Citations

Abstract Aims Pericardiocentesis is usually completed under fluoroscopy. The electroanatomic mapping (EAM) system allows visualizing puncture needle tip (NT) while displaying the electrogram recorded from NT, making it possible to obtain epicardial access (EA) independent of fluoroscopy. This study was designed to establish and validate a technique by which EA is obtained under guidance of three-dimensional (3D) EAM combined with NT electrogram. Methods and results 3D shell of the heart was generated, and the NT was made trackable in the EAM system. Unipolar NT electrogram was continuously monitored. Penetration into pericardial sac was determined by an increase in NT potential amplitude and an injury current. A long guidewire of which the tip was also visible in the EAM system was advanced to confirm EA. Epicardial access was successfully obtained without complication in 13 pigs and 22 patients. In the animals, NT potential amplitude was 3.2 ± 1.0 mV when it was located in mediastinum, 5.2 ± 1.6 mV when in contact with fibrous pericardium, and 9.8 ± 2.8 mV after penetrating into pericardial sac (all P ≤ 0.001). In human subjects, it measured 1.54 ± 0.40 mV, 3.61 ± 1.08 mV, and 7.15 ± 2.88 mV, respectively (all P < 0.001). Fluoroscopy time decreased in every 4–5 cases (64 ± 15, 23 ± 17, and 0 s for animals 1–4, 5–8, 9–13, respectively, P = 0.01; 44 ± 23, 31 ± 18, 4±7 s for patients 1–7, 8–14, 15–22, respectively, P < 0.001). In five pigs and seven patients, EA was obtained without X-ray exposure. Conclusion By tracking NT in the 3D EAM system and continuously monitoring the NT electrogram, it is feasible and safe to obtain EA with minimum or no fluoroscopic guidance.

Objectives: To assess clinicians’ prescribing practices for anticoagulation in older adults with atrial fibrillation or atrial flutter (AF/F) and determine factors common among those without anticoagulation. Methods: We performed a community-based retrospective cohort study of adults aged 65 years and older with a history of nonvalvular AF/F to determine the rate of oral anticoagulation utilization. We also assessed for associations between anticoagulation use and comorbid conditions and common geriatric syndromes. Results: A total of 3832 patients with a diagnosis of nonvalvular AF/F were included (mean [SD] age, 79.9 [8.4] years), 2693 (70.3%) of whom were receiving anticoagulation (51.7%, a vitamin K antagonist; 48.1%, a direct-acting oral anticoagulant). Patients with higher Elderly Risk Assessment index (ERA) scores, a surrogate for health vulnerability, received anticoagulation less often than patients with lower scores. The percentage of patients with a history of falling was higher among those who did not receive anticoagulation than among those who did (44.4% vs 32.8%; P < .001). Similarly, a diagnosis of dementia was more common in the no-anticoagulation group than the anticoagulation group (18.5% vs 12.7%; P < .001). Conclusions: A substantial proportion of older adults with AF/F do not receive anticoagulation. Those without anticoagulation had higher risk of health deterioration based on higher ERA scores and had a higher incidence of dementia and fall history. This suggests that the presence of geriatric syndromes may influence the decision to withhold anticoagulation.

Abstract Background: Non-small cell lung cancer (NSCLC) makes up ~85% of lung cancers, and its major subtypes are adenocarcinoma (AD) and squamous cell carcinoma (SC). The histology classification of NSCLC has significant therapeutic and prognostic implications. As liquid biopsies are rapid and non-invasive, computational methods to classify NSCLC subtypes using cell-free DNA (cfDNA) are desired. Methods: Using The Cancer Genome Atlas (TCGA) NSCLC methylation data, we developed a method to classify AD and SC subtypes from cfDNA samples. We mapped TCGA methylation data to Guardant Infinity’s promoter regions and transformed them to allow for the transfer of the TCGA trained model to Infinity cfDNA epigenomic data. An advantage of this approach is that TCGA training data originates from the primary tumor, while cfDNA samples have low tumor fraction (TF) and may also contain signals from metastatic tumors. We trained a penalized Logistic Regression model with LASSO. To better fit the model to Infinity cfDNA data, we performed region filtering. Results: Our model effectively classified AD and SC subtypes from TCGA samples (AUC 0.97) (10-fold cross validation; Table 1). When evaluating on cfDNA samples with epigenomic TF ≥ 1%, the final model shows reasonable performance (AUC 0.94) (Table 1); the performance decreases when reduced to TF &gt; 0.05% (AUC 0.89) as expected (Table 1). When evaluating cfDNA from uncategorized lung samples, the predicted AD probabilities have significant association with KRAS mutations (p-value = 0.027). Conclusion: Our results show that the penalized Logistic Regression model trained with tissue TCGA methylation data through mapping, transformation, and region selection can classify NSCLC subtypes from cfDNA samples. This method may offer a fast, non-invasive tool to inform subtype-based clinical decisions, especially in the setting of poorly-differentiated carcinomas, and to identify subtype switches upon resistance to targeted therapies. Table 1: Model evaluation on tissue TCGA samples and cfDNA Infinity samples (different TF cutoffs) Sample type N samples AUC Accuracy Sensitivity Specificity Precision F1 score tissue TCGA 907 0.97 0.93 0.94 +/- 0.02 0.93 +/- 0.02 0.94 +/- 0.02 0.94 +/- 0.01 cfDNA Infinity 17 (TF ≥ 1%) 0.94 0.88 0.83 +/- 0.3 0.91 +/- 0.17 0.83 +/- 0.3 0.83 +/- 0.21 cfDNA Infinity 29 (TF &gt; 0.05%) 0.89 0.83 0.88 +/- 0.23 0.81 +/- 0.17 0.64 +/- 0.28 0.74 +/- 0.2 Citation Format: Laura Tung, Denis Tolkunov, Catalin Barbacioru, Deepika Kale, Scott Shell, Jill Tsai, Leylah Drusbosky, Kaushal Parikh, Han-Yu Chuang. Non-small cell lung cancer (NSCLC) histology classification using DNA methylation data captured from liquid biopsies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3499.

Abstract Background Variations in climate have been associated with a greater risk of surgical site infections, urinary tract infections, and changes in the skin microbiome; however, limited data exist on the impact of climate on inflatable penile prosthesis (IPP) infections. Aim We sought to evaluate the impact of climate on the risk of IPP infections in a large international, multicenter cohort. Methods We performed a multi-institutional, retrospective study of patients undergoing IPP surgery. We then evaluated whether the month or season, during which surgery was performed, affected device infections. Implant infections were defined as infections requiring device explantation. A univariate logistic regression analysis was undertaken. Outcomes Our primary outcome was implant infection. Results A total of 5289 patients with a mean age of 62.2 ± 10.8 years received IPP placement. There was a fairly even distribution of implants performed in each season. A total of 103 (1.9%) infections were recorded. There were 32 (31.1%) IPP infections in patients who underwent surgery in the summer, followed by 28 (27.2%) in the winter, 26 (25.2%) in the spring, and 17 (16.5%) in the fall. No statistically significant differences were recorded in terms of season (P = .19) and month (P = .29). The mean daily temperature (P = .43), dew point (P = .43), and humidity (P = .92) at the time of IPP placement was not associated with infection. Clinical Implications These findings provide reassurance to prosthetic urologists that infection reduction strategies do not need to be tailored to local climate. Strengths and Limitations Climate data were not directly recorded for each hospital, but rather based on the monthly averages in the city where the surgery was performed. Conclusion The climate at time of IPP placement and time of year of surgery is not associated with IPP infection risk.

PURPOSE Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 ( FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202 ) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

ImportancePreventive bilateral salpingo-oophorectomy is offered to women at high risk of ovarian cancer who carry a pathogenic variant in BRCA1 or BRCA2; however, the association of oophorectomy with all-cause mortality has not been clearly defined.ObjectiveTo evaluate the association between bilateral oophorectomy and all-cause mortality among women with a BRCA1 or BRCA2 sequence variation.Design, Setting, and ParticipantsIn this international, longitudinal cohort study of women with BRCA sequence variations, information on bilateral oophorectomy was obtained via biennial questionnaire. Participants were women with a BRCA1 or BRCA2 sequence variation, no prior history of cancer, and at least 1 follow-up questionnaire completed. Women were followed up from age 35 to 75 years for incident cancers and deaths. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs for all-cause mortality associated with a bilateral oophorectomy (time dependent). Data analysis was performed from January 1 to June 1, 2023.ExposuresSelf-reported bilateral oophorectomy (with or without salpingectomy).Main Outcomes and MeasuresAll-cause mortality, breast cancer–specific mortality, and ovarian cancer–specific mortality.ResultsThere were 4332 women (mean age, 42.6 years) enrolled in the cohort, of whom 2932 (67.8%) chose to undergo a preventive oophorectomy at a mean (range) age of 45.4 (23.0-77.0) years. After a mean follow-up of 9.0 years, 851 women had developed cancer and 228 had died; 57 died of ovarian or fallopian tube cancer, 58 died of breast cancer, 16 died of peritoneal cancer, and 97 died of other causes. The age-adjusted HR for all-cause mortality associated with oophorectomy was 0.32 (95% CI, 0.24-0.42; P &amp;lt; .001). The age-adjusted HR was 0.28 (95% CI, 0.20-0.38; P &amp;lt; .001) and 0.43 (95% CI, 0.22-0.90; P = .03) for women with BRCA1 and BRCA2 sequence variations, respectively. For women with BRCA1 sequence variations, the estimated cumulative all-cause mortality to age 75 years for women who had an oophorectomy at age 35 years was 25%, compared to 62% for women who did not have an oophorectomy. For women with BRCA2 sequence variations, the estimated cumulative all-cause mortality to age 75 years was 14% for women who had an oophorectomy at age 35 years compared to 28% for women who did not have an oophorectomy.Conclusions and RelevanceIn this cohort study among women with a BRCA1 or BRCA2 sequence variation, oophorectomy was associated with a significant reduction in all-cause mortality.

Importance Magnetic resonance imaging (MRI) surveillance is offered to women with a pathogenic variant in the BRCA1 or BRCA2 gene who face a high lifetime risk of breast cancer. Surveillance with MRI is effective in downstaging breast cancers, but the association of MRI surveillance with mortality risk has not been well defined. Objective To compare breast cancer mortality rates in women with a BRCA1 or BRCA2 sequence variation who entered an MRI surveillance program with those who did not. Design, Setting, and Participants Women with a BRCA1 or BRCA2 sequence variation were identified from 59 participating centers in 11 countries. Participants completed a baseline questionnaire between 1995 and 2015 and a follow-up questionnaire every 2 years to document screening histories, incident cancers, and vital status. Women who had breast cancer, a screening MRI examination, or bilateral mastectomy prior to enrollment were excluded. Participants were followed up from age 30 years (or the date of the baseline questionnaire, whichever was later) until age 75 years, the last follow-up, or death from breast cancer. Data were analyzed from January 1 to July 31, 2023. Exposures Entrance into an MRI surveillance program. Main Outcomes and Measures Cox proportional hazards modeling was used to estimate the hazard ratios (HRs) and 95% CIs for breast cancer mortality associated with MRI surveillance compared with no MRI surveillance using a time-dependent analysis. Results A total of 2488 women (mean [range] age at study entry 41.2 [30-69] years), with a sequence variation in the BRCA1 (n = 2004) or BRCA2 (n = 484) genes were included in the analysis. Of these participants, 1756 (70.6%) had at least 1 screening MRI examination and 732 women (29.4%) did not. After a mean follow-up of 9.2 years, 344 women (13.8%) developed breast cancer and 35 women (1.4%) died of breast cancer. The age-adjusted HRs for breast cancer mortality associated with entering an MRI surveillance program were 0.20 (95% CI, 0.10-0.43; P &amp;lt; .001) for women with BRCA1 sequence variations and 0.87 (95% CI, 0.10-17.25; P = .93) for women with BRCA2 sequence variations. Conclusion and Relevance Results of this cohort study suggest that among women with a BRCA1 sequence variation, MRI surveillance was associated with a significant reduction in breast cancer mortality compared with no MRI surveillance. Further studies of women with BRCA2 sequence variations are needed to ascertain these women obtain the same benefits associated with MRI surveillance.