Arginase1 Deficiency in Monocytes/Macrophages Upregulates Inducible Nitric Oxide Synthase To Promote Cutaneous Contact Hypersensitivity.

The innate immune components that modulate allergic contact hypersensitivity (CHS) responses are poorly defined. Using human skin from contact dermatitis patients and a mouse model of CHS, we find that hapten allergens disrupt the Arginase1 (Arg1) and inducible NO synthase (iNOS) dynamic in monocytes/macrophages (mono/MΦ), which renders those cells ineffectual in suppressing skin inflammation. Mice lacking Arg1 in MΦ develop increased CHS characterized by elevated ear thickening, mono/MΦ-dominated dermal inflammation, and increased iNOS and IL-6 expression compared with control mice. Treatment of Arg1flox/flox; LysMCre+/- mice with a selective NOS inhibitor or knockout of Nos2, encoding iNOS, significantly ameliorates CHS. Our findings suggest a critical role for Arg1 in mono/MΦ in suppressing CHS through dampening Nos2 expression. These results support that increasing Arg1 may be a potential therapeutic avenue in treating allergic contact dermatitis.

A comparison of knowledge acquisition and perceived efficacy of a traditional vs flipped classroom-based dermatology residency curriculum.

Flipped and traditional classroom models were compared in the Duke University Medical Center (Durham, North Carolina) dermatology residency program for the 2014-2015 academic year. The residents participated in 12 lectures-6 traditional and 6 flipped-that were paired for similar content. Each lecture was followed by a survey comprised of 10 factual questions and 10 perception questions. Generalized linear regression models were used to study the differences in quiz scores between the 2 classroom models after adjusting for other baseline covariates. There was not a significant difference in mean factual quiz scores between the two classroom models. Results indicated significant perception differences in favor of the flipped classroom model, such as participation (P < .001), enjoyment (P=.038 and P=.026), efficiency (P=.033), and boards (P=.050) and clinical preparedness (P=.034).

Each procedure matters: threshold for surgeon volume to minimize complications and decrease cost associated with adrenalectomy.

BACKGROUND: An association has been suggested between increasing surgeon volume and improved patient outcomes, but a threshold has not been defined for what constitutes a "high-volume" adrenal surgeon. METHODS: Adult patients who underwent adrenalectomy by an identifiable surgeon between 1998-2009 were selected from the Healthcare Cost and Utilization Project National Inpatient Sample. Logistic regression modeling with restricted cubic splines was utilized to estimate the association between annual surgeon volume and complication rates in order to identify a volume threshold. RESULTS: A total of 3,496 surgeons performed adrenalectomies on 6,712 patients; median annual surgeon volume was 1 case. After adjustment, the likelihood of experiencing a complication decreased with increasing annual surgeon volume up to 5.6 cases (95% confidence interval, 3.27-5.96). After adjustment, patients undergoing resection by low-volume surgeons (<6 cases/year) were more likely to experience complications (odds ratio 1.71, 95% confidence interval, 1.27-2.31, P = .005), have a greater hospital stay (relative risk 1.46, 95% confidence interval, 1.25-1.70, P = .003), and at increased cost (+26.2%, 95% confidence interval, 12.6-39.9, P = .02). CONCLUSION: This study suggests that an annual threshold of surgeon volume (≥6 cases/year) that is associated with improved patient outcomes and decreased hospital cost. This volume threshold has implications for quality improvement, surgical referral and reimbursement, and surgical training.

Projecting Survival in Papillary Thyroid Cancer: A Comparison of the Seventh and Eighth Editions of the American Joint Commission on Cancer/Union for International Cancer Control Staging Systems in Two Contemporary National Patient Cohorts.

BACKGROUND: This study aims to compare the seventh and eighth editions of the American Joint Commission on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, node, metastasis staging system for patients with papillary thyroid cancer (PTC) in two national patient cohorts. METHODS: Adult PTC patients undergoing surgery were selected from the Surveillance, Epidemiology and End Results (SEER) program (2004-2012) and the National Cancer Database (2004-2012). Staging criteria for the seventh and eighth AJCC/UICC editions were applied separately to each cohort. Survival probabilities were estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards models were used to estimate the association of stage with survival in both settings. The Akaike information criterion was used to assess model performance. RESULTS: About 23% of patients were downstaged from the seventh to the eighth edition in SEER, while 24% were downstaged in the National Cancer Database. Disease-specific survival (DSS) and overall survival (OS) were significantly related to stage at diagnosis when using both the seventh and eighth editions of the AJCC/UICC staging system (p < 0.001). Patients classified into higher stages (III and IV) in the eighth edition showed a worse prognosis than those classified into similar stages in the seventh edition. After adjustment, PTC stages as defined by both editions were significantly associated with DSS and OS. With respect to both DSS and OS, the eighth edition PTC model appeared to be a better fit to the data (smaller Akaike information criterion values) compared to the seventh edition. CONCLUSION: Based on these large contemporary national cohorts, the eighth edition AJCC/UICC tumor, node, metastasis classification for PTC is superior to the seventh edition for predicting survival.

Lymphovascular invasion is associated with survival for papillary thyroid cancer.

Data are limited regarding the association between tumor lymphovascular invasion and survival for patients with papillary thyroid cancer (PTC). This study sought to examine lymphovascular invasion as an independent prognostic factor for patients with PTC undergoing thyroid resection. The National Cancer Data Base (2010-2011) was queried for patients with PTC who underwent total thyroidectomy or lobectomy. Patients were classified into two groups based on the presence/absence of lymphovascular invasion. Demographic, clinical and pathological features were evaluated for all patients. A Cox proportional hazards model was utilized to identify factors associated with survival. Results show that 45,415 patients met inclusion criteria; 11.6% had lymphovascular invasion. Patients with lymphovascular invasion were more likely to have larger tumors (2.8cm vs 1.5cm, P<0.01), metastatic lymph nodes (74.1% vs 32.5%, P<0.01), and distant metastases (3.0% vs 0.5%, P<0.01). They were also more likely to receive radioactive iodine (69.3% vs 44.9%, P<0.01). Unadjusted overall 5-year survival was lower for patients who had tumors with lymphovascular invasion (86.6% vs 94.5%) (log-rank P<0.01). After adjustment, increasing patient age (HR=1.06, P<0.01), male gender (HR=1.68, P<0.01), presence of metastatic lymph nodes (HR=1.77, P<0.01), distant metastases (HR=3.49, P<0.01), and lymphovascular invasion (HR=1.88, P<0.01) were associated with compromised survival. For patients with lymphovascular invasion, treatment with RAI was associated with reduced mortality (HR=0.43, P<0.01). The presence of lymphovascular invasion among patients with PTC is independently associated with compromised survival. Patients who have PTC with lymphovascular invasion should be considered higher risk, and adjuvant RAI should be more strongly considered.