IL-17C is a functionally distinct member of the IL-17 family that binds IL-17RE/A to promote innate defense in epithelial cells and regulate Th17 cell differentiation. We demonstrate that IL-17C (not IL-17A) is the most abundant IL-17 isoform in lesional psoriasis skin (1058pg/ml vs. 8pg/ml; p<0.006) and localizes to keratinocytes (KCs), endothelial cells (ECs) and leukocytes. ECs stimulated with IL-17C produce increased TNFα and KCs stimulated with IL-17C/TNFα produce similar inflammatory gene response patterns as those elicited by IL-17A/TNFα, including increases in IL-17C, TNFα, IL-8, IL-1α/β, IL-1F5, IL-1F9, IL-6, IL-19, CCL20, S100A7/A8/A9, DEFB4, LCN2 and PI3 (p<0.05); indicating a positive pro-inflammatory feedback loop between the epidermis and ECs. Psoriasis patients treated with etanercept rapidly decrease cutaneous IL-17C levels, suggesting IL-17C/TNFα-mediated inflammatory signaling is critical for psoriasis pathogenesis. Mice genetically engineered to overexpress IL-17C in KCs develop well-demarcated areas of erythematous, flakey “involved” skin adjacent to areas of normal appearing “uninvolved” skin despite increased IL-17C expression in both areas (p<0.05). Uninvolved skin displays increased angiogenesis and elevated S100A8/A9expression (p<0.05) but no epidermal hyperplasia; whereas involved skin exhibits robust epidermal hyperplasia, increased angiogenesis and leukocyte infiltration and upregulated TNFα, IL-1α/β, IL-17A/F, IL-23p19, VEGF, IL-6 and CCL20 (p<0.05) suggesting that IL-17C, when coupled with other pro-inflammatory signals, initiates the development of psoriasiform dermatitis. This skin phenotype was significantly improved following 8 weeks of TNFα inhibition. These findings identify a role for IL-17C in skin inflammation and suggest a pathogenic function for the elevated IL-17C observed in lesional psoriasis skin.

Objective We sought to determine the reliability of surgeon-specific postoperative complication rates after colectomy. Background Conventional measures of surgeon-specific performance fail to acknowledge variation attributed to statistical noise, risking unreliable assessment of quality. Methods We examined all patients who underwent segmental colectomy with anastomosis from 2008 through 2010 participating in the Michigan Surgical Quality Collaborative (MSQC) Colectomy Project. Surgeon-specific complication rates were risk-adjusted according to patient characteristics with multiple logistic regression. Hierarchical modeling techniques were used to determine the reliability of surgeon-specific risk-adjusted complication rates. We then adjusted these rates for reliability. To evaluate the extent to which surgeon-level variation was reduced, surgeons were placed into quartiles based on performance and complication rates were compared before and after reliability adjustment Results A total of 5,033 patients (n=345 surgeons) undergoing partial colectomy reported a risk-adjusted complication rate of 24.5%. Approximately 86% of the variability of complication rates across surgeons was explained by measurement noise, while the remaining 14% represented true signal. Risk-adjusted complication rates varied from 0% to 55.1% across quartiles prior to adjusting for reliability. Reliability adjustment greatly diminished this variation, generating a 1.2 fold difference (21.4%-25.6%). A caseload of 168 colectomies across three years was required to achieve a reliability of >0.7, which is considered a proficient level. Only one surgeon surpassed this volume threshold. Conclusions The vast majority of surgeons do not perform enough colectomies to generate a reliable surgeon-specific complication rate. Risk-adjusted complication rates should be viewed with caution when evaluating surgeons with low operative volume, as statistical noise is a large determinant in estimating their surgeon-specific complication rates.

We assessed regional differences in potentially discretionary [<3 units of red blood cell (RBC)] transfusions across 56 medical centers and 11,200 patients undergoing isolated non-emergent coronary artery bypass (CABG) surgery. Regional variation in overall RBC rates remained after risk adjustment, perhaps due to differences in regional practice environments. Objective A number of established regional quality improvement collaboratives have partnered to assess and improve care across their regions under the umbrella of the “Cardiac Surgery Quality IMPROVEment (IMPROVE) Network”. The first effort of the IMPROVE Network has been to assess regional differences in potentially discretionary [<3 units of red blood cell (RBC)] transfusions. Methods We examined 11,200 patients undergoing isolated non-emergent coronary artery bypass (CABG) surgery across 56 medical centers in four IMPROVE Network regions between January 2008 and June 2012. Each center submitted the most recent 200 patients who received 0, 1, or 2 units of RBC transfusion during the index admission. Patient and disease characteristics, intra-operative practices, and percentage of cases receiving RBC transfusions were collected. Region-specific transfusion rates were calculated, after adjusting for pre- and intra-operative factors among region-specific centers. Results There were small, but significant, differences in patient case mix across regions. RBC transfusions of 1 or 2 units occurred among 25.2% (2,826/11,200) of CABG procedures. Significant variation in use and number of RBCs existed across regions [None: 74.8% (min:max 70.0%, 84.1%), 1 unit: 9.7% (5.1%, 11.8%), 2 units: 15.5% (9.1%, 18.2%)], p<0.001. Variation in overall transfusion rates remained after adjustment (9.1% – 31.7%, p<0.001). Conclusions Delivery of small volumes of RBC transfusions was common, yet varied across geographic regions. These data suggest that differences in regional practice environments, including transfusion triggers and anemia management, may contribute to variability in RBC transfusion rates.

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