Cumulative Occurrence Research Articles

Thrombospondin 2 as a Predictive Biomarker for HCC inHepatitis C Patients: A Longitudinal Study Following DAA Therapy.

This multicentre study investigated the dynamics of thrombospondin 2 (TSP2) levels during direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV) infected patients and evaluated TSP2's potential as a predictive marker for hepatocellular carcinoma (HCC). All 134 participants achieved sustained virological response at 12 weeks (SVR12) with DAA therapy, and serum TSP2 levels significantly decreased from before and after treatment (p < 0.001). During the median follow-up period of 6.0 years, HCC after DAA therapy was observed in 16 patients (11.9%). Patients with serum TSP2 High (≥ 32 ng/mL) at SVR12 had a significantly higher cumulative occurrence of HCC than did those without (26.5% vs. 7.0%, p = 0.0033). A multivariate Cox proportional hazards model identified male gender (HR 4.84, p = 0.005), HCC history (HR 4.61, p = 0.017) and TSP2 High (HR 3.93, p = 0.009) as significant independent predictors of HCC occurrence after DAA therapy. The model had a high concordance index of 0.878. Additionally, combining TSP2 High and FIB-4 High (≥ 3.538) at SVR12 yielded high specificity and negative predictive value (0.941 and 0.917, respectively) for predicting HCC. Kaplan-Meier analysis showed a higher HCC incidence in the TSP2 High + FIB-4 High group (log-rank p < 0.0001). In conclusion, TSP2 may be a promising biomarker for personalised HCC surveillance in DAA-treated hepatitis C patients.

Efficacy and safety of oral versus intravenous cyclophosphamide in treatment of connective tissue disease-related interstitial lung disease.

Interstitial lung disease (ILD) resulting from connective tissue disease (CTD) greatly undermines people's health. Cyclophosphamide (CYC) is a widely used agent in treating CTD-ILD. We compared the efficacy and safety of oral and intravenous CYC in CTD-ILD treatment. The retrospectively enrolled CTD-ILD patients were divided into the oral and intravenous CYC groups. The chest high-resolution computed tomography examination, forced vital capacity (FVC), lung carbon monoxide diffusion capacity (Dlco) determinations, and 6 min walk test (6MWT) were performed pre-treatment and at the 3rd, 6th, and 12th months posttreatment. Radiographic ILD severity was assessed using the Warrick score. Krebs Von den Lungen-6, surfactant protein A (SP-A), SP-D, and erythrocyte sedimentation rate (ESR) before and at the 12th month post-treatment were determined. CYC cumulative dose and occurrence of adverse reactions during treatment were recorded. CYC cumulative dose in the intravenous CYC group was reduced. Compared with oral CYC treatment, intravenous CYC caused decreased Warrick score and increased FVC and 6MWT at the 6th month, and elevated DLco at the 3rd and 6th months posttreatment. SP-A, SP-D and ESR levels in both groups were reduced 12 months posttreatment, with a more evident decrease in the intravenous CYC group. Intravenous CYC had lower total adverse reaction incidence. Compared with oral CYC, intravenous CYC decreases Warrick score and increases FVC and 6MWT at 6 months posttreatment, and reduces SP-A, SP-D, and ESR levels after 12 months of treatment, which shows low CYC cumulative dose and adverse reaction incidence in treating CTD-ILD.

Survival outcomes in patients with de novo metastatic Merkel cell carcinoma according to site of metastases.

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignancy of the skin with a predilection for metastases. This study investigates the clinical outcomes in patients presenting with de novo Stage IV MCC according to the metastatic site(s) at presentation. Patients who presented with one or more sites of distant metastatic MCC at initial diagnosis between 2009 and 2023 were identified. The presence or absence of one or more metastases in each organ was categorized for each patient at the time of diagnosis. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Competing risk analysis was used to estimate the cumulative occurrence risk of MCC-specific death. Fisher's exact test was used for response rate analysis. Results were considered statically significant if p < 0.05. Thirty-four patients presented with de novo distant metastatic MCC. There was no association between the number of metastatic sites at diagnosis and OS (p= 0.58), PFS (p=0.79), or response rates (p=0.53). However, the presence of bone metastases was associated with significantly shorter OS (8.2 versus 25.2 months, HR: 2.4, 95% CI 1.01-5.7, p= 0.04). MCC-specific death in patients with lymph node metastases was significantly lower than in patients without (HR: 0.28, 95% CI: 0.09-0.87, p= 0.013). The presence of bone metastases tended to associate with an increased risk of MCC-specific death, although not statistically significant. The location of metastases was not associated with the response rate to first-line treatment. There was no significant association between site of metastases and PFS. In this cohort of patients with de novo metastatic MCC, the presence of bone metastases, but not the number of organs involved, was associated with significantly worse OS. The presence of lymph node metastases was associated with lower MCC-specific death. Further research is warranted in larger cohorts to investigate the impact of the location of metastases on clinical outcomes.

Surgical management of rare tumors (Part 1).

With an annual cumulative occurrence of approximately 15,000 in North America, all childhood cancers are rare. Very rare cancers as defined by both the European Cooperative Study Group for Rare Pediatric Cancers and the Children's Oncology Group fall into two principal categories: those so uncommon (fewer than 2 cases/million) that their study is challenging even through cooperative group efforts (e.g., pleuropulmonary blastoma and desmoplastic small round cell tumor) and those that are far more common in adults and therefore rarely studied in children (e.g., thyroid, melanoma, and gastrointestinal stromal tumor). Treatment strategies for these latter tumors are typically based on adult guidelines, although the pediatric variants of these tumors may harbor different genetic signatures and demonstrate different behavior. If melanoma and differentiated thyroid cancer are excluded, other rare cancer types account for only 2% of the cancers in children aged 0 to 14. This article highlights several of the most common rare tumor types.

A demultiplexer-based dual-path switching true random number generator

This paper presents a demultiplexer (DEMUX) based dual-path switching true random number generator (TRNG). Unlike the classical single chain TRNG, the proposed TRNG utilizes DEMUXs to separate the cumulative jitter and occurrence of metastability in two paths. It also uses Ring Oscillator (RO) to increase the uncertainty of path switching time. Therefore, two sources of entropy are skilfully combined and no post-processing circuitry is required. The proposed structure is implemented on Xilinx Virtex-7 FPGA development board. The experimental results show that the proposed structure is able to achieve a high throughput of 500 Mbps with 33 Look-up Tables (LUTs) and 4 Flip-Flops (FFs). This effectively improves the throughput with high quality entropy and low hardware overhead.

The Preparation Phase of the 2023 Kahramanmaraş (Turkey) Major Earthquakes from a Multidisciplinary and Comparative Perspective

On 6 February 2023, Turkey experienced its most powerful earthquake in over 80 years, with a moment magnitude (Mw) of 7.7. This was then followed by a second earthquake of Mw 7.6 just nine hours later. According to the lithosphere–atmosphere–ionosphere coupling (LAIC) models, such a significant seismic activity is expected to cause anomalies across various observables, from the Earth’s surface to the ionosphere. This multidisciplinary study investigates the preparatory phase of these two major earthquakes by identifying potential precursors across the lithosphere, atmosphere, and ionosphere. Our comprehensive analysis successfully identified and collected various anomalies, revealing that their cumulative occurrence follows an accelerating trend, either exponential or power-law. Most anomalies appeared to progress from the lithosphere upward through the atmosphere to the ionosphere, suggesting a sequential chain of processes across these geospheres. Notably, some anomalies deviated from this overall trend, manifesting as oscillating variations. We propose that these anomalies support a two-way coupling model preceding major earthquakes, highlighting the potential role of fluid chemistry in facilitating these processes.

Remodeling of the Proximal Sealing Zone and Sac Shrinkage after Endovascular Aortic Repair or Fenestrated Endovascular Aortic Repair

Variations in sac shrinkage (SS) are noted between endovascular aneurysm repair for abdominal aortic aneurysm (AAA) and fenestrated endovascular aneurysm repair for short neck AAA. These variations may originate from difference in the geometry and length of proximal sealing, which influences the quality and durability of the seal. This study aimed to explore the disparities in aneurysm exclusion and sac remodeling across these 2 scenarios. This study involved a retrospective analysis of prospectively collected data from 2014 to 2021. Of 486 endovascular abdominal aortic repair cases, 33 that exclusively used a low permeability expanded polytetrafluoroethylene infrarenal device, strictly adhering to the instructions for use (IFUs), were selected. Concurrently, 30 cases of fenestrated repair that utilized modified polyester woven fabric devices proximally with consistent use of the aforementioned low-permeability devices infrarenally were examined. The quality of both proximal and distal sealing zones in fenestrated repairs was maintained within the range specified in the expanded polytetrafluoroethylene infrarenal device's IFUs, ensuring consistent sealing integrity for reliable group comparisons. Key metrics used for analysis were the detection of endoleaks and measurements of sac dimensions. Additional analyses included comparisons of demographic data and postoperative diameter changes in the proximal sealing zone (PZ) (encompassing 0, 5, 10, 15, and 20mm below the most proximal sealing stent). The demographic data and preoperative maximum-minimum diameter of the aneurysms did not differ between the groups. Proximal neck dilatation was similarly observed after both procedures. Immediately after the procedure, the incidence of lumbar arterial type II endoleaks was significantly lower after fenestrated repair than that after endovascular aortic repair (EVAR, 10% vs. 39.4%, P=0.0094). At the final observation, EVAR substantially reduced the PZ length (-4.73±15.30%), while fenestrated repair maintained the length (21.98±24.34%; P<0.0001). The preservation of the sealing length in fenestrated repairs was attributable to dilation occurring within the sealing range of the proximal device, oversized to accommodate the larger diameters in the more proximal sections of the aorta. The cumulative occurrence of SS (>5mm) following fenestrated repair increased faster than that after endovascular repair (P=0.002). Although aortic neck dilatation progressed similarly in both groups, fenestrated repair maintained the sealing length and demonstrated a greater extent of SS, even under the challenging circumstances in PZ. The superior postoperative results were linked to both the durability of proximal sealing and a lower occurrence of lumbar arterial type II endoleaks, stemming from the effective shuttering of the collateral sources in the proximal lumbar or intercostal arteries.

The Preparation Phase of the 2022 ML 5.7 Offshore Fano (Italy) Earthquake: A Multiparametric–Multilayer Approach

This paper presents an analysis of anomalies detected during the preparatory phase of the 9 November 2022 ML = 5.7 earthquake, occurring approximately 30 km off the coast of the Marche region in the Adriatic Sea (Italy). It was the largest earthquake in Italy in the last 5 years. According to lithosphere–atmosphere–ionosphere coupling (LAIC) models, such earthquake could induce anomalies in various observable variables, from the Earth’s surface to the ionosphere. Therefore, a multiparametric and multilayer approach based on ground and satellite data collected in each geolayer was adopted. This included the revised accelerated moment release method, the identification of anomalies in atmospheric parameters, such as Skin Temperature and Outgoing Longwave Radiation, and ionospheric signals, such as Es and F2 layer parameters from ionosonde measurements, magnetic field from Swarm satellites, and energetic electron precipitations from NOAA satellites. Several anomalies were detected in the days preceding the earthquake, revealing that their cumulative occurrence follows an exponential trend from the ground, progressing towards the upper atmosphere and the ionosphere. This progression of anomalies through different geolayers cannot simply be attributed to chance and is likely associated with the preparation phase of this earthquake, supporting the LAIC approach.

Internal solitary wave in the Lombok Strait: Satellite-observed spatiotemporal characteristics and their propagations modulated by the Indonesian Throughflow

The Lombok Strait shows active large-amplitude internal solitary waves (ISWs) and is also a primary gateway for the Indonesian Throughflow (ITF), which is a critical ocean current affecting the ocean ecosystem. This study collected 858 satellite images from 2018 to 2022, and ISW wave crests were extracted. Analysis shows that ISW 5-year cumulative occurrences reached the highest/ lowest of 136/28 days, with a 29 %/6 % frequency in October/ June. Satellite and reanalysis data revealed that ISW occurrence and propagation speed correlate to ITF variations. Enhanced southward ITF corresponds to less ISW occurrence and decreased/increased northward/southward ISW propagation speed. To understand how ITF modulates ISWs, three-dimensional MITgcm simulations were employed. Results show that when southward ITF decreases, ISWs tend to generate earlier/later, thus leading to a longer/shorter propagation distance for ISWs in the north/ south direction, revealing a suppressive effect on northward ISW generation.

Molecular dynamics simulation of fatigue damage formation in single-crystal/polycrystalline aluminum

The fatigue plasticity mechanisms and local defect characteristics of engineering materials are critical for addressing fatigue damage. This study aims to identify the formation mechanisms of fatigue damage and delineate the microstructural characteristics that resisted or facilitated fatigue-induced plastic accumulation. The fatigue mechanical properties and microstructural evolution processes of single-crystal/polycrystalline aluminum were investigated through strain-controlled fatigue testing, considering three distinct strain amplitudes. The initiation and cumulative occurrence of local plasticity in single-crystal aluminum occur at the intersections of slip planes, which serve as sources of dislocations. The cumulative formation of irreversible surface steps results in local stress concentration, ultimately leading to fatigue damage at the free surface. Polycrystalline aluminum undergoes grain rotation and merging during cyclic loading, leading to a gradual increase in grain size during plastic deformation. The initiation and cumulative occurrence of local plasticity occur at grain boundaries, ultimately leading to fatigue damage at the grain boundaries.

Age-specific prevalence of the different clinical presentations of AD and FTD in young-onset dementia

BackgroundStudies have shown that the prevalence of all-variants Alzheimer’s disease (AD) and frontotemporal dementia (FTD) both increase with age, even before the age of 65. However, it is not known whether their different clinical presentations all increase in prevalence with age in the same way.MethodsWe studied the prevalence of the different clinical presentations of young-onset AD and FTD by 5-year age groups in a population-based study identifying all dementia patients with a diagnosis of AD and FTD and symptoms onset before age 65 in the Modena province, Italy. By using regression models of cumulative occurrences, we also estimated age-specific prevalence and compared the growth curves of the clinical presentations.ResultsThe prevalence of all-variants AD increased with age, from 18/1,000,000 in the 40–44 age group to 1411/1,000,000 in the 60–64 age group. The prevalence of all-variants FTD also increased with age, from 18/1,000,000 to 866/1,000,000. An estimation of age-specific prevalence functions of each clinical presentation showed that atypical non-amnestic AD and aphasic FTD grew the most in early ages, followed by the behavioural variant of FTD (bvFTD). Then, around the age of 60, amnestic AD took over and its age-specific prevalence continued to increase disproportionally compared to all the other clinical variants of AD and FTD, which, instead, started to decrease in prevalence.ConclusionsAmnestic AD is the clinical presentation that increases the most with advancing age, followed by bvFTD, suggesting that there is a differential vulnerability to the effect of ageing within the same neurodegenerative disease.

Hydrologic simulation of a neotropical alpine catchment influenced by conductive topsoils in the Ecuadorian Andes

Highly conductive topsoils in neotropical high-elevation grassland-dominated ecosystems, or so-called paramos in the Andean region, influence the local rainfall-runoff processes predominated by saturation-excess overland flow as the primary source of freshwater. The Soil and Water Assessment Tool (SWAT) model has shown limitations when applied to mountainous catchments with highly conductive soils that generate surface runoff as saturation-excess overland flow. In this study, we enhanced SWAT to simulate runoff as saturation-excess overland flow and examined the hydrological responses of an intensively monitored paramo catchment in Ecuador. The model setup considered a detailed representation of the hydro-physical properties of the soils at different depths, including high infiltration and lateral flow rates in the hillslopes and restricted groundwater interactions, a characteristic of the páramo catchments. SWAT reasonably reproduced the daily discharge during dry and wet periods and the cumulative occurrence of high and low flows. The performance metrics NSE, RSR, and PBIAS values during calibration/validation period were 0.86/0.84, 0.31/0.4, and −11.2/-7.58, respectively. The runoff ratio and partitioning of the total runoff into the lateral flow and surface runoff were physically meaningful. More significantly, SWAT was able to simulate saturation-excess overland flow, which is dominant compared to infiltration excess, and it is a distinctive characteristic of páramo catchments. Nevertheless, the model showed limitations in simulating low flows.

Reclassifying historical disasters: From single to multi-hazards

Multi-hazard events, characterized by the simultaneous, cascading, or cumulative occurrence of multiple natural hazards, pose a significant threat to human lives and assets. This is primarily due to the cumulative and cascading effects arising from the interplay of various natural hazards across space and time. However, their identification is challenging, which is attributable to the complex nature of natural hazard interactions and the limited availability of multi-hazard observations. This study presents an approach for identifying multi-hazard events during the past 123 years (1900–2023) using the EM-DAT global disaster database. Leveraging the ‘associated hazard’ information in EM-DAT, multi-hazard events are detected and assessed in relation to their frequency, impact on human lives and assets, and reporting trends. The interactions between various combinations of natural hazard pairs are explored, reclassifying them into four categories: preconditioned/triggering, multivariate, temporally compounding, and spatially compounding multi-hazard events. The results show, globally, approximately 19 % of the 16,535 disasters recorded in EM-DAT can be classified as multi-hazard events. However, the multi-hazard events recorded in EM-DAT are disproportionately responsible for nearly 59 % of the estimated global economic losses. Conversely, single hazard events resulted in higher fatalities compared to multi-hazard events. The largest proportion of multi-hazard events are associated with floods, storms, and earthquakes. Landslides emerge as the predominant secondary hazards within multi-hazard pairs, primarily triggered by floods, storms, and earthquakes, with the majority of multi-hazard events exhibiting preconditioned/triggering and multivariate characteristics. There is a higher prevalence of multi-hazard events in Asia and North America, whilst temporal overlaps of multiple hazards predominate in Europe. These results can be used to increase the integration of multi-hazard thinking in risk assessments, emergency management response plans and mitigation policies at both national and international levels.

Cumulative seizure occurrence and the predictors of seizure in low- and high-grade gliomas

Objective: We aimed to determine the cumulative seizure occurrence, 1-year, and 5-years of preoperative seizures in gliomas, and an update on the predictors. Methods: This was a retrospective analysis of 239 patients with histopathologically confirmed gliomas in University Malaya Medical Centre, Malaysia, between 2008-2020. Kaplan-Meier curves were used to determine the cumulative incidence of seizures. Logistic regression was performed to determine the predictors of preoperative seizures. Results: A total of 80/239 patients (33.5%) had preoperative seizures. They were more commonly seen in those with younger age of presentation (40.0% in those &lt;40 years old vs. 26.9% in ≥40 years old, p&lt;0.05) and low-grade tumors (42.2% vs. 28.8% in high-grade tumors). Those with cortical involvement, especially the frontal lobe, or without focal deficit, headache, nausea, or vomiting were more likely to have seizures preoperatively. Logistic regression identified three significant predictors for preoperative seizure: absence of focal deficits at presentation (OR 6.090, 95% CI 3.110-11.925, p&lt;0.001), cortical location (OR 3.834, 95% CI 1.363-10.786, p&lt;0.05) and absence of headache at presentation (OR 2.487, 95% CI 1.139-5.431, p&lt;0.05). The cumulative incidence of seizure was 29% at one year and 32% at 5-year for gliomas. Specifically, the seizure incidence was higher in low-grade gliomas (39% at 1-year) and certain tumor types such as ganglioglioma (50%), oligodendroglioma (48%), and astrocytoma (45%). Conclusion: The cumulative incidence of preoperative seizures in low-grade gliomas and certain tumor types is high. The predictors included cortical involvement and absence of focal neurological deficit or headache at presentation.

Investigation of Stroke Risk Factors and Prognostic Indicators in NVAF Patients with Low CHA2DS2-VASc Scores.

The prognosis of patients with nonvalvular atrial fibrillation (NVAF) with a low CHA2DS2-VASc score (0-1) following a stroke is not well studied. In this investigation, stroke risk factors and prognostic markers in low-risk NVAF patients who are nonetheless at risk for stroke were examined.From January 2012 to January 2022, we retrospectively assessed atrial fibrillation (AF) patients at Xiamen University's Zhongshan Hospital for ischemic stroke. Along with a control group of patients with CHA2DS2-VASc scores of 0-1 who weren't suffering from a stroke, patients with CHA2DS2-VASc scores of 0-1 at the time of stroke were included in the study. Using multivariate logistic regression, independent risk factors were identified. To assess the cumulative occurrences of in-hospital mortality in patients with NVAF-related stroke, the Kaplan-Meier method was used.The study included 156 out of 3.237 inpatients with AF-related stroke who had CHA2DS2-VASc ratings of 0-1. Left atrial diameter (LAD) (odds ratio [OR]: 1.858, 95% confidence interval (CI) 1.136-3.036, P = 0.013), D-dimer (OR: 2.569, 95% CI 1.274-5.179, P = 0.008), and NT-proBNP (OR: 4.558, 95% CI 2.060-10.087, P = 0.000) were found to be independent risk factors for stroke in NVAF patients with a low CHA2DS2-VASc score. During hospitalization, nine patients with NVAF-related stroke died. In patients with NVAF-related stroke, NT-proBNP (hazard ratio: 3.504, 95% CI 1.079-11.379, P = 0.037) was an indicator of mortality risk.Patients with NVAF and CHA2DS2-VASc scores of 0-1 had independent risk factors for stroke in the form of LAD, D-dimer, and NT-proBNP. Notably, in low-risk NVAF patients with stroke, NT-proBNP was discovered to be a potent predictor of in-hospital death.

Female Sex Effect on Anti-CD19 CART Cell Therapy for Relapsed/Refractory B-Cell Lymphoma: A Grupo Español De Trasplante y Terapia Celular (GETH-TC) Study

Introduction Recent studies have shown the potential implication of sexual disparity on the immune system, emphasizing the significant roles of androgens and estrogens in immune cell function and their potential implications for immune responses and antitumor immunity. Anti-CD19 CART therapy is a new immunotherapy pillar for patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). However, this treatment has major limitations, including high individual variability with life-threatening toxicities, antigen escape, poor tumor infiltration, T cell exhaustion, and an immunosuppressive microenvironment. The underlying mechanisms responsible for these issues remain unknown and may potentially involve sex-based differences. To date, no studies addressed sex differences in CART therapy. Methods Data from consecutive patients with R/R LBCL from the Grupo Español de Trasplante y Terapia Celular (GETH-TC) who received commercial anti-CD19 CART infusion between November 2018 and December 2022 were retrospectively collected from electronic medical records at 12 Spanish institutions. Patients were divided by sex into two groups for analysis and stratified by patient/disease characteristics and CART cell product. A t-test comparison between the two cohorts was performed. The primary endpoint was comparing 1-year progression-free survival (1y-PFS) between the groups. Secondary endpoints were overall survival (OS), relapse incidence/progression of disease (RI/POD), non-relapse mortality (NRM), cytokine release syndrome (CRS) and immune-effector cells associated neurotoxicity (ICANS) cumulative incidence. Patient sex variable was added into the Cox Proportional-Hazards model for a multivariate analysis for each endpoint in addition to all the variables which were statistically significant in univariate analysis (α=0.05). Results A total of 479 patients received anti-CD19 CART infusion. Among them, 185 patients (39%) were female and 294 patients (61%) were male. No statistically significant differences were found in patient, disease and CART characteristics between the two cohorts ( Table 1). At 1-year post-infusion, PFS and OS were 39% (95% confidence interval [CI]: 34-44%) and 57% (95% CI: 51-62%), respectively. ( Fig. 1). On multivariate analysis, female sex had a favorable impact on 1-year PFS (HR=1.33; 95% CI: 1.01-1.75, p=0.04) but not on OS. A subset analysis on females revealed no significant differences in outcomes based on pre and postmenopausal age (p=0.23), with a fixed cut-off at 50 years. The 1 year RI/POD and NRM rates were 56% (95% CI: 52-60%) and 5% (95% CI:3-7%), respectively. Female sex was significantly associated with a lower RI/POD at one year (HR=0.68; 95% CI:1.10-1.96, p=0.01) but not with NRM. Regarding safety, the 1-month cumulative incidences of CRS grade ≥2 and ≥3 were 47% (95% CI: 41-53%) and 11% (95% CI:7-15%), respectively, without statistically significant correlation to female sex in univariate and multivariate analysis. However, the 1-month cumulative occurrence of ICANS grade ≥2 (28%, 95% CI: 26%-30%) and ≥3 (16%, 95% CI: 14%-18%) were significantly associated with female sex in univariate analysis (p&amp;lt;0.01 and p=0.02, respectively), with a trend towards significance in multivariate analysis (HR=1.4; 95% CI: 0.99-1.2, p=0.06 and HR=1.48; 95% CI:0.90-2.44, p=0.12). Conclusions In this retrospective analysis we compared for the first time the clinical outcomes of female and male patients who received anti-CD19 CARTs for R/R LBCL. Our findings suggest that, in a real-world setting, female sex is linked to improved survival outcomes, lower relapse rates, and a tendency toward higher neurotoxicity. This observation, without disparities in female outcomes based on pre and postmenopausal age, could suggest that such effect is potentially related to androgens and not to estrogens-dependent mechanisms on T cells. Sex differences, possibly related to hormonal mechanisms, should be further investigated to discover newer therapeutic mechanisms to increase the efficacy of adoptive cell therapies.

Optimizing slope unit-based landslide susceptibility mapping using the priority-flood flow direction algorithm

Regional-scale landslide susceptibility assessments are challenging and have recently captured the attention of scientists and technicians. A slope unit is a typical map unit that enhances the readability of landslide susceptibility maps (LSMs) by reducing ridge effects. Slope units are commonly obtained via the subbasin division (SBD) method from a digital elevation model (DEM) containing sink features, such as depressions, pits and flats. The SBD method addresses the depression problem by filling features but subsequently faces unresolved problems with parallel slope-unit boundaries. The main objective of this study was to introduce the priority-flood flow direction (PFD) algorithm to exploit flow information for depressions and compare PFD-improved slope units to SBD-based slope units in corresponding LSMs. An LSM case study was generated using an artificial neural network in Yan’an city, China, where loess ridge and hill landforms are developed. Data for a total of 447 landslides were obtained from historical records and field surveys to construct a landslide inventory map, where 313 landslides (70%) and 134 landslides (30%) were used for training and validation, respectively. Then, 9 conditioning factors related to landslides were prepared as inputs to generate six LSMs by combining two map units and three catchment area thresholds. These factors included elevation, slope, river distance, road distance, rainfall, normalized difference vegetation index (NDVI), aspect, land use and lithology. Finally, the resulting LSMs were validated and compared between the PFD and SBD methods using the precision, recall, accuracy, F1 score, success rate and prediction rate based on receiver operating characteristic (ROC) and cumulative landslide occurrence (CLO) curves. The results showed that the improved slope units produced no parallel boundaries, and the environment-factor layers generated based on these slope units prevented the generation of parallel factor-subclass boundaries, thus reducing striped distributions of factors and optimizing patterns in the LSMs. The PFD-improved LSM yielded ROC-based success rates ranging from 0.8849 to 0.8901, which were better than those obtained for the SBD-based LSM, at 0.8779–0.8823. The prediction rate revealed that the PFD-improved slope units were more suitable for large regions, as they provide more stable performance than the SBD-based slope units at large scales. The PFD algorithm resolved the problem of parallel boundaries and optimized LSM patterns, resulting in enhanced performance over the SBD method in large-scale research. The study results could be useful for local government management and land use planning in large regions.

Patient-level outcomes of patients undergoing resorbable magnesium scaffold (RMS) implantation stratified according to different subgroups: a post-hoc analysis of SHERPA MAGIC study

Abstract Background The SHERPA-MAGIC is an investigator-driven, multicenter, prospective, single-arm study that enrolled patients undergoing resorbable magnesium scaffold (RMS) implantation in 18 Italian centers. The results from the first 543 patients supported the safety and long-term performance of RMS in a real-world population. Purpose The present post-hoc analysis aimed to assess differences in adverse events at patient-level (patient-oriented composite endpoints, POCE, defined as the composite of all-cause death, myocardial infarction -MI- and ischemia-driven coronary revascularization) at the longest follow-up between different subgroups of the final study population (n=543). Methods We identified the subgroups according to different variables: age, sex, cardiovascular risk factors, clinical presentation, left ventricle ejection fraction, multivessel disease, multivessel PCI, and antiplatelet therapy. If the analysis highlighted a subgroup of patients at higher risk of adverse events, to understand if this finding is related to RMS implantation or to the characteristic itself, a propensity score matched analysis was conducted comparing patients of the SHERPA-MAGIC study with a matched cohort of patients receiving second generation drug eluting stent. The endpoint for the comparison between the two matched cohorts was POCE. Results The mean age of the final study population was 56±9 years. 433 (78%) patients were men, and the most common clinical presentation was MI (n=402, 74%). At the median follow-up of 3.5 [2.6-4.3] years, the cumulative occurrence of the primary endpoint (vessel-oriented composite endpoints, VOCE, including cardiac death, target vessel MI, and ischemia-driven target vessel revascularization) was 37 (5.8%, 95%CI 4.1%-7.9%) and 54 (9.9%, 95% CI 7.5%-12.7%) patients met criteria for POCE. There was no significant difference among POCE in the subgroup analysis (Figure 1), with the exception of patients with MI as clinical presentation. As compared to patients admitted for chronic coronary syndrome, MI patients showed a significantly higher POCE rate (11.4 vs 5.6%, CI 8.5-14.9, p=0.04). Therefore, a propensity score matched analysis was conducted comparing MI patients of the SHERPA-MAGIC study with a matched cohort of MI patients from the Acute coRonary sYndrOmes proSpective regisTry Of Ferrara (ARYOSTO) study (NCT02438085) treated with second-generation DES. We did not find significant differences in the cumulative occurrence of POCE between SHERPA MAGIC and ARYOSTO (11.4% vs. 12.5% respectively, p=0.71) (Figure 2). Conclusions The present analysis confirmed the safety and effectiveness of RMS across several subgroups of patients stratified by clinical and procedural characteristics. We found that MI patients had an higher occurrence of POCE, but this was not related to RMS implantation. Indeed, a similar MI population treated with second generation DES showed the same long-term outcome.Fig 1POCE difference between subgroupsFig 2Propensity matched MI populations

Abstract 15962: Validation of the Senescence-Associated Secretome to Predict Mortality in Patients With Degenerative Aortic Valve Stenosis

Introduction: The senescence-associated secretory phenotype (SASP) is a potential driver of age-related risk reflecting advanced biological aging. Circulating SASP components include pro-inflammatory cytokines, growth modulators and matrix remodelling proteases. Aortic valve stenosis (AVS) is the prototypical inflammatory age-associated cardiovascular disease. Hypothesis: To identify circulating SASP components with an impact on prognosis in elderly pts with AVS. Methods: In a derivation cohort (n=120), circulating levels of 24 SASP components were measured using Luminex Multiplex ELISA, before undergoing TAVR. ROC curves and Youden-index derived optimal cut-off values were used to assess the predictive power of each SASP for long-term mortality. In a validation cohort (n=198), the significant predictors of mortality identified in the derivation cohort, as well as a panel of 3 independent predictors in multivariate analyses, were prospectively validated. Results: In the derivation cohort, 9 out of 24 SASP components significantly predicted mortality in univariate analyses with AUC&gt;0.62; only 3 (GDF-15, ICAM-1, and osteoprotegerin) remained independent predictors in multivariate analyses (all p&lt;0.03). All 3 were confirmed as significant independent predictors of mortality in the validation cohort (see AUC curves). After adjustment for clinical parameters, a score based on the cumulative number of these 3 SASP components showed a substantial increase in long-term mortality after TAVR for each additional positive marker (see KM-curves). Conclusions: This study validates high levels of 3 SASP components reflecting different pathophysiological pathways of senescence as independent predictors of long-term mortality in AVS. Their cumulative occurrence provides a deeply improved discrimination power and, may serve as a much needed risk stratification tool in elderly patients with AVS undergoing TAVR.

Detection of Amyotrophic Lateral Sclerosis (ALS) Comorbidity Trajectories Based on Principal Tree Model Analytics.

The multifaceted nature and swift progression of Amyotrophic Lateral Sclerosis (ALS) pose considerable challenges to our understanding of its evolution and interplay with comorbid conditions. This study seeks to elucidate the temporal dynamics of ALS progression and its interaction with associated diseases. We employed a principal tree-based model to decipher patterns within clinical data derived from a population-based database in Taiwan. The disease progression was portrayed as branched trajectories, each path representing a series of distinct stages. Each stage embodied the cumulative occurrence of co-existing diseases, depicted as nodes on the tree, with edges symbolizing potential transitions between these linked nodes. Our model identified eight distinct ALS patient trajectories, unveiling unique patterns of disease associations at various stages of progression. These patterns may suggest underlying disease mechanisms or risk factors. This research re-conceptualizes ALS progression as a migration through diverse stages, instead of the perspective of a sequence of isolated events. This new approach illuminates patterns of disease association across different progression phases. The insights obtained from this study hold the potential to inform doctors regarding the development of personalized treatment strategies, ultimately enhancing patient prognosis and quality of life.