were used to assess wound closure, angiogenesis, and collagen content. Ethanol exposure resulted in a significant but transient delay in wound closure at day 2 postwounding (28 +/- 4% vs. 17 +/- 1%). In addition, total collagen content was significantly reduced by up to 37% in wounds from ethanol-treated mice compared with controls. The most significant effect of ethanol exposure on wounds was on vascularity because angiogenesis was reduced by up to 61% in wounds from ethanol-treated mice. The reduction in vessel density occurred despite near-normal levels of proangiogenic factors VEGF and FGF-2, suggesting a direct effect of ethanol exposure on endothelial cell function. Further evidence for a direct effect was observed in an in vitro angiogenesis assay because the exposure of endothelial cells to ethanol reduced angiogenic responsiveness to just 8.33% of control in a cord-forming assay. These studies provide novel information regarding the effect of a single dose of ethanol on multiple parameters of the wound healing process in vivo and suggest a potential mechanism by which ethanol impairs healing after traumatic injury.

Monocyte chemoattractant protein-1 (MCP-1) and macrophage infiltration into the skin after burn injury in aged mice.

Clinical observations and laboratory studies have shown a delay in dermal wound healing in aged subjects. Since macrophages play a key role in wound healing, we investigated age related differences in MCP-1 production and monocyte recruitment to the wound following burn injury using a murine model. The present study shows that there is an increase in MCP-1 levels in the burned-normal skin interface at 1-day post burn in both young and aged burned mice compared to sham injured mice. However, the levels of MCP-1 in aged burned mice (133.16+/-36.55pg/mg protein) were approximately half the levels of young burned mice (286.15+/-45.36pg/mg protein, P<0.05). Additionally, at 4 days post burn, MCP-1 levels in aged mice (290.73+/-101.98) reached the same levels as in young mice (243.97+/-36.71). There was no difference in macrophage accumulation into the wound between young and aged at either time point. These data demonstrate that the difference in dermal MCP-1 levels between the young and aged is not associated with a difference in macrophage infiltration to the wound following burn injury, suggesting that the lower MCP-1 content in the aged is possibly affecting other phases of wound healing in the aged.

Elevated monocyte chemoattractant protein-1 levels following thermal injury precede monocyte recruitment to the wound site and are controlled, in part, by tumor necrosis factor-alpha.

In previous studies, mice given a full-thickness scald injury had an influx of neutrophils into the skin that followed a local increase in a neutrophil chemoattractant. Because macrophages are known to infiltrate the wound area after neutrophils and are essential for normal wound repair, studies were designed to characterize the time course of macrophage accumulation in the wound and to identify the factor(s) responsible for this influx. A macrophage infiltrate into the wound was observed at 4 days post-injury and persisted through at least 10 days. This influx was preceded by an initial fourfold increase in dermal monocyte chemoattractant protein-1 levels at 24 hours post-injury (p < 0.05). This elevation in monocyte chemoattractant protein-1 was enhanced at 4 and 10 days postburn resulting in a sixfold increase over baseline (p < 0.01). Levels of tumor necrosis factor-alpha, a proinflammatory cytokine known to induce chemokine production, were elevated at 90 minutes after injury in burn- versus sham-injured groups (p < 0.05). Furthermore, administration of tumor necrosis factor-alpha neutralizing antibody in vivo reduced the dermal levels of monocyte chemoattractant protein-1 seen at 10 days postburn by 57% (p < 0.01); however, macrophage accumulation was not altered. Thus, elevated systemic TNF-alpha levels may influence the local chemokine milieu following burn injury.

Interleukin-4 treatment restores cellular immunity after ethanol exposure and burn injury.

BACKGROUND: Previous studies from this laboratory showed that the suppression of cell-mediated immunity after the combined injury of ethanol exposure and burn is mediated by increased presence of the proinflammatory cytokine interleukin (IL)-6. IL-4 is a T-helper cell type 2 lymphocyte-derived cytokine that serves to down-regulate the inflammatory response. Therefore, the goal of this study was to evaluate the effects of ethanol exposure and burn injury on lymphocyte production of IL-4 and to determine whether administration of IL-4 could improve cellular immunity after ethanol exposure and burn injury through modulation of IL-6 levels. METHODS: Mice were subjected to a 15% total body-surface area burn (or sham) injury 30 min after being given a single dose of alcohol (or saline) designed to achieve a blood alcohol level of 100 mg/dl. Thirty minutes after burn, mice were treated with IL-4 (or vehicle) and were killed 24 hr later. RESULTS: Lymphocytes from ethanol/burn mice secreted significantly less IL-4 in comparison to all other groups of mice (p < 0.05). Administration of IL-4 resulted in a complete restoration of the delayed-type hypersensitivity (p < 0.01) and splenocyte proliferative responses (p < 0.05) and a significant reduction in circulating and splenic macrophage-derived IL-6 (p < 0.05). Addition of IL-4 (100 or 300 pg/ml) to cultures generated from ethanol/burn and vehicle mice resulted in a complete restoration of splenocyte proliferation and a concomitant attenuation of macrophage IL-6 production. CONCLUSIONS: These studies suggest that the loss of lymphocyte production of IL-4 after ethanol exposure and burn injury may contribute to the exaggerated production of IL-6, a known mediator of immune suppression after injury. Moreover, the administration of IL-4 may be beneficial for patients with injuries that are characterized by a dysregulated inflammatory response.