Improved concordance of challenging human epidermal growth factor receptor 2 dual in-situ hybridisation cases with the use of a digital image analysis algorithm in breast cancer.

AIMS: Accurate assessment of human epidermal growth factor receptor 2 (HER2) expression by HER2 immunohistochemistry and in-situ hybridisation (ISH) is critical for the management of patients with breast cancer. The revised 2018 ASCO/CAP guidelines define 5 groups based on HER2 expression and copy number. Manual pathologist quantification by light microscopy of equivocal and less common HER2 ISH groups (groups 2-4) can be challenging, and there are no data on interobserver variability in reporting of these cases. We sought to determine whether a digital algorithm could improve interobserver variability in the assessment of difficult HER2 ISH cases. METHODS AND RESULTS: HER2 ISH was evaluated in a cohort enriched for less common HER2 patterns using standard light microscopy versus analysis of whole slide images using the Roche uPath HER2 dual ISH image analysis algorithm. Standard microscopy demonstrated significant interobserver variability with a Fleiss's kappa value of 0.471 (fair-moderate agreement) improving to 0.666 (moderate-good) with the use of the algorithm. For HER2 group designation (groups 1-5), there was poor-moderate reliability between pathologists by microscopy [intraclass correlation coefficient (ICC) = 0.526], improving to moderate-good agreement (ICC = 0.763) with the use of the algorithm. In subgroup analysis, the algorithm improved concordance particularly in groups 2, 4 and 5. Time to enumerate cases was also significantly reduced. CONCLUSION: This work demonstrates the potential of a digital image analysis algorithm to improve the concordance of pathologist HER2 amplification status reporting in less common HER2 groups. This has the potential to improve therapy selection and outcomes for patients with HER2-low and borderline HER2-amplified breast cancers.

"Cyst" on the forearm of a 28-year-old female: Case report of a CIC-rearranged sarcoma.

Capicua transcriptional repressor (CIC)-rearranged sarcomas are part of the group of Ewing-like sarcomas or atypical Ewing sarcomas which, thanks to the progress in molecular diagnosis, are being defined by particular genetic abnormalities separating this group into distinct entities with their own particular histological and immunohistochemical features, as well as different survival outcomes. We report the case of a healthy 28-year-old female presenting with a tender lesion on her forearm which after ultrasound examination was clinically favored to represent an infected sebaceous cyst. Hematoxylin-eosin staining showed a lobulated neoplasm within the subcutis composed of poorly differentiated epithelioid to round cells with a small amount of amphophilic cytoplasm. Frequent mitotic figures and tumor necrosis were present. Immunohistochemical studies showed patchy focal CD99 membranous positivity, negative WT1 and TLE1 staining and diffuse nuclear positivity for ETV4 (performed at outside laboratory). FISH analysis showed significant CIC rearrangement enabling a final diagnosis of an undifferentiated small round cell sarcoma harboring the t(4;19)(q35;q13.1) and CIC-DUX4 fusion. This case shows the importance of awareness of this entity as, unlike Ewing sarcoma, these lesions present in the soft tissues rather than bone and may, as in this case, arise in the superficial soft tissues and be submitted to a dermatopathology practice.

Implementing a prediabetes clinical decision support system in a large primary care system: Design, methods, and pre-implementation results.

BACKGROUND: Early detection of prediabetes and management of cardiovascular (CV) risk factors to prevent CV disease is essential, but clinicians are often slow to address this risk. Clinical decision support (CDS) systems, with appropriate implementation, can potentially improve prediabetes identification and treatment. METHODS/DESIGN: 34 Midwestern primary care clinics were randomized to receive or not receive access to a prediabetes (PreD) CDS tool. Between October 2016 and December 2019, primary care clinicians (PCPs) received Pre-D CDS alerts during visits with adult patients identified with prediabetes and who met minimal inclusion criteria and had at least one CV risk factor not at goal. The PCP Pre-D CDS included a summary of six modifiable CV risk factors and patient-specific treatment recommendations. Study outcomes included total modifiable CV risk, six modifiable CV risk factors, use of CV medications, and referrals. The Consolidated Framework for Implementation Research was used to examine CDS implementation processes. DISCUSSION: This cluster-randomized pragmatic trial allowed PCPs the opportunity to improve CV risk in a timely manner for patients with prediabetes. Effectiveness will be assessed using an intent-to-treat analysis. Implementation processes and outcomes will be assessed through interviews, surveys, and electronic health record data harvested by the CDS tool itself. Pre-implementation interviews and activities identified key strategies to incorporate as part of the Pre-D CDS implementation process to ensure acceptability and high use rates. Analyses are ongoing and trial results are expected in mid-2021.

Researching the Effectiveness of Tree of Life: an Imbeleko Approach to Counseling Refugee Youth.

With the growing worldwide refugee crisis, there is a need for evidence-based interventions that specifically deal with the consequences of cumulative trauma-exposure in refugee youth. Refugee children have unique service needs and differ from their non-refugee peers in terms of sociocultural trauma, language, culture, and educational barriers. This article explains the complexities associated with understanding refugee youth and presents a proposal for studying the possible benefits of Tree of Life therapy. At the present time, Tree of Life therapy has no evidence-base because the published studies of Tree of Life with refugee and/or immigrant youth have sample sizes of one, six, eight, and twenty-nine. As a culturally-grounded, strength-based group counseling approach, Tree of Life therapy addresses traumatic experiences, recognizes participants' cultural differences, highlights individual skills, and aids in instilling both confidence and hope for the future. Ncazelo Ncube, the co-founder and main developer of Tree of Life, describes this therapy as a collective narrative practice that considers cultural beliefs and values (2006, 2010, 2018, 2019). The proposed research design is to study the effectiveness of the Tree of Life in Canada, the United States, the United Kingdom, and South Africa. The research plan is to use pragmatic, group-randomized controlled trials in the "real world" settings of schools and agencies in each of the four countries. In addition, the article describes the development of the Roots and Wings Questionnaire for Children and Youth, a culturally relevant, child-friendly questionnaire. The Tree of Life is a readily available therapy with great potential for helping traumatized refugee youth as well as other trauma-impacted young people worldwide.

Therapeutic implications of immune-profiling and EGFR expression in salivary gland carcinoma.

BACKGROUND: Data relating to the efficacy of immune checkpoint inhibitors (ICI) for salivary gland carcinomas (SGC) is gradually evolving with responses varying among different histotypes. To address these disparities, this retrospective analysis examined the prevalence of recognized biomarkers of response to ICI; namely programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), combined positive score (CPS), epidermal growth factor receptor (EGFR), and microsatellite instability (MSI) in patients with SGC with an aim to determine any prognostic or survival benefits and stratify the use of ICI in this disease. PATIENTS AND METHODS: Of 52 patients with primary SGC eligible for this study, the most common histological types were adenoid cystic carcinoma (n = 17, 33%), salivary duct carcinoma (n = 14, 27%), mucoepidermoid carcinoma (n = 11, 21%), and acinic cell carcinoma (n = 6, 11%). Immunohistochemistry (IHC) was performed using the Ventana Discovery Ultra auto-staining platform for EGFR, PD-1, PD-L1, and mismatch repair (MMR) proteins. CPS ≥1 defined PD-L1 positive cases and log-rank testing was performed to examine the relationship between PD-L1 expression status and disease-free survival (DFS) and overall survival (OS). RESULTS: CPS positivity was seen in 9 (17.3%) patients, none of which were adenoid cystic carcinoma. All 52 (100%) cases expressed retained MMR proteins inferring microsatellite stability (MSS) and EGFR expression was identified in 45 of 52 (86.5%) patients. CPS positivity (score ≥1) was significantly associated with advanced pathological T status (P = .021), advanced pathological N status (P = .006), high histological tumor grade (P = .045), and positive histological margin (P = .023). Patients with PD-L1 positivity in tumor cells did not have an inferior 3-year OS (P = .93). CONCLUSION: The data from this retrospective study highlighting the uniform microsatellite stability alongside the low prevalence of CPS positivity suggests that only a minority of SGC patients may benefit from ICI therapy alone. The high rates of EGFR expression in SGC may be a target to augment immune checkpoint therapy response.

Examining the Effects of Video Modeling and Prompts to Teach Activities of Daily Living Skills.

Video modeling has been shown to be effective in teaching a number of skills to learners diagnosed with autism spectrum disorders (ASD). In this study, we taught two young men diagnosed with ASD three different activities of daily living skills (ADLS) using point-of-view video modeling. Results indicated that both participants met criterion for all ADLS. Participants did not maintain mastery criterion at a 1-month follow-up, but did score above baseline at maintenance with and without video modeling. • Point-of-view video models may be an effective intervention to teach daily living skills. • Video modeling with handheld portable devices (Apple iPod or iPad) can be just as effective as video modeling with stationary viewing devices (television or computer). • The use of handheld portable devices (Apple iPod and iPad) makes video modeling accessible and possible in a wide variety of environments.