Citations

Abstract Background/Introduction High-density mapping catheters enhance the speed and accuracy of 3-dimensional data collection. However, differences in data acquisition, efficiency, and system processing are not well quantified, even for catheters with similar form factors. Purpose Compare in-vivo and bench performance of the HD Grid X (EnSite X v 5.0.1) and Optrell (Carto v 8.1.1) catheters. Criteria include mapping and modeling efficiency, electrogram (EGM) amplitude dependence on orientation, and resolution of low voltage boundaries. Methods In-vivo: In 6 swine, 5 physicians used each catheter in a randomized order to create models of equivalent detail of the left atrium (LA) and ventricle (LV) during atrial pacing. Comparable mapping parameters were selected between the respective mapping systems. Each mapping catheter was then placed in a stable location at 3 different anatomical sites in the LA and rotated while collecting manual map points. In the right atrium (RA), an independent operator placed groups of 5-6 radiofrequency (RF) lesions with a focal ablation catheter. Each physician, being blinded to the ablated areas, remapped the RA and identified the area(s) they assessed as being ablated. The indicated regions were measured on the mapping system and compared to the actual ablated area(s) observed during necropsy. Bench: Using a wavefront emulator platform, 2 propagation patterns were created—case 1: a single uniform wavefront propagating across the platform, and case 2: two uniform wavefronts colliding in the center of the platform creating a low-voltage region. For both cases, during map collection, the catheter was oriented at 3 different angles (0, 45, and 90 deg.) relative to the propagation direction. For case 1, the EGM amplitudes were compared. For case 2, the spatial resolution of the low-voltage region was defined by the full-width at half max (FWHM), i.e., the measured width of the area containing less than half the max amplitude. Results In-Vivo: Median rate of mapping point acquisition for Grid X was higher than Optrell by 167% (p=0.02; 48,18 points/s) in the LA and 39% (p=0.03; 18,13 points/s) in the LV. Median time for model completion for Grid X was shorter than Optrell by 39% (p=0.047; 318s, 525s) in the LA and 45% (p=0.02; 342s, 620s) in the LV. Grid X measured higher amplitude EGMs in all 3 LA locations (Fig 1). The mean error in the lesion areas identified by Grid X was 25% lower than Optrell (p=0.04; 154, 204 mm²). Bench: In case 1, Grid X recorded a median normalized amplitude which was 58% larger than Optrell (Fig 1). In case 2, Grid X recorded a median voltage resolution which was 34% finer than Optrell (Fig 2). Conclusion Design considerations beyond catheter shape may impact mapping quality and speed. Grid X collects mapping and geometry data faster, is less reliant on catheter orientation to collect high voltage EGMs, and more accurately defines low voltage boundaries compared to Optrell.Figure 1:EGM Amplitude DataFigure 2:Voltage Resolution

Abstract Background Type 8 long QT syndrome (LQT8) is characterised by prolonged QT interval and a high burden of ventricular repolarisation abnormalities including sudden cardiac death. Purpose Patients and clinicians face uncertainties about the daily risk of cardiac arrest, particularly during physical performance. Therefore, we aim to establish a risk assessment based on systematically collected data. Methods We analysed eight patients genetically confirmed to carry CACNA1C variants, of whom three had cardiac arrests in early childhood, while others were discovered incidentally. One patient met criteria for cardiac-only Timothy syndrome. All patients performed cardiopulmonary exercise testing (CPET) with several having multiple studies over time, resulting in a total of 19 CPETs. Echocardiograms were available for all patients, and Holter monitor results for all but one patient. All CPETs were conducted on beta-blockade. Results On resting ECG the average heart rate was 66.5 ± 10.7 beats per minute (bpm). Average QT at diagnosis was 476.8 ± 47.8 ms, with a corrected QTc of 487.9 ± 37.2 ms. Two patients had sinus arrhythmia and three were atrially paced at rest. No ventricular arrhythmias were observed at rest. On initial CPET, average peak oxygen uptake was 29.3 ± 8.5 ml/kg/min (82 ± 25% predicted) at a peak heart rate of 141.6 ± 24.3 bpm (73 ± 13% predicted). Peak respiratory exchange ratio averaged 1.09 ± 0.13. On initial CPET, four patients developed premature ventricular contractions (PVCs), but only in one patient were more than 5 per minute detected. That patient had a high PVC burden with multiple runs of non-sustained ventricular tachycardia. There were no episodes of syncope or cardiac arrest across all 19 CPETs. Conclusions Our cases demonstrate the safety and utility of exercise testing in CACNA1C-related disease. Longitudinal follow-up revealed diverse electrophysiological findings, including QT prolongation and reduced chronotropic response. From our data it is suggested that CPET is safe to perform on appropriate therapy and exercise should be encouraged.

The adult chronic pancreatitis (CP) working group, formed at the inception of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC), has developed a robust framework and infrastructure to conduct clinical, translational, and mechanistic studies of CP. At its core is PRO spective Evaluation of C hronic Pancreatitis for E pid E miologic and Translational Stu D ies (PROCEED), the first longitudinal cohort study of CP in US adults, launched in 2017. PROCEED has developed a well-annotated clinical data set of over 2000 deeply-phenotyped participants, a biorepository and an imaging repository. Investigators have published promising data on blood-based and imaging-based biomarkers of CP diagnosis and pain, which are awaiting validation. Clinical observations include classification of patients into mechanism-based pain phenotypes using responses to PROMIS questionnaires, prevalence and predictors of opioid use, prevalence of psychological comorbidity, and osteopathy in CP patients. Pilot clinical trials have evaluated the effect of oral indomethacin on pancreatic fluid prostaglandin E2 levels and Internet-based cognitive behavioral therapy (CBT) for chronic pain. Results of pilot trials have led to an ongoing definitive randomized clinical trial for CBT. The rich environment and resources have facilitated mentorship and academic development of many early-stage investigators. Investigators outside of the consortium have opportunities for collaboration. In the next 5 years, the working group plans to further strengthen the research platform, complete primary and key secondary analyses of PROCEED and ancillary studies, continue efforts to develop biomarkers for diagnosis and prognosis of CP, and complete ongoing clinical trials to address unanswered questions in the field.

Objective: To describe cochlear implant outcomes in a patient with bilateral rapidly progressive hearing loss secondary to Kelch-like protein–11 (KLHL11) IgG rhombencephalitis. Patient: A 26-year-old male presenting to neurotology clinic at a tertiary care center for evaluation of bilateral rapidly progressive sensorineural hearing loss, unresponsive to systemic corticosteroid therapy. Interventions: Bilateral simultaneous cochlear implantation. Main Outcome Measures: Postimplant speech testing (CNC word, AzBio sentence scoring), and changes to hearing function with fluctuations in systemic disease symptomatology. Results: Preoperative testing demonstrated poor speech perception (bilateral AzBio sentence in quiet: 43%, right-sided CNCw score: 38%, and left-sided CNCw score: 0%). Despite systemic disease progression of KLHL11-IgG rhombencephalitis, including worsening cerebellar ataxia and dysarthria, cochlear implant performance did not decrease at the time of last follow-up. At 1-year, binaural and monaural speech testing were both significantly improved compared with the 1-month testing (bilateral AzBio sentence in quiet: 91%, right-sided CNCw score: 70%, and left-sided CNCw score: 32%). Conclusions: Cochlear implantation may offer meaningful auditory rehabilitation in patients with KLHL11-IgG associated rhombencephalitis with relative auditory nerve sparing, despite ongoing disease progression. Further studies are required to evaluate the durability and generalizability of cochlear implantation across the spectrum of disease-related hearing loss.

Abstract Extramedullary disease (EMD) is increasingly recognized in relapsed/refractory multiple myeloma (MM), with central nervous system involvement (CNS-MM) representing a rare but highly aggressive manifestation associated with dismal outcomes. Data on its incidence and optimal management, particularly in the era of cellular and bispecific therapies, remain limited. We conducted a retrospective analysis of patients with MM with pathology-confirmed EMD treated at our institution between January 2000 and December 2023. CNS-MM was defined by parenchymal or leptomeningeal involvement. Clinical features, cytogenetics, treatments, and outcomes were analyzed, with predictors of CNS involvement evaluated among patients with EMD. Among 304 patients with EMD, 20 (6.5%) had CNS-MM. CNS involvement occurred a median of 19.2 months after MM diagnosis, though 15% presented at diagnosis. CNS-MM was strongly associated with high-risk cytogenetics (odds ratio [OR], 3.7) and additional visceral EMD (OR, 4.6). Median overall survival (OS) from CNS-MM diagnosis was 4.2 months. Outcomes were significantly improved in patients receiving chimeric antigen receptor T-cell therapy or bispecific antibodies, with a median OS of 19.2 months vs 1.2 months in those who did not receive immune effector therapies. Intrathecal (IT) chemotherapy demonstrated limited and transient benefit. In conclusion, CNS-MM is an aggressive complication enriched in high-risk, multifocal EMD with extremely poor prognosis. Cellular and bispecific therapies show promising activity and may meaningfully improve survival, whereas IT therapy appears to have limited efficacy. Prospective studies are needed to define optimal treatment strategies for CNS-MM.

Background: Alzheimer's disease (AD) is a leading cause of death worldwide, with growing prevalence as life expectancy increases. An important neurological hallmark of AD is the deposition of extracellular neuritic amyloid-β (Aβ) plaques that can disrupt synaptic transmission and cause neuronal death. More recent studies suggest that targeting Aβ species can slow the progression of cognitive decline in AD. Review Summary: This narrative review examines the efficacy of monoclonal antibodies targeting the amyloid-β (Aβ) protein in the treatment of AD. It discusses the mechanisms by which these antibodies aim to mitigate amyloid pathology and explores their clinical outcomes in various trials. The review highlights the importance of amyloid plaque reduction to less than 25 Centiloids observed through amyloid positron emission tomography (PET) scans as a predictor of slowing cognitive decline. The findings suggest that targeting insoluble amyloid plaques is crucial for achieving clinical benefits in AD treatment. This review also discusses the phenomenon of amyloid-related imaging abnormalities (ARIA) that may be associated with monoclonal antibody therapy. Conclusion: Monoclonal antibodies that target Aβ monomers, soluble oligomers and protofibrils, and insoluble fibrils/plaques were developed, and not all have provided clinical benefit. Emerging evidence suggests that it is important to reduce amyloid plaque burden to less than 25 Centiloids, consistent with a visually negative amyloid PET scan, in order to slow cognitive decline in early symptomatic AD.

Myths and misconceptions about the evaluation and treatment of constipation persist. Many widely prevalent misconceptions about laxatives, specifically stimulant laxatives, interfere with the effective management of constipation. Although some of these myths and misconceptions have been dispelled in recent years, there is additional room for improving the awareness and understanding of the pathophysiology of constipation, the mechanisms of action and the efficacy and safety of available therapies. An evolution in our understanding of pathophysiology and the availability of new treatments requires that primary care practitioners be better positioned to treat this common disorder that reduces patients’ quality of life and negatively impacts the healthcare system. This review defines constipation and elucidates various factors that contribute to its aetiology, including lifestyle, dietary habits, medications and underlying medical conditions. This review addresses and refutes common myths and misconceptions about constipation, such as the belief that regular bowel movements must occur daily or the use of laxatives leads to dependence. This review also highlights the importance of distinguishing between normal and abnormal bowel habits and emphasises the need for individualised management approaches to address constipation effectively. Finally, the review discusses different classes of laxatives, dispelling misconceptions about their safety, efficacy and potential for misuse, with a specific focus on stimulant laxatives. In summary, this review enhances awareness and knowledge of this prevalent disorder, provides evidence-based insights into common myths and misconceptions surrounding constipation and promotes more informed decision-making regarding constipation and the use of laxatives.

Although Rosai-Dorfman disease has nonspecific imaging features, imaging remains essential for delineating disease extent, predicting prognosis, and assessing treatment response once the diagnosis is established through integrated clinical, imaging, and histopathologic evaluation.