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Background/Objectives: The management of early breast cancer (BC) includes surgery, followed by adjuvant radiotherapy, chemotherapy, hormone therapy, or immunotherapy. However, the influence of these interventions in metabolic reprogramming remains unknown. This study explored alterations in the plasma metabolome of BC patients following distinct treatments to deepen our understanding of BC pathophysiology, outcomes, and the identification of potential biomarkers. Methods: We included 52 women diagnosed with BC and candidates for surgery as primary oncological treatment. Blood samples were collected at diagnosis, two weeks post-surgery, and one month post-radiotherapy. Plasma samples from 49 healthy women served as controls. Targeted metabolomics assessed 74 metabolites spanning carbohydrates, amino acids, lipids, nucleotide pathways, energy metabolism, and xenobiotic biodegradation. Results: Before treatment, the BC patients exhibited notable changes in carbohydrate, nucleotide, lipid, and amino acid metabolism. We noticed a gradual restoration of specific metabolite levels (hypoxanthine, 3-phosphoglyceric acid, xylonic acid, and maltose) throughout different treatments, suggesting a normalization of the nucleotide and carbohydrate metabolic pathways. Moreover, we observed increased dodecanoic acid concentrations, a metabolite associated with cancer protection. These variations distinguished patients from controls with high specificity and sensitivity. Conclusions: Our preliminary study suggests that oncological treatments modify the metabolism of patients towards a favorable profile with a decrease in the pathways that favor cell proliferation and an increase in the levels of anticancer molecules. These findings emphasize the pivotal role of metabolomics in recognizing the biological pathways influenced by each cancer treatment and the resulting metabolic consequences. Furthermore, it aids in identifying potential biomarkers for disease onset and progression. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for over 85% of cases and poor prognosis in advanced stages. This study explored shifts in circulating metabolite levels in NSCLC patients versus healthy controls and examined the effects of conventionally fractionated radiation therapy (CFRT) and stereotactic body radiation therapy (SBRT). We enrolled 91 NSCLC patients (38 CFRT and 53 SBRT) and 40 healthy controls. Plasma metabolite levels were assessed using semi-targeted metabolomics, revealing 32 elevated and 18 reduced metabolites in patients. Key discriminatory metabolites included ethylmalonic acid, maltose, 3-phosphoglyceric acid, taurine, glutamic acid, glycocolic acid, and d-arabinose, with a combined Receiver Operating Characteristics curve indicating perfect discrimination between patients and controls. CFRT and SBRT affected different metabolites, but both changes suggested a partial normalization of energy and amino acid metabolism pathways. In conclusion, metabolomics identified distinct metabolic signatures in NSCLC patients with potential as diagnostic biomarkers. The differing metabolic responses to CFRT and SBRT reflect their unique therapeutic impacts, underscoring the utility of this technique in enhancing NSCLC diagnosis and treatment monitoring. [ABSTRACT FROM AUTHOR]

Acute respiratory tract infections, including influenza A (FluA), respiratory syncytial virus (RSV) infection, and COVID-19, can aggravate to levels requiring hospitalization, increasing morbidity and mortality. Identifying biomarkers for an accurate diagnosis and prognosis of these infections is a clinical need. We performed a cross-sectional study aimed to investigate the changes in circulating levels of arachidonic acid, interleukin 6 (IL-6), and C-reactive protein (CRP) in patients with FluA, RSV, or COVID-19, and to analyze the potential of these parameters as diagnosis or prognosis biomarkers. We analyzed serum samples from 172 FluA, 80 RSV, and 217 COVID-19 patients, and 104 healthy volunteers. Individuals with lung viral diseases showed reduced arachidonic acid concentrations compared to healthy people, with these differences being most pronounced in the order COVID-19 > RSV > FluA. Conversely, IL-6 and CRP levels were elevated across diseases, with IL-6 emerging as the most promising diagnostic biomarker, with areas under the curve (AUC) of the receiver operating characteristics plot higher than 0.85 and surpassing arachidonic acid and CRP. Moreover, IL-6 displayed notable efficacy in distinguishing between FluA patients who survived and those who did not (AUC = 0.80). These findings may provide useful tools for diagnosing and monitoring the severity of acute viral respiratory tract infections, ultimately improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Clostridioides difficile infections (CDI) vary in severity from mild diarrhea to life-threatening conditions like pseudomembranous colitis or toxic megacolon, often leading to sepsis and death. The COVID-19 pandemic prompted changes in healthcare practices, potentially affecting CDI incidence, though reported data are inconclusive. We studied factors influencing CDI incidence and outcomes at a university hospital throughout the COVID-19 pandemic years. Methods: We conducted a retrospective study on all adult hospitalized CDI cases from 1 January 2020 to 31 December 2022 in Hospital Universitari de Sant Joan in Reus. We collected demographic information, comorbid conditions, and concurrent infections. Results: While overall CDI and COVID-19 rates decreased in 2022, a notable increase in CDI infections was observed among oncological patients and those undergoing some aggressive treatments, such as colonoscopies or gastroscopies. The prevalence of comorbidities remained unmodified, and there were declines in prior gastrointestinal surgeries and proton pump inhibitor prescriptions. Factors associated with patient fatality or prolonged hospitalization included older age, cancer, chronic kidney disease, higher Charlson and McCabe indices, elevated C-reactive protein, and low albumin concentrations. Conclusions: Our study shows the evolving landscape of CDI during the COVID-19 pandemic and emphasizes the impact of delayed diagnoses and treatments exacerbated by telemedicine adoption. Identified risk factors for CDI-related mortality or prolonged hospital stays underscore the importance of targeted interventions in high-risk populations. [ABSTRACT FROM AUTHOR]

Paraoxonase-1 (PON1) is an antioxidant enzyme associated with high-density lipoproteins (HDL). Reduced serum PON1 activity is found in diseases marked by oxidative stress and inflammation, but its role in obesity remains unclear. This study investigated PON1 activities and concentrations in morbidly obese individuals and explored the impacts of the genetic polymorphism PON1 rs662 and non-alcoholic fatty liver disease on enzymatic properties. We recruited 1349 morbidly obese patients undergoing bariatric surgery and 823 non-obese volunteers. PON1-related variables, including arylesterase, paraoxonase, and lactonase activities and PON1 concentrations, were examined. Our results showed that morbidly obese individuals exhibited higher PON1 concentrations but lower enzymatic activities than non-obese individuals. We observed inverse associations of arylesterase and paraoxonase activities with waist circumference (rho = −0.24, p < 0.001, and rho = −0.30, p < 0.001, respectively) and body mass index (rho = −0.15, p = 0.001, and rho = −0.23, p < 0.001), as well as direct associations of arylesterase, paraoxonase, and lactonase activities with HDL cholesterol (rho = 0.11, p = 0.005, rho = 0.20, p < 0.001, and rho = 0.20, p < 0.001). No significant differences were observed regarding metabolic syndrome, type 2 diabetes mellitus, hypertension, dyslipidemia, rs662 polymorphism allele frequencies, or the diagnosis of non-alcoholic steatohepatitis. Nevertheless, correlations were found between certain PON1-related variables, steatosis, and ballooning. In conclusion, changes in PON1-related variables in morbidly obese patients are dependent on the disease itself and HDL levels. The relationships between these variables and specific liver histological changes raise intriguing questions for consideration in future studies. [ABSTRACT FROM AUTHOR]

ABSTRACT Background: There is growing evidence that natural products, mostly plant-derived polyphenols, are important in the relationship between nutrients and health in humans. Purpose: We aimed to investigate if verbascoside [...]

SARS-CoV-2 infection in already-vaccinated individuals is still possible and may require hospitalization. The aim of the present study was to evaluate the clinical evolution of patients with COVID-19 admitted to a public hospital. The outcomes were assessed in relation to the predominant viral variant and the vaccination status. This retrospective study was performed on 1295 COVID-19-positive patients who attended a 352-bed university hospital between 2021 and 2022. Clinical variables and vaccination status were recorded. Of the patients, 799 had not been vaccinated (NV, 61.7%), 449 were partially vaccinated (PV, 34.7%), and 47 were completely vaccinated (CV, 3.6%). The mean age of the CV patients was significantly higher than that of PV and NV. Additionally, they had higher percentages of chronic diseases. The outcomes depended on age but not on vaccination status. There were 209 patients admitted during the Omicron-infection period, of whom 70 (33.5%) were NV, 135 (64.6%) were PV, and 4 (1.9%) were CV. In conclusion, correct vaccination greatly reduces the risk of acquiring severe COVID-19. Partial vaccination does not guarantee protection of the population. This highlights the need for continuous vaccination promotion with all recommended doses, while also investigating alternative treatments for those patients who do not respond to the vaccines. [ABSTRACT FROM AUTHOR]

Several studies have shown that the plasma RNA of SARS-CoV-2 seems to be associated with a worse prognosis of COVID-19. In the present study, we investigated plasma RNA in COVID-19 patients treated with low-dose radiotherapy to determine its prognostic value. Data were collected from the IPACOVID prospective clinical trial (NCT04380818). The study included 46 patients with COVID-19 pneumonia treated with a whole-lung dose of 0.5 Gy. Clinical follow-up, as well as laboratory variables, and SARS-CoV-2 serum viral load, were analyzed before LDRT, at 24 h, and one week after treatment. The mean age of the patients was 85 years, and none received any of the SARS-CoV-2 vaccine doses. The mortality ratio during the course of treatment was 33%. RT-qPCR showed amplification in 23 patients. Higher mortality rate was associated with detectable viremia. Additionally, C-reactive protein, lactate dehydrogenase, and aspartate aminotransferase were significant risk factors associated with COVID-19 mortality. Our present findings show that detectable SARS-CoV-2 plasma viremia 24 h before LDRT is significantly associated with increased mortality rates post-treatment, thus downsizing the treatment success. [ABSTRACT FROM AUTHOR]

Hypertension is a common chronic medical condition. Treatment is not satisfactory in a significant proportion of patients with primary hypertension, despite the concurrent use of three or more medications with different mechanisms of action. Such treatment-resistant hypertension is a clinical challenge associated with poor prognosis and needs further investigation. The efficacy of lifestyle changes has not been established yet in patients with resistant hypertension, and educational efforts appear clinically irrelevant in patients who must achieve behavioral changes without supervision. A 6-month multidisciplinary pilot intervention enrolled 50 patients with established resistant hypertension. The aims were: (1) to examine whether intensive and supervised lifestyle changes contribute to decreasing blood pressure in this condition, and (2) to identify which components affect compliance and feasibility. The program provided intensive changes in nutrition, physical exercise, and control of sleep disturbances supervised by nutritionists, physiotherapists, and psychologists. Nurses and pharmacists followed up on adherence to the antihypertensive medication. The primary outcome was 24 h blood pressure control. Data in patients with full compliance (n = 30) indicate that lifestyle modifications in resistant hypertension significantly reduced 24 h both systolic and diastolic blood pressure (p < 0.01), body mass index (p < 0.01), medication burden (p = 0.04), improving physical fitness, and cardiovascular risk markers such as heart rate (p = 0.01) and augmentation index (p = 0.02). The adherence to the intervention was moderate, with an attrition rate of 12%. A modified version reducing visits and explorations will likely improve compliance and can be used to assess the long-term maintenance of these benefits in managing resistant hypertension by diverse healthcare providers. [ABSTRACT FROM AUTHOR]

Viral infections cause metabolic dysregulation in the infected organism. The present study used metabolomics techniques and machine learning algorithms to retrospectively analyze the alterations of a broad panel of metabolites in the serum and urine of a cohort of 126 patients hospitalized with COVID-19. Results were compared with those of 50 healthy subjects and 45 COVID-19-negative patients but with bacterial infectious diseases. Metabolites were analyzed by gas chromatography coupled to quadrupole time-of-flight mass spectrometry. The main metabolites altered in the sera of COVID-19 patients were those of pentose glucuronate interconversion, ascorbate and fructose metabolism, nucleotide sugars, and nucleotide and amino acid metabolism. Alterations in serum maltose, mannonic acid, xylitol, or glyceric acid metabolites segregated positive patients from the control group with high diagnostic accuracy, while succinic acid segregated positive patients from those with other disparate infectious diseases. Increased lauric acid concentrations were associated with the severity of infection and death. Urine analyses could not discriminate between groups. Targeted metabolomics and machine learning algorithms facilitated the exploration of the metabolic alterations underlying COVID-19 infection, and to identify the potential biomarkers for the diagnosis and prognosis of the disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Epithelial-to-mesenchymal transition (EMT) is a cellular program that enables epithelial cells to transition toward a mesenchymal phenotype with augmented cellular motility. Although EMT is a fundamental, non-pathological process in embryonic development and tissue repair, it also confers biological aggressiveness to cancer cells, including invasive behavior, tumor- and metastasis-initiating cancer stem cell activity, and greater resistance to all the cancer treatment modalities. Whereas alterations in the metabolic microenvironment are known to induce EMT, it is also true that the EMT process involves a very marked metabolic remodeling. However, whether there is a causal or merely an ancillary relationship between metabolic rewiring and the EMT phenomenon has not yet been definitively clarified. Here, we combined several technology platforms to assess whether the accompanying changes in the metabolic profile and mitochondria functioning that take place during the EMT process are independent or not of the non-tumorigenic versus tumorigenic nature of epithelial cells suffering a mesenchymal conversion. Understanding the metabolic basis of the non-tumorigenic and tumorigenic EMT provides fundamental insights into the causation and progression of cancer and may, in the long run, lead to new therapeutic strategies. Epithelial-to-mesenchymal transition (EMT) is key to tumor aggressiveness, therapy resistance, and immune escape in breast cancer. Because metabolic traits might be involved along the EMT continuum, we investigated whether human breast epithelial cells engineered to stably acquire a mesenchymal phenotype in non-tumorigenic and H-RasV12-driven tumorigenic backgrounds possess unique metabolic fingerprints. We profiled mitochondrial–cytosolic bioenergetic and one-carbon (1C) metabolites by metabolomic analysis, and then questioned the utilization of different mitochondrial substrates by EMT mitochondria and their sensitivity to mitochondria-centered inhibitors. "Upper" and "lower" glycolysis were the preferred glucose fluxes activated by EMT in non-tumorigenic and tumorigenic backgrounds, respectively. EMT in non-tumorigenic and tumorigenic backgrounds could be distinguished by the differential contribution of the homocysteine-methionine 1C cycle to the transsulfuration pathway. Both non-tumorigenic and tumorigenic EMT-activated cells showed elevated mitochondrial utilization of glycolysis end-products such as lactic acid, β-oxidation substrates including palmitoyl–carnitine, and tricarboxylic acid pathway substrates such as succinic acid. Notably, mitochondria in tumorigenic EMT cells distinctively exhibited a significant alteration in the electron flow intensity from succinate to mitochondrial complex III as they were highly refractory to the inhibitory effects of antimycin A and myxothiazol. Our results show that the bioenergetic/1C metabolic signature, the utilization rates of preferred mitochondrial substrates, and sensitivity to mitochondrial drugs significantly differs upon execution of EMT in non-tumorigenic and tumorigenic backgrounds, which could help to resolve the relationship between EMT, malignancy, and therapeutic resistance in breast cancer. [ABSTRACT FROM AUTHOR]