Log Rank Research Articles

Combined 3D left ventricular-arterial coupling and 3D left atrial-ventricular coupling indices could better predict MACE in young patients with STEMI

Abstract Background Left ventricular arterial coupling index (VAC) proved to be a key determinant of cardiovascular performance. Previous trials also emphasized the prognostic value of left atrial-ventricular coupling index (LACI) that was independently associated with cardiovascular death and all-cause mortality. Both indices have been associated with disease severity and adverse outcomes. Purpose We aimed to evaluate the prognostic role of 3D VAC, 3D LACI and their combination assessed by 3D echocardiography in a cohort of young patients with STEMI. Patients and methods In this prospective study we enrolled 76 young consecutive patients (under 50 years old) with STEMI treated by primary PCI who underwent both 2D and 3D echocardiography. 3D VAC was calculated as the ratio between arterial elastance (EA) and end-systolic left ventricular elastance (EES), based on a formula proposed by Chen. 3D LACI was determined as the ratio between 3D left atrial end-diastolic volume (minimal atrial volume) and 3D left ventricular end-diastolic volume. Patients were followed up for one year after STEMI and the primary endpoint was the occurrence of MACE defined as death from cardiovascular causes, heart failure requiring hospital admission, or repeat revascularisation. Results Out of 76 patients, 15.8% had an adverse event during the 12 months follow up period. We divided the patients in two groups according to the presence or absence of MACE. Patients with MACE had higher VAC (2.15±0.62 vs. 1.25±0.29%, p<0.0001) and higher LACI (25.1±7.17% vs. 18.3±6.58%, p=0.002). In ROC analysis VAC and LACI combined had the best AUC for MACE prediction (AUC 0.961, p<0.0001), followed by VAC (AUC 0.922, P<0.0001), and then, LACI (AUC 0.772, P<0.001). For each variable we determined a cut off value. A value over 1.7 for VAC and 23.83% for LACI can predict unfavourable outcome with 83.3% sensitivity and 97.1% specificity for VAC and 67% sensitivity and 80% specificity for LACI. In both univariate and multivariate COX regression analysis, both VAC and LACI remained independent predictors for MACE. Moreover, their combination proved to have better predictive value for adverse events compared to each taken separately. We divided the study population into 4 groups: Group 1: VAC < 1.7 and LACI < 23.83%. Group 2: VAC <1.7 and LACI > 23.83%. Group 3: VAC > 1.7 and LACI < 23.83% and Group 4: VAC > 1.7 and LACI >0.23.83%. Kaplan Meier analysis shows significant differences among groups (log rank χ2 = 35.48, p < 0.0001). Calculation of Kaplan-Meier curves for the four groups indicated that the combination of the VAC > 1.7 and LACI > 23.83% had the strongest predictive power for MACE. Conclusion In conclusion 3D VAC and 3D LACI combined are better at predicting adverse events than each variable taken separately and could be used for a more accurate risk stratification in young patients with STEMI.

CMR-derived pulmonary artery to aorta ratio as a predictor of adverse outcome in patients with cardiac transthyretin amyloidosis

Abstract Introduction Cardiac transthyretin amyloidosis (ATTR) represents a heart failure phenotype often accompanied by pulmonary hypertension. The pulmonary artery to aorta ratio (PA/Ao), as assessed on cardiac computed tomography or cardiac magnetic resonance (CMR), has demonstrated to indicate risk for adverse events in a variety of cardiovascular diseases, particularly in heart failure and pulmonary hypertension. However, its prognostic value in cardiac ATTR remains unknown. Aim We aimed to investigate the prognostic value of the PA/Ao ratio in patients with cardiac ATTR. Methods Data of consecutive patients diagnosed with cardiac ATTR undergoing CMR were prospectively collected. PA/Ao ratios were measured from CMRs using axial images (Figure 1A). Adverse outcome, defined as heart failure related hospitalizations and/or mortality, was recorded during follow-up. Results Among the 190 confirmed cardiac ATTR patients (mean age 76±11 years, 79% males), encompassing hereditary transthyretin (vATTR, n=22) and senile (wtATTR, n=168) types, the median pulmonary artery diameter was 28mm (IQR 25-31) and the median ascending aorta diameter was 35mm (IQR 33-39). Over the median follow-up period of 28 months (IQR 11-50 months), 84 (44%) patients experienced an adverse event. Kaplan Meier curves demonstrated an increased risk for adverse outcome in patients with PA/Ao ratios above the median of ≥0.8 (p<0.001 by log rank test, see Figure 1B). In univariate analysis, a high PA/Ao ratio was associated with adverse outcome (HR=10.3, 95% CI=2.59–41.1, p<0.001). When adjusted for age, sex, body mass index and right ventricular function, the PA/Ao ratio remained significantly related to adverse outcome (adj. HR=10.8, 95% CI=1.76–65.8, p=0.010). Conclusion A PA/Ao ratio ≥0.8 on CMR is associated with heart failure hospitalization and death in patients with cardiac ATTR. This threshold, notably lower than the commonly reported ≥1.0 in other patient populations, holds promise for future risk stratification.

Early ablation leads to better outcome in patients < 55 years with persistent atrial fibrillation

The question of optimal timing for catheter ablation of atrial fibrillation (AF) to achieve best outcomes remains a crucial clinical issue. As AF occurs less frequently in younger patients, data regarding Diagnosis-to-Ablation Time (DAT) is especially limited in patients under the age of 55 years with persistent AF. We therefore analyzed the temporal relationship between initial AF presentation and timing of catheter ablation in this cohort. We conducted a retrospective single-centre study of patients ≤ 55 years with persistent AF who underwent first-time catheter ablation at our center. The cohort was divided into patients that underwent catheter ablation after diagnosis of persistent AF within a DAT of ≤ 12 months and patients with a DAT of > 12 months. A total of 101 patients (median age 51 years; female n = 19 (18.8%)) with persistent AF were included. Ablation was performed within 12 months (“early DAT”) in 51 patients and > 12 months (“late DAT”) in 50 patients. Pulmonary vein isolation was performed using high-power short-duration (HPSD) radiofrequency ablation. Median DAT was 5 months (1–12 months) in the early ablation group and 36 months (13–240 months) in the late ablation group. The median follow-up was 11.3 months (0.03–37.1 months). The rate of any atrial arrhythmia recurrence after a 30-day blanking period was significantly lower in the early DAT group (13/51 patients; 25.5%) as compared to the late DAT group (26/50 patients; 52.0%) (log rank test; p = 0.003). Catheter ablation performed > 12 months after the initial AF diagnosis was an independent predictor for the occurrence of any atrial arrythmia (OR: 2.58; (95%-CI: 1.32–5.07). Early first-time catheter ablation (DAT ≤ 12 months) in patients ≤ 55 years with persistent AF is associated with a significantly lower rate of arrhythmia recurrence.

Effectiveness of a dynamic seat cushion on recovery and recurrence of neck and low back pain in office workers: a secondary analysis of a randomized controlled trial

BackgroundNeck and low back pain are prevalent issues among office workers due to prolonged sitting, necessitating effective interventions. Dynamic seat cushion, designed to promote postural shifts, have emerged as promising solutions to address this concern. This study aims to evaluate the effectiveness of a dynamic seat cushion on recovery and recurrence of neck and/or low back pain in office workers.MethodsThis study used 6-month follow-up data of a randomized controlled trial, involving 66 office workers who reported neck and/or low back pain during the trial. At baseline, participants were cluster-randomized into an intervention group, which received a dynamic seat cushion designed to encourage postural shifts, or a control group, which received a placebo seat pad. Health outcomes included recovery duration and recurrence of pain. Analyses utilized log rank test and Cox proportional hazard models.ResultsThe recovery rate from neck and/or low back pain was 100% for the intervention group, and 86% for the control group. The median recovery duration of participants who reported pain during the 6-month period was 1 month in the intervention group and 3 months in the control group. The intervention group had a higher probability of recovery compared to the control group (HRadj 4.35, 95% CI 1.87–10.11; p < 0.01). The recurrence rate of neck and low back pain was 27% in the intervention group, which was 75% in the control group. The Hazard Ratio, after adjustment, for the intervention group compared to the control group was 0.50 (95% CI = 0.11–2.12).ConclusionsA dynamic seat cushion that encourages postural shifts shortened recovery duration of neck and low back pain among office workers. Due to small numbers, a potentially relevant reduction in the recurrence of neck and low back pain could not be statistically confirmed. A power analysis was not conducted for this secondary analysis, and future studies should be designed with adequate sample sizes to explore the recurrence of pain with greater statistical power.Trial registrationThis trial is retrospectively registered under the Thai Clinical Trials Registry: TCTR20230623002 (23/06/2023).

Clinical Frailty Scale score is a predictor of short-, mid- and long-term mortality in critically ill older adults (≥ 70years) admitted to the emergency department: an observational study.

The estimated prognos of a patient might influence the expected benefit/risk ratio of different interventions. The main purpose of this study was to investigate the Clinical Frailty Scale (CFS) score as an independent predictor of short-, mid- and long-term mortality in critically ill older adults (aged ≥ 70) admitted to the emergency department (ED). This is a retrospective, single-center, observational study, involving critically ill older adults, recruited consecutively in an ED. All patients were followed for 6.5-7.5years. The effect of CFS score on mortality was adjusted for the following confounders: age, sex, Charlson's Comorbidity Index, individual comorbidities and vital parameters. All patients (n = 402) were included in the short- and mid-term analyses, while patients discharged alive (n = 302) were included in the long-term analysis. Short-term mortality was analysed with logistic regression, mid- and long-term mortality with log rank test and Cox proportional hazard models. The CFS was treated as a continuous variable in the primary analyses, and as a categorical variable in completing analyses. There was a significant association between mortality at 30days after ED admission and CFS score, adjusted OR (95% CI) 2.07 (1.64-2.62), p < 0.0001. There was a significant association between mortality at one year after ED admission and CFS score, adjusted HR (95% CI) 1.75 (1.53-2.01), p < 0.0001. There was a significant association between mortality 6.5-7.5years after discharge and CFS score, adjusted HR (95% CI) 1.66 (1.46-1.89), p < 0.0001. Adjusted HRs are also reported for long-term mortality, when the CFS was treated as a categorical variable: CFS-score 5 versus 1-4: HR (95% CI) 1.98 (1.27-3.08); 6 versus 1-4: HR (95% CI) 3.60 (2.39-5.44); 7 versus 1-4: HR (95% CI) 3.95 (2.38-6.55); 8-9 versus 1-4: HR (95% CI) 20.08 (9.30-43.38). The completing analyses for short- and mid-term mortality indicated a similar risk-predictive value of the CFS. Clinical frailty scale score was independently associated with all-cause short-, mid- and long-term mortality. A nearly doubled risk of death was observed in frail patients. This information is clinically relevant, since individualised treatment and care planning for older adults should consider risk of death in different time perspectives.

Systematic review of extrahepatic hepatic artery pseudoaneurysm following adult liver transplantation: Risk factors and treatment modalities.

Hepatic artery pseudoaneurysm (HAP) is a rare vascular complication following liver transplantation (LTx) with treatment choice frequently driven by institutional experience. Approximately, 10% of hepatic grafts are lost from this complication, requiring re-transplantation and placing further demand on the already present organ shortage. Secondly, patients with HAP can present with catastrophic bleeding, with reported mortality of up to 78%. We aim to identify risk factors associated with HAP and assess the survival benefit of different treatment modalities used (endovascular and open surgical techniques). Early detection may facilitate semi-elective management of this condition. A systematic search was performed in PubMed, Medline and Embase up to 1 October 2023. Case series with ≥5 patients focusing on adult patients who developed extrahepatic pseudoaneurysm following LTx were included. A total of 11 studies were pooled, comprising of 118 patients with survival data available in 61 patients. The most common presentation was haemorrhagic shock or luminal haemorrhage (75.5%). Bile leak was documented in 66.7% (28/42), 15.2% (18/118) associated foregut pathologies and 28.6% (14/49) of microbiology cultures grew a fungal organism. Flow preserving strategies (stenting, revascularization) trended towards better survival at 120 months compared to non-flow preserving strategies (embolization, HAL); however, this was not statistically significant following log rank (Mantel-Cox) analysis (P 0.169). Any patient following LTx presenting with haemorrhagic shock or luminal bleeding needs HAP excluded urgently. HAP management is complex, requiring careful consideration of patient specific presentation, anatomic factors and associated pathologies.

Prognostic Impact of Acute and Chronic Inflammatory Interleukin Signatures in the Tumor Microenvironment of Early Breast Cancer

Interleukins play dual roles in breast cancer, acting as both promoters and inhibitors of tumorigenesis within the tumor microenvironment, shaped by their inflammatory functions. This study analyzed the subtype-specific prognostic significance of an acute inflammatory versus a chronic inflammatory interleukin signature using microarray-based gene expression analysis. Correlations between these interleukin signatures and immune cell markers (CD8, IgKC, and CD20) and immune checkpoints (PD-1) were also evaluated. This study investigated the prognostic significance of an acute inflammatory IL signature (IL-12, IL-21, and IFN-γ) and a chronic inflammatory IL signature (IL-4, IL-5, IL-10, IL-13, IL-17, and CXCL1) for metastasis-free survival (MFS) using Kaplan–Meier curves and Cox regression analyses in a cohort of 461 patients with early breast cancer. Correlations were analyzed using the Spearman–Rho correlation coefficient. Kaplan–Meier curves revealed that the prognostic significance of the acute inflammatory IL signature was specifically pronounced in the basal-like subtype (p = 0.004, Log Rank). This signature retained independent prognostic significance in multivariate Cox regression analysis (HR 0.463, 95% CI 0.290–0.741; p = 0.001). A higher expression of the acute inflammatory IL signature was associated with longer MFS. The chronic inflammatory IL signature showed a significant prognostic effect in the whole cohort, with higher expression associated with shorter MFS (p = 0.034). Strong correlations were found between the acute inflammatory IL signature and CD8 expression (ρ = 0.391; p &lt; 0.001) and between the chronic inflammatory IL signature and PD-1 expression (ρ = 0.627; p &lt; 0.001). This study highlights the complex interaction between acute and chronic inflammatory interleukins in breast cancer progression and prognosis. These findings provide insight into the prognostic relevance of interleukin expression patterns in breast cancer and may inform future therapeutic strategies targeting the immune–inflammatory axis.

Pre-treatment of hyponatremia as a biomarker for poor immune prognosis in advanced or metastatic gastric cancer: A retrospective case analysis

ABSTRACT Hyponatremia, a prevalent electrolyte imbalance among tumor patients, has often been overlooked regarding its prognostic significance for immunotherapy. In this study, we delved into the prognostic ramifications of hyponatremia in advanced gastric cancer (AGC) patients undergoing immunotherapy. Enrolling AGC patients diagnosed between December 2014 and May 2021, we extracted pertinent data from electronic medical records, with a median follow-up of 35.8 months. Kaplan–Meier curves illuminated patients’ progression-free survival (PFS) and overall survival (OS), while survival disparities were tested using the Mantel–Haenszel log rank test. COX and logistic regressions were employed to scrutinize the correlation between serum sodium levels and prognosis in 268 AGC patients, both at baseline and during treatment. Notably, patients with hyponatremia exhibited shorter PFS (4.7 vs 2.1 months, p = .001*) and OS (12.5 vs 3.9 months, p < .001*). Serum sodium emerged as an independent prognostic factor for both PFS (HR = 1.773; 95% CI 1.067–2.945; p = .001*) and OS (HR = 1.773; 95% CI 1.067–2.945; p = .003*). Subgroup analysis revealed that AGC patients with hyponatremia derived no benefit from immunotherapy in terms of PFS and OS. Strikingly, a decrease in serum sodium during immunotherapy was associated with early relapse and mortality. Based on these findings, we hypothesize that hyponatremia portends poor prognostic outcomes in AGC patients treated with immunotherapy and may serve as a valuable prognostic biomarker. However, further large-scale prospective studies are warranted to validate these observations.

A Study in Pituitary Neuroendocrine Tumors (PitNETs): Real-Life Data Amid Baseline and Serial CT Scans.

We aimed to evaluate CT-related PIs diameters following 3 aspects: a cross-sectional analysis based on the age' groups at first PI diagnosis and on the gender distribution and a longitudinal analysis in PIs with <0.5 cm versus ≥0.5 cm as the largest diameter at baseline. A retrospective, real-life, multi-centric study in adults with NF micro-PIs was performed. 208 subjects (92.79% females) were included (average age 43.18 ± 12.58 y). The mean largest diameter (between transversal and longitudinal diameters) was 0.55 ± 0.16cm, and 44.71% of the PIs were located on the right part of the pituitary gland. The patients were divided into 10 age-groups (21 to 70 y), and no difference was observed between the mean largest diameters of these groups (p = 0.693). Females and males had a similar age at PIs diagnosis (p = 0.353), transverse diameter (p = 0.910), longitudinal diameter (p = 0.229), and PI location (p = 0.368). Serial CT scans (2 to 4 per patient) included a median (Q1-Q3) of 20 (12-36) months for the second CT scan, 58 (36-84) for the third CT scan, 78 (53-118) for the fourth CT scan, and a total follow-up between baseline and last CT scan of 40 (13-72) months. The initial largest diameter correlated with the diameter change between the baseline and the last CT (r = -0.575, p = 0.000). The largest PI diameter was similar between each serial CT scan (p = 0.840). According to the cut-off value of 0.5 cm diameter (for initial largest tumor diameter), group A (N = 78, 37.50%, <0.5 cm) and group B (N = 130, 62. 50%; ≥0.5 cm) had similar age at baseline (43.83 ± 12.72 versus 42.79 ± 12.54 y, p = 0.565) and PIs locations (right, left, median). The largest PI diameter remained smaller in group A versus B amid the second CT scan (p = 0.000) and the last CT scan (p = 0.009). The largest diameter change from the first to the last CT scan showed an increase in group A (median of +0.10 cm, p = 0.000) and a decrease in group B (median of -0.01 cm, p = 0.002); this diameter change was different in group A versus B (p = 0.000). The cumulative probability of tumor-growth-free survival showed different survival functions (log rank p = 0.000): group A exhibited a more gradual decrease versus B; at 60 months, the cumulative probability was 0.32 ± 0.08 for group A versus 0.75 ± 0.07 for B. During follow-up, all PIs remained NF, and no hypopituitarism was noted (as limits, we mention that dynamic hypopituitarism testing was selectively performed). NF micro-PIs in adults showed a similar age and sex distribution. During follow-up, PIs with a largest diameter < 0.5 cm increased after a median of 40 months but remained <1 cm, while in PIs with ≥0.5 cm, the largest diameter decreased. This highlights a lower predictability in tumor behavior than expected, particularly in larger micro-PIs that, overall, remained without relevant clinical implications after surveillance.

Multiple triglyceride-derived metabolic indices and incident cardiovascular outcomes in patients with type 2 diabetes and coronary heart disease

BackgroundTriglyceride (TG) and its related metabolic indices are recognized as important biomarker gauging cardiovascular diseases. This study aimed to explore the association between multiple TG-derived metabolic indices including the atherogenic index of plasma (AIP), triglyceride-glucose (TyG) index, triglyceride glucose-body mass index (TyG-BMI) and cardiovascular outcomes to identify valuable predictors for cardiovascular prognosis in patients with type 2 diabetes (T2DM) and coronary heart disease (CHD).MethodsData of 1034 patients with T2DM and CHD from China-Japan Friendship Hospital between January 2019 and March 2022 were collected and analyzed. Multivariate Cox proportional hazards models and restricted cubic spline (RCS) analysis were conducted to examine the associations between AIP, TyG index, TyG-BMI and major adverse cardiac and cerebrovascular events (MACCEs). The area under the receiver operating characteristic (ROC) curve (AUC) was used to screen the most valuable predictor. Kaplan-Meier curve analysis was employed to examine the relationship between the predictor and prognosis. The goodness-of-fit of models was evaluated using the calibration curve and χ2 likelihood ratio test. Subgroup analysis and interaction test were performed to control for confounding factors.ResultsThe overall incidence of MACCEs was 31.04% during a median of 13.3 months of follow-up. The results showed that AIP, TyG index and TyG-BMI were all positively correlated with the risk of MACCEs in patients with T2DM and CHD (P < 0.05). Furthermore, ROC (AUC = 0.899) suggested that AIP had the strongest ability to predict the risk of MACCEs, and the highest AIP values enhanced the risk by 83.5% in the population. RCS model demonstrated that AIP was nonlinearly associated with the incident cardiovascular outcomes (P for nonlinear = 0.0118). The Kaplan-Meier analysis for MACCEs grouped by the AIP tertiles indicated that the probability of cumulative incidences of MACCEs was significantly higher in patients with a higher AIP (all Log rank P < 0.001). Meanwhile, the calibration curve demonstrated an excellent goodness-of-fit of the multivariate model (χ2 = 13.210, P = 0.105). Subgroup analysis revealed that the trend of positive association of AIP with cardiovascular risk was similar across subgroups except in non-hypertensive individuals.ConclusionOur study, for the first time, may provide valuable information that multiple TG-derived metabolic indices play a crucial role in the risk of MACCEs and it is recommended to monitor the AIP for lipid management in patients with established T2DM and CHD.

The Role of Atrial Premature Complexes in Exercise Test in Predicting Atrial Fibrillation in Patients Without Obstructive Coronary Artery Disease.

Atrial fibrillation (AF) is usually triggered by frequent atrial premature complexes (APC) and atrial tachycardias originated in the pulmonary veins. The aim of the current study is to clarify the relationship between AF and APCs observed during treadmill exercise testing through long-term patient follow-up. Our study only examined the data of patients who did not have any obstructive coronary artery disease and had an exercise test. In total, 1559 patients were included in this research. The study data were divided into two groups according to the development of AF during follow-up. The patients who developed any type of AF during the follow-up period were classified as AF (+). Mean follow-up time for AF (+) and (-) groups were 48 and 47 months, respectively. In the univariable analysis, age, LAAP, and the presence of APCs (HR: 3.906, 95% CI: 2.848-5.365, p < 0.001) during the treadmill exercise test were significantly associated with the development of AF. In the multivariable analysis, age (adjusted HR: 1.063, 95% CI: 1.043-1.083, p < 0.001) and the presence of APCs during the treadmill exercise test (adjusted HR: 2.504, 95% CI: 1.759-3.565, p < 0.001) emerged as independent risk factors for the development of AF. The AF-free survival was significantly lower in the APCs (+) patients compared with the APCs (-) patients (log rank p < 0.001). Our study revealed that individuals without obstructive CAD who exhibited frequent APCs during treadmill exercise tests were more likely to develop AF.

Endoscopic Management of Post-Esophagectomy Delayed Gastric Conduit Emptying (DGCE): Results from a Cohort Study in a Tertiary Referral Center with Comparison between Procedures

Background/Objectives: Delayed gastric conduit emptying (DGCE) occurs in 15–39% of patients who undergo esophagectomy. Intra-Pyloric Injection of Botulinum Toxin (IPBT), Pneumatic Balloon Dilation (PBD), and the same session combination (BTPD) represent the main endoscopic procedures, but comparative data are currently unavailable. Methods: We retrospectively analyzed prospectively collected data on all consecutive patients with DGCE treated endoscopically with IPBT, PBD, or BTPD. ISDE Diagnostic Criteria were used for DGCE diagnosis and classification. A Gastric Outlet Obstruction Score was used for clinical staging. All patients undergoing IPBT received 100 UI of toxin, while those undergoing PBD were dilated up to 20 mm. Clinical success (CS) was defined as the resolution of symptoms/resumption of feeding at discharge or expanding dietary intake at any rate. Recurrence was defined as symptom relapse after more than 15 days of well-being requiring endoscopic/surgical intervention. Results: A total of 64 patients (81.2% male, 90.6% Ivor-Lewis esophagectomy, 77.4% adenocarcinoma) with a median age of 62 years (IQR 55–70) were enrolled: 18 (28.1%) in the IPBT group, 24 (37.5%) in the PBD group, and 22 (34.4%) in the BTPD group. No statistically significant differences were found in the baseline characteristics, surgical techniques, and median follow-up among the three groups. BTPD showed a higher CS rate (100%) compared to the PD and BTPD groups (p = 0.02), and a Kaplan–Meier analysis with a log–rank test revealed that the BTPD group was associated both with a significatively shorter mean time to refeed of 1.16 days (95% CI 0.8–1.5; p = 0.001) and a shorter median time to discharge of one day (95% CI 1–3; p = 0.0001). Conclusions: Endoscopic management of DGCE remains challenging. Waiting for further strong evidence, BTPD can offer patients a higher clinical efficacy rate and a shorter time to refeed and be discharged.

Oncological Outcomes of Open Versus Minimally Invasive Surgery for Ductal Adenocarcinomas of Pancreatic Head: A Propensity Score Matching Analysis.

Minimally invasive pancreatic resections (MIPRs) have been shown to be safe and feasible, but there is still a lack of high-level evidence on oncological outcomes for cephalic pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to compare the oncological outcomes of patients undergoing MIPR and open pancreatic resection (OPR) for pancreatic head cancer in a single high-volume center. Data from a prospectively collected database of patients who underwent radical-intent surgery for resectable and borderline resectable PDAC of the head at our institution between January 2013 and May 2023 were retrieved and analyzed, comparing the surgical and oncological outcomes of MIPR and OPR, using a propensity score matching analysis. In the study period, 220 patients were selected. After matching, a total of 81 MIPRs and 81 OPRs were compared. No difference was found regarding R0 rate (OPR 83.9% vs. MIPR 74.1%, p = 0.122). Median overall survival (24 and 31 months for the OPR and MIPR groups, respectively; log rank p = 0.665) and disease-free survival (12 and 21 months for the OPR and MIPR groups, respectively; log rank p = 0.118) did not differ between the groups. The MIPR group was associated with a greater number of harvested lymph nodes (22 vs. 16, p = 0.0008), longer operative time (565 vs. 420 min, p < 0.0001), and shorter length of stay (12 vs. 18 days; p = 0.0001). No differences between the groups were found regarding all other postoperative and pathological outcomes. Regarding oncological outcomes, MIPR appeared to be comparable to OPR for treating patients with PDAC of the head. Despite an increased operative time, MIPR was associated with a greater number of LNs harvested and a shorter length of stay.

MUC17 is a potential new prognostic biomarker and promotes pancreatic cancer progression in obstructive jaundice.

Our working group has previously shown that bile acids (BAs) accelerate carcinogenic processes in pancreatic cancer (PC) in which mucin 4 (MUC4) expression has a central role. However, the role of other mucins in PC are less clear, especially in bile-induced cancer progression. The study aim was to investigate expression of MUC17 in BAs- or human serum-treated pancreatic ductal adenocarcinoma (PDAC) cell lines and use different assays with RNA silencing/overexpression to study the role of MUC17 in cancer progression. Protein expression of MUC17 was evaluated in 55 human pancreatic samples by immunohistochemistry, and Kaplan-Meier survival analysis was used to compare survival curves. Expression of MUC17 increased in PDAC patients, especially in obstructive jaundice (OJ) and the elevated MUC17 expression associated with poorer overall survival (10.66±1.99 vs. 15.05±2.03 months; Log rank: 0.0497). Treatment of Capan-1 and AsPC-1 cells with BAs or with human serum obtained from PDAC + OJ patients enhanced the expression of MUC17, as well as the proliferative potential of the cells, whereas knockdown of MUC17 alone or in combination with MUC4 decreased BAs-induced carcinogenic processes. Our results demonstrated that MUC17 has a central role in bile-induced PC progression, and in addition to MUC4, this isoform also can be used as a novel prognostic biomarker.

Efficacy of tablet glucocorticoids depending on their starting dose in patients with type 2 amiodarone-induced thyrotoxicosis: a prospective randomized study

Background: Glucocorticoids are the first-line pharmacotherapy for amiodarone-induced destructive thyroiditis. Despite the availability of clinical guidelines, there is no unified approach to patient management (indications for prescription, starting dose, duration of therapy and withdrawal algorithm). The issues of dose-dependent effect of glucocorticoids, verification of factor of delayed treatment response, prediction of severity and duration of thyrotoxicosis remain unresolved. Aim: To evaluate the efficacy of various regimens of tablet glucocorticoids in patients with type 2 amiodarone-induced thyrotoxicosis. Methods: This was a prospective randomized open-label comparative controlled trial of the efficacy of two starting doses of prednisolone 30 mg (n = 22) and 60 (n = 22) mg daily. The study groups were comparable for gender (men to women ratio 2:1), age, anthropometric and main clinical and laboratory characteristics. After euthyroidism has been achieved, thyroid function was assessed twice at 1 and 2 months during the dose reduction and at 1, 3, 6, 9, and 12 months after prednisolone withdrawal. The follow up was 15 to 24 months. The efficacy of therapy was evaluated by the time to euthyroidism, thyrotoxicosis duration, rate of recurrent waves of destruction and relapses. We looked for predictors of delayed treatment response and severe and prolonged thyrotoxicosis. Results: There were no significant differences in the time to euthyroidism (Mantel-Cox log rank test 0.859), duration of thyrotoxicosis (Mantel-Cox log rank test 0.813), rate of recurrent waves of destruction (0.721) and relapses (0.464). Within 30 days of therapy, remission was obtained in 11/22 (50.0%) patients in active control group (prednisolone 30 mg) and in 12/22 (54.5%) patients in the 60 mg group. Delayed response ( 60 days) was defined by recurrent waves of destruction (RR = 34.7, 95% CI: 3.7–321.8; R² = 0.430; p = 0.002). High risk of severe thyrotoxicosis was predicted by the age ≤ 54 years (AUC 0.749 ± 0.095, 95% CI: 0.562–0.936; p = 0.038; sensitivity 71.4%, specificity 62.2%). The duration of thyrotoxicosis was associated with body mass index (B = -7.4, R = 0.481, R² = 0.0231; p = 0.024) and cumulative amiodarone dose (B = 0.4, R = 0.472, R² = 0.223; p = 0.026). A combination of adverse events (hyperglycemia, infection, proximal myopathy, change in appearance, hematomas) and their severity were more frequent in the patients who had received the 60 mg prednisolone starting dose (p = 0.014). Conclusion: Compared to lower doses, the use of high doses of glucocorticoids is associated with a greater severity of side effects and does not ensure any significant acceleration of thyrotoxicosis remission. The potential factors of unfavorable clinical course of type 2 amiodarone-induced thyrotoxicosis are age, body mass index, and cumulative dose of amiodarone.

POLQ immunostaining behaves as a prognostic factor for pancreatic carcinoma.

DNA polymerase theta (POLQ) is a translesion synthesis polymerase essential for the repair of double strand breaks by the error-prone TMEJ (Theta Mediated End Joining) pathway. Although POLQ participates in maintaining genome stability, several studies have shown that its overexpression correlates with cancer progression and poor prognosis. Due to the fact that its role as a biomarker in pancreatic cancer remains unexplored, we aimed to study the usefulness of POLQ H-score as a prognostic factor in a pancreatic cancer patient cohort. We evaluated POLQ gene expression using a web-based tool to deliver gene expression profiling and interactive analyses based on TCGA and GTEx (GEPIA) and we examined the POLQ immunostaining in 152 biliopancreatic cancer surgical specimens using tissue microarrays. Association with survival was evaluated by Kaplan Meier curves and uni-multivariate Cox regression. GEPIA analysis showed statistical differences according to POLQ mRNA levels in Disease Free Survival (DFS) (log rank 0.023, HR 2.8, p=0.029) and Overall Survival (OS) (log rank 0.011, HR 3.1, p=0.016). For immunohistochemistry (IHC) evaluation, POLQ H-score was calculated, and showed statistical differences for OS in Kaplan Meier curves (log rank 0.001) and uni-multivariate analysis (HR 2.27; 95% CI 1.24-4.15, p=0.008). Our results indicate that POLQ is an independent prognostic factor in pancreatic cancer when analyzed by immunostaining, which is in agreement with the results shown by the POLQ gene expression analysis (GEPIA).

8743 Regulation Of Tryptophan 2,3-Dioxygenase 2 And Androgen Receptor In Triple-Negative Breast Cancer

Abstract Disclosure: L. Kuo: None. K. Lacey: None. N. Spoelstra: None. J.K. Richer: None. Background: Triple Negative Breast Cancer (TNBC) is an aggressive subtype with a peak recurrence rate within 3-5 years after initial diagnosis. Androgen receptor (AR) and Tryptophan 2,3-dioxygenase 2 (TDO2) are elevated in TNBC cells grown under anchorage-independent conditions and facilitate anoikis resistance. Several studies reported that the luminal AR subset of TNBC showed a positive enrichment of the tryptophan (TRP) catabolism pathway gene signature. Recent studies have demonstrated that aryl hydrocarbon receptor (AhR) inhibition decreases AR promoter transcriptional activity in prostate cancer. We have observed that TNBC with high AR have high levels of genes/proteins in the tryptophan catabolism pathway including the rate limiting enzyme TDO2. Hypothesis: TDO2 activity regulates AR expression through the downstream tryptophan catabolite kynurenine (KYN), which binds and activates AhR and AhR and AR may work together to promote TNBC progression. Methods: Human TNBC cell lines: MDA-MB-453, BT549, SUM159PT ​ were used in this study and the expression of TDO2 and AR were examined by immunohistochemistry (IHC) and western blot. TDO2 was stably knocked down (KD) via shRNA or overexpressed (OE) using lentivirus transduction. Mass spectrometry-based metabolomics were used to measure changes in TRP catabolite levels, and a cytokine array (R&amp;D) was utilized to analyze conditioned media. Results: TDO2 and AR protein are positively correlated in human TNBC cell lines. Although overexpression of TDO2 did not alter AR protein expression in SUM159PT, in the human MDA-MB-453, which have high levels of AR, knockdown of TDO2 (shTDO2) reduced AR protein by 40% and production of kynurenine (KYN) was reduced by 50% (p&amp;lt;0.0001). This suggests that TDO2 activity, specifically KYN binding to AhR, may influence AR protein levels. Conditioned media (CM) from TDO2 OE and KD respectively increased and decreased CXCL5 and IGFBP2. Lastly, TCGA database analysis of TNBC tumors with high levels of both AhR and AR showed significantly shorter patient survival (HR=1.47, log rank p=0.046) compared to those with tumors with lower amounts of both genes. Conclusion: TDO2 and AR are positively correlated in human TNBC cell lines. Tumors with high levels of both AR and AhR result in significantly shorter survival time for TNBC patients. Knockdown of TDO2 significantly reduced KYN production and AR expression in luminal AR TNBC cell lines and future experiments will focus on the underlying mechanism behind this and whether it is dependent on KYN-mediated activation of AhR and if AhR stabilizes AR in TNBC. Presentation: 6/3/2024

8743 Regulation of Tryptophan 2,3-Dioxygenase 2 and Androgen Receptor in Triple-Negative Breast Cancer

Abstract Disclosure: L. Kuo: None. K. Lacey: None. N. Spoelstra: None. J.K. Richer: None. Background: Triple Negative Breast Cancer (TNBC) is an aggressive subtype with a peak recurrence rate within 3-5 years after initial diagnosis. Androgen receptor (AR) and Tryptophan 2,3-dioxygenase 2 (TDO2) are elevated in TNBC cells grown under anchorage-independent conditions and facilitate anoikis resistance. Several studies reported that the luminal AR subset of TNBC showed a positive enrichment of the tryptophan (TRP) catabolism pathway gene signature. Recent studies have demonstrated that aryl hydrocarbon receptor (AhR) inhibition decreases AR promoter transcriptional activity in prostate cancer. We have observed that TNBC with high AR have high levels of genes/proteins in the tryptophan catabolism pathway including the rate limiting enzyme TDO2. Hypothesis: TDO2 activity regulates AR expression through the downstream tryptophan catabolite kynurenine (KYN), which binds and activates AhR and AhR and AR may work together to promote TNBC progression. Methods: Human TNBC cell lines: MDA-MB-453, BT549, SUM159PT ​ were used in this study and the expression of TDO2 and AR were examined by immunohistochemistry (IHC) and western blot. TDO2 was stably knocked down (KD) via shRNA or overexpressed (OE) using lentivirus transduction. Mass spectrometry-based metabolomics were used to measure changes in TRP catabolite levels, and a cytokine array (R&amp;D) was utilized to analyze conditioned media. Results: TDO2 and AR protein are positively correlated in human TNBC cell lines. Although overexpression of TDO2 did not alter AR protein expression in SUM159PT, in the human MDA-MB-453, which have high levels of AR, knockdown of TDO2 (shTDO2) reduced AR protein by 40% and production of kynurenine (KYN) was reduced by 50% (p&amp;lt;0.0001). This suggests that TDO2 activity, specifically KYN binding to AhR, may influence AR protein levels. Conditioned media (CM) from TDO2 OE and KD respectively increased and decreased CXCL5 and IGFBP2. Lastly, TCGA database analysis of TNBC tumors with high levels of both AhR and AR showed significantly shorter patient survival (HR=1.47, log rank p=0.046) compared to those with tumors with lower amounts of both genes. Conclusion: TDO2 and AR are positively correlated in human TNBC cell lines. Tumors with high levels of both AR and AhR result in significantly shorter survival time for TNBC patients. Knockdown of TDO2 significantly reduced KYN production and AR expression in luminal AR TNBC cell lines and future experiments will focus on the underlying mechanism behind this and whether it is dependent on KYN-mediated activation of AhR and if AhR stabilizes AR in TNBC. Presentation: 6/3/2024

Clinical and echocardiographic parameters associated with outcomes in patients with moderate secondary mitral regurgitation

BackgroundSignificant secondary mitral regurgitation (SMR) is known to be associated with worse prognosis. However, data focusing specifically on moderate SMR and associated risk factors are lacking. In the present study,...

The prognostic value of [18F]FDG PET/CT texture analysis prior to transplantation for unresectable colorectal liver metastases.

To determine whether heterogeneity in colorectal liver metastases (CRLM) 18F fluorodeoxyglucose [18F]FDG distribution is predictive of disease-free survival (DFS) and overall survival (OS) following liver transplantation (LT) for unresectable CRLM. The preoperative [18F]FDG positron emission tomography/computed tomography examinations of all patients in the secondary cancer 1 and 2 studies were retrospectively assessed. Maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV), and six texture heterogeneity parameters (joint entropyGLCM, dissimilarityGLCM, grey level varianceSZM, size zone varianceSZM, and zone percentageSZM, and morphological feature convex deficiency) were obtained. DFS and OS for patients over and under the median value for each of these parameters were compared by using the Kaplan Meier method and log rank test. Twenty-eight out of 40 patients who underwent LT for unresectable CRLM had liver metastases with uptake above liver background and were eligible for inclusion. Low MTV (p < 0.001) and dissimilarityGLCM (p = 0.016) were correlated to longer DFS. Low MTV (p < 0.001) and low values of the texture parameters dissimilarityGLCM (p = 0.038), joint entropyGLCM (p = 0.015) and zone percentageSZM (p = 0.037) were significantly correlated to longer OS. SUVmax was not correlated to DFS and OS. Although some texture parameters were able to significantly predict DFS and OS, MTV seems to be superior to predict both DFS and OS following LT for unresectable CRLM.