👤 Fillipe Dantas Pinheiro

Prior evidence indicate that differences in treatment settings between patients with colorectal cancer (CRC) from high-poverty areas (HPA, ≥ 20% residents living under poverty level) and low-poverty areas (LPA) might have contributed to disparities in their health outcomes. We sought to determine whether certain hospitals predominantly provided surgical care for patients with CRC from HPAs and examine associated patient outcomes. We identified patients undergoing surgery for nonmetastatic CRC diagnosed during 1/1/2009-12/31/2019 from SEER-Medicare. We defined poverty-area-serving (PAS) hospitals as hospitals with ≥ 50% patients from HPAs. We compared in-hospital adverse events, 30 day readmission, and long-term mortality between patients from HPAs and LPAs treated at PAS and non-PAS hospitals using logistic and Cox regression. Our cohort included 81,992 patients with CRC (median age = 78 years, 53.8% female, 15.9% in HPAs) treated by 991 hospitals. The 180 (18.2%) PAS hospitals treated 64.2% of patients from HPAs versus 2.6% from LPAs. Compared with patients from LPAs treated at non-PAS hospitals, patients from HPAs treated at PAS hospitals had more frequent in-hospital adverse events (OR[95%CI] = 1.17[1.07-1.29]), 30-day readmission (OR[95%CI] = 1.33[1.20-1.47]), worse all-cause (HR[95%CI] = 1.16[1.10-1.22]), and cancer-specific mortality (HR[95%CI] = 1.23[1.15-1.32]). A group of PAS hospitals treated a significant proportion of patients with CRC from HPAs and few from LPAs and was associated with worse short- and long-term patient outcomes. These findings highlight the presence and negative impact of healthcare segregation by area-level poverty and systemic inequities faced by individuals from HPAs. Multilevel resources are needed to address quality of care and other healthcare-associated needs for individuals from disadvantaged areas. Show less

Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere-related genes, with MYBPC3 being the most common. Documenting potential genotype-phenotype associations may allow for more personalized genetic counselling. Observational case-control, cohort, and cross-sectional studies reporting genotype-phenotype associations and the occurrence of predefined events were selected from Cochrane and Medline databases. A random- effects meta-analysis was conducted. Twenty-four studies were included, with 3869 patients enrolled. The mean age at diagnosis of HCM associated with mutations in the MYBPC3 gene was 39.8 years (95 % CI 32.96 to 46.55), and the mean maximum left ventricular thickness was 20.4 mm (95 % CI 19.72 to 21.06). Proportion rates were 12.6 % (95 % CI 5.7 to 21.5 %) for septal reduction therapy, 20.4 % (95 % CI 11.9 to 30.2 %) for the development of heart failure New York Heart Association (NYHA) III/IV functional class, 16.1 % (95 % CI 10.3 to 22.6 %) for the occurrence of atrial fibrillation, and 26 % (95 % CI 17.0 to 36.1 %) for ventricular tachycardia. Cardioverter-defibrillators were implanted in 31.4 % (95 % CI 18.6 to 45.6 %) for secondary prevention, and sudden cardiac arrest occurred in 14.7 % (95 % CI 7.8 to 23.0 %) of patients. Cardiovascular death occurred in 8.6 % of patients over a median of 73 months of follow-up. This is the largest meta-analysis of MYBPC3 HCM patients to date. We were able to obtain data on the proportion rates of events in this population, which allows to answer some questions about the clinical course of HCM disease associated with mutations in the MYBPC3 gene more clearly. We found not only a late disease onset and low mortality risk, but importantly, a non-negligible risk of developing severe heart failure throughout life. Show less

Branched-chain amino acid (BCAA) metabolism is perturbed in patients with pancreatic cancer, but the contribution of systemic or pancreas-intrinsic BCAA catabolism to pancreatic carcinogenesis is unclear. We show here that pancreas-specific loss of DBT, the E2 subunit of the branched-chain keto-acid dehydrogenase (BCKDH) complex required for BCAA oxidation, strikingly exacerbates premalignant pancreatic intraepithelial neoplasia (PanIN) lesions in KC ( Show less

Understanding the immunopathogenesis of COVID-19 has yielded valuable insights into predicting adverse outcomes-particularly mortality. However, significant gaps persist in our comprehension of the complex interplay among the proposed pathophysiological mechanisms. Here, we aim to investigate the immunological factors associated with mortality in critically ill, unvaccinated COVID-19 patients admitted to the intensive care unit (ICU). We conducted a single-center, prospective study involving 56 unvaccinated COVID-19 patients admitted to the ICU. Plasma cytokine levels at admission were quantified using enzyme-linked immunosorbent assay (ELISA). Continuous variables were presented as median (IQR), and categorical variables as frequencies and percentages. Non-parametric tests assessed group differences. Logistic regression and receiver operating characteristic (ROC) curve analyses identified predictors of mortality, with bootstrapping (1000 re-samplings; 95 % BCa CI) applied for model validation. Deceased patients exhibited significantly higher levels of interleukin (IL)-1β, IL-2, IL-6, transforming growth factor (TGF)-β, and interferon (IFN)-γ compared to survivors. Conversely, IL-10 and IL-27 were associated with favorable outcomes. Logistic regression modeling identified elevated IL-2 and IFN-γ levels as significant predictors of mortality. Notably, individual ROC curve analyses demonstrated that IL-1β and TGF-β had excellent discriminatory ability for mortality, while IFN-γ, IL-2, and IL-27 showed very good to excellent discriminatory capacity. Our results indicate that distinct cytokine profiles differentiate survivors from non-survivors in critically ill, unvaccinated COVID-19 patients. These findings highlight the importance of cytokine dysregulation in severe COVID-19 cases and suggest potential targets for prognostic approaches. Further research is warranted to validate these results and translate them into effective clinical management strategies. Show less

Metabolic syndrome (MS) is a condition that, when associated with ischemic heart disease and cardiovascular events, can be influenced by genetic variants and determine more severe coronary atherosclerosis. To examine the contribution of genetic polymorphisms to the extension and severity of coronary disease in subjects with MS and recent acute coronary syndrome (ACS). Patients (n = 116, 68% males) aged 56 (9) years, with criteria for MS, were prospectively enrolled to the study during the hospitalization period after an ACS. Clinical and laboratory parameters, high-sensitivity C-reactive protein, thiobarbituric acid reactive substances, adiponectin, endothelial function, and the Gensini score were assessed. Polymorphisms of paraoxonase-1 (PON-1), methylenotetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (ENOS), angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT1R), apolipoprotein C3 (APOC3), lipoprotein lipase (LPL) were analysed by polymerase chain reaction (PCR) technique, followed by the identification of restriction fragment length polymorphisms (RFLP, and a genetic score was calculated. Parametric and non-parametric tests were used, as appropriate. Significance was set at p < 0.05. Polymorphisms of PON-1, MTHFR and ENOS were not in the Hardy-Weinberg equilibrium. The DD genotype of LPL was associated with higher severity and greater extension of coronary lesions. Genetic score tended to be higher in patients with Gensini score < P50 (13.7 ± 1.5 vs. 13.0 ± 1.6, p = 0.066), with an inverse correlation between genetic and Gensini scores (R = -0.194, p = 0.078). The LPL polymorphism contributed to the severity of coronary disease in patients with MS and recent ACS. Combined polymorphisms were associated with the extension of coronary disease, and the lower the genetic score the more severe the disease. Show less

GITR is a T-cell costimulatory receptor that enhances cellular and humoral immunity. The agonist anti-mouse GITR antibody DTA-1 has demonstrated efficacy in murine models of cancer primarily by attenuation of T Show less

This study evaluated the impact of 9 single nucleotide polymorphisms (SNPs) in 6 candidate genes (APOB, APOA5, APOE, APOC3, SCAP, and LDLR) over dyslipidemia in HIV-infected patients on stable antiretroviral therapy (ART) with undetectable viral loads. Blood samples were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas, and Rio Grande in Brazil. The SNPs were genotyped by conventional polymerase chain reaction (PCR) and real-time PCR. The prevalence of dyslipidemia was particularly high among the protease inhibitors-treated patients (79%). APOE (rs429358 and rs7412) genotypes and APOA5 -1131T>C (rs662799) were associated with plasma triglycerides (TG) and low-density-lipoprotein cholesterol levels (LDL-C). The APOA5 -1131T>C (rs662799) and SCAP 2386A>G (rs12487736) polymorphisms were significantly associated with high-density-lipoprotein cholesterol levels. The mean values of the total cholesterol and LDL-C levels were associated with both the APOB SP Ins/Del (rs17240441) and APOB XbaI (rs693) polymorphisms. In conclusion, our data support the importance of genetic factors in the determination of lipid levels in HIV-infected individuals. Due to the relatively high number of carriers of these risk variants, studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen. Show less

Type 2 diabetes mellitus is a metabolic, vascular, and neuropathic disease with a high risk of atherosclerotic events due to dyslipidemic states. Polymorphisms in Apolipoprotein A5 gene (APOA5) have been associated with increased triglyceride levels in many different populations. This study aimed to identify the frequencies of the APOA5 -1131T>C and SW19 polymorphisms and evaluate their effects on lipid levels in patients with type 2 diabetes. Genotyping of APOA5 -1131T>C and SW19 polymorphisms was performed by PCR-RFLP in 146 diabetic patients and in controls (n = 173), from 30 to 80 years of age. Diabetic patients were divided into two groups: patients not treated with lipid lowering drugs (group G1; n = 62) and those treated with lipid lowering drugs (group G2, n = 84). Lipids and lipoproteins were determined enzymatically. Among participants not treated with lipid-lowering drugs (diabetics G1 and controls; n = 235), the -1131C was associated with lower LDLc levels (p = 0.015). In the diabetic patients, the 19W allele was associated with higher triglyceride levels (p = 0.004). In G1 diabetic patients, the combined analysis of APOA5 -1131T>C and SW19 polymorphisms showed that [TC or CC] + SS carriers presented lower total cholesterol levels than did other genotype combinations (p = 0.049). It could therefore be concluded that APOA5 -1131T>C and SW19 polymorphisms influence lipid levels in type 2 diabetic patients. Show less