Search Results (719)

Background/Objectives: Although the binarism between type I and II endometrial cancer was dismissed and substituted with molecular classification, histopathological features remain of paramount importance. Hence, analysing survival outcomes according to histological type, our aim is to clarify whether the morphological features of the tumour retain prognostic relevance in the context of advanced disease. Methods: This is a retrospective analysis led within the Thames Valley Cancer Alliance Network. Results: We include 148 FIGO 2009 stage III–IV patients affected by endometrioid endometrial cancer (EEC) G1, G2, and G3, carcinosarcoma (CS), serous carcinoma (SC), and clear cell carcinoma (CCC) of the uterus. Five year overall survival (OS) is distinct among the histological groups (p-value < 0.001), being 73.3% for G2 endometrioid, 49.2% for G3 endometrioid, 8.3% for CS, and 28.4% for SC. The divergence was marked also for 5 year progression-free survival (PFS) (p-value < 0.001) as follows: for G2 endometrioid, was 76.4%; for G3 endometrioid, 52.7%; and for carcinosarcoma, 5.9%. PFS after 18 months for serous carcinoma was 5.7%. The multivariate analysis found G3 endometrioid (HR 2.91, 95% CI 1.20–7.11, p-value 0.018), carcinosarcoma (HR 12.15, 95% CI 5.07–29.11, p-value < 0.001), and serous carcinoma (HR 4.84, 95% CI 2.16–10.83, p-value < 0.001) as independent predictors of poor survival, as well as cervical invasion (HR 1.83, 95% CI 1.10–3.05, p-value 0.020) as the only histopathological feature confirmed. Regarding progression-free only carcinosarcoma (HR 14.91, 95% CI 5.28–41.11) and serous carcinoma (HR 17.68, 95% CI 6.41–48.75) were associated with an increased risk of recurrence. Conclusions: Our findings testify that, beyond the disease stage, histological subtype remains a major determinant of survival outcome. Cervical involvement is associated with a more aggressive disease, possibly correlated to death beyond relapse. Prospective trials involving advanced stage endometrial cancer, stratified by histological subtype and integrated with the molecular classification, are required. Full article

In this paper, we investigate the relationship between spot and futures contracts in the context of spot prices being higher than futures (backwardation). We focus on the persistence in stickiness during backwardation periods by covering major agricultural commodities (corn, oats, soybeans, soybean oil, wheat, and hard red wheat). The period of investigation, January 2000–August 2022, comprises many subperiods, including the pre-2008 global financial crisis, the global financial crisis, the single event of 2014, and the post-2014 stability and growth in world trade. We find the presence of price backwardation and its stickiness for corn and wheat, with the most significant determinants being convenience yield and interest risk. Full article

In Catholic Eucharistic theology, an influential metanarrative claims that the Catholic Church mitigated its condemnation of Berengarius of Tours, frequently claiming St. Thomas Aquinas and the Council of Trent as evidence for such a mitigation. The authors of this metanarrative claim that Catholic teaching prohibits the “crass realism” of Christ being “physically” present in the Eucharist. This paper first argues that the authors of the metanarrative have misinterpreted their historical evidence, particularly regarding the entailments of Christ’s substantial presence in these sources. It then argues, on the strength of the encyclical Mysterium Fidei, that the semantic range of “physically” can cover the same meaning as “corporeally,” allowing Catholic theologians to say that Christ is physically present in the Eucharist, subject to the appropriate qualifications of the Ro-man Catechism and Mysterium Fidei about the non-local presence of Christ. Full article

Heart transplantation is severely limited by the shortage of suitable donor grafts, partly due to myocardial vulnerability to ischemia–reperfusion injury and the lack of standardized preservation strategies. Current solutions only partially maintain myocardial viability, compromising post-transplant function. To address this issue, we made further improvements to our preservation solution, LYPS (Lyon Preservation Solution), based on mitochondrial metabolic activation and the limitation of membrane depolarization. We first evaluated commonly used extracellular solutions (Celsior and St. Thomas (ST)) on cardiac cell lines (H9C2) exposed to 20 h of cold (4 °C) simulated ischemia followed by 2 h of simulated reperfusion. In parallel, the same three solutions were compared in isolated pig hearts subjected to 20 h of cold static storage followed by reperfusion, with a group directly reperfused with blood at 37 °C serving as the control. Heart function was assessed using a non-working heart preparation, while mitochondrial functions and electrophysiological analysis were evaluated via biopsies and isolated cardiomyocytes. LYPS provided superior protection against cell death and mitochondrial membrane potential loss in vitro, outperformed ST in preserving mitochondrial function, and limited troponin I release by the heart. During reperfusion, LYPS-treated hearts showed improved functional recovery and contractility and better rhythmicity with almost no defibrillation requirements. These effects may involve the modulation of the repolarizing IK₁ current. Overall, LYPS effectively preserves myocardial viability and function, representing a promising strategy to enhance graft quality during long-term cold preservation, even through using cold static storage. Full article

Severe discrepancy between availability of donor organs suitable for clinical transplantation and the proportion of patients on the waiting list has resulted in several clinical problems. First, waiting times for a suitable organ match have become increasingly long, leading to higher mortality while awaiting transplantation. Second, to address this issue, more “marginal” donor lungs have been used in the last two decades, inevitably leading to higher risk of perioperative and long-term complications. The ex vivo lung perfusion (EVLP) technology has been used to recondition marginal donor organs for clinical transplantation. There remains a further untapped pool of donor organs that are currently deemed too injured even for reconditioning via currently available EVLP strategies and are therefore discarded without reconditioning attempts. As the clinical use of EVLP has reached its full potential, further adjunct technologies, such as selective NET removal, cytokine removal and cell therapy techniques, may improve reconditioning outcomes and lead to increased number of donor organs transplanted. Moreover, NET removal may significantly improve donor organ quality and, therefore, the outcomes of recipients after lung transplantation. Such adjunct technology may also provide short- and longer-term benefits in reduction in early graft failure (primary graft dysfunction, PGD) and longer-term chronic lung allograft dysfunction (CLAD, previously known as chronic rejection) via more favorable early immune priming of organs. In this article we present current evidence and future perspectives on this novel intervention strategy that can be used on human donor lungs with the view to increase the utilization rate in lung transplantation in the near future. Full article

Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD). Abnormal maternal lipid profiles in pregnancy are associated with pregnancy complications including preeclampsia, gestational diabetes, and pre-term delivery as well as increased ASCVD risk for both mother and child. Dyslipidemia management remains a central tenet for atherosclerotic cardiovascular disease prevention for women who are thinking about becoming pregnant or are already pregnant. Effective individualized guidance and multidisciplinary lifestyle/dietary strategies, along with targeted pharmacological interventions, are required for the successful management of lipid disorders in pregnancy in order to optimize outcomes. This review discusses the physiological changes occurring in lipid metabolism during pregnancy and provides an overview of the current strategies for managing dyslipidemia during pregnancy, with a special focus on consideration of pharmacological therapy. Full article

Objectives: The ability of clinicians to predict prolonged mechanical ventilation (MV) in patients with acute hypoxemic respiratory failure (AHRF) is inaccurate, mainly because of the competitive risk of mortality. We aimed to assess the performance of machine learning (ML) models for the early prediction of prolonged MV in a large cohort of patients with AHRF. Methods: We analyzed 996 ventilated AHRF patients with complete data at 48 h after diagnosis of AHRF from 1241 patients enrolled in a prospective, national epidemiological study, after excluding 245 patients ventilated for <2 days. To account for competing mortality, we used multinomial regression analysis (MNR) to model prolonged MV in three categories: (i) ICU survivors (regardless of MV duration), (ii) non-survivors ventilated for 2–7 days, (iii) non-survivors ventilated for >7 days. We performed 4 × 10-fold cross-validation to validate the performance of potent ML techniques [Multilayer Perceptron (MLP), Support Vector Machine (SVM), Random Forest (RF)] for predicting patient assignment. Results: All-cause ICU mortality was 32.8% (327/996). We identified 12 key predictors at 48 h of AHRF diagnosis: age, specific comorbidities, sequential organ failure assessment score, tidal volume, PEEP, plateau pressure, PaO₂, pH, and number of organ failures. MLP showed the best predictive performance [AUC 0.86 (95%CI: 0.80–0.92) and 0.87 (0.80–0.93)], followed by MNR [AUC 0.83 (0.76–0.90) and 0.84 (0.77–0.91)], in distinguishing ICU survivors, with non-survivors ventilated 2–7 days and >7 days, respectively. Conclusions: Accounting for ICU mortality, MLP and MNR offered accurate patient-level predictions. Further work should integrate clinical and organizational factors to improve timely management and optimize outcomes. This study was initially registered on 3 February 2025 at ClinicalTrials.gov (NCT06815523). Full article

Arrhythmia-induced cardiomyopathy (AIC) represents a potentially reversible form of LV dysfunction in which sustained atrial fibrillation (AF) and irregular, often rapid, ventricular activation drive maladaptive electrical, structural, and metabolic remodeling. Beyond simple rate effects, AIC reflects perturbed calcium handling, oxidative stress, and fibro-inflammatory signaling that propagate atrial–ventricular crosstalk and energetic failure. Clinically, attribution remains challenging because AF may be the cause, consequence, or marker of underlying myocardial disease; however, substantial improvement in LVEF after durable rhythm control is strongly supportive of an AIC component. A disciplined diagnostic pathway—integrating rhythm burden quantification, echocardiographic deformation indices, cardiac magnetic resonance, and natriuretic peptide trajectories—can refine pre-test probability and guide treatment intensity. Early rhythm control has emerged as a disease-modifying strategy in AF with HF, with catheter ablation often central to burden reduction and reverse remodeling; in parallel, rapid initiation of guideline-directed HF therapy and targeted cardiometabolic interventions may favor substrate regression and facilitate durable sinus rhythm. Uncertainties persist regarding standardized AIC case definition, arrhythmia burden thresholds that secure sustained recovery, optimal sequencing of rhythm- and substrate-directed therapies, and criteria for de-escalation of HF treatment after recovery. This review synthesizes contemporary mechanistic, diagnostic, and therapeutic evidence on AIC in AF and delineates priorities for future trials. Full article

Background/Objectives: A knowledge gap persists regarding anticoagulation therapy after endovascular stent insertion for malignant superior vena cava obstruction (mSVCO). Guidelines are supported by retrospective studies with a radiological focus and lack specific drug recommendations. No studies to date have captured the multi-disciplinary nature of decision-making over time. Methods: This single-center retrospective service evaluation includes patients with solid organ malignancy who received a stent for mSVCO between July 2016 and May 2022. Patient and treatment characteristics, clinical outcomes and prescribing decisions were collected from medical records and analyzed. Results: Of 49 patients (55% female, mean age 59), 73% had metastatic extra-thoracic disease at stent insertion. Technical success was achieved in 98% of cases and 92% survived to discharge. Forty-eight patients were followed until death. Median survival was 2.4 months. Post-procedure imaging (performed in 55% of patients) revealed 10 (21%) cases of systemic venous thromboembolism and 7 cases of stent thrombosis. Forty-four (91%) patients received anticoagulation therapy (62% therapeutic dose low molecular weight heparin). Those with thrombotic complications were fitter pre-procedurally than the rest of the cohort. There was one case of major bleeding. Twenty-two instances of therapy modification occurred following the initial plan, including nine changes due to a patient preference for oral therapy. Conclusion: Patients undergoing stenting for mSVCO demonstrate high thrombotic risk and a poor prognosis. Anticoagulation plans are frequently modified post discharge due to changing risk profiles and patient preferences. Multi-disciplinary collaboration is essential to support patient-centered and individualized management. Future research should investigate direct oral anticoagulants and anti-platelet therapy and develop risk assessment tools for this population. Full article

Background: Lobectomy has long been the gold standard for early-stage NSCLC, but recent trials challenge its universality. The Japanese JCOG0802 trial demonstrated superior overall survival with segmentectomy versus lobectomy, whereas the North American CALGB140503 trial showed non-inferiority of sublobar resection, including wedge and segmentectomy, compared with lobectomy. Methods: This commentary critically evaluates evidence from JCOG0802 and CALGB140503 in the context of wider thoracic surgical practice. We examine trial disparities, the role of real-world data, heterogeneity in surgical approach and lymph node staging, the impact of robotics on segmentectomy adoption, and the application of segmental resection in pulmonary metastasectomy. Results: The divergent trial findings reflect differences in populations, nodal staging, and surgical definitions. Worldwide, variability in sublobar practice and inconsistent nodal assessment present challenges to oncological reliability. Robotics has facilitated a rapid increase in anatomical segmentectomy but risks shifting surgical intent from necessity to feasibility. In metastasectomy, segmentectomy may improve local control but remains unproven in randomised studies. Emerging strategies such as IVLP and molecular profiling offer potential to refine patient selection and outcomes. Conclusion: Sublobar resection represents a paradigm shift in the surgical management of small NSCLC. Ensuring oncological validity in real-world practice requires rigorous nodal staging, equitable access to technology, and prospective evaluation of segmentectomy in both primary and metastatic disease. Future advances will depend on aligning surgical precision with biologically informed patient selection. Full article

Diabetes mellitus (DM) is a global health challenge that contributes to numerous complications. As a chronic metabolic disorder, DM leads to persistent microvascular and macrovascular damage, ultimately impairing the function of multiple organ systems. Cardiovascular diseases (CVD), including heart failure (HF), are among the most serious diabetes-related outcomes, accounting for substantial morbidity and mortality worldwide. Traditionally, diabetic HF has been attributed to coexisting conditions such as hypertensive heart disease or coronary artery disease. However, a high prevalence of HF is observed in individuals with DM even in the absence of these comorbidities. In recent years, the phenomenon of diabetes-induced HF has attracted considerable scientific interest. Gaining insight into the mechanisms by which diabetes elevates HF risk and drives key molecular and cellular alterations is essential for developing effective strategies to prevent or reverse these pathological changes. This review consolidates current evidence and recent advances regarding the cellular and molecular pathways underlying diabetes-related HF. Full article

Patent foramen ovale (PFO) is implicated in cryptogenic stroke and other clinical syndromes, with transcatheter closure demonstrating superiority over medical therapy in selected patients. Most closure devices are composed of nitinol, a nickel–titanium alloy, raising concerns in individuals with nickel hypersensitivity, one of the most prevalent contact allergies worldwide. Although typically manifesting as localized dermatitis, nickel allergy has been associated with systemic reactions after device implantation, including chest pain, palpitations, migraines, dyspnea, and cutaneous eruptions. Recent evidence indicates that nickel-sensitive patients experience a significantly higher incidence of post-procedural device-related symptoms. Nevertheless, severe reactions remain rare, and the benefits of PFO closure generally outweigh the risks. The predictive value of pre-implantation patch testing remains uncertain, and the lack of nickel-free alternatives constrains device selection. Management strategies are empirical, relying on symptomatic treatment with corticosteroids, antihistamines, or device explantation in refractory cases. Future research should focus on elucidating the pathophysiology of nickel-induced hypersensitivity in cardiovascular implants, improving diagnostic algorithms, and developing biocompatible, nickel-free devices. A multidisciplinary approach involving cardiologists, dermatologists, and allergists is essential to optimize outcomes in this complex subset of patients. Full article

Scholars universally regard Udayana’s Nyāyakusumāñjali (NK), or Flower Offering of Logic, as one of the great works of classical Indian philosophy, and more specifically, of rational or natural theology. But an important aspect of this masterpiece has not been appreciated by contemporary scholars: Udayana’s many references in the NK to Hinduism’s traditional sacrifices and sacred scriptures are integral to the philosophical case he develops for the existence of a Supreme Being. Or so we contend. We explain our interpretation of the NK through detailed examination of what we take to be the main argument of its first two chapters, an argument that only an extraordinary, omniscient being could have authored the Vedas, the Hindu scriptures. Then we show the importance of this argument for understanding the NK as a whole, including its final chapter, the chapter that has been the focus of most scholars. Though appeal to the Vedas is integral to Udayana’s full argument for the existence of a Supreme Being, his argument is not circular, we maintain; nor was he defending fideism. We believe that Udayana’s approach has relevance for persons of any faith who wish to affirm the centrality of the holy scriptures of their faith to their religious beliefs while recognizing the power of philosophical argument for the existence of a Supreme Being. Full article

Bleeding remains the most common complication following transcatheter aortic valve implantation (TAVI), despite a decline in its incidence over time. Periprocedural (≤30 days) major or life-threatening bleeding is reported to occur in 2.0–6.6% of patients undergoing TAVI. Major bleeding events carry a significant risk of mortality, with rates of 14.1% at 30 days and 27.8% at one year. The timely identification and management of patients at an elevated risk are therefore essential. Preventive measures include optimizing antithrombotic therapies, utilizing ultrasound-guided femoral access, employing single arterial access or a radial artery for secondary access, and administering unfractionated heparin under close monitoring. Long-term follow-up is essential for recognizing and managing late hemorrhages. In this review, we aimed to provide an in-depth analysis of bleeding events associated with TAVI and the most recent updates regarding the antithrombotic therapy of TAVI patients and its clinical impact. Full article