Institut Marqués, Spain, Barcelona
Recent publications
INTRODUCTION Identifying the link between early Alzheimer's disease (AD) pathological changes and neurodegeneration in asymptomatic individuals may lead to the discovery of preventive strategies. We assessed longitudinal brain atrophy and cognitive decline as a function of cerebrospinal fluid (CSF) AD biomarkers in two independent cohorts of cognitively unimpaired (CU) individuals. METHODS We used longitudinal voxel‐based morphometry (VBM) in combination with hippocampal subfield segmentation. Changes in neuroimaging and cognitive variables were inspected using general linear models (GLMs) adjusting by age, sex, apolipoprotein E (APOE) status, follow‐up time, and years of education. RESULTS In both cohorts, baseline CSF amyloid beta (Aβ) biomarkers significantly predicted medial temporal lobe (MTL) atrophy rates and episodic memory (EM) decline independently of CSF phosphorylated tau (p‐tau). DISCUSSION Our data suggest that soluble Aβ dyshomeostasis triggers MTL longitudinal atrophy and EM decline independently of CSF p‐tau. Our data underscore the need for secondary preventive strategies at the earliest stages of the AD pathological cascade. Highlights We assessed brain atrophy and cognitive decline in asymptomatic individuals. Aβ biomarkers predicted MTL atrophy independently of p‐tau. Our results underscore the importance of undertaking Alzheimer's preclinical trials.
Over the last few decades the pharmaceutical industry has generated a vast corpus of knowledge on the safety and efficacy of drugs. Much of this information is contained in toxicology reports, which summarise the results of animal studies designed to analyse the effects of the tested compound, including unintended pharmacological and toxic effects, known as treatment-related findings. Despite the potential of this knowledge, the fact that most of this relevant information is only available as unstructured text with variable degrees of digitisation has hampered its systematic access, use and exploitation. Text mining technologies have the ability to automatically extract, analyse and aggregate such information, providing valuable new insights into the drug discovery and development process. In the context of the eTRANSAFE project, we present PretoxTM (Preclinical Toxicology Text Mining), the first system specifically designed to detect, extract, organise and visualise treatment-related findings from toxicology reports. The PretoxTM tool comprises three main components: PretoxTM Corpus, PretoxTM Pipeline and PretoxTM Web App. The PretoxTM Corpus is a gold standard corpus of preclinical treatment-related findings annotated by toxicology experts. This corpus was used to develop, train and validate the PretoxTM Pipeline, which extracts treatment-related findings from preclinical study reports. The extracted information is then presented for expert visualisation and validation in the PretoxTM Web App. Scientific Contribution While text mining solutions have been widely used in the clinical domain to identify adverse drug reactions from various sources, no similar systems exist for identifying adverse events in animal models during preclinical testing. PretoxTM fills this gap by efficiently extracting treatment-related findings from preclinical toxicology reports. This provides a valuable resource for toxicology research, enhancing the efficiency of safety evaluations, saving time, and leading to more effective decision-making in the drug development process.
LBA331 Background: 10-20% of GC are HER-2 positive. The role of perioperative anti-HER2-directed treatment is yet undefined. Methods: This randomized, open-label phase II-trial investigates the benefit of perioperative chemotherapy (CT) alone or in combination with either T or T and P for HER-2+ gastric (GC) and esophagogastric junction cancer (EGJC). 172 patients (pts) with centrally confirmed, positive HER-2 status and resectable GC or EGJC (UICC TNM stages Ib-III) were included. Pts were randomized in a 1:2:2 ratio to: Arm A (CT alone) (35 pts); Arm B (CT+ T [8mg/kg, followed by 6mg every 3 weeks]) (67 pts); Arm C (CT + T+ P [840mg every 3 weeks]) (70 pts). CT was initially cisplatin (80 mg/m ² d1) and capecitabine (2 x 1000 mg/m ² /d d1) for 3 cycles before and after surgery. After publication of FLOT-4 (Al-Batran, Lancet 2019), the protocol was amended. CT changed to four cycles FLOT, with FOLFOX or CAPOX as alternative for pts ineligible for FLOT. In arm B and C, T and P were continued beyond CT at the same dose for a total of 17 cycles. Out of 172 pts randomized, 161 fulfilled all key eligibility criteria and started their allocated treatment (per protocol population). Centrally determined major pathological response rates (mpRR) were 33.3%, 53.3% and 37.9% in Arm A: B: C after amending the protocol while, in contrast, they were 8.3%, 16.7% and 12.5% before (ASCO 2024, abstract 4057). Here, we present progression-free-(PFS) and overall survival (OS) after a median follow-up of 4.3 years. Results: In Arm A: B: C, 63.6%, 64.7%, 50.4% and 51.9%, 61.0%, 47.9% of pts were progression-free at 3 and 5 years. As compared to CT alone, HRs for PFS versus CT+T were 0.88 (90% CI, 0.51 to 1.53) and for CT+T+P 1.40 (90% CI, 0.82 to 2.37). Survival rates at 3 and 5 years in arm A: B: C were 75.6%, 76.9%, 65.2% and 60.5%, 67.5% and 62.6 %. As compared to CT alone, HRs for OS for CT+T and CT+T+P were 0.89 (95% CI, 0.42 to 1.88)) and 1.29 (95% CI, 0.62 to 2.66). For results before and after amendment see table. Conclusions: Non-significant advantages in terms of PFS and OS were observed for the addition of T to CT before, but not after the amendment. CT+T+P was detrimental. These results reflect the challenge of using mpRR as surrogate for survival in the perioperative treatment of GC. Clinical trial information: NCT 02205047 . PFS and OS results before and after amendment. Before amendment: Arm PFS (%) at 3 Years (95% CI) Hazard Ratio (95% CI) OS (%) at 3 Years (95% CI) Hazard Ratio (95% CI) CT(N=14) 57.1(28.4, 78.0) 1.00 78.6(47.3, 92.5) 1.00 CT+T(N=26) 64.2(42.5, 79.5) 0.64(0.24, 1.72) 83.6(62.0, 93.5) 0.77(0.25, 2.44) CT+T+P(N=28) 50.4(30.1, 67.6) 1.18(0.48, 2.93) 68.3(46.3, 82.8) 1.28(0.44, 3.75) After amendment: CT(N=19) 68.4(42.8, 84.4) 1.00 73.3(47.2, 87.9) 1.00 CT+T(N=38) 65.0(47.5, 78.0) 1.12(0.46, 2.75) 72.2(54.3, 84.0) 0.99(0.37, 2.69) CT+T+P(N=36) 50.4 (32.9, 65.7) 1.62(0.67, 3.90) 62.2(42.6, 76.8) 1.30(0.49, 3.48)
563 Background: HCC MDTs involve specialists collaborating on patient cases to create personalized treatment plans. Implementing MDTs can be challenging in countries with limited resources and high disease burdens. In China, there were 368,000 new liver cancer cases in 2022 representative of 40% of global cases. Therefore, evaluating MDT practices at leading hospitals in China may offer valuable insights that could help improve HCC MDT practices worldwide. Methods: This study selected hospitals with distinct MDT models: one for all new patients and one for complex cases. Hospitals handling over 1,000 HCC cases annually were chosen. Desk research and virtual interviews with MDT members from three leading Chinese hospitals—The First Affiliated Hospital of USTC, The First Affiliated Hospital of SYSU, and Tongji Hospital—were conducted to analyze their MDTs and determine key best practices. Results: We identified 6 key best practice in HCC MDTs at these leading Chinese hospitals. 1) Quality Control on MDT process: Leading hospitals ensure the MDT’s efficient execution and effective outcomes. E.g., USTC established a quality control team to audit the MDT process. 2) Real-World Evidence: Leading hospitals prioritize the construction of real-world databases linked to MDT-care to inform impact on outcomes. E.g., SYSU's preliminary data shows impact of MDT care on survival rates (From 2006 to 2010, 5,627 patients who underwent radical liver cancer resection with MDT care saw their five-year survival rate reach 60%, a notable improvement over historical averages) 3) Comprehensive Teams: These hospitals typically have robust teams, involving around 10 specialties. E.g., Tongji Hospital’s MDTs involve ~10 specialties for holistic care. 4) Patient Journey Coverage: MDTs manage patients from diagnosis to rehabilitation, providing a holistic approach to patient management. 5) Guideline-based treatment decisions: They follow latest guidelines coupled with access to approved therapies to make treatment decisions 6) Training: Young physicians are invited to actively participate in MDT consultations (e.g., through case preparation and presentation, etc.). Conclusions: Evaluation of MDT practices at leading China institutes highlights key best practices that could be adopted to enhance care quality for patients with HCC. The ongoing efforts and successes of these institutions provide a model for broader adoption and standardization of MDT practices across the country.
562 Background: As the sixth most common malignancy worldwide, hepatocellular carcinoma (HCC) accounted for 4.7% of all new cancer diagnoses in 2022. Low- and middle-income countries seem to bear a disproportionate burden of the disease, with over 50% of new HCC cases estimated to occur in China and Africa. Research on multidisciplinary team (MDT) practices in these regions is limited. The objective of this study is to compare MDT practices in the management of HCC in HICs and LMICs. Methods: Data on MDT practices from hospitals that manage HCC in Italy, Spain, Switzerland, Germany, Denmark, Canada and the USA, representing HICs, and in China, South Africa and Egypt, representing LMICs were collected through virtual semi-structured interviews and workshops. Results: Ten key areas of differences were identified (Table 1) that could be categorized as organizational/regulatory or clinical. In HIC institutions, the focus currently is on optimizing MDTs as standard of care approach accessible to all patients with HCC; MDT principles are often integrated into national policies. In LMICs, emphasis is on establishing MDTs and expanding their capacity; patient access to MDT care is not a mandatory requirement, nor regulated in national policy. Of note, LMICs are seeking early technology adoption to overcome some potential barriers to MDT interactions; online formats are more often explored to facilitate participation and AI-assisted diagnostic tools are explored to compensate for absence of radiologists. Absence of screening and surveillance for early detection in HCC is more common in LMICs, and therefore likely that patients more often present with advanced stage disease. Also, with limited diagnostic modalities, diagnostic work-up and staging may be sub-optimal. Conclusions: Significant variation exists in HCC MDT practices between HICs and LMICs. The ultimate goal of this study is to develop a format for clinical MDTs that will facilitate interaction between HICs and LMICs. Consideration for the differences highlighted above is crucial for the development of this concept. 10 key areas highlighting differences identified between HICs and LMICs. MDT development direction: Standard of Care for all patients vs. specific session for complex cases National/regional regulatory requirements Institutionalizing MDT principles MDT composition (specialists) Use of digital tools Reimbursement Access to therapeutic options Stage presentation of HCC patients Use of clinical staging Patient follow-up after MDT discussion
214 Background: Acquired resistance (AR) to first-line (1L) chemotherapy (CT) + anti-EGFR inhibitors is a major challenge in the management of RAS WT mCRC patients (pts). While AR in later lines has been explained with point mutations in the EGFR pathway, its real mechanisms in 1L remain poorly understood. Tumor molecular biology can be dynamically studied through circulating tumor DNA (ctDNA) analysis, a real-time, non-invasive approach to detect AR. In this context, we conducted the multicenter prospective PLATFORM-B study, which enrolled 100 RAS WT mCRC pts receiving 1L CT + cetuximab across 15 Spanish Medical Oncology Departments, alongside 30 RAS MUT pts (control) treated with 1L CT + bevacizumab. Peripheral blood samples have been collected at baseline (BL), week 8, and disease progression (PD). Next-generation sequencing analysis (Ion S5 system) of ctDNA at PD revealed AR mutations in only 10% of pts, suggesting that alterations in the EGFR pathway may only partially explain AR in 1L. Therefore, we conducted shallow whole-genome sequencing (shWGS) to further characterize genomic profiles possibly related with novel mechanisms of AR. Methods: Baseline and PD samples with sufficient remaining plasma were considered for this analysis. shWGS was performed with a coverage ranging 0.5X to 2.0X and analyzed using ichorCNA pipeline to evaluate various genomic characteristics such as copy number alterations (CNA), tumor fraction (TF), subclonal fraction (SF), and ploidy. Molecular results were correlated to clinical-pathological features and outcomes. Results: Overall, 35 mCRC pts (27 RAS WT and 8 RAS MUT ) were included in the study. At BL ( N = 26), median TF (mTF) was 0.19, median ploidy 2, median SC fraction 0.5, median SC genome fraction 0.21, and median subclonal CNA fraction 0.41. At PD ( N = 33), mTF was 0.08, median ploidy 2, median SC fraction 0.5, median SC genome fraction 0.17, and median subclonal CNA fraction 0.38. Of all the features analyzed, only the TF showed potential prognostic value. At BL, pts with TF levels above the median had poorer overall survival (OS) compared to those with lower levels, approaching statistical significance ( P = .055). At PD, higher TF levels were statistically significantly associated with worse OS ( P = .02). No meaningful differences between the RAS WT and RAS MUT groups were observed. Specific variations in CNA, TF, SF, or ploidy under treatment are being correlated to clinical data to seek for predictive value. Conclusions: This preliminary analysis of the PLATFORM-B using shWGS showed the prognostic value of TF. Further analyses are undergoing to better understand the molecular landscape of acquired resistance to 1L anti-EGFR-based therapy in RAS WT mCRC pts.
Background: The STRACK project aims to improve post-stroke patient management and the transition from acute to primary care thanks to improvements in patient pathways and monitoring cardiovascular risk factors: heart failure, diabetes, atrial fibrillation, dyslipidemia and hypertension. Collaboration between primary care centers and hospital staff was essential for the project’s success by delivering personalized care and home monitoring devices to patients through access to a digital platform. STRACK was launched with a european value-based contracting process and Roche Diag. as partner. Methods: The three-year project was launched in May 2021, during first year all specialties and professionals participated in the development and planning of the project and were trained in the use of the devices and own digital platform. First STRACK patient was enrolled in May 2022. Once these post-stroke patients have been identified, they are given a personalized monitoring plan depending on the individuals’ risk factors, the personalized care and rehabilitation plans are tracked and followed. For a year post-discharge, a nursing and administrative team follows the data that the patient enters remotely or is automatically available on their mobile application. Results: STRACK has evolved the continuum of care by 421patient in July 2024 and ongoing, by integrating comprehensive monitoring of cardiometabolic risk factors (heart failure, diabetes, atrial fibrillation, dyslipidemia, hypertension) into a patient discharge plan, identified as key to avoiding stroke recurrence and improving control of vascular risk factors are monitored. Preliminary results of 231 patients (May 2022-2023) with full one year follow-up comparing with historical cohort (May 2018-2019) showed: Reduction in unnecessary visits (weighted): -26,3%. Reduction in admissions for stroke recurrence or related to stroke, (heart attack, angina, peripheral embolism, etc.): Stroke, 30days: -100%; Related to stroke, (365d: -47,7%; 30d: -57,0%). Reduction in cardiovascular admissions ( 30d: -100%; 365d: -31,4%). Best treatment adherence: 81,2% (72% previously) Conclusion: The great value of STRACK is knowing the evolution of stroke patients post-discharge through strict self-monitoring of clinical parameters, following prior health education. STRACK has managed to achieve reduction in stroke recurrence and adverse events and readmissions for cardiovascular risk factors, reducing emergency visits for vascular events.
Value-based medicine places the patient and their health status at the center of the intervention through the use of Patient-Reported Outcome Measures (PROMs). The ideal would be that these outcome measurements were answered directly by the patient but in many cases it is a caregiver or a healthcare professional who collects the person's health status perception. This reason could lead to a bias in the results. Our aim was to compare whether there were differences in the perception of health status depending on who answered these questionnaires. Stroke patients discharged from six European hospitals were included in a 1-year follow-up program based on a holistic communication tool (web platform for professionals and app for patients/caregivers) called NORA. PROMs at 7-90 days were collected through NORA-app. In case that the patient or caregiver didn't have access to a smartphone, the data collection was carried out by a professional healthcare who contacted them to manage PROMs by a phone call. Main outcome measures include: HAD-depression and HAD-anxiety (defined as pathological by a score ≥10 points in each of the subscales) and PROMIS-10 (cut-offs raws values of normality were defined as: Physical-PROMIS>13 and Mental-PROMIS>11). Median scores per collector were compared. In addition, a social questionnaire was collected from app-users'. Over two years, 5116 stroke patients were included in Harmonics project, 60% were men with a mean age of 70.2 years and median mRS of 2(1- 3) at hospital discharge. From them, 2432 were actively monitored and 1498 reported PROMs (428 patients (28.6%), 376 (25.1%) caregivers and 694 (46.3%) professionals). P-value < 0.05 was considered significant for all tests at 90 days. Median PROMs results are shown in Table-1. The social questionnaire (Figure-1) showed significant differences between male and female patients. From the total, 26.6% women and 11.7% men leave alone (p-value = 0.005). At the patients group 77.9% women considered they can take care of their basic needs’ vs 85.9% men (p-value= 0.036). Significant differences were found between the three groups of collectors, with professionals being the ones who perceive a better state of patient health through the collected PROMs collected. Among patients and caregivers groups, worse outcomes were reported by the last one. When using PROMs the collector should avoid bias in reporting the results and direct patient response should be encouraged.
Introduction: 3 to 5% of patients undergoing endovascular thrombectomy present impossible catheter access to the occlusion site from transfemoral access (TFA), largely attributed to complex arterial anatomy. Radial access can be an effective bailout strategy, but intraprocedural delays may negatively impact outcomes. Novel image processing algorithms allow for advanced characterization of vascular pathways from baseline neuroimaging, enabling the exploration of predictive models of impossible TFA before arterial puncture. Methods: A retrospective cohort of patients with an anterior large vessel occlusion who received thrombectomy from TFA between 2017 and 2023 were included in this study. A previously described automatic vascular analysis software was used to generate centerline graphs from the aorta to the intracranial occlusion site from baseline CTA. ArterialGNet, a graph neural network based on graph attention designed to integrate descriptors of centerline pathways extracted at three different distance scales, was trained for impossible TFA prediction. Five-fold cross validation was used for model derivation. The method was compared to a previously introduced random forest ensemble model with extreme gradient boosting (XGBRF) based on six vascular tortuosity descriptors of the aortic and supra-aortic regions. Results: A total of 745 patients (aged 78 years IQR 68-85, 56% women) were included in this study. Patients treated between 2017 to 2022 (n=568, 3.2% with impossible TFA) were used for model training and validation. Patients treated in 2023 (n=177, 3.4% with impossible TFA) were held out for testing. In validation, the best-performing configuration of ArterialGNet achieved a C-statistic of 0.82 (95%CI 0.74-0.90), similar to the baseline model (0.82, 95%CI 0.77-0.88). Comparable outcomes were observed in the final testing for ArterialGNet (0.84, 95%CI: 0.82–0.86). In contrast, the XGBRF model exhibited signs of overfitting (0.65, 95% CI: 0.53–0.78). In final testing, ArterialGNet predicted impossible TFA with a sensitivity of 0.80 (95%CI 0.66-0.94) and a specificity of 0.84 (95%CI 0.76-0.91). Median processing time for ArterialGNet was below 4 min. Conclusions: A novel model for impossible TFA prediction was validated with a large dataset. Impossible TFA prediction before arterial puncture may assist in decision support for initial access selection in thrombectomy, reducing intraprocedural delays and potentially improving clinical outcomes.
Introduction: Patients suffering from transient ischemic attack (TIA) are at high risk of ischemic stroke (IS). This study describes clinical characteristics and outcomes in patients with a first non-cardioembolic TIA. Methods: Using two US administrative claims databases (MarketScan and Optum’s de-identified Clinformatics® Data Mart Database [CDM]) converted to the Observational Medical Outcomes Partnership (OMOP) common data model, we conducted an observational, retrospective cohort study of adults with a first diagnosis of non-cardioembolic TIA between 2012 and 2022. Demographic and clinical characteristics were described at baseline, and incidence rates of IS, intracranial bleeding, and bleeding leading to hospitalization with sensitivity analyses at different time points were calculated. Results: Overall, 203,757 patients were included in the study, 97,481 from MarketScan, 106,276 from CDM. Mean age was 62 years in MarketScan and 72 years in CDM. Patients were mostly women (57.6% in MarketScan, 59.3% in CDM). At baseline, prevalence of comorbidities was high (hypertension 66% and 84%, hyperlipidemia 53% and 75%, coronary artery disease 18% and 31%, diabetes 25% and 38% in MarketScan and CDM, respectively). Median follow-up time was 569 days in MarketScan and 716 days in CDM. At 1 year follow-up, incidence rates per 100 person-years of IS, intracranial bleeding, and bleeding leading to hospitalization were 10.9, 0.9, and 4.2, respectively, in MarketScan and 20.2, 1.6, and 7.6 respectively, in CDM. Sensitivity analyses showed that most IS events occurred within 7 days of the index event. Additional event rates and sensitivity analyses are shown in Table 1. Conclusion: Results from two US claims databases show that the annual risk of IS is higher than expected following a first TIA diagnosis, especially when including the first 7 days in the ascertainment. Implementation of guideline directed antiplatelet therapies, or new antithrombotic strategies, is needed.
Introduction: Challenging anatomy and tortuous vessels have been associated with poor outcomes in endovasculat treatment (EVT) of stroke. We aim to examine the relation between intracranial vascular features and EVT outcomes. Methods: A pre-existing automatic vascular analysis software of vessels on head-and-neck baseline CTA, was adapted to semi-automatically extract the vascular centerline segment from the internal carotid artery (ICA) origin to the thrombus site. Manual intervention was limited to approximate thrombus location placement and side of occlusion. For each vascular segment, the tortuosity index (TI), the overall mean diameter of the entire segment (OMD) and the last 5 mm (diameter at occlusion site) were computed. We defined: first pass effect (FPE: eTICI≥2c at first pass), successful recanalization (mTICI ≥ 2b), excellent recanalization (mTICI ≥ 2c), intracranial hemorrhage (ICH) and symptomatic ICH (sICH). Results: 437 cases with intracranial vessel occlusions in the anterior circulation, treated with EVT between 2017 and 2022 (41% women, median age 81 [IQR 70-88] years), were analyzed (M1: 261 (59.7%); proximal M2: 111(25.4%); M2 distal: 65 (14.9%). Significant differences were found in the diameter at the occlusion site: distal M2: 2.42±0.74mm, proximal M2: 2.43±0.77mm, M1: 2.93±0.80mm (p<0.001) and in the TI: distal M2: 0.52±0.06, proximal M2: 0.50±0.08, M1: 0.47±0.08 (p< 0.001). In the entire population, a larger OMD predicted a lower likelihood of FPE (OR:0.51 (95% CI:0.32-0.80) and a higher risk of ICH (OR:1.79 (95% CI:1.08-2.98). Additionally, a larger diameter at the occlusion site predicted a higher risk of ICH (OR:1.36; 95% CI: 1.05, 1.77) for the entire population and especially for proximal M2 occlusions (OR: 1.91, CI:1.05-3.47). Conclusions: Anatomical vascular features automatically extracted from CTA before the procedure can help predict the likelihood of recanalization or the risk of hemorrhagic complications. Further analysis will explore specific anatomical markers that increase the risk of complications, especially in distal occlusions.
Introduction: Elevated blood pressure (BP) is common in acute intracerebral hemorrhage (ICH) and is associated with poor neurological outcomes. However, about a quarter of patients present with normal BP, and this group is understudied. We aimed to evaluate the association between patterns of BP course and clinical outcomes. Methods: We conducted a retrospective cohort study using prospectively collected data from consecutive acute ICH patients who were scanned within 6 hours of symptom onset over a 7-year period. Patients underwent 24-hour noninvasive BP monitoring, and clinical outcomes were recorded at 24 hours. Patients were treated under a rapid (target achievement ≤60 minutes), intensive (target SBP <140 mmHg), and sustained (target stability for 24 hours) BP protocol when systolic BP (SBP) was ≥150 mmHg. Patterns of BP course were classified as Early High when SBP was ≥150 mmHg on admission, Late High when SBP was <150 mmHg on admission but increased to ≥150 mmHg within the first 24 hours, requiring treatment, and Steady Low when SBP spontaneously remained <150 mmHg from admission to the 24-hour follow-up. The primary outcome was early neurologic deterioration (END), defined as an increase in NIHSS score by ≥4 points or death within 24 hours. Multiple logistic regression analysis was adjusted for age, sex, anticoagulation, onset-to-imaging time, ICH volume, and intraventricular extension. Results: We included 424 patients (mean age 72.1±13.7 years, 263 [62.0%] male). At baseline, mean SBP was 168.2±28.3 mmHg, median onset-to-imaging time 124 (80–218) minutes, and median ICH volume 14.9 (5.8–39.3) mL. The distribution of BP patterns was as follows: Early High in 335 (79.0%) patients, Late High in 65 (15.3%), and Steady Low in 24 (5.7%). END occurred in 147 (34.7%) patients. There was a steady increase in the frequency of END across BP patterns: Steady Low 12.5% (3/24), Late High 26.2% (17/65), and Early High 37.3% (127/335) ( P =0.012, Figure 1). The occurrence of SBP ≥150 mmHg (Early or Late High) was independently associated with END (aOR 7.6, 95% CI 1.9–53.3). Conclusions: Most acute ICH patients experienced an SBP ≥150 mmHg within 24 hours, even among those who initially presented with lower BP. Patients who initially had SBP <150 mmHg but later experienced an increase to ≥150 mmHg were at a significantly higher risk of END. Overall, BP elevation, regardless of initial BP levels, is a strong predictor of END in acute ICH patients.
Background: Current evidence suggests higher physical activity (PA) levels are associated with a reduced risk of colorectal cancer (CRC). However, the mediating role of the circulating metabolome in this relationship remains unclear. Methods: Targeted metabolomics data from 6,055 participants in the EPIC cohort were used to identify metabolites associated with PA and derive a metabolomic signature of PA levels. PA levels were estimated using the validated Cambridge PA index based on baseline questionnaires. Mediation analyses were conducted in a nested case-control study (1,585 cases, 1,585 controls) to examine whether individual metabolites and the metabolomic signature mediated the PA-CRC association. Results: PA was inversely associated with CRC risk (odds ratio [OR] per category change: 0.90, 95% confidence intervals [CI]: 0.83, 0.97; p-value = 0.009). PA levels were associated with 24 circulating metabolites after false discovery rate correction (FDR), with the strongest associations observed for phosphatidylcholine acyl-alkyl (PC ae) C34:3 (FDR-adjusted p-value = 1.18 × 10⁻¹⁰) and lysophosphatidylcholine acyl (lysoPC a) C18:2 (FDR-adjusted p-value = 1.35 × 10⁻⁶). PC ae C34:3 partially mediated the PA-CRC association (natural indirect effect: 0.991, 95% CI: 0.982, 0.999; p-value = 0.04), explaining 7.4% of the association. No mediation effects were observed for the remaining metabolites or the overall PA metabolite signature. Conclusions: PC ae C34:3 mediates part of the PA-CRC inverse association, but further studies with improved PA measures and extended metabolomic panels are needed. Impact: These findings provide insights into PA-related biological mechanisms influencing CRC risk and suggest potential targets for cancer prevention interventions.
The real-time ionospheric data streams are continuously being provided by a number of International GNSS service analysis centers such as Centre National d’Etudes Spatiales (CNES), Chinese Academy of Sciences (CAS), Universitat Politècnica de Catalunya (UPC), and Wuhan University, however, the performance evaluation of these Real-Time Global Ionosphere Map (RT-GIM) products is essential. We assess the quality and consistency of these RT-GIM products from the declining phase of solar cycle 24 (year 2017) to the maximum of solar cycle 25 (year 2024) by comparing with Final GIMs provided by Center for Orbit Determination in Europe (CODE) and Jason-3 altimetry satellite. The results suggest that during the low solar activity periods (2017–2022), all the RT-GIMs perform almost similar. However, the performance of the CNES and CAS RT-GIMs strongly deteriorates as the solar cycle proceeds towards the maximum (2022–2024) with annual RMS values remains between 9 and 7.5 TECU. The external validation vs Jason-3 during this maximum period suggested that the accuracy of the UPC RTGIMs is nearly identical to the final CODE GIMs at typically 4–10 TECU in standard deviation over oceans, while performance degradations are recorded for rest of the RTGIMs exhibiting high standard deviations. Results suggest that the high RMS errors in GIMs from CNES and CAS might be related to the geomagnetic inclination misalignments followed by the map projections as both maps form single peak along geomagnetic equator during high solar activities. In addition, under the presence of a severe G4-class geomagnetic storm, CNES RT-GIMs undergoes severe accuracy degradation across all continents recording a − 20 to − 40 TECU bias offset. Meanwhile, UPC RT-GIM remain the most consistent and stable performer (both, globally and over oceans) that provides accurate global ionospheric information which is promising for their applications in real-time precise GNSS positioning.
We prove that any convex geometry A=(U,C)\mathcal {A} =(U,\mathcal {C}) on n points and any ideal I=(U,C)\mathcal {I} =(U',\mathcal {C} ') of A\mathcal {A} can be realized as the intersection pattern of an open convex polyhedral cone KRnK\subseteq {{\mathbb {R}}}^n with the orthants of Rn{{\mathbb {R}}}^n. Furthermore, we show that K can be chosen to have at most m facets, where m is the number of critical rooted circuits of A\mathcal {A} . We also show that any convex geometry of convex dimension d is realizable in Rd{{\mathbb {R}}}^d and that any multisimplicial complex (a basic example of an ideal of a convex geometry) of dimension d is realizable in R2d{{\mathbb {R}}}^{2d} and that this is best possible. From our results it also follows that distributive lattices of dimension d are realizable in Rd{{\mathbb {R}}}^{d} and that median systems are realizable. We leave open whether each median system of dimension d is realizable in RO(d){{\mathbb {R}}}^{O(d)}.
Objective To examine the association between serum thyroid-stimulating hormone (TSH) levels with handgrip strength (HGS) and dynapenia in euthyroid postmenopausal women. Methods This was an exploratory cross-sectional study among 385 participants from the Department of Obstetrics, Gynecology, and Reproduction of the Dexeus Women's University Hospital, Barcelona, Spain. Age, age at menopause, adiposity, alcohol consumption, body mass index (BMI), and smoking status were recorded. TSH was determined by electrochemiluminescence immunoassay. HGS was measured using a digital dynamometer, and physical activity was assessed by the International Physical Activity Questionnaire. Dynapenia was considered when HGS was <20 kg. A directed acyclic graph was designed to identify confounding variables. Multivariable linear and logistic regression models were adjusted by age, age at menopause, adiposity, BMI, glomerular filtration rate, glycated hemoglobin, physical activity, and smoking status. Results Multivariable linear regression model showed that age ( β = −0.22; 95% CI, −0.28 to −0.16), adiposity ( β = −0.15; 95% CI, −0.22 to −0.07), BMI ( β = 0.15; 95% CI, 0.04-0.25), glomerular filtration rate ( β = −0.04; 95% CI, −0.07 to −0.01), and physical activity ( β = 0.79; 95% CI, 0.07-1.5) were significantly associated with HGS. Instead, serum TSH levels were not significantly associated ( β = 0.21; 95% CI, −0.10 to 0.51). Multivariable logistic regression model showed that dynapenia was associated with age (OR, 1.20; 95% CI, 1.12-1.31) and glomerular filtration rate (OR, 1.03; 95% CI, 1.00-1.05). No significant association between TSH and dynapenia was observed (OR, 0.98; 95% CI, 0.78-1.23). Conclusions In this study of postmenopausal women, normal TSH levels were not associated with low HGS or dynapenia.
In the context of injectable biologic products approved or in development for chronic spontaneous urticaria (CSU), it is important to capture which treatment attributes matter most to patient and what trade-offs patients are willing to make. The CHOICE-CSU study aimed to quantify patient preferences toward injectable treatment attributes among patients with CSU, inadequately controlled by H1-antihistamines. This was a two-phase cross-sectional patient preference study in adult patients with a diagnosis of CSU, inadequately controlled by H1-antihistamines. A qualitative phase collected patients’ insights and relevant treatment attributes that mattered to them, and the outputs were used for the quantitative phase to create the actual injectable treatment profiles with attributes and levels such as: efficacy, safety, and mode of administration. The quantitative phase used discrete choice experiment (DCE) methodology. Eligible patients were asked to make hypothetical choices between 12 treatment profile pairs, created by Sawtooth SoftwareTM. The DCE data were analyzed using hierarchical Bayesian logistic regression models, enabling the quantification of the relative importance of each attribute/level during the decision-making process. A total of 450 respondents participated in the DCE. The key attributes driving respondent preference amongst injectable treatment options were type of administration device (relative importance 18.5%), complete control of urticaria (relative importance 17.4%), and resolution of angioedema (relative importance 16.4%). Keeping all other attributes and levels equal, the predicted choice share was higher for a profile with an auto-injector versus one with a pre-filled syringe (72.9% versus 27.1%). The CHOICE-CSU study is the first study to provide a quantitative assessment of preferences that patients with CSU, inadequately controlled by H1-antihistamines, have for injectable treatment attributes. Symptom-free periods are the most important overriding therapy goal for patients, and patients will accept some inconveniences, such as administration mode, to achieve this. Additionally, when efficacy is equivalent, administration ease of injectable therapies is valued by patients. As new CSU oral treatment options emerge, additional testing of patient preference toward oral treatments will be required.
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13 members
Sergi Novo
  • IVF Laboratory
Marisa López-Teijón
  • Fertility Unit
Federica Moffa
  • Fertilty Unit
Dalia Beatriz Rodríguez Barredo
  • Hospital Quirón-Dexeus, España, Barcelona
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Barcelona, Spain