Baseline Patient Characteristics Research Articles

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma Across Multiple Clinically Relevant Subgroups in the NAVIGATOR Study.

Many patients with severe asthma continue to experience symptoms and exacerbations despite treatment with standard-of-care therapy. In the phase 3 NAVIGATOR study, tezepelumab significantly reduced exacerbations over 52weeks compared with placebo in patients with severe, uncontrolled asthma. This analysis assessed the efficacy of tezepelumab in reducing asthma exacerbations in various clinically relevant subgroups of patients in NAVIGATOR. NAVIGATOR was a phase 3, multicentre, randomized, double-blind, placebo-controlled study. Participants (12-80years old) with severe, uncontrolled asthma were randomized 1:1 to receive tezepelumab 210mg or placebo subcutaneously every 4weeks for 52weeks. Pre-specified and post hoc analyses were performed to evaluate the annualized asthma exacerbation rate (AAER) over 52weeks in clinically relevant subgroups of patients defined by baseline patient characteristics, medical history, exacerbation triggers, medication eligibility and medication use before and during the study. Tezepelumab reduced the AAER over 52weeks compared with placebo across a wide range of patient subgroups assessed. Reductions in exacerbations were similar across subgroups defined by baseline patient characteristics, ranging from 48% (95% confidence interval [CI]: 21, 65) to 60% (95% CI: 44, 71) in subgroups analysed by sex, smoking history and body mass index. Among the asthma-related comorbidity subgroups investigated, patients with aspirin or NSAID sensitivity had the greatest reductions in AAER with tezepelumab compared with placebo (83%; 95% CI: 66, 91). In patients eligible to receive dupilumab, tezepelumab reduced exacerbations compared with placebo by 64% (95% CI: 54, 71). Reductions in the AAER with tezepelumab compared with placebo were also observed irrespective of exacerbation trigger category and the number of asthma controller medications patients were receiving at baseline. These findings further support the benefits of tezepelumab in patients with severe, uncontrolled asthma and can help to inform healthcare providers' treatment decisions. NAVIGATOR (NCT03347279).

Temporary immobilization methods for closed low-energy ankle fracture-dislocations: comparative analysis of a retrospective cohort.

Ankle fracture-dislocations (AFD) often necessitate staged management involving temporary external fixation (EF) due to mechanical instability or blistering. However, limited literature exists on the optimal temporary immobilization method for low-energy closed AFD. This study compared baseline patient and fracture characteristics, along with clinical and radiological outcomes between AFD initially immobilized with EF versus splinting. A retrospective cohort study was conducted involving patients with AFD temporarily immobilized using EF or splinting, followed by definitive open reduction and internal fixation. Quality of reduction (QOR) was assessed for each patient post-initial immobilization and after the definitive surgery. The study encompassed 194 patients: 138 treated with a splint (71.1%) and 56 (28.9%) with EF. Secondary loss of reduction had occurred in three patients who were splinted (2.2%). The mean ages in the EF and splint groups were 63.2 and 56.1years, respectively (p = 0.01). Posterior malleolus fracture (PMF) and blisters were more prevalent in EF patients (69.6% vs. 43.5% for PMF and 76.8% vs. 20.3% for blisters, respectively; p = 0.05 and p < 0.01). Postoperative complication rates were 8.9% for EF versus 10.9% for splinting (p = 0.69). Satisfactory final QOR was attained in 79.8% of patients treated with a splint versus 64.3% with EF (p = 0.02). Patients immobilized by EF presented with poorer baseline characteristics and had more unstable injuries. Nevertheless, postoperative complication rates were comparable. Thus, EF appears to be a valuable tool for standardizing outcomes in AFD patients with a less favorable prognosis.

Intravenous versus oral ‘l-ornithine-l-aspartate’ in overt hepatic encephalopathy: a randomized comparative study

Hepatic encephalopathy (HE), a morbid ordeal affecting chronic liver disease patients always insists for the search of a rational, superior & infallible agent beyond the time-proven standards i.e., Lactulose & Rifaximin. In this RCT, we compared the efficacy of intravenous (IV) l-ornithine-l-aspartate(LOLA) versus Oral LOLA in patients with chronic liver disease(CLD) enduring overt Hepatic Encephalopathy(OHE). 40 CLD patients with OHE were randomly assigned IV or oral LOLA in a 1:1 ratio. Patients were graded for HE and monitored for serum ammonia levels from day 1 to day 5. The aim was to compare IV versus oral LOLA efficacy in HE grades improvement and its correlation with ammonia levels. The study was registered with clinical trials registry-India, CTRI/2020/12/029943. Baseline characteristics of patients in both groups were similar. The mean difference in ammonia levels from day 1 to day 5 was 55.4 ± 32.58 µmol/L in the IV LOLA group and 60.75 ± 13.82 µmol/L in the oral LOLA group (p = 0.511). Significant reductions in ammonia levels were observed from day 1 to day 5 within each group (p < 0.001). HE grade & ammonia correlated positively in both groups. LOLA, regardless of administration route, has demonstrated efficacy in OHE.

Biodegradable Polymer Versus Polymer-Free Ultrathin Sirolimus-Eluting Stents: Analysis of the Stent Arm Registry From the HOST-IDEA Randomized Trial.

The efficacy and safety of each third-generation drug-eluting stent with ultrathin struts and advanced polymer technology remain unclear. We investigated the clinical outcomes of percutaneous coronary intervention using the Coroflex ISAR polymer-free sirolimus-eluting stent (SES) or Orsiro biodegradable polymer SES. The HOST-IDEA trial (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Coronary Intervention With Next-Generation Drug-Eluting Stent Platforms and Abbreviated Dual Antiplatelet Therapy), initially designed with a 2×2 factorial approach, sought to randomize patients undergoing percutaneous coronary intervention based on dual antiplatelet therapy duration (3 versus 12 months) and stent type (Coroflex ISAR versus Orsiro). Despite randomizing 2013 patients for dual antiplatelet therapy duration, the stent arm transitioned to a registry format during the trial. Among these, 328 individuals (16.3%) were randomized for Coroflex ISAR or Orsiro SES, while 1685 (83.7%) underwent percutaneous coronary intervention without stent-type randomization. In this study, the Coroflex ISAR (n=559) and Orsiro groups (n=1449) were matched using a propensity score. The prespecified primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization at 12 months. The baseline patient and procedural characteristics were well balanced between the Coroflex ISAR and Orsiro groups after propensity score matching (n=559, each group). The Coroflex ISAR group was significantly associated with a higher rate of target lesion failure, mainly driven by clinically driven target lesion revascularization, compared with the Orsiro group (3.4% versus 1.1%; hazard ratio, 3.21 [95% CI, 1.28-8.05]; P=0.01). A higher risk of target lesion failure in the Coroflex ISAR group was consistently observed across various subgroups. The rates of any bleeding (hazard ratio, 0.85 [95% CI, 0.51-1.40]; P=0.52) and major bleeding (hazard ratio, 1.58 [95% CI, 0.61-4.08]; P=0.34) were comparable between the 2 groups. In this propensity score-matched analysis of the stent arm registry from the HOST-IDEA trial, the Orsiro SES was associated with significantly better outcomes in terms of 1-year target lesion failure, mainly driven by clinically driven target lesion revascularization, than the Coroflex ISAR SES. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02601157.

Renal denervation for the management of refractory ventricular arrhythmias

Abstract Background While catheter ablation (CA) has proven effective in managing ventricular arrhythmias (VA) associated with structural heart disease, a portion of patients continue to experience refractory VA despite medical treatment and multiple CA procedures. In such cases, additional techniques, such as autonomic neuromodulation, have been explored. Renal denervation (RDN), traditionally performed for the treatment of resistant arterial hypertension, inhibits the afferent renal sympathetic pathway, leading to reduced efferent sympathetic overactivation on a systemic level. Due to this mechanism, it has also been studied for the management of arrhythmias, including atrial fibrillation and VA, with favorable results. Objective To assess the effectiveness and safety of RDN for the management of refractory VA storms in high-risk patients. Methods A retrospective analysis of RDN procedures for electrical storms, conducted at a tertiary center between February 2020 and September 2023. We analyzed baseline patient characteristics, procedural details, and acute complications. Recurrence of VA after RDN was assessed at one and six months. Results A total of 7 patients underwent RDN for the treatment of refractory VA. The mean age was 56 ± 10 years (6 male). The primary diagnosis was ischemic cardiomyopathy (n=5), with a mean left ventricular ejection fraction (LVEF) of 20 ± 5%, and no history of resistant arterial hypertension. All patients had an implantable cardioverter-defibrillator (ICD) (two with concomitant resynchronization therapy). Five patients had undergone previous endocardial VA ablation. Of the two patients without prior VA ablation, one had a contraindication because of a large left ventricle thrombus, and the other was submitted to an electrophysiological study, but without inducible ventricular tachycardia. In the four weeks before RDN, patients exhibited a mean of 12 ± 18 sustained VA episodes, meeting the criteria for electrical storm (3 ≥ episodes in 24h). During the procedure, there was a mean of 7 ± 8 radiofrequency applications in the right renal artery and 6 ± 10 in the left renal artery. No acute complications were observed. One month after the procedure, VA episodes were reduced to a mean of 0 ± 1, with only two patients experiencing recurrent VA. After six months, the absence of VA recurrence remained consistent, with only one patient experiencing new episodes. There were no deaths during this period. Conclusion In our pilot study, RDN appeared to be a safe and effective treatment for the management of VA.VA episodes before and after RDN

#2609 Comparison of baseline patient characteristics of the CONVINCE randomized controlled trial with existing trial and registry populations

Abstract Background and Aims The generalizability of randomized controlled trials (RCTs) results is based on representativeness of the population involved. Trial populations may have different baseline characteristics compared to the general population that could benefit from the intervention. We compare the baseline characteristics of patients involved in the CONVINCE trial with those involved in all previous RCTs and representative registries of patients receiving hemodialysis as renal replacement therapy. Method Based on world class methods for systematic reviews, we identified all RCTs comparing hemodiafiltration (HDF) with hemodialysis (HD) published up to January 2024 and extracted data on baseline patient characteristics. Where data were missing, authors have been contacted and data so far obtained were included in this analysis (Fig. 1). Additional contact attempts are being performed. In addition, a comprehensive search was conducted to identify renal registries from all geographic regions. Those without information in English, without information on HDF and registries focusing on special patient groups (e.g. transplantation only) were excluded. This registry data will not be analyzed in this abstract as we are in progress of extracting the patient data from the latest registry annual reports available up to January 2024 for further analysis. Results We have selected 11 RCTs for further analysis, with the selection criteria and outcomes presented in Fig. 1. Key patient characteristics from RCTs were compared with those of patients in the CONVINCE trial using descriptive statistics and forest plots (Fig. 1). Comparison of differences was analyzed with the Kruskal-Wallis-Test. Interpretation of the results are as follows: • Age: Mean age of 76.5 years noted in Morena et al. (2017) because study inclusion criterion was ≥65 years. Other RCTs ranged from 54.1 to 68 years, which is consistent with 62.4 years in the CONVINCE trial (χ2 = 10, df = 10, p = 0.44). • Sex: 16.7% and 50% female noted in Selby et al. (2006) and Meert et al. (2009) respectively probably due to limited sample size (12 patients and 14 patients respectively). Other RCTs ranges from 30.4% to 42.5%, which is consistent with 36.0% in the CONVINCE trial (χ2 = 11, df = 11, p = 0.44). • Diabetes comorbidities: Ranges from 17.8% to 45%. CONVINCE trial is 35.0% (χ2 = 6, df = 6, p = 0.42). • Cardiovascular diseases comorbidities: Range from 26.4% to 45%. CONVINCE trial is 45% (χ2 = 3, df = 3, p = 0.39). • AVF as vascular access: value of 100% in Pedrini et al. (2011) because it was an inclusion criterion. Other RCTs ranged from 79.4% to 90%, which is consistent with 82% in the CONVINCE trial (χ2 = 7, df = 7, p = 0.43). There were no significant differences between CONVINCE and other RCTs data regarding all 5 patient baseline characteristics. Conclusion Our analysis showed the CONVINCE trial has no significant differences in patient baseline characteristics compared to previous RCTs. For a more comprehensive evaluation of representativeness of the trial's population, we are currently retrieving missing data from the trial authors and analyzing data from hemodialysis registries.

#2892 The role of physical activity in onco-nephrology; a new weapon in the management of urological malignancies

Abstract Background and Aims New clinical evidence demonstrated that Physical Activity (PA) brings numerous benefits both at the level of Health-RelatedQuality of Life (HRQoL), biological mechanisms and at the psychological level. Indeed, it is well known that cancer treatments results in a series of symptoms and side effects that debilitates the patients with cancer and can be counteracted with physical activity. PA has an effect on several aspects of biological mechanisms: sex hormones, metabolic hormones, inflammation and adiposity, and immune function. Furthermore, strong evidence shows that aerobic or combined (aerobic and endurance) training reduces symptoms of anxiety, depression and fatigue. Combined training also leads to improvements in HRQoL, preventing and improving muscle loss and sarcopenia. This study aims to assess the influence of physical activity on this improved scenario. Method A consecutive cohort of 82 pts was enrolled in the Urological Department at San Raffaele Scientific Institute between 2018-2021. The control group (CT) was composed of 31 patients affected by CKD alone (GFR &amp;lt; 60 ml/min/1.73 m2, K-DIGO 2012 classification) and 51 patients with CKD and a recent history of urological malignancies (within 12 months) represented the case group (CS). Inclusion criteria were: Age (&amp;gt;18 years old), eGFR (&amp;lt;60 ml/min/1.73), Malnutritional Screening Tool (MST&amp;lt;2), Urological Cancer aggressiveness (no metastatic process), Informed consent (signed). Each patient underwent an initial nephrological and nutritional evaluation during which a conventional CKD Mediterranean-like diet with a controlled protein intake (MCPD) (0.6-1 g total protein/kg body weight/die and 30-35 kcal/kg body weight/die) was prescribed together with physical activity recommendation according to The National Kidney Foundation (NKF) for a period of 6 months (±2 months). Physical activity recommendations included some aerobic exercise for 30 min on most days of the week, plus other activities to increase muscle strength (exercises with resistance bands) e/o to improve flexibility (such as stretching) once or twice a week. To assess the influence of physical activity within the collaborative nephrologist-nutritionist approach (NNCA) on enhanced kidney function, the Rapid Assessment of Physical Activity (RAPA) test was administered to each patient. The test consists of two indicators: RAPA 1 will indicate aerobic physical activity levels (from 0=sedentary to 7=physically active), while RAPA 2 will indicate other types of exercises (0=none; 1=strength; 2=flexibility; 3=both). Subsequently, Bioelectrical Impedance Analysis (BIA) was conducted on all participants in the cohort to collect data on Body Cell Mass per height squared (BCM/h2), Phase Angle (PA), Extracellular Mass (ECM)/BCM, and Extracellular to Intracellular water ratio (ECW/ICW). Statistical analysis: Linear regression and Pearson's Chi-Squared test; Data analysis: R programming language and RStudio integrated development environment. Results Table 1 shows the patient's baseline characteristics. Table 2 shows anthropometric indices and parameters at pre- and post-dietary and nephrological intervention. Table 3 underlines the poor condition prevalent in CKD patients with or without oncological history, also confirmed by the low level of usual physical activity detected by the RAPA test at T0. Sure enough, our population was mainly inactive and sedentary. Results show that, after the intervention, our patients became regularly active (RAPA 1 score T0: 2.47; RAPA 1 score T1: 3.17; Delta = + 0.7, p &amp;lt; 0.0001); the same trend was observed for RAPA 2 score (observed increase 14%, p &amp;lt; 0.002). Conclusion Based on these findings, it can be inferred that standard clinical care should incorporate thorough assessment of both nutritional status and PA. The adoption of a MCPD, coupled with exercise training within a collaborative nephrologist-nutritionist approach, emerges as a potential strategy to enhance the HRQoL of this particular kind of patient.

#2186 Lower psoas muscle volume is associated with CKD progression

Abstract Background and Aims Renal rehabilitation is important for keeping quality of life and kidney function of patients with CKD. Psoas muscle is representative of total body muscle and its cross-sectional area divided by squared height (PMI) is known to be associated with CKD prognosis. However, the selection of the slice of computer tomography (CT) used for calculation of PMI is arbitrary and may be a source of bias. Recently, AI technology using raw helical CT data has facilitated the measurement of total volume of the psoas major muscle (PMV), which is theoretically less biased by measurer. The aim of this study is to investigate the association between PMV and the progression of CKD. Method This is a pilot retrospective observational study using electrical health records (EHR) in Hyogo Prefectural Nishinomiya Hospital, Japan. We extracted patients with CKD who had taken abdominal CT in 2021 by nephrologists for evaluation of urological anatomy or clinical reasons. PMV was automatically extracted and measured by SYNAPSE VICENT (Fuji Film Medical), a commercially available software. Baseline laboratory data and patient characteristics were collected through EHR with a margin of 90 days from CT scan. The outcome of CKD progression was defined as a 40% decrease in eGFR from baseline. Survival analysis was performed by using the Cox proportional hazards model. Results We enrolled 145 consecutive CKD patients and excluded 37 whose observation period was less than 90 days. PMV was significantly greater in male than in female, positively associated with younger age and higher body mass index (BMI). PMV adjusted for age, sex, and BMI (adjPMV) decreased in a stepwise manner as baseline CKD stage advanced from G2 (N = 23) to G3b (N = 18) but was comparable in G4 (N = 37) and G5 (N = 6). The subjects were then divided into two groups (High-PMV and Low-PMV) according to whether their adjPMV were greater or less than the median value in each CKD stage. The High- and Low-PMV groups were comparable in age (71 ± 13 vs. 72 ± 13), female sex (42% vs. 45%), eGFR (41 ± 21 vs. 42 ± 22), urinary albumin-to-creatinine ratio (UACR), CRP, the prevalence of diabetes at baseline, respectively. PMI and PMV were significantly greater in High-PMV than in Low-PMV group (7.7 ± 1.8 vs. 5.8 ± 1.6 and 307 ± 110 vs. 205 ± 64, respectively). During the median follow up of 1.6 years, 40 events occurred. Hazards ratio for CKD progression was significantly lower in High-PMV group (0.48 [95% confidence interval: 0.25-0.95]) than Low-PMV group after adjusting for known risk factors (age, sex, eGFR, and UACR). Conclusion Preserved psoas muscle volume measured by a theoretically less biased method may be associated with better prognosis in CKD. A larger study in a different cohort, longitudinal observation, and interventional studies are warranted for future investigation.

#367 PROTECT and NefIgArd two-year proteinuria and eGFR outcomes in adults with IgA nephropathy: matching-adjusted indirect comparison

Abstract Background and Aims Immunoglobulin A (IgA) nephropathy is a rare kidney disorder characterized by deposition of IgA in the glomeruli causing progressive loss of kidney function and increased risk of kidney failure. In the absence of a head-to-head trial, this study used unanchored matching-adjusted indirect comparison (MAIC) of clinical trial data to compare two-year efficacy outcomes between Sparsentan in PROTECT and targeted-release formulation (TRF) budesonide plus real-world optimized and stable renin-angiotensin system inhibition (RASi) standard-of-care (SoC) in NefIgArd. Method We conducted an unanchored MAIC using individual patient level data from the PROTECT trial and aggregate data from the NefIgArd trial. Patients in the sparsentan arm of PROTECT were weighted to match key baseline characteristics of patients in the targeted-release formulation (TRF) budesonide + RASi SoC arm of NefIgArd based on publicly accessible, clinically pertinent baseline characteristics and prognostic factors using the method of moments. After weighting, percentage reduction of urine protein-creatinine ratio (UPCR) relative to baseline and two-year eGFR total slope (based on available data, chronic slope estimates are currently not available from NefIgArd) were estimated. A mixed model for repeated measures (MMRM) was used for UPCR relative percentage reduction and a random effect coefficient model for eGFR total slope. A two-tailed z-test with a pooled standard error was conducted for the indirect comparison. Results After assessing PROTECT and NefIgArd cross-trial characteristics on key outcome definitions, inclusion and exclusion criteria, and patient population, the two trials were considered sufficiently similar for unanchored MAIC. After weighting individual patient data from PROTECT, all matched baseline patient characteristics were well-balanced between arms of the two trials. Comparative results showed patients treated with sparsentan in PROTECT (−43.2% relative reduction in UPCR) exhibited a greater mean percentage reduction in proteinuria at two-years compared to TRF budesonide + RASi SoC (−30.7% relative reduction in UPCR), a relative percentage reduction of 18.1% (p = 0.03; Fig. 1A). For eGFR total slope, patients treated with sparsentan exhibited a slower decline in kidney function compared to TRF budesonide + RASi SoC, a difference of 0.54 ml/min/1.73 m2 per year; however, this difference was not statistically significant (p = 0.35; Fig. 1B). Conclusion Aligned to an earlier analysis of percentage reduction in proteinuria at 9-months (−37%, p &amp;lt; 0.0001 favoring sparsentan), our MAIC results show that sparsentan in PROTECT was associated with a greater relative percentage reduction in proteinuria at two-years compared to TRF budesonide plus real-world optimized and stable RASi SoC in NefIgArd. eGFR total slope for sparsentan in PROTECT was comparable to that reported for TRF budesonide plus real-world optimized and stable RASi SoC in NefIgArd. Results comparing chronic slope may provide a better indication of the long-term nephroprotective value of both therapies.

Validation of the Safety and Efficacy of Apixaban as Postoperative Thromboembolism Prophylaxis for Patients with Gynecologic Malignancies.

Venous thromboembolism is a preventable complication of gynecologic cancer surgery that leads to postoperative morbidity and mortality. This study compared apixaban with enoxaparin to identify whether apixaban had the same safety and efficacy for patients undergoing gynecologic cancer surgery. The study identified patients with a gynecologic malignancy who underwent surgery and were prescribed apixaban at discharge between June 2020 and April 2023. International Classification of Diseases 10 codes were used to identify patients who had a thromboembolism within 90 days or a bleeding event within 60 days after surgery. The rates of events for patients prescribed apixaban were compared with those for a historical cohort of patients who received enoxaparin. Fisher's exact tests were used to compare categorical variables, and t tests were used to compare continuous variables. A logistic regression was performed to compare the odds of thromboembolism between the two groups. Baseline patient characteristics differed in terms of body mass index (BMI), race, route of surgery, and type of cancer. Of the 490 patients in the apixaban cohort, 12 (2.4%) had a thromboembolism compared with 3 (2.1%) of the 138 patients in the enoxaparin group (adjusted odds ratio [aOR], 1.02; 95% confidence interval [CI] 0.30-4.70; p > 0.999). The odds ratio was adjusted for BMI, age, and route of surgery. A bleeding event occurred for 1 (0.2%) of the 490 patients in the apixaban group and for 1 (0.7%) of the 138 patients in the enoxaparin group. This validation study showed that apixaban is a safe and effective method of postoperative venous thromboembolism prophylaxis. The data provide support to previous data and guideline updates recommending the use of apixaban for postoperative prophylaxis.

#368 Matching-Adjusted Indirect Comparisons of eGFR slopes in the PROTECT study with UK RaDaR IgA nephropathy population and the control arm of NefIgArd

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is a rare kidney disorder characterized by deposition of IgA in the glomeruli leading to an increased risk of kidney failure. The PROTECT clinical trial in IgAN was designed to determine the long-term (approximately 2 year) nephroprotective potential of treatment with sparsentan compared to a blinded active control angiotensin receptor blocker (ARB) irbesartan, titrated to the maximum labelled dose after randomization (achieved in 97% of patients). To understand PROTECT clinical trial results relative to delivery of standard of care (SoC) treatment for IgAN in other clinical settings, this study compared two-year eGFR total slope outcomes between the two arms of PROTECT and delivery of SoC in two populations applying similar eligibility criteria: Method Using individual patient data (IPD) from PROTECT, unanchored matching-adjusted indirect comparisons (MAICs) were performed. Patients in both arms of PROTECT were weighted to match key baseline characteristics of the two comparator populations. Matching was based on published clinical characteristics using the method of moments. After weighting, two-year eGFR total slopes were calculated using random coefficients models. Two-tailed z-tests with pooled standard errors were used for indirect comparison. Results Based on assessment of cross-data source characteristics, populations were found to be sufficiently comparable for unanchored MAIC. After weighting IPD from PROTECT, all matched baseline patient characteristics were well-balanced between data sources. Comparative results showed that patients treated with maximally titrated irbesartan or sparsentan in PROTECT exhibited a slower decline in kidney function compared to SoC delivered in a real-world setting (RaDaR), with differences of: Similar results were observed compared to SoC delivered in a clinical trial (NefIgArd), with differences of: Conclusion Both “maximally tolerated dose of ARB” (as recommended in the KDIGO guideline for IgAN) using irbesartan in PROTECT and sparsentan were associated with significantly slower decline in kidney function compared to real-world SoC treatment for IgAN (RaDaR) and delivery of physician defined, optimized SoC (&amp; placebo) in the context of a clinical trial (NefIgArd). 2-year eGFR slope differences between clinical trials in IgAN need to be considered in the context of what is achieved in current clinical practice. With existing real-world and emerging clinical trial data in IgAN, MAIC is an approach that can be applied to compare outcomes between relevant, sufficiently aligned data sources.

#2389 Enhancing immunoglobulin A nephropathy management: insights from the IGAN-MIC project

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) comprises a substantial proportion of primary glomerulonephritis cases in China, yet comprehensive nationwide data regarding its diagnosis and treatment are lacking. The Immunoglobulin A Nephropathy Management Quality Improvement Initiative Project in China (IGAN-MIC) seeks to establish an IgAN cohort collaboration network to comprehend real-world IgAN management practices in China. Method The IGAN-MIC project convened 15 Chinese experts from 14 regions to form an expert committee to develop a registry of IgAN patients to evaluate regional differences in IgAN management from 2015 to 2024. The registry will involve comprehensive data collection from electronic medical records, encompassing key aspects including demographic and clinical characteristics, renal biopsies, diagnoses, comorbidities, laboratory findings, and treatment modalities, facilitating a detailed analysis of disease progression and changes in treatment strategies from initial diagnosis through subsequent follow-up periods. Results The IGAN-MIC project has garnered applications from 78 healthcare institutions, with 7 of them already incorporated into the initiative and initiated data collection. As of January 1, 2024, the project has enrolled 543 pathologically confirmed IgAN patients diagnosed between 2015 and 2023 from these 7 centers. At the time of diagnosis, the median (IQR) of age was 38.00 (30.00, 48.00) years; 54.51% were females; the median (IQR) of eGFR was 75.41 (51.93, 104.09) mL/min/1.73 m2 and the median (IQR) 24-hour urinary protein was 1263.50 (645.30, 2362.64) mg/day. For these patients, the utilization rates of RAS inhibitors (RASi), SGLT2 inhibitors (SGLT2i) and glucocorticoids at initial treatment were 53.41%, 3.51%, and 42.73% respectively. The utilization rate of SGLT2i from 2022 to 2023 was 9.90%, as the first indication for SGLT2i in CKD was approved in China in September 2022. A detailed outline of patient baseline characteristics is presented in Table 1 below. Conclusion These initial findings in the registry showed that the Chinese IgAN patients were young, had mildly reduced renal function, and with massive proteinuria at the time of initial diagnosis. For initial treatment, only half of the patients received RASi, and only one tenth received SGLT2i. More education needs to be focused on promoting guideline-directed medical therapies in the future. Given that nationwide data on Chinese IgAN patients are limited, the IGAN-MIC project is anticipated to broaden its registry to include more healthcare institutions and Chinese IgAN patients in the future, with the aim of providing a more in-depth understanding of the changing clinical presentations and ongoing follow-up scenarios among IgAN patients, contributing crucial insights to the clinical management of IgAN.

Derivation and validation of a nomogram incorporating modifiable lifestyle factors to predict development of colorectal adenomas after negative index colonoscopy

This retrospective cohort study aimed to identify baseline patient characteristics involving modifiable lifestyle factors that are associated with the development of colorectal adenomas, and establish and validate a nomogram for risk predictions among high-risk populations with negative index colonoscopy. A total of 83,076 participants who underwent an index colonoscopy at the Tianjin Union Medical Center between 2004 and 2019 were collected. According to meticulous inclusion and exclusion criteria, 249 subjects were enrolled and categorized into the primary and validation cohorts. Based on the primary cohort, we utilized the LASSO-Cox regression and the univariate/multivariate Cox proportional hazards (Cox-PH) regression parallelly to select variables, and incorporated selected variables into two nomogram models established using the multivariate Cox-PH regression. Comparison of the Akaike information criterion and the area under the receiver operating characteristic curve of the two models demonstrated that the nomogram model constituted by four covariates retained by the LASSO-Cox regression, including baseline age, body mass index, physical activity and family history of colorectal cancer (CRC) in first-degree relatives, performed better at predicting adenoma-free survival probabilities. Further validation including the concordance index, calibration plots, decision curve analysis and Kaplan–Meier survival curves also revealed good predictive accuracy, discriminating ability, clinical utility and risk stratification capacity of the nomogram model. Our nomogram will assist high-risk individuals with negative index colonoscopy to prevent colorectal adenoma occurrence and CRC morbidity with improved cost-effectiveness.

A formative mixed methods evaluation of a new Ross program: why context matters

BackgroundThe Ross procedure is a technically complex operation to address the pathology of the aortic valve. Prior attempts at widespread implementation have been plagued with variations in effectiveness. We report our initial programmatic outcomes using dissemination and implementation (D&I) science frameworks, with an aim to define both programmatic efficacy and effectiveness. The study design was a single center, explanatory sequential mixed methods evaluation of a Ross surgery program from June 2020 to April 2023. Quantitative measures for baseline patient characteristics and postoperative outcomes were summarized. Qualitative measures were obtained using semi-structured interviews and characterized using implementation science frameworks.ResultsA total of 71 patients underwent the Ross procedure at a single academic center. Mean age was 40 years (± 13). There were no perioperative deaths or valve-related reinterventions (0%). During the follow-up period, 2 (2.8%) patients required re-operation and 2 (2.8%) required balloon dilation of the pulmonary homograft. Qualitative measures noted communication and prospective self-audit facilitated measures of effectiveness, as dichotomy within expected vs. observed outcomes led to program modifications. Collaboration across hospital systems promoted adoption and implementation, which led to the incorporation of the Ross procedure into accepted organizational practice.ConclusionsIn this formative evaluation, limited-efficacy outcomes demonstrated similar programmatic success to data from other established centers. With the prerequisite center volume and case selection, the Ross procedure is a safe and efficacious treatment for aortic valvular disease. Implementation science can be used both in real-time and retrospectively to guide organizational efforts to improve outcomes and to improve the translation of results across centers.

Cost-effectiveness of empagliflozin as add-on to standard of care for chronic kidney disease management in the United Kingdom

ABSTRACT Objective The sodium-glucose co-transporter-2 inhibitor empagliflozin was approved for treatment of adults with chronic kidney disease (CKD) on the basis of its demonstrated ability to slow CKD progression and reduce the risk of cardiovascular death. This analysis was performed to assess the cost effectiveness of empagliflozin plus standard of care (SoC) versus SoC alone in the treatment of CKD in the UK. Methods A comprehensive, patient-level CKD progression model that simulates the evolution of risk factors for disease progression based on CKD-specific equations and clinical data was used to project a broad range of CKD-related complications. Patient baseline characteristics, distribution across Kidney Disease Improving Global Outcomes (KDIGO) health states, and changes in estimated glomerular filtration rate (eGFR), urine albumin-creatinine ratio (uACR), and other parameters while on treatment, were derived from the EMPA-KIDNEY trial. UK cost and utilities/disutilities were sourced from the literature. Univariate and probabilistic sensitivity analyses were conducted. Annual discounting of 3.5% was applied on costs and outcomes. Results Over a 50-year horizon, SoC resulted in per-patient costs, life years, and QALYs of £95,930, 8.55, and 6.28, respectively. Empagliflozin plus SoC resulted in an incremental gain in life years (+1.04) and QALYs (+0.84), while decreasing per-patient costs by £6,019. Empagliflozin was more effective and less costly (dominant) with a net monetary benefit of £22,849 at the willingness-to-pay threshold of £20,000. Although treatment cost was higher for empagliflozin, this was more than offset by savings in kidney replacement therapy. Empagliflozin remained highly cost-effective in patients with and without diabetes, and across scenario and sensitivity analyses. Limitations This analysis is limited by reliance on short-term clinical trial data and by uncertainties in modelling CKD progression. Conclusions Empagliflozin as an add-on to SoC for treatment of adults with CKD represents cost-effective use of UK National Health Service (NHS) resources.

Impact of osteoporotic risk in men undergoing transcatheter aortic valve replacement: a report from the LAPLACE-TAVI registry.

Low body weight and advanced age are among the best predictors of osteoporosis. Osteoporosis Self-Assessment Tool (OST) values are calculated by a simple formula [(body weight in kilograms - age in years) × 0.2] to identify patients at increased risk of osteoporosis. In our recent single-center study, we demonstrated an association between OST and poor outcomes in postmenopausal women after transcatheter aortic valve replacement (TAVR). We aimed to investigate the impact of osteoporotic risk in men with aortic stenosis who underwent TAVR in a large cohort. In this multi-center study, 1,339 men who underwent TAVR between April 2010 and July 2023 were retrospectively analyzed. Women were excluded from the present study. All patients were deemed appropriate for TAVR after a review by a multidisciplinary team. Baseline characteristics of patients were compared by dividing patients into three tertiles, based on the OST value: ≤ -6.16, -6.16 to -4.14, and -4.14 < for tertiles 1, 2, and 3, respectively. Primary endpoint was all-cause mortality after TAVR. Tertile 1 (patients with the lowest OST values) included older patients with smaller body mass index, lower hemoglobin and albumin levels. In addition, they had greater clinical frailty scale, slower 5-meter walk test, weaker hand grip strength, and more cognitive impairment, indicating increased frailty. They were more severely symptomatic, with lower ejection fractions, smaller aortic valve areas, and more tricuspid regurgitation than were patients in the other two groups. Multivariate analysis revealed that OST tertiles 3 was associated with decreased risk of all-cause mortality (hazard ratio, 0.66; 95% confidence interval, 0.48-0.90), compared with OST tertile 1 as a reference. For OST tertiles 1, 2, and 3, the estimated 1-year survival rates of all-cause mortality post-TAVR were 83.6% ± 1.9%, 91.1% ± 1.4%, and 93.1% ± 1.3%, respectively, (log-rank, p <0.001). In conclusions, in men as same as women, osteoporotic risk assessed by OST values was overlapped with increased frailty. The simple OST formula was useful for predicting all-cause mortality in patients undergoing TAVR in large registry datasets.

Overall Survival in Patients with Esophageal Cancer and Clinical Complete Response after Radio Chemotherapy: Should a Watchful Waiting Strategy be the new Standard of Care?

Abstract Background The current standard of care for curative treatment of esophageal cancer (EC) consists of neoadjuvant radio chemotherapy (RCT) followed by resection. However, an organ-sparing approach with a watchful waiting (WW) strategy and resection only in case of cancer recurrence is gaining importance in patients with clinical complete response (cCR) after RCT. Nevertheless, data on overall survival, particularly in subgroups with and without tumor recurrence, is limited. Aims To compare overall survival (OS) rates in patients with cCR based on initial management and at time of recurrence. Methods We retrospectively analyzed data from all patients with EC and cCR to RCT between 01/2014 and 12/2021. OS- and disease-free survival was calculated using Kaplan-Meier survival analysis. Results Of 96 patients with cCR after RCT, 45 underwent resection (47%), and 51 (53%) a WW approach. There were no significant differences in baseline patient or tumor characteristics. In the WW group, 28 patients (55%) had cancer recurrence. Of those, 11 patients (of 28, 39%) underwent either salvage esophagectomy or endoscopic submucosal dissection in curative intent. No significant difference in OS could be detected in patients with WW and either no recurrence or recurrence treated in curative intention (p=0.716). Further, OS was significantly longer in those patients than in patients with primary resection (p=0.031) and WW patients with recurrence and palliative treatment (p&amp;lt;0.001). (Fig 1). Conclusion In a WW concept for patients with EC and cCR after RCT, patients with cancer recurrence can achieve the same OS as patients without recurrence if treated in curative intention. Moreover, OS in both those patient groups was superior to that of patients undergoing direct resection after RCT, supporting a WW approach as at least safe and applicable in clinical practice. Further prospective data are needed to determine the value of WW as standard of care for patients with cCR following neoadjuvant RCT.

Coronary Embolism Among Patients With ST-Segment-Elevation Myocardial Infarction and Atrial Fibrillation: An Underrecognized But Deadly Association.

The prevalence and impact of coronary emboli (CE) in patients with ST-segment-elevation myocardial infarction (STEMI) and atrial fibrillation (AF) have not been specifically studied. The objective was to describe the clinical characteristics and outcomes of patients with AF and CE in a large series of patients with STEMI. We investigated 2292 consecutive patients with STEMI and among them 225 patients with AF: 46 patients with a STEMI related to CE (group A) and 179 patients with a STEMI related to an atherosclerotic cause (group B). Compared with the 2067 patients without AF and CE (group C), patients with AF and CE were older (73 versus 59 years, P<0.05), more likely to be female (43% versus 22%, P<0.05), and presented more frequently with cardiogenic shock at admission (26% versus 9%, P<0.05). The baseline characteristics of patients with AF (group A versus B) did not differ significantly according to STEMI pathogenesis. In the unadjusted analysis, the 45-day mortality was higher in patients with CE and AF (group A versus group C: 20% versus 4%; P<0.05 and group A versus group B: 20% versus 8%, P=not significant); this trend persisted at 2-year follow-up (group A versus group C: 24% versus 6%; P<0.05 and group A versus group B: 24% versus 17%, P=not significant). After stabilized inverse exposure probability weighting adjustment, a higher 45-day mortality rate was confirmed in patients with CE and AF (group A versus group C: 18% versus 5%, P<0.05). In patients presenting with STEMI and AF, CE was associated with excess early mortality. URL: clinicaltrials.gov. Identifier: NCT05679843.

Effect of chemotherapy on prognosis in patients with primary pancreatic signet ring cell carcinoma: A large real-world study based on machine learning.

Primary pancreatic signet ring cell carcinoma (PSRCC), an extremely rare histologic variant of pancreatic cancer, has a poor prognosis. This study aimed to investigate the prognostic value of chemotherapy in PSRCC. Patients with PSRCC between 2000 and 2019 were identified using the Surveillance Epidemiology and End Results (SEER) database. The main outcomes in this study were cancer-specific survival (CSS) and overall survival (OS). The baseline characteristics of patients were compared using Pearson's Chi-square test. Kaplan-Meier analysis was used to generate the survival curves. Least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression models, and Random Survival Forest model were used to analyze the prognostic variables for OS and CSS. The variance inflation factors (VIFs) were used to analyze whether there was an overfitting problem. A total of 588 patients were identified. Chemotherapy was an independent prognostic factor for OS and CSS, and significantly associated with OS (HR = 0.33, 95% CI = 0.27-0.40, P <0.001) and CSS (HR = 0.32, 95% CI = 0.26-0.39, P <0.001). Chemotherapy showed beneficial effects on OS and CSS in patients with PSRCC and should be recommended in clinical practice.

A quality assurance study of the development of quality of care in outpatient clinics for treatment of addiction in Greenland

Introduction In 2016, a new addiction treatment service, Allorfik, was introduced in Greenland. Allorfik has, throughout the implementation and after, used auditing of patient records with feedback to develop the quality of care in treatment. Audits and feedback are routinely done in each treatment center. This study wishes to investigate the development of the quality of treatment through the case notes from the journal audits. Methodology This study is based on case notes audits from 2019, 2020 and 2021. In the audits, the focus has been on the quality of documentation and content for ten specific areas in each patient record. Each area was scored on a Likert scale of 0–4 for both outcomes. Statistical analyses were done using Stata 17, and P-values < 0.05 were considered statistically significant. We present baseline characteristics for patients and illustrate the development of quality for both outcomes as time trends with scatter plots. Results The analysis was based on data from 454 patients and audits of their case notes. The mean number of weeks in treatment is 12.72, and the mean age for the people in the audited case notes is 39. Time had a positive effect on both outcomes, and so each month, documentation increased by 0.21 points (p-value = <0.001), and content increased by 0.27 points (p-value = <0.001). Conclusion For documentation and content, the quality level has increased significantly with time, and the quality of case notes is at an excellent level at the final audits of all treatment centers.