Citations

The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous ) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.

The increased use of intelligent automation (IA) is challenging organisations to rethink their business models and focus on agility, consumer centricity, innovation and operations excellence. Recognising the global impact of COVID-19, rapid changes in technology, data-driven decision-making and competition for differentiated talent, the Department of Management Engineering and Consulting (ME&C) prioritised the next skilling of talent to proactively prepare for the increased use of IA. This paper discusses our strategic approach, best practice interventions and diversity of methods to prepare ME&C staff. In alignment with Mayo Clinic’s new strategy to the year 2030, which is a catalyst for staff to develop the skills needed to transform healthcare, ME&C leveraged the 70-20-10 model for learning and development. Various next skilling interventions were adopted to disseminate knowledge and accelerate skill building across the IA continuum of discovery, translation and application. Commercial digital offerings were used, and various Mayo Clinic offerings (eg a series of artificial intelligence [AI] seminars, a journal club and an IA community of practice) were introduced. A crowdsourcing website was created to promote learnings focused on industry insights on AI, robotics, cloud computing, digital transformation and platform scalability. ME&C staff engaged with multidisciplinary teams on the execution of IA strategic priorities. Through diverse interventions, ME&C validated the importance of experimenting, learning from experiences (inside and outside Mayo Clinic) and developing reusable assets such as frameworks and playbooks. While engaging in initiatives that covered a constellation of technologies, staff learnt about the applied value of emerging technologies, business implications and considerations for consumer and staff experiences. We believe that our project will inform other organisations in their quest to build IA capabilities to accelerate business transformation while developing talent.

ImportanceCutaneous squamous cell carcinoma (CSCC) is the second most common malignant disease in the US. Although it typically carries a good prognosis, a subset of CSCCs are highly aggressive, carrying regional and distant metastatic potential. Due to its high incidence, this aggressive subset is responsible for considerable mortality, with an overall annual mortality estimated to equal or even surpass melanoma. Despite this morbidity, CSCC is excluded from national cancer registries, making it difficult to study its epidemiology and outcomes. Therefore, the bulk of the CSCC literature is composed of single-center and multi-institutional retrospective cohort analyses. Given variations in reporting measures and analyses in these studies, interpretability between studies and the ability to pool results are limited.ObjectiveTo define standardized reporting measures for retrospective CSCC studies.FindingsAn expert panel was convened to determine standardized guidelines for recording and analyzing retrospective CSCC data. A total of 13 dermatologists and dermatologic surgeons with more than 5 years of posttraining experience and considerable experience with performing CSCC outcomes research were recruited to the panel. Consensus recommendations were achieved for CSCC retrospective study reporting measures, definitions, and analyses.Conclusions and RelevanceThe recommendations in this report present the potential to standardize future CSCC retrospective studies. With such standardization, future work may have greater interstudy interpretability and allow for pooled analyses.

Background This study sought to characterize the tipping point values (the functional scores that patients deem dysfunctional enough to warrant surgery) for patients undergoing first revision reverse total shoulder arthroplasty (rTSA). Methods This study was a retrospective review of a prospectively collected single-institution database of patients undergoing first revision rTSA between August 2015 and December 2019. Tipping point evaluation utilized preoperative scores including the American Shoulder and Elbow Surgeons (ASES), raw and normalized Constant, Shoulder Pain and Disability Index (SPADI), Simple Shoulder Test (SST), and University of California-Los Angeles (UCLA) scores, and active range of motion including abduction, forward elevation (FE), external rotation (ER), and internal rotation score (IR) prior to elective revision rTSA. Results We included 125 revision rTSAs. Tipping points were 37.6 ASES score, 30.5 raw Constant score, 35.5 normalized Constant score, 68.1 SPADI, 3.7 SST, 13.2 UCLA score, 64° abduction, 69° FE, 23° ER, and 3.1 IR. Higher SST was found for older patients and patients with a lower body mass index. Lower abduction and FE tipping points were reported in patients undergoing revision rTSA for rotator cuff failure, unexplained pain, and implant wear. Discussion These tipping points can help surgeons counsel patients regarding when to undergo revision rTSA. Level of evidence Level III; retrospective cohort study; treatment study.

Abstract INTRODUCTION Tau‐positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis. METHODS Using head‐to‐head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed “CenTauR” [CTR]). JPM is a statistical model that simultaneously models the relationships between head‐to‐head and anchor point data. JPM was compared to a linear regression approach analogous to the one used in the amyloid PET Centiloid scale. RESULTS A strong linear relationship was observed between CTR values across brain regions. Using the JPM approach, CTR estimates were similar to, but more accurate than, those derived using the linear regression approach. DISCUSSION Preliminary findings using the JPM support the development and adoption of a universal scale for tau‐PET quantification. Highlights Tested a novel joint propagation model (JPM) to harmonize quantification of tau PET. Units of common scale are termed “CenTauRs”. Tested a Centiloid‐like linear regression approach. Using five cohorts with head‐to‐head tau PET, JPM outperformed linearregressionbased approach. Strong linear relationship was observed between CenTauRs values across brain regions.

Objective To identify the optimal incentive protocol for maximising participation while managing study costs during the Voyage trial. Design Prospective cohort (Voyage trial) of colorectal cancer (CRC) incidence and mortality outcomes in individuals screened with multitarget stool DNA (mt-sDNA) served as the population. A subset was randomised to receive postage stamps as a pre-consent incentive, or as a post-consent incentive after completion of the consent and questionnaire. Descriptive statistics from year 1 are reported. Results During year 1 of the Voyage trial, a total of 600 258 individuals with mt-sDNA orders received at Exact Sciences Laboratories were randomly selected and invited to participate. Of those, 26 429 (4.4%) opted in, 14 365 of whom (54.3%) consented. The opt-in and consent samples were similar to the target population with respect to sex but differed by geographic residence and age (p<0.001). For the embedded incentive experiment, 2333 were randomised to the pre-incentive arm, while 2342 were randomised to the post-incentive arm. Overall consent rate in the incentive trial was 56.4% (60.9% for the pre-consent incentive arm (1421/2333) vs 52.0% for the post-consent incentive arm (1217/2342), p<0.001). Cost reduction was observed for the pre-consent incentive group, and higher response rates were seen among older versus younger individuals. Conclusions Pre-consent incentive option was associated with a higher participation rate and lower costs and was used for the remainder of study recruitment. CRC incidence and mortality vary with age; thus, adjusting for differential participation by age and region will be important in analyses of Voyage data. Trial registration number NCT04124406.

PURPOSE The autosomal dominant cancer predisposition disorders hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) are genetic conditions for which early identification and intervention have a positive effect on the individual and public health. The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify carriers of HBOC and LS. METHODS Participants were recruited from three geographically and racially diverse sites in the United States (Rochester, MN; Phoenix, AZ; Jacksonville, FL). Participants underwent Exome+ sequencing (Helix Inc, San Mateo, CA) and return of results for specific genetic findings: HBOC ( BRCA1 and BRCA1) and LS ( MLH1, MSH2, MSH6, PMS2, and EPCAM). Chart review was performed to collect demographics and personal and family cancer history. RESULTS To date, 44,306 participants have enrolled in Tapestry. Annotation and interpretation of all variants in genes for HBOC and LS resulted in the identification of 550 carriers (prevalence, 1.24%), which included 387 with HBOC (27.2% BRCA1, 42.8% BRCA2) and 163 with LS (12.3% MSH6, 8.8% PMS2, 4.5% MLH1, 3.8% MSH2, and 0.2% EPCAM). More than half of these participants (52.1%) were newly diagnosed carriers with HBOC and LS. In all, 39.2% of HBOC/LS carriers did not satisfy National Comprehensive Cancer Network (NCCN) criteria for genetic evaluation. NCCN criteria were less commonly met in underrepresented minority populations versus self-reported White race (51.5% v 37.5%, P = .028). CONCLUSION Our results emphasize the need for wider utilization of germline genetic sequencing for enhanced screening and detection of individuals who have LS and HBOC cancer predisposition syndromes.

Abstract: Paradoxical embolism represents a critical and potentially fatal complication that can be associated with pulmonary embolism (PE). This case details a unique case of massive PE, further complicated by embolic stroke occurring during catheter-directed thrombolytic therapy. There was no evidence of thrombosis during the initial evaluation with lower extremity Doppler ultrasound, abdominal computed tomography scan, and transthoracic echocardiography. Differentials for the source of the emboli include unrecognized left atrial appendage thrombus, pulmonary arteriovenous malformations, and a patent left foramen ovale. Our findings highlight the complexities and treatment challenges of massive PE.

Background: Conventional normative samples include individuals with undetected Alzheimer’s disease neuropathology, lowering test sensitivity for cognitive impairment. Objective: We developed Mayo Normative Studies (MNS) norms limited to individuals without elevated amyloid or neurodegeneration (A–N–) for Rey’s Auditory Verbal Learning Test (AVLT). We compared these MNS A–N– norms in female, male, and total samples to conventional MNS norms with varying levels of demographic adjustments. Methods: The A–N– sample included 1,059 Mayo Clinic Study of Aging cognitively unimpaired (CU) participants living in Olmsted County, MN, who are predominantly non-Hispanic White. Using a regression-based approach correcting for age, sex, and education, we derived fully-adjusted T-score formulas for AVLT variables. We validated these A–N– norms in two independent samples of CU ( n = 261) and mild cognitive impairment (MCI)/dementia participants ( n = 392) > 55 years of age. Results: Variability associated with age decreased by almost half in the A–N– norm sample relative to the conventional norm sample. Fully-adjusted MNS A–N– norms showed approximately 7– 9% higher sensitivity to MCI/dementia compared to fully-adjusted MNS conventional norms for trials 1– 5 total and sum of trials. Among women, sensitivity to MCI/dementia increased with each normative data refinement. In contrast, age-adjusted conventional MNS norms showed greatest sensitivity to MCI/dementia in men. Conclusions: A–N– norms show some benefits over conventional normative approaches to MCI/dementia sensitivity, especially for women. We recommend using these MNS A–N– norms alongside MNS conventional norms. Future work is needed to determine if normative samples that are not well characterized clinically show greater benefit from biomarker-refined approaches.