Citations

ABSTRACT Background Atrial fibrillation (AF) is a prevalent arrhythmia that frequently coexists with cardiomyopathy, leading to deteriorated cardiovascular outcomes. Analyzing the trends associated with these conditions is essential for improving prevention strategies and management practices. Methods CDC WONDER (1999–2023) data were analyzed to assess AF with cardiomyopathy‐related mortality in patients aged ≥ 25. Using Joinpoint regression analysis, we calculated age‐adjusted mortality rates (AAMRs) per 100,000 patients and average annual percentage changes (AAPCs) to analyze mortality trends. Results AF with cardiomyopathy is responsible for 126,377 deaths among adults aged 25 and older. Alarmingly, AAMRs have surged from 1.8 per 100,000 in 1999 to 3.0 in 2023 (AAPC: 2.11, p < 0.001). The upward trend remains pronounced, particularly between 2016 and 2021, with an annual percentage change of 6.17 ( p = 0.02). Disparities in mortality rates are striking. Men face a higher AAMR than women (3.1 vs. 1.5), and Black individuals bear the heaviest burden at 2.4, closely followed by Whites at 2.3. Regionally, Vermont stands out with the highest AAMR at 3.6, while New York reports the lowest at 1.3. Both rural and urban areas maintain equal AAMRs of 2.1, yet the increase in rural regions is particularly concerning, reflecting an AAPC of 2.44 compared to 1.78 in urban settings. Conclusion The rising mortality rates from AF with cardiomyopathy in patients, particularly among men, Black individuals, and rural residents, demand urgent action. These concerning trends underscore a public health crisis that must be addressed.

Importance An estimated 70% to 80% of older adults develop delirium in the intensive care unit (ICU). Objective To determine if a slow-tempo music (60-80 beats/min) listening intervention decreases delirium duration, delirium severity, pain, or anxiety in older adults undergoing mechanical ventilation. Design, Setting, and Participants This multicenter randomized clinical trial with concealed outcomes assessments was conducted in older adults undergoing mechanical ventilation from February 2020 to December 2023. Patients were enrolled from the ICUs of 2 hospitals affiliated with the Indiana University School of Medicine and from the Mayo Clinic in Rochester, Minnesota. Intervention A music intervention comprising classical and contemporary tracks, delivered twice daily through noise-canceling headphones and tablets for up to 7 days, was compared to active control listening to a silence track delivered under identical conditions. Main Outcomes and Measures The primary outcome was delirium/coma-free days during the 7-day intervention period assessed by the Confusion Assessment Method for the ICU (CAM-ICU) and the Richmond Agitation-Sedation Scale. The secondary outcomes were delirium severity assessed by the CAM-ICU-7, pain assessed by the Critical Care Pain Observation Tool, and anxiety assessed by the visual analog scale for anxiety (VAS-A). Results A total of 158 patients were randomized (mean [SD] age, 68 (9.2) years; 72 [45.5%] female and 86 [54.4%] male). In an intention-to-treat analysis, no differences were found in the number of delirium/coma-free days in the music intervention group compared with control (median [IQR] days, 2.5 [0-5] vs 3 [0-5]; P = .66). There were also no statistically significant differences in the mean CAM-ICU-7 scores, mean pain scores, or mean VAS-A scores over the 7-day intervention period. By end of the 7-day period, both music intervention and control groups had similar mean (SD) CAM-ICU-7 scores (2.72 [2.80] vs 2.56 [2.72]), Critical Care Pain Observation Tool scores (0.20 [0.55] vs 0.61 [1.29]), and VAS-A scores (43.6 [24.7] vs 28.8 [38.4]). Conclusions and Relevance In this randomized clinical trial among older adults undergoing mechanical ventilation, a slow-tempo music intervention did not demonstrate a statistically significant decrease in delirium duration, delirium severity, pain, or anxiety symptoms. Trial Registration ClinicalTrials.gov Identifier: NCT04182334

AbstractAbstract Background Central nervous system (CNS) tumors are a significant cause of morbidity and mortality in Sub-Saharan Africa (SSA). This project aimed to assess and map out the current neuro-oncology capacity in SSA, brain tumor registries, and biobanks. Methods This cross-sectional study utilized an online survey to gather data from healthcare professionals involved in CNS tumor care across SSA through the Society for Neuro-Oncology SSA (SNOSSA). The survey captured information on the availability of neuro-oncology practitioners, neuropathology, molecular diagnostics, cancer registries, and biobanking. Results A total of 145 respondents representing 70 healthcare institutions across 22 countries participated. Of the 70 institutions, specialties included neurosurgery (89%, 62/70), anatomic pathology (74%, 52/70), and medical oncology (71%, 50/70). For radiologic evaluation, 64% (45/70) of responding institutions reported having both CT and MRI. Access to molecular testing through immunohistochemistry or next-generation sequencing was available in 46% (32/70) of responding institutions. Multidisciplinary tumor boards were available for CNS cases in 86% (60/70) of responding institutions. Brain tumor-specific registries were available in 29% (20/70) of responding institutions, and 10% (7/70) maintained brain tumor biorepositories. Conclusion This study demonstrates that SSA has substantial potential in neuro-oncology care practice capacity and facilities. The most significant gaps were in neuropathology and molecular testing, which makes widespread implementation of the WHO 2021 diagnosis challenging. Understanding the prevalence of CNS tumor subtypes in SSA is difficult due to the low number of brain tumor registries and biobanks.

Introduction and importance: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, often presenting with nodal or extranodal masses. However, involvement of the chin region is extremely rare and underreported in literature. This case highlights an unusual extranodal manifestation of germinal center B-cell-like (GCB) DLBCL. Case presentation: A 56-year-old man with a history of hypertension and type II diabetes presented with an 8-month history of a painless, progressively enlarging chin mass. Prior antibiotic therapy failed to resolve the lesion. Examination revealed a firm, 4 × 3 cm subcutaneous swelling involving skin and mucosa. Computed tomography (CT) and positron emission tomography/CT imaging revealed hypermetabolic soft tissue lesions in the chin and right buccogingival region. Histopathology and immunohistochemistry confirmed GCB-type DLBCL. The patient received six cycles of rituximab, cyclophosphamide, pirarubicin, vincristine, and prednisolone chemotherapy, resulting in a significant reduction in lesion size and metabolic activity. Follow-up showed no recurrence. Clinical discussion: This case highlights the diagnostic challenges posed by extranodal DLBCL in atypical locations. Misdiagnosis as an infection led to a delayed diagnosis. Immunophenotyping revealed expression of both B- and T-cell markers, which complicated the classification of the lymphoma. A prior history of spontaneously resolving axillary masses suggested an indolent precursor phase that later transformed into aggressive DLBCL. Conclusion: DLBCL may present in rare extranodal sites such as the chin, mimicking benign conditions. Persistent lesions unresponsive to antibiotics should prompt a malignancy workup. Comprehensive evaluation, including imaging and immunohistochemistry, is critical for timely diagnosis and effective treatment. Further research is needed to understand unusual immunophenotypes and progression pathways in DLBCL.

ABSTRACT Background and Purpose Corticospinal tract (CST) integrity is an imaging biomarker for predicting upper extremity motor recovery, but data are limited in acute ischemic stroke patients. Our study aimed to assess the impact of CST disruption on upper extremity motor recovery after acute ischemic stroke. Methods We enrolled patients with upper extremity motor deficits within 7 days of stroke onset. Patients’ clinical status was assessed for the upper extremity Fugl–Meyer assessment motor component (UE‐FM) within 7 days of stroke and at 15, 30, and 90 days. MRI with tractography was performed within 7 days of stroke. Diffusion tensor images (DTI) were processed to produce maps of fractional anisotropy (FA), apparent diffusion, axial, radial, and mean diffusivity. FA maps were used to assess CST asymmetry index (CST‐AI). Fisher's exact tests for categorical variables, two‐sample t ‐tests for normally distributed numerical data, and Wilcoxon rank sums for non‐normally distributed numeric data were used. Results A total of 21 patients were enrolled in the study with a mean age of 66 (±14) years and median baseline upper extremity motor component score (UE‐FM) of 42 (median) [range: 23, 53]. Baseline UE‐FM was not predictive of a 10‐point change at 90 days ( p = 0.4469). CST‐AI was predictive of recovery at 15 days ( p = 0.0373), and axial diffusivity was predictive of recovery at 90 days ( p = 0.0402). All other imaging variables did not predict recovery. Conclusion Our data suggest that upper extremity motor recovery after acute ischemic stroke is impacted by CST integrity. Further studies are needed to validate our findings.

Background Postoperative atrial fibrillation occurs in ~40% after cardiac surgery. Mineralocorticoid receptor antagonists (MRA) are known to reduce chronic atrial fibrillation (AF) development and burden. We evaluated the association of preoperative MRA use with postoperative atrial fibrillation and investigated atrial cell types modulated by MRAs during cold preservation. Methods We studied 19 042 cardiac surgery patients at Mayo Clinic. Propensity 1:3 matching identified 298 MRA users and 894 non‐users. A subgroup analysis of patients on any preoperative diuretic was performed to isolate cardiac‐specific effects of MRAs, matching 298 MRA users to 894 non‐MRA diuretic users. AF recurrence was assessed for up to 6‐years. Single‐nucleus RNA sequencing (snRNA‐seq) was performed on human donor atria exposed to canrenone (a water‐soluble MRA) during cold preservation with ex‐vivo reperfusion, and expression profiles were compared with atria from patients with AF. Results After matching, preoperative MRA use was associated with a lower incidence of postoperative atrial fibrillation (19.8% versus 31.8%, P <0.001). In the diuretic‐only subgroup, MRA users also had lower postoperative atrial fibrillation (19.8% versus 33.2%, P <0.001). MRA use was associated with a reduced incidence of paroxysmal and chronic AF at 6‐years. snRNA‐seq identified a cardiomyocyte subpopulation, CM2, with high mineralocorticoid receptor expression where canrenone suppressed cold preservation‐induced mineralocorticoid receptor target gene expression, which was conversely elevated in chronic AF. Canrenone also attenuated stress‐response in atrial macrophages and pericytes. Conclusions Preoperative MRAs were associated with reduced postoperative and long‐term AF after cardiac surgery. Mechanistically, our ex‐vivo human atrial model revealed that MRAs suppress mineralocorticoid receptor ‐driven atrial stress responses, particularly in conduction‐relevant cardiomyocytes.

Loss of fragile X messenger ribonucleoprotein (FMRP) causes fragile X syndrome (FXS), an inherited neurodevelopmental disorder resulting in intellectual disability and autism spectrum disorder; however, the molecular function of FMRP remains uncertain. Here, using cell lines and fibroblasts and induced pluripotent stem cell–derived neurons from healthy individuals and patients with FXS, we showed that FMRP regulates collided ribosomes by recruiting activating signal cointegrator 1 complex subunit 3 (ASCC3), an early-acting ribosome-associated quality control (RQC) factor to collided ribosomes, and either positively or negatively regulating translation, depending on transcript context. Disease-associated ASCC3 variants that perturbed ASCC3-FMRP interaction were also found to be defective in ribosome association and handling of collided ribosomes. In cells of a patient with FXS and the Fmr1 KO mouse model, ASCC3 abundance was reduced, and overexpression of ASCC3 in the brains of fetal Fmr1 KO mice promoted neuronal migration. In addition, CRISPR-mediated activation of ASCC3 by lateral ventricular injection of adeno-associated virus (AAV) ameliorated synaptic defects and improved locomotor activity, cognitive deficits, obsessive-compulsive–like behavior, and social interaction deficits after 1 month in 2-month-old Fmr1 KO mice compared with untreated Fmr1 KO controls. In conclusion, these data implicated FMRP in the handling of collided ribosomes to maintain protein homeostasis during neurodevelopment and synaptogenesis and demonstrated proof of concept that targeting RQC may offer alternative treatment strategies for FXS.

592 Background: While not all fevers occurring during hematopoietic stem cell transplantation (HCT) are dangerous, episodes of febrile neutropenia tend to be managed aggressively given the significant mortality and morbidity associated with infectious complications of transplantation. This can potentially lead to unnecessary diagnostic testing, antibiotic treatment, and prolonged hospital stays for non-infectious fever etiologies such as engraftment. Our group has previously demonstrated that high-frequency body temperature monitoring (HFTM) using a wearable device detects fevers earlier in transplant recipients (Flora et al, Cancer Cell, 2021). We hypothesized that applying supervised machine learning to HFTM data collected from inpatient allogeneic HCT patients would allow for accurately distinguishing between non-infectious and infectious etiologies of fever and could potentially guide safe de-escalation of antibiotics. Methods: We analyzed 74 independent fever events detected in HCT patients (n=42) outfitted with an FDA-cleared, wireless sensor measuring axillary temperatures every 2 minutes for the duration of their respective hospitalizations. After data filtering, independent fever events were then retrospectively grouped by fever etiology using physician-determined annotation as previously described (Flora et al., 2021). A split ratio of 80:20 was used to create training and test sets from the parent data set, consisting of 59 and 15 fever events for each split, respectively. Training sets were used to create a classification algorithm identifying bacterial infections requiring antibiotics using the machine learning model XGBoost. The performance of this model was then evaluated using test sets of the remaining fevers (n=15). Results: Averaging over 1000 test sets of 15 independent fevers comprising 5 bacterial infection-related fevers and 10 non-infectious fevers, our model correctly identified 82% (mean recall) of cases requiring antibiotics with a mean precision of 0.41. The model also correctly identified 42% of non-infectious fevers (mean true negative rate, 0.42) that would otherwise have been treated with unnecessary antibiotics. The mean AUCPR was 0.58, with the best performing individual model achieving an AUCPR of 0.97. Conclusions: The preliminary results of this study demonstrate that our classification model shows promise for differentiating fevers requiring antibiotics due to bacterial infections from other non-infectious fever etiologies. Prospective studies further developing supervised machine learning models for subcategorization of febrile neutropenia could pave the way for safely de-escalating antibiotics in HCT and other immunocompromised patients undergoing cancer treatment monitored using HFTM.