Images in clinical medicine: Rhinophyma.

A 42-year-old man presented with impaired nasal breathing and a slowly growing mass on the tip of the nose. Examination revealed a multilobulated sebaceous nodule protruding from the nasal tip.

Cutaneous adverse effects of targeted therapies: Part I: Inhibitors of the cellular membrane.

There has been a rapid emergence of numerous targeted agents in the oncology community in the last decade. This exciting paradigm shift in drug development lends promise for the future of individualized medicine. Given the pace of development and clinical deployment of targeted agents with novel mechanisms of action, dermatology providers may not be familiar with the full spectrum of associated skin-related toxicities. Cutaneous adverse effects are among the most frequently observed toxicities with many targeted agents, and their intensity can be dose-limiting or lead to therapy discontinuation. In light of the often life-saving nature of emerging oncotherapeutics, it is critical that dermatologists both understand the mechanisms and recognize clinical signs and symptoms of such toxicities in order to provide effective clinical management. Part I of this continuing medical education article will review in detail the potential skin-related adverse sequelae, the frequency of occurrence, and the implications associated with on- and off-target cutaneous toxicities of inhibitors acting at the cell membrane level, chiefly inhibitors of epidermal growth factor receptor, KIT, and BCR-ABL, angiogenesis, and multikinase inhibitors.

Cutaneous adverse effects of targeted therapies: Part II: Inhibitors of intracellular molecular signaling pathways.

The last decade has spawned an exciting new era of oncotherapy in dermatology, including the development of targeted therapies for metastatic melanoma and basal cell carcinoma. Along with skin cancer, deregulation of the PI3K-AKT-mTOR and RAS-RAF-MEK-ERK intracellular signaling pathways contributes to tumorigenesis of a multitude of other cancers, and inhibitors of these pathways are being actively studied. Similar to other classes of targeted therapies, cutaneous adverse effects are among the most frequent toxicities observed with mitogen-activated protein kinase pathway inhibitors, PI3K-AKT-mTOR inhibitors, hedgehog signaling pathway inhibitors, and immunotherapies. Given the rapid expansion of these families of targeted treatments, dermatologists will be essential in offering dermatologic supportive care measures to cancer patients being treated with these agents. Part II of this continuing medical education article reviews skin-related adverse sequelae, including the frequency of occurrence and the implications associated with on- and off-target cutaneous toxicities of inhibitors of the RAS-RAF-MEK-ERK pathway, PI3K-AKT-mTOR pathway, hedgehog signaling pathway, and immunotherapies.

Results of the Behavioral Health Readiness Evaluation and Decision-Making Instrument Study.

INTRODUCTION: Recent reports have demonstrated behavioral health (BH) system and individual provider challenges to BH readiness success. These pose a risk to winning on the battlefield and present a significant safety issue for the Army. One of the most promising areas for achieving better BH readiness results lies in improving readiness decision-making support for BH providers. The Walter Reed Army Institute of Research (WRAIR) has taken the lead in addressing this challenge by developing and empirically testing such tools. The results of the Behavioral Health Readiness Evaluation and Decision-Making Instrument (B-REDI) field study are herein described. METHODS: The B-REDI study received WRAIR Institutional Review Board approval, and BH providers across five U.S. Army Forces Command installations completed surveys from September 2018 to March 2019. The B-REDI tools/training were disseminated to 307 providers through random clinic assignments. Of these, 250 (81%) providers consented to participate and 149 (60%) completed both initial and 3-month follow-up surveys. Survey items included a wide range of satisfaction, utilization, and proficiency-level outcome measures. Analyses included examinations of descriptive statistics, McNemar's tests pre-/post-B-REDI exposure, Z-tests with subgroup populations, and chi-square tests with demographic comparisons. RESULTS: The B-REDI resulted in broad, statistically significant improvements across the measured range of provider proficiency-level outcomes. Net gains in each domain ranged from 16.5% to 22.9% for knowledge/awareness (P = .000), from 11.1% to 15.8% for personal confidence (P = .001-.000), and from 6.2% to 15.1% for decision-making/documentation (P = .035-.002) 3 months following B-REDI initiation, and only one (knowledge) failed to maintain a statistically significant improvement in all of its subcategories. The B-REDI also received high favorability ratings (79%-97% positive) across a wide array of end-user satisfaction measures. CONCLUSIONS: The B-REDI directly addresses several critical Army BH readiness challenges by providing tangible decision-making support solutions for BH providers. Providers reported high degrees of end-user B-REDI satisfaction and significant improvements in all measured provider proficiency-level domains. By effectively addressing the readiness decision-making challenges Army BH providers encounter, B-REDI provides the Army BH health care system with a successful blueprint to set the conditions necessary for providers to make more accurate and timely readiness determinations. This may ultimately reduce safety and mission failure risks enterprise-wide, and policymakers should consider formalizing and integrating the B-REDI model into current Army BH practice.

Malignant melanoma in the elderly: different regional disease and poorer prognosis.

PURPOSE: Age is a poor prognostic factor in melanoma patients. Elderly melanoma patients have a different presentation and clinical course than younger patients. We evaluated the impact of age ≥70 years (yrs) on the diagnosis and natural history of melanoma. METHODS: Retrospective review of 610 patients with malignant melanoma entered into a prospective sentinel lymph node (SLN) database, treated from June 1997 to June 2010. Disease characteristics and clinical outcomes were compared between patients ≥70 yrs vs. <70 yrs of age. RESULTS: 237 patients (39%) were ≥70 yrs. Elderly patients had a higher proportion of head and neck melanomas (34% vs. 20%, p<0.001), and greater mean tumor thickness (2.4mm vs. 1.8mm, p<0.001). A greater proportion of T3 or T4 melanoma was seen in the elderly (p<0.001) as well as a greater mean number of mitotic figures: 3.6/mm(2) vs. 2.7/mm(2) (p=0.005). Despite greater mean thickness, the incidence of SLN metastases was less in the ≥70 yrs group with T3/T4 melanomas (18% vs. 33%, p=0.02). The elderly had a higher rate of local and in-transit recurrences, 14.5% vs. 3.4% at 5 yrs (p<0.001). 5 yr disease-specific mortality and overall mortality were worse for those ≥70 yrs: 16% vs. 8% (p=0.004), and 30% vs. 12% (p<0.001), respectively. CONCLUSIONS: Elderly (≥70 yrs) melanoma patients present with thicker melanomas and a higher mitotic rate but have fewer SLN metastases. Melanoma in the elderly is more common on the head and neck. Higher incidence of local/in-transit metastases is seen among the elderly. Five-year disease-specific mortality and overall mortality are both worse for these patients.

The impact of biopsy technique on upstaging, residual disease, and outcome in cutaneous melanoma.

BACKGROUND: After skin biopsy of malignant melanoma, the findings in the subsequent wide local excision (WLE) sometimes result in upgrading of the T-category. Herein, we examine the influence of biopsy technique on residual disease in melanoma WLE specimens and on upstaging. METHODS: We performed a retrospective review of data from malignant melanoma patients who underwent sentinel lymph node biopsy between 1997 and 2010. RESULTS: A total of 609 patients were biopsied by shave (51%), punch (19%), and excision (30%). Residual disease was seen in 240 patients (39%) at WLE, of whom 60% had undergone shave biopsy. Fifty-nine patients had a T-category upgrade after WLE (10% of all patients); 64% were sampled by shave. Seven percent of patients with a T-category upgrade had negative margins initially. Positive biopsy margin and greater thickness predicted T-category upgrade. CONCLUSIONS: Partial biopsy for melanoma resulted in more residual disease at WLE and a higher rate of T-category upgrade. Moreover, the presence of negative margins at biopsy did not ensure lack of residual disease.

Timing of wound closure in open fractures based on cultures obtained after debridement.

BACKGROUND: The timing of wound closure in open fractures has remained an inexact science. Numerous recommendations have been made for the management of these injuries regarding the optimal time to perform competent wound closure, with all advice based on subjective parameters. The purpose of this study was to determine the utility of a prospective protocol with use of wound cultures obtained after irrigation and debridement as a guide to the timing of wound closure following an open fracture of an extremity. METHODS: Four hundred and twenty-two open fractures had emergency irrigation and debridement, fracture stabilization, and open wound management. Wound cultures were obtained for aerobic and anaerobic analysis following debridement. At forty-eight hours after debridement, patients were again returned to surgery. If the initial culture results were positive, a repeat irrigation and debridement was carried out, and additional cultures were obtained after debridement. This procedure was repeated, and the wound was not closed until negative culture results were achieved. RESULTS: Of the 422 open fractures, 346 were available for long-term follow-up. The overall deep infection rate was 4.3%. Gustilo Type-II fractures had a deep infection rate of 4%, and Type-III fractures had an infection rate of 5.7%. Type-III fractures demonstrated differences among the fracture patterns within this type, as infection developed in 1.8% of Type-IIIA injuries, 10.6% of Type-IIIB fractures, and 20% of Type-IIIC fractures. Fractures requiring multiple debridement procedures and those in patients with diabetes or an increased body mass index demonstrated higher rates of infection. With the numbers studied, fractures in which the wound was closed in the presence of positive cultures (a protocol breach) did not have a significantly increased risk of deep infection (p = 0.0501). CONCLUSIONS: The use of this standardized protocol was shown to achieve a very low rate of deep infection compared with historical controls. An increased number of irrigation and debridement procedures are required to achieve this improved outcome. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.