Multicenter Observational Study Research Articles

The evaluation of myocarditis in patients with Still's disease; clinical findings from the multicentre international AIDA Network Still's Disease Registry.

To evaluate the cardiac involvement in patients with Still's disease with a focus on myocarditis included in the multicenter AIDA (AutoInflammatory Disease Alliance) network Still's disease registry. To exploit the predictive factors for myocarditis in deriving a clinical risk patient profile for this severe manifestation. A multicenter observational study was built up assessing consecutive patients with Still's disease characterized by the cardiac involvement among those included in the AIDA Network Still's Disease Registry. The cardiac involvement was defined according to the presence of pericarditis, tamponade, myocarditis, and/or aseptic endocarditis. In total, 73 patients with Still's disease and cardiac involvement were assessed (mean age 36.3±19.9 years, 42.5% male sex); out of them, 21.9% were children. The most common cardiac manifestation was the pericarditis in 90.4% of patients, 26.0% presented with myocarditis, and less frequently endocarditis (2.7%) and tamponade (1.4%). Comparing clinical features of patients with myocarditis than others, significantly increased frequencies of skin rash, and pleuritis as well as higher values of systemic score were recognised. Furthermore, an enhanced mortality rate was registered in patients with myocarditis. In regression models, the skin rash and the systemic score independently predicted the myocarditis. The characteristics of patients with Still's disease and cardiac involvement were assessed in the AIDA network. The most common feature was the pericarditis but also a more severe clinical picture was reported in patients with myocarditis. The latter was associated with increased mortality rate and with higher systemic score, identifying patients to be carefully managed.

Clinical impact of ceftazidime/avibactam on the treatment of suspected or proven infections in a large cohort of patients with haematological malignancies: a multicentre observational real-world study.

To evaluate clinical impact of ceftazidime/avibactam on treating infections due to MDR Gram-negative bacteria in patients with haematological malignancies (HMs). We conducted a retrospective, observational study at 17 Italian haematological wards that included patients with HMs receiving ceftazidime/avibactam for the treatment of suspected or proven infections. The primary endpoint was all-cause mortality 30 days after infection onset. Secondary endpoints included the development of in vitro ceftazidime/avibactam resistance, adverse reactions and infection relapse. Of 198 patients enrolled, 66 had fever of unknown origin and 132 had microbiologically proven infections (MPIs). Enterobacterales were responsible for 98 MPIs, with KPC producers accounting for 75% of these, and carbapenem-resistant Pseudomonas aeruginosa caused 25% of MPIs. The overall 30-day mortality rate was 17.7%. Infection relapse occurred in four patients with MPI. Patients who died within 30 days of infection onset tended to have pre-existing cerebrovascular diseases, a Charlson Comorbidity Index > 4 and septic shock at infection onset and had received inadequate initial antibiotic therapy. Thirty-day mortality was independently associated with septic shock at infection onset and inappropriate initial antibiotic therapy. Our study provides further evidence about the effectiveness of ceftazidime/avibactam in treating infections in patients with HMs.

Population pharmacokinetics of rilpivirine following oral administration and long-acting intramuscular injection in real-world people with HIV

BackgroundThe pharmacokinetics of long-acting rilpivirine has mostly been studied in clinical trials, which do not fully address the uncertainties that arise in routine clinical situations.Aims and methodsOur population analysis aims to establish percentile curves for rilpivirine concentrations in people with HIV (PWH) followed-up in a routine clinical setting, while identifying patient-related factors that may influence rilpivirine exposure. A total of 238 PWH enrolled in our nationwide multicenter observational study contributed to 1038 concentrations (186 and 852 concentrations after oral and intramuscular injection, respectively).ResultsRilpivirine pharmacokinetics were best described by a two-compartment model with an oral to intramuscular relative bioavailability factor. A simple zero-order absorption process was retained for oral administration while a parallel first-order absorption was used for intramuscular administration, with 27.6% of the dose released via a fast absorption pathway and the remaining fraction via a slow absorption pathway. Our model estimated that long-acting rilpivirine reaches steady-state after 2.5 years and has an elimination half-life of 18 weeks, consistent with published estimates. In females, a 45.6% reduction in the proportion of the dose absorbed via the rapid absorption pathway was observed. However, this resulted in no more than 15% difference in trough concentrations (Ctrough) compared to males, which was not considered to be clinically relevant.ConclusionOverall, our model-based simulations showed that only approximately 50% of long-acting rilpivirine Ctrough would be above the 50 ng/mL threshold associated with optimal therapeutic response, while approximately 85% of Ctrough would be above the first quartile of concentrations observed in Phase III trials (32 ng/mL).

Association of low muscle strength with incident pneumonia in older patients with heart failure.

Patients with heart failure (HF) are at an increased risk of developing pneumonia, leading to a high mortality. A decrease in muscle strength due to aging or concomitant disease may contribute to the development of pneumonia in older adults. We sought to investigate the relationship between low muscle strength and pneumonia incidence in older patients hospitalized for worsening HF. We carried out a sub-analysis of the FRAGILE-HF, a prospective multicenter observational study, including 1266 consecutive older (≥65 years) patients hospitalized with HF (mean age 80.2±7.8 years; 57.4% male; left ventricular ejection fraction 46±17%) and information of incident pneumonia observed after discharge. Patients were followed up for two years post-discharge. A total of 88 patients (7.0%) developed pneumonia after discharge, with an incidence of 42.7 per 1,000 person-years. A total of 893 patients with low muscle strength, defined as handgrip strength <28kg for men and <18kg for women according to international criteria, were more likely to develop pneumonia than those with normal muscle strength (p <0.001; log-rank test). Low muscle strength was a significant predictor of incident pneumonia (adjusted hazard ratio with 95% confidence interval: 2.65 [1.31-5.35], p=0.007). Furthermore, the mortality rates were 43.2% in patients who developed pneumonia and 19.3% in those who did not, indicating a heightened risk of death following the onset of pneumonia (adjusted hazard ratio: 4.25 [2.91-6.19], p<0.001). In older patients hospitalized for HF, low muscle strength was associated with incident pneumonia after discharge.

The Clinical Significance of Interstitial Pneumonia with Autoimmune Features in Cryptogenic Organizing Pneumonia: A Prospective Multicenter Observational Study

Background: There are cases of idiopathic interstitial pneumonias (IIPs) that do not meet the diagnostic criteria for connective tissue disease but have clinical features suggestive of autoimmune process. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept for these patients. Although several prospective studies on IPAF have been conducted, its clinical significance in cryptogenic organizing pneumonia (COP) remains unclear. Methods: Patients aged ≥20 years with suspected COP were prospectively enrolled between June 2018 and December 2022. Among the enrolled patients, those diagnosed with COP based on computed tomography (CT) and bronchoalveolar lavage (BAL) findings were compared between the IPAF and non-IPAF groups. Results: A total of 56 patients were enrolled in this study. Of these, 30 were diagnosed with COP and included in the analysis. Clinical and serological features were positive in two and six patients, respectively. Each feature was exclusive, and eight patients (26.7%) were diagnosed with IPAF. There were no differences between the IPAF and non-IPAF groups in terms of clinical features, including BAL findings, laboratory data, CT findings, and clinical course. During the one-year follow-up period, the frequency of COP exacerbation did not differ between the IPAF and non-IPAF groups, and no cases of systemic autoimmune disease or death occurred in either group. Conclusions: The COP characteristics of the IPAF and non-IPAF groups are similar in all aspects, and distinguishing between the two groups may be of little significance.

Equimolar oxygen-nitrous oxide (EMONO) in dental pediatric care: which patients achieve therapeutic effects? A French national exploratory prospective observational multicenter study.

Equimolar oxygen-nitrous oxide mixture (EMONO) is considered as a reference for dental care in children. Completion of dental treatment has usually been used as a criterion to assess EMONO treatment. However, other patient-reported outcomes are needed. We sought to assess the prevalence of complete therapeutic effects (analgesia and anxiolysis) experienced by children during dental care under EMONO and identifying associated factors. A national prospective observational multicentric study was conducted between September 2018 and June 2020 in 13 French university hospitals. Participants were children between 3 and 15years of age requiring dental care under EMONO. 677 children were analyzed. Anxiolysis and analgesia were experienced by a large majority of patients (86.5% and 79.0%, respectively, and 73% experienced both effects). Several factors were associated with both analgesia and anxiolysis effects: the presence of expected effects (no loss of judgment and slight decrease in level of consciousness), the absence of agitation and distress, a positive perception of EMONO and ethnicity. Most patients benefit from the therapeutic effects (anxiolysis and analgesia) expected by EMONO during dental treatment. It is reassuring to observe that most sociodemographic characteristics and medical history do not seem to influence the effectiveness of care. The study was registered at www. gov under the reference number NCT03453411.

Why Symptoms Linger in Quiescent Crohn's Disease: Investigating the Impact of Sulfidogenic Microbes and Sulfur Metabolic Pathways.

Even in the absence of inflammation, persistent symptoms in patients with Crohn's disease (CD) are prevalent and worsen quality of life. We previously demonstrated enrichment in sulfidogenic microbes in quiescent Crohn's disease patients with (qCD + S) vs without persistent GI symptoms (qCD-S). Thus, we hypothesized that sulfur metabolic pathways would be enriched in stool while differentially abundant microbes would be associated with important sulfur metabolic pathways in qCD + S. We performed a multicenter observational study nested within SPARC IBD. Quiescent inflammation was defined by fecal calprotectin level < 150 mcg/g. Persistent symptoms were defined by CD-PRO2. Active CD (aCD) and non-IBD diarrhea-predominant irritable bowel syndrome (IBS-D) were included as controls. Thirty-nine patients with qCD + S, 274 qCD-S, 21 aCD, and 40 IBS-D underwent paired shotgun metagenomic sequencing and untargeted metabolomic profiling. The fecal metabolome in qCD + S was significantly different relative to qCD-S and IBS-D but not aCD. Patients with qCD + S were enriched in sulfur-containing amino acid pathways, including cysteine and methionine, as well as serine, glycine, and threonine. Glutathione and nicotinate/nicotinamide pathways were also enriched in qCD + S relative to qCD-S, suggestive of mitochondrial dysfunction, a downstream target of H2S signaling. Multi-omic integration demonstrated that enriched microbes in qCD + S were associated with important sulfur metabolic pathways. Bacterial sulfur metabolic genes, including CTH, isfD, sarD, and asrC, were dysregulated in qCD + S. Finally, sulfur metabolites with and without sulfidogenic microbes showed good accuracy in predicting the presence of qCD + S. Microbial-derived sulfur pathways and downstream mitochondrial function are perturbed in qCD + S, which implicate H2S signaling in the pathogenesis of this condition. Future studies will determine whether targeting H2S pathways results in improved quality of life in qCD + S.

Differences in association between hypoalbuminaemia and mortality among younger versus older patients on haemodialysis

Abstract Background Ageing often impacts on biomarker production. Yet, clinical/optimal thresholds to guide clinical decisions do not consider this. Serum albumin decreases with age, but hypoalbuminaemia is defined as serum albumin &amp;lt;4.0 g/dL. This study explores whether age might affect serum albumin levels and its association with mortality in haemodialysis patients. Methods COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) is a prospective, open cohort, observational study of haemodialysis patients followed for 3 years. Binary logistic and linear regression were used to analyse the association between age and hypoalbuminaemia or serum albumin (continuous). Cox proportional hazard multivariate regression was used to examine the relationship between hypoalbuminaemia and mortality in patients younger and older than 65 years. Time-dependent receiver operating characteristic (ROC) curves were used to assess the discriminatory ability of serum albumin and optimal thresholds for predicting mortality. Results The present analysis included 5,585 patients. The odds of experiencing hypoalbuminaemia increased with age (adjusted odds ratios = 1.56[95%CI: 1.31-1.86], 1.89[95%CI: 1.59-2.24], 2.68[95%CI: 2.22-3.23] for 56-65, 66-75 and &amp;gt; 75 years respectively (reference ≤55 years; p-value for trend: &amp;lt;0.001)). Survival analysis showed that the association between hypoalbuminaemia and mortality was weaker in patients aged ≥65 compared to &amp;lt;65 years (Hazard Ratios: 1.36[95%CI: 1.17-1.57] and 1.81[95%CI:1.42-2.31] respectively; p-value for interaction 0.004). The ability of albumin levels to predict mortality was consistently higher in younger patients. Optimal albumin thresholds for predicting mortality were 3.7 g/dL in patients younger than 65 years and 3.5 g/dL in patients 65 years and older. Conclusions Ageing is accompanied by lower albumin levels, and the association between hypoalbuminaemia and mortality may be modified by age. Different clinical thresholds that consider age may better discriminate risks associated with hypoalbuminaemia.

Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter study.

Diagnostic boundaries between immune thrombocytopenia (ITP) and other thrombocytopenic states such as thrombocytopenic myelodysplastic syndromes, may be difficult to establish, and the detection of somatic mutations by next generation sequencing (NGS) may be of aid. Here we aimed at characterizing the prevalence and clinical significance of clonal hematopoiesis in ITP. In this multicentric retrospective observational study we enrolled 167 adult ITP patients, followed at 13 centers in Italy, UK, and USA. Patients underwent NGS evaluation after a median of 3.6 years from ITP onset and 83% had received at least one therapy line, median 2 (0-9) lines; 51 out of 167 patients had at least one mutation (30%). After exclusion of germline variants and polymorphisms, 18.5% (31/167) were defined as having clonal hemopoiesis. Most commonly mutated genes were TET2, DNMT3A, SRSF2, and ASXL1 (median VAF 29%); 19 of 31 subjects (68%) had high-risk variants, and 8 multiple mutations. Mutated patients were more frequently elderly males and showed a shorter time from first to second line therapy, particularly with TPO-RA. Additionally, clonal hematopoiesis was associated with increased thrombotic risk (26% vs 8% in NGS-negative cases, p=0.01), independently from TPO-RA exposure, though with an age effect. These data demonstrated the prevalence of clonal hematopoiesis in 18% of adult ITP patients, being associated with older age, relapsed/refractory disease, and high risk of thrombotic complications.

Abstract B013: An mDETECT assay for monitoring treatment response in metastatic breast cancer patients

Abstract Metastatic breast cancer treatment response is currently assessed every 3-6 months and this long delay results in many patients undergoing ineffective and toxic treatments for long periods of time. We have developed the methylation DETEction of Circulating Tumour DNA (mDETECT) assay, a targeted DNA methylation-based Next Generation Sequencing liquid biopsy that detects cancer-specific patterns in all subtypes of breast cancer. The assay targets 60 differentially hypermethylated regions in breast cancer across the genome and assesses over 400 individual CpGs with an average of 8 CpGs per target amplicon. The assay has been assessed on DNA from 73 breast cancer tumour samples which on average had 40 regions hypermethylated per patient with similar rates across all subtypes. We will present results from plasma samples from locally advanced and metastatic breast cancer patients along with plasma from age-matched, healthy female controls. A prospective, multi-centre observational cohort study to monitor metastatic breast cancer patients using the mDETECT liquid biopsy as they undergo treatment is active and recruiting patients. Blood is drawn with every standard-of-care blood draw for up to 3 years. Plasma has been assessed using the mDETECT assay to determine the methylation status of the DNA at each time point. 35 patients have been enrolled to date with ongoing recruitment up to 150 patients. Patients are being monitored with the mDETECT assay for earlier detection of disease progression on a treatment. They will also be monitored through treatment changes to assess a patient’s initial response to a given treatment. Changes in mDETECT levels will be correlated with clinical response to determine if the mDETECT breast cancer assay can detect a response to treatment at an earlier timepoint. This assay could allow for improved monitoring of treatment response allowing clinicians to make informed decisions, improving outcomes and prolonging patient’s lives. Citation Format: Keira Frosst, Brooke Wilson, Katrina Cristall, Catherine Crawford-Brown, Christopher R Mueller. An mDETECT assay for monitoring treatment response in metastatic breast cancer patients [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 B013.

HPB SO08 - Safety of Robotic cholecystectomy as index training procedure – the UK experience

Abstract Background A recent large retrospective cohort study reported a higher risk of bile duct injury associated with robotic cholecystectomy when compared to the laparoscopic approach. Considering that most robotic training pathways, including the one followed in the UK, utilise robotic cholecystectomy as index training procedure, such findings mandate evaluation of the safety profile of robotic cholecystectomy in the UK to ensure its use as an alternative approach to laparoscopic cholecystectomy is not putting patients at risk. We aimed to conduct a multi-centre observational study to evaluate the safety profile of robotic cholecystectomy performed within the UK HPB Robotic training program. Method A retrospective analysis of prospectively collected data from eleven centres participating in the UK robotic HPB training program was conducted. All adult patients undergoing robotic cholecystectomy for symptomatic gallstone disease or gallbladder polyp were considered. Bile duct injury, conversion to open procedure, conversion to subtotal cholecystectomy, length of hospital stay, 30-day re-admission, and post-operative complications were the evaluated outcome parameters. Results A total of 600 patients were included. The median age was 53 (IQR 65 - 41) years and the majority (72.7%; 436/600) were female. The main indications for robotic cholecystectomy were biliary colic (55.5%, 333/600), cholecystitis (18.8%, 113/600), gallbladder polyps (7.7%, 46/600) and pancreatitis (6.2%, 37/600). The median length of stay was 0 (IQR: 0-1) days. Of the included patients, 88.5% (531/600) were discharged on the day of procedure with 30-day re-admission rate of 5.5% (33/600). There were no bile duct injuries and the rate of conversion to open was 0.8% (5/600) with subtotal cholecystectomy rate of 0.8% (5/600). Conclusion This current study confirms that robotic cholecystectomy can be safely implemented to routine practice with a low risk of bile duct injury, low conversion to open surgery and low need for subtotal cholecystectomy.

Cognitive reserve against Alzheimer's pathology is linked to brain activity during memory formation.

The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we test this hypothesis in the continuum from cognitively normal to at-risk stages for Alzheimer's Disease (AD) to AD dementia using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function is measured using task fMRI of visual memory encoding. Using a multivariate moderation analysis, we identify a CR-related activity pattern underlying successful memory encoding that moderates the detrimental effect of AD pathological load on cognitive performance. CR is mainly represented by a more pronounced expression of the task-active network encompassing deactivation of the default mode network (DMN) and activation of inferior temporal regions including the fusiform gyrus. We devise personalized fMRI-based CR scores that moderate the impact of AD pathology on cognitive performance and are positively associated with years of education. Furthermore, higher CR scores attenuate the effect of AD pathology on cognitive decline over time. Our findings primarily provide evidence for the maintenance of core cognitive circuits including the DMN as the neural basis of CR. Individual brain activity levels of these areas during memory encoding have prognostic value for future cognitive decline.

Abstract 4138704: Safety and Efficacy of Generic Atorvastatin in Korean Dyslipidemia Patients: A Non-Interventional Observational Study

Background: Statins are widely used for controlling dyslipidemia. However, most evidences for dyslipidemia prevention and treatment with statins are based on studies involving Caucasian populations, resulting in limited data on Korean patients. This study was conducted to evaluate the efficacy lipid profile and safety of generic atorvastatin in a real-world clinical setting among Korean dyslipidemia patients. Methods: This study was conducted as a non-interventional, multi-center observational study. It was carried out across 264 institutions and clinics from October 2017 to July 2021. Total 16,992 participants were enrolled. The safety and efficacy evaluation cohorts consisted of 16,803 and 11,035 subjects, respectively. The liver function evaluation cohort included 13,889 subjects. The main eligibility criteria were dyslipidemia patients prescribed generic atorvastatin according to approved indications. Adverse event rates were collected for safety evaluation, and lipid profiles, including LDL-C, were collected for efficacy evaluation. Results: In the safety endpoint evaluation, 1,612 adverse events were reported in 1,027 subjects (6.11%). Common adverse events such as dizziness, headache, and constipation, which were frequently observed in this study, were within the approved labels. Muscle pain occurred in 0.14% of subjects, and myopathy, myositis, rhabdomyolysis, and CK abnormalities or increases were reported in 0.01% of subjects, respectively. Most of the adverse events were confirmed to be mild or resolved, and the study was completed without changing the dose. All abnormal liver function test results were reported in less than 1% of subjects (AST increase: 0.14%, ALT increase: 0.1%, ALP increase: 0.01%, γ-GT increase: 0.01%). The mean LDL-C decreased from 117.31 mg/dL to 89.97 mg/dL, showing a statistically significant improvement in LDL-C levels (p &lt; 0.0001). Conclusions: Generic atorvastatin demonstrated tolerable safety as well as significant efficacy on lipid profile. Generic atorvastatin might be safe and effective for Korean patients with dyslipidemia.

Abstract Su904: The association between base excess on arrival at the hospital and neurological outcome of adult out-hospital cardiac arrest: observational study

Background: The relationship between base-excess (BE) values, which take into account the time interval from cardiac arrest to blood test, and neurological outcome after out-of-hospital cardiac arrest (OHCA) is not well understood. The purpose of this study was to evaluate the association between BE on arrival at the hospital and neurological outcomes in OHCA patients. Methods: The CRITICAL study, a prospective, multicenter observational study in Osaka, Japan, registered consecutive OHCA patients who were transported to 16 participating critical care centers from 2012 to 2021. We included adult patients aged 18 years with witnessed OHCA whose BE values on hospital arrival was available, and divided patients into quartiles based on BE values of initial blood test on arrival at the hospital: Q1 (BE ≤ −21.1 mmol/L), Q2 (−21.1 &lt; BE ≤ −15.7 mmol/L), Q3 (−15.7 &lt; BE ≤ −10.4 mmol/L), and Q4 (BE &gt; −10.4 mmol/L). The primary outcome was one-month survival with favorable neurological outcome, defined as cerebral performance category scale 1 or 2. Results: A total of 23,854 patients were registered, and 6,066 of them were eligible for analyses. Neurologically favorable outcome was the lowest in the Q1 group (3.2% [49/1,528]), followed by the Q2 (4.7% [70/1,493]), Q3 (9.8% [148/1,515]), and Q4 (23.5% [359/1,530]) group. In the multivariable logistic regression analysis, the adjusted odds ratio of Q1 compared with Q4 for one-month favorable neurological outcome was 0.13 (95% CI 0.090–0.18). The proportion of one-month favorable neurological outcome decreased progressively across decreasing quartiles (p for trend &lt; 0.001). In subgroup analysis, there was an interaction between presence of return of spontaneous circulation (ROSC) before blood test and neurological outcome (p for interaction &lt; 0.001). The neurological outcome worsened as the BE values decreased among those who achieved ROSC before the blood test (p for trend &lt; 0.001), but not in those without ROSC (p for trend = 0.078). There was not a significant interaction between BE values without ROSC before blood test and time from witness to blood test (p for interaction = 0.501). Conclusions: We demonstrated that lower BE values at hospital arrival were associated with worse neurological outcome. The BE values may be one of the effective prognostic indications for neurological outcome, especially in OHCA patients with ROSC before hospital arrival.

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 4137534: Troponin Can Predict Late Gadolinium Enhancement on Cardiac MRI in COVID-19 Vaccine-Associated Myocarditis

Background/Aim: We previously reported that late gadolinium enhancement (LGE) on cardiac MRI (CMR) was as high as 82% in pediatric patients with COVID-19 vaccine-associated myocarditis (C-VAM) despite mild clinical symptoms and normal left ventricular function. As LGE can be a harbinger for future adverse events including arrhythmias, heart failure or sudden cardiac death, we sought to identify predictors for LGE in C-VAM, specifically assessing troponin as a screening marker for C-VAM patients at risk for myocardial scarring who could then be referred for a confirmatory CMR with LGE. Methods: In this longitudinal multicenter retrospective observational study across 38 U.S. member institutions of the M yocarditis A fter C OVID V accination (MACiV) study network, 333 patients with C-VAM based on CDC criteria were included from April 2021 to November 2022. Data collected included demographics, laboratory values, clinical and cardiac imaging characteristics and outcomes. Using logistic regression, troponin levels at presentation were assessed as a log transformed continuous variable and categorized into tertiles. Results: The C-VAM patients were predominantly white (67%) adolescent males (91%, 15.7± 2.8 years). There were 216/333 (65%) patients who had both a reported troponin value and had a CMR. On univariate analysis, elevated troponin increased the probability of having LGE (OR=1.29, 95% CI: 1.06, 1.58, p=0.012). Even after controlling for age, race, sex, number of vaccine doses and left ventricular ejection fraction (OR=1.32, 95% CI: 1.06, 1.65, p=0.013). Patients &gt;15 years compared to those ≤15 years of age were 2.94 (95% CI: 1.28, 6.75, p=0.011) times more likely to have LGE at presentation. Patients with troponin levels in the highest tertile compared to lowest tertile were 2.66 times (95% CI: 1.04, 6.83, p=0.042) more likely to have LGE along with a greater involvement &gt; 4 AHA myocardial segments with LGE (p=0.004) Conclusions: Higher troponin values are associated with presence of late gadolinium enhancement on cardiac MRI in patients with COVID-19 vaccine-associated myocarditis. Troponin levels at presentation may facilitate risk stratification and function as a screening tool to identify those C-VAM patients with the greatest likelihood of myocardial scarring, who may benefit from undergoing CMR for tissue characterization.

Antimicrobial Resistance of Escherichia coli for Uncomplicated Cystitis: Korean Antimicrobial Resistance Monitoring System

Objectives: Uncomplicated cystitis is a leading form of bacterial UTI; the most common causative bacterium worldwide is Escherichia coli. This internet-based, prospective, multicenter, and national observational study aimed to report the antimicrobial resistance of E. coli in patients with uncomplicated cystitis through the use of the Korean Antimicrobial Resistance Monitoring System (KARMS) in 2023. Results: Data for a total of 654 patients were retrieved from the KARMS database. The mean (standard deviation) patient age was 55.9 (18.3) years. The numbers of postmenopausal women and patients with recurrent cystitis were 381 (59.4%) and 78 (11.9%), respectively. Regarding antimicrobial susceptibility, 96.8% were susceptible to fosfomycin, 98.9% to nitrofurantoin, 50.9% to ciprofloxacin, and 82.4% to cefotaxime. Extended-spectrum beta-lactamase positivity was 14.4% (89/616), and was significantly higher in tertiary hospitals (24.6%, p &lt; 0.001) and recurrent cystitis (27.6%, p &lt; 0.001). Fluoroquinolone resistance was significantly higher in tertiary hospitals (57.8%, p &lt; 0.001), postmenopausal women (54.2%, p &lt; 0.001), and recurrent cystitis (70.3%, p &lt; 0.001). In addition, postmenopausal status (95% confidence interval [CI]: 1.44–3.17, odds ratio [OR] 2.13, p &lt; 0.001), recurrent cystitis (95% CI: 1.40–4.66, OR 2.56, p = 0.002) and tertiary hospitals (95% CI: 1.00–2.93, OR 1.71, p = 0.049) were associated with significantly increased fluoroquinolone resistance. Methods: Any female patient diagnosed with clinical uncomplicated cystitis and microbiologically proven E. coli infection in 2023 was eligible for this study. Patient data were obtained from the web-based KARMS database. The antimicrobial susceptibility of E. coli was analyzed according to clinical factors, including hospital region, hospital type, menopause status, and recurrence status. Conclusions: The antimicrobial resistance of E. coli in patients with uncomplicated cystitis in the Republic of Korea has reached a serious level, especially in fluoroquinolone resistance. Therefore, major efforts should be made to reduce antimicrobial resistance.

Abstract 4125252: Pre-Hematopoietic Stem Cell Transplantation Echocardiographic Indices and Post-Transplant Cardiovascular Outcomes

Introduction: Hematopoietic stem cell transplantation (HSCT) is associated with adverse cardiovascular (CV) events including the development of heart failure (HF) and arrythmias. While transthoracic echocardiogram (TTE) is routinely obtained prior to HSCT, its role in predicting the incidence of HSCT related CV events is poorly understood. Methods: We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center from 2008-2019. In this analysis, we included patients from UMHS with a baseline TTE. Data on pre-HSCT TTE parameters and post-HSCT CV outcomes were collected through manual chart review. Left ventricular (LV) function and dimensions were categorized into normal, mildly abnormal, and moderately/severely abnormal based on American Society of Echocardiography guidelines. The primary outcomes were new-onset HF and atrial fibrillation/flutter post-HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT CV risk score. Results: Of the 2071 patients (mean age at HSCT 55.5 + 12.9 years; 59.5% male) with a pre-HSCT TTE (median 25 days pre-HSCT), 116 (5.6%) and 128 (6.2%) patients experienced HF and atrial fibrillation/flutter, respectively, over a median period of 2.2 years. Greater abnormalities in left ventricular internal diameter at end-diastole (LVIDd) and end-systole (LVIDs) were linearly associated with a higher risk of HF (P-trend 0.018 and 0.004, respectively) (Table). Similarly, moderately/severely abnormal LVIDd was associated with a 2.41-fold (95% CI: 1.07, 5.43) increase in risk of atrial fibrillation/flutter (Table). Pre-HSCT ejection fraction (EF) was not associated with either endpoint. Conclusion: LV dilation, even when mild, was notably associated with increased risk of developing new HF or atrial arrythmias post-HSCT, regardless of EF. Whether evidence of LV dilation should prompt the initiation of guideline directed medical therapy to minimize the risk of incident HF warrants further study.

Abstract 4135582: Sociodemographic Trends in Diabetes Medications after Metformin: the BESTMED (oBservational Evaluation of Second line Therapy MEdications in Diabetes) Study

Objective: Though updated American Diabetes Association (ADA) guidelines recommend initiating GLP1 receptor agonists (GLP1) or SGLT2 inhibitors (SGLT2i) for persons with type 2 diabetes mellitus (PWT2DM) with high CV risk, metformin was previously recommended as 1st-line treatment. For PWT2DM at moderate CV risk, it is unknown which 2nd-line drug optimizes CV outcomes. Our multicenter observational study describes US-wide trends in 2nd-line T2DM medication use (DPP4 inhibitors [DPP4i], GLP1s, SGLT2i and sulfonylureas [SU]) overall and in key sociodemographic subgroups between 2014-2023. Methods: This is a secondary analysis of the oBservational Evaluation of Second line Therapy Medications in Diabetes (BESTMED) study, which used a new-user design to evaluate associations between 2nd-line medications and CV events in PWT2DM at moderate CV risk. The database comprised EHRs and insurance claims for 75,224 PWT2DM from 10 health systems and 2 insurance plans on metformin who initiated a 2nd medication from 1/2013 to 1/2023. Data were obtained from orders or prescription fills. Prescription class was regressed on calendar time via multinomial logistic regression to model trends in prescribing patterns, adjusted for sociodemographic variables. Subgroup analyses were performed by adjustment factors; CIs and p-values for differences were calculated via nonparametric bootstrap (B=200). Due to large sample size, statistical significance was interpreted at p&lt;0.05 and annual rate of change &gt;0.5%. Results: We included 75,224 T2DM adults (median A1c 7.8%), of whom 18%,17%, 18%, and 47% initiated DPP4i, GLP1, SGLT2i, SU respectively. From 2014 - 2023, SGLT2i and GLP1 increased: 5.7 to 28.8%, and 3.5 to 30.3%, and DPP4i and SUs decreased: 25.3 to 11.6%, and 65.6 to 29.3%, respectively. Annual rate of change for SGLT2i was higher in men(3.0% vs 2.1%/year; p&lt;0.001) and in &gt; 65 y (3.0% vs 2.4%; p&lt;0.001), and for GLP1s was higher in those &lt;65 y (3.6% vs 2.1%; p&lt;0.001), women (3.5% vs 2.5%; p&lt;0.001), Hispanic ethnicity (3.2% vs 2.7%; p=0.005), and with class II/III obesity (4.1% versus 2.6% per year; p&lt;0.001). There was no evidence that these trends differed by race, insurance, or SDI. Conclusion: In this nationwide study of prescribing patterns PWT2DM at moderate CV risk, prevalences of 2nd-line T2DM therapies are approaching current ADA guidelines for initial therapy for those at high CV risk. Differences between sociodemographic groups appear aligned with clinical expectations.

Abstract 4137644: Association of Prolonged QTc with Development of Heart Failure after Hematopoietic Stem Cell Transplantation

Background: Use of hematopoietic stem cell transplantation (HSCT) continues to rise in the United States, particularly in older age groups; however, HSCT is associated with various cardiovascular complications including heart failure (HF). We sought to examine whether prolonged QTc prior to HSCT was associated with the risk of HF post-HSCT. Methods: We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center (RUMC) between 2008-2019. In this analysis, only patients from the UMHS site were included (n=2,435). Baseline electrocardiogram (EKG) data were recorded prior to transplant (median (IQR) 14 (3, 30) days). QTc prolongation was defined per CTCAE grading criteria as Normal (&lt;440ms), Grade 1 (440-480ms), and Grade ≥2 (&gt;480ms). The primary outcome was new-onset HF defined as a diagnosis documented by health care providers after the date of hospitalization for HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT cardiovascular risk score. Results: Of the 2,435 patients (mean age at HSCT 55±13.4 years; 59.7% male; 90.5% White), 534 (21.9%) had long QTc pre-HSCT. Of those, 440 were Grade 1 and 94 were Grade ≥2. In all, 138 HF events occurred over median period of 2.3 (1.0-5.3) years. The 5-year cumulative incidence of HF was 5.0% in patients with normal QTc, 8.4% in patients with Grade 1 QTc prolongation, and 19.0% in patients with Grade ≥2 QTc prolongation (Figure). Patients with Grade 1 and Grade ≥2 prolongation had a 1.57 (95% CI: 1.05, 2.33) and 2.71 (95% CI: 1.51, 4.86) times higher risk of HF, respectively, compared to those with normal QTc. Conclusions: In this contemporary cohort of adult HSCT patients, those with QTc prolongation prior to HSCT had a higher incidence of HF compared to normal QTc, with greater degree of prolongation associated with higher risk. These findings highlight the importance of accounting for the QTc as part of the pre-transplant cardiovascular evaluation