Kaplan-Meier Research Articles

Carotid Plaque Score is Associated with 10-year Major Adverse Cardiovascular Events in Low-Intermediate Risk Patients Referred to a General Cardiology Community Clinic.

Atherosclerotic carotid plaque assessments have not been integrated into routine clinical practice due to the time-consuming nature of both imaging and measurements. Plaque score, Rotterdam method, is simple, quick, and only requires 4-6 B-mode ultrasound images. The aim was to assess the benefit of plaque score in a community cardiology clinic to identify patients at risk for major adverse cardiovascular events (MACE). Patients ≥40 years presenting for risk assessment were given a carotid ultrasound. Exclusions included a history of vascular disease or MACE and being >75 years. Kaplan-Meier curves and hazard ratios were performed. The left and right common carotid artery (CCA), bulb, and internal carotid artery (ICA) were given 1 point per segment if plaque present (plaque score 0 to 6). Administrative data holdings at ICES were used for 10-year event follow-up. Of 8,472 patients, 60% were females (n = 5,121). Plaque was more prevalent in males (64% vs 53.9%; P <0.0001). The 10-year MACE cumulative incidence estimate was 6.37% with 276 events (males 6.9 % vs females 6.0%; P = 0.004). Having both maximal CCA IMT <1.00 mm and plaque score = 0, was associated with less events. A plaque score <2 was associated with a low 10-year event rate (4.1%) compared to 2-4 (8.7%) and 5-6 (20%). A plaque score ≥2 can re-stratify low-intermediate risk patients to a higher risk for events. Plaque score may be used as a quick assessment in a cardiology office to guide treatment management of patients.

Impact of SGLT2 Inhibitors on Atrial Fibrillation Recurrence after Catheter Ablation in Type 2 Diabetes Mellitus: A Meta-Analysis of Reconstructed Kaplan-Meier Curves with Trial Sequential Analysis.

The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in managing cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) is evolving. This meta-analysis seeks to explore the influence of SGLT2i on the recurrence of atrial fibrillation (AF) following catheter ablation (CA) in individuals with T2DM qualitatively and quantitatively. A comprehensive literature search was conducted in electronic databases. Studies meeting predefined criteria were included. Individual patient data (IPD) were used from reconstructed time-to-event data to estimate hazard ratios (HRs) and 95% confidence intervals for AF recurrence. IPD meta-analysis was followed by a direct meta-analysis to assess the risk of AF recurrence. A total of five studies [one randomized controlled trial (RCT) and four cohort studies] were included in this study, and five studies were included in the qualitative analysis, while four studies comprising 1043 patients with T2DM were included in the quantitative analysis. The pooled Kaplan-Meier curve based on reconstructed data showed a significantly lower risk of AF recurrence in the SGLT2i group compared with all antidiabetic drugs (log-rank P = 0.00011) and dipeptidyl-peptidase IV inhibitors (DPP4i) (log-rank P = 0.01). Cox regression analysis showed consistent results. Direct meta-analysis showed that SGLT2i, compared with all antidiabetic medications (HR 0.57, 95% CI [0.44, 0.73], I2) and DPP4i (HR 0.41, 95% CI [0.24, 0.70], I2), was associated with a lower risk of AF recurrence. SGLT2i are associated with a reduced risk of AF recurrence after CA in patients with T2DM. These results suggest that SGLT2i is promising in improving clinical outcomes for this population.

Clinical Characteristics and Prognosis of Early-Onset Hepatocellular Carcinoma: A Retrospective Cohort Study Based on Population Data.

The incidence of young patients diagnosed with hepatocellular carcinoma (HCC) is projected to rise. This study aimed to investigate the distinctive characteristics of adolescent and young adult (AYA) patients with HCC and identify the risk factors that impact their survival. This study included 1005 AYA patients and 55,435 older adult (OA) patients with HCC, using data from the Surveillance, Epidemiology, and End Results database. Propensity score matching was used to adjust for baseline differences in patient characteristics. The Kaplan-Meier curve and log-rank test are utilized to compare the overall survival between the two groups. The Cox proportional hazards regression model was used for subgroup analysis to identify risk factors for overall survival in AYA patients. AYA patients exhibited a higher proportion of advanced clinical stage (49.15% vs 37.57%, P < 0.001) and fibrolamellar hepatocellular carcinoma (14.13% vs 0.09%, P < 0.001), but a lower incidence of alpha-fetoprotein positivity (32.04% vs 45.32%, P < 0.001) and cirrhosis (8.86% vs 18.32%, P < 0.001). The subgroup analysis results indicated that AYA patients had a more favorable prognosis than OA patients in most subgroups. Undifferentiated carcinoma emerged as the predominant risk factor for AYA patients (Hazard Ratio [HR], 6.08 [2.53-14.62]), whereas partial hepatectomy was determined to be the most advantageous factor (HR, 0.29 [0.23-0.37]). AYA patients with HCC exhibit more aggressive characteristics but demonstrate a better prognosis compared to the OA group, necessitating personalized surveillance and treatment.

Real-World First-Line Maintenance Niraparib Monotherapy Use Following Chemotherapy Plus Bevacizumab: The SW1TCH Study.

Clinical trials have demonstrated prolonged survival associated with niraparib first-line maintenance (1LM) therapy, compared with placebo, for patients with ovarian cancer (OC). However, data are limited on real-world 1LM niraparib monotherapy use, particularly as switch 1LM, following first-line (1L) combination chemotherapy plus bevacizumab. This real-world study aimed to describe patient demographics, clinical characteristics, and clinical outcomes of patients with OC receiving 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab. This retrospective observational study used data from a US-based nationwide database of deidentified, electronic health record-derived data. Patients diagnosed with OC during the study period (1 January 2011-30 November 2022, inclusive) were eligible if they received 1L chemotherapy plus bevacizumab treatment followed by 1LM niraparib monotherapy, initiated between 1 January 2017 (inclusive) and 2 September 2022. Patients were followed from index date (initiation of niraparib 1LM) until the first occurrence of death, end of follow-up, or end of study. Clinical outcomes were time to treatment discontinuation (TTD) and time to next treatment (TTNT). Kaplan-Meier curves were used to estimate TTD, TTNT, and 95% confidence intervals (CIs). Among 93 patients selected, median age at index was 67years (interquartile range [IQR] 60-72 years). Most patients had BRCA wild-type/homologous recombination (HR)-proficient or BRCA wild-type/HR unknown disease (75.3%). In all, 18 (19.4%) patients had HR-deficient disease. Five (5.4%) patients had unknown test results for both BRCA and HR deficiency status. Median follow-up time was 16.3months (IQR 8.7-25.4months), and median time from end of 1L therapy to 1LM initiation was 35.0days (IQR 25.0-53.9days). Median TTD was 9.3months (95% CI 6.1-11.3months). Median TTNT was 12.9months (95% CI 11.5-19.0months). This real-world study provided insights into switch maintenance with 1LM niraparib monotherapy, which may be a viable treatment option for patients with advanced OC.

Taper versus discontinuation of tocilizumab in patients with giant cell arteritis: Real-world experience from a tertiary center

IntroductionFollowing the approval of tocilizumab (TCZ) for giant cell arteritis (GCA), recent studies have shown a high relapse frequency after abrupt discontinuation of TCZ. However, a thorough exploration of TCZ tapering compared to abrupt discontinuation has never been undertaken. Likewise, adverse events have only been scarcely investigated in routine care. This study aimed to compare the incidence of relapses in GCA patients undergoing TCZ tapering compared to abrupt discontinuation. MethodsWe performed a single-center retrospective cohort study from 2012 to 2022. Data from GCA patients treated with TCZ was obtained from the Electronic Patients Record. Relapse-free survival is reported in Kaplan-Meier plots and tapering versus abrupt discontinuation were compared using a Wilcoxon-Brewlos-Gehan test. ResultsWe included 155 patients receiving TCZ treatment for GCA, of which 104 discontinued TCZ. Among the 104 patients discontinuing TCZ, 42 (40 %) experienced a relapse within the first year. A total of 57 patients underwent taper with 6/38 (16 %) and 2/19 (11 %) relapsing while receiving TCZ every second or third week, respectively. In comparison, 59 patients underwent abrupt discontinuation with 27 (46 %) relapsing during follow-up. The patients undergoing abrupt TCZ discontinuation demonstrated a significantly shorter time to relapse compared to all tapered patients (p = 0.02) as well as patients tapered from weekly TCZ treatment to every second week (p < 0.01). Furthermore, 15 % of patients discontinued TCZ due to adverse events. ConclusionThis is the first study indicating that TCZ taper induced longer relapse-free survival than abrupt discontinuation, implying that taper may be favored over discontinuation in patients with GCA.

Temporal trends in acute decompensated heart failure outcomes: A single-center 11-year retrospective analysis

BackgroundAcute Decompensated Heart Failure (ADHF) is associated with frequent hospitalizations, posing a significant health and economic burden globally. Despite advancements in heart failure management, studies delineating temporal trends in ADHF outcomes are sparse.Methods: in this retrospective analysis, ADHF patients admitted to Shamir Medical Center from 2007 to 2017 were categorized into two cohorts: early (2007–2011) and recent (2012–2017). Clinical characteristics, in-hospital interventions, and outcomes were compared. Survival analysis was performed using Kaplan-Meier methods with log-rank tests. Results8332 admitted patients were analyzed, 4366 (52.4 %) in the early period, and 3966 (47.6 %) in the recent period. In the recent cohort, ischemic heart disease decreased significantly (from 45.2 % to 34.7 %), while hypertension and smoking rates increased. Additionally, a significant increase in coronary artery bypass grafting (from 0.8 % to 3.5 %) and beta-blockers prescription (from 45.5 % to 63.4 %) post-discharge was observed. However, no substantial improvement in in-hospital mortality (8.9 % in early vs. 8.0 % in recent), 30-day (3.2 % in early vs. 3.1 % in recent), 1-year (23.3 % in early vs. 23.8 % in recent), or 5-year survival rates was noted between cohorts. A subset analysis of patients admitted to cardiology departments showed a significant reduction in in-hospital mortality in the recent cohort (12.3 % in early vs. 6.3 % in recent), yet without a corresponding long-term survival benefit. ConclusionsAdvancements in heart failure management over the 11-year study period did not demonstrate an improvement in clinical outcomes for ADHF patients, highlighting the challenge of translating advancements in the medical care of ADHF patients into long-term survival benefits.

The nutritional metabolic risk index as a predictor of all-cause and cardiovascular mortality: a national cohort study

BackgroundRecent studies show that malnutrition increases all-cause mortality by 1.11 times and cardiovascular mortality by 2.60 times. Similarly, metabolic syndrome raises overall mortality by 40% and cardiovascular mortality by 37%. This research assesses the Nutritional Metabolic Risk Index (NMRI) for predicting these mortality risks. MethodsWe analyzed data from 14,209 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018, where the NMRI was calculated based on the ratio of GNRI to TyG-WHtR. The relationship between NMRI and mortality was investigated using Kaplan-Meier methods and Cox regression models, with restricted cubic splines (RCS) employed to examine non-linear associations. The predictive capabilities of NMRI, GNRI, and TyG-WHtR for mortality were assessed using receiver operating characteristic curve(ROC) curve analysis. ResultsOver a median follow-up period of 89 months, there were 1,358 all-cause deaths and 345 cardiovascular deaths recorded. Cox regression analysis indicated that each unit increase in NMRI was associated with an 8% reduction in all-cause mortality risk and a 15% reduction in cardiovascular mortality risk. RCS analysis found a nonlinear negative correlation between NMRI and both all-cause and cardiovascular mortality. NMRI demonstrated superior predictive accuracy for all-cause mortality (AUC: 0.696, 95% CI: 0.682-0.710) and cardiovascular mortality (AUC: 0.713, 95% CI: 0.689-0.737) compared to GNRI and TyG-WHtR (P<0.05). ConclusionsThe NMRI is inversely associated with the risk of all-cause and cardiovascular mortality in American adults.

Incidence, antimicrobial resistance and mortality of Klebsiella pneumoniae bacteraemia in Shanghai, China, 2018–2022

Background Klebsiella pneumoniae (KP) accounts for high antimicrobial resistance and mortality rates of bloodstream infections (BSIs). Objectives To investigate incidence, antimicrobial resistance and risk factors for mortality of KP BSIs in East China. Methods A retrospective study of patients with KP BSIs was conducted in a tertiary care hospital from 2018 to 2022. Medical records of all hospitalised patients with KP BSIs were reviewed and analysed. The incidence, antimicrobial resistance and mortality of KP BSIs were evaluated. The Kaplan-Meier method was used to plot survival curves and logistic regression was used to analyse risk factors for crude 30-day mortality. Results A total of 379 inpatients with KP BSIs were enrolled. The incidence of patients with KP BSIs was fluctuating between 4.77 and 9.40 per 100,000 patient-days. The crude 30-day mortality rate of these patients was 26.39%. Of the 379 KPisolates, 197 (51.98%) were carbapenem-resistant (CR) and 252 (66.49%) were multidrug-resistant (MDR). All isolates showed the lowest resistance to tigecycline (13.77%) and polymyxin B (14.61%). Cases with MDR/CR isolates had significantly longer length of hospital stay, higher crude 30-day mortality and medical costs than non-MDR/non-CR isolates. Age, CR phenotype, paracentesis, indwelling central venous catheter (CVC), use of carbapenems, tetracyclines, polymyxins B, and irrational empiric treatment were independently associated with crude 30-day mortality. Conclusion MDR/CR KP BSIs are associated with increased mortality, healthcare costs and prolonged hospitalisation. Patients with advanced age, CR phenotype, paracentesis, CVC, exposure to some antibiotics, and irrational empirical antibiotic treatment are at higher mortality risk.

FINAL outcome ANALYSIS FROM THE PHASE II TUXEDO-1 TRIAL OF TRASTUZUMAB-DERUXTECAN IN HER2-positive breast cancer PATIENTS WITH active brain metastases.

Brain metastases (BM) are a devastating complication of HER2-positive metastatic breast cancer (BC) and treatment strategies providing optimized local and systemic disease control are urgently required. The antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) and overall survival (OS) over trastuzumab emtansine but data regarding intracranial activity is limited. In the primary outcome analysis of TUXEDO-1, a high intracranial response rate (RR) was reported with T-DXd. Here, we report final PFS and OS results. TUXEDO-1 accrued adult patients with HER2-positive BC and active BM (newly diagnosed or progressing) without indication for immediate local therapy. The primary endpoint was intracranial RR; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analysed in the per-protocol population. At 26.5 months median follow-up, median PFS was 21 months (95% CI 13.3-n.r.) and median OS was not reached (95% CI 22.2-n.r.). With longer follow-up, no new safety signals were observed. The most common grade 3 adverse event was fatigue (20%). Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL was maintained over the treatment period. T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive BC BM in line with results from the pivotal trials. These results support the concept of ADCs as systemic therapy for active BM.

The remarkable antitumor efficacy of corticosteroid treatment in patients with refractory thymomas

BackgroundSome case reports have found that corticosteroid treatments shrunk thymoma lesions remarkably after the failure of chemotherapy or surgery. However, few studies have comprehensibly evaluated the antitumor effects of corticosteroids in patients with invasive thymomas. MethodsWe reviewed the medical records of 13 consecutively enrolled patients with locally advanced or metastatic thymomas treated via corticosteroid monotherapies from January 2010 to March 2021 in our institute. A Cox's proportional hazard model and the Kaplan-Meier method were used to identify factors associated with survival. ResultsThe median follow-up time was 26 months (range, 13–115 months). The median initial dose of corticosteroid was 0.90 mg/kg/day prednisolone equivalent (range, 0.4–1.1 mg/kg/day). Of the 13 cases, 7 (53.8%, 95% CI: 0.25–0.81) exhibited a partial response and 5 (38.5%, 95% CI: 0.14–0.68) stable disease. The median progression-free survival was 5.7 months [95% confidence interval (CI): 1.5–9.6 months]. The median overall survival was 25.3 months (95% CI: 7.1–not attained). The median duration of corticosteroid use was 3 months (range, 1–64 months). Patients with WHO subtype B thymomas exhibited a better overall response rate to corticosteroids than did patients with other disease subtypes (75%, 95% CI: 0.19–0.99). Adverse events of Grade 3 or more were not observed. ConclusionsCorticosteroids are clinically valuable for patients with thymomas.

The Novel-B-Cell-Related Gene Signature Predicts the Prognosis and Immune Status of Patients with Esophageal Carcinoma.

The current understanding of the prognostic significance of B cells and their role in the tumor microenvironment (TME) in esophageal carcinoma (ESCA) is limited. We conducted a screening for B-cell-related genes through the analysis of single-cell transcriptome data. Subsequently, we developed a B-cell-related gene signature (BRGrisk) using LASSO regression analysis. Patients from The Cancer Genome Atlas cohort were divided into a training cohort and a test cohort. Patients were categorized into high- and low-risk groups based on their median BRGrisk scores. The overall survival was assessed using the Kaplan-Meier method, and a nomogram based on BRGrisk was constructed. Immune infiltration profiles between the risk groups were also compared. The BRGrisk prognostic model indicated significantly worse outcomes for patients with high BRGrisk scores (p < 0.001). The BRGrisk-based nomogram exhibited good prognostic performance. Analysis of immune infiltration revealed that patients in the high-BRGrisk group had notably higher levels of immune cell infiltration and were more likely to be in an immunoresponsive state. Enrichment analysis showed a strong correlation between the prognostic gene signature and cancer-related pathways. IC50 results indicated that patients in the low-BRGrisk group were more responsive to common drugs compared to those in the high-BRGrisk group. This study presents a novel BRGrisk that can be used to stratify the prognosis of ESCA patients and may offer guidance for personalized treatment strategies aimed at improving prognosis.

External validation of a 2-year all-cause mortality prediction tool developed using machine learning in patients with stage 4-5 chronic kidney disease.

Chronic kidney disease (CKD) is associated with increased mortality. Individual mortality prediction could be of interest to improve individual clinical outcomes. Using an independent regional dataset, the aim of the present study was to externally validate the recently published 2-year all-cause mortality prediction tool developed using machine learning. A validation dataset of stage 4 or 5 CKD outpatients was used. External validation performance of the prediction tool at the optimal cutoff-point was assessed by the area under the receiver operating characteristic curve (AUC-ROC), accuracy, sensitivity, and specificity. A survival analysis was then performed using the Kaplan-Meier method. Data of 527 outpatients with stage 4 or 5 CKD were analyzed. During the 2years of follow-up, 91 patients died and 436 survived. Compared to the learning dataset, patients in the validation dataset were significantly younger, and the ratio of deceased patients in the validation dataset was significantly lower. The performance of the prediction tool at the optimal cutoff-point was: AUC-ROC = 0.72, accuracy = 63.6%, sensitivity = 72.5%, and specificity = 61.7%. The survival curves of the predicted survived and the predicted deceased groups were significantly different (p < 0.001). The 2-year all-cause mortality prediction tool for patients with stage 4 or 5 CKD showed satisfactory discriminatory capacity with emphasis on sensitivity. The proposed prediction tool appears to be of clinical interest for further development.

Sarcopenia, sarcopenic obesity and the clinical outcome of the older inpatients with COVID-19 infection: a prospective observational study

ObjectiveWe aimed to investigate the impact of sarcopenia and sarcopenic obesity (SO) on the clinical outcome in older patients with COVID-19 infection and chronic disease.MethodsWe prospectively collected data from patients admitted to Huadong Hospital for COVID-19 infection between November 1, 2022, and January 31, 2023. These patients were included from a previously established comprehensive geriatric assessment (CGA) cohort. We collected information on their pre-admission condition regarding sarcopenia, SO, and malnutrition, as well as their medical treatment. The primary endpoint was the incidence of intubation, while secondary endpoints included in-hospital mortality rates. We then utilized Kaplan-Meier (K-M) survival curves and the log-rank tests to compare the clinical outcomes related to intubation or death, assessing the impact of sarcopenia and SO on patient clinical outcomes.ResultsA total of 113 patients (age 89.6 ± 7.0 years) were included in the study. Among them, 51 patients had sarcopenia and 39 had SO prior to hospitalization. Intubation was required for 6 patients without sarcopenia (9.7%) and for 18 sarcopenia patients (35.3%), with 16 of these being SO patients (41%). Mortality occurred in 2 patients without sarcopenia (3.3%) and in 13 sarcopenia patients (25.5%), of which 11 were SO patients (28%). Upon further analysis, patients with SO exhibited significantly elevated risks for both intubation (Hazard Ratio [HR] 7.43, 95% Confidence Interval [CI] 1.26–43.90, P < 0.001) and mortality (HR 6.54, 95% CI 1.09–39.38, P < 0.001) after adjusting for confounding factors.ConclusionsThe prevalence of sarcopenia or SO was high among senior inpatients, and both conditions were found to have a significant negative impact on the clinical outcomes of COVID-19 infection. Therefore, it is essential to regularly assess and intervene in these conditions at the earliest stage possible.

PANoptosis-based molecular subtype and prognostic model predict survival and immune landscape in esophageal cancer

PurposeTo establish a prognostic model to predict the survival of patients with esophageal cancer (EC).MethodsWe extracted the expression profiles of prognostic-related genes and clinicopathological data from TCGA and GEO databases. Subsequently, a comprehensive bioinformatics analysis was conducted to construct a prognostic model utilizing LASSO and multivariate Cox regression. The stability of the risk signature was validated through Kaplan-Meier and ROC curve analyses on the training, internal testing, and external testing sets. Furthermore, we developed a nomogram that incorporates the risk score and clinical features to predict the suvival. Additionally, a nomogram incorporating the risk score and relevant clinical parameters was developed to enhance survivorship prediction. Furthermore, we delved into exploring the correlation between the risk score and immune cell abundance, expression of cancer checkpoints, as well as responses to immunotherapy and chemotherapeutic agents.ResultsIn this study, we successfully identified 19 prognosis-related genes out of a pool of 65 PANoptosis-related genes (PRGs) sourced from existing literature. Through consensus clustering analysis, we classified patients into two distinct groups as PANcluster A and B. Furthermore, the risk score derived from the five PANoptosis-related signatures emerged as an independent prognostic factor among patients with EC. To enhance the prognostic accuracy, we devised a nomogram integrating the risk score with clinical risk characteristics, enabling the prediction of 1-year, 2-year, and 3-year overall survival (OS) rates. Notably, individuals classified in the high-risk group demonstrated poorer prognoses compared to their low-risk counterparts. Furthermore, the risk score displayed substantial correlations with immune cell abundance, expression levels of cancer checkpoints, and responses to immunotherapy and chemotherapeutic agents. These pivotal findings underscore the significance of considering PANoptosis-related patterns in improving prognostic assessment and predicting treatment responses in patients diagnosed with esophageal cancer.ConclusionWe constructed a reliable prognostic risk model for EC utilizing five PRGs. The developed nomogram serves as a valuable tool in predicting patient outcomes, offering crucial insights that can inform and guide treatment decisions for individuals diagnosed with EC.

Synergistic prognostic impact of hemoglobin and skeletal muscle index in patients with colorectal cancer

Background & AimsRecent studies have indicated that comorbidities such as sarcopenia and anemia can influence the prognosis of patients with colorectal cancer (CRC). However, the synergistic effects of sarcopenia and anemia on the survival of CRC patients are not yet comprehensively understood. This study aimed to investigate the relationship between anemia and sarcopenia and their synergistic effect on survival in patients with CRC. MethodsA total of 1629 patients who underwent colorectal surgery were retrospectively reviewed. Patients were categorized into four hemoglobin-sarcopenia combined classifications (HS grade) according to their hemoglobin and skeletal muscle index (SMI) levels: hemoglobin low/SMI low (HS1), hemoglobin low/SMI high (HS2), hemoglobin high/SMI low (HS3), and hemoglobin high/SMI high (HS4). Association with overall survival (OS) was analyzed using both univariable and multivariable analyses. ResultsIn total, 1024 patients with stage I-III CRC were analyzed. Patient allocation according to HS grade was 124 (12.1%) in HS1, 298 (29.1%) in HS2, 135 (13.2%) in HS3, and 467 (45.6%) in HS4. The Kaplan-Meier curves of OS showed statistically significant differences according to anemia and sarcopenia status as well as to HS grade (all P < 0.001). Univariable analysis of factors associated with OS revealed statistical significance in absence of anemia (hazard ratio [HR] 0.550, 95% confidence interval [CI] 0.400-0.756, P < 0.001], absence of sarcopenia (HR 0.560, P < 0.001), and HS grade (HS2, HR 0.515, P = 0.002; HS3, HR 0.468, P = 0.006; HS4, HR 0.325, P < 0.001). Multivariable analysis showed that compared to the HS1 group, the HS2 and HS4 groups showed significantly better OS (HS2, HR 0.527, 95% CI 0.340-0.817, P = 0.004; HS4, HR 0.574, 95% CI 0.361-0.912, P = 0.018). ConclusionsSarcopenia, characterized by a low SMI and the presence of anemia before surgery, was associated with reduced OS among patients with non-metastatic CRC.

Retention Rate of Ixekizumab in Psoriatic Arthritis: A Real-World Study

We aimed to examine the drug retention rate (DRR) of the interleukin-17 inhibitor ixekizumab in a real-world monocentric cohort of psoriatic arthritis (PsA) patients and to assess the predictors of drug discontinuation. Consecutive PsA patients who underwent treatment with ixekizumab from October 2019 to February 2023 were enrolled in this observational, retrospective, monocentric study. Clinical records were assessed at baseline and throughout the follow-up period. We collected sociodemographic data, smoking habits, body mass index, the presence of Human Leukocyte Antigen B27, comorbidities, disease involvement and duration, previous therapy, discontinuation of ixekizumab, reasons for discontinuation, and adverse events (AEs). DRR was evaluated as time to drug discontinuation and assessed through Kaplan–Meier curves. Baseline factors predicting drug discontinuation were investigated through logistic regression models. Eighty PsA patients were included in this study. Ixekizumab was administered at a dose of 160 mg by subcutaneous injection at baseline, followed by 80 mg every four weeks thereafter. Ixekizumab had a 38-month-cumulative DRR of 43.8%, accounting for both inefficacy and AEs. When considering only inefficacy, the DRR was 62.6%. Comorbidities (p = 0.665), obesity (p = 0.665), smoking (p = 0.884), disease duration ≤ 2 years (p = 0.071), axial (p = 0.131) and skin involvement (p = 0.460), and previous therapies, including conventional synthetic (p = 0.504) and biological (p = 0.474) Disease-Modifying Antirheumatic Drugs (bDMARDs), as well as the number of previous bDMARDs or targeted synthetic Disease-Modifying Antirheumatic Drugs (tsDMARDs), did not significantly affect the DRR (p = 0.349). Multivariate analysis found no independent predictors of drug discontinuation. The most frequent AEs leading to discontinuation were skin reactions; no severe infections were observed. In our real-world study, comorbidities, disease duration, and previous therapies did not affect the DRR of ixekizumab. Ixekizumab had a favorable safety profile, with no severe AEs observed.

O-314 Investigating the embryonic contribution to recurrent pregnancy loss: a retrospective analysis of embryo quality, chromosomal status and morphokinetics in 11,169 embryos

Abstract Study question What is the embryonic contribution, in terms of embryo quality, chromosomal status and morphokinetics, to the reproductive success of recurrent pregnancy loss (RPL) patients? Summary answer RPL patients undergoing PGT-A had significantly fewer embryos available for biopsy, higher aneuploidy rates and showed morphokinetic alterations around the time of blastulation. What is known already RPL is diagnosed following the loss of two or more pregnancies before the 24th week of gestation. RPL has a multifactorial etiology encompassing both maternal and embryonic factors, such as uterine malformations, the presence of anti-phospholipid antibodies, maternal obesity or embryo aneuploidy, among others. While some studies have shown increased rates of chromosomal abnormalities in blastocysts from idiopathic RPL patients, a comprehensive characterization of the embryonic contribution to the disorder remains limited, and the role of embryo morphokinetics is still underexplored. Study design, size, duration This retrospective cohort study analyzed 11,169 embryos from 3,005 PGT-A cycles performed across 9 European fertility clinics between January 2017 and July 2023. Differences in the number of biopsied embryos, aneuploidy rates and embryo quality were compared between RPL and non-RPL patients. Morphokinetic timings were evaluated in a subset of 704 RPL embryos from 2 fertility centers, which was then compared to a separate cohort of embryos (n = 952) derived from double gamete donation cycles (n = 134). Participants/materials, setting, methods Genetic and clinical outcomes were assessed by multivariate analyses adjusting for maternal age, paternal age, the presence of male factor and embryo grade, as appropriate. Kaplan-Meier survival curves were constructed for each morphokinetic parameter (tPNf, t2, t3, t4, t5, t8, tSB and tB) and analyzed by Cox regression using maternal age and male factor as adjusting variables. P-values &amp;lt;0.05 were considered statistically significant. Main results and the role of chance RPL patients undergoing PGT-A represented 15.47% (n = 465/3,005) of the cohort and were significantly younger than the rest of the patients (34,97±6.6 vs 36.38±6.6, p &amp;lt; 0.0001). RPL patients obtained significantly fewer blastocysts available for biopsy (coefficient -0.39, 95%CI: -0.703- -0.076, p = 0.01) and had significantly higher aneuploidy rates (OR = 1.19, 95%CI: 1.06-1.35, p = 0.004). However, embryo quality (excellent vs. rest, p &amp;gt; 0.05) was comparable between the two groups (n = 11,169 embryos). As anticipated, biochemical and clinical pregnancy rates were comparable between RPL patients and non-RPL patients (OR = 0.94, 95%CI:0.72-1.24, p = 0.68; OR = 0.95, 95%CI: 0.72-1.24, p = 0.71, respectively), however patients with RPL presented with significantly higher miscarriage rates (OR = 1.66, 95% CI:1.03-2.74, p = 0.04). Compared to double donation embryos, RPL embryos exhibited significant delays in all analyzed times (tPNf: 23.7±3.1 vs. 22.7±3.1; t2: 26.5±4.1 vs. 25.6±3.4; t3: 37.1±5.4 vs. 36.0±4.7; t4: 39.2±6.3 vs. 37.9±5.3; t5: 50.2±7.9 vs. 49.3±7.4; tsB: 99.4±10.3 vs. 97.9±9.7; tB: 110.3±11.5 vs. 106.4±11.8; p &amp;lt; 0.05). Notably, delays in blastocyst formation were also observed when adjusting for maternal age and male factor (Hazard Ratio=0.38, 95% CI: 0.18-0.79, p = 0.009). Significantly, morphokinetic alterations persisted even when exclusively comparing euploid RPL embryos to the double donation group (n = 41, t8: Hazard Ratio=1.78, 95% CI: 1.22-2.57, p = 0.002; tsB: Hazard Ratio=1.70, 95% CI: 1.17-2.48, p = 0.006). Limitations, reasons for caution The main limitation of the study is its retrospective design, where known RPL risk factors leading to the selection of a PGT-A cycle were not considered, potentially introducing biases. Wider implications of the findings These findings highlight the intricate interplay between embryo quality, aneuploidy, and morphokinetics in RPL, guiding personalized patient management. Higher embryo aneuploidy and morphokinetic alterations observed even in euploid RPL embryos suggest an embryonic role, underscoring the condition’s multifactorial nature and urging exploration of molecular mechanisms linking embryonic factors to RPL. Trial registration number not applicable

327 Impact of Adjuvant Chemotherapy/Radiotherapy on the 5 Year Overall Survival of Patients with Non-Metastatic Rectal Cancer in Bulgaria - a Retrospective Population-Wide Observational Study

Abstract Introduction Survival rates of patients with non-metastatic rectal cancer (RC) have increased, due the use of adjuvant chemotherapy/radiotherapy post-surgery, recommended by the National Comprehensive Cancer Network (NCCN) [1–3]. The aim of the study was to analyse the impact of adjuvant chemotherapy/radiotherapy on the 5-year overall survival (OS) of patients diagnosed with non-metastatic RC patients in Bulgaria. Method This is a retrospective population wide observational study of 8968 cases registered with Colorectal cancer in the Bulgarian National Cancer Registry (BNCR) between 2015 and 2016. The mean and median age of patients with left colon (LCC) and right colon (RCC) along with rectal cancer (RC) was analysed. The impact of adjuvant chemotherapy and radiotherapy on the 5-Year OS for non-metastatic RC was analysed. Kaplan-Meier curve with log rank, ANOVA and chi-squared tests were used to estimate the statistical significance. Results The mean age at diagnosis for RCC, LCC and RC was 68.9, 67.41 and 66.4 respectively (p-Value=&amp;lt;0.001). The median age at diagnosis was 69, 68 and 67 for RCC, LCC and RC respectively. Our study showed that patients with non-metastatic RC that received both adjuvant chemotherapy and radiotherapy had a higher 5-year OS compared to patients who received either chemotherapy, radiotherapy or neither therapy (61.4%, 59.5%, 56.2%, 51.8%), p-Value=0.007. Less than 40% of patients received either adjuvant chemotherapy or radiotherapy. Conclusions Adjuvant chemotherapy/radiotherapy improves the 5-Year OS for patients with non-metastatic RC. NCCN guidelines should be implemented in Bulgaria [1–3]. Bulgaria will benefit by implementing an organised screening programme [4].

Untangling biliary reconstruction in liver transplants for primary sclerosing cholangitis.

Biliary reconstruction technique during liver transplant (LT) for primary sclerosing cholangitis (PSC) remains controversial. This study aimed to evaluate the incidence of biliary complications in patients with PSChaving a duct-to-duct (DD) anastomosis or Roux-en-Y hepaticojejunostomy (HJ). A retrospective medical record review of patients with PSC undergoing LT at a single center between June 1st, 2000 and December 31st, 2022 was performed. Primary and secondary endpoints were the incidence of biliary strictures (anastomotic [BAS] and non-anastomotic strictures [NAS]) and non-stricture complications, respectively. Univariable and multivariable regression analyses were performed to identify associations with BAS formation. Patient survival was assessed using a Kaplan-Meier curve. From 105 transplants performed for 101 patients, 54 (51.4%) and 51 (48.5%) received DD and HJ anastomoses. Mean recipient age and follow-up was 47±13years and 98±69months. BAS was more common (48.1% vs. 27.5%, OR 2.45, 95% CI 1.09-5.54, p=0.03) and occurred earlier (4.8months, IQR 2.3-13.1 vs. 41.8months, IQR 7.2-88.7, p=0.001) in the DD than the HJ group. NAS (seen in 36.2% of transplants) had a comparable incidence (p=0.53) in HJ (38.9%) and DD (33.3%) groups. No difference was seen between cohorts regarding time to NAS, requirement for extended biliary dilatation programs (clinically significant biliary stricture), bile leak, and graft failure. On multivariable analysis, only the anastomotic technique was associated with BAS (DD adjusted OR 3.00, 95% CI 1.19-7.56, p=0.02). In carefully selected patients with PSC, DD anastomosis yielded similar outcomes to HJ anastomosis after liver transplantation.

Hepatic arterial infusion chemotherapy plus camrelizumab and apatinib for advanced hepatocellular carcinoma.

There is limited information on combination of hepatic arterial infusion chemotherapy (HAIC) and systemic therapy for advanced hepatocellular carcinoma (Ad-HCC). We aim to compare the efficacy and safety of HAIC plus camrelizumab (a PD-1 inhibitor) and apatinib (an VEGFR-2 inhibitor) versus camrelizumab and apatinib for Ad-HCC. From April 2019 to October 2022, 416 patients with Ad-HCC who received either HAIC plus camrelizumab and apatinib (TRIPLET protocol, n = 207) or camrelizumab and apatinib (C-A protocol, n = 209) were reviewed retrospectively. The propensity score matching (PSM) was used to reduce selective bias. Overall survival (OS) and progression-free survival (PFS) were compared using the Kaplan-Meier method with the log-rank test. Cox regression analyses of independent prognostic factors were evaluated. After PSM 1:1, 109 patients were assigned to two groups. The median OS of not reached in the TRIPLET group was significantly longer than that of 19.9months in the C-A group (p < 0.001), while in the TRIPLET group, the median PFS of 11.5months was significantly longer than that of 9.6months in the C-A group (p < 0.001). Multivariate analyses showed that the factors significantly affected the OS were CTP grade, tumor number > 3, and TRIPLET treatment (p < 0.001). Grade 3/4 adverse events occurred at a rate of 82.1% vs. 71.3% in TRIPLET and C-A groups, respectively. The TRIPLET protocol has promising survival benefits in the management of patients with Ad-HCC, with acceptable safety. The study has been retrospectively registered at Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ , ChiCTR2300075828).