Large Study Research Articles

Reduction in Synovitis Following Genicular Artery Embolization in Knee Osteoarthritis: A Prospective Ultrasound and MRI Study

Background/Objectives: Genicular artery embolization (GAE) has demonstrated potential as a treatment for knee osteoarthritis by targeting inflammation and pain, although current evidence remains limited. This study used imaging biomarkers to objectively assess synovitis and possible ischemic complications following GAE. Methods: This was a prospective, single-center trial including participants with mild-to-moderate knee osteoarthritis. Ultrasound, contrast-enhanced (CE), and non-CE-MRI were performed two days before and one and six months after GAE. Ultrasound biomarkers included synovial hypertrophy, effusion, and Doppler activity. A combined effusion-synovitis score was assessed on non-CE-MRI, while CE-MRI allowed differentiation between synovium and effusion and was used to calculate whole-joint and local synovitis scores. The post-GAE MRIs were reviewed for ischemic complications.Results: Seventeen participants (aged 43–71) were treated. Significant reductions were observed in ultrasound-assessed synovial hypertrophy and Doppler activity, as well as in CE-MRI local and whole-joint synovitis scores. While reductions in effusion were noted in both ultrasound and MRI, these changes did not reach statistical significance. At one month, MRI revealed three cases of nonspecific osteonecrosis-like areas, which resolved completely by six months.Conclusions: This study demonstrated a reduction in synovitis and no permanent ischemic complication following GAE in knee osteoarthritis. Larger studies with longer follow-up are needed to confirm the long-term efficacy and safety of the procedure.

Benefit-finding in children with advanced cancer and their parents.

Although pediatric cancer often causes significant stress for families, most childhood cancer survivors are resilient and do not exhibit severe or lasting psychopathology. Research demonstrates some survivors may report benefit-finding or positive outcomes following this stressful life event. However, considerably less research has included families of children who are unlikely to survive their illness. Thus, this study investigated benefit-finding among parents and their children with advanced cancer, as well as associated demographic and medical factors. Families (N = 72) of children with advanced cancer (ages 5-25) were recruited from a large pediatric hospital. Advanced cancer was defined as relapsed or refractory disease, an estimated prognosis of <60%, or referral to end-of-life care. Participants completed a demographic survey and the Benefit Finding Scale at enrollment. Children, mothers, and fathers reported moderate to high benefit-finding scores. Correlations between family members were weak and non-significant. Children reported significantly higher benefit-finding than fathers. Demographic and medical factors were not associated with benefit-finding in children, mothers, or fathers. Families of children with advanced cancer reported moderate to high benefit-finding regardless of background or medical factors. Children identified benefits of their cancer experience independent of the experiences of their mothers and fathers. Larger studies should continue to examine factors associated with positive and negative outcomes in the context of childhood cancer to inform interventions.

Exploring feasibility of fNIRS to assess delayed inhibition effect of prefrontal cortex for acute stress by acupuncture on GV20: a pilot study

IntroductionAcupuncture on the acupuncture point GV20 has been considered effective for managing psychoneurological disorders since ancient times, and GV20 is now regularly used to treat stress-related diseases (SRDs), including psychoneurological disorders. Although reports indicating that acupuncture stimulation of GV20 alone regulates cerebral blood flow (CBF) in brain regions associated with SRDs have been scattered, from the perspective of the need for earlier action, the effects on subjective stress as self-reported in the stress state of healthy individuals and CBF changes in related prefrontal cortex (PFC) subregions, which is based as underlying mechanism, remain unclear. Therefore, there is a need to explore effective methods for analyzing such effects.MethodsMultiple consecutive mental arithmetic tasks were performed to induce sufficient stress in healthy university students. Real acupuncture or sham acupuncture was performed on GV20, and subjective stress and CBF changes in PFC subregions were observed before and after acupuncture using functional near-infrared spectroscopy, which were analyzed based on the general linear model method and correlation analysis.ResultsSubjective stress was suppressed and recovered significantly faster in the true acupuncture group than in the sham acupuncture group. Furthermore, significant negative correlations were found between subjective stress and CBF in several PFC subregions during and after the tasks, with more correlated regions on the left side than on the right side of the PFC. Among them, the CBF of the left ventrolateral PFC (vl-PFC) was suggested to be maintained in the true acupuncture group under repeated tasks load, which was inferred to be correlated with delayed decreases in subjective stress after acupuncture.DiscussionThis pilot study showed that fNIRS is feasible for assessing delayed PFC inhibition in acute stress by acupuncture on GV20. Acupuncture treatment on GV20 resulted in early suppression of subjective stress and early recovery. The neuroscientific rationale for this finding may lie in its effect on maintaining CBF in the left vl-PFC related to delayed inhibition of subjective stress, and would make it reasonable to apply acupuncture to GV20 in healthy individuals. Larger studies are needed to corroborate these findings and obtain reliable conclusions.

Piloting a Diagnostic Foot and Ankle Fracture Sonographic Algorithm with Rural and Adolescent Patients

Background: Foot and ankle injuries are a common presenting complaint to the Emergency Department (ED) and are often assessed with plain radiography. Rural environments may not have access to radiography mandating the referral or transfer patients to regional centers for definitive diagnosis. The Ottawa Foot and Ankle Rules (OFAR) is a clinical decision rule that can assist in ruling out fractures. Point of care ultrasound (POCUS) can augment this decision rule. The objective of this study was to assess both the feasibility and test characteristics of a previously described POCUS augmented clinical assessment, OFAR-POCUS, for adolescent and adult patients with foot and ankle pain in a rural environment. Methods: This was a prospective cohort study from June to August 2022 including patients with chief complaint of foot or ankle injury presenting to a rural clinic. Patients were included if they had positive finding(s) on the OFAR Test and required radiographic imaging. Patients were excluded if they did not consent, speak English, were unable to be scanned, had obvious joint deformities, had altered mental status, were not physiologically stable, had other injuries preventing sonography, were pregnant, or had previous injury with internal fixation, osteomyelitis, or rheumatoid arthritis. POCUS was performed before transport for radiography. POCUS examiners were POCUS novices who underwent a one and a half to two-hour, standardized foot and ankle POCUS training session. All POCUS studies were reviewed by two emergency medicine ultrasound fellowship trained faculty for quality assurance. Standard test characteristics were calculated for bedside clinician and expert POCUS interpretations compared to the radiographic control. Results: Thirteen POCUS examiners performed exams on 20 patients included in analysis; four patients had fractures on radiograph (20%). The bedside clinician POCUS interpretation had sensitivity (SN) = 100% (95% Cl, 40%-100%), specificity (SP) =94% (95% Cl, 70%-100%), and negative likelihood ratio (-LR) = 16.00 (95% Cl, 2.40-106.73). Expert POCUS interpretation had SN=75% (95% Cl, 19%-99%), SP=75% (95% Cl, 48%-93%), and -LR=0.33 (95% Cl, 0.06-1.86). Conclusion: A POCUS enhanced clinical strategy for clinically significant foot and ankle fractures in adolescent and adult patients in a rural setting is feasible. Larger studies are required to further characterize test characteristics and use of foot and ankle POCUS where plain radiography is unavailable.

The impact of CYP2D6 on donepezil concentration and its lack of effect on the treatment response and adverse effect in Korean patients with Alzheimer's disease.

Donepezil, an acetylcholinesterase inhibitor, is widely used for managing the symptoms of Alzheimer's disease (AD), yet its clinical response varies widely among individuals. This study aims to investigate the influence of CYP2D6 genetic variants on donepezil concentration, treatment response, and adverse effects in Korean patients with AD dementia. We conducted a longitudinal study involving 76 patients receiving either 5 mg or 10 mg of donepezil. Genetic testing identified 9 CYP2D6 alleles, categorizing patients by metabolizing abilities. Blood sampling for plasma concentrations of donepezil were performed at steady-state. Mini-Mental State Examination (MMSE) were conducted at 12, 24 and 36 months after the initiation of treatment. Adverse events were collected throughout the study period. Donepezil plasma concentrations differed significantly among metabolizer statuses (mean 56.8 ± 27.1 ng/ml in normal metabolizers vs. 69.6 ± 30.1 ng/ml in intermediate metabolizers, p = 0.042), but these differences did not affect cognitive function over three years as assessed by MMSE. Additionally, there was no significant correlation between donepezil plasma concentration and adverse events. Our study is the first to elucidate the associations between CYP2D6 genotype and the concentration, clinical response or adverse events of donepezil in Korean patients with AD dementia. Larger studies are necessary to fully understand the impact of CYP2D6 genetic variants on therapeutic outcomes with donepezil.

Internet-based treatment for provoked vulvodynia: factors associated with treatment outcomes

Abstract Introduction Previous research has indicated that internet-based Acceptance and Commitment Therapy (ACT) can reduce pain during intercourse and increase pain acceptance in individuals with provoked vulvodynia, but the factors associated with treatment outcomes remain unknown. Aim This study aimed to investigate factors associated with changes in pain acceptance following an internet treatment based on ACT. Methods This exploratory study used data from the EMBLA study, a multicenter randomized controlled trial that investigated the effects of internet-based ACT for provoked vulvodynia. The examined factors included sociodemographics, medical history, pain and sexual behavior, and psychosocial characteristics. Linear regression analysis was employed to assess the association of these factors with pain acceptance, including interaction effects. Results were adjusted for multiple testing using Bonferroni correction. Outcomes The outcome measure was pain acceptance assessed on the scale Chronic Pain Questionnaire–Revised, which comprises two sub-scales: activity engagement and pain willingness. Results Before adjustment, greater improvement in overall pain acceptance and the subscale activity engagement was seen participants in the intervention group who had a history of physical violence or sexual assault. Increased time spent on the treatment platform per week was also associated with greater improvement in pain acceptance. Participants who reported gastrointestinal problems before the internet-based treatment showed better treatment outcomes in activity engagement. Previous contact with a psychologist or counselor was associated with less improvement in activity engagement. The intervention was less effective on the subscale pain willingness with increased age and for those reporting urinary problems. No associations remained statistically significant after adjustment for multiple testing. Clinical implications Previous exposure to violence and sexual assault, concomitant gastrointestinal or urinary problems, and adherence to treatment should be further investigated in larger studies on factors associated with treatment outcomes after internet treatment based on ACT, especially regarding pain. Strengths and limitations This was a novel and exploratory study and provides information for researchers in future investigations of how individual characteristics may influence treatment outcomes. A range of variables were explored in the models, underscoring the importance of future studies to strengthen the findings. One limitation concerns the sample size, which was fairly small considering the nature of the study. Conclusion After correcting for multiple testing, no factors were found to be statistically associated with changes in pain acceptance after the treatment.

Recommender systems use in weight management mHealth interventions: A scoping review.

The use of recommender systems in mobile health apps for weight control has grown, but user app uptake and engagement remain limited. The objective of our scoping review was to explore the influence of recommender systems on mHealth app user engagement, identify the theoretical frameworks that have been applied on digital health interventions designed for weight management, and examine the key aspects that support tailoring user engagement through recommender systems. Based on existing literature, we identified 13 articles on recommender systems for weight management. Themes emerged, including theoretical underpinnings, authors' domain knowledge, user motivation, and design. Most studies used constructs from the social cognitive theory. We found inconsistencies between authors' domain knowledge and the intervention's content, with few professionals from the health and psychology fields. Only 46% of articles measured user engagement, whereas gamification and tailored messages were common app features. Despite some positive weight change results, more attention is needed toward implementing behavior theory and other strategies to promote app user engagement. Future studies should more accurately measure user motivation and identify the best features and behavioral constructs to increase app user interaction. Larger studies with a more diverse population are needed to generalize findings and evaluate weight loss maintenance and physical activity habits among users of recommender system.

Pulpitis tendency in teeth with vital pulp restored with composite resins: a cross-sectional retrospective study

Background: This study evaluates pulpitis tendency in vital teeth restored with composite resin after at least one year, focusing on the effect of cavity depth and the use of a base material on pulp status. Methods: A retrospective analysis was conducted on 212 patients with one tooth restored by dental senior students. At the follow-up, periapical and bitewing radiographs, cold tests, percussion, and palpation were performed. Cavity depth was measured from bitewing radiographs, and the periapical index (PAI) was recorded. The restored teeth were compared with contralateral sound teeth to assess the impact of the resin on pulp tissue. Results: Composite resin restorations significantly affected pulp status compared to intact teeth (p=0.002). Five out of 212 teeth became necrotic, and four developed symptomatic irreversible pulpitis (SIP). Four necrotic cases occurred in cavities deeper than 3.60 mm, and all SIP cases were associated with cavities deeper than 3.10 mm. Cavity depth was a significant predictor of adverse pulpal outcomes. However, using calcium hydroxide as a base did not significantly affect pulp health. Conclusions: The study concludes that composite resin restorations, mainly in deep cavities, can negatively impact pulp vitality. Cavity depth is a key factor in the risk of pulp necrosis and SIP, while calcium hydroxide base did not reduce pulpitis incidence. Larger studies with longer follow-up periods are recommended to confirm these findings and explore potential protective factors.

The New Era of mRNA Vaccines: The Success of the Covid-19 Vaccines and the Safety Concerns in Adolescents

Abstract A remarkable scientific achievement during the Covid pandemic is the rapid development and deployment of the mRNA vaccines which played a crucial role in reducing the Covid-related morbidity and mortality. The first-time safe use of the mRNA vaccine platform in humans opened up a new era in vaccinology. In the near future, the mRNA vaccine platform is likely to be used for other diseases as well. Though the Covid mRNA vaccine has been found to be safe in children, a matter of concern is the rare adverse event myocarditis, which was mostly observed among male adolescents. In this setting, we briefly discuss mRNA vaccine-related myocarditis and suggest that the safety concerns need to be alleviated by larger studies with long-term follow-up. We also stress the need for the generation of safety data from children in lower- and middle-income countries as there is limited experience with mRNA vaccines in such settings. The underlying mechanisms need to be understood well as the mRNA vaccine platform holds enormous promise for the future development of vaccines for several diseases.

Abstract 4141448: Evaluation of cardiac amyloidosis with cardiac MRI and association with endomyocardial biopsy findings

Introduction: Late gadolinium enhancement (LGE) observed on cardiac magnetic resonance imaging (CMR) has emerged as a potential indicator of myocardial involvement in cardiac amyloidosis (CA). However, discerning which LGE patterns in amyloidosis distinguish it from other cardiomyopathies remains unclear. This study aims to compare LGE characteristics in a predominantly African American cohort who underwent endomyocardial biopsies. Despite advancements in cardiac imaging techniques, the endomyocardial biopsy remains the gold standard for amyloidosis diagnosis. Insights garnered from this analysis could enhance diagnostic precision and facilitate earlier detection. Methods: In this retrospective study at MedStar Union Memorial Hospital in Baltimore, MD, patients who underwent both endomyocardial biopsy and CMR were included. The study compared individuals with biopsy-proven amyloidosis (both AL and ATTR) to those with negative biopsy results. LGE patterns were selected based on their frequent use in CMR interpretation. Statistical analysis employed Pearson chi-square and t-tests. Results: The cohort comprised 42 patients who underwent biopsy, with 13 patients (31%) with positive biopsy results. Among them, 24 were men (57%), and 81% identified as African American. Demographic, anthropomorphic, and objective clinical findings are detailed in Table 1. The average age of the cohort was 68 years, with those with biopsy-proven amyloidosis significantly older (75 vs. 61 years, p = 0.002). Although the biopsy-positive group exhibited a lower absolute NT-pro-BNP, the difference was not statistically significant. The most prevalent LGE patterns among the biopsy-positive group were diffuse (62%) and basal (31%). Notably, 69% of biopsy-positive patients exhibited an LGE pattern described as infiltrative. However, 38% of the biopsy-negative group also manifested infiltrative patterns on LGE, a difference not statistically significant compared to the biopsy-positive group. The positive predictive value of an infiltrative LGE pattern was low (45%). Conclusion: This study compares CMR LGE patterns in biopsy proven CA. Despite findings of an infiltrative LGE pattern on CMR, when using endomyocardial biopsy as the gold standard, the positive predictive value of LGE in differentiating CA patients was low. Further research and larger studies are warranted to explore additional imaging modalities or biomarkers that may complement or refine the diagnostic algorithm for CA.

Abstract Su205: Using Emergency Medical Services Monitors for Cardiac Arrest Patients in the Emergency Department is Associated with Faster Initial Rhythm Analysis and Defibrillation

Introduction: The 2020 American Heart Association guidelines for Cardiopulmonary Resuscitation (CPR) emphasizes the importance of high-quality CPR and early defibrillation in improving cardiac arrest (CA) survival. Using our emergency department (ED) CA video review registry, we can capture metrics to reliably assess the effectiveness of different approaches to CA management. Goals/Hypothesis: We propose that emergency medical services (EMS) pads and defibrillators should be used to initially analyze cardiac rhythm in the ED. We hypothesize that this “EMS Equipment” approach is associated with shorter time to first ED rhythm detection and defibrillation, higher chest compression fraction (CCF), and improved return of spontaneous circulation (ROSC) rates. Methods: This is a single center, retrospective cohort study using our CA video review registry between 10/03/2018 – 2/20/2024. Atraumatic, out-of-hospital CA patients ≥18 years were included while patients arriving to the ED with ROSC were excluded. The “EMS Equipment” group utilized EMS pads and defibrillators while the “ED Equipment” group utilized ED pads and defibrillators for the first ED rhythm analysis. Wilcoxon rank sum tests were used to assess differences in time to first rhythm check and first defibrillation among the two groups. Chi-square tests were used to assess whether the proportions of patients achieving above median CCF, ROSC, survival to admission and discharge in the two groups were different. Results: A total of 247 patients were included in the analysis with 69 patients in the EMS Equipment group (27.9%) and 178 patients in the ED Equipment group (72.1%). The EMS Equipment group had a shorter median time to first ED rhythm detection (96 vs. 255 seconds, p &lt;0.00001). Among the 63 patients defibrillated in the ED, the EMS Equipment group had a shorter median time to first ED defibrillation (103 vs. 413 seconds, p = 0.0024). There was no significant difference in CCF, ROSC rates, survival to admission or discharge. ROSC was achieved in 36% of cases. Conclusion: In conclusion, initial rhythm analysis with EMS pads and defibrillators was associated with shorter time to initial ED rhythm detection and defibrillation, but not improved CCF, ROSC rates, and survival. Larger studies are needed to verify these exploratory results in more diverse settings.

Accuracy of adult height predictions in patients with axial leg deviations using the Modified and the Abbreviated Modified Fels Knee System.

The accurate estimation of residual growth is crucial for the appropriate timing of growth-guiding surgery in patients with axial leg deviations. Skeletal age methods such as the Modified and the Abbreviated Modified Fels Knee System were developed on historical patient cohorts and the applicability to the modern pediatric population with axial leg deviation has not yet been evaluated. Are both final adult height prediction methods (the Modified Fels Knee System (FKS) and the Abbreviated Modified Fels Knee System (aFKS)) accurate to determine SA and the final adult height on long leg radiographs in patients with axial leg deviations?Which multiplier table shows highest association between predicted and true final adult body height?Do FKS- and aFKS- skeletal age determination methods improve final adult body height prediction accuracy compared to the simple use of chronological age? A single center, retrospective study of 31 patients who underwent temporary hemiepiphysiodesis due to axial leg deviations in the frontal plane between 2018 and 2020 was conducted. Skeletal age at the time of surgery was determined on an anterior-posterior long leg X-ray using FKS and aFKS. Adult height predictions were calculated using three different multiplier tables (Paley et al., Sanders-Greulich and Pyle (SGP), Sanders-Peak Height Velocity (PHV)). The accuracy of adult height prediction was determined by comparing the mean differences and mean absolute differences between predicted and true adult height. All adult height predictions overestimated the true adult height. The final height prediction using aFKS and the SGP multiplier showed the lowest overestimation (mean 3.2 cm, SD 5.5 cm). The PHV multiplier table showed the highest correlation between predicted and true adult height (FHPRE_FKS_PHV: r = 0.913, p < 0.001 and FHPRE_aFKS_PHV: r = 0.862, p < 0.001). The simple use of chronological age at the time of surgical intervention (CASI) with the Paley multiplier table showed the highest median delta absolute values and lowest correlations with true adult height (median 7.4 cm, 25%-75% percentile: 3.5-10.0 cm, r = 0.838, p < 0.001). Nevertheless, no significant differences in delta absolute values between various adult height predictions methods could be shown. Overall, the results of the present retrospective cohort study show that there was no significant improvement in final height prediction accuracy when using the FKS or the aFKS method compared to the simple use of chronological age. One reason could be that patients with varus/valgus malalignment have specific growth characteristics that are not accounted for in multiplier tables or the FKS and aFKS method. Since there is no significant difference in prediction accuracy between the methods, the choice of method may depend on other factors, such as clinical preference or availability of resources. However, due to the small sample size, the study cannot definitively rule out potential differences between the prediction methods, and larger studies are required to validate these findings.

Abstract 4138545: Mitral Valve Replacement is associated with favourable Functional and Clinical Outcome as compared with Restrictive Mitral Annuloplasty in Patients with Severe Ischemic Mitral Regurgitation. A prospective longitudinal analysis

Background: Restrictive mitral annuloplasty (RMA) and chordal-sparing mitral valve replacement (MVR) are common options for treatment of chronic severe ischemic mitral regurgitation. Research question: in patients with severe ischemic mitral regurgitation the most effective surgical approach remains controversial Aim: to test whether MVR provides superior clinical and functional outcomes compared with RMA. Methods: a prospective longitudinal analysis on 187 patients (age: 66 ± 9 year; EF:35 ± 8 %) undergoing MVR or RMA and CABG for severe ischemic mitral regurgitation. Six-minute walking test and echocardiography were performed at preoperative baseline, at 1 year and at a median FU of 5 year (interquartile range: 2.9). Brain natriuretic peptide levels were also obtained. Mitral regurgitation was defined through a comprehensive and integrative approach. Recurrent mitral regurgitation was defined as a vena contracta ≥ 3 mm at follow-up, in patients with no persistent regurgitation at discharge. The primary outcome was a 5-year composite of all-cause mortality and rehospitalization for heart failure. Survival analysis was performed with Kaplan-Meier method. Cox regression analysis was used to verify any independent predictor of composite end-point Results: Baseline preoperative data were similar between the two group. Mitral valve replacement was performed in 49% of patients (n=92) and RMA in 51 % (n=95). At 5 year patients referred to prostheses showed significant improvement in six-minute walking test as compared to RMA (MVR: 290 ± 70 meters vs MRA: 165± 56 meters) (p &gt; 0.01) ( Figure 1 ). The brain natriuretic peptide values did not differ between the two group at 1 year whereas were significantly lower in the MVR group at 5 years (MVR: 135 pg/ml; interquartile range:100 vs RMA: 486 pg/ml; interquartile range: 68 (p&lt;0.01) ( Figure 2 ). At 5 years freedom from all-cause death and rehospitalization for heart failure was higher in the MVR group as compared to RMA (84 ±8.9% vs 61 ±12%, p&lt;0.01) ( Figure 3 ). According to the Cox analysis recurrent mitral regurgitation was found to be a predictor of clinical outcome (HR:5.4, 95% CI:1.3-23.2, p= 0.023). Conclusions: In patients with severe ischemic mitral regurgitation referred for surgery, chordal- sparing MVR and CABG may improve functional capacity, clinical outcome and brain natriuretic peptide levels, compared with RMA and CABG. The impact of these findings remains to be defined by larger studies on longer term

Abstract 4123563: High Prevalence of Unrecognized Actionable Cardiac Arrhythmias in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease

Background: Patients with chronic obstructive pulmonary disease (COPD) are at high risk for developing arrhythmias due to hypoxemia, right heart failure and use of beta-agonists inhalers. Symptoms related to arrhythmias can often be masked or confounded by symptoms related to COPD exacerbation and remain undiagnosed. Objective: To identify the incidence of actionable arrhythmias in patients with no prior cardiology follow-up and moderate–severe COPD with continuous monitoring. Methods: An automatic referral for electrophysiology (EP) consult was generated in patients with moderate-severe COPD if they answered yes to one of the following: palpitations, dizziness, abnormal ECG, near syncope. Upon consultation with EP specialist, implantation of loop reorder was discussed (ILR) with the patient. Patients were then monitored for 12 months via remote monitoring. Actionable arrhythmia was defined the arrhythmia that correlated with symptoms triggered by the patient, necessitated adjustment of medications (including initiation of anticoagulation), catheter ablation and implantation of implantable cardiac defibrillator (ICD) or permanent pacemaker (PPM). Results: Out of 62 patients referred 22 (35.5%) agreed to undergo ILR implantation. Of the 22 (50.0% female, 62 ± 9.5 years) patients implanted with an ILR, 15 (68.2%) had an actionable arrhythmia after a mean follow-up of 2.7± .3 months. These included 14 symptomatic events requiring medication adjustment (10 atrial tachycardias, 4 ventricular events), 7 cases of atrial fibrillation (requiring initiation of anticoagulation in all cases and catheter ablation in 1), 1 case of sinus node dysfunction requiring pacemaker implantation, and 1 episodes of sustained ventricular tachycardia requiring ICD implantation. Conclusion: Continuous monitoring had high yield in diagnosing significant arrhythmic events in patients with moderate-severe COPD. Awareness should be raised about the high arrhythmic risk of this population and the role of continuous monitoring should be sought in larger studies.

Abstract 4120657: A Personal Risk Assessment Device in Patients with Chest Pain

Introduction: Early prehospital chest pain assessment improves acute coronary syndrome (ACS) outcomes and can reduce unnecessary Emergency Room (ER) visits but requires medical personnel and electrocardiographic (ECG) equipment. Objective: To evaluate the feasibility of a personal credit-card sized chest pain self-assessment device (HeartBeam, Santa Clara, CA, USA) in diagnosing ACS. Methods: ACS risk was estimated by serial likelihood ratio analysis of 3 components: pre-existing coronary heart disease (CHD) risk (pre-calculated based on pooled ASCVD equation), chest pain characteristics (interactive proprietary questionnaire), and integrated near-orthogonal 3-lead self-recorded vectorcardiogram (VCG) with optional comparison to baseline using portable handheld HeartBeam recorder. Final ACS risk was graded High/Intermediate/Low by the cloud-based proprietary algorithm. High risk was considered positive for ACS. Results: 184 ER patients with chest pain (Age 57 +/- 7years, 90 Male, 43 (23%) ACS) comprised learning (n=96) and test (n=88) sets. ACS sensitivity was 28/28 (100%) in learning and 15/16 (94%) in test set with specificity of 43% and 42% respectively. In the subset of patients with pain-free portable VCG recorded 9 months later used as a “reverse baseline” (n=110) sensitivity was 17/17 (100%) and 11/12 (92%), specificity 54% and 58% in learning and test set, respectively (p&gt;0.1 with no baseline). Single patient missed by the analysis had known coronary disease with usual anginal episode resulting in minor troponin leak. In “reverse baseline” analysis 41/110 (37%) patients were classified as Low risk compared to 18/184 (10%) without baseline (p&lt;0.001), all negative for ACS. Based on the analysis of CHD risk factors, chest pain characteristics, and 12-lead ECG, a consensus of 3-member ER chest pain unit physicians panel had sensitivity/specificity of 94/54% for the whole and 93/48% for the “reverse baseline” groups (p&gt;0.1 with HeartBeam device). Conclusion: HeartBeam chest pain self-assessment device provides accurate ACS detection comparable to expert ER physicians using 12 lead ECG. The presence of baseline recording reduces the number of false positive results. If confirmed in larger studies, it can be used to facilitate outpatient chest pain assessment and triage by remote physicians and patients themselves.

Abstract 4138281: Relationship of Collagen Metabolism Biomarkers, Left Atrial Fibrosis and Ablation Outcome in Atrial Fibrillation

Introduction: Inflammation and fibrinogenesis in the left atrium are hypothesized to play a major role in the development of atrial fibrillation (AF). We previously showed that collagen metabolism biomarkers (CMB) are significantly elevated in patients with AF compared to healthy controls. Objective: We sought to investigate the relationship between CMB, Left Atrial Fibrosis (LAF) and AF recurrence after ablation. Methods: Patients with AF undergoing ablation evaluation (N= 96) were prospectively enrolled between 2015 – 2020. Plasma samples were collected prior to ablation and analyzed for CMB using commercially available ELISA kits. Sixty-four patients underwent AF ablation and were followed for 6 months for AF recurrence. CMR was performed in 48 patients using cine and 3D high resolution, late gadolinium enhancement imaging on 3T MRI to measure LAF. Patients were classified into 2 groups dichotomized by the median LAF value. Results: Mean age was 60.3 ± 10.3 years, mean BMI 29.7 ± 4.9 kg/m2, mean CHA2DS2-VASc score 1.9 ± 1.4 and 27% were women. Paroxysmal AF was present in 52.5%. The median LAF score was 13.6% (IQR 9.8 – 21.7). High PINP, high CITP and low TIMP-2 were associated with high LAF score (Table 1). High CITP was also associated with recurrence of AF after ablation {4.26 ng/ml (IQR 3.22 - 4.65) vs 3.26 ng/ml (IQR1.92 - 4.25), P = 0.02}. Conclusion: Higher levels of PINP and CITP were significantly associated with higher LAF score in AF patients. TIMP-2 was associated with low LAF. Higher CITP was also associated with AF recurrence after ablation. Further larger studies are needed to better understand the relationship between collagen biomarkers, LA fibrosis and their clinical impact on rhythm control in AF.

Abstract 4132159: Dietary Intake of Niacin and Risk of Cardiovascular Mortality in The Golestan Cohort Study

Introduction: Recent studies have linked niacin metabolism with vascular inflammation and cardiovascular disease (CVD); however, the association is still inconclusive regarding dietary intake, and the findings may not be generalizable to various populations. In this longitudinal study within a Middle Eastern population, we aimed to assess the relationship between dietary intake of B vitamins, including niacin, and the risk of CVD mortality. Methods: Our study utilized data from the Golestan Cohort Study, which has tracked 50,045 participants aged 40-75 years since 2004. We excluded subjects who reported extreme total energy intake or had a positive history of cancer, CVD, or diabetes at baseline. Vitamin B intake estimations including thiamin, riboflavin, niacin, pyridoxamine, folate, and cobalamin intake were derived from the baseline food frequency questionnaire, noting that supplement use was uncommon in this cohort. To adjust for calorie intakes, we employed the nutrient density method. Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for cardiovascular mortality, using the lowest quintile of intake as the reference group for vitamins and adjusting for potential confounders. Results: We analyzed 42,456 subjects with a mean age of 51.5 ± 8.7 years at baseline. During 579,339 person-years of follow-up (median: 14.1 years), 3,065 CVD deaths were recorded. The median dietary intake of niacin was 25.3 mg/d (Recommended Dietary Allowance = 14-16 mg/d). We observed significant associations between niacin intake (HR Q5 vs. Q1 = 1.13, 95% CI = 1.01-1.26, P trend &lt;0.05) and CVD mortality. When niacin was modeled as a continuous linear variable, it was associated with a greater risk of CVD mortality (HR = 1.05, 95% CI = 1.01-1.09) per 2 mg/1000Kcal/d increase. None of the other B vitamin intakes evaluated were associated with CVD mortality in this population. Conclusion: These findings suggest that among B vitamins, only dietary niacin intake was positively associated with CVD mortality. Further confirmation in larger studies is needed.

Abstract 4125300: Prognostic Value of NT-proBNP and the H 2 FPEF Score on Empagliflozin-associated Left Ventricular Remodeling: Insights from the EMPA-HEART and EMPA-HEART 2 CardioLink Trial

Background: NT-proBNP is a prognostic and diagnostic marker for heart failure while the H 2 FPEF score is used to aid in diagnosing heart failure with preserved ejection fraction. Aims: These post hoc analyses of the randomized controlled EMPA-HEART CardioLink-6 and EMPA-HEART 2 CardioLink-7 trials examined how baseline NT-proBNP and the H 2 FPEF score influenced empagliflozin-associated left ventricular (LV) remodeling in people with either type 2 diabetes and coronary artery disease or without diabetes but with cardiovascular risk factors. Methods: A total of 242 participants were assigned to either empagliflozin 10 mg QD (n=118) or placebo (n=124) for 6 months. NT-proBNP was measured and cardiac MRI performed at baseline and end-of-study. Two independent analyses were performed. One divided the participants into those with baseline NT-proBNP &lt; and ≧125 pg/mL and the other into those with H 2 FPEF score ≦2 and ≧3. The relationships between empagliflozin-associated LV mass and functional changes with baseline NT-proBNP and H 2 FPEF scores were assessed with linear models that adjusted for baseline differences (ANCOVA). Results: Mean age of the pooled cohort was 60.6 years; 14.0% were females, 37.2% had type 2 diabetes. Mean (SD) LV ejection fraction (LVEF) was 58.0 (10.2) %; median (IQR) NT-proBNP 77.5 (33, 164) pg/mL; mean (SD) H 2 FPEF score 2.9 (1.4). Empagliflozin (vs placebo) did not significantly alter LV mass index (mean [SD] -1.35 g/m 2 [0.75]; P=0.07) and LV end-systolic volume index (LVESVi; mean [SD] -1.37 mL/m 2 [0.74]; P=0.07) but did improve LVEF (mean [SD] 2.08% [0.82]; P=0.01). The effect of empagliflozin based on the subgroups of baseline NT-proBNP and H 2 FPEF scores are shown in Figures 1 and 2, respectively. Conclusions: These post hoc analyses suggest that lower baseline NT-proBNP levels and H 2 FPEF scores may be associated with more favourable reverse LV remodelling by empagliflozin and should be validated in larger studies.

Interventions in women with type 2 diabetes mellitus in the pre-pregnancy, pregnancy and postpartum periods to optimise care and health outcomes: A systematic review.

Type 2 diabetes is a chronic condition affecting increasing numbers of women of reproductive age. Recent UK data show more severe adverse offspring outcomes (stillbirth, neonatal death) than in infants of those with Type 1 diabetes. This systematic review aimed to evaluate randomised controlled trials (RCTs) undertaken in the pre-pregnancy, pregnancy and the postpartum periods in women with Type 2 diabetes, to optimise care and health outcomes. Six electronic databases were searched for eligible studies from January 2000 to September 2023; eligibility included RCTs of behavioural components, supplementation, pharmacotherapy and/or medical devices. Studies were screened in duplicate, and data were extracted on outcomes including behavioural, anthropometry, clinical measures and maternal and offspring outcomes. A narrative synthesis was performed. Eleven trials (12 papers) were included (total 1356 women with Type 2 diabetes, n = 25-502). Ten interventions were conducted in pregnancy, and one in the postpartum period. No pre-pregnancy RCTs were identified. Interventions included pharmacotherapies and supplementation, a diabetes-specific antenatal programme, continuous glucose monitoring and postpartum exercise. We found a paucity of interventions limited by inadequate design, statistical power and poor reporting. The largest Type 2 diabetes pregnancy study to date demonstrated evidence of benefit for adding metformin to a standard insulin regimen compared to insulin alone. Other interventions need replication in larger studies among more diverse groups. This review identified few RCTs targeting women of reproductive age with Type 2 diabetes particularly lacking in the preconception and postpartum periods. Tailored pre-pregnancy, pregnancy and postpartum interventions for women with Type 2 diabetes to optimise care and health outcomes are urgently needed.

BIOM-32. GENOMIC DETERMINANTS OF DIFFUSELY INFILTRATIVE GLIOMATOSIS CEREBRI PATTERN

Abstract Gliomatosis cerebri (GC), though no longer a distinct pathological entity in WHO 2021, is a unique and aggressive phenotype of diffuse gliomas with extensive and widespread infiltration. GC can present as primary de novo or secondary after treatment. We aimed to study the genomic determinants of GC. We identified 72 GC cases from 2013-2023 at MD Anderson Cancer Center. Cases were confirmed by detailed radiographic review. This included 57 glioblastoma (79%), 13 IDH mutant astrocytoma (18%), 1 IDH mutant oligodendroglioma (1.4%), and 1 high-grade astrocytoma with piloid features (1.4%). 53/72 (73.6%) were primary and 19/72 (26.4%) were secondary GC. We used 40 patients without the GC pattern as controls. Among glioblastoma GC cases and in comparison with controls, mutations in PTEN and EGFR were significantly associated with the GC pattern: 18/57 (32%) vs 3/38 (7.9%), p-value=0.01 and 23/57 (40%) vs 6/38 (16%), p-value=0.013, respectively. This held true in primary but not secondary GC. Out of 20 most commonly mutated genes in GC, mutations in EGFR, TERT, and MDM4 were associated with worse PFS: p-value=0.004, p-value=0.007, p-value=0.013, respectively and mutations in TERT and MDM4, but not EGFR, were associated with worse OS: p-value=0.003, p-value=0.015, respectively. Secondary GC was associated with IDH mutation compared to control non-GC cases: 8/19 (42%) vs 2/40 (5%), p-value=0.001. As expected, IDH mutation was associated with improved PFS, p-value&amp;lt;0.001 and OS, p-value=0.003 in GC. No genes were significantly associated with laterality of GC. We found novel associations between PTEN and EGFR mutations and the GC phenotype and IDH mutation with the occurrence of secondary GC after treatment. While MDM4 is not associated with outcomes in gliomas, we show that MDM4 mutation is associated with poor survival in GC. These findings shed light into molecular basis of GC and need to be further validated in larger studies.