Long-Term Freedom From Ventricular Arrhythmias in ARVC With Endocardial Only Ablation: Predictors of Success.

BACKGROUND: Although the epicardial predominance of substrate abnormalities has been well demonstrated in early stages of arrhythmogenic right ventricular cardiomyopathy (ARVC), endocardial (ENDO) ablation may suffice to eliminate ventricular tachycardia (VT) in some patients. OBJECTIVES: This study aimed to report the long-term outcomes of ENDO-only ablation in ARVC patients and factors that predict VT-free survival. METHODS: We included consecutive patients with Task Force Criteria diagnosis of ARVC undergoing a first ENDO-only VT ablation between 1998 and 2020. Ablation was predominantly guided by activation/entrainment mapping for mappable VTs and pace mapping/targeting abnormal electrograms for unmappable VTs. The primary endpoint was freedom from any recurrent sustained VT after the last ENDO-only ablation. RESULTS: Seventy-four ARVC patients underwent ENDO-only VT ablation. VT noninducibility was achieved in 49 (66%) patients. During median follow-up of 6.6 years (Q1-Q3: 3.4-11.2 years), 40 (54.1%) patients remained free from any VT recurrence with rare VT ≤2 episodes in additional 12.2%. Among patients with noninducibility, VT-free survival was 75.5% during long-term follow-up. In multivariable analysis, >45 y of age at diagnosis (HR: 0.41; 95% CI: 0.17-0.98) and VT noninducibility (HR: 0.36; 95% CI: 0.16-0.80) were predictors of VT-free survival. CONCLUSIONS: Long-term VT-free survival can be achieved in over half of ARVC patients following ENDO-only VT ablation, increasing to over 75% if VT noninducibility is achieved. Our results support consideration of a stepwise ENDO-only approach before proceeding to epicardial ablation if VT noninducibility can be achieved particularly in older patients.

The Safety and Efficacy of Epicardial Carbon Dioxide Insufflation Compared With Conventional Epicardial Access.

BACKGROUND: Epicardial (Epi) access is commonly required during ventricular tachycardia ablation. Conventional Epi (ConvEpi) access targets a "dry" pericardial space presenting technical challenges and risk of complications. Recently, intentional puncture of coronary venous branches with Epi carbon dioxide insufflation (EpiCO2) has been described as a technique to improve Epi access. The safety of this technique relative to conventional methods remains unproven. OBJECTIVES: The authors sought to compare the feasibility and safety of EpiCO2 to ConvEpi access. METHODS: All patients at a high-volume center undergoing Epi access between January 2021 and December 2023 were included and grouped according to ConvEpi or EpiCO2 approach. Access technique was according to the discretion of the operator. RESULTS: Epi access was attempted in 153 cases by 17 different operators (80 ConvEpi vs 73 EpiCO2). There was no difference in success rate whether the ConvEpi or EpiCO2 approach was used (76 [95%] cases vs 67 [91.8%] cases; P = 0.4). Total Epi access time was shorter in the ConvEpi group compared with the EpiCO2 group (16.3 ± 11.6 minutes vs 26.9 ± 12.7 minutes; P < 0.001), though the total procedure duration was similar. Major Epi access-related complications occurred in only the ConvEpi group (6 [7.5%] ConvEpi vs 0 [0%] EpiCo2; P = 0.02). Bleeding ≥80 mL was more frequently observed following ConvEpi access (14 [17.5%] cases vs 4 [5.5%] cases; P = 0.02). After adjusting for age, repeat Epi access, and antithrombotic therapy, EpiCO2 was associated with a reduction in bleeding ≥80 mL (OR: 0.27; 95% CI: 0.08-0.89; P = 0.03). CONCLUSIONS: EpiCO2 access is associated with lower rates of major complication and bleeding when compared with ConvEpi access.

Two-Year Results of Ceramic-on-Ceramic Hip Resurfacing in an International Multicenter Cohort.

BACKGROUND: Hip resurfacing arthroplasty (HRA) is a bone-conserving alternative to total hip arthroplasty. We present the 2-year clinical and radiographic follow-up of a novel ceramic-on-ceramic HRA in an international multicenter cohort. METHODS: Patients undergoing HRA between September 2018 and January 2021 were prospectively included. Patient-reported outcome measures (PROMs) in the form of the Forgotten Joint Score, Hip Disability and Osteoarthritis Outcome Score Jr., Western Ontario and McMaster Universities Arthritis Index, Oxford Hip Score, and University of California, Los Angeles, Activity Score were collected preoperatively, and at 1 and 2 years postoperation. Serial radiographs were assessed for migration, component alignment, evidence of osteolysis or loosening, and heterotopic ossification formation. RESULTS: The study identified 200 patients who reached a minimum 2-year follow-up (mean 3.5 years). Of these, 185 completed PROMs follow-up at 2 years. There was a significant improvement in Hip Disability and Osteoarthritis Outcome Score (P < .001) and Oxford Hip Score (P < .001) between the preoperative, 1-year, and 2-year outcomes. Patients had improved activity scores on the University of California, Los Angeles, Active Score (P < .001), with 45% reporting a return to high-impact activity at 2 years. At 1 and 2 years, the Forgotten Joint Score was not significantly different (P = .38). There was no migration, osteolysis, or loosening of any of the implants. No fractures were reported over the 2-year follow-up, with only 1 patient reporting a sciatic nerve palsy. There were 2 revisions, 1 for unexplained pain at 3 months due to acetabular component malposition and 1 at 33.5 months for acetabular implant failure. CONCLUSIONS: The ceramic-on-ceramic resurfacing at 2 years postoperation demonstrates promising results with satisfactory outcomes in all recorded PROMs. Further long-term data are needed to support the widespread adoption of this prosthesis as an alternative to other HRA bearings.

Current updates for hyperuricemia and gout in age-related macular degeneration.

The escalating prevalence of metabolic syndrome poses a significant public health challenge, particularly among aging populations, with metabolic dysfunctions contributing to pro-inflammatory states. In this review, we delved into the less recognized association between hyperuricemia (HUA), a manifestation of metabolic syndrome and a primary risk factor for gout, and age-related macular degeneration (AMD), a sight-threatening ailment predominantly affecting the elderly. In recent years, inflammation, particularly its involvement in complement pathway dysregulation, has gained prominence in AMD pathophysiology. The contradictory role of uric acid (UA) in intercellular and intracellular environments was discussed, highlighting its antioxidant properties in plasma and its pro-oxidant effects intracellularly. Emerging evidence suggests a potential link between elevated serum uric acid levels and choroid neovascularization in AMD, providing insights into the role of HUA in retinal pathologies. Various pathways, including crystal-induced and non-crystal-induced mechanisms, were proposed to indicate the need for further research into the precise molecular interactions. The implication of HUA in AMD underscores its potential involvement in retinal pathologies, which entails interdisciplinary collaboration for a comprehensive understanding of its impact on retina and related clinical manifestations.

DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes.

OBJECTIVE: Youth-onset type 2 diabetes (T2D) is physiologically distinct from adult-onset, but it is not clear how the two diseases differ at a molecular level. In utero exposure to maternal type 2 diabetes (T2D) is known to be a specific risk factor for youth-onset T2D. DNA methylation (DNAm) changes associated with T2D but which differ between youth- and adult-onset might delineate the impacts of T2D development at different ages and could also determine the contribution of exposure to in utero diabetes. METHODS: We performed an epigenome-wide analysis of DNAm on whole blood from 218 youth with T2D and 77 normoglycemic controls from the iCARE (improving renal Complications in Adolescents with type 2 diabetes through REsearch) cohort. Associations were tested using multiple linear regression models while adjusting for maternal diabetes, sex, age, BMI, smoking status, second-hand smoking exposure, cell-type proportions and genetic ancestry. RESULTS: We identified 3830 differentially methylated sites associated with youth T2D onset, of which 3794 were moderately (adjusted p-value < 0.05 and effect size estimate > 0.01) associated and 36 were strongly (adjusted p-value < 0.05 and effect size estimate > 0.05) associated. A total of 3725 of these sites were not previously reported in the EWAS Atlas as associated with T2D, adult obesity or youth obesity. Moreover, three CpGs associated with youth-onset T2D in the PFKFB3 gene were also associated with maternal T2D exposure (FDR < 0.05 and effect size > 0.01). This is the first study to link PFKFB3 and T2D in youth. CONCLUSION: Our findings support that T2D in youth has different impacts on DNAm than adult-onset, and suggests that changes in DNAm could provide an important link between in utero exposure to maternal diabetes and the onset of T2D.

Pregnancy is linked to faster epigenetic aging in young women.

A central prediction of evolutionary theory is that energy invested into reproduction comes at the expense of somatic maintenance and repair, accelerating biological aging. Supporting this prediction are findings that high fertility among women predicts shorter lifespan and poorer health later in life. However, biological aging is thought to begin before age-related health declines, limiting the applicability of morbidity and mortality for studying the aging process earlier in life. Here, we examine the relationship between reproductive history and biological aging in a sample of young (20 to 22yo) men and women from the Cebu Longitudinal Health and Nutrition Survey, located in the Philippines (n = 1,735). We quantify biological aging using six measures, collectively known as epigenetic clocks, reflecting various facets of cellular aging, health, and mortality risk. In a subset of women, we test whether longitudinal changes in gravidity between young and early-middle adulthood (25 to 31yo) are associated with changes in epigenetic aging during that time. Cross-sectionally, gravidity was associated with all six measures of accelerated epigenetic aging in women (n = 825). Furthermore, longitudinal increases in gravidity were linked to accelerated epigenetic aging in two epigenetic clocks (n = 331). In contrast, the number of pregnancies a man reported fathering was not associated with epigenetic aging among same-aged cohort men (n = 910). These effects were robust to socioecological, environmental, and immunological factors, consistent with the hypothesis that pregnancy accelerates biological aging and that these effects can be detected in young women in a high-fertility context.

A Residual U-Net Neural Network for Seismocardiogram Denoising and Analysis During Physical Activity.

Seismocardiogram (SCG) signals are noninvasively obtained cardiomechanical signals containing important features for cardiovascular health monitoring. However, these signals are prone to contamination by motion noise, which can significantly impact accuracy and robustness of the measurements. A deep learning model based on the U-Net architecture is proposed to recover SCG signals contaminated by motion noise induced by walking. The model performance was evaluated through qualitative visualization, as well as quantitative analyses. Quantitative analyses included distance-based comparisons before and after applying our model. Analyses also included assessments of the model's efficacy in improving the performance of downstream tasks related to health parameter estimation during walking. Experimental findings revealed that the denoising model improved similarity to clean signals by approximately 90%. The performance of the model in enhancing heart rate estimation demonstrated a mean absolute error of 1.21 BPM and a root-mean-squared error (RMSE) of 1.97 BPM during walking after denoising with 9.16 BPM and 10.38 BPM improvements, respectively, compared to without denoising. Furthermore, the RMSEs of aortic opening and aortic closing time estimation after denoising for one dataset with catheter ground truth were 7.29 ms and 19.71 ms during walking, respectively, with 50.33 ms and 51.91 ms RMSE improvements compared to without denoising. And for another dataset with ICG-derived PEP ground truth, the RMSE of aortic opening time estimation after denoising was 10.21 ms during walking, with 38.74 ms RMSE improvement compared to without denoising. The proposed model attenuates motion noise from corrupted SCG signals while preserving cardiac information. This development paves the way for improved ambulatory cardiac health monitoring using wearable accelerometers during daily activities.

Transepithelial phototherapeutic keratectomy for treatment-resistant recurrent corneal erosion syndrome.

BACKGROUND: To evaluate the efficacy and safety of trans-epithelial phototherapeutic keratectomy (TE-PTK) as a treatment for recurrent corneal erosion syndrome (RCES) in patients with symptoms refractory to conventional treatments. METHODS: All patients who received TE-PTK treatment for RCES had failed 3 or more conventional treatments and were reviewed, and if met criteria, approved by healthcare workers of the British Columbia public health authority (Medical Services Plan (MSP). A retrospective chart review and telephone survey were conducted at the Pacific Laser Eye Centre (PLEC). Exclusion criteria were ocular co-morbidities potentially affecting treatment efficacy. RESULTS: This study included 593 eyes of 555 patients (46.2% male; 50.9 ± 14.2 years old) who underwent TE-PTK. The leading identified causes of RCES were trauma (45.7%) and anterior basement membrane dystrophy (44.2%). The most common pre-PTK interventions were ocular lubricants (90.9%), hypertonic solutions (77.9%), and bandage contact lenses (50.9%). Thirty-six eyes had undergone surgical interventions such as stromal puncture, epithelial debridement, or diamond burr polishing. Post-PTK, 78% of patients did not require any subsequent therapies and 20% required ongoing drops. Six patients (1.1%) reported no symptom improvement and required repeat TE-PTK for ongoing RCES symptoms after initial TE-PTK. All 6 eyes were successfully retreated with TE-PTK (average time to retreatment was 11.3 ± 14.9 months). There was no significant difference in best corrected visual acuity pre- vs. post-operatively. The mean post-operative follow-up was 60.5 months (range: 5-127 months). CONCLUSION: TE-PTK has a good efficacy and safety profile for treatment-resistant RCES. The third-party public health-reviewed nature of this study, the low recurrence rate of RCES, and the low PTK retreatment rate suggest that TE-PTK might be considered for wider use in the management of RCES.

Class 1C Antiarrhythmics for Premature Ventricular Complex Suppression in Nonischemic Cardiomyopathy With Implantable Cardioverter-Defibrillators.

BACKGROUND: Premature ventricular complexes (PVCs) are common and associated with worse outcomes in patients with heart failure. Class 1C antiarrhythmic drugs (AADs) effectively suppress PVCs, but guidelines currently restrict their use in structural heart disease. OBJECTIVES: This study aimed to assess the safety and efficacy of class 1C AADs in patients with nonischemic cardiomyopathy (NICM) and implantable cardioverter-defibrillators (ICDs). METHODS: All patients with NICM and an ICD treated with flecainide or propafenone at the Hospital of the University of Pennsylvania between 2014 and 2022 were identified. PVC burden, left ventricular ejection fraction (LVEF), and biventricular pacing percentage were compared before and during class 1C AAD treatment. Safety outcomes included sustained atrial and ventricular arrhythmias, heart failure admissions, and death. RESULTS: We identified 34 patients, 23 receiving flecainide and 11 propafenone. Most patients (62%) had failed other AADs or catheter ablation (68%) prior to class 1C AAD initiation. PVC burden decreased from 20% ± 13% to 6% ± 7% (P < 0.001), LVEF increased from 33% ± 9% to 37% ± 10% (P = 0.01), and biventricular pacing percentage increased from 85% ± 9% to 93% ± 7% (P = 0.01). Sustained ventricular tachycardia (2 vs 9 patients) and admissions for decompensated heart failure (2 vs 3 patients) decreased compared with the 12 months prior to class 1C AAD initiation. CONCLUSIONS: Class 1C AADs effectively suppressed PVCs in patients with NICM and ICDs, leading to increases in LVEF and biventricular pacing percentage. In this limited sample, their use was safe. Larger studies are needed to confirm the safety of this approach.

Combining soft robotics and telerehabilitation for improving motor function after stroke.

Telerehabilitation and robotics, either traditional rigid or soft, have been extensively studied and used to improve hand functionality after a stroke. However, a limited number of devices combined these two technologies to such a level of maturity that was possible to use them at the patients' home, unsupervised. Here we present a novel investigation that demonstrates the feasibility of a system that integrates a soft inflatable robotic glove, a cloud-connected software interface, and a telerehabilitation therapy. Ten chronic moderate-to-severe stroke survivors independently used the system at their home for 4 weeks, following a software-led therapy and being in touch with occupational therapists. Data from the therapy, including automatic assessments by the robot, were available to the occupational therapists in real-time, thanks to the cloud-connected capability of the system. The participants used the system intensively (about five times more movements per session than the standard care) for a total of more than 8 hr of therapy on average. We were able to observe improvements in standard clinical metrics (FMA +3.9 ± 4.0, p < .05, COPM-P + 2.5 ± 1.3, p < .05, COPM-S + 2.6 ± 1.9, p < .05, MAL-AOU +6.6 ± 6.5, p < .05) and range of motion (+88%) at the end of the intervention. Despite being small, these improvements sustained at follow-up, 2 weeks after the end of the therapy. These promising results pave the way toward further investigation for the deployment of combined soft robotic/telerehabilitive systems at-home for autonomous usage for stroke rehabilitation.

Sustained Pericarditis Recurrence Risk Reduction With Long-Term Rilonacept.

BACKGROUND: Rilonacept, a once-weekly interleukin-1 alpha and beta cytokine trap, reduced pericarditis recurrence in the phase 3 study, RHAPSODY (Rilonacept Inhibition of Interleukin-1 Alpha and Beta for Recurrent Pericarditis: A Pivotal Symptomatology and Outcomes Study). The RHAPSODY long-term extension further explored recurrent pericarditis natural history and treatment duration decision-making during 24 additional months of open-label rilonacept treatment. METHODS AND RESULTS: Seventy-four patients commenced the long-term extension, with a median (maximum) total rilonacept duration of 22 (35) months. Individually, 18 months after the most proximal pericarditis recurrence, investigators decided to continue rilonacept on study, suspend rilonacept for off-treatment observation (rescue allowed), or discontinue the study. The annualized incidence of pericarditis recurrence on rilonacept up to the 18-month decision milestone was 0.04 events/patient-year versus 4.4 events/patient-year prestudy while on oral therapies. At the 18-month decision milestone, 64% (33/52) continued rilonacept, 15% (8/52) suspended rilonacept for observation, and 21% (11/52) discontinued the study. Among the 33 patients (1/33; 3.0%) continuing rilonacept (median time to recurrence could not be estimated due to too few events), a single recurrence occurred 4 weeks after a treatment interruption. Among patients suspending rilonacept, 75% (6/8) experienced recurrence (median time to recurrence, 11.8 weeks [95% CI, 3.7 weeks to not estimable]). There was a 98% reduction in risk of pericarditis recurrence among patients continuing rilonacept treatment after the 18-month decision milestone versus those suspending treatment for observation (hazard ratio, 0.02; P<0.0001). CONCLUSIONS: In the RHAPSODY long-term extension, continued rilonacept treatment resulted in continued response; treatment suspension at the 18-month decision milestone was associated with pericarditis recurrence. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03737110.

Absence of the Klotho Function Causes Cornea Degeneration with Specific Features Resembling Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy.

The Klotho loss-of-function mutation is known to cause accelerated senescence in many organs, but its effects on the cornea have not been published. The present study aims to investigate the effects of the Klotho null mutation on cornea degeneration and to characterize the pathological features. Mouse corneas of Klotho homozygous, heterozygous, and wild-type mice at 8 weeks of age for both genders were subject to pathological and immunohistological examinations. The results show an irregular topography on the corneal surface with a Klotho null mutation. Histological examinations revealed a reduced corneal epithelial cell density, endothelial cell-shedding, and decreased cornea stromal layer thickness in the absence of the Klotho function. Furthermore, guttae formation and the desquamation of wing cells were significantly increased, which was comparable to the characteristics of Fuchs endothelial corneal dystrophy and bullous keratopathy. The mechanism analysis showed multi-fold abnormalities, including oxidative stress-induced cornea epithelium apoptosis and inflammation, extracellular matrix remodeling in the stroma, and a disruption of epithelial repair, presumably through the epithelial-mesenchymal transition. In conclusion, cornea degeneration was observed in the Klotho loss-of-function mutant mice. These pathological features support the use of Klotho mutant mice for investigating age-related cornea anomalies, including Fuchs endothelial corneal dystrophy, bullous keratopathy, and dry eye diseases.

Gluteal Tendinopathy Is Associated With Lower Patient-Reported Outcome Measures in Total Hip Arthroplasty With a Posterior Approach: A Prospective Cohort Study of 1,538 Patients.

BACKGROUND: Gluteal tendinopathy (GT) is found in 20 to 25% of patients undergoing total hip arthroplasty (THA). Despite this, there is a scarcity of literature assessing the association between GT and THA outcomes. The aim of this study was to evaluate whether intraoperative diagnosis of GT negatively affected postoperative outcomes. METHODS: Consecutive patients undergoing primary THA for osteoarthritis via a posterior approach over 5 years were recruited in a prospective study. Gluteal tendinopathy was assessed and graded at the time of surgery, but not repaired. A total of 1,538 (93%) completed the patient-reported outcome measures (PROMs) at 1 year after surgery and were included in the analysis. The PROMs included the Oxford Hip Score (OHS), Hip Disability and Osteoarthritis Outcome Score Joint Replacement (HOOS JR), and EuroQol 5-Dimension, and were collected preoperatively and one year after THA. RESULTS: The gluteal tendons were graded as 4 distinct grades: normal (n = 1,023, 66%), tendinopathy but no tear (n = 337, 22%), partial thickness tear (n = 131, 9%), and full thickness tear (n = 47, 3%). The occurrence of GT was associated with age, body mass index, and sex. There was no significant difference in baseline OHS or HOOS JR scores according to GT grade. As GT grade increased, lower median 1-year OHS (P = .001) and HOOS JR (P = .016) were observed. This association was confirmed by linear regression analysis with 1-year OHS (B = 0.5, 95% CI = -0.9 to -0.1, P = .011) when controlled for age and sex. CONCLUSIONS: Gluteal tendinopathy was commonly observed and was associated with inferior 1-year PROMs in patients undergoing THA via posterior approach. Increasing degree of tendinopathy was a negative prognostic factor for outcomes and patient satisfaction. LEVEL OF EVIDENCE: Level 2 (High quality prospective cohort study).

Transforming modeling in neurorehabilitation: clinical insights for personalized rehabilitation.

Practicing clinicians in neurorehabilitation continue to lack a systematic evidence base to personalize rehabilitation therapies to individual patients and thereby maximize outcomes. Computational modeling- collecting, analyzing, and modeling neurorehabilitation data- holds great promise. A key question is how can computational modeling contribute to the evidence base for personalized rehabilitation? As representatives of the clinicians and clinician-scientists who attended the 2023 NSF DARE conference at USC, here we offer our perspectives and discussion on this topic. Our overarching thesis is that clinical insight should inform all steps of modeling, from construction to output, in neurorehabilitation and that this process requires close collaboration between researchers and the clinical community. We start with two clinical case examples focused on motor rehabilitation after stroke which provide context to the heterogeneity of neurologic injury, the complexity of post-acute neurologic care, the neuroscience of recovery, and the current state of outcome assessment in rehabilitation clinical care. Do we provide different therapies to these two different patients to maximize outcomes? Asking this question leads to a corollary: how do we build the evidence base to support the use of different therapies for individual patients? We discuss seven points critical to clinical translation of computational modeling research in neurorehabilitation- (i) clinical endpoints, (ii) hypothesis- versus data-driven models, (iii) biological processes, (iv) contextualizing outcome measures, (v) clinical collaboration for device translation, (vi) modeling in the real world and (vii) clinical touchpoints across all stages of research. We conclude with our views on key avenues for future investment (clinical-research collaboration, new educational pathways, interdisciplinary engagement) to enable maximal translational value of computational modeling research in neurorehabilitation.

NSF DARE-transforming modeling in neurorehabilitation: a patient-in-the-loop framework.

In 2023, the National Science Foundation (NSF) and the National Institute of Health (NIH) brought together engineers, scientists, and clinicians by sponsoring a conference on computational modelling in neurorehabiilitation. To facilitate multidisciplinary collaborations and improve patient care, in this perspective piece we identify where and how computational modelling can support neurorehabilitation. To address the where, we developed a patient-in-the-loop framework that uses multiple and/or continual measurements to update diagnostic and treatment model parameters, treatment type, and treatment prescription, with the goal of maximizing clinically-relevant functional outcomes. This patient-in-the-loop framework has several key features: (i) it includes diagnostic and treatment models, (ii) it is clinically-grounded with the International Classification of Functioning, Disability and Health (ICF) and patient involvement, (iii) it uses multiple or continual data measurements over time, and (iv) it is applicable to a range of neurological and neurodevelopmental conditions. To address the how, we identify state-of-the-art and highlight promising avenues of future research across the realms of sensorimotor adaptation, neuroplasticity, musculoskeletal, and sensory & pain computational modelling. We also discuss both the importance of and how to perform model validation, as well as challenges to overcome when implementing computational models within a clinical setting. The patient-in-the-loop approach offers a unifying framework to guide multidisciplinary collaboration between computational and clinical stakeholders in the field of neurorehabilitation.

Exertional Angina in a Young Woman Caused by Large Cardiac Paraganglioma.

Coronary ischemia is uncommon in patients in their third decade of life. We present a 21-year-old woman with classic exertional angina secondary to a large cardiac paraganglioma. Cardiac paragangliomas are rare extra-adrenal neuroendocrine tumors that arise from chromaffin cells. Cardiac symptoms can be related to catecholamine excess or anatomical compression.

Use of therapeutic plasma exchange to remove lipoprotein X in a patient with vanishing bile duct syndrome presenting with cholestasis, pseudohyponatremia, and hypercholesterolemia: A case report and review of literature.

INTRODUCTION: Lipoprotein X (Lp-X) is an abnormal lipoprotein found in multiple disease conditions, including liver dysfunction and cholestasis. High Lp-X concentrations can interfere with some laboratory testing that may result in spurious results. The detection of Lp-X can be challenging, and there is currently a lack of consensus regarding the management of Lp-X other than treating the underlying disease. CASE PRESENTATION: A 42-year-old female with Hodgkin's lymphoma treated with dexamethasone, high dose cytarabine and cisplatin and vanishing bile duct syndrome confirmed by liver biopsy presented with cholestasis, pseudohyponatremia (sodium, 113 mmol/L; reference range 136-146 mmL/L; serum osmolality, 303 mOsm/kg), and hypercholesterolemia (> 2800 mg/dL, reference range < 200 mg/dL). Lp-X was confirmed by lipoprotein electrophoresis (EP). Although she did not manifest any specific signs or symptoms, therapeutic plasma exchange (TPE) was initiated based on laboratory findings of extreme hypercholesterolemia, spuriously abnormal serum sodium, and HDL values, and the potential for short- and long-term sequelae such as hyperviscosity syndrome, xanthoma, and neuropathy. During the hospitalization, she was treated with four 1.0 plasma volume TPE over 6 days using 5% albumin for replacement fluid. After the first TPE, total cholesterol (TC) decreased to 383 mg/dL and sodium was measured at 131 mmol/L. The patient was transitioned into outpatient maintenance TPE to eliminate the potential of Lp-X reappearance while the underlying disease was treated. Serial follow-up laboratory testing with lipoprotein EP showed the disappearance of Lp-X after nine TPEs over a 10-week period. LITERATURE REVIEW: There are seven and four case reports of Lp-X treated with TPE and lipoprotein apheresis (LA), respectively. While all previous case reports showed a reduction in TC levels, none had monitored the disappearance of Lp-X after completing a course of therapeutic apheresis. CONCLUSION: Clinicians should have a heightened suspicion for the presence of abnormal Lp-X in patients with cholestasis, hypercholesterolemia, and pseudohyponatremia. Once Lp-X is confirmed by lipoprotein EP, TPE should be initiated to reduce TC level and remove abnormal Lp-X. Most LA techniques are not expected to be beneficial since Lp-X lacks apolipoprotein B. Therefore, we suggest that inpatient course of TPE be performed every other day until serum sodium, TC and HDL levels become normalized. Outpatient maintenance TPE may also be considered to keep Lp-X levels low while the underlying disease is treated. Serum sodium, TC, and HDL levels should be monitored while on maintenance TPE.

Evaluation of organized atrial arrhythmias after cryptogenic stroke.

Background: Long-term rhythm monitoring to detect atrial fibrillation (AF) following a cryptogenic stroke (CS) is well established. However, the burden of organized atrial arrhythmias in this population is not well defined. Objective: The purpose of this study was to assess the incidence and risk factors for organized atrial arrhythmias in patients with CS. Methods: We evaluated all patients with CS who received an insertable cardiac monitor (ICM) between October 2014 and April 2020. All ICM transmissions categorized as AF, tachycardia, or bradycardia were reviewed. We evaluated the time to detection of organized AF and the combination of either organized atrial arrhythmia or AF. Results: A total of 195 CS patients with ICMs were included (51% men; mean age 66 ± 12 years; mean CHA2DS2-VASC score 4.6). Over mean follow-up of 18.9 ± 11.2 months, organized atrial arrhythmias lasting ≥30 seconds were detected in 45 patients (23%), of whom 62% did not have AF. Seventeen patients had both organized atrial arrhythmia and AF, and another 21 patients had AF only. Compared to those with normal left atrial size, patients with left atrial enlargement had a higher adjusted risk for development of atrial arrhythmias (mild left atrial enlargement: hazard ratio 1.99; 95% confidence interval 1.06-3.75; moderate/severe left atrial enlargement: hazard ratio 3.06; 95% confidence interval 1.58-5.92). Conclusion: Organized atrial arrhythmias lasting ≥30 seconds are detected in nearly one-fourth of CS patients. Two-thirds of these patients did not have AF. Further studies are required to evaluate the impact of organized atrial arrhythmias on recurrent stroke risk.

A Comparison of Normalization Techniques for Individual Baseline-Free Estimation of Absolute Hypovolemic Status Using a Porcine Model.

Hypovolemic shock is one of the leading causes of death in the military. The current methods of assessing hypovolemia in field settings rely on a clinician assessment of vital signs, which is an unreliable assessment of hypovolemia severity. These methods often detect hypovolemia when interventional methods are ineffective. Therefore, there is a need to develop real-time sensing methods for the early detection of hypovolemia. Previously, our group developed a random-forest model that successfully estimated absolute blood-volume status (ABVS) from noninvasive wearable sensor data for a porcine model (n = 6). However, this model required normalizing ABVS data using individual baseline data, which may not be present in crisis situations where a wearable sensor might be placed on a patient by the attending clinician. We address this barrier by examining seven individual baseline-free normalization techniques. Using a feature-specific global mean from the ABVS and an external dataset for normalization demonstrated similar performance metrics compared to no normalization (normalization: R2 = 0.82 ± 0.025|0.80 ± 0.032, AUC = 0.86 ± 5.5 × 10-3|0.86 ± 0.013, RMSE = 28.30 ± 0.63%|27.68 ± 0.80%; no normalization: R2 = 0.81 ± 0.045, AUC = 0.86 ± 8.9 × 10-3, RMSE = 28.89 ± 0.84%). This demonstrates that normalization may not be required and develops a foundation for individual baseline-free ABVS prediction.