Concordance between pathologists and between specimen types in detection of HER2-low breast carcinoma by immunohistochemistry.

CONTEXT: Recent clinical trials indicate that HER2-targeted therapy may benefit HER2-low breast cancer patients including HER2 score 1+ or 2+ and no gene amplification. Concordance between pathologists and between core biopsy and surgical excision in establishing HER2-low status was evaluated. DESIGN: 57 patients with HER2 negative breast cancer (IHC 0, 1+, or 2+, no gene amplification) by core biopsy were included. Core biopsy and representative tumor from corresponding surgical excision was immunostained for HER2. Original HER2 IHC scores were interpreted using 2018 guidelines. Three pathologists independently interpreted again under 2023 guidelines. Kappa statistic evaluated agreement of HER2 IHC scores. RESULTS: Applying 2023 guidelines, HER2 IHC scores were concordant among study pathologists in 46 of 57 (81 %) core biopsy and 50 of 57 (88 %) surgical resections. Kappa statistics were 0.78 and 0.85 (substantial agreement), for inter-pathologist agreement of core biopsy and surgical resections under 2023 guidelines; 0.55 (moderate agreement) for agreement between first interpretation by 2018 guidelines and second interpretation by 2023 guidelines; and 0.13 (slight agreement) for agreement in HER2 consensus scores between outside core and surgical resection and 0.49 (moderate agreement) for inside core and surgical resection. Low HER2 expression was found in 28 of 57 (49 %) core biopsy and in 25 of 57 (44 %) surgical excisions. CONCLUSIONS: Interobserver agreement among study pathologists was good in core biopsy and surgical excisions, applying updated 2023 guidelines. Intratumoral heterogeneity in protein expression and preanalytical factors may result in variable identification of HER2-low status in core biopsy and surgical excision specimens.

Patient factors associated with telehealth quality and experience among adults with chronic conditions.

Objective: To evaluate patient-reported experiences of telehealth and disparities in access, use, and satisfaction with telehealth during the COVID-19 pandemic. Materials and methods: We examined data from the fifth wave of the COVID-19 & Chronic Conditions (C3) study conducted between December 2020 and March 2021. Results: Of the 718 participants, 342 (47.6%) reported having a telehealth visit within the past 4 months. Participants who had a recent telehealth visit were younger, reported worse overall health and chronic illness burden, and living below poverty level. Among participants who had a telehealth visit, 66.7% reported telephone visits and most participants (57.6%) rated telehealth quality as better-or-equal-to in-person visits. Inadequate health literacy was associated with lower likelihood of reporting telehealth quality and usefulness. In multivariable analyses, lower patient activation (adjusted odds ratio (AOR) 0.19, 95% CI, 0.05-0.59) and limited English proficiency (AOR 0.12, 95% CI, 0.03-0.47) were less likely to report telehealth as being better than in-person visits; lower patient activation (AOR 0.06, 95% CI, 0.003-0.41) and income below poverty level (AOR 0.36, 95% CI, 0.13-0.98) were associated with difficulty remembering telehealth visit information. Discussion: Most participants reported usefulness and ease of navigating telehealth. Lower socioeconomic status, limited English proficiency, inadequate health literacy, lower educational attainment, and low patient activation are risks for poorer quality telehealth. Conclusion: The COVID pandemic has accelerated the adoption of telehealth, however, disparities in access and self-reported visit quality persist. Since telemedicine is here to stay, we identify vulnerable populations and discuss potential solutions to reduce healthcare disparities in telehealth use.

Exploratory pilot study to characterize the immune landscapes of malignant pleural effusions and their corresponding primary tumors from patients with breast carcinoma and lung adenocarcinoma.

INTRODUCTION: Malignant pleural effusion (MPE) is a frequent complication of advanced malignancies. In this pilot study, we characterized the immune landscapes of MPEs, compared them to their primary tumor (PT) samples from breast carcinoma (BC) and lung adenocarcinoma (LADC), and tested the utility of multiplexed image technology in cytological samples. MATERIALS AND METHODS: We evaluated the immune contexture of 6 BC and 5 LADC MPEs and their PTs using 3 multiplex immunofluorescence panels. We explored the associations between sample characteristics and pleural effusion-free survival. RESULTS: No MPE samples had positive programmed death-ligand 1 expression in malignant cells, although 3 of 11 PTs has positive programmed death-ligand 1 expression (more than 1% expression in malignant cells). Overall, in LADC samples, cluster of differentiation 3 (CD3)+ T cells and CD3+CD8+ cytotoxic T cells predominated (median percentages for MPEs versus PTs: 45.6% versus 40.7% and 4.7% versus 6.6%, respectively) compared with BC. CD68+ macrophages predominated in the BC samples (medians for MPEs 61.2% versus PTs for 57.1%) but not in the LADC samples. Generally in PTs, CD3+CD8+ forkhead box P3+ T cells and the median distances from the malignant cells to CD3+CD8+Ki67+ and CD3+ programmed cell death protein 1 + T cells correlated to earlier MPE after PT diagnosis. CONCLUSIONS: The immune cell phenotypes in the MPEs and PTs were similar within each cancer type but different between BC versus LADC. An MPE analysis can potentially be used as a substitute for a PT analysis, but an expanded study of this topic is essential.

Disparities in Patient Portal Use Among Adults With Chronic Conditions.

Importance: Disparities in patient access and use of health care portals have been documented. Limited research has evaluated disparities in portal use during and after the COVID-19 pandemic. Objective: To assess prevalence of health care portal use before, during, and after the most restrictive phase of the pandemic (2019-2022) among the COVID-19 & Chronic Conditions (C3) cohort and to investigate any disparities in use by sociodemographic factors. Design, Setting, and Participants: This cohort study uses data from the C3 study, an ongoing, longitudinal, telephone-based survey of participants with multiple chronic conditions. Participants were middle aged and older-adult primary care patients who had an active portal account, recruited from a single academic medical center in Chicago, Illinois, between 2019 and 2022. Data were analyzed between March and June 2022. Main Outcomes and Measures: Outcomes of portal use (ie, number of days of portal login by year) were recorded for all study participants by the electronic data warehouse. All parent studies had uniform sociodemographic data and measures of social support, self-efficacy, health literacy, and health activation. Results: Of 536 participants (mean [SD] age, 66.7 [12.0] years; 336 [62.7%] female), 44 (8.2%) were Hispanic or Latinx, 142 (26.5%) were non-Hispanic Black, 322 (60.1%) were non-Hispanic White, and 20 individuals (3.7%) identified as other race, including Asian, Native American or Alaskan Native, and self-reported other race. In multivariable analyses, portal login activity was higher during the 3 years of the COVID-19 pandemic compared with the 2019 baseline. Higher portal login activity was associated with adequate health literacy (incidence rate ratio [IRR], 1.51; 95% CI, 1.18-1.94) and multimorbidity (IRR, 1.38; 95% CI, 1.17-1.64). Lower portal activity was associated with older age (≥70 years: IRR, 0.69; 95% CI, 0.55-0.85) and female sex (IRR, 0.77; 95% CI, 0.66-0.91). Compared with non-Hispanic White patients, lower portal activity was observed among Hispanic or Latinx patients (IRR, 0.66; 95% CI, 0.49-0.89), non-Hispanic Black patients (IRR, 0.68; 95% CI, 0.56-0.83), and patients who identified as other race (IRR, 0.42; 95% CI, 0.28-0.64). Conclusions and Relevance: This cohort study using data from the C3 study identified changes in portal use over time and highlighted populations that had lower access to health information. The COVID-19 pandemic was associated with an increase in portal use. Sociodemographic disparities by sex and age were reduced, although disparities by health literacy widened. A brief validated health literacy measure may serve as a useful digital literacy screening tool to identify patients who need further support.

Novel syndromic neurodevelopmental disorder caused by de novo deletion of CHASERR, a long noncoding RNA.

Genes encoding long non-coding RNAs (lncRNAs) comprise a large fraction of the human genome, yet haploinsufficiency of a lncRNA has not been shown to cause a Mendelian disease. CHASERR is a highly conserved human lncRNA adjacent to CHD2-a coding gene in which de novo loss-of-function variants cause developmental and epileptic encephalopathy. Here we report three unrelated individuals each harboring an ultra-rare heterozygous de novo deletion in the CHASERR locus. We report similarities in severe developmental delay, facial dysmorphisms, and cerebral dysmyelination in these individuals, distinguishing them from the phenotypic spectrum of CHD2 haploinsufficiency. We demonstrate reduced CHASERR mRNA expression and corresponding increased CHD2 mRNA and protein in whole blood and patient-derived cell lines-specifically increased expression of the CHD2 allele in cis with the CHASERR deletion, as predicted from a prior mouse model of Chaserr haploinsufficiency. We show for the first time that de novo structural variants facilitated by Alu-mediated non-allelic homologous recombination led to deletion of a non-coding element (the lncRNA CHASERR) to cause a rare syndromic neurodevelopmental disorder. We also demonstrate that CHD2 has bidirectional dosage sensitivity in human disease. This work highlights the need to carefully evaluate other lncRNAs, particularly those upstream of genes associated with Mendelian disorders.

Complete genome sequences of nine Rhodococcus equi phages.

We report genomes of nine phages isolated from Actinobacteria Rhodococcus equi NRRL B-16538. Six of these phages belong to actinobacteriophage cluster CR, which otherwise contains Gordonia phages; two form the CF cluster; and one is a singleton. Genome lengths are 62,017-80,980 bp with 63.9%-67.3% GC content.

Breast Angiosarcoma: Imaging Features With Histopathologic Correlation.

Breast angiosarcoma is a rare malignancy of endothelial origin that can be categorized as primary angiosarcoma (PAS) or secondary angiosarcoma (SAS) based on etiology. Primary angiosarcoma typically affects younger women with no known risk factors, whereas SAS of the breast typically develops in older women who have undergone breast cancer treatment. There are two types of SAS, one that develops in the setting of chronic lymphedema and one that develops as a radiation-associated neoplasm after breast-conserving therapy (BCT). Clinically, PAS often presents as a palpable mass that may be rapidly growing, whereas SAS presents with skin changes such as erythematous plaques or nodules or with areas of skin discoloration. Mammographically, the appearance of PAS can be nonspecific and may be obscured by the dense tissue that is characteristic of the young patient population it typically affects. Cases of mammographically occult PAS have been visible at US and MRI. Mammography and US have been found to be less sensitive than MRI for the diagnosis of secondary radiation-associated angiosarcoma. Angiosarcomas, both PAS and SAS, are graded, depending on degree of differentiation, as low, intermediate, or high grade. Endothelial markers such as ERG and CD31 immunohistochemical stains are used to support the diagnosis of angiosarcomas. In this article, we review the clinical presentation, imaging findings, associated histopathology, and treatment of primary and secondary breast angiosarcoma.