The Repeatability and Agreement of Ocular Parameters Measured with the MYAH and Myopia Master Devices between Expert and Non-Expert Practitioners.

In myopia control, it is essential to measure the axial length (AL) and corneal parameters, and to monitor whether changes in these parameters have occurred over time. The aim of this study was to analyse the repeatability and agreement between expert and non-expert practitioners in ocular parameters measured by the MYAH and Myopia Master. Three repeated measurements (n = 42) were recorded with the MYAH and Myopia Master by two (an expert and a non-expert) observers in a randomized order. The AL, K1, K2, and white-to-white (WTW) distance were collected. The intraobserver repeatability was excellent in all parameters measured with both devices in both observers. The AL outcome presented the best repeatability with the MYAH and Myopia Master (intraclass correlation coefficient, ICC = 1.0; coefficient of variation, CV ≤ 0.06% for both observers), while the WTW presented poorer results (ICC ≤ 0.991; CV ≤ 0.52%). The Myopia Master provides a significantly (p ≤ 0.01) flatter K1 and K2 as well as a lower WTW (p ≤ 0.01) than the MYAH. No statistically significant difference in AL measurements was found with either device (p ≥ 0.10; ICC = 1.0). None of the parameters showed differences (p ≥ 0.12) between the expert and non-expert observer. The MYAH and Myopia Master provide consistent measurements in a healthy adult population regardless of the previous clinical experience of the observer. AL measurements should be used interchangeably but K1, K2, and WTW should be used interchangeably with caution.

Enhancing evidence-based practice into healthcare: Exploring the role of scientific skills in occupational therapists.

BACKGROUND: Research utilization and evidence-based practice (EBP) in occupational therapy rely on essential scientific skills. Despite prior research exploring factors influencing EBP, a gap remains in understanding the specific scientific competencies crucial for effective EBP application. OBJECTIVES: To (1) describe the level of scientific skills for EBP and research application, and (2) investigate the factors influencing higher scientific competence among 1159 Spanish-speaking occupational therapists. MATERIAL AND METHODS: We assessed the scientific skills using the HACTO-Screen online survey. Recruitment was conducted through a non-probability convenience sampling method between April to June 2020, using social networks and email dissemination to education and professional organizations in Spain and Spanish-speaking Latin American countries. RESULTS: Out of a total score of 115 points, participants showed a moderate level of scientific skills (mean: 62.7, SD: 21.6), with literature searching skills ranking the highest and scientific writing skills ranking the lowest. Associations were found between greater scientific competence and advanced degrees, ongoing research training, and on-the-job research. CONCLUSIONS: Continuous research training, higher academic degrees, and active research engagement are essential for enhancing scientific competence among occupational therapists. SIGNIFICANCE: Targeted training to enhance scientific skills and promote research utilization are crucial in advancing EBP in occupational therapy.

Effects of Tai-Chi on Quality of Life in People With Neurodegenerative Diseases. A systematic Review of Randomised Clinical Trials.

OBJECTIVE: This systematic review aimed to evaluate the effects of Tai Chi on the health-related quality of life (HRQoL) of people with neurodegenerative diseases. DATA SOURCE: This review followed the guidelines of the updated PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020. A systematic search in five electronic databases (Medline via PubMed, Web of Science, Scopus, PEDro, and OTseeker) was performed. STUDY INCLUSION AND EXCLUSION CRITERIA: Randomized control trials (RCTs) examining Tai Chi interventions to improve HRQoL in patients with neurodegenerative diseases published through March 2023 were included. DATA EXTRACTION: Data were extracted from each study by two independent researchers into a data extraction form based on the Cochrane recommendations. Methodological quality and risk of bias were assessed. DATA SYNTHESIS: A meta-analysis was performed using Review Manager 5.3 software. RESULTS: Of the 439 records that were screened, eight RCTs met the eligibility criteria. They assessed cognitive decline (n = 2) or Parkinson's disease (n = 6). RCT comparison groups included active interventions or usual care. The duration of Tai Chi therapy ranged from 8 to 24 weeks. A sensitivity analysis using a fixed effect model indicated that Tai Chi therapy significantly increased HRQoL [P < 001, SMD (95% CI) = .41 [.21, .60], I2 = 4%]. CONCLUSION: Tai Chi can effectively improve the HRQoL of people with neurodegenerative diseases, but the heterogeneity across intervention was relatively high. Further studies are needed as research into the benefits of Tai Chi in neurodegenerative disease rehabilitation is still limited.

Oncological outcomes in robot-assisted radical prostatectomy: the value of PSA density as a preoperative predictive factor.

Background: Pretreatment assessment of patients diagnosed with localized prostate cancer (PCa) is essential for therapeutic decision-making. Currently available staging systems based on prostate-specific antigen (PSA), Gleason score, and clinical stage allow for determining the prognostic characteristics of these patients. Several studies have evaluated the preoperative use of prostate-specific antigen density (PSAD) as a prognostic factor for further risk stratification. To date, the role of PSAD in this setting is still an object of debate. Objectives: The present analysis aimed to assess the predictive potential of PSAD for adverse oncological outcomes after robot-assisted radical prostatectomy (RARP) and to compare its accuracy to preoperative PSA (pPSA). Design and methods: We retrospectively reviewed 427 patients diagnosed with localized PCa who underwent RARP at a single institution between January 2015 and January 2020. Generating receiver operator characteristic (ROC) curves, calculating areas under the curves (AUCs), and using a linear regression model, we analyzed the association of PSAD and pPSA with postoperative positive surgical margins (PSM), Gleason score ⩾ 7, persistent PSA, and biochemical recurrence (BCR), with a median follow-up of 47 months. Results: PSAD showed a significant association with PSM (p < 0.0001), PSA persistence (p < 0.0001), and Gleason ⩾ 7 (p < 0.0001), without being statistically significant in predicting BCR (p = 0.098). The predictive value of PSAD was comparable to pPSA for outcomes of PSA persistence (AUC 0.727 versus 0.771) and Gleason ⩾ 7 (AUC 0.683 versus 0.649). Conclusion: PSAD is a predictive factor for postoperative oncological outcomes of PSM, Gleason score ⩾ 7, and persistence of PSA. Despite the need for further studies, PSAD could be useful as a prognostic parameter in conjunction with established staging systems.

Oncological outcomes in robot-assisted radical prostatectomy: the value of PSA density as a preoperative predictive factor Prostate-specific antigen density (PSAD) has an established role in the diagnostic process of prostate cancer (PCa). However, controversy remains on the assessment of its value as a pretreatment prognostic factor. The aim of our study was to evaluate the predictive ability of PSAD for oncological outcomes in PCa patients treated with robot-assisted radical prostatectomy (RARP) and to compare with the value of preoperative PSA (pPSA). The present analysis showed a significant association of PSAD with positive surgical margins (PSM), Gleason Score >=7 and prostate-specific antigen (PSA) persistence after RARP. Moreover, PSAD demonstrated to perform comparably to pPSA in predicting the outcomes of clinically significant PCa (csPCa) and post-RARP PSA persistence. Therefore, PSAD is considered a preoperative predictive factor potentially useful in conjunction with other previously established prognostic criteria and clinical features.

Smart Design of ZnFe and ZnFe@Fe Nanoparticles for MRI-Tracked Magnetic Hyperthermia Therapy: Challenging Classical Theories of Nanoparticles Growth and Nanomagnetism.

Iron Oxide Nanoparticles (IONPs) hold the potential to exert significant influence on fighting cancer through their theranostics capabilities as contrast agents (CAs) for magnetic resonance imaging (MRI) and as mediators for magnetic hyperthermia (MH). In addition, these capabilities can be improved by doping IONPs with other elements. In this work, the synthesis and characterization of single-core and alloy ZnFe novel magnetic nanoparticles (MNPs), with improved magnetic properties and more efficient magnetic-to-heat conversion, are reported. Remarkably, the results challenge classical nucleation and growth theories, which cannot fully predict the final size/shape of these nanoparticles and, consequently, their magnetic properties, implying the need for further studies to better understand the nanomagnetism phenomenon. On the other hand, leveraging the enhanced properties of these new NPs, successful tumor therapy by MH is achieved following their intravenous administration and tumor accumulation via the enhanced permeability and retention (EPR) effect. Notably, these results are obtained using a single low dose of MNPs and a single exposure to clinically suitable alternating magnetic fields (AMF). Therefore, as far as the authors are aware, for the first time, the successful application of intravenously administered MNPs for MRI-tracked MH tumor therapy in passively targeted tumor xenografts using clinically suitable conditions is demonstrated.

Association between telomere length and neuropsychological function at 4-5 years in children from the INMA project: a cross-sectional study.

Shortened telomere length (TL) has been associated with lower cognitive performance, different neurological diseases in adults, and certain neurodevelopmental disorders in children. However, the evidence about the association between TL and neuropsychological developmental outcomes in children from the general population is scarce. Therefore, this study aimed to explore the association between TL and neuropsychological function in children 4-5 years of age. We included 686 children from the INMA Project, a population-based birth cohort in Spain. Leucocyte TL was determined by quantitative PCR method, and neuropsychological outcomes were measured using the McCarthy Scales of Children's Abilities (MCSA). Multiple linear regression models were used to estimate associations adjusted for potential confounding variables. Main findings showed that a longer TL was associated with a higher mean working memory score (ß = 4.55; 95% CI = 0.39, 8.71). In addition, longer TL was associated with a higher mean global quantitative score (ß = 3.85; 95% CI = -0.19, 7.89), although the association was marginally significant. To our knowledge, this is the first study that shows a positive association between TL and better neuropsychological outcomes in children. Although further research is required to confirm these results, this study supports the hypothesis that TL is essential in protecting and maintaining a child's health, including cognitive functions such as working memory.

Cytomegalovirus-induced inactivation of TSC2 disrupts the coupling of fatty acid biosynthesis to glucose availability resulting in a vulnerability to glucose starvation.

IMPORTANCE: Viruses modulate host cell metabolism to support the mass production of viral progeny. For human cytomegalovirus, we find that the viral UL38 protein is critical for driving these pro-viral metabolic changes. However, our results indicate that these changes come at a cost, as UL38 induces an anabolic rigidity that leads to a metabolic vulnerability. We find that UL38 decouples the link between glucose availability and fatty acid biosynthetic activity. Normal cells respond to glucose limitation by down-regulating fatty acid biosynthesis. Expression of UL38 results in the inability to modulate fatty acid biosynthesis in response to glucose limitation, which results in cell death. We find this vulnerability in the context of viral infection, but this linkage between fatty acid biosynthesis, glucose availability, and cell death could have broader implications in other contexts or pathologies that rely on glycolytic remodeling, for example, oncogenesis.

Gastric variceal bleeding as a form of presentation of a pancreatic neuroendocrine tumor / Sangrado por varices gástricas como forma de presentación de un tumor neuroendocrino pancreático

NETs (neuroendocrine tumors) constitute a heterogeneous group of epithelial-type neoplasms with a predominantly neuroendocrine differentiation. Although the most common locations are the pancreas, digestive tract, and lung, this type of neoplasm can arise in virtually any organ in the body. They are rare tumors with a wide variety of clinical presentations. Symptomatic tumors are more frequent in younger patients and present at more advanced pathological stages. We present the case of a 42-year-old male with idiopathic splenomegaly and bicytopenia (anaemia and thrombocytopenia) under study by haematology department who was admitted due to an episode of melena and hemoglobin of 4.5 mg/dl. Isolated gastric varices (IGV1) with red spots were confirmed at gastroscopy and endoscopic variceal obturation using cyanoacrylate was performed in two sessions. An endoscopic ultrasonography was performed, showing thrombosis of the splenic vein extending towards the splenoportal confluence with anechoic serpiginous structures outside and inside the gastric wall suggestive of collateral circulation with gastric varices (GV). An increase in portal caliber was observed, with no signs of liver cirrhosis. Computed tomography confirms the findings. Two months/week/days later he was readmitted with rebleeding signs after starting anticoagulant treatment, so it was decided to perform a splenectomy due to failure of the endoscopic treatment. Histology revealed infiltration of the spleen by a well-differentiated neuroendocrine tumor (NET). Gallium PET/CT and Octreotid scan showed uptake in the body and tail of the pancreas with positivity for somatostatin receptors previously undetected by other means. Finally, treatment was completed with distal pancreatectomy and splenoportal axis trombectomy with vascular esplenic resection and the patient was discharged from hospital.(AU)

Suramin, a drug for the treatment of trypanosomiasis, reduces the prothrombotic and metastatic phenotypes of colorectal cancer cells by inhibiting hepsin.

Recently, our group identified serine-protease hepsin from primary tumor as a biomarker of metastasis and thrombosis in patients with localized colorectal cancer. We described hepsin promotes invasion and thrombin generation of colorectal cancer cells in vitro and in vivo and identified venetoclax as a hepsin inhibitor that suppresses these effects. Now, we aspire to identify additional hepsin inhibitors, aiming to broaden the therapeutic choices for targeted intervention in colorectal cancer. METHODS: We developed a virtual screening based on molecular docking between the hepsin active site and 2000 compounds from DrugBank. The most promising drug was validated in a hepsin activity assay. Subsequently, we measured the hepsin inhibitor effect on colorectal cancer cells with basal or overexpression of hepsin via wound-healing, gelatin matrix invasion, and plasma thrombin generation assays. Finally, a zebrafish model determined whether hepsin inhibition reduced the invasion of colorectal cancer cells overexpressing hepsin. RESULTS: Suramin was the most potent hepsin inhibitor (docking score: -11.9691 Kcal/mol), with an IC50 of 0.66 µM. In Caco-2 cells with basal or overexpression of hepsin, suramin decreased migration and significantly reduced invasion and thrombin generation. Suramin did not reduce the thrombotic phenotype in the hepsin-negative colorectal cancer cells HCT-116 and DLD-1. Finally, suramin significantly reduced the in vivo invasion of Caco-2 cells overexpressing hepsin. CONCLUSION: Suramin is a novel hepsin inhibitor that reduces its protumorigenic and prothrombotic effects in colorectal cancer cells. This suggests the possibility of repurposing suramin and its derivatives to augment the repertoire of molecular targeted therapies against colorectal cancer.

Successfully Managing Severe Anemia in a Trauma Patient Who Refused Blood Transfusion: A Case Report.

BACKGROUND Surgical management in patients who undergo traumatic blood loss but who refuse blood transfusion can be challenging, but physicians and surgeons must comply with the wishes and beliefs of their patients. This report describes the management of severe anemia, with hemoglobin level of 2.5 g/dL, in a 71-year-old male Korean trauma patient who declined blood transfusion. CASE REPORT A 71-year-old man was admitted to hospital with severe blood loss following trauma. He declined blood transfusion due to his religious belief as a Jehovah's Witness. On day 4, the patient's hemoglobin level dropped from 7.7 to 3.9 g/dL. Despite the need for blood transfusion, the patient refused. Hence, therapeutic strategies, including crystalloid fluid resuscitation, bleeding control, vasopressor support, erythropoietin administration, supplementation with iron, folic acid, and vitamin B12, coagulopathy correction, oxygen consumption reduction, and mechanical ventilation were implemented. Following 16 days of supportive management, the hemoglobin reached 7.4 g/dL. However, it suddenly decreased on day 41 (2.5 g/dL) due to episodes of melena secondary to an actively bleeding gastric ulcer, which was successfully managed with endoscopic hemostasis. Despite increased vasopressor dosage and addition of vasopressin and hydrocortisone, the patient became unresponsive with persistent hypotension. Methylene blue was used as the final therapeutic agent. The patient responded well and subsequently recovered without blood transfusion. CONCLUSIONS This report has presented the clinical challenges of managing the case of a patient who requires but declines blood transfusion and has highlighted the approach to clinical care while respecting the wishes of the patient.

Ventilatory, phonatory and swallowing impairments in advanced neuromuscular disease patients / Alteraciones ventilatorias, fonatorias y deglutorias en pacientes con enfermedad neuromuscular avanzada

Purpose: To analyze the ventilatory, phonatory and swallowing impairments and their relation with physical status in a group of advanced Neuromuscular Disease (NMD).Methods: A cross-sectional observational study was utilized 48 participants from the Association of NMD of Granada (Granada, España), university clinical research, University of Granada. A total of 24 advanced NMD patients and 24 healthy controls matched for age and sex were recruited. Advanced NMD patients were divided in two groups according to the level of their overall physical status (NMD higher physical status group or NMD lower physical status group). Hand grip strength, ventilatory, phonatory and swallowing features were analyzed.Results: There were significant differences (p<.05) among NMDs groups in ventilatory function. There were significant differences (p<.05) between NMDs groups in ventilatory, phonatory and swallowing function. Finally, there were significant differences (p<.05) among advanced NMDs groups in swallowing function and orofacial evaluation. Conclusion: Patients with lower physical status have higher risk of suffer ventilatory, phonatory and swallowing complications after diagnosis of NMD.(AU)

Propósito: Analizar las alteraciones ventilatorias, fonatorias y deglutorias y su relación con el estado físico en un grupo de Enfermos Neuromusculares (ENM) avanzados.Métodos: Se realizó un estudio observacional transversal con 48 participantes de la Asociación de ENM de Granada (Granada, España), y de la facultad de ciencias de la salud de la Universidad de Granada. Se reclutaron un total de 24 pacientes con ENM avanzada y 24 controles sanos emparejados por edad y sexo. Los pacientes con ENM avanzada se dividieron en dos grupos según el nivel de su estado físico general (grupo de ENM de mayor estado físico o grupo de ENM de menor estado físico). Se analizó la fuerza de agarre de las manos y las características ventilatorias, fonatorias y deglutorias.Resultados:Se encontraron diferencias significativas (p<0,05) entre los grupos de ENM en la función ventilatoria. También, se observaron diferencias significativas (p<0,05) entre los grupos de ENM en la función fonatoria y deglutoria. Por último, existieron diferencias significativas (p<0,05) entre los grupos de ENM avanzados respecto a la condición miofuncional orofacial.Conclusiones: Los pacientes con menor estado físico tienen mayor riesgo de sufrir complicaciones ventilatorias, fonatorias y deglutorias tras el diagnóstico de ENM.(AU)

A dynamical method to objectively assess infantile nystagmus based on eye tracking. A pilot study

Purpose The purpose of this research is to propose a new method for the easy, inexpensive and objective quantification of nystagmus using eye-tracking records collected during a simple reading task that could be implantable in clinical practice to assess patients with nystagmus. Methods This is a prospective, observational pilot study. Eye movements of 4 nystagmus patients and 9 healthy children during a reading task (a paragraph with 82 words) on a 15′’ monitor were collected and compared. Data are time series indicating the gaze position on the screen. Two quantifiers were proposed: IndS (based on the speed of movements) and IndF (based on the variation of the gaze trajectory). Results The indices proposed reflect differences in the behavior of eye movements between the two groups. Nystagmus patients present higher values of IndS - indicating smaller number of slow movements (16% of movements with speeds <0.33 1/s for nystagmus and 85% for the control group, with p = 0.01) - and higher values of IndF - indicating higher gaze fluctuation (p = 0.01). Differences were not related with reading speed as show the mean and standard deviation: the nystagmus group required 115±45 s to complete the task and the control group 151±85 s; p = 0.73. Conclusions The proposed indices provide a new method that allows an objective assessment of nystagmus, with potential use in clinical and research practice to improve the follow-up of patients by monitoring the nystagmus over time or treatment. (AU)

Gastric variceal bleeding as a form of presentation of a pancreatic neuroendocrine tumor.

NETs (neuroendocrine tumors) constitute a heterogeneous group of epithelial-type neoplasms with a predominantly neuroendocrine differentiation. Although the most common locations are the pancreas, digestive tract, and lung, this type of neoplasm can arise in virtually any organ in the body. They are rare tumors with a wide variety of clinical presentations. Symptomatic tumors are more frequent in younger patients and present at more advanced pathological stages. We present the case of a 42-year-old male with idiopathic splenomegaly and bicytopenia (anaemia and thrombocytopenia) under study by haematology department who was admitted due to an episode of melena and hemoglobin of 4.5 mg/dl. Isolated gastric varices (IGV1) with red spots were confirmed at gastroscopy and endoscopic variceal obturation using cyanoacrylate was performed in two sessions. An endoscopic ultrasonography was performed, showing thrombosis of the splenic vein extending towards the splenoportal confluence with anechoic serpiginous structures outside and inside the gastric wall suggestive of collateral circulation with gastric varices (GV). An increase in portal caliber was observed, with no signs of liver cirrhosis. Computed tomography confirms the findings. Two months/week/days later he was readmitted with rebleeding signs after starting anticoagulant treatment, so it was decided to perform a splenectomy due to failure of the endoscopic treatment. Histology revealed infiltration of the spleen by a well-differentiated neuroendocrine tumor (NET). Gallium PET/CT and Octreotid scan showed uptake in the body and tail of the pancreas with positivity for somatostatin receptors previously undetected by other means. Finally, treatment was completed with distal pancreatectomy and splenoportal axis trombectomy with vascular esplenic resection and the patient was discharged from hospital.

Rapid and Automated Method for Detecting and Quantifying Adulterations in High-Quality Honey Using Vis-NIRs in Combination with Machine Learning.

Honey is one of the most adulterated foods, usually through the addition of sweeteners or low-cost honeys. This study presents a method based on visible near infrared spectroscopy (Vis-NIRs), in combination with machine learning (ML) algorithms, for the correct identification and quantification of adulterants in honey. Honey samples from two botanical origins (orange blossom and sunflower) were evaluated and adulterated with low-cost honey in different percentages (5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, and 50%). The results of the exploratory analysis showed a tendency to group the samples according to botanical origin, as well as the presence of adulteration. A supervised analysis was performed to detect the presence of adulterations. The best performance with 100% accuracy was achieved by support vector machines (SVM) and random forests (RF). A regression study was also carried out to quantify the percentage of adulteration. The best result was obtained by support vector regression (SVR) with a coefficient of determination (R2) of 0.991 and a root mean squared error (RMSE) of 1.894. These results demonstrate the potential of combining ML with spectroscopic data as a method for the automated quality control of honey.

Cytomegalovirus-induced inactivation of TSC2 disrupts the coupling of fatty acid biosynthesis to glucose availability resulting in a vulnerability to glucose limitation.

Human cytomegalovirus (HCMV) modulates cellular metabolism to support productive infection, and the HCMV UL38 protein drives many aspects of this HCMV-induced metabolic program. However, it remains to be determined whether virally-induced metabolic alterations might induce novel therapeutic vulnerabilities in virally infected cells. Here, we explore how HCMV infection and the UL38 protein modulate cellular metabolism and how these changes alter the response to nutrient limitation. We find that expression of UL38, either in the context of HCMV infection or in isolation, sensitizes cells to glucose limitation resulting in cell death. This sensitivity is mediated through UL38's inactivation of the TSC complex subunit 2 (TSC2) protein, a central metabolic regulator that possesses tumor-suppressive properties. Further, expression of UL38 or the inactivation of TSC2 results in anabolic rigidity in that the resulting increased levels of fatty acid biosynthesis are insensitive to glucose limitation. This failure to regulate fatty acid biosynthesis in response to glucose availability sensitizes cells to glucose limitation, resulting in cell death unless fatty acid biosynthesis is inhibited. These experiments identify a regulatory circuit between glycolysis and fatty acid biosynthesis that is critical for cell survival upon glucose limitation and highlight a metabolic vulnerability associated with viral infection and the inactivation of normal metabolic regulatory controls.

Venetoclax is a potent hepsin inhibitor that reduces the metastatic and prothrombotic phenotypes of hepsin-expressing colorectal cancer cells.

Introduction: Hepsin is a type II transmembrane serine protease and its expression has been linked to greater tumorigenicity and worse prognosis in different tumors. Recently, our group demonstrated that high hepsin levels from primary tumor were associated with a higher risk of metastasis and thrombosis in localized colorectal cancer patients. This study aims to explore the molecular role of hepsin in colorectal cancer. Methods: Hepsin levels in plasma from resected and metastatic colorectal cancer patients were analyzed by ELISA. The effect of hepsin levels on cell migration, invasion, and proliferation, as well as on the activation of crucial cancer signaling pathways, was performed in vitro using colorectal cancer cells. A thrombin generation assay determined the procoagulant function of hepsin from these cells. A virtual screening of a database containing more than 2000 FDA-approved compounds was performed to screen hepsin inhibitors, and selected compounds were tested in vitro for their ability to suppress hepsin effects in colorectal cancer cells. Xenotransplantation assays were done in zebrafish larvae to study the impact of venetoclax on invasion promoted by hepsin. Results: Our results showed higher plasma hepsin levels in metastatic patients, among which, hepsin was higher in those suffering thrombosis. Hepsin overexpression increased colorectal cancer cell invasion, Erk1/2 and STAT3 phosphorylation, and thrombin generation in plasma. In addition, we identified venetoclax as a potent hepsin inhibitor that reduced the metastatic and prothrombotic phenotypes of hepsin-expressing colorectal cancer cells. Interestingly, pretreatment with Venetoclax of cells overexpressing hepsin reduced their invasiveness in vivo. Discussion: Our results demonstrate that hepsin overexpression correlates with a more aggressive and prothrombotic tumor phenotype. Likewise, they demonstrate the antitumor role of venetoclax as a hepsin inhibitor, laying the groundwork for molecular-targeted therapy for colorectal cancer.

Redefining cardiac damage staging in aortic stenosis: the value of GLS and RVAc.

AIMS: Cardiac damage staging has been postulated as a prognostic tool in patients undergoing transcatheter aortic valve replacement (TAVR). The aims of our study are (i) to validate cardiac damage staging systems previously described to stratify patients with aortic stenosis (AS), (ii) to identify independent risk factors for 1-year mortality in patients with severe AS undergoing TAVR, and (iii) to develop a novel staging model and compare its predictive performance to that of the above mentioned. METHODS AND RESULTS: Patients undergoing TAVR from 2017 to 2021 were included in a single-centre prospective registry. Transthoracic echocardiography was performed in all patients before TAVR. Logistic and Cox's regression analysis were used to identify predictors of 1-year all-cause mortality. In addition, patients were classified based on previously published cardiac damage staging systems, and the predictive performance of the different scores was measured.Four hundred and ninety-six patients (mean age 82.1 ± 5.9 years, 53% female) were included. Mitral regurgitation (MR), left ventricle global longitudinal strain (LV-GLS) and right ventricular-arterial coupling (RVAc) were independent predictors of all-cause 1-year mortality. A new classification system with four different stages was developed using LV-GLS, MR, and RVAc. The area under the receiver operating characteristic curve was 0.66 (95% confidence interval 0.63-0.76), and its predictive performance was superior compared with the previously published systems (P < 0.001). CONCLUSION: Cardiac damage staging might have an important role in patients' selection and better timing for TAVR. A model that includes LV-GLS, MR, and RVAc may help to improve prognostic stratification and contribute to better selection of patients undergoing TAVR.