Citations

Abstract Cytogenetics has long represented a critical component in the clinical evaluation of hematologic malignancies. Chromosome banding studies provide a simultaneous snapshot of genome-wide copy number and structural variation, which have been shown to drive tumorigenesis, define diseases, and guide treatment. Technological innovations in sequencing have ushered in our present-day clinical genomics era. With recent publications highlighting novel sequencing technologies as alternatives to conventional cytogenetic approaches, we, an international consortium of laboratory geneticists, pathologists, and oncologists, describe herein the advantages and limitations of both conventional chromosome banding and novel sequencing technologies and share our considerations on crucial next steps to implement these novel technologies in the global clinical setting for a more accurate cytogenetic evaluation, which may provide improved diagnosis and treatment management. Considering the clinical, logistic, technical, and financial implications, we provide points to consider for the global evolution of cytogenetic testing.

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.

Objective: To analyze insulin delivery and glycemic metrics throughout the menstrual cycle for women with type 1 diabetes using closed loop control (CLC) insulin delivery. Methods: Menstruating women using a CLC system in a clinical trial were invited to record their menstrual cycles through a cycle-tracking application. Sixteen participants provided data for this secondary analysis over three or more complete cycles. Insulin delivery and continuous glucose monitoring (CGM) data were analyzed in relation to reported cycle phases. Results: Insulin delivery and CGM metrics remained consistent during cycle phases. Intraparticipant variability of CGM metrics and weight-based insulin delivery did not change through cycle phases. Conclusions: For this sample of menstruating women with type 1 diabetes using a CLC system, insulin delivery and glycemic metrics remained stable throughout menstrual cycle phases. Additional studies in this population are needed, particularly among women who report variable glycemic control during their cycles. Trial Registration: NCT03591354.

Abstract The World Health Organization category of myeloid/lymphoid neoplasms with eosinophilia and PDGFRA rearrangements is composed of a heterogeneous group of neoplasms that can present as a myeloproliferative neoplasm, acute myeloid leukemia, myeloid sarcoma, or lymphoblastic leukemia/lymphoma. The overall outcome of these neoplasms is favorable with imatinib therapy. Herein, we describe an adult female patient with a myeloid neoplasm accompanied by eosinophilia and a novel USP25::PDGFRA gene fusion.

Background and objectives Urinary stone disease has been associated with inflammation, but the specific cell interactions that mediate events remain poorly defined. This study compared calcification and inflammatory cell patterns in kidney tissue from radical nephrectomy specimens of patients without and with a history of urinary stone disease. Design, setting, participants, & measurements Nontumor parenchyma of biobanked radical nephrectomy specimens from age- and sex-matched stone formers ( n =44) and nonstone formers ( n =82) were compared. Calcification was detected by Yasue staining and inflammatory cell populations by immunohistochemistry for CD68 (proinflammatory M1 macrophages), CD163 and CD206 (anti-inflammatory M2 macrophages), CD3 (T lymphocytes), and tryptase (mast cells). Calcifications and inflammatory cells were quantified in cortex and medulla using Image-Pro analysis software. Results Calcification in the medulla of stone formers was higher than in nonstone formers ( P <0.001). M1 macrophages in the cortex and medulla of stone formers were greater than in nonstone formers ( P <0.001), and greater in stone former medulla than stone former cortex ( P =0.02). There were no differences in age, sex, body mass index, tumor characteristics (size, stage, or thrombus), vascular disease status, or eGFR between the groups. M2 macrophages, T lymphocytes, and mast cells did not differ by stone former status. There was a correlation between M1 macrophages and calcification in the medulla of stone formers (rho=0.48; P =0.001) and between M2 macrophages and calcification in the medulla of nonstone formers (rho=0.35; P =0.001). T lymphocytes were correlated with calcification in the cortex of both nonstone formers (rho=0.27; P =0.01) and stone formers (rho=0.42; P =0.004), whereas mast cells and calcification were correlated only in the cortex of stone formers (rho=0.35; P =0.02). Conclusions Higher medullary calcification stimulated accumulation of proinflammatory rather than anti-inflammatory macrophages in stone formers.

AbstractMagnetic resonance imaging (MRI) is a valuable imaging modality for the assessment of both cardiac and non‐cardiac structures. With a growing population of patients with cardiovascular implantable electronic devices (CIEDs), 50%–75% of these patients will need an MRI. MRI‐conditional CIEDs have demonstrated safety of MRI scanning with such devices, yet non‐conditional devices such as hybrid CIEDs which have generator and lead brand mismatch may pose a safety risk. In this retrospective study, we examined the outcomes of patients with hybrid CIEDs undergoing MRI compared to those patients with non‐hybrid CIEDs. A total of 349 patients were included, of which 24 patients (7%) had hybrid CIEDs. The primary endpoint was the safety of MRI for patients with hybrid CIEDs as compared to those with non‐hybrid devices, measured by the rate of adverse events, including death, lead or generator failure needing immediate replacement, loss of capture, new onset arrhythmia, or power‐on reset. Secondary endpoints consisted of pre‐ and post‐MRI changes of decreased P‐wave or R‐wave sensing by ≥50%, changes in pacing lead impedance by ≥50 ohms, increase in pacing thresholds by ≥ 0.5 V at 0.4 ms, and decreasing battery voltage of ≥ 0.04 V. The primary endpoint of any adverse reaction was present in 1 (4.2%) patient with a hybrid device, and consistent of atrial tachyarrhythmia, and in 10 (3.1%) patients with a non‐hybrid device, and consisted of self‐limited atrial and non‐sustained ventricular arrhythmias; this was not statistically significant. No significant differences were found in the secondary endpoints. This study demonstrates that MRI in patients with hybrid CIEDs does not result in increased patient risk or significant device changes when compared to those patients who underwent MRI with non‐hybrid CIEDs.

ObjectiveInvestigate oncologic and functional outcomes associated with transhyoid and lateral pharyngotomy (transpharyngeal) approaches in the treatment of oropharyngeal squamous cell carcinoma (OPSCC).Study DesignRetrospective review.SettingSingle institution (tertiary care center).MethodsThis is a retrospective case series of patients with OPSCC undergoing transpharyngeal resection from 1990 to 2017 at Mayo Clinic. Oncologic outcomes, postoperative complications, objective swallowing data, and rates of tracheostomy and percutaneous gastrostomy tube dependence were recorded.ResultsOf 83 patients meeting inclusion criteria, 56 (68%) were human papillomavirus positive. Overall survival rates at 5 and 10 years following surgery were 85% and 80%, respectively. Cancer‐specific survival rates at these same time points were 90% and 88%. Following treatment, 35 of 49 patients (71%) had a Functional Oral Intake Scale score ≥5, indicating total oral intake of multiple consistencies; 79 of 82 (96%) were without tracheostomy or laryngectomy; and 71 of 81 (88%) were on a full oral diet.ConclusionTranspharyngeal approaches provide adequate functional and oncologic outcomes in the majority of patients with OPSCC. These results may have important implications for patients who are not candidates for, or are unwilling to undergo, nonoperative therapy or for those without access to radiation therapy.

Abstract INTRODUCTION The Cancer Research Education and Engagement (CaRE2) Health Equity Center seeks to eliminate cancer disparities within Black and Latinx communities through research, training, education, and community engagement. The goal of this presentation is to share the unique model of community engagement that was implemented by the CaRE2 Center's Community Outreach Core (COC) during the COVID-19 pandemic. METHODS During the COVID-19 pandemic, the COC hosted community outreach events to address prostate and pancreatic cancer disparities. We overcame the challenges of COVID-19 by hosting these programs over Zoom, Facebook, and Twitter and allowing participants to interact and ask questions. The use of these platforms allowed us to develop and implement the innovative “bed to bedside” model, which allowed participants to gain a well-rounded understanding of the cancer process from cancer survivors, physicians, and researchers of color. The goal of these events were to 1) increase awareness of the importance of prostate and pancreatic cancer screening, 2) educate patients and community members about potential prostate and pancreatic cancer treatments, 3) raise awareness on prostate and pancreatic cancer research, and 4) address the causes and solutions to prostate and pancreatic cancer disparities in the Black and Latinx community. RESULT A total of 4 events were conducted between September and November of 2021, reaching a total of 30 persons directly and about 30 more through social media. At each event, evidence-based prostate cancer and pancreatic cancer education was disseminated. Of the attendees, 48% identified as Black or African American and 14% as Latino(x). Attendees were given the option to provide feedback and 90% of attendees agreed or strongly agreed that the presentations met their expectations. One benefit of conducting outreach activities via these platforms was the ability for more individuals to attend and the elimination of transportation barriers. Participants reported that attending virtually was easy to navigate and provided a suitable environment given the ongoing pandemic. Participants also reported that they enjoyed the “bed to bedside” model and shared that hearing from a survivor of color led to them feeling more comfortable in considering cancer screening. CONCLUSION The Care2 COC, in partnership with the community, is addressing disparities in the Black and Latinx population. One of the barriers that we had to overcome was continuing community outreach during the COVID-19 pandemic. The decision to provide health education outreach over social platforms, was essential to maintain our reach and impact. This allowed for the implementation of the “bed to bedside” model that included the different perspectives of care. We concluded that this model was effective and helped normalize the treatment process. We also concluded that outreach to the community should continue to provide cancer information via virtual formats especially as the COVID-19 related incidence and mortality begins to increase. Citation Format: Jessica Otero, Fern Webb, Folakemi Odedina, Nissa Askins, Linda Behar-Horenstein, Lourdes Baez-Conde, Mariana Stern, Sandra Suther, Renee Reams. Multifaceted approaches to engaging Black and Latinx populations: From bed to bedside [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-059.