Citations

Introduction Coronavirus disease 2019 accelerated the use of virtual visits within health care. We examined the utility of telemedicine for conducting visits in a tertiary head and neck practice. Methods A retrospective study was conducted on patients presenting via video to a tertiary-level head and neck clinic between January 2020 and December 2020. Patient demographics were collected in addition to visit indication, diagnostic imaging/tests at the time of visit, and post-visit plan. Visits were deemed successful if evaluation by video was sufficient in determining a clinical plan and did not require deferment of recommendations for subsequent in-person consult visits and/or work-up (labs, imaging). Logistic regression was performed to identify variables that served as significant predictors of successful video visits. Results A total of 124 video visits were reviewed. Video visits were successful for the initial evaluation 88.7% of the time ( n = 110). Computerized tomographic scans were the most available diagnostic test, available for 54% of patients ( n = 67), followed by biopsy report 30.6% ( n = 38). Visit indication had a statistically significant effect on whether a treatment plan could be made ( p = 0.024). For new patients with parotid masses ( n = 42), definitive treatment plans could be made 97.6% of the time ( n = 41). Patients presenting with an indication of thyroid mass (odds ratio: 0.19 (confidence interval: 0.00072–0.50), p = 0.018) and other neck mass (odds ratio: 0.035 (confidence interval: 0.0014, 0.90), p = 0.043) were at significantly lesser odds than parotid patients to have a successful video visit. Discussion In this study, virtual visits were successful for a high percentage of head and neck visits, particularly among patients seeking evaluation for parotid-related concerns.

Abstract To determine the survival benefit of allogeneic hematopoietic cell transplantation (allo-HCT) in chronic myelomonocytic leukemias (CMML), we assembled a retrospective cohort of CMML patients 18-70 years old diagnosed between 2000 and 2014 from an international CMML dataset (n = 730) and the EBMT registry (n = 384). The prognostic impact of allo-HCT was analyzed through univariable and multivariable time-dependent models and with a multistate model, accounting for age, sex, CMML prognostic scoring system (low or intermediate-1 grouped as lower-risk, intermediate-2 or high as higher-risk) at diagnosis, and AML transformation. In univariable analysis, lower-risk CMMLs had a 5-year overall survival (OS) of 20% with allo-HCT vs 42% without allo-HCT (P < .001). In higher-risk patients, 5-year OS was 27% with allo-HCT vs 15% without allo-HCT (P = .13). With multistate models, performing allo-HCT before AML transformation reduced OS in patients with lower-risk CMML, and a survival benefit was predicted for men with higher-risk CMML. In a multivariable analysis of lower-risk patients, performing allo-HCT before transformation to AML significantly increased the risk of death within 2 years of transplantation (hazard ratio [HR], 3.19; P < .001), with no significant change in long-term survival beyond this time point (HR, 0.98; P = .92). In higher-risk patients, allo-HCT significantly increased the risk of death in the first 2 years after transplant (HR 1.46; P = .01) but not beyond (HR, 0.60; P = .09). Performing allo-HCT before AML transformation decreases life expectancy in lower-risk patients but may be considered in higher-risk patients.

7562 Background: Lymphoma is the 6th most common cancer and a top 10 cause of cancer deaths. To date, there are no blood test approaches to population screening, and accurate surveillance markers are limited. Methylated DNA markers (MDMs) are broadly informative for early detection of cancer but have not been extensively studied for lymphomas. We sought to discover and validate MDMs in DNA extracted from lymphoma tissue, then test these MDMs in archival blood plasma specimens. Methods: Reduced representation bisulfite sequencing (RRBS) was performed on DNA extracted from a discovery set of frozen tissues of classic Hodgkin lymphoma (CHL, n=24), non-Hodgkin lymphoma (NHL, n=78: T-cell-TCL (8); diffuse large B-cell-DLBCL (18); follicular-FL (12); mantle cell-MCL (20); marginal zone-MZL (15)), and lymphoma cell line samples (27); controls included benign lymph node (n=11) and healthy donor buffy coat (n=30). 30 MDMs were ranked by fold-change and AUC and used to design methylation-specific PCR assays for biological validation on independent DNA samples extracted from FFPE tissue from 13 normal lymph node and 63 lymphoma samples and 36 buffy coats from healthy patients. Target enrichment long-probe quantitative-amplified signal assays were developed for 16 MDMs and then assayed in plasma-extracted, bisulfite-converted DNA samples from 390 independent treatment-naïve lymphoma patients (100 CHL and 290 NHL:100 DLBCL, 73 FL, 41 MCL, 41 MZL, 35 TCL), and 210 controls without cancer. Lymphoma plasma samples and 159 controls were provided by the Lymphoma SPORE (CA97274); 51 controls came from a 7-county population archive. Classification of lymphoma cases vs controls was modeled with random forest method and cross-validated across 500 bootstrap samples of each dataset. Results: For MDMs tested in DNA from independent biological validation samples, cross-validated random forest models identified 60/63 cases (95% sensitivity) and 12/13 normal controls (92% specificity). In plasmas, a panel of 16 MDMs ( ZNF503, VWA5B1, HOXA9_5195, GABRG3, ITGA5, MAX_chr17_793, BNC1_2407, CDK20, MAX_chr4_184, TPBG, DNAH14, SYT2, CACNG8, FAM110B, and NRN1) detected 78% (95% CI, 74-82%) of lymphoma cases at 90% specificity. Excluding MZL and TCL, sensitivity increased to 84% (80-88%) including 26/49 (53% (38-67%)) of stage I and 59/71 (83% (71-90%)) of stage II cases. Conclusions: MDMs show promise to detect lymphoma. These markers could be evaluated as part of multicancer early detection testing and could also be evaluated as response markers to treatment and subsequent surveillance.[Table: see text]

AbstractBackgroundInfection remains a major complication of cardiac implantable electronic devices and can lead to significant morbidity and mortality. Implantable devices that avoid transvenous leads, such as the subcutaneous implantable cardioverter‐defibrillator (S‐ICD), can reduce the risk of serious infection‐related complications, such as bloodstream infection and infective endocarditis. While the 2017 AHA/ACC/HRS guidelines include recommendations for S‐ICD use for patients at high risk of infection, currently, there are no clinical trial data that address best practices for the prevention of S‐ICD infections. Therefore, an expert panel was convened to develop a consensus on these topics.MethodsAn expert process mapping methodology was used to achieve consensus on the appropriate steps to minimize or prevent S‐ICD infections. Two face‐to‐face meetings of high‐volume S‐ICD implanters and an infectious diseases specialist, with expertise in cardiovascular implantable electronic device infections, were conducted to develop consensus on useful strategies pre‐, peri‐, and postimplant to reduce S‐ICD infection risk.ResultsExpert panel consensus on recommended steps for patient preparation, S‐ICD implantation, and postoperative management was developed to provide guidance in individual patient management.ConclusionAchieving expert panel consensus by process mapping methodology for S‐ICD infection prevention was attainable, and the results should be helpful to clinicians in adopting interventions to minimize risks of S‐ICD infection.

Abstract The diagnosis of acute promyelocytic leukemia (APL) relies on the identification of PML::RARA fusion. While the majority of APL cases harbor a typical t(15;17)(q24;q21), atypical genetic mechanisms leading to the oncogenic PML::RARA fusion have been reported yet their frequency and scope remain poorly characterized. We assessed the genetic findings of 831 cases with APL investigated with concurrent chromosome banding analysis and dual‐color dual‐fusion fluorescence in situ hybridization (D‐FISH) analysis at our institution over an 18.5‐year timeframe. Seven hundred twenty‐three (87%) cases had a typical balanced t(15;17) with both testing modalities. Atypical karyotypic results including complex translocations, unbalanced rearrangements and insertional events occurred in 50 (6%) cases, while 6 (0.7%) cases were cryptic by conventional chromosome studies despite PML::RARA fusion by D‐FISH evaluation. Atypical FISH patterns were observed in 48 (6%) cases despite apparently balanced t(15;17) on chromosome banding analysis. Two hundred fifty (30%) cases displayed additional chromosome abnormalities of which trisomy/tetrasomy 8 (37%), del(7q)/add(7q) (12%), and del(9q) (7%) were most frequent. Complex and very complex karyotypes were observed in 81 (10%) and 34 (4%) cases, respectively. In addition, 4 (0.5%) cases presented as an apparently doubled, near‐tetraploid stemline clone. This report provides the largest appraisal of cytogenetic findings in APL with conventional chromosome and PML::RARA D‐FISH analysis. By characterizing the frequency and breadth of typical and atypical results through the lens of these cytogenetic testing modalities, this study serves as a pragmatic source of information for those involved in the investigation of APL in both the clinical and research laboratory settings.

AbstractIntroductionAtrial fibrillation (AF) ablation is increasingly performed worldwide. As comfort with AF ablation increases, the procedure is increasingly used in patients that are older and in those with more comorbidities. However, it is not well established whether AF ablation in the elderly, especially those >75 years old, has comparable safety and efficacy to younger populations.ObjectiveTo compare the efficacy and safety profiles in patients older than 75 years undergoing AF ablation with younger patients.MethodsDatabases from EMBASE, Medline, PubMed, and Cochrane, were searched from inception through September 2021. Studies that compared the success rates in AF catheter ablation and all complications rates between patients who were older vs under 75 years were included. Effect estimates from the individual studies were extracted and combined using random effect, generic inverse variance method of DerSimonian and Laird.ResultsTwenty‐seven observational studies were included in the analysis consisting of 363,542 patients who underwent AF ablation. Comparing patients older than 75 years old to younger patients, there was no difference in the success of ablation rates between elderly and younger patients (pooled OR 0.85: 95% CI:0.69–1.05, p = .131). On the other hand, AF ablation in the elderly was associated with higher complication rates (pooled OR 1.42: 95% CI:1.21–1.68, p < .001).ConclusionAs AF ablation is expanded to elderly populations, our study found that AF ablation success rates were similar in both elderly and younger patients. However, older patients experience higher rates of complications that should be considered when offering the procedure and as a means to improve outcomes with future innovations.

Abstract Aims CD40 and its ligand, CD40L, play a critical role in driving atherosclerotic plaque development. Disrupted CD40-signalling reduces experimental atherosclerosis and induces a favourable stable plaque phenotype. We recently showed that small molecule-based inhibition of CD40-tumour necrosis factor receptor associated factor-6 interactions attenuates atherosclerosis in hyperlipidaemic mice via macrophage-driven mechanisms. The present study aims to detail the function of myeloid CD40 in atherosclerosis using myeloid-specific CD40-deficient mice. Method and Results Cd40flox/flox and LysM-cre Cd40flox/flox mice on an Apoe−/− background were generated (CD40wt and CD40mac−/−, respectively). Atherosclerotic lesion size, as well as plaque macrophage content, was reduced in CD40mac−/− compared to CD40wt mice, and their plaques displayed a reduction in necrotic core size. Transcriptomics analysis of the CD40mac−/− atherosclerotic aorta revealed downregulated pathways of immune pathways and inflammatory responses. Loss of CD40 in macrophages changed the representation of aortic macrophage subsets. Mass cytometry analysis revealed a higher content of a subset of alternative or resident-like CD206+CD209b− macrophages in the atherosclerotic aorta of CD40mac−/− compared to CD40wt mice. RNA-sequencing of bone marrow-derived macrophages of CD40mac−/− mice demonstrated upregulation of genes associated with alternatively activated macrophages (including Folr2, Thbs1, Sdc1, and Tns1). Conclusions We here show that absence of CD40 signalling in myeloid cells reduces atherosclerosis and limits systemic inflammation by preventing a shift in macrophage polarization towards pro-inflammatory states. Our study confirms the merit of macrophage-targeted inhibition of CD40 as a valuable therapeutic strategy to combat atherosclerosis.

Introduction We examined the suitability of using a video visit platform to perform postoperative parotidectomy evaluation at a tertiary care, multiple-surgeon otolaryngology center. Methods A retrospective case review was conducted of patients who underwent parotidectomy and postoperative video visits between November 2019 and December 2020. Success of video visit, plan if applicable, and post-visit outcomes were reviewed. Video visits were designated as successful if the physician could assess for complications in the postoperative course (e.g. first bite pain, Frey syndrome, ear numbness, unplanned visits to the emergency department, unplanned return to the operating room), perform examination of facial nerve function, and formulate care recommendations per clinical judgement without deferment of recommendations for a subsequent in-person visit. Results There were 96 postoperative video visits with 91 unique parotidectomy patients. Demographics: 28/63 male/female; average age, 54y. All video visits were suitable for successful postoperative parotidectomy patient evaluation. Eight visits (8.3%) consisted of patients presenting with common postoperative complications (e.g. eye dryness, first bite pain) and warranted care recommendations. In only two cases did the patient require further in-person procedural (hematoma evacuation, seroma aspiration) follow-ups. For the other 91.7% of visits (n = 88), no additional recommendations were required as patients experienced uncomplicated postoperative courses. Of all the patients, 26.1% (n = 23) were instructed to follow-up for routine surveillance. All other patients, 73.9% (n = 65) were instructed to follow-up as needed. Conclusion Postoperative parotidectomy evaluation is highly amenable to being performed by video. A telemedicine option offers convenience for patients in the majority of cases without compromising clinical assessment and judgment for the physician.