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Cardiovascular diseases (CVDs) are the leading cause of death worldwide. This study focused on evaluating the impact of a Mediterranean-type diet combined with physical exercise on CVD risk factors of high-risk individuals. A randomized clinical trial (RCT) recruited individuals (≥50 years old) with no history of acute myocardial infarction, but with high CVD risk criteria according to the SCORE2/SCORE2 OP. Anthropometric and biochemical parameters were assessed at baseline and after 12 weeks of diet and exercise intervention. Participants were randomly assigned into 3 groups: no intervention group (Group 1a), physical exercise group (Group 1b), and physical exercise (±2 h/week) plus diet group (Group 2). Briefly, the dietary intervention was based on the principles of an isocaloric Mediterranean diet (MD), with seven main meals/week centered on plant-based foods (legumes and pulses). The combined effect of exercise and the diet showed significant decrease in WC (p = 0.002), BST (p < 0.001), visceral fat (p < 0.001), and TG (p = 0.029), compared with control groups. The intervention significantly increased legume intake (p < 0.001), as well as adherence to the MD, which associates with WC decrease (p = 0.024) and visceral fat (p = 0.017). A combined intervention of exercise and diet should be endorsed as an efficient modifier of cardiometabolic parameters.
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Doenças Cardiovasculares , Dieta Mediterrânea , Exercício Físico , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/prevenção & controle , Idoso , Circunferência da Cintura , Fatores de Risco , Gordura Intra-AbdominalRESUMO
Background Drugs are a frequent cause of nephrotoxicity, especially in the context of acute kidney disease (AKD), with a significant number of cases being drug-associated. The WHO's VigiBase is a powerful tool for identifying drugs described and associated with the development of AKD. Methods We retrieved data from the period 1968 to 2022 regarding notifications of adverse drug reactions (ADR). The extracted medications were evaluated for their nephrotoxicity based on the bibliographic score (BS) developed through pre-selected references. The main medications involved were classified as 'non-nephrotoxic', 'potentially nephrotoxic', and 'nephrotoxic'. We utilized the IC025 and reporting odds ratio (ROR) disproportionality indexes to study the relationship between medications and the odds of being included in an AKD notification. Results During the period, a total of 33,932,051 notifications were obtained, revealing 435,677 cases related to drug-associated AKD following MedDRA term filtering, predominantly affecting males aged 45-64. We identified 8,991 active ingredients or suspected combinations associated with AKD development, with the ATC class A - Alimentary Tract and Metabolism being the most frequently described. Among the medications most strongly associated with this phenotype, classes J and N stood out. Among the most notable medications collected, 8.3% were classified as "non-nephrotoxic," 16.7% as "potentially nephrotoxic," and 75% as "known nephrotoxic." Notable active ingredients included cobicistat + elvitegravir + emtricitabine + tenofovir disoproxil (IC025 8.7; ROR 786.96), inotersen (IC025 7.7; ROR 604.57), emtricitabine + tenofovir disoproxil (IC025 7.9; ROR 432.36), esomeprazole (IC025 6.8; ROR 184.23), and pantoprazole (IC025 6.3; ROR 109.86), with proton pump inhibitors dominating the top four positions among the most frequently involved medications. Conclusion AKD is a frequent adverse reaction in VigiBase, with a significantly high reported mortality rate. Evaluation of the notifications revealed medications with a high disproportionality index and a strong association with AKD. We also highlight the potential nephrotoxic role of less suspected medications. This study emphasizes the need to consider AKD as a condition potentially associated with iatrogenic etiology, highlighting various medications and their respective involvement in the various possible manifestations of AKD.
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BACKGROUND: The aftermath of the COVID-19 pandemic continues to affect millions worldwide, resulting in persisting postvirus complaints and impacting peoples' quality of life. Long COVID, characterized by lingering symptoms like fatigue and mental illness, can extend beyond a few months, necessitating further research to understand its implications. OBJECTIVE: This study aims to quantify the degree of physical and psychological fatigue in patients following COVID-19 infection and examine its correlation with mental health disorders. METHODS: Using a consecutive nonrandom sampling technique, we will conduct a prospective cohort multicenter observational study in 5 Portuguese hospitals. Symptomatic adult patients with previous COVID-19 attending follow-up consultations will be enrolled. We will include patients who had mild, moderate, and severe acute disease. We will assess clinical outcomes related to COVID-19, including the type of respiratory support such as high-flow nasal cannula, noninvasive ventilation, and invasive mechanical ventilation. The exclusion criteria will include previous severe psychiatric disorders confirmed by a psychiatrist; refusal or inability to respond to the questionnaire; concomitant neurological disorder; persistent fatigue symptoms during the 6 months before infection; and the need for invasive mechanical ventilation during COVID-19 infection due to a high prevalence of postintensive care syndrome. Our primary outcome is the prevalence of fatigue in patients with post-COVID-19 depression and/or anxiety, as measured by the Chalder Fatigue Scale (CFQ-11) and the Hospital Anxiety and Depression Scale (HADS). The secondary outcomes will include an assessment of health-related quality of life via the EQ-5D questionnaire and an exploration of the prevalence of symptoms of posttraumatic stress disorder (PTSD) using the 14-item Posttraumatic Stress Scale (PTSS-14). We will also examine the association between mental health symptoms and the severity of acute COVID-19. The post-COVID-19 data will be collected at least 6 months after the positive test and no longer than 9 months during the clinical appointment. RESULTS: We expect our multicenter study on patients post COVID-19 to reveal a significant link between mental illness symptoms and both physical and psychological fatigue. Patients with heightened depression and anxiety may report increased levels of fatigue. Additionally, we expect to find persistent PTSD symptoms in a subset of participants, indicating the enduring psychological impact of the virus. CONCLUSIONS: This study may underscore the need for integrated care addressing physical and mental health in patients post COVID-19. The observed connections emphasize the importance of considering mental well-being for long-term health outcomes. Despite study limitations, our findings contribute valuable insights for future treatment strategies and highlight the necessity for comprehensive mental health support in post-COVID-19 care. This research provides valuable insights into the mental health implications of COVID-19 and its impact on post-COVID-19 fatigue and the overall well-being of affected individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT05323318; https://clinicaltrials.gov/study/NCT05323318. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51820.
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PURPOSE: AML is a hematologic cancer that is clinically heterogeneous, with a wide range of clinical outcomes. DNA methylation changes are a hallmark of AML but are not routinely used as a criterion for risk stratification. The aim of this study was to explore DNA methylation markers that could risk stratify patients with cytogenetically normal AML (CN-AML), currently classified as intermediate-risk. MATERIALS AND METHODS: DNA methylation profiles in whole blood samples from 77 patients with CN-AML in The Cancer Genome Atlas (LAML cohort) were analyzed. Individual 5'-cytosine-phosphate-guanine-3' (CpG) sites were assessed for their ability to predict overall survival. The output was validated using DNA methylation profiles from bone marrow samples of 79 patients with CN-AML in a separate data set from the Gene Expression Omnibus. RESULTS: In the training set, using DNA methylation data derived from the 450K array, we identified 2,549 CpG sites that could potentially distinguish patients with CN-AML with an adverse prognosis (intermediate-poor) from those with a more favorable prognosis (intermediate-favorable) independent of age. Of these, 25 CpGs showed consistent prognostic potential across both the 450K and 27K array platforms. In a separate validation data set, nine of these 25 CpGs exhibited statistically significant differences in 2-year survival. These nine validated CpGs formed the basis for a combined prognostic biomarker panel, which includes an 8-CpG Somatic Panel and the methylation status of cg23947872. This panel displayed strong predictive ability for 2-year survival, 2-year progression-free survival, and complete remission in the validation cohort. CONCLUSION: This study highlights DNA methylation profiling as a promising approach to enhance risk stratification in patients with CN-AML, potentially offering a pathway to more personalized treatment strategies.
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Biomarcadores Tumorais , Metilação de DNA , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Prognóstico , Biomarcadores Tumorais/genética , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Ilhas de CpG , Idoso de 80 Anos ou mais , Adulto JovemRESUMO
Cancer patients often undergo rounds of trial-and-error to find the most effective treatment because there is no test in the clinical practice for predicting therapy response. Here, we conduct a clinical study to validate the zebrafish patient-derived xenograft model (zAvatar) as a fast predictive platform for personalized treatment in colorectal cancer. zAvatars are generated with patient tumor cells, treated exactly with the same therapy as their corresponding patient and analyzed at single-cell resolution. By individually comparing the clinical responses of 55 patients with their zAvatar-test, we develop a decision tree model integrating tumor stage, zAvatar-apoptosis, and zAvatar-metastatic potential. This model accurately forecasts patient progression with 91% accuracy. Importantly, patients with a sensitive zAvatar-test exhibit longer progression-free survival compared to those with a resistant test. We propose the zAvatar-test as a rapid approach to guide clinical decisions, optimizing treatment options and improving the survival of cancer patients.
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Neoplasias Colorretais , Peixe-Zebra , Animais , Feminino , Humanos , Masculino , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Medicina de Precisão/métodos , Intervalo Livre de Progressão , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
(1) Background: Relapsed HGSOC with ascites and/or pleural effusion is a poor-prognostic population and poorly represented in clinical studies. We questioned if these patients are worth treating. In other words, if these patients received the most effective treatment, would it change the course of this disease? To our knowledge this is the first real-life study to evaluate this question in this low-survival population. (2) Methods: To tackle this question we performed a retrospective, multi-centric, real-life study, that reviewed relapsed HGSOC patients with ascites and/or pleural effusion. Our rationale was to compare the OS of two groups of patients: responders, i.e., patients who had an imagological response to treatment (complete/partial response/stable disease, RECIST criteria) versus non-responders (no response/progression upon treatment). We evaluated the predictive value of clinical variables that are available in a real-life setting (e.g., staging, chemotherapy, surgery, platinum-sensitivity). Multivariate logistic regression and survival analysis was conducted. A two-step cluster analysis SPSS tool was used for subgroup analysis. Platinum sensitivity/resistance was also analyzed, as well as multivariate and cluster analysis. (3) Results: We included 57 patients, 41.4% first line responders and 59.6% non-responders. The median OS of responders was 23 months versus 8 months in non-responders (p < 0.001). This difference was verified in platinum-sensitive (mOS 28 months vs. 8 months, p < 0.001) and platinum-resistant populations (mOS 16 months vs. 7 months, p < 0.001). Thirty-one patients reached the second line, of which only 10.3% responded to treatment. Three patients out of thirty-one who did not respond in the first line of relapse, responded in the second line. In the second line, the mOS for the responders' group vs. non-responders was 31 months versus 13 months (p = 0.02). The two step cluster analysis tool found two different subgroups with different prognoses based on overall response rate, according to consolidation chemotherapy, neoadjuvant chemotherapy, FIGO staging and surgical treatment. Cluster analysis showed that even patients with standard clinical and treatment variables associated with poor prognosis might achieve treatment response (the opposite being also true). (4) Conclusions: Our data clearly show that relapsed HGSOC patients benefit from treatment. If given an effective treatment upfront, this can lead to a ~3 times increase in mOS for these patients. Moreover, this was irrespective of patient disease and treatment characteristics. Our results highlight the urgent need for a sensitivity test to tailor treatments and improve efficacy rates in a personalized manner.