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For many new oncological drugs, including target therapy and immunotherapy, the treatment should be continued as long as the patient is deriving clinical benefit from therapy or until unacceptable toxicity occurs. Drug survival or Time to treatment discontinuation (Ttd) or persistence have become important intermediate efficacy endpoints, especially in real-world settings due to their strong correlation with endpoints such as Time to treatment failure (Ttf) and Progression free survival (Pfs). Our methodology is based on validated indicators and information technology tools, to develop continuous and updated oncology drug utilization reports in hospital setting which include data about enrolment curves, Ttd, adherence, dose intensity, dose changes and budget impact.

Environmental performance of a multi-energy liquid air energy storage (LAES) system in cogeneration asset - A life cycle assessment-based comparison with lithium ion (Li-ion) battery.

Increase in energy demand is shaping both developed and developing countries globally. As a result, the endeavour to reduce carbon emissions also encompasses electrical energy storage systems to ensure environmentally friendly power production and distribution. Currently, the scientific community is actively exploring and developing new storage technologies for this purpose.

Role of AMBRA1 in mitophagy regulation: emerging evidence in aging-related diseases.

Aging is a gradual and irreversible physiological process that significantly increases the risks of developing a variety of pathologies, including neurodegenerative, cardiovascular, metabolic, musculoskeletal, and immune system diseases. Mitochondria are the energy-producing organelles, and their proper functioning is crucial for overall cellular health. Over time, mitochondrial function declines causing an increased release of harmful reactive oxygen species (ROS) and DNA, which leads to oxidative stress, inflammation and cellular damage, common features associated with various age-related pathologies.

Imagination vs. routines: festive time, weekly time, and the predictive brain.

This paper examines the relationship between societal structures shaped by traditions, norms, laws, and customs, and creative expressions in arts and media through the lens of the predictive coding framework in cognitive science. The article proposes that both dimensions of culture can be viewed as adaptations designed to enhance and train the brain's predictive abilities in the social domain. Traditions, norms, laws, and customs foster shared predictions and expectations among individuals, thereby reducing uncertainty in social environments.

Crystal structure of archaeal IF5A-DHS complex reveals insights into the hypusination mechanism.

The translation factor IF5A is highly conserved in Eukarya and Archaea and undergoes a unique post-translational hypusine modification by the deoxyhypusine synthase (DHS) enzyme. DHS transfers the butylamine moiety from spermidine to IF5A using NAD as a cofactor, forming a deoxyhypusine intermediate. IF5A is a key player in protein synthesis, preventing ribosome stalling in proline-rich sequences during translation elongation and facilitating translation elongation and termination.

Healthcare Systems and Artificial Intelligence: Focus on Challenges and the International Regulatory Framework.

Background: Nowadays, healthcare systems are coping with the challenge of countering the exponential growth of healthcare costs worldwide, to support sustainability and to guarantee access to treatment for all patients.

Methods: Artificial Intelligence (AI) is the technology able to perform human cognitive functions through the creation of algorithms. The value of AI in healthcare and its ability to address healthcare delivery issues has been a subject of discussion within the scientific community for several years.

The lack of head-to-head randomised trials and the consequences for patients and national health service: The case of non-small cell lung cancer.

Introduction: To introduce a drug to the market, it's not mandatory for it to be more effective and safer than the current treatment for the same condition. Consequently, head-to-head studies between the two best treatments for the same condition are not required, and this could result in a lack of information for patients, clinicians, and decision-makers. This study aims to evaluate the presence of head-to-head studies among the drugs used for the treatment of non-small cell lung cancer (NSCLC).

Antidepressant deprescribing: State of the art and recommendations-A literature overview.

Introduction: In recent years, the consumption of antidepressants has arisen. However, deprescribing antidepressant therapy is very complicated. The aim of this study was to implement practical recommendations for the development of guidelines to be used for antidepressant deprescription in clinical practice.

Intermediate dose enoxaparin in hospitalized patients with moderate-severe COVID-19: a pilot phase II single-arm study, INHIXACOVID19.

Background: Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19.

Methods: A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45-60 kg, 80 mg for 61-100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.

The ubiquitin ligase TRIM32 promotes the autophagic response to Mycobacterium tuberculosis infection in macrophages.

Mycobacterium tuberculosis (Mtb) is known to evade host immune responses and persist in macrophages for long periods. A mechanism that the host uses to combat Mtb is xenophagy, a selective form of autophagy that targets intracellular pathogens for degradation. Ubiquitination of Mtb or Mtb-containing compartments is a key event to recruit the autophagy machinery and mediate the bacterial delivery to the lysosome.

Use of Tranexamic Acid With Resuscitative Endovascular Balloon Occlusion of the Aorta is Associated With Higher Distal Embolism Rates: Results From the American Association of Surgery for Trauma Aortic Occlusion and Resuscitation for Trauma and Acute Care Surgery Trial.

Introduction: Tranexamic acid (TXA) use has been associated with thrombotic complications.

Objective: We aim to investigate outcomes associated with TXA use in the setting of high- (HP) and low-profile (LP) introducer sheaths for resuscitative endovascular balloon occlusion of the aorta (REBOA).

Participants: The Aortic Occlusion and Resuscitation for Trauma and Acute Care Surgery (AORTA) database was queried for patients who underwent REBOA using a low-profile 7 French (LP) or high-profile, 11-14 French (HP) introducer sheaths between 2013 and 2022.

Immune Thrombocytopenia Onset and Relapse During the COVID-19 Pandemic. A Monocenter Study.

Background And Objectives: Several infections and vaccinations can provoke immune thrombocytopenia (ITP) onset or relapse. Information on ITP epidemiology and management during the Covid-19 pandemic is scarce. In a large monocenter ITP cohort, we assessed the incidence and risk factors for: 1) ITP onset/relapse after Covid19 vaccination/infection; 2) Covid19 infection.

Time to treatment discontinuation in first-line non-small cell lung carcinoma: an overview.

Objective: Time To Discontinuation (TTD) is defined as the time from the start of treatment to the end of treatment, usually occurring due to loss of efficacy or occurrence of adverse events. It has become an important surrogate efficacy endpoint especially in real-world studies due to its correlation with endpoints such as Progression Free Survival (PFS). The aim of the study is to conduct a literature review of all studies reporting TTD in first-line therapy of Non-Small Cell Lung Cancer (NSCLC).

Sustained response off therapy after fostamatinib: A chronic refractory ITP case report.

Fostamatinib is a SYK-inhibitor drug recently approved by the FDA and EMA for treating chronic immune thrombocytopenia. This drug induces a response in about 40% of patients and has a good toxicity profile. It is known that discontinuing thrombopoietin receptor agonists (TRAs) with the maintenance of sustained response off therapy is possible.

Methods for informing people with amyotrophic lateral sclerosis/motor neuron disease of their diagnosis.

Background: Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), causes increasing physical impairment and disability. People with ALS/MND face huge physical challenges, and the diagnosis can be a source of great psychological distress for both people with ALS/MND and their carers. In such a context, how news of the diagnosis is broken is important.

Cover with caution: Management of the Left Subclavian Artery in TEVAR for trauma.

Background: Elective Thoracic Endovascular Aortic Repair (TEVAR) with left subclavian artery coverage (LSA-C) without revascularization is associated with increased rates of ischemic stroke. In patients with blunt thoracic aortic injury (BTAI) requiring TEVAR, LSA-C is frequently required in over one-third of patients. This study aimed to evaluate outcomes of TEVAR in BTAI patients with and without LSA-C.

Oligometastatic Prostate Cancer Treated with Metastasis-Directed Therapy Guided by Positron Emission Tomography: Does the Tracer Matter?

The superior diagnostic accuracy of [68Ga]Ga-prostate-specific membrane antigen-11 (PSMA) ([68Ga]Ga-PSMA-11) compared to [18F]F-Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT) in Prostate Cancer (PCa) is established. However, it is currently unclear if the added diagnostic accuracy actually translates into improved clinical outcomes in oligometastatic PCa patients treated with [68Ga]Ga-PSMA-11 PET-guided metastasis-directed therapy (MDT). The present study aimed to assess the impact of these two imaging techniques on Progression-Free Survival (PFS) in a real-world sample of oligometastatic PCa patients submitted to PET-guided MDT.

Structural-Functional Relationship of the Ribonucleolytic Activity of aIF5A from .

The translation factor IF5A is a highly conserved protein playing a well-recognized and well-characterized role in protein synthesis; nevertheless, some of its features as well as its abundance in the cell suggest that it may perform additional functions related to RNA metabolism. Here, we have undertaken a structural and functional characterization of aIF5A from the crenarchaeal model organism. We confirm the association of aIF5A with several RNA molecules in vivo and demonstrate that the protein is endowed with a ribonuclease activity which is specific for long and structured RNA.

Adherence, persistence and switching rates of apixaban, dabigatran and rivaroxaban in non-valvular atrial fibrillation: a multicentre real-life analysis at 3 years.

Introduction: Adherence to and persistence with long-term treatment with oral anticoagulants play a significant role in preventing adverse events and mortality in patients with cardiac conditions. The aim of this study was to evaluate the adherence, persistence and switching rate at 3 years in real-life patients with non-valvular atrial fibrillation receiving treatment with first-line new oral anticoagulants.

Methods: The study assessed all patients treated with drugs with the ATC codes B01AA, B01AE, B01AF and dispensed in pharmacies in the Lanciano-Vasto-Chieti and Pescara Local Health Units from 1 January 2011 to 30 September 2021.

A multicentre study with real-world data of the use of palbociclib in the treatment of breast cancer: Treatment duration correlates with dose reductions.

Objective: Palbociclib, a highly selective reversible CDK4-6 kinase inhibitor, is indicated in combination with an aromatase inhibitor or in combination with fulvestrant in women who had received prior endocrine treatment. Studies have demonstrated the efficacy of palbociclib in combination with fulvestrant in increasing progression-free survival in patients who relapsed or progressed on previous endocrine therapy, or in combination with aromatase inhibitor in patients who had not received previous treatments. We analysed the prescribing patterns of palbociclib in real practice correlating it with the evidence of treatment-related toxicity management and to time-to-treatment discontinuation and treatment adherence.

Targeting mTOR and eIF4E: a feasible scenario in ovarian cancer therapy.

Ovarian carcinoma is one of the most common causes for cancer death in women; lack of early diagnosis and acquired resistance to platinum-based chemotherapy account for its poor prognosis and high mortality rate. As with other cancer types, ovarian cancer is characterized by dysregulated signaling pathways and protein synthesis, which together contribute to rapid cellular growth and invasiveness. The mechanistic/mammalian target of rapamycin (mTOR) pathway represents the core of different signaling pathways regulating a number of essential steps in the cell, among which protein synthesis and the eukaryotic initiation factor 4E (eIF4E), the mRNA cap binding protein, is one of its downstream effectors.

The Pattern of Retinal Ganglion Cell Loss in Wolfram Syndrome is Distinct From Mitochondrial Optic Neuropathies.

Purpose: To describe the clinical phenotype of a cohort of patients with Wolfram syndrome (WS), focusing on the pattern of optic atrophy correlated with brain magnetic resonance imaging (MRI) measurements, as compared with patients with OPA1-related dominant optic atrophy (DOA).

Design: Retrospective, comparative cohort study.

Methods: We reviewed 25 patients with WS and 33 age-matched patients affected by OPA1-related DOA.