Citations

Multimodality imaging plays a pivotal role in ventricular tachycardia (VT) ablation by providing critical insights into arrhythmogenic substrates and guiding procedural strategies. This updated review explores the integration of various imaging techniques, including echocardiography, cardiac magnetic resonance (CMR), multidetector computed tomography (MDCT), electroanatomical mapping (EAM), and nuclear imaging, to optimize VT ablation outcomes. Echocardiography, particularly transthoracic echocardiography (TTE), is an essential first-line tool for evaluating structural heart disease and left ventricular function. Moreover, echocardiography aids in risk stratification and procedural planning by detecting regional wall motion abnormalities and thrombus formation. Meanwhile, intracardiac echocardiography (ICE) enhances ablation precision by providing real-time catheter visualization, improving procedural success, and reducing complications such as cardiac tamponade. Nonetheless, CMR is the gold standard for myocardial tissue characterization, enabling the identification of scar burden and conduction channels critical for VT pathogenesis. Late gadolinium enhancement (LGE) facilitates preprocedural planning by localizing arrhythmogenic substrates, predicting VT recurrence risk, and informing ablation strategies. Additionally, T1- and T2-mapping techniques refine the assessment of myocardial fibrosis and inflammation, further improving patient selection and outcomes. MDCT complements CMR by offering high-resolution anatomical visualization and aids in delineating scar distribution, epicardial fat, and vascular structures, informing safe and effective ablation approaches. The integration of these imaging modalities significantly enhances VT ablation precision, reduces recurrence rates, and improves patient outcomes.

Background Oral anti-cancer treatment is commonly used, and non-adherence can negatively affect outcomes. The Oral Oncolytic Non-Adherence Estimator (ORACLE) was designed to prospectively categorize patients into risk levels by considering constructs such as self-efficacy, health literacy, perception of treatment, quality of life, social support, and regimen complexity. Validating this estimator is essential. Methods A content validation survey evaluated representativeness, clarity, and factor structure of each construct in ORACLE. A multidisciplinary panel of 8 content experts and 4 lay experts completed the survey. Results were analyzed to evaluate inter-rater agreement, content validity index (CVI), and factorial validity index (FVI). Post-survey workgroup discussions reviewed results and considered tool adjustments. Results All 12 invited experts completed the survey. The average CVI for content experts was 0.88 for representativeness and 0.98 for clarity. The average CVI for lay experts was 0.95 for clarity. The average FVI was 0.88, with self-efficacy and negative perception constructs yielding the lowest scores (0.63 and 0.75, respectively). ORACLE revisions addressed survey results and expert feedback on health literacy, social support, and regimen complexity. Conclusions Strong CVI for content and lay experts (94% and 95%) and strong FVI for content experts (98%) verify that the tool is understandable and addresses non-adherence issues, establishing validity of construct clarity and representativeness. Content validity of the first pre-treatment oral oncolytic non-adherence risk estimator was established, providing a reliable tool to identify patients at higher risk of non-adherence.

Abstract Background/Introduction Acute coronary syndrome (ACS) is common among elderly patients and is associated with a high risk of complications. Managing ACS, particularly dual antiplatelet therapy (DAPT), poses challenges due to the increased risk of recurrent hemorrhagic and ischemic events in this population. Purpose This study evaluated cardiovascular outcomes in patients ≥75 years that were initiated on DAPT with aspirin (ASA) plus either ticagrelor or clopidogrel following an acute myocardial infarction (AMI). Methods We used the TriNetX repository to identify adult patients (≥75 years) diagnosed with AMI between January 1, 2011, and December 31, 2021, who subsequently initiated DAPT and were not on anticoagulation. Patients were stratified into two cohorts: ASA + ticagrelor and ASA + clopidogrel. Outcomes assessed included major bleeding, repeat coronary intervention, all-cause mortality, all-cause hospitalizations, stroke, new-onset atrial fibrillation, and pacemaker implantation. Follow-up time was restricted to one year. A 1:1 propensity score matching algorithm was applied using the greedy nearest-neighbor method with a caliper of 0.1 pooled standard deviations to ensure balance (i.e., comorbidities, medications, laboratory values) between the two cohorts. Logistic regression models were used to calculate adjusted odds ratios (aOR), and Cox proportional hazards models estimated hazard ratios (HR). Results Before propensity score matching (PSM), 19,859 patients were in the ASA + ticagrelor cohort, and 47,032 were in the ASA + clopidogrel cohort. Post-PSM, 19,746 patients remained in each cohort, with a mean age of 82.2 years and a mean follow-up duration of 298.77 days for the ASA + ticagrelor cohort and 297.59 days for the ASA + clopidogrel cohort. The ASA + ticagrelor cohort had a higher incidence of major bleeding (aOR 1.19 [95% CI, 1.08–1.31]) and pacemaker implantation (aOR 1.14 [95% CI, 1.02–1.29]) compared to the ASA + clopidogrel cohort. Event-free survival analysis showed lower survival rates for major bleeding (HR 1.18 [95% CI, 1.07–1.30]) and pacemaker implantation (HR 1.14 [95% CI, 1.01–1.28]). No significant differences were observed between cohorts in repeat coronary interventions (aOR 0.95 [95% CI, 0.88–1.03]), atrial fibrillation (aOR 1.03 [95% CI, 0.97–1.08]), all-cause mortality (aOR 1.03 [95% CI, 0.96–1.12]), all-cause hospitalization (aOR 1.01 [95% CI, 0.97–1.05]), or stroke (aOR 0.95 [95% CI, 0.86–1.04]). Conclusions In elderly patients, DAPT with ASA + ticagrelor was associated with higher rates of major bleeding and need for pacemaker compared to ASA + clopidogrel. Given the similar risks of recurrent coronary intervention and mortality between the two regimens, these findings highlight the need for careful consideration when selecting ticagrelor over clopidogrel in this population.

Abstract KIF5A (Kinesin family member 5A) is a motor protein that functions as a key component of the axonal transport machinery. Variants in KIF5A are linked to several neurodegenerative diseases, mainly spastic paraplegia type 10 (SPG10), Charcot-Marie-Tooth disease type 2 (CMT2), and amyotrophic lateral sclerosis (ALS). These diseases share motor neuron involvement but vary significantly in clinical presentation, severity, and progression. KIF5A variants are mainly categorized into N-terminal variants associated with SPG10/CMT2 and C-terminal variants linked to ALS. This study utilized a novel multiplex NULISA targeted platform to analyze plasma proteome from KIF5A -linked SPG10, ALS patients and compared to healthy controls. Our results revealed distinct proteomic signatures, with significant alterations in proteins related to synaptic function, and inflammation. Notably, neurofilament light polypeptide, a biomarker for neurodegenerative diseases, was elevated in KIF5A ALS but not in SPG10 patients. Moreover, these findings can now be taken forward to gain mechanistic understanding of axonopathies linking to N- vs C-terminal KIF5A variants affecting both central and peripheral nervous systems.

Bladder cancer is a biologically heterogeneous disease with variable clinical presentations, outcomes and responses to therapy. Thus, the clinical utility of single biomarkers for the detection and prediction of biological behavior of bladder cancer is limited. We have previously identified and validated a bladder cancer diagnostic signature composed of 10 biomarkers, which has been incorporated into a multiplex immunoassay bladder cancer test, Oncuria™. In this study, we evaluate whether these 10 biomarkers can assist in the prediction of bladder cancer clinical outcomes. Tumor gene expression and patient survival data from bladder cancer cases from The Cancer Genome Atlas (TCGA) were analyzed. Alignment between the mRNA expression of 10 biomarkers and the TCGA 2017 subtype classification was assessed. Kaplan–Meier analysis of multiple gene expression datasets indicated that high expression of the combined 10 biomarkers correlated with a significant reduction in overall survival. The analysis of three independent, publicly available gene expression datasets confirmed that multiplex prognostic models outperformed single biomarkers. In total, 8 of the 10 biomarkers from the Oncuria™ test were significantly associated with either luminal or basal molecular subtypes, and thus, the test has the potential to assist in the prediction of clinical outcome.

Abstract BACKGROUND AND AIMS NEK8/NPHP9 encodes a protein that localizes to the primary cilium. Biallelic NEK8 variants are known to cause multiorgan developmental defects, including kidney cystic dysplasia and extensive extra-renal defects, with heterozygous carrier parents being asymptomatic [1]. This autosomal recessive inheritance is the most common inheritance mode for ciliopathies. Complementary to this, we now propose a dominant negative effect for specific heterozygous NEK8 missense variants in the kinase domain resulting in an autosomal-dominant ciliopathy. METHOD We performed genetic testing in patients from several medical centers. To explore the consequences of the identified NEK8 variants, we are performing cilia staining assays in patients' skin fibroblast and kidney cells, as well as in mIMCD3 cells overexpressing the identified variants. Furthermore, we are examining the impact of the NEK8 variants on replication stress response. RESULTS We identified three distinct heterozygous NEK8 variants in 12 families (Table 1), all leading to missense alterations in the kinase domain. Interestingly the p.Arg45Trp variant is a recurrent variant we detected in 10 unrelated families. All patients have a kidney phenotype that varies from mild focal segmental glomerulosclerosis to prenatal presentation with polycystic kidneys. Most patients have kidney failure needing kidney replacement therapy at varying ages of onset. In all patients, we thoroughly checked whether a second variant could be found. Furthermore, the large symptomatic family and de novo occurrences favor a dominant inheritance mode. Our preliminary results from functional studies show abnormal primary cilia formation in serum-starved cells as well as increased replication stress. CONCLUSION We present the first evidence for a pathogenic effect of heterozygous NEK8 variants. Remarkably our patients present with a kidney limited phenotype as compared to the multiorgan defects found in patients with biallelic variants. This reveals a new mode of inheritance for NEK8 variants and expands genotype-phenotype correlations for this gene.

Purpose To quantify the financial impact of an anterior cruciate ligament (ACL) injury on the remaining career earnings of National Basketball Association (NBA) players. Methods We performed a retrospective review of all NBA players who had an ACL rupture between 2000 and 2019. Players were matched to healthy controls by age, position, body mass index, and player efficiency rating at the time of injury (index year). Player information collected included demographic information, position, team role, draft pick, date of injury, contract length, and earnings during the 3 years before and 7 years after the index year, as well as new contract length and earnings after injury. Results A total of 12 players (22%) did not return to play (RTP). No statistically significant difference in annual earnings was present at any time point between cohorts. When we examined the mean difference in earnings between the first 3 post‐index seasons and the 3 pre‐index seasons, both the ACL and control cohorts showed increased salaries as players’ careers progressed, without a significant difference in earnings. When comparing cohorts, we found no significant difference in the length and earnings of contracts during the index year. Furthermore, there was no significant difference in the length or earnings of the first new contract signed after the index year between cohorts. Additionally, NBA players who were able to RTP after ACL reconstruction were more likely to experience increased earnings if they had greater experience and performance prior to their injury ( P < .01). Conclusions Our study found that NBA players did not experience diminished earnings after RTP from an ACL reconstruction when compared with matched controls. Furthermore, no differences were seen in lengths of new contracts or in contract earnings between cohorts. Players with greater experience and performance prior to injury were more likely to have increased earnings after ACL reconstruction. Level of Evidence Level III, retrospective case‐control study.