Optimizing Detection of Lymphatic Invasion in Primary Cutaneous Melanoma With the Use of D2-40 and a Paired Melanocytic Marker.

ABSTRACT: Dual immunohistochemical (IHC) staining with D2-40 and S100 improves detection of lymphatic invasion (LI) in primary cutaneous melanoma. However, limited data exist evaluating this technique using other melanocytic markers, and thus, the optimal marker for detection of LI is unestablished. To address this knowledge gap, a case-control study was performed comparing melanoma specimens from 22 patients with known lymphatic spread (LS) with a control group of 11 patients without LS. Specimens underwent dual IHC staining with D2-40 and MART-1, SOX-10, and S100 to evaluate for LI. Receiver operating characteristic analysis was used to estimate each stain's accuracy for detection of LI. The LS group was more likely to be ≥65 years (P = 0.04), have a tumor thickness of ≥1 mm (P < 0.01), and have ulcerated tumors (P = 0.02). Detection of LI with D2-40/MART-1 significantly correlated with LS (P = 0.03), and the D2-40/MART-1 stain was most accurate for LI based on receiver operating characteristic curve analysis (area under the curve [AUC] 0.705) in comparison with D2-40/SOX-10 (AUC 0.575) and D2-40/S100 (AUC 0.633). These findings suggest that MART-1 may be the optimal melanocytic marker to combine with D2-40 for detection of LI in melanoma. Further studies are needed to determine the utility of routinely performing these stains for histopathologic analysis of melanoma.

Histopathologic synoptic reporting of invasive melanoma: How reliable are the data?

BACKGROUND: Synoptic reporting is recommended by many guideline committees to encourage the thorough histologic documentation necessary for optimal management of patients with melanoma. METHODS: One hundred fifty-one pathologists from 40 US states interpreted 41 invasive melanoma cases. For each synoptic reporting factor, the authors identified cases with "complete agreement" (all participants recorded the same value) versus any disagreement. Pairwise agreement was calculated for each case as the proportion of pairs of responses that agreed, where paired responses were generated by the comparison of each reviewer's response with all others. RESULTS: There was complete agreement among all reviewers for 22 of the 41 cases (54%) on Breslow thickness dichotomized at 0.8 mm, with pairwise agreement ranging from 49% to 100% across the 41 cases. There was complete agreement for "no ulceration" in 24 of the 41 cases (59%), with pairwise agreement ranging from 42% to 100%. Tumor transected at base had complete agreement for 26 of the 41 cases (63%), with pairwise agreement ranging from 31% to 100%. Mitotic rate, categorized as 0/mm2 , 1/mm2 , or 2/mm2 , had complete agreement for 17 of the 41 cases (41%), with pairwise agreement ranging from 36% to 100%. Regression saw complete agreement for 14 of 41 cases (34%), with pairwise agreement ranging from 40% to 100%. Lymphovascular invasion, perineural invasion, and microscopic satellites were rarely reported as present. Respectively, these prognostic factors had complete agreement for 32 (78%), 37 (90%), and 18 (44%) of the 41 cases, and the ranges of pairwise agreement were 47% to 100%, 70% to 100%, and 53% to 100%, respectively. CONCLUSIONS: These findings alert pathologists and clinicians to the problem of interobserver variability in recording critical prognostic factors. LAY SUMMARY: This study addresses variability in the assessment and reporting of critical characteristics of invasive melanomas that are used by clinicians to guide patient care. The authors characterize the diagnostic variability among pathologists and their reporting methods in light of recently updated national guidelines. Results demonstrate considerable variability in the diagnostic reporting of melanoma with regard to the following: Breslow thickness, mitotic rate, ulceration, regression, and microscopic satellites. This work serves to alert pathologists and clinicians to the existence of variability in reporting these prognostic factors.

Histological immune response patterns in sentinel lymph nodes involved by metastatic melanoma and prognostic significance.

BACKGROUND: To further characterize the micromorphometric immunological pattern to metastatic melanoma in sentinel lymph node (SLN) biopsies and completion lymph node (CLN) dissections and their relation to 5-year overall survival (OS). METHODS: Retrospective cohort of 49 patients from 1996 to 2005 with a positive SLN who underwent CLN dissection (CLD) was studied. Micromorphometric characteristics included follicular center count (FCC)/profile, sinus histiocytosis, metastatic size, tumor infiltrating lymphocytes (intranodal), paracortical dendritic cells, germinal center reaction and morphology. Comparison of Kaplan-Meier survival curves used the exact log-rank statistic. RESULTS: In the high-FCC (n = 5-51) vs the low-FCC (n < 5) lymph nodes, a delayed separation occurred at 3 years, with 5-year OS rates being 73% vs 54% in the high- and low-FCC groups, respectively. Improved survival up to 3 years was also noted in CLDs that showed a higher FCC when compared to the prior SLN. Patients with metastatic deposits >2 mm had significantly lower 5-year survival (both <.001). CONCLUSIONS: Nodal micromorphometric features (ie, FCC) are probably related to host immune response to metastasis. Quantitative evaluation of lymphoid follicular centers could provide valuable prognostic information to help to stratify patients.

Mitigating Barriers to Doctoral Education for Nurses.

AIM: This article reports preliminary outcomes of the Guiding Initiative for Doctoral Education, which promotes success in doctoral study. BACKGROUND: Nurses face challenges as they move intentionally, effectively, and expediently toward earning the doctorate. Selecting the doctoral education best suited to individual career goals is essential for success. METHOD: An intensive, daylong program focused on setting goals, generating personal action plans, and mobilizing resources to promote success in application and return to the role of student. RESULTS: Based on 70 nurses who participated in seven programs, 22 (31 percent) were admitted to their doctoral program of choice (6 PhD, 15 DNP, 1 EdD). CONCLUSION: Nurses benefit from and value learning about the options for doctoral study, requirements for educational opportunities, the nature of the commitment required, challenges commonly encountered during the process, and the impact advanced education can be expected to have on immediate and long-term career opportunities.

High ALDH1 expression correlates with better prognosis in tumorigenic malignant melanoma.

Aldehyde dehydrogenase 1 (ALDH1) has been proposed as biomarker of stem cells for certain human cancers. ALDH1 expression has been correlated with poor patient outcomes in a variety of malignancies but better patient outcomes in others, and its prognostic significance in malignant melanoma is unclear. Thus, 68 melanoma patients with comprehensive clinical and pathologic follow-up data were used to construct a tissue microarray. A modified histological score (H-score) with a maximum score of 300 was used to quantify immunohistochemical staining for ALDH1. Survival time was defined as the time between diagnosis and melanoma-specific death. Using univariate logistic regression, a low (<80 H-score) ALDH1 score showed 3.7-fold increase in risk for melanoma-specific death within 10 years when compared with high (>80) ALDH1 levels (P=0.017). Odds of MSD were lower by a factor of ~0.9 for each 10-point increase in H-Score. Median survival time was 44.1 months and 180.9 months for patients with low and high ALDH1 expression, respectively. Using multivariate analysis, ALDH1 H-score was found to be an independent prognostic factor. These findings suggest that ALDH1 expression in malignant melanoma has a favorable effect on patient survival. Further study is needed elucidate the function of this enzymatic protein in melanoma progression.

p15 Expression Differentiates Nevus from Melanoma.

Most melanomas are driven by BRAF(V600E)-activating mutations, while nevi harboring the same mutations have growth arrest. Although decreased p16 expression has been associated with melanoma formation, in recent work, p15 represented a primary effector of oncogene-induced senescence in nevomelanocytes that was diminished in melanomas. This study determined whether decreased p15 levels represent a general biomarker for the transition from nevus to melanoma. We performed p15 and p16 IHC analyses on a random series of nevi and melanomas. Staining was evaluated and graded for percentage and intensity to determine the H score. For real-time quantitative RT-PCR analysis of p15, RNA was extracted from FFPE sections from 14 nevus and melanoma samples via macrodissection. A two-sided t-test was used to evaluate between-group differences in mean H scores and qΔCt values. p15 Expression was significantly increased in melanocytic nevi compared with melanomas (mean H scores, 254.8 versus 132.3; P < 0.001). On p15 staining, the H score differential was greater than that with p16 staining [122.5 (P < 0.001) and 64.8 (P = 0.055), respectively]. Real-time quantitative RT-PCR analysis revealed a lower mean qΔCt value in melanomas, consistent with lower p15 expression (P = 0.018). Together, these data support the hypothesis that decreased p15 expression is a robust biomarker for distinguishing nevus from melanoma.

Atypical retiform hemangioendothelioma arising in a patient with Milroy disease: a case report and review of the literature.

Retiform hemangioendothelioma (RH) is a rare vascular neoplasm with a high rate of local recurrence and low metastatic potential. We describe an unusual case of RH in a 45-year-old patient with Milroy disease, with a prominent solid component diffusely involving a chronic lymphedematous leg. This case is consistent with the postulated relationship between lymphedema and vascular neoplasms developing as a result of local immune dysfunction, and highlights the need to closely monitor patients with Milroy disease for pathologic changes. Our case highlights a unique example of RH with atypical features. There are several noteworthy unusual clinical and histologic findings including diffuse involvement of an entire limb, solid component with cytologic atypia, D2-40 expression, and first-time-reported association with Milroy disease. Given the atypical histologic presentation of cytologic atypia, solid areas and atypical immunohistochemical profile with D2-40 positivity, this case could cause diagnostic difficulty, especially in the setting of such a broad clinical differential.

The Doctor of Nursing Practice: From Start-Up to Impact.

AIM: This article reflects on the progress of the doctor of nursing practice (DNP) degree and its place in health care. BACKGROUND: The DNP originated over 10 years ago, long enough for a comprehensive evaluation. METHOD: Rogers' Diffusion of Innovation Theory is used to trace the history of the DNP. Nurse leaders from service and academia (n = 120) share strategies and innovations, and evaluate DNP education with a focus on outcomes and impact. RESULTS: As schools of nursing target DNPs to become faculty to mitigate the shortage, participants agreed it is time to focus on graduating strong leaders prepared to transform health care. CONCLUSION: A growing number of nurses practicing in diverse roles have earned the DNP from programs that vary considerably in rigor. Demand for the competencies, skills, and experience which DNPs bring to practice is high as organizations adapt to the accountable care environment.

Perceptions about hemodialysis and transplantation among African American adults with end-stage renal disease: inferences from focus groups.

BACKGROUND: Disparities in access to kidney transplantation (KT) remain inadequately understood and addressed. Detailed descriptions of patient attitudes may provide insight into mechanisms of disparity. The aims of this study were to explore perceptions of dialysis and KT among African American adults undergoing hemodialysis, with particular attention to age- and sex-specific concerns. METHODS: Qualitative data on experiences with hemodialysis and views about KT were collected through four age- and sex-stratified (males <65, males ≥65, females <65, and females ≥65 years) focus group discussions with 36 African American adults recruited from seven urban dialysis centers in Baltimore, Maryland. RESULTS: Four themes emerged from thematic content analysis: 1) current health and perceptions of dialysis, 2) support while undergoing dialysis, 3) interactions with medical professionals, and 4) concerns about KT. Females and older males tended to be more positive about dialysis experiences. Younger males expressed a lack of support from friends and family. All participants shared feelings of being treated poorly by medical professionals and lacking information about renal disease and treatment options. Common concerns about pursuing KT were increased medication burden, fear of surgery, fear of organ rejection, and older age (among older participants). CONCLUSIONS: These perceptions may contribute to disparities in access to KT, motivating granular studies based on the themes identified.

Second Life simulation as a strategy to enhance decision-making in diabetes care: a case study.

AIMS AND OBJECTIVES: The case study evaluated the Second Life perceived usability and the decision-making of insulin administration via situational awareness at two different simulation freezes during Second Life simulation. BACKGROUND: Due to safety issues stemming from nursing knowledge deficits of insulin administration, the use of simulation via practice in a virtual immersive environment, Second Life was evaluated in a case study of practicing nurses. DESIGN: This case study used a single convenience group, post-test design. METHODS: Perceived usability was evaluated using the System Usability Scale. Evaluation of decision-making was evaluated via Situational Awareness Score at two simulation freezes in the Second Life simulation with practicing nurses (n = 12). RESULTS: Nurses with more years of practice reported difficulty in using Second Life. As age increased, the total Situational Awareness Score decreased. Day shift nurses were more likely to obtain a High Situational Awareness Score. CONCLUSIONS: Although usability was nearly obtained, virtual immersive environments for nurses has promise to provide practice in aiding clinical decision-making. RELEVANCE TO CLINICAL PRACTICE: Finding a new platform to allow all nurses to practice difficult clinical decisions is key. A virtual immersive environment, like Second Life, can provide simulation for nurses to practice making such difficult decisions.

Addressing Burnout in the Primary Care Setting: The Impact of an Evidence-Based Mindfulness Toolkit.

BACKGROUND: Burnout is insidious and manifests over prolonged, repeated exposure to occupational stressors. There is a growing crisis among health care workers (HCWs) due to high levels of burnout and associated adverse outcomes. Identifying and addressing burnout can be problematic due to extensive variances of perceived occupational stressors across HCWs. PURPOSE: Mindfulness-based training can enhance individual HCWs' abilities to perceive and constructively respond to stresses endemic in the health care environment. It can reduce the prevalence of burnout in the primary care setting. An evidence-based multimodal Mindfulness-Based Stress Reduction toolkit (MBSR TK) was designed, implemented, and evaluated for its impact on HCWs' self-reported stress levels (SRSL). IMPLEMENTATION STRATEGIES: A pre-post-program evaluation explored the impact of a multimodal toolkit program on HCW SRSL with the Mini-Z burnout survey (MZBS). The MBSR TK program, consisting of a 45 minute introduction and 4 biweekly 15 minute mindfulness sessions offering acupressure, meditation, journaling for gratitude, and self-compassion was designed, delivered, and evaluated with HCWs across 2 military primary care clinics in South Texas. RESULTS: All HCWs across 2 Air Force family practice clinics were invited to participate in all toolkit components. Seventy percent of all HCWs (N = 90) attended the introduction session. Thirty-seven (41%) HCWs completed pre and post MZBSs, and these responses are included in the data analysis section. The most represented HCWs were registered nurses, physician assistants, and technicians, respectively, at 24%, 21%, and 18%. The Wilcoxon Signed-Rank test examined changes in HCWs' SRSL after participation in the MBSR TK program. HCWs who attended the introduction plus one biweekly session showed statistically significant decreases in self-reported stress (P = 0.018) and burnout (P = 0.045) and a significant increase in electronic health record proficiency (P = 0.033). CONCLUSIONS: Multimodal mindfulness toolkits to address SRSL burnout are practical, accessible, easily implemented, adaptive to any environment, and can decrease burnout with participation with just one 15 minute session. This MBSR TK implementation effectively lowered self-reported stress in HCWs who are repeatedly challenged to adapt to various settings around the world during peacetime, wars, natural disasters, humanitarian crises, and now, pandemics.

Applying the RIME Framework to Level Nurse Practitioner Curriculum Competencies.

BACKGROUND: Nurse practitioner (NP) faculty assess student acquisition of knowledge through examinations, simulation, and clinical performance. PROBLEM: Developing appropriately leveled curriculum, assessments, and clinical expectations that accurately capture student maturation presents a challenge. APPROACH: The Reporter, Interpreter, Manager, Educator (RIME) provided the framework for doctor of nursing practice NP curriculum redesign to enhance student performance and content mastery. Faculty used a gap analysis approach, iteratively leveling specialty content, course competencies, examination questions, simulation cases, and clinical expectations using the building blocks of RIME. OUTCOMES: Objective scores on student evaluations for clinical courses exceeded the threshold established, including 83% of simulation encounters. Faculty implemented targeted methods to remediate areas of underperformance. CONCLUSIONS: Structuring the course competencies and preceptor feedback around RIME made it easier to pinpoint specific deficiencies and target remediation. It also helped guide discussions about the minimum acceptable standard for student performance.

A latent class analysis of DSM-IV alcohol use disorder criteria and binge drinking in undergraduates.

BACKGROUND: Adolescent and adult samples have shown that the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) abuse and dependence criteria lie on a continuum of alcohol problem severity, but information on criteria functioning in college students is lacking. Prior factor analyses in a college sample (Beseler et al., 2010) indicated that a 2-factor solution fit the data better than a single-factor solution after a binge drinking criterion was included. The second dimension may indicate a clustering of criteria related to excessive alcohol use in this college sample. METHODS: The present study was an analysis of data from an anonymous, online survey of undergraduates (N = 361) that included items pertaining to the DSM-IV alcohol use disorder (AUD) diagnostic criteria and binge drinking. Latent class analysis (LCA) was used to determine whether the criteria best fit a categorical model, with and without a binge drinking criterion. RESULTS: In an LCA including the AUD criteria only, a 3-class solution was the best fit. Binge drinking worsened the fit of the models. The largest class (class 1, n = 217) primarily endorsed tolerance (18.4%); none were alcohol dependent. The middle class (class 2, n = 114) endorsed primarily tolerance (81.6%) and drinking more than intended (74.6%); 34.2% met criteria for dependence. The smallest class (class 3, n = 30) endorsed all criteria with high probabilities (30 to 100%); all met criteria for dependence. Alcohol consumption patterns did not differ significantly between classes 2 and 3. Class 3 was characterized by higher levels on several variables thought to predict risk of alcohol-related problems (e.g., enhancement motives for drinking, impulsivity, and aggression). CONCLUSIONS: Two classes of heavy-drinking college students were identified, one of which appeared to be at higher risk than the other. The highest risk group may be less likely to "mature out" of high-risk drinking after college.

Living kidney donors and their family caregivers: developing an evidence-based educational and social support website.

CONTEXT: Although graft and patient survival rates for living kidney donation are improved, some healthcare providers question whether volunteer donors and their informal caregivers are fully informed of the donation process and the risks involved. Donors and their family caregivers have reported that they receive limited information about the predonation and donor recovery process. Offering web-based information and social support is one way to address this gap. STRATEGY: Living kidney donor candidates and their family caregivers participating in the Living Donor Information Network for Caregiving (LINC) have access to a variety of online informational resources and a social support discussion forum throughout their living kidney donation experience. Strategies in the development and implementation of an online information and social-support resource are presented. CONCLUSIONS: Use of the LINC website for information and support may assist health care providers in identifying potential barriers in the current donation process and provide direction for enhancing knowledge and confidence among donors and family caregivers.

Artificial light at night alters diurnal and nocturnal behavior and physiology in green anole lizards.

Artificial light at night (ALAN) disrupts biological rhythms across widely diverse organisms. To determine how energy is allocated by animals in different light environments, we investigated the impacts of ALAN on behavior and physiology of diurnal green anole lizards (Anolis carolinensis). Two groups of 24 adult lizards (half males, half females) were maintained in a controlled lab setting for six weeks. One group was exposed to a simulated natural summer light-dark cycle; the other was exposed to ALAN that simulated urban, nocturnal light exposure. After an acclimation period, we conducted four behavioral trials. One trial examined behavioral time allocation over two 24 h periods, and three others were conducted during mid-day and mid-night: open field tests, to examine exploratory behavior; foraging trials, to examine prey consumption; and social interaction trials, to examine same-sex interactions. We then measured each lizard's snout-vent length and mass of its body, abdominal fat pads, liver, and, for males, testes. Lizards exposed to ALAN were more likely to be awake at night, using nocturnal light to explore, forage, and display to conspecifics. However, during the day, ALAN lizards were less likely to be awake, slower to move, and females displayed less frequently. ALAN lizards had heavier fat pads and testes, but ALAN did not impact body mass, liver mass, or snout-vent length. In sum, ALAN appears to cause a broad shift towards increased nocturnal activity and may alter metabolic and reproductive processes. Future work should examine the fitness consequences of these behavioral and physiological changes.

Exploration Into Donor-Recipient Relationship After Living-Donor Liver Transplantation Using Gift-Exchange Theory.

AIM: This qualitative study aimed to explore the donor-recipient relationships following living-donor liver transplantation. METHOD: A 1-time cross-sectional qualitative interview was conducted with liver transplant recipients (n = 17) and living liver donors (n = 11) post-transplant. The interviews were transcribed verbatim and analyzed manually by using thematic content analysis. RESULTS: The mean age of the recipients and the donors was 54.41 ± 8.0 (range 39-71) and 36.6 ± 7.69 (range 28-57) years, respectively. Following the interviews, 2 overarching themes emerged: (1) Became care providers, and (2) differentiation in relationships after transplantation. A total of 3 sub-themes were explained under "differentiation in relationships after transplantation;" feeling guilty, becoming closer and more intense owing to a feeling of indebtedness, and putting some distance owing to a feeling of indebtedness. CONCLUSION: The study focused on the reciprocation stage according to gift-exchange theory. During reciprocation, although recipients expressed positive feelings such as gratitude, closer relationships, and special bonds; they also reported negative feelings like guilt and indebtedness resulting in a purposeful distancing from their donors. Most donors understood what the recipients felt, but they wanted their relationship to return to normal. Married female donors had worse experiences, such as divorce or a weakened marital relationship after donation.

Education Priorities and What Matters to Those Considering Living Kidney Donation.

INTRODUCTION: Although informed consent content elements are prescribed in detailed regulatory guidance, many live kidney donors describe feeling underprepared and under informed. The goal of this pilot study was to explore the educational components needed to support an informed decision-making process for living kidney donors. METHODS/APPROACH: A qualitative description design was conducted with thematic analysis of 5 focus groups with 2 cohorts: living kidney donor candidates (n = 11) and living kidney donors (n = 8). FINDINGS: The educational components needed to engage in an informed decision-making process were: 1) contingent upon, and motivated by, personal circumstances; 2) supported through explanation of risks and benefits; 3) enhanced by understanding the overall donation experience; and 4) personalized by talking to another donor. DISCUSSION: Tailoring education to meet the needs for fully informed decision-making is essential. Current education requirements, as defined by regulatory bodies, remain challenging to transplant teams attempting to ensure fully informed consent of living kidney donor candidates. Information on the emotional, financial, and overall life impact is needed, along with acknowledgement of relational ties driving donor motivations and the hoped-for recipient outcomes. Discussion of care practices, and access to peer mentoring may further strengthen the informed decision-making process.

Taking the leap from clinical practice to academic faculty: A beginner's guide.

ABSTRACT: Exploring new roles and responsibilities available to clinicians offers a path to renovate a nurse practitioner's career. The role of academician and nurse faculty broadens career horizons, presents a sense of autonomy, and offers unique opportunities to teach, participate in research, build leadership skills, and contribute to the health care delivery system at a higher level. Advance practice nurses often consider a shift to academia but are concerned about the unfamiliarity of the entire process. This article offers elements a clinician will likely encounter throughout the transition to a faculty role. These include expectations for the application and interview, negotiating for a position, and orientation to the role of an academic.

A preliminary investigation of the brain injury family intervention: impact on family members.

PRIMARY OBJECTIVE: To evaluate the benefits of the Brain Injury Family Intervention (BIFI) for families of persons with acquired brain injury and identify factors related to outcomes. RESEARCH DESIGN: Pre-test, post-test design with outcomes measured immediately after and 3 months following intervention. METHODS AND PROCEDURES: Family members and survivors participated in five 2-hour sessions over 10 weeks which included discussions of typical effects of brain injury, coping with loss and change, managing stress and intense emotions, effective problem-solving, setting reasonable goals and taking care of one's self. Guided by principles of family systems theory (FST) and cognitive behaviour therapy (CBT), the manualized treatment included educational, skill building and psychological support components. MAIN OUTCOMES AND RESULTS: Analysis of data derived from family members indicated a greater number of met needs and perceptions of fewer obstacles to receiving services post-treatment and at 3 months follow-up. Before and after treatment, unmarried caregivers reported more unmet needs. Family members of persons with longer acute care lengths of stay reported more unmet needs and greater perceived obstacles to services. Post-treatment differences in family members' psychological distress, satisfaction with life and functioning were not identified. CONCLUSIONS: The investigation provided evidence that family members benefit from interventions designed to meet their unique needs after brain injury. Uncertainties remain about the benefits of intervention to general family functioning and life satisfaction.