Clinical Utility of Melanoma Sentinel Lymph Node Biopsy Nomograms.

BACKGROUND: For patients with melanoma, the decision to perform sentinel lymph node biopsy (SLNB) is based on the estimated risk of lymph node metastasis. We assessed 3 melanoma SLNB risk-prediction models' statistical performance and their ability to improve clinical decision making (clinical utility) on a cohort of melanoma SLNB cases. STUDY DESIGN: Melanoma patients undergoing SLNB at a single center from 2003 to 2021 were identified. The predicted probabilities of sentinel lymph node positivity using the Melanoma Institute of Australia, Memorial Sloan Kettering Cancer Center (MSK), and Friedman nomograms were calculated. Receiver operating characteristic and calibration curves were generated. Clinical utility was assessed via decision curve analysis, calculating the net SLNBs that could have been avoided had a given model guided selection at different risk thresholds. RESULTS: Of 2,464 melanoma cases that underwent SLNB, 567 (23.0%) had a positive sentinel lymph node. The areas under the receiver operating characteristic curves for the Melanoma Institute of Australia, MSK, and Friedman models were 0.726 (95% CI, 0.702 to 0.750), 0.720 (95% CI, 0.697 to 0.744), and 0.721 (95% CI, 0.699 to 0.744), respectively. For all models, calibration was best at predicted positivity rates below 30%. The MSK model underpredicted risk. At a 10% risk threshold, only the Friedman model would correctly avoid a net of 6.2 SLNBs per 100 patients. The other models did not reduce net avoidable SLNBs at risk thresholds of ≤10%. CONCLUSIONS: The tested nomograms had comparable performance in our cohort. The only model that achieved clinical utility at risk thresholds of ≤10% was the Friedman model.

Interventions to enhance the research productivity of academic staff in higher education schools of nursing: A systematic review.

AIM: Synthesize and present peer-reviewed evidence of interventions that enhance the research productivity of academics in Schools of Nursing in Higher Education Institutions. BACKGROUND: Pressures on academics in Schools of Nursing worldwide to increase or maintain high research productivity persist and numerous Higher Education Institutions across the world have developed interventions to increase productivity. Given evidence that the COVID-19 pandemic has resulted in a withdrawal from research, understanding which interventions best support and improve research productivity is urgent. Increasing research capacity is crucial but only one element in increasing productivity. No recent attempt has been made to synthesise the knowledge gained from these more wide-ranging initiatives. DESIGN: A mixed-methods systematic review, registered in PROSPERO, searching four academic databases (CINAHL, ERIC, MEDLINE, PsycINFO) from 1/01/2010-20/04/2022. All primary research studies of relevant interventions were included if they described the intervention, reported its outcomes and were published in the English language in peer-reviewed journals. RESULTS: 1637 studies were assessed against eligibility criteria, resulting in 20 included studies. No studies were excluded based on quality. Data pertaining to understandings of 'research productivity', barriers to research productivity, interventions and outcomes of interventions were extracted. The most often used measures were the frequency or staff-output ratio of funding, publications and presentations, while the less commonly used were the number of conference abstracts submitted/accepted and awards. Subjective measures were less commonly used. Barriers to research productivity fell into three broad categories: resource constraints, lack of priority for research and barriers related to the attitudes, knowledge and skills of School of Nursing academics. Interventions covered nine broad areas. Half of the interventions were multi-stranded, including a wide range of components to increase research productivity while the other half comprised one component only, such as writing groups and mentoring. All interventions had a positive impact on research productivity, however, heterogeneity in the measurement of impact, the duration of interventions, sources of comparative data and research design made comparison of interventions challenging. CONCLUSIONS: The review identified a need for future research to explore the barriers among under-represented groups of academics in Schools of Nursing across a broader geographical area; and what works for various sub-groups of academics. It also identified a need for a valid, standardised tool to assess the effectiveness of interventions to increase research productivity of academics in Schools of Nursing.

Neoadjuvant therapy for melanoma: A critical appraisal.

The treatment of advanced melanoma has significantly changed since the development of targeted and immune therapy. To date, these agents have primarily been used in the adjuvant or metastatic setting. Given several theoretical advantages, there is increased interest in the use of these new therapeutics in the neoadjuvant setting. In this review, we detail the potential benefits and pitfalls of neoadjuvant therapy for melanoma, review the currently available data, and describe ongoing neoadjuvant trials.

ATP-Sensitive Potassium Channel Opener Diazoxide Reduces Myocardial Stunning in a Porcine Regional With Subsequent Global Ischemia Model.

Background ATP-sensitive potassium channels are inhibited by ATP and open during metabolic stress, providing endogenous myocardial protection. Pharmacologic opening of ATP potassium channels with diazoxide preserves myocardial function following prolonged global ischemia, making it an ideal candidate for use during cardiac surgery. We hypothesized that diazoxide would reduce myocardial stunning after regional ischemia with subsequent prolonged global ischemia, similar to the clinical situation of myocardial ischemia at the time of revascularization. Methods and Results Swine underwent left anterior descending occlusion (30 minutes), followed by 120 minutes global ischemia protected with hyperkalemic cardioplegia±diazoxide (N=6 each), every 20 minutes cardioplegia, then 60 minutes reperfusion. Cardiac output, time to wean from cardiopulmonary bypass, left ventricular (LV) function, caspase-3, and infarct size were compared. Six animals in the diazoxide group separated from bypass by 30 minutes, whereas only 4 animals in the cardioplegia group separated. Diazoxide was associated with shorter but not significant time to wean from bypass (17.5 versus 27.0 minutes; P=0.13), higher, but not significant, cardiac output during reperfusion (2.9 versus 1.5 L/min at 30 minutes; P=0.05), and significantly higher left ventricular ejection fraction at 30 minutes (42.5 versus 15.8%; P<0.01). Linear mixed regression modeling demonstrated greater left ventricular developed pressure (P<0.01) and maximum change in ventricular pressure during isovolumetric contraction (P<0.01) in the diazoxide group at 30 minutes of reperfusion. Conclusions Diazoxide reduces myocardial stunning and facilitates separation from cardiopulmonary bypass in a model that mimics the clinical setting of ongoing myocardial ischemia before revascularization. Diazoxide has the potential to reduce myocardial stunning in the clinical setting.

Soil Heating in Fire (SheFire): A model and measurement method for estimating soil heating and effects during wildland fires.

Fire has transformative effects on soil biological, chemical, and physical properties in terrestrial ecosystems around the world. While methods for estimating fire characteristics and associated effects aboveground have progressed in recent decades, there remain major challenges in characterizing soil heating and associated effects belowground. Overcoming these challenges is crucial for understanding how fire influences soil carbon storage, biogeochemical cycling, and ecosystem recovery. In this paper, we present a novel framework for characterizing belowground heating and effects. The framework includes (1) an open-source model to estimate fire-driven soil heating, cooling, and the biotic effects of heating across depths and over time (Soil Heating in Fire model; SheFire) and (2) a simple field method for recording soil temperatures at multiple depths using self-contained temperature sensor and data loggers (i.e., iButtons), installed along a wooden stake inserted into the soil (i.e., an iStake). The iStake overcomes many logistical challenges associated with obtaining temperature profiles using thermocouples. Heating measurements provide inputs to the SheFire model, and modeled soil heating can then be used to derive ecosystem response functions, such as heating effects on microorganisms and tissues. To validate SheFire estimates, we conducted a burn table experiment using iStakes to record temperatures that were in turn used to fit the SheFire model. We then compared SheFire predicted temperatures against measured temperatures at other soil depths. To benchmark iStake measurements against those recorded by thermocouples, we co-located both types of sensors in the burn table experiment. We found that SheFire demonstrated skill in interpolating and extrapolating soil temperatures, with the largest errors occurring at the shallowest depths. We also found that iButton sensors are comparable to thermocouples for recording soil temperatures during fires. Finally, we present a case study using iStakes and SheFire to estimate in situ soil heating during a prescribed fire and demonstrate how observed heating regimes would influence seed and tree root vascular cambium survival at different soil depths. This measurement-modeling framework provides a cutting-edge approach for describing soil temperature regimes (i.e., soil heating) through a soil profile and predicting biological responses.

Diazoxide preserves myocardial function in a swine model of hypothermic cardioplegic arrest and prolonged global ischemia.

OBJECTIVE: Adenosine triphosphate potassium sensitive channels provide endogenous myocardial protection via coupling of cell membrane potential to myocardial metabolism. Adenosine triphosphate potassium sensitive channel openers, such as diazoxide, mimic ischemic preconditioning, prevent cardiomyocyte swelling, preserve myocyte contractility after stress, and provide diastolic protection. We hypothesize that diazoxide combined with hyperkalemic cardioplegia provides superior myocardial protection compared with cardioplegia alone during prolonged global ischemia in a large animal model. METHODS: Twelve pigs were randomized to global ischemia for 2 hours with a single dose of cold blood (4:1) hyperkalemic cardioplegia alone (n = 6) or with diazoxide (500 µmol/L) (n = 6) and reperfused for 1 hour. Cardiac output, myocardial oxygen consumption, left ventricular developed pressure, left ventricular ejection fraction, diastolic function, myocardial troponin, myoglobin, markers of apoptosis, and left ventricular infarct size were compared. RESULTS: Four pigs in the cardioplegia alone group could not be weaned from cardiopulmonary bypass. There were no differences in myoglobin, troponin, or apoptosis between groups. Diazoxide preserved cardiac output versus control (74.5 vs 18.4 mL/kg/min, P = .01). Linear mixed regression modeling demonstrated that the addition of diazoxide to cardioplegia preserved left ventricular developed pressure by 36% (95% confidence interval, 9.9-61.5; P < .01), dP/dt max by 41% (95% confidence interval, 14.5-67.5; P < .01), and dP/dt min by 33% (95% confidence interval, 8.9-57.5; P = .01). It was also associated with higher (but not significant) myocardial oxygen consumption (3.7 vs 1.4 mL O2/min, P = .12). CONCLUSIONS: Diazoxide preserves systolic and diastolic ventricular function in a large animal model of prolonged global myocardial ischemia. Diazoxide as an adjunct to hyperkalemic cardioplegia may allow safer prolonged ischemic times during increasingly complicated cardiac procedures.

Enhancing knowledge of mental health issues among children's nursing students: evaluation of a service user-led workshop.

BACKGROUND: Over the past 20 years, the number of children and young people with mental health issues has increased. During their clinical placements, children's nursing students often encounter such service users, as well as mothers with mental health issues such as postnatal depression. Many of these students have reported feeling inadequately prepared to meet the needs of these service users. AIM: To evaluate a service user-led workshop to improve the knowledge and confidence of children's nursing students in caring for children and young people with mental health issues. METHOD: One university in the south of England ran an interactive workshop as part of a final-year module for BSc and MSc children's nursing students. The workshop was facilitated by service users who had experienced mental health issues. Questionnaires were administered before and after the workshop to collect data from students who attended, then quantitative and qualitative analyses of the data were conducted. FINDINGS: This study found that children's nursing students gained knowledge and confidence in caring for children and young people with mental health issues after attending the workshop. Four themes were identified from the pre-questionnaire data: fear and anxiety; boundaries; mixed experiences; and learning on the job. The themes of boundaries and learning on the job were identified again in the post-questionnaire data, as well as the additional themes of 'being with, rather than doing' and 'further knowledge'. CONCLUSION: Service user involvement is an essential aspect of nurse education due to its positive and motivating effects on students. Future research could explore the optimal type of service user input required at different stages of nurse education, to ensure that it enhances the development of students' knowledge and confidence.

Diagnostic Point-of-Care Ultrasound: Recommendations From an Expert Panel.

Diagnostic point-of-care ultrasound (PoCUS) has emerged as a powerful tool to help anesthesiologists guide patient care in both the perioperative setting and the subspecialty arenas. Although anesthesiologists can turn to guideline statements pertaining to other aspects of ultrasound use, to date there remains little in the way of published guidance regarding diagnostic PoCUS. To this end, in 2018, the American Society of Anesthesiologists chartered an ad hoc committee consisting of 23 American Society of Anesthesiologists members to provide recommendations on this topic. The ad hoc committee convened and developed a committee work product. This work product was updated in 2021 by an expert panel of the ad hoc committee to produce the document presented herein. The document, which represents the consensus opinion of a group of practicing anesthesiologists with established expertise in diagnostic ultrasound, addresses the following issues: (1) affirms the practice of diagnostic PoCUS by adequately trained anesthesiologists, (2) identifies the scope of practice of diagnostic PoCUS relevant to anesthesiologists, (3) suggests the minimum level of training needed to achieve competence, (4) provides recommendations for how diagnostic PoCUS can be used safely and ethically, and (5) provides broad guidance about diagnostic ultrasound billing.

Assessment of Frailty Can Guide Decision Making for Utilization of Sentinel Lymph Node Biopsy in Patients with Thick Melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is often omitted in selected patients with advanced primary melanoma, although the justification/criteria for omission have been debated. OBJECTIVE: We sought to determine whether assessment of frailty could serve as an objective marker to guide selection for SLNB in patients with advanced primary melanoma. METHODS: Patients presenting with clinical stage IIC (ulcerated, > 4 mm Breslow thickness) cutaneous melanoma from January 1999 through June 2019 were included. Frailty was assessed using the Memorial Sloan Kettering Frailty Index (MSK FI), a composite score of functional status and medical comorbidities. Five-year melanoma-specific survival (MSS) and overall survival (OS) were estimated using Cox regression, and predictors of OS were identified using competing risk models. RESULTS: MSS did not differ between patients who did (n = 451) or did not undergo SLNB (n = 179) [63.2% vs. 65.0%, p = 0.14]; however, omission of SLNB was associated with decreased 5-year OS (29% vs. 44%, p < 0.001). In a multivariable competing risk model, selection for SLNB omission was an independent predictor of death from non-melanoma causes (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.2-2.3, p < 0.001). After incorporation of the MSK FI score into the multivariable model in this subset, MSK FI (HR 2.4, 95% CI 1.5-4.1, p < 0.001), but not SLNB omission, was an independent predictor of poorer OS. CONCLUSION: We observed worse OS in patients with thick melanoma selected not to undergo SLNB, which was attributed to death due to non-melanoma causes. Formal assessment of frailty may provide an objective prognostic measure to guide selective use of SLNB in these patients.

Therapeutic Implications of Detecting MAPK-Activating Alterations in Cutaneous and Unknown Primary Melanomas.

PURPOSE: Cutaneous and unknown primary melanomas frequently harbor alterations that activate the MAPK pathway. Whether MAPK driver detection beyond BRAF V600 is clinically relevant in the checkpoint inhibitor era is unknown. EXPERIMENTAL DESIGN: Patients with melanoma were prospectively offered tumor sequencing of 341-468 genes. Oncogenic alterations in 28 RTK-RAS-MAPK pathway genes were used to construct MAPK driver groups. Time to treatment failure (TTF) was determined for patients who received first-line programmed cell death protein 1 (PD-1) monotherapy, nivolumab plus ipilimumab, or subsequent genomically matched targeted therapies. A Cox proportional hazards model was constructed for TTF using driver group and clinical variables. RESULTS: A total of 670 of 696 sequenced melanomas (96%) harbored an oncogenic RTK-RAS-MAPK pathway alteration; 33% had ≥1 driver. Nine driver groups varied by clinical presentation and mutational burden. TTF of PD-1 monotherapy (N = 181) varied by driver, with worse outcomes for NRAS Q61 and BRAF V600 versus NF1 or other alterations (median 4.2, 7.5, 22, and not reached; P < 0.0001). Driver group remained significant, independent of tumor mutational burden and clinical features. TTF did not vary by driver for nivolumab plus ipilimumab (N = 141). Among 172 patients with BRAF V600 wild-type melanoma who progressed on checkpoint blockade, 27 were treated with genomically matched therapy, and eight (30%) derived clinical benefit lasting ≥6 months. CONCLUSIONS: Targeted capture multigene sequencing can detect oncogenic RTK-RAS-MAPK pathway alterations in almost all cutaneous and unknown primary melanomas. TTF of PD-1 monotherapy varies by mechanism of ERK activation. Oncogenic kinase fusions can be successfully targeted in immune checkpoint inhibitor-refractory melanoma.

Neoadjuvant immunotherapy for melanoma.

Clinical trials have demonstrated the efficacy of immunotherapy, especially checkpoint blockade inhibitors, in the treatment of patients with metastatic melanoma. More recently, improvements in survival have been reported in patients with high-risk resectable melanoma when these agents are used in the adjuvant setting. Increasing interest in neoadjuvant immunotherapy for high-risk resectable melanoma has been fueled by early reports of significant efficacy. We review the rationale and data behind utilizing neoadjuvant immunotherapy.

Sentinel Lymph Node Biopsy for T1b Melanoma: Balancing Prognostic Value and Cost.

BACKGROUND: The purpose of this study is to report the additional prognostic information and cost associated with sentinel lymph node biopsy (SLNB) for patients with T1b melanoma. PATIENTS AND METHODS: An institutional database was queried for patients with T1b melanoma (0.8-1.0 mm or < 0.8 mm with ulceration) with at least 5 years of follow-up. Results of SLNB, completion lymphadenectomy (CLND), recurrence, and melanoma-specific survival (MSS) were assessed. Institutional costs of melanoma care were converted to Medicare proportional dollars. A Markov model was created to estimate long-term costs. RESULTS: Among the total 392 patients, 238 underwent SLNB. Median follow-up was 10.5 years. SLNB was positive in 19 patients (8.0%). Patients who underwent SLNB had higher 10-year nodal recurrence-free survival (98.6% vs. 91.2%, p < 0.001) but not MSS (94.4% vs. 93.2%, p = 0.55). Ulceration (HR 4.7, p = 0.022) and positive sentinel node (HR 11.5, p < 0.001) were associated with worse MSS. Estimates for 5-year costs reflect a fourfold increase in total costs of care associated with SLNB. However, a treatment plan that forgoes adjuvant therapy for resected stage IIIA melanoma but offers systemic therapy for a node-basin recurrence would nullify the additional cost of SLNB. CONCLUSIONS: SLNB is prognostic for T1b melanoma. Its impact on the overall cost of melanoma care is intimately tied to systemic therapy in the adjuvant and recurrent settings.

Sentinel lymph node biopsy predicts systemic recurrence in digital papillary adenocarcinoma.

BACKGROUND AND OBJECTIVES: Digital papillary adenocarcinoma (DPA) is a rare, aggressive neoplasm of sweat gland origin. It can recur at local, regional, or distant sites. There is limited knowledge about the role of sentinel lymph node biopsy (SLNB) in predicting recurrence in these patients. We present our experience with this uncommon tumor to evaluate the role of SLNB in predicting outcome. METHODS: Medical records of all patients who underwent surgical treatment for biopsy-proven upper extremity DPA at the study institution were reviewed. Descriptive statistics and Fisher's exact test were used to analyze data. RESULTS: Twenty-one patients were identified. Most patients were male (71%), and the median age was 51 years. SLNB was performed in 18 patients; three were positive for nodal metastatic disease (17%). At a median follow-up of 53 months, there were no local recurrences and two cases of systemic recurrence. No patient with a negative sentinel lymph node has evidence of metastasis or recurrence. Fisher's exact test demonstrated a significant association between a positive SLNB and recurrence (P = .02). CONCLUSION: SLNB revealed metastatic disease in 17% of patients with DPA and appears to predict systemic recurrence in this small series.