Clinical Outcomes In Patients Research Articles

Abstract 4140168: Association of left and right branch blocks with clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF)

Background: Although left (LBBB) and right (RBBB) bundle branch blocks play a critical role in cardiovascular pathogenesis, the associations of LBBB and RBBB with cardiovascular (CV) outcomes, especially in patients with HFpEF is understudied compared with normal QRS. Aim: We assessed clinical outcomes of LBBB and RBBB in patients with HFpEF who were admitted for acute decompensated heart failure compared with those without bundle branch blocks. Method: A cross-sectional study was conducted using the National Inpatient Sample (NIS) database from 2019. We only included adult hospitalizations with HFpEF admitted for acute decompensated heart failure in the study. Hospitalized records were categorized into three groups (LBBB, or RBBB, and those with normal QRS). Clinical outcomes included atrial fibrillation (AF), ventricular fibrillation (VF), complete heart block (CHB), sick sinus rhythm (SSR), cardiac arrest (CA), length of stay (LOS) and in-hospital mortality. Propensity score (PS) inverse probability of treatment weighting and matching were applied to determine the association between BBB types and CV outcomes and validated associations in sensitivity analyses. Results: A total of 334511 hospitalizations with HFpEF included LBBB (6818, 2%) and RBBB (7948, 2.4%) were analyzed. Compared to normal QRS, LBBB was associated with VF (odds ratio [OR]=2.47, p<0.001), SSR (OR=1.72, p<0.001), CHB (OR=2.77, p<0.001) and longer LOS (relative risk [RR]=1.15, p<0.001) after adjusting for covariates in PS analysis. Similarly, RBBB was associated with AF (OR=1.30, p<0.001), VF (OR=1.59, p=0.033), SSR (OR=1.72, p<0.001), CHB (OR=2.81, p<0.001), CA (OR=1.19, p<0.001), and longer LOS (RR=1.08, p<0.001) [Table 1]. These associations remained consistent in multiple validation analyses including after additionally adjusting for obesity, hypertension and diabetes. Conclusion: In hospitalized records with acute decompensated HFpEF, BBB was associated with increased risk of CV outcomes and longer hospital length of stay. The extent of association with multiple CV outcomes varied according to RBBB and LBBB.

The PI3K-AKT-mTOR axis persists as a therapeutic dependency in KRASG12D-driven non-small cell lung cancer.

KRASG12C and KRASG12D inhibitors represent a major translational breakthrough for non-small cell lung cancer (NSCLC) and cancer in general by directly targeting its most mutated oncoprotein. However, resistance to these small molecules has highlighted the need for rational combination partners necessitating a critical understanding of signaling downstream of KRAS mutant isoforms. We contrasted tumor development between KrasG12C and KrasG12D genetically engineered mouse models (GEMMs). To corroborate findings and determine mutant subtype-specific dependencies, isogenic models of KrasG12C and KrasG12D initiation and adaptation were profiled by RNA sequencing. We also employed cell line models of established KRAS mutant NSCLC and determined therapeutic vulnerabilities through pharmacological inhibition. We analysed differences in survival outcomes for patients affected by advanced KRASG12C or KRASG12D-mutant NSCLC. KRASG12D exhibited higher potency in vivo, manifesting as more rapid lung tumor formation and reduced survival of KRASG12D GEMMs compared to KRASG12C. This increased potency, recapitulated in an isogenic initiation model, was associated with enhanced PI3K-AKT-mTOR signaling. However, KRASG12C oncogenicity and downstream pathway activation were comparable with KRASG12D at later stages of tumorigenesis in vitro and in vivo, consistent with similar clinical outcomes in patients. Despite this, established KRASG12D NSCLC models depended more on the PI3K-AKT-mTOR pathway, while KRASG12C models on the MAPK pathway. Specifically, KRASG12D inhibition was enhanced by AKT inhibition in vitro and in vivo. Our data highlight a unique combination treatment vulnerability and suggest that patient selection strategies for combination approaches using direct KRAS inhibitors should be i) contextualised to individual RAS mutants, and ii) tailored to their downstream signaling.

Aquaporin-4 activation facilitates glymphatic system function and hematoma clearance post-intracerebral hemorrhage.

Efficient clearance of hematomas is crucial for improving clinical outcomes in patients with intracerebral hemorrhage (ICH). The glymphatic system, facilitated by aquaporin-4 (AQP4), plays a crucial role in cerebrospinal fluid (CSF) entry and metabolic waste clearance. This study examined the role of the glymphatic system in ICH pathology, with a focus on AQP4. Collagenase-induced ICH models were established, with AQP4 expression regulated through mifepristone as an agonist, TGN-020 as an inhibitor, and Aqp4 gene knockout. Fluorescence tracing and multimodal magnetic resonance imaging (MRI) were employed to observe glymphatic system functionality, hematoma, and edema volumes. Neurological deficit scoring was performed using the modified Garcia Scale. AQP4 expression was quantified using RT-qPCR and Western blotting, and cellular localization was explored using immunofluorescence. The brain tissue sections were examined for neuronal morphology, degenerative changes, and iron deposition. Three days post-ICH, the AQP4 agonist group showed increased AQP4 protein expression and perivascular polarization, decreased hemoglobin levels, and reduced iron deposition. Conversely, the inhibition group exhibited contrasting trends. AQP4 activation improved glymphatic system function, leading to a wider distribution, improved neurological function, and reduced hematoma. Pharmacological inhibition and genetic knockout of AQP4 have opposing effects. The glymphatic system, facilitated by AQP4, plays a crucial role in hematoma clearance following cerebral hemorrhage. Upregulation of AQP4 improves glymphatic system function, facilitates hematoma clearance, and promotes brain tissue recovery.

Abstract 4136677: High Visceral-to-Subcutaneous Fat Ratio is Correlated with Increased Cardiovascular Events in Patients with Low Waist Circumference Suspected of Coronary Artery Disease

Introduction: Waist circumference (WC) has been recognized as an appropriate index of obesity and is closely associated with the amount of abdominal fat. Although abdominal fat distribution (AFD), which is represented by the ratio of visceral adipose tissue (VAT) to subcutaneous adipose tissue (SAT) area (V/S ratio), is possibly related to an increased risk of cardiovascular disease (CVD), few studies have explored the relationship between AFD and CVD outcomes. This study aimed to assess the influence of AFD based on the V/S ratio and physique categorized by WC on long-term clinical results in patients with suspected coronary artery disease (CAD). Methods: We evaluated 931 consecutive patients (mean age, 67 years; 42.4% women) with suspected CAD who underwent computed tomography (CT) angiography. The patients also underwent plain abdominal CT to assess and measure VAT and SAT areas; V/S ratio was calculated to assess AFD. The patients were divided into four groups based on the median V/S ratio (0.624) and reference values of WC for metabolic syndrome in Japan (85 cm for men, 90 cm for women). We assessed the relationship between the V/S ratio and long-term clinical outcomes in each WC group. The main outcome was major adverse cardiac events (MACEs, including cardiac death, any coronary revascularization, acute coronary syndrome, and emergency hospitalization due to cardiac cause). Results: Over a median follow-up of 1869 days, although the incidence of any cardiovascular event was not related to the V/S ratio among patients with high WC, a higher incidence of MACE and cardiac death was noted among patients with low WC in the high V/S ratio group than in the low V/S ratio group. Furthermore, Kaplan–Meier analysis revealed a significantly lower MACE-free survival rate among patients with low WC in the high V/S ratio group than in the low V/S ratio group, despite of no differences being noted among high WC patients in both the V/S ratio groups (Figure). Conclusion: Only in patients with low WC, a high V/S ratio was linked to increased risks of MACE. Thus, high V/S ratio may be an essential risk factor for CVD, specifically in patients with low WC. However, AFD did not influence CVD prognosis in patients with high WC.

Abstract 4121812: Longitudinal Trajectory-Based Classification of Heart Failure with preserved Ejection Fraction: A Machine Learning Approach

Background: Heart failure (HF) with preserved ejection fraction (HFpEF) is a complex syndrome characterized by heterogeneous pathophysiology and dynamic changes in cardiac structure and function. Current research predominantly focuses on left ventricular ejection fraction (LVEF) or left ventricular structures with predefined categories. This study hypothesized that applying unsupervised methodologies to longitudinal echocardiography will reveal distinct trajectory patterns in cardiac structure and function related to clinical outcomes in HFpEF patients. Methods: This retrospective cohort study, conducted at UC Davis Medical Center (2014 to 2022), consisted of adult patients with HFpEF. The inclusion criteria included ICD HF codes, a left ventricular ejection fraction (LVEF) ≥50%, and a Brain natriuretic peptide (BNP) ≥100 pg/ml or N-terminal-pro BNP (NT-proBNP) ≥225 pg/ml. Longitudinal data were analyzed using unsupervised machine learning, including UMAP for dimensionality reduction and Gaussian Mixture Models for clustering. Primary and secondary outcomes included all-cause mortality and changes in BNP levels, respectively. Results: The study included 1,626 patients. The cohort had a median age of 69 years, was 57.5% female, and 51.8% white. Three distinct echocardiographic trajectory patterns emerged (p<.05) among the HFpEF cohort. Trajectory #1 (n=568) exhibited a high-stable pattern with the highest mortality rates, Trajectory #2 (n=512) showed a high-decreasing pattern with high mortality rates, and Trajectory #3 (n=546) had a low-increasing pattern with the lowest mortality rates. Trajectories varied significantly in baseline characteristics and longitudinal echocardiographic changes, with Trajectory #3 having a lower baseline left ventricular mass index (p<.001) and a higher mean arterial pressure ( p =.001) compared to the other trajectories. Kaplan-Meier survival analysis indicated significant differences in survival among the trajectories ( p =.004). Conclusion: The study utilized unsupervised analysis of longitudinal echocardiographic data to identify three distinct HFpEF trajectories, each associated with unique clinical features and outcomes. These findings underscore the heterogeneity of HFpEF and highlight the potential trajectory-based patient stratification to improve targeted intervention strategies. Future validation in larger, multicenter cohorts is warranted to enhance HFpEF management and patient prognosis.

Multicentre retrospective analysis of physician-modified fenestrated/inner-branched endovascular repair for complex aortic aneurysms.

In this multicentre retrospective observational study, we present the early outcomes of physician-modified fenestrated/inner-branched endovascular repair for pararenal and thoraco-abdominal aortic aneurysms in patients at high risk for open surgical repair. We comprehensively reviewed the clinical data and outcomes of consecutive patients treated with physician-modified fenestrated/inner-branched endovascular repair for pararenal or thoraco-abdominal aortic aneurysms at six centres between December 2020 and December 2021. Primary end-points included technical success, in-hospital mortality rates, major adverse events. Seven and 31 patients (median age, 80.5 years) had pararenal and thoraco-abdominal aortic aneurysms, respectively, involving 93 renal-mesenteric arteries incorporated through 10 fenestrations or 83 inner branches. Seven patients (18.4%) were treated non-elective conditions. The technical success rate was 89.5%. The median operative time was 334.5 min. Ten patients (26.3%) experienced major adverse events, including in-hospital mortality in six patients (15.8%), acute kidney injury in three patients (7.9%), respiratory failure in three patients (7.9%), bowel ischaemia in one patient (2.6%), stroke in one patient (2.6%), and paraplegia in one patient (2.6%). Among elective cases, in-hospital deaths occurred in three patients (9.7%), while in non-elective cases, the mortality rate was higher, with three patients (42.9%) succumbing. The median follow-up duration was 14 months. physician-modified fenestrated/inner-branched endovascular repair is a viable treatment for pararenal or thoraco-abdominal aortic aneurysms in patients at high risk for open surgical repair. It provides customization without location constraints or production delays, but further validation is needed to ensure long-term reliability.

Abstract 4136819: Necrotizing Enterocolitis is More Common After Hybrid Stage 1 Palliation Than Norwood Without Clear Risk Factors

Background: Infants with congenital heart disease are at high risk of developing necrotizing enterocolitis (NEC), with increased morbidity and mortality compared to infants without heart disease who develop NEC. Shunted single ventricle patients are at even higher risk. The hybrid stage 1 palliation (HS1P) is an alternative to the Norwood procedure for high-risk single ventricle patients or as initial palliation for patients with future two ventricle repair, as bridge to transplant, or as destination therapy. Few small studies have shown similar or slightly higher rates of NEC after HS1P compared to after Norwood. Aims: To evaluate the incidence, risk factors, and outcomes of NEC in HS1P versus Norwood patients. Methods: This is a single-center retrospective cohort study of all neonates who underwent HS1P or Norwood procedure from 2011-2022. Demographic data and episodes of NEC (defined using modified Bell’s criteria) were collected. NEC incidences and risk factors were compared between HS1P and Norwood patients using Chi-square test. For HS1P patients, more extensive data were collected including planned and final physiologic outcomes (single ventricle palliation, biventricular repair, transplant, and destination) and primary patient risk factors that led to HS1P. Risk factors and clinical outcomes of HS1P patients with and without NEC were compared using standard univariate tests. Results: The cumulative incidence of NEC in the HS1P group was 53% versus 37% in the Norwood group (p=0.01) and HS1P patients had more NEC episodes than the Norwood group (median 2 vs 1, p=0.03). Suspected NEC (stage 1A/1B) accounted for 70-75% of NEC cases in both groups. Only two infants, both in the HS1P group, had surgical (stage 3B) NEC. We found no differences in baseline demographics between patients with and without NEC in both HS1P and Norwood groups. In the HS1P group, NEC was associated with longer hospital length of stay (LOS), (median 49 days vs 23 days, p<0.0001) and greater need for tube feeds at 1 year (32% of the NEC group exclusively orally fed versus 43% of the non-NEC group, p=0.03). Final physiologic outcome was not associated with development of NEC in the HS1P group (p=0.38). Conclusions: While the exact risk factors or predictors are not clear, NEC is more common after HS1P compared to Norwoods and is associated with longer hospital LOS and late feeding difficulty. Further studies to better understand the physiologic causes of NEC in the HS1P population are needed.

Abstract 4127071: Pulmonary Artery Catheter Utilization in Cardiogenic Shock: Clinical Characteristics and Outcomes

Background: The pulmonary artery catheter (PAC) is used for hemodynamic monitoring, but its impact on patient outcomes, especially in cardiogenic shock (CS), is controversial. Several studies have shown no significant benefits and noted complications, leading to a decline in PAC use. However, PAC use appears to have increased recently in guiding management decisions in CS. Our study aims to assess the clinical characteristics and outcomes of CS patients receiving PACs versus not. Methods: We included patients with CS admitted to a tertiary academic medical center between May 2015 and December 2023. Variables were compared using Kruskal-Wallis, chi-squared, and Fisher's exact tests. Hemodynamic parameters were collected from either right heart catheterization or from a PAC. Endpoints included native heart survival to discharge, durable left ventricular assist device (LVAD) implantation, heart transplant (HTx), and 30-day and 1-year survival from discharge. Results: The study group consisted of 742 patients with CS. Of these, 385 (52%) received a PAC and 357 (48%) did not. The baseline characteristics of the two groups are shown in Table 1A . PAC patients had more severe shock, worse hemodynamics, and higher rates of temporary mechanical circulatory support (MCS) use. Hemodynamic measurements at shock onset differed, with PAC patients having higher right atrial pressures and lower cardiac index by Fick. Clinical outcomes and MCS related complications are shown in Table 1B. There was no significant difference in native heart survival at discharge, but HTx and durable LVAD implantation was higher in the PAC group. PAC placement was associated with longer hospital stays and more MCS related complications, including bleeding and hemolysis. The 30-day survival rate was similar between groups, and 1-year survival was marginally higher in the PAC group. Conclusion: PAC patients exhibited more severe clinical characteristics, longer hospital stays, higher rates of temporary MCS use and complications, durable LVAD implantation, and HTx. Short-term survival rates were similar, but 1-year survival was slightly better for PAC patients. Further studies are needed to provide clearer insights into PAC use in CS.

Abstract 4135270: Clinical and Procedural Outcomes after Transcatheter Aortic Valve Replacement vs Surgical Aortic Valve Replacement in Severe Aortic Stenosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: A growing body of evidence from randomized controlled trials (RCTs) has demonstrated the superiority of transcatheter aortic valve replacement (TAVR) over surgical aortic valve replacement (SAVR) irrespective of surgical risk in patients with severe aortic stenosis (SAS). Given the rise in TAVR procedures, analyzing trends in outcomes over time is critical to aid clinical decision-making. Hence, we pooled RCT data for a robust assessment of clinical and procedural outcomes in SAS patients undergoing TAVR and SAVR. Methods: PUBMED and SCOPUS were queried until April 2024. Trials were classified into high and low-risk groups based on surgical risk. The outcomes were analyzed at 30 days (short-term), 1 year (mid-term), and 5 years (long-term). Estimates were calculated as random effects risk ratios (RRs) with 95% confidence intervals (CI). Results: 10 RCTs with a total of 10,252 patients were included. There was no significant association between TAVR and SAVR in reducing all-cause mortality at 30 days (RR: 0.84 [0.64, 1.10]; Figure 1a). While TAVR was associated with a significantly lower all-cause mortality at 1 year (RR: 0.82 [0.68-0.97]; Figure 1b), it was linked with a significantly higher all-cause mortality at 5 years (RR: 1.14 [1.07-1.21]; Figure 1c). Myocardial infarction and stroke were similar in both groups up to 5 years. TAVR was associated with a lower risk of acute kidney injury for up to 1 year and atrial fibrillation for up to 5 years but a higher risk of new permanent pacemaker implantation and aortic valve re-intervention for up to 5 years. In low-risk patients, TAVR showed no significant differences from SAVR for all-cause mortality at 30 days and 5 years, but it was significant at 1 year. In high-surgical-risk patients, all-cause mortality was comparable between TAVR AND SAVR at 30 days and 1 year, with a higher rate observed with TAVR at 5 years. Conclusion: Compared with SAVR, TAVR was superior in reducing all-cause mortality at 1 year in low-risk patients and inferior in reducing all-cause mortality at 5 years in high-risk patients. A thorough evaluation of anatomical, clinical, and procedural factors is crucial to tailor the optimal intervention for each patient.

Abstract 4113420: Assessing the Clinical Impact of Cardiac Intensivists in Cardiac Intensive Care Units.: Results from the RESCUE registry

Background: Presence of dedicated intensive care unit physicians is associated with reduced intensive care unit mortality. However, there is limited information regarding the impact of cardiac intensivists in cardiac intensive care units. Research Questions: What is the role of cardiac intensivists in influencing clinical outcomes for adult patients admitted to cardiac intensive care units? Aims: To investigate the association between cardiac intensivist-directed care and clinical outcomes in adult patients admitted to cardiac intensive care units. Methods: This retrospective study used data from the SMART-RESCUE registry, which is a multicenter, retrospective, and prospective registry of patients presenting with cardiogenic shock. The study involved 1,247 patients enrolled from January 2014 to December 2018 at 12 tertiary centers in Korea. These patients, who were suffering from cardiogenic shock, were divided into two groups depending on whether their care involved a cardiac intensivist. Results: The study found that the all-cause mortality rate was 33.6%. The in-hospital mortality rate was significantly lower in the group managed by cardiac intensivists (25.4%) compared to the group without (40.1%). Similarly, cardiac death rates were lower in the cardiac intensivist group (20.5%) than in the non-cardiac intensivist group (35.4%). In patients undergoing extracorporeal membrane oxygenation, mortality at centers with cardiac intensivists was 38.0%, compared to 62.2% at centers without. The use of dopamine was lower and norepinephrine use was higher and the vasoactive-inotropic score was lower in the cardiac intensivist group. Conclusion: Cardiac intensivist involvement in patient care within cardiac intensive care units was associated with a reduction in in-hospital mortality and administration of vasopressors and inotropes according to cardiogenic shock guidelines, indicating a beneficial effect on clinical outcomes.

The First Case of a Cat Infected with Burkholderia pseudomultivorans, a Member of the Burkholderia cepacia Complex

The Burkholderia cepacia complex (Bcc) is a group of bacteria with similar biological properties which are an important cause of opportunistic infections. Identification of the Bcc species is important to understand clinical outcomes in human patients. However, there are few studies of Bcc species infecting companion animals such as cats. This report shows for the first time an infection with B. pseudomultivorans, a member of Bcc, in veterinary medicine. A 9-year-old, FIV-positive, mixed-breed cat was subjected to immunosuppressive therapy, developed septic shock, and died. In the bone marrow specimen collected postmortem, numerous short bacilli—some of which were phagocytosed by leukocytes—were observed. By bacteriological examination, the Bcc-like bacteria were isolated from the bone marrow sample. Genetic analysis showed that the recA gene sequence detected from the present case exhibited the highest homology (98–100%) to that of B. pseudomultivorans. Based on these examinations, the present case was diagnosed as B. pseudomultivorans infection. The findings of this study highlight the need for investigation of the Bcc species in veterinary practice to help in treatment decisions and the prognostic evaluation of Bcc infections.

Abstract 4137688: Inhibition of Cardiac Fibrosis and Pro-Fibrotic Collagen Hormone Endotrophin by VS-041, a Novel Drug Candidate for Heart Failure with Preserved Ejection Fraction

Introduction: Endotrophin, a collagen type VI–derived signaling peptide, has been linked to cardiac metabolic dysregulation, inflammation, and fibrosis. Several matrix metalloproteinases (MMPs), incl. MMP2 and MMP9, have been shown to cleave collagen 6A3 and release endotrophin. Baseline plasma endotrophin levels in heart failure with preserved ejection fraction (HFpEF) patients were shown to be strongly and independently associated with increased risk of poor outcomes (death or HF-admissions). VS-041 is a novel drug candidate for HFpEF that inhibits key MMPs implicated in cardiac fibrosis and diastolic dysfunction. Previously, VS-041 demonstrated robust efficacy in the Dahl Salt Sensitive rat model of hypertension and HFpEF, improving diastolic function and dose-proportionally reducing left ventricle (LV) fibrosis. Hypothesis: Inhibition of endotrophin release by VS-041 could contribute to its anti-fibrotic mechanism and serve as a potential biomarker of MMP inhibition (target engagement) in patients. Methods and Results: The effect of VS-041 on production of endotrophin was investigated in a “Scar-in-a-Jar” model using primary human cardiac fibroblasts isolated from adult healthy ventricles. Fibroblasts were treated with 10 ng/mL platelet-derived growth factor (PDGF) AB in the presence of 0.03, 0.3, or 3 µM VS-041, or DMSO control. The concentration of endotrophin in the medium was assessed via the ELISA nordicPRO-C6 TM (Nordic Bioscience A/S). After 4 days of treatment, VS-041 at 0.3 µM and 3 µM significantly inhibited PDGF AB-stimulated production of endotrophin. Cumulative inhibitory effects of VS-041 could still be observed after 12 days of culture. The antifibrotic activity of VS-041 was also tested in a model of extensive cardiac fibrosis in 16-months old C57BL/6 mice exacerbated by angiotensin II infusion at 1 mg/kg/day for 28 days. Oral treatment with VS-041 at 75 mg/kg BID resulted in a 62% reduction (p<0.01) of LV fibrosis as assessed by morphometry of Masson trichrome stained sections. VS-041 also improved the diastolic echocardiography parameters IVRT and E/a ratio. Conclusions: The production of endotrophin by fibroblasts is diminished by VS-041 and, therefore, its plasma levels could be explored as a biomarker of in vivo MMP inhibition by VS-041. Additionally, the inhibition of endotrophin release by VS-041 could be causatively linked to reduction of cardiac fibrosis and potentially translate into improved clinical outcomes in HFpEF patients.

Clinical and Radiographic Results in Thoracic Hyperkyphosis Surgical Treatment Considering the Optimal Distal Fusion Area

Introduction: The aim of this retrospective study was to evaluate the clinical and radiographic outcomes of patients who underwent posterior correction and fusion for thoracic hyperkyphosis, with a focus on determining the optimal distal fusion level. Methods: From 2006 to 2012, 26 patients with a median age of 16.8 years (range 14–25), diagnosed with either idiopathic hyperkyphosis or Scheuermann’s kyphosis, underwent posterior fusion and Ponte osteotomies at two medical centers. Radiographic evaluations were performed preoperatively, immediately postoperatively, and at the final follow-up and included assessments of fusion extension, Cobb angle, sagittal balance, and the presence of junctional kyphosis or discopathy. Results: The median follow-up period was 12.3 years (range 11–17). Good clinical outcomes were observed in 24 patients, with no cases of hardware failure. The distal fusion area included the first lordotic vertebra in 17 patients, the sagittal stable vertebra in four patients, and both in five patients. Cobb angle correction was maintained at 50% at the final follow-up (p > 0.05). Significant sagittal balance correction was achieved in 87% of patients immediately postoperatively and was maintained at the final follow-up (p > 0.05). Junctional kyphosis occurred in two patients whose fusion area included only the first lordotic vertebra. Conclusions: Including at least the first lordotic vertebra in the fusion area is crucial for preventing junctional kyphosis. Extending the fusion to the stable vertebra can reduce the incidence of distal junctional kyphosis, especially in symptomatic young adult patients, potentially avoiding the need for revision surgery.

The Warming Management Measures May Need to Be Further Enhanced During Scoliosis Correction and Internal Fixation Surgery: A Retrospective Cohort Study.

The incidence of intraoperative hypothermia (IPH) exceeds 70% during spinal surgery, which can lead to many adverse outcomes, including increased intraoperative blood loss/transfusion and delayed recovery. We aimed to evaluate the comprehensive efficiency of a kind of enhanced warming measure on patients undergoing spinal surgery. A retrospective analysis was conducted on the clinical data, surgical procedures, and outcomes of consecutive patients admitted to the department of orthopedics of a hospital from December 2019 to May 2023 and undergoing spinal surgery (scoliosis correction and internal fixation surgery). The impact of the perioperative warming measures on surgical temperature variation and postoperative recovery was analyzed. The surgical patients who received normal active warming measures (quilt, blood transfusion and infusion warming, flushing fluid warming) were the control group (Normal Warming Group [NWG], n = 199), and the enhanced active warming measures (NWG and forced air warming) were the experimental group (Enhanced Warming Group [EWG], n = 201). Incidence of IPH was the primary endpoint of this study. EWG exhibited a significantly reduced incidence of IPH and average frequency of hypothermia per patient compared with NWG (respectively, p < 0.01) and demonstrated notable reductions in intraoperative blood loss, urine output, anesthesia recovery time, and duration of arousal (respectively, p < 0.05, p < 0.01, and p < 0.001). Postoperatively, EWG showed a significantly reduced incidence of shivering (p < 0.001) and had lower costs for postoperative antibiotic use and albumin administration (respectively, p < 0.05 and p < 0.01). So we infer that the occurrence of hypothermia during spinal surgery may seem unavoidable, but EWG can effectively lower the occurrence of IPH and its adverse outcomes, and then somewhat alleviate the postoperative treatment burden. However, given that this study is a retrospective cohort study, it is not yet possible to definitively prove the above conclusions, so we will design relevant prospective clinical studies to prove that the optimization of temperature management may be crucial to ensure optimal overall recovery outcomes.

Abstract 4138690: A Case of Hypertrophic Cardimyopathy: Digenic Variants of Uncertain Significance Mutations in MHY7 and RYR2 Genes

Introduction: Hypertrophic Cardiomyopathy (HCM) is primarily a disease caused by mutations in single genes, but around 5% of HCM patients, exhibit 2 (digenic) or more (oligogenic) causal mutations in the same gene or in different genes. We present a case of familial HCM with variants of uncertain significance (VUS) mutations in the MYH7 and RYR2 genes, highlighting the complexity of genetic inheritance and its implications on disease severity. Case presentation: A 40-year-old male presented with a history of hypertension, HCM, and two prior myocardial infarctions. He had syncope, non-sustained ventricular tachycardia, and a family history of sudden cardiac death (SCD) in his maternal grandfather. A dual-chamber ICD was placed for primary prevention of SCD because of his high-risk profile. Echocardiography demonstrated normal LV size and function with moderate asymmetric septal hypertrophy. Cardiac MRI indicated diffuse asymmetric hypertrophy and a 10.9% LV myocardial scar burden. Left heart catheterization revealed normal coronary arteries with LVOT gradient up to 60 mmHg, consistent with HCM. Genetic testing revealed VUS in the MYH7 (c.1305G&gt;A, p.Met435Ile) and RYR2 (c.10528C&gt;A, p.Arg3510Ser) genes (Figure 1). Further family genetic testing confirmed these VUS mutations in multiple relatives (Figure 2). Discussion: The identification of VUS mutations in MYH7 and RYR2 genes in multiple family members highlights the complexity of genetic inheritance in HCM. These findings underscore the challenges in clinical interpretation and risk stratification, as the co-occurrence of mutations in different genes may have synergistic effects on disease severity and phenotype expression. Comprehensive genetic evaluation, including family studies, is crucial for understanding the clinical significance of these mutations and guiding personalized management strategies. Further research is needed to elucidate the impact of VUS mutations on the clinical outcomes of HCM patients.

Clinical outcomes after extra-articular resection of hip joint tumour using a custom-made osteotomy guide and 3D-printed endoprosthesis with posterior column preserved.

For rare cases when a tumour infiltrates into the hip joint, extra-articular resection is required to obtain a safe margin. Endoprosthetic reconstruction following tumour resection can effectively ensure local control and improve postoperative function. However, maximizing bone preservation without compromising surgical margin remains a challenge for surgeons due to the complexity of the procedure. The purpose of the current study was to report clinical outcomes of patients who underwent extra-articular resection of the hip joint using a custom-made osteotomy guide and 3D-printed endoprosthesis. We reviewed 15 patients over a five-year period (January 2017 to December 2022) who had undergone extra-articular resection of the hip joint due to malignant tumour using a custom-made osteotomy guide and 3D-printed endoprosthesis. Each of the 15 patients had a single lesion, with six originating from the acetabulum side and nine from the proximal femur. All patients had their posterior column preserved according to the surgical plan. Postoperative pathological assessment revealed a negative surgical margin was achieved in all patients. At final follow-up, 13.3% (2/15) died and no recurrence occurred. The overall survival was 81.7% at five years. None of the patients showed any signs of aseptic loosening, and no wound healing issues were observed. In total, 20% (3/15) developed complications, with two cases of early hip dislocation and one case of deep infection. The cumulative incidence of mechanical and non-mechanical failure in this series was 13.7% and 9.3%, respectively, at five years. In this cohort, the mean time to full weightbearing was 5.89 (SD 0.92) weeks and the mean Musculoskeletal Tumor Society score was 24.1 (SD 4.4). For patients with a hip joint tumour who met the inclusion criteria and were deemed suitable for posterior column preservation, a custom-made osteotomy guide combined with 3D-printed endoprosthesis is worth performing when treating patients who require extra-articular resection of the hip joint, as it can achieve adequate margin for local control, maximize bone preservation to maintain pelvic ring integrity, reduce the risk of complications by simplifying the surgical procedure, and allow for more precise reconstruction for better function.

Abstract 4137895: Serum High-density Lipoprotein-Associated Paraoxonase-1 Levels Predict Recurrent Cardiovascular Events after Stent Implantation in Patients with Stable Angina Pectoris

Background: Poor clinical outcomes for patients undergoing hemodialysis (HD) after drug-eluting stent (DES) implantation have been reported. High-density lipoprotein (HDL) cholesterol is well-established as a negative risk factor for coronary artery disease, and its anti-oxidant property has been attributed mainly to the HDL-bound enzyme paraoxonase-1 (PON-1). Myeloperoxidase (MPO), a pro-oxidant enzyme released from activated neutrophils, has been shown to alter the atheroprotective function of HDL to a dysfunctional form. The aim of this study was to investigate the relationship between plasma MPO and serum PON-1 levels after implantation of DES in patients with stable angina pectoris (SAP) with and without HD. Methods: Serum PON-1 concentrations and PON-arylesterase activity were measured in 183 patients with SAP after DES implantation (HD group, n=37; non-HD group, n=146) with a sandwich ELISA method. Cardiovascular events were defined as sudden cardiac death, fatal or non-fatal myocardial infarction, cerebral infarction and other non-fatal events including unstable angina pectoris or coronary revascularization. Results: Serum PON-1 concentrations and PON-arylesterase activity were significantly lower in the HD group than in the non-HD group (PON-1 concentrations, P&lt;0.0001; PON-arylesterase activity, P&lt;0.0001). In addition, plasma MPO in patients undergoing HD were significantly higher than in patients not undergoing HD (P&lt;0.0001). Moreover, plasma MPO showed a significant inverse correlation with serum PON-1 concentrations and PON-arylesterase activity (concentration: R= -0.24, P=0.0013; arylesterase-activity: R=-0.24, P=0.0014). Cardiovascular event rates were significantly higher in the HD group than in the non-HD group (67.6% vs. 43.8%, P&lt;0.01). Kaplan-Meier survival analysis showed that the low-PON-1 group (&lt;58.0 mg/mL, median) had a significantly worse outcome than the high-PON-1 group ( P =0.013). Multivariate analysis showed that a low serum PON-1 concentration was the only independent predictor of cardiovascular events (odds ratio, 1.93; 95% confidence interval, 1.10 to 3.40, P =0.024). Conclusions: These findings demonstrate that plasma MPO have a significant inverse correlation with PON-1 in patients undergoing HD and suggest that an imbalance between pro-oxidants and anti-oxidants may contribute to the progression and destabilization of human coronary atherosclerotic lesions in patients with SAP who undergo HD following DES implantation.

Abstract 4136036: Five-year Outcomes of Heart-Kidney Transplant Recipients Bridged with Durable Mechanical Circulatory Support: Less AMR Better Survival?

Introduction: Despite the increased risk of sensitization in patients receiving pre-transplant durable mechanical circulatory support (D-MCS), it has been suggested that removing D-MCS at the time of transplant may lead to a drop in HLA-antibody levels. Whether this may reduce rejection rates and improve long-term outcomes in patients undergoing heart-kidney transplantation (HKTx) has not been widely investigated. Therefore, we aim to investigate the impact of pre-transplant D-MCS on 5-year clinical outcomes of patients undergoing HKTx. Methods: We included 98 patients undergoing HKTx between 2010 and 2018 at a single center. Recipient pre-transplant characteristics and clinical outcomes were compared between patients receiving D-MCS (n=24) versus non-D-MCS patients (n=74). The D-MCS cohort included those who received total artificial heart (n=13), left ventricular assist device (n=8), and biventricular assist devices (n=3). Endpoints included 1- and 5-year survival, 1-year-freedom from acute cellular rejection (defined as grade 2R or 3R), 1-year-freedom from antibody-mediated rejection (AMR, defined as pathologic AMR of grade ≥1), 5-year freedom from cardiac allograft vasculopathy (CAV, stenosis ≥30% by angiography), 5-year freedom from non-fatal major adverse cardiac events (NF-MACE including myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), and 5-year freedom from left ventricular dysfunction (LVEF ≤40). Results: At 1 year, freedom for AMR was numerically higher in the D-MCS group (100 vs. 90.2%, P=0.12). Additionally, the 5-year post-transplant survival rate was higher in the D-MCS group (95.8% vs. 80.8%), but it did not reach statistical significance (P=0.091). Comparable outcomes were noted for other outcomes, including 5-year freedom from CAV, NF-MACE, or LVD (Table 1 ). Conclusion: The current study hints at better 5-year survival in HTKx recipients receiving pre-transplant D-MCS, which could be attributed to lower rates of AMR in this population. Future larger studies are warranted to further validate these findings.

NCMP-30. GLUCOCORTICOID-INDUCED HYPERGLYCEMIA IN BRAIN TUMOR PATIENTS: A SINGLE CENTER RETROSPECTIVE STUDY

Abstract BACKGROUND Glucocorticoid (GC) therapies are integral in managing brain tumor-associated cerebral edema and neurological deficits in the neuro-oncology perioperative setting. Despite their effectiveness, GCs can induce significant morbidity, including hyperglycemia. METHODS This single-center retrospective study at the University of North Carolina neurological surgery department examines the incidence and risk factors for glucocorticoid-induced hyperglycemia in brain tumor patients treated with high-dose GCs. Data from clinical databases, electronic medical records, laboratory systems, and pathology information banks will be utilized. Documented glucose measurements, glycated hemoglobin test (HbA1c) and clinical outcomes (mortality, infection, hypoglycemia) in brain cancer patients treated with Glucocorticoid (GC) that developed hyperglycemia will be compared with brain tumor patient with normoglycemia. RESULTS We will document the total number of brain tumor patients referred over the study period, eligibility rates, and the percentage that developed glucocorticoid-induced diabetes (defined as two glucose measurements ≥200 mg/dL within the first week of treatment). Timing of hyperglycemia onset, treatments received, and risk factors for developing glucocorticoid-induced diabetes will also be analyzed. CONCLUSIONS The findings could underscore the necessity for proactive screening for glucocorticoid-induced diabetes in brain tumor patients to mitigate the associated morbidity. This study may guide future research on the benefits of optimized glucose control on clinical outcomes in patients with GC-induced hyperglycemia. Keywords: brain tumor, steroid-induced hyperglycemia, glucocorticoid-induced diabetes, dysglycemia, risk factors, outcomes.

Effects of Vitamin C Supplements on Clinical Outcomes and Hospitalization Duration for Patients with Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis.

Vitamin C has been used as an essential antioxidant to reduce the inflammatory response associated with pneumonia and acute respiratory distress syndrome in patients with the 2019 coronavirus disease (COVID-19), but its effect on clinical outcomes remains controversial and inconclusive. The purpose of this study was to conduct a meta-analysis and systematic review to assess the effects of vitamin C supplementation on the severity of COVID-19 in hospitalized patients. Web of Science, Embase, Cochrane Library, PubMed, CNKI, CSTJ, Wan fang, and CBM databases were searched for publications between January 2020 and December 2023 that met the inclusion criteria. The meta-analyses of outcomes in more than one study were performed using Review Manager software. Heterogeneity was evaluated using the I2 statistic. A randomized controlled trial, cohort studies, and retrospective studies in which vitamin C supplementation was supplemented as monotherapy or in combination, compared with placebo, no treatment, or other standard treatment without vitamin C were included. After screening, 22 studies, with a total of 6831 patients, were selected for assessment. Odds ratios (ORs) with 95% CIs were calculated using fixed- and random-effects models. The meta-analysis showed significant effects of vitamin C on alleviating clinical outcomes in patients with COVID-19 (OR = 0.76, 95% CI = 0.65-0.89, P = .0007) but no shortening of the length of hospitalization (OR = 1.16, 95% CI = -0.13-2.44, P = .08) compared with the control group. Notably, vitamin C supplements significantly reduced the mortality risk (OR = 0.64, 95% CI = 0.51-0.80, P = .0001) and the incidence of severity (OR = 0.59, 95% CI = 0.43-0.80, P = .0006) in COVID-19 patients. The findings suggest that vitamin C supplements may have a beneficial effect on clinical outcomes, as well as reducing severity and mortality in COVID-19 patients, but more clinical randomized controlled trials are needed to evaluate the role of vitamin C in treating COVID-19. PROSPERO registration no. CRD42023491517.