Outcome Of Therapy Research Articles

Predicting poor functional outcomes for patients with large computed tomography perfusion core infarctions treated with endovascular thrombectomy

Objective Stroke patients with large core infarctions benefit from endovascular intervention, though only approximately 20% are functionally independent at 90 days. We studied prognostic factors for patients presenting with a large computed tomography perfusion (CTP) core. Methods Retrospective analysis from a health system stroke registry, including consecutive thrombectomy patients treated within 24 hours from August 2020-December 2022 with an anterior circulation large vessel occlusion and CTP core infarct ≥50 milliliters. Logistic regression was used to determine independent predictors of 90-day modified Rankin Scale (mRS) score 4–6. The prognostic ability of previously reported scales was also assessed. Results In 118 included patients, with mean age 64.3 ± 14.1 years, poor functional outcomes were present in 66 subjects (55.9%). The multivariable regression analysis demonstrated that higher presenting National Institutes of Health Stroke Scale (NIHSS) score (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.02–1.23, p = 0.014), elevated glucose (OR 1.02, 95% CI 1.01–1.03, p = 0.002), absence of treatment with intravenous thrombolysis (OR 4.01, 95% CI 1.35–11.95, p = 0.013), and poor revascularization (OR 4.76, 95% CI 1.24–18.37, p = 0.023) were independently associated with primary outcome. The Charlotte Large artery occlusion Endovascular therapy Outcome Score (CLEOS) predicted 90-day mRS 4–6 (per 25-point increase, OR 1.22, 95% CI 1.10–1.34, p<0.001) and mRS 5–6 (per 25-point increase, OR 1.21, 95% CI 1.10–1.33, p<0.001). Nineteen of 20 (95%) patients with CLEOS ≥ 675 had 90-day mRS scores of 4–6, while 10 of 12 (83.3%) with CLEOS ≥ 725 had 90-day mRS scores of 5–6. Conclusion We report prognostic factors that can risk stratify thrombectomy patients with large CTP core infarctions.

Opportunities and challenges of using circulating tumor DNA to predict lung cancer immunotherapy efficacy.

Immune checkpoint inhibitors (ICIs), particularly anti-programmed death 1 (PD-1)/ programmed death ligand 1 (PD-L1) antibodies, have led to significant progress in lung cancer treatment. However, only a minority of patients have responses to these therapies. Detecting peripheral blood of circulating tumor DNA (ctDNA) allows minimally invasive diagnosis, characterization, and monitoring of lung cancer. ctDNA has potential to be a prognostic biomarker and a predictor of the response to ICI therapy since it can indicate the genomic status and tumor burden. Recent studies on lung cancer have shown that pretreatment ctDNA analysis can detect residual proliferative disease in the adjuvant immunotherapy setting and evaluate tumor burden in patients with metastatic disease. Early ctDNA dynamics can not only predict the clinical outcome of ICI therapy but also help distinguish between pseudoprogression and real progression. Furthermore, in addition to quantitative assessment, ctDNA can also detect genetic predictors of response to ICI therapy. However, barriers still exist in the application of ctDNA analysis in clinical lung cancer treatment. The predictive value of ctDNA in lung cancer immunotherapy requires further identification and resolution of these challenges. This review aims to summarize the existing data of ctDNA analysis in patients receiving immunotherapy for lung cancer, understand the limitations of clinical treatment, and discuss future research directions.

Laser therapy for Bell's palsy: a systematic review and meta-analysis of randomized trials.

This meta-analysis investigated therapeautic effects of laser therapies in patients with Bell's palsy (BP). The authors performed the literature search in the PubMed, Embase, and Cochrane Library databases using the following search terms: (facial paralysis OR Bell's palsy OR facial palsy OR idiopathic facial paralysis) AND (laser OR low-level laser OR photobiomodulation OR phototherapy). Relevant studies published before October 29th 2024 were identified. Randomized trials comparing the outcomes of laser therapies with other interventions, including electrical stimulation and control or usual care in patients with BP were included. The mean difference (MD) was determined as the effect size for continuous outcomes, and outcome accuracy was determined using 95% confidence intervals (CIs). Twelve studies were included, with a total of 597 patients. Nine studies were further included in the quantitative analysis. Our meta-analysis revealed that laser therapy significantly improved disease severity (House-Brackmann facial paralysis scale) (MD = -1.51, 95% CI = -2.43 to -0.59), facial asymmetry (Sunnybrook facial grading system) (MD = 20.63, 95% CI = 10.33 to 30.94), and facial function and disability (Facial disability index) (MD = 17.91, 95% CI = 5.60 to 30.22) when compared with control care in adult patients. Moreover, laser therapy significantly improved facial severity (MD = 21.05, 95% CI = 16.77 to 25.33) when compared with electrical stimulation. In addition, no adverse effects of laser therapy were reported. Laser therapy has favorable effects on disease severity, facial asymmetry, and facial function and disability for patients with BP.

Identifying Factors That Might Affect Outcomes of Exercise-Based Therapies in Long-COVID

Background: Long-COVID, which might develop after a SARS-CoV-2 infection, is a rather new disease without standardized treatment strategies. A large number of approaches that integrate physical activity have been described in the literature, and this systematic review aims to examine changes in symptom severity, physical fitness, respiratory symptoms and quality of life during training and identify factors that might influence the respective outcomes. Methods: A literature search was conducted using the databases Pubmed, PEDro, BioMed Central, EBSCOhost, ProQuest and the ZBSport from 13 February 2024 to 27 February 2024, and 39 studies fulfilled the search criteria. Results: The analyzed study designs varied regarding the type of intervention (isolated vs. multidisciplinary), duration and intensity of training sessions and overall length of the program. Individualized holistic concepts of physical activity paralleled by additional approaches demonstrated high effectiveness. However, many of the participants continue to suffer from Long-COVID after the intervention. Conclusions: Long-COVID treatment should be individualized, multifactorial and not limited in time and should consider each patient’s pre-existing conditions and individual course of the disease to provide the best possible support and care.

Clinical Outcomes of Isoniazid Preventive Therapy Amongst Persons Living with HIV Attending a Referral Hospital: A Cross-sectional Study

Clinical Outcomes of Isoniazid Preventive Therapy Amongst Persons Living with HIV Attending a Referral Hospital: A Cross-sectional Study

Chest pain and coronary artery disease in cardiac amyloidosis: Prevalence, mechanisms, and clinical implications.

Amyloidosis is a systemic disease affecting multiple organs, and often presents with cardiac involvement, with two primary underlying pathologies: amyloid light chain- and transthyretin cardiac amyloidosis. Chest pain can occur in both types with variable clinical presentations. This narrative review describes the relationship between CA and chest pain. A PubMed search (June 03. 2024) identified 393 articles related to chest pain in CA. Twenty-eight studies, in English and with full text, were selected. Articles included were case reports, reviews, perfusion- and autopsy studies. In CA patients 10-20% report chest pain as the initial symptom preceding the diagnosis, and the overall prevalence of chest pain is 38% of patients with CA and it is related to an increased risk of heart failure hospitalization. The mechanisms leading to chest pain in CA patients include increased left ventricular diastolic pressure, infiltration of amyloid fibrils inside and around coronary arteries, and amyloid compression of the microvasculature. The mechanisms commonly lead to elevations of plasma troponin levels, which are higher in amyloid patients with chest pain compared to amyloid patients without chest pain. Symptomatic treatment of chest pain can be challenging due to the low tolerability of medical therapy and poor outcomes of coronary interventions in alleviating the pain and with a higher rate of complications. Our review underscores the importance of recognizing chest pain as a CA symptom, particularly in the elderly. Persistent troponin elevation without coronary artery disease could indicate CA. Screening-based and longitudinal studies are crucial for understanding the relationship between chest pain and CA. Acknowledging the significance of chest pain in CA may facilitate early intervention and improve patient outcomes.

Preliminary Evidence of Sleep Improvements Following Psilocybin Administration, and their Involvement in Antidepressant Therapeutic Action.

Psilocybin is a rapidly-emerging treatment for depression, yet its impact on sleep is not well understood. We sought to explore the literature on sleep and psilocybin use, and explore the topic using our own primary data. Whilst clinical trials demonstrate large depressive symptom improvements, the impact of psilocybin on sleep quality or insomnia symptoms, has not been directly studied. Using our own preliminary-data we demonstrated that both depressive-symptoms and sleep-disturbances decreased significantly following psilocybin use, though sleep improvements were smaller compared to depressive symptoms. More severe sleep-disturbances at baseline were linked to lower probability of depression remission, underscoring a potential interaction between sleep and psilocybin's efficacy. Addressing sleep disturbances could enhance therapeutic outcomes in psilocybin-assisted therapy and could lead to more effective, personalized treatment-strategies. Future research should focus on populations with sleep disorders, and on examining causal-pathways of sleep physiology's impact on psilocybin efficacy.

High incidence of complications following intraoral extractions and treatment of periapical infections in the management of domestic rabbit (Oryctolagus cuniculus) dental disease (51 cases).

To describe the outcome of common medical therapies, intraoral dental procedures, extraoral surgical interventions, and resulting complications of treatment in client-owned rabbits diagnosed with dental disease. The medical records of 51 client-owned domestic rabbits presenting for veterinary care and management of dental disease from 2013 to 2023 at 2 veterinary teaching hospitals were reviewed. Of the patients managed with coronal reduction and occlusal adjustment, none developed significant complications. Of the patients that required intraoral dental extractions, 41% developed postprocedural complications, including incomplete tooth extraction. Following periapical infection and the formation of an odontogenic abscess for which surgical intervention was implemented, 25% of patients developed complications, including abscess recurrence and sepsis. Meloxicam was the most frequently prescribed analgesic medication for all procedures reviewed. Trimethoprim-sulfamethoxazole combination oral suspension was the most frequently prescribed antibiotic following coronal reduction, occlusal adjustment, and dental extractions, and parenteral penicillin G procaine was the most frequently prescribed antibiotic following periapical infection-related interventions. Seven patients had documentation of natural death or humane euthanasia secondary to progressive dental disease. The risk of postprocedural complications during the management of dental disease must be considered and discussed given the high rate of potential complications. With the increasing popularity of rabbits as companion animals, dental disease is considered one of the most common reasons for veterinary care in this species. Rabbits undergoing intraoral dental procedures and extraoral surgical interventions for the treatment of acquired and progressive dental disease are at risk of developing adverse postprocedural sequelae that must be considered before attempting intervention. This report adds to the growing body of scientific literature related to the management of this challenging disease process.

HPB SO45 - Level 1 evidence comparing aggressive versus non-aggressive intravenous fluid therapy in acute pancreatitis

Abstract Background Fluid balance in the management of acute pancreatitis (AP) is challenging and has been described as a “double-edged sword” whereby adequate fluids are required to counteract systemic hypovolaemia whilst excessive fluids may exacerbate systemic oedema. Given that data generated from randomised studies are conflicting, the optimal rate and type of fluid resuscitation for AP are yet to be determined. We aimed to perform a comprehensive meta-analysis of all existing randomized controlled trials (RCTs) to evaluate comparative outcomes of aggressive versus non-aggressive intravenous fluid (IVF) therapy in patients with AP. Method A systematic search of electronic data sources and bibliographic reference lists were conducted. All RCTs reporting outcomes of aggressive versus non-aggressive IVF therapy in AP were included and their risk of bias were assessed. Effect sizes were determined for overall mortality, systemic inflammatory response syndrome (SIRS), sepsis, respiratory failure, pancreatic necrosis, severe pancreatitis, clinical improvement, AKI, and length of stay using random-effects modelling. Trial sequential analysis was conducted to determine risk of types 1 or 2 errors. Results Ten RCTs enrolling 993 patients with AP who received aggressive (n = 475) or non-aggressive (n = 518) IVF therapy were included. Aggressive IVF therapy was associated with significantly higher rate of sepsis (OR:2.68, P=0.0005) and longer length of stay (MD:0.94, P<0.00001). There was no statistically significant difference in mortality (RD:0.02, P=0.31), SIRS (OR:0.93, P=0.89), respiratory failure (OR:2.81, P=0.07), pancreatic necrosis (OR:1.98, P = 0.06), clinical improvement (OR:1.12, P=0.83), severe pancreatitis (OR:1.31, P=0.38) or AKI (OR:1.06, P=0.91). Subgroup analysis demonstrated higher morbidity and mortality with aggressive fluids in severe AP. Trial sequential analysis detected risk of type 2 error. Conclusion Aggressive IVF therapy may be associated with higher morbidity in patients with acute pancreatitis compared with the non-aggressive approach, particularly in patients with more severe disease. It may also prolong length of hospital stay. The available evidence is subject to type 2 error indicating the need for adequately powered RCTs.

HPB O03 - Snapshot Audit of RELEVANCE: REal worLd outcomEs of adjuVant therapy in pANcreatic CancEr

Abstract Background Evidence-based medicine plays a critical role in shaping clinical practices and setting patient expectations. While randomized controlled trials (RCTs) of adjuvant chemotherapy in pancreatic cancer have demonstrated improved survival rates with newer regimens, their selective inclusion criteria often favor patients with better prognoses. This study aims to compare real-world outcomes with those from RCTs to evaluate the effectiveness of adjuvant therapies in typical clinical settings. Method In this retrospective study, we examined overall survival (OS) among patients who received adjuvant chemotherapy (gemcitabine, gemcitabine-capecitabine, or FOLFIRINOX) following the resection of pancreatic ductal adenocarcinoma. We compared survival curves from RCTs (ESPAC 4, PRODIGE-24) with those from real-world cohorts selected based on RCT criteria. Data were collected retrospectively from medical records and institutional databases, covering OS, disease-free survival (DFS), and adverse events. Results From July 2014 to December 2019, 303 pancreatic ductal adenocarcinoma patients underwent resections, with 209 (69%) receiving adjuvant chemotherapy: 91 (44%) received gemcitabine, 69 (34%) gemcitabine-capecitabine, and 37 (18%) FOLFIRINOX. The median OS for gemcitabine was 21.6 months, close to ESPAC 4’s 25.5 months. Gemcitabine-capecitabine had a median OS of 25.2 months versus ESPAC 4’s 28 months. FOLFIRINOX had a lower median OS in our cohort (19.9 months) compared to PRODIGE 24’s 54.4 months. Additionally, gemcitabine OS in PRODIGE 24 was higher (35 months) than in our data. FOLFIRINOX had a 17% completion rate. Conclusion The real-world outcomes for gemcitabine-based adjuvant therapy align closely with RCT results, while FOLFIRINOX appears less effective in typical clinical settings, possibly due to tolerance issues. These findings highlight the importance of incorporating real-world data in clinical decision-making to better predict patient outcomes and improve treatment strategies for pancreatic cancer. Further research is needed to bridge the gap between RCTs and real-world practices, especially concerning patient selection and treatment tolerability.

Abstract B048: Microfluidic isolation of immune cell-derived extracellular vesicles in head and neck cancer patients on immune-checkpoint blockade

Abstract Background: Immune-checkpoint blockade (ICB), with or without chemotherapy, is the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). However, only a minority of patients get clinical benefit from it. The combined expression of PD-L1 in a tumor section is currently the only biomarker approved for response prediction. Yet, its invasive nature and suboptimal predictive performance underscores the need for new, non- invasive surrogates of immune activity in patients undergoing ICB. Extracellular vesicles (EVs) carry key molecules critical for cell-cell communication and have the potential to be used as a non-invasive, real-time biomarker of systemic immune activity, essential for success in ICB- based therapy. Methods: We used a multichannel, microfluidic device that employs an immune- affinity approach, ‘herringbone chip’ (EVHB-Chip), to retrospectively isolate EVs from twelve HNSCC patients before and after the first cycle of ICB. One mL of plasma was used per patient per time point. For each patient, two devices were serially used, with each sample continuously following through each chip in a non-destructive manner—the first device aimed to isolate B cell EVs (antibodies against CD19 and CD20). The second device was optimized to capture T cell EVs (against CD274/PD-L1). Digital-droplet PCR was performed after EVs were isolated to detect the RNA transcripts in the EV cargo. Serial sampling was performed for six out of the twelve patients. Response assessment was conducted via RECIST1.1 criteria or clinical evaluation. Results: Most of our cohort was male 7/12 (57%) and had oral cavity 4/12 (33%) or oropharynx 4/12 (33%) tumors. Additionally, 11/12 (91%) patients received ICB monotherapy. Most of the cohort had a PD-L1 ≤ 1 (7/12; 58%), 7/12 patients experienced disease progression (PD), 4/12 experienced stable disease (SD), and one patient had a partial response (PR). Most of the RNA signal in pre-ICB samples was obtained from CD20 (12/12; 100%), followed by CD45 (10/12; 83%), CD19 (9/12; 75%), and CD274/PD-L1 (5/12; 41%). No difference was found in the RNA signal pre-ICB between responders and non-responders (p=0.1). For the patients with serial sampling available, the signal from CD274/PD-L1 increased after one infusion of ICB in 4/6 patients and remained negative in one. A trend towards a high amount of T cell-derived EVs was observed for the entire cohort (p=0.07; p=0.08) when comparing the amount of RNA via our EV marker (GAPDH, ACTB) between T and B cell devices. Patients with higher than 11.4/mL copies of CD19 (median value for the cohort) in the pre-ICB plasma sample tended to have a higher overall survival (HR 0.26, 95% CI: 0.06-1.13; p-value: 0.05) and progression-free survival (HR 0.28, 95% CI: 0.07-1.16; p-value: 0.06). Conclusion: The EVHB-Chip allowed for the detection and profiling of T and B cell-derived EVs in pre-ICB plasma samples of HNSCC patients undergoing ICB in this pilot cohort. Higher CD19 signal pre-ICB could potentially impact response and survival outcomes in ICB-based therapies. Citation Format: Andrew R. Levy, Daniel A Ruiz Torres, Uma Paithankar, Raheel Ahmad, Daniel C Rabe, Daniel L Faden, Shannon L Stott. Microfluidic isolation of immune cell-derived extracellular vesicles in head and neck cancer patients on immune-checkpoint blockade [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B048.

Novel prognostic factors and combination therapy outcomes in Morbihan disease: insights from an Asian population.

This study aimed to identify novel prognostic factors for Morbihan disease (MD) treatment outcomes and evaluate the efficacy of combination therapy in an Asian population, addressing the gaps in current understanding of this rare condition. We conducted a retrospective analysis of MD patients diagnosed and treated at a tertiary hospital between 2017 and 2023. Patients received combinations of oral medications (tetracycline, isotretinoin, corticosteroids), topical treatments (tacrolimus, ivermectin), and intralesional steroid injections. Treatment response (TR) was defined as complete symptom remission, while partial remission or recurrence was considered a poor response (PR). Clinical, histological, and biochemical parameters were analyzed to identify prognostic factors. The study included 24 patients (18 men; mean age 61.3 years). Ten patients (41.7%) achieved TR, while 14 (58.3%) showed PR. Significant prognostic factors for TR included shorter symptom duration (≤ 3 months, p = 0.016), lower LDL cholesterol levels (≤ 89mg/dL, p = 0.046), combination treatment with oral and topical medications (p = 0.033 at 6 months), and partial response at 1 month (p = 0.017). GLMM analysis identified the number of visits (p < 0.001), symptom duration (p = 0.020), and dyslipidemia (p = 0.006) as significant prognostic factors. Histologically, perivascular and perifollicular lymphocytic infiltration were the most common findings (83.3%). Notably, 50% of patients were ANA-positive, challenging previous diagnostic criteria. This study identifies novel prognostic factors for favorable outcomes in MD, including early intervention and lipid management. Combination therapy, particularly with tacrolimus ointment, shows promise in improving treatment responses. These findings suggest a potential link between lipid metabolism and MD pathophysiology, opening new avenues for targeted therapies.

Comprehensive analysis of single-cell and bulk RNA sequencing reveals postoperative progression markers for non-muscle invasive bladder cancer and predicts responses to immunotherapy.

Non-muscle-invasive bladder cancer (NMIBC) is renowned for its high recurrence, invasiveness, and poor prognosis. Consequently, developing new biomarkers for risk assessment and investigating innovative therapeutic targets postoperative in NMIBC patients are crucial to aid in treatment planning. Differential gene expression analysis was performed using multiple Gene Expression Omnibus (GEO) datasets to identify differentially expressed genes (DEGs) between NMIBC and normal tissue, as well as between NMIBC and muscle-invasive bladder cancer (MIBC). Functional enrichment analysis was conducted based on the DEGs identified. Subsequently, prognosis-related genes were selected using Kaplan-Meier (KM) analysis and Cox regression analysis. The Boruta algorithm was utilized to further screen for core DEGs related to postoperative progression in NMIBC based on the aforementioned prognosis-related genes. Single-cell and clinical correlation studies were performed to verify their expression across various stages of bladder cancer. To investigate the link between core genes and the immune microenvironment, single-sample gene set enrichment analysis (ssGSEA) was utilized, and Receiver Operating Characteristic (ROC) and KM analyses were performed to confirm predictive power for immune therapy outcomes. Machine learning (ML) models were constructed using the DepMap dataset to predict the efficacy of core gene inhibitors in treating bladder cancers. The prognostic performance of the core genes was evaluated using ROC curve analysis. An online prediction tool was developed based on the core genes to provide prognostic predictions. Finally, RT-qPCR, CCK-8, and Transwell assays were used to verify the pro-tumor effects of the GINS2 in bladder cancer. A total of 70 DEGs were identified, among which 11 prognostic genes were obtained through KM analysis, and an additional 8 prognostic genes were obtained through COX analysis. The Boruta algorithm selected AURKB, GINS2, and UHRF1 as the three core DEGs. Single-cell and clinical variable correlation analyses indicated that the core genes promoted the progression of bladder cancer. The analysis of immune infiltration revealed a strong positive association between the core genes and both activated CD4 T cells and Type 2 helper T cells. Two random forest (RF) models were constructed to effectively predict the treatment effect of bladder cancer after targeted inhibition of AURKB and GINS2. In addition, an online nomogram tool was developed to effectively predict the risk of postoperative progression in NMIBC patients undergoing TURBT. Finally, RT-qPCR, CCK8, and Transwell assays showed that GINS2 promoted the growth and progression of bladder cancer. AURKB, GINS2, and UHRF1 have the potential to enhance postoperative management of NMIBC patients undergoing transurethral resection of bladder tumor (TURBT) and can predict immunotherapy response, establishing them as promising therapeutic targets.

Abstract 4137113: The Effectiveness of Cardiac Resynchronization Therapy in Patients with Cardiac Sarcoidosis: A Retrospective Analysis

Background: Cardiac sarcoidosis (CS) manifests in a wide range of clinical presentations, including conduction system abnormalities, ventricular arrhythmias, and systolic heart failure. Although cardiac resynchronization therapy (CRT) has shown efficacy in treating select nonischemic cardiomyopathy patients, its specific impact on CS patients remains less explored. This study aimed to evaluate the outcomes of CRT therapy in CS patients, focusing on implantable cardioverter defibrillator (ICD) therapies, heart failure (HF) hospitalizations and mortality. Methods: We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent device implantation (ICD or Permanent Pacemaker (PPM)) with or without CRT therapy at Johns Hopkins Hospital between 2004 and 2024. Baseline characteristics and echocardiographic parameters were assessed. Heart failure hospitalizations, the frequency of ATP (Anti-Tachycardia Pacing) or ICD shocks, and all-cause mortality were also evaluated as the outcomes. Results: The study included 212 patients (40.1% female, average age 52.8 ± 11.1 years). Eighty-five patients underwent CRT implantation (82 CRT-D and 3 CRT-P), whereas the rest received either an ICD or a PPM without CRT therapy. Most CRT devices (58.82%) were upgrades from an initial PPM or ICD. Over a follow-up of 6.15 ± 4.43 years, 27 (12.74%) patients were hospitalized for heart failure (HF), 86 (40.56%) experienced ATP or ICD shocks, and 17 (8.02%) died. The composite outcome was observed in 103 patients (48.5%), with no significant differences between CRT and non-CRT groups ( P = .51). Survival analysis indicated significantly reduced freedom from HF hospitalizations in the CRT group compared to non-CRT group ( P = .01). However, ATP/ICD shocks did not have a significant difference. CRT recipients showed an improvement in left ventricular ejection fraction (LVEF) from 35.3 ± 12.6% to 38.9 ± 13.6% at 6 months ( P = .01). Non-recipients showed no significant change in LVEF ( P = .43). Conclusions: Over an average six-year follow-up period, CRT upgrade does not appear to affect ATP/ICD shock and mortality in CS patients, although it is associated with significantly higher rates of heart failure (HF) hospitalizations compared to CS patients with an ICD or PPM alone. These findings underscore the complex response of CS patients to CRT, highlighting the need for further research to optimize treatment strategies within this subgroup.

Abstract 4122763: Health Status Outcomes of Antianginal Therapies in Patients After Coronary Revascularization: Insights From the GREAT Disease Registry Study

Background: The impact of antianginal therapies on the health status of coronary artery disease (CAD) patients who have undergone coronary revascularization has not been extensively researched. This study aimed to investigate the effect of nicorandil on the health status in patients after coronary revascularization, measured by the Seattle Angina Questionnaire (SAQ). Methods: We analyzed data from 1,556 patients enrolled in the GREAT Disease Registry Study (Clinicaltrial No. NCT05050773) between September 2021 and May 2022. Changes in SAQ summary score (SAQ-SS) from baseline to 3, 6, 9, and 12 months were assessed. Statistical methods included a linear mixed-effects model and propensity score matching (PSM) for comparative analysis. Results: Among the 1,038 patients receiving revascularization analyzed (22.7% female; mean age [SD], 59.9 [10.2] years), 648 (62.4%) received nicorandil, while 390 (37.6%) did not. In the linear mixed-effects model analysis, statistically significant improvements were observed with nicorandil in SAQ-SS across all time points ( Table 1 ), indicating beneficial effects of nicorandil on health status outcomes after revascularization. Sensitive analysis was conducted using the PSM method. After PSM adjustment, both groups comprised 321 patients each. The change in SAQ-SS from baseline to 12 months was significantly greater in the nicorandil group (19.2 ± 14.06 points) compared to the non-nicorandil group (14.91 ± 12.9 points, p &lt; 0.001). Conclusions: These findings indicated that nicorandil is associated with improved health status outcomes in CAD patients who have undergone coronary revascularization.

Abstract 4126672: Clinical Predictors and Outcomes of Catheter-Directed Therapies in Patients with Intermediate-Risk Central Pulmonary Embolism

Background: The management of intermediate-risk pulmonary embolism (PE) is unclear. The use of catheter-directed therapies (CDTs) in these patients has increased. However, their selection is not standardized, and outcomes of CDT compared to anticoagulation alone (ACA) are limited. Research Question: What are the clinical predictors of using CDT and their outcomes compared to ACA? Methods: Single center, 11-year, retrospective study of patients with intermediate-risk central PE. We stratified data by CDT use vs. ACA. We used the simplified pulmonary embolism severity index (sPESI) and right ventricular (RV) dysfunction as surrogates of PE severity and the VTE-BLEED score for baseline bleeding risk. We looked for predictors of CDT use and bleeding complications on multivariate logistic regression analyses. Results: Of 490 patients identified, 110 (22%) underwent CDT (Figure 1, Table 1). Higher BMI (OR 1.04, 95% CI 1.01-1.06; p=0.002), prior venous thromboembolism (VTE) episodes (OR=1.92, 95% CI 1.05-3.50; p=0.032), saddle PE (OR=3.42, 95% CI 2.00-5.85; p&lt;0.0001), RV dysfunction (OR=6.93, 95% CI 3.53-13.57; p&lt;0.0001), and creatinine elevation (OR=1.36, 95% CI 1.13-1.64; p=0.001) were independently associated with CTD use (Table 2). After adjusting for PE severity and bleeding risk, CDT was independently associated with bleeding complications (OR=3.77, 95% CI 1.74-8.15; p=0.001) (Table 3). The overall in-hospital mortality was low (3%, n=13). Conclusions: Higher BMI, prior VTE, saddle PE, RV dysfunction, and creatinine elevation were independently associated with CDT use. The CDT group had more major bleeding without mortality difference compared to ACA. Further studies are needed to standardize the use of CDT in intermediate-risk PE.

Abstract 4137925: Long-term Outcome of Initial Thoracic Endovascular Repair or Medical Therapy in Acute Uncomplicated Type B Aortic Dissection: Real-world Data from a Nationwide Claims-Database in Japan.

Introduction: Thoracic endovascular aortic repair (TEVAR) has emerged as a promising treatment option for patients with type B aortic dissection (TBAD). However, there is a lack of evidence regarding the long-term morbidity of initial TEVAR compared to optimal medical therapy (OMT) in acute uncomplicated TBAD (uTBAD). Objective: To evaluate real-world data(RWD) on the long-term outcome of Japanese patients with acute uTBAD using a nationwide claims database. Methods: This retrospective cohort study utilizes JMDC, a nationwide claims database under Japan's universal healthcare system. We included patients who were initially hospitalized with a diagnosis of acute TBAD. We defined acute uTBAD by excluding those who died within one month, suffered aortic rupture, traumatic thoracic aortic injury, underwent open-chest surgery, experienced stroke or paralysis, or had less than six months of history in the JMDC. Patients who underwent TEVAR within three months of the index hospitalization (TEVAR group) were compared with those who received optimal medical therapy (OMT group). Propensity score (PS) matching was performed based on age, sex, and year of hospitalization. Using the Kaplan-Meier method, we calculated the cumulative rate of all-cause mortality and aorta-related events. Results: Of 18,445 patients diagnosed with aortic disease between January 2005 and December 2020, 641 were included in the study (OMT group: n=580, TEVAR group: n=61). After PS-matching, demographics of the groups (OMT_PSM: n=183 vs. TEVAR_PSM: n=61) were female (12.6% vs. 13.1%), median age (54 years [IQR, 48-60] vs. 54 years [IQR, 50-61]) and follow-up time (18 months [8-32] vs. 19 months [9-32]), respectively. Kaplan-Meier curves for the aortic-related events (Figure1, 2) are shown as long-term outcomes. Conclusions: This study successfully demonstrated that the estimated 5-year aortic-related event rate in acute uTBAD patients undergoing OMT is approximately 20%, demonstrating the relevance of the RWD source. However, the number of death events in the TEVAR and OMT groups was not sufficient to provide statistical power. Therefore, further studies are warranted to evaluate the long-term prognosis of initial TEVAR for uTBAD.

Abstract 4118341: Outcomes of Heart Failure with Preserved Ejection Fraction Patients With Concurrent Opioid Use: Insights From the National Inpatient Sample

Background: Opioid use has increased significantly in the past few decades, impacting cardiac and non-cardiac patients. As heart failure with preserved ejection fraction (HFpEF) comprises half of all heart failure cases, understanding its management and effect on outcomes is crucial. This study aims to evaluate the outcomes of chronic opioid therapy on HFpEF patients. Methods: Studying the National Inpatient Sample (2016-2020), we identified adult HFpEF patients using the appropriate ICD-10 codes -after excluding patients with end-stage renal disease (ESRD)- and compared outcomes between chronic opioid users and non-users. Multivariate logistic and linear regression analyses were performed, adjusting for multiple patient and hospital confounders. The primary outcome was all-cause in-hospital mortality while secondary outcomes included acute kidney injury/hemodialysis (AKI/HD), cardiogenic shock, cardiac arrest, mechanical ventilation, length of stay, and total charges. Results: Among 1,557,344 HFpEF patients, 21,655 (1.4%) were on opioids chronically. Inpatient mortality was not significantly different between patients who were on opioids and those who were not. (adjusted odds ratio [aOR] 1.01, 95% CI 0.85 - 1.2, p=0.89). There was a non-significant increased risk of cardiogenic shock (aOR 1.14, 95% CI 0.87 - 1.5, p=0.35) and cardiac arrest (aOR 1.05, 95% CI 0.8 - 1.36, p=0.74) in patients on chronic opioids. Chronic opioids were associated with increased risk of AKI/HD (aOR 1.12, 95% CI 1.04 - 1.2, p=0.002) and mechanical ventilation (aOR 1.29, 95% CI 1.16 - 1.43, p&lt; 0.001). Opioid use was also associated with longer hospital stay (adjusted MD [aMD] 1.07 days, 95% CI 0.75 - 1.39, p&lt;0.001) and a non-significant increase in total charges (aMD $2,593, 95% CI -$2,044 - $7,229, p=0.27). Conclusions: While chronic opioid use in hospitalized HFpEF patients did not significantly impact in-hospital mortality, it was associated with increased risk of other adverse events and longer hospital stay. Further research is needed to understand the impact of chronic opioid use on HFpEF patients.

Abstract 4119891: Risk Factors of Anemia in Pulmonary Arterial Hypertension Patients with Endothelin Receptor Antagonists Administration and Related Treatment

Background: Endothelin receptor antagonists (ERAs) demonstrated significant efficiency in delaying clinical deterioration and improving survival of patients with pulmonary arterial hypertension (PAH). However, the frequent occurrence of anemia after ERAs administration has gained clinical attention currently, whereas the etiology of anemia is unclear. The risk factors of ERAs associated anemia remained undefined. Therefore, we aim to investigate risk factors of developing anemia after ERAs treatment and whether iron supplement could correct anemia. Method: A retrospective cohort study was performed among patients with PAH who received ERAs between January, 2017 and December, 2019 in Fuwai hospital. The primary outcome was development of anemia after ERAs therapy and secondary outcome was correction of anemia after iron supplement. Results: A total of 120 patients with PAH were included in the study and 28 patients developed anemia during follow up . Distinctively, all the patients who developed anemia were female. After ERAs administration, iron metabolism (Ferritin 95.29±144.79 μg/L versus 69.9±118.25 μg/L, P &lt;0.001) and hemoglobin (154.21±23.80 g/L versus 136.12±28.61 g/L, P &lt;0.001) reduced significantly in the total cohort with patients who developed anemia more significant. Baseline iron metabolism (Ferritin: HR 0.98, 95%CI 0.96-0.99, P =0.02) was independently associated with development of anemia after ERAs administration. Compared with patients with iron replete, patients with iron deficiency had over 9-fold risk of developing anemia after receiving ERAs (HR = 9.59, 95%CI 3.62-25.41, P &lt; 0.01). Iron supplement could effectively correct anemia. Conclusion: It is advised that patients receiving ERAs monitor iron metabolism and hemoglobin regularly, especially females and those with low hemoglobin level and compromised iron homeostasis before ERAs administration, which facilitates prevention and early detection of anemia. ERAs-related anemia is mostly mild, oral iron supplement could effectively reverse anemia and aberrant iron metabolism.

Abstract 4113494: Gut Microbiota Modulation by Immunosuppression and Cardiac Cell Therapy in a Nonhuman Primate Ischemia/Reperfusion Model of Cardiac Regeneration

End-stage ischemic heart disease necessitates heart transplantation, and emerging cell therapy presents a promising solution to address donor scarcity. Disruption of gut microbiota significantly influences various diseases and treatments, including transplantation. However, the impact of immunosuppression and cardiac cell therapy on gut microbiota remains largely unexplored. To elucidate this relationship, we investigated gut microbiota dynamics in response to immunosuppression and cell therapy in a nonhuman primate (NHP) cardiac ischemia/reperfusion (IR) model, with controlled genetic, dietary, and environmental factors. Immunosuppression enriched anaerobes (Faecalibacterium, Streptococcus, Anaerovibrio, Dialister), increasing gut microbiota diversity. These changes correlated with metabolic shifts towards amino acid metabolism and nucleosides/nucleotides biosynthesis. Combined treatment of human induced pluripotent stem cell (iPSC)-derived endothelial cells (EC) and cardiomyocytes (CM) also increased gut microbiota diversity, with specific genera alterations. The EC/CM co-treatment group displayed gut microbiota resembling the pre-injury group, with host metabolism shifting towards amino acid and fatty acid/lipid biosynthesis post-cell therapy. These observed microbiota changes and metabolic shifts could serve as biomarkers for monitoring cell therapy and immunosuppression outcomes, offering potential therapeutic targets to enhance efficacy.