Upfront osimertinib and as sequential therapy in patients with -mutant non-small cell lung cancer (NSCLC): benefit across patients groups in a real-world retrospective cohort-the smile study.

Background: Osimertinib is the preferred first-line (L1) treatment for epidermal growth factor receptor-mutant (m) advanced non-small cell lung cancer (aNSCLC). Intensification of L1 with chemotherapy or amivantamab has shown improved outcomes at the cost of increased toxicity, raising questions about the optimal patients selection. A sequence involving first-generation tyrosine kinase inhibitor (TKI) (1G) followed by osimertinib might be considered.

Frequency of driver oncogenic alterations in NSCLC and estimated indoor radon exposure in Europe (RADON EUROPE study).

Background: Geographical variations in the frequency of oncogenic driver alterations in non-small cell lung cancer (NSCLC) are observed worldwide, likely influenced by genetic and environmental factors. Radon, a leading cause of lung cancer in nonsmokers, may influence NSCLC's molecular profile.

Objectives: This study aims to explore the potential correlation between estimated indoor radon concentrations and the frequency of driver alterations in NSCLC across Europe.

Prevalence and characteristics of lung cancer in families harboring Pathogenic Germline Variants in cancer predisposing genes: A 20-year retrospective analysis.

Introduction: Genetic predisposition for lung cancer has historically been underexplored. However, increasing evidence indicates the presence of pathogenic germline variants (PGV) in cancer predisposition genes among patients with lung cancer, highlighting a need for further investigation. Here, we report the prevalence and characteristics of lung cancer in families harboring PGVs studied in our genetic counseling unit (GCU).

FTO inhibition mitigates high-fat diet-induced metabolic disturbances and cognitive decline in SAMP8 mice.

This study investigated the effects of fat mass and obesity-associated (FTO) inhibition on cognitive function and metabolic parameters of senescence-accelerated mouse prone 8 (SAMP8) mice fed a high-fat diet (HFD). SAMP8 mice fed an HFD exhibited increased body weight, impaired glucose tolerance, and elevated serum leptin levels. In epididymal white adipose tissue (eWAT), pharmacological treatment with FB23, a well-established FTO inhibitor, increased leptin production and modulated genes involved in lipid metabolism (Cpt1a, Atgl, Hsl, Fas), oxidative stress (OS) (Bip, Edem), and inflammation (Mcp1, Tnfα).

Inhibition of ATP-citrate lyase by bempedoic acid protects against abdominal aortic aneurysm formation in mice.

Abdominal aortic aneurysm (AAA) is a prevalent degenerative disease characterized by an exacerbated inflammation and destructive vascular remodeling. Unfortunately, effective pharmacological tools for the treatment of this disease remain a challenge. ATP-citrate lyase (ACLY), the primary enzyme responsible for acetyl-CoA biosynthesis, is a key regulator of inflammatory signaling in macrophages and lymphocytes.

Validation of the Lung Immune Prognostic Index in patients with untreated advanced non-small cell lung cancer: Post hoc analysis of the IMpower 130, 131 and 150 trials.

Introduction: LIPI has been strongly correlated with immunotherapy (IT) outcomes in advanced NSCLC. Limited data is available for upfront chemotherapy (CT) + IT combinations. We aimed to study its prognostic value in 1st-line CT +/- IT +/- antiangiogenics.

The FLARE Score and Circulating Neutrophils in Patients with Cancer and COVID-19 Disease.

Purpose: Inflammation and neutrophils play a central role in both COVID-19 disease and cancer. We aimed to assess the impact of pre-existing tumor-related inflammation on COVID-19 outcomes in patients with cancer and to elucidate the role of circulating neutrophil subpopulations.

Methods: We conducted a multicenter retrospective analysis of 524 patients with cancer and SARS-CoV-2 infection, assessing the relationship between clinical outcomes and circulating inflammatory biomarkers collected before and during COVID-19 infection.

Sex Differences Affect the NRF2 Signaling Pathway in the Early Phase of Liver Steatosis: A High-Fat-Diet-Fed Rat Model Supplemented with Liquid Fructose.

Sex differences may play a role in the etiopathogenesis and severity of metabolic dysfunction-associated steatotic liver disease (MASLD), a disorder characterized by excessive fat accumulation associated with increased inflammation and oxidative stress. We previously observed the development of steatosis specifically in female rats fed a high-fat diet enriched with liquid fructose (HFHFr) for 12 weeks. The aim of this study was to better characterize the observed sex differences by focusing on the antioxidant and cytoprotective pathways related to the KEAP1/NRF2 axis.

Tackling Non-Small Cell Lung Cancer in Young Adults: From Risk Factors and Genetic Susceptibility to Lung Cancer Profile and Outcomes.

Lung cancer has traditionally been associated with advanced age; however, its increasing incidence among young adults raises concerning questions regarding its etiology and unique considerations for this population. In contrast to the older population, the onset of lung cancer at younger age may be attributed to a complex interplay of incompletely understood individual susceptibility and prevalent environmental risk factors beyond tobacco smoke exposure, such as radon gas and air pollution, which are widespread globally. Consequently, this leads to distinct clinical and molecular profiles, requiring a tailored approach.

Rethinking strategies in SCLC: Lessons learned from tiragolumab in the SKYSCRAPER-02 study.

The addition of tiragolumab, an anti-TIGIT inhibitor, to chemotherapy plus atezolizumab demonstrated promising early results for lung cancer. Unfortunately, the phase 3 study SKYSCRAPER-02 did not confirm the anticipated benefit of tiragolumab combination in recalcitrant small-cell lung cancer, reiterating the need for a more accurate population selection in clinical trials.

Characterisation and Outcomes of Patients with Solid Organ Malignancies Admitted to the Intensive Care Unit: Mortality and Impact on Functional Status and Oncological Treatment.

Background: Despite the increasing number of ICU admissions among patients with solid tumours, there is a lack of tools with which to identify patients who may benefit from critical support. We aim to characterize the clinical profile and outcomes of patients with solid malignancies admitted to the ICU.

Methods: Retrospective observational study of patients with cancer non-electively admitted to the ICU of the Hospital Clinic of Barcelona (Spain) between January 2019 and December 2019.

Incidental pathogenic germline alterations detected through liquid biopsy in patients with solid tumors: prevalence, clinical utility and implications.

Liquid biopsy, a minimally invasive approach for detecting tumor biomarkers in blood, has emerged as a leading-edge technique in cancer precision medicine. New evidence has shown that liquid biopsies can incidentally detect pathogenic germline variants (PGVs) associated with cancer predisposition, including in patients with a cancer for which genetic testing is not recommended. The ability to detect these incidental PGV in cancer patients through liquid biopsy raises important questions regarding the management of this information and its clinical implications.

Geographic differences in lung cancer: focus on carcinogens, genetic predisposition, and molecular epidemiology.

Lung cancer poses a global health challenge and stands as the leading cause of cancer-related deaths worldwide. However, its incidence, mortality, and characteristics are not uniform across all regions worldwide. Understanding the factors contributing to this diversity is crucial in a prevalent disease where most cases are diagnosed in advanced stages.

Adipose Tissue Protects against Hepatic Steatosis in Male Rats Fed a High-Fat Diet plus Liquid Fructose: Sex-Related Differences.

Non-alcoholic fatty liver disease is a sexual dimorphic disease, with adipose tissue playing an essential role. Our previous work showed that female rats fed a high-fat high-fructose diet devoid of cholesterol (HFHFr) developed simple hepatic steatosis dissociated from obesity. This study assessed the impact of the HFHFr diet on the male rat metabolism compared with data obtained for female rats.

Epidemiology and risk factors for recurrence in biliary source bloodstream infection episodes in oncological patients.

We aimed to describe the characteristics and outcomes of biliary source bloodstream infections (BSIs) in oncological patients. Secondarily, we analyzed risk factors for recurrent BSI episodes. All episodes of biliary source BSIs in oncological patients were prospectively collected (2008-2019) and retrospectively analyzed.

Bempedoic acid for nonalcoholic fatty liver disease: evidence and mechanisms of action.

Purpose Of Review: Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent progressive condition that lacks a specific pharmacological treatment. ATP-citrate lyase (ACLY) is one of the emergent targets for the treatment of NAFLD. This review aims to summarize the role of ACLY in NAFLD, provide evidence of the beneficial effects of the ACLY inhibitor bempedoic acid (BemA) in NAFLD and discuss the mechanisms involved.

Immune-Related Uncommon Adverse Events in Patients with Cancer Treated with Immunotherapy.

Immunotherapy has dramatically changed the therapeutic landscape of oncology, and has become standard of care in multiple cancer types in front or late lines of therapy, with some longstanding responses and outstanding results. Notwithstanding, its use has brought a totally unique spectrum of adverse events, characterized by a myriad of diverse manifestations affecting nearly every organ and system of the body, including the endocrine, nervous, cardiac, respiratory and gastrointestinal systems. Uncommon adverse events, defined as those occurring in less than 1% of patients, comprise an even more heterogeneous group of diseases that are being seen more recurrently as the use of immune check-point inhibitors increases and indications spread in different tumor types and stages.

Catheter-related thrombosis (CRT) in patients with solid tumors: a narrative review and clinical guidance for daily care.

Central venous access devices (CVADs) including central venous catheters and peripherally inserted central catheters (PICCs) are essential in the treatment of cancer. Catheter-related thrombosis (CRT) is the most frequent non-infectious complication associated with the use of central lines. The development of CRT may cause to delays in oncologic treatment and increase morbidity leading to potentially life-threatening complications.

KHK, PNPLA3 and PPAR as Novel Targets for the Anti-Steatotic Action of Bempedoic Acid.

Bempedoic acid (BemA) is an ATP-citrate lyase (ACLY) inhibitor used to treat hypercholesterolemia. We studied the anti-steatotic effect of BemA, and the mechanisms involved, in a model of fatty liver in female rats obtained through the administration of a high-fat diet supplemented with liquid fructose (HFHFr) for three months. In the third month, a group of rats was treated with BemA (30 mg/kg/day) by gavage.

ChREBP-driven DNL and PNPLA3 Expression Induced by Liquid Fructose are Essential in the Production of Fatty Liver and Hypertriglyceridemia in a High-Fat Diet-Fed Rat Model.

Scope: The aim of this study is to delineate the contribution of dietary saturated fatty acids (FA) versus liquid fructose to fatty liver and hypertriglyceridemia.

Methods And Results: Three groups of female rats are maintained for 3 months in standard chow (CT); High-fat diet (46.9% of fat-derived calories, rich in palmitic and stearic FA, HFD); and HFD with 10% w/v fructose in drinking water (HFHFr).

Bempedoic acid as a PPARα activator: new perspectives for hepatic steatosis treatment in a female rat experimental model.

Introduction: In its initial stages, nonalcoholic fatty liver disease presents hypertriglyceridemia and accumulation of lipids in the liver (hepatic steatosis). Bempedoic acid is an ATP:citrate lyase inhibitor that promotes a dual inhibition of the synthesis of cholesterol and fatty acids. However, its effect in the prevention / treatment of hepatic steatosis and hypertriglyceridemia has not been investigated.

Chronic liquid fructose supplementation does not cause liver tumorigenesis but elicits clear sex differences in the metabolic response in Sprague-Dawley rats.

Background: Non-alcoholic fatty liver disease (NAFLD) has increased over the last decades and may evolve into hepatocellular carcinoma (HCC). As HCC is challenging to treat, knowledge on the modifiable risk factors for NAFLD/HCC (e.g.