Marcos Ferreira Minicucci

Septic cardiomyopathy is recognized as an acute, transient, and reversible condition. However, septic insult may induce latent changes characteristic of cardiac remodeling, with future consequences. Therefore, the present study aimed to evaluate the morphological and functional cardiac changes in the acute and subacute phases (with 7-day follow-up) in male Wistar rats subjected to experimental sepsis using a cecal ligation and puncture (CLP) model. In the acute phase, the animals underwent echocardiographic assessment at baseline and 48 h after the induction of sepsis. In the subacute 7 days follow-up, animals were allocated in control and sepsis groups. After this period, the animals underwent echocardiographic assessment, followed by euthanasia, papillary muscle testing, and subsequent morphometric and biochemical analyses. Fecal samples from six animals per group were collected at baseline and after 7 days for microbiota analysis. In the acute phase, echocardiographic assessment revealed that, following sepsis, animals exhibited reduced systolic function. In the subacute 7 days follow-up, both echocardiogram and papillary muscles revealed cardiac dysfunction in the sepsis group. Cardiomyocyte cross-sectional area and collagen content were significantly greater in the sepsis group compared with that in the control group. Analysis of maximal enzymatic activities involved in cardiac energy metabolism and oxidative stress biomarkers revealed no significant differences between groups. Considering microbiota assessment, beta diversity analysis revealed significant differences between septic animals and controls. In conclusion, sepsis was associated with persistent systolic/diastolic dysfunction, cardiomyocyte hypertrophy, and fibrosis after 7 days. These data suggest that septic cardiomyopathy should not be considered merely an acute, transient, and reversible condition in this experimental context.

Doxorubicin is an effective chemotherapeutic agent, but it causes gastrointestinal toxicity that impairs treatment efficacy and quality of life. This study investigated the effects of liraglutide, a GLP-1 analog, on acute doxorubicin-induced gut toxicity in rats. Sixty male Wistar rats were assigned to four groups: Control (C), Doxorubicin (D), Liraglutide (L), and Doxorubicin + Liraglutide (DL). Groups L and DL received liraglutide (0.6 mg/kg, s.c.) for two weeks. D and DL were given a single dose of doxorubicin (20 mg/kg, i.p). After 48 h, the distal colon, feces, and blood were collected. Results: Doxorubicin caused crypt disruption, goblet cell loss, apoptosis, and reduced fecal short-chain fatty acids. Levels of TNF-α, NF-κB, Bcl-2, TLR4, and antioxidant enzymes were unchanged among groups. Microbiota analysis showed similar α-diversity but altered β-diversity. Doxorubicin reduced Bacteroidetes and increased Proteobacteria, with higher Arcanobacterium and Clavibacter genera abundance. Liraglutide alone decreased Bacteroidetes and increased Corynebacterium and Actinobaculum genera. Combined treatment showed no significant effects. We conclude that acute doxorubicin administration induces intestinal structural damage, reduces short-chain fatty acids, and changes microbiota composition. Although liraglutide alters microbial profiles, it does not attenuate doxorubicin-induced gut toxicity.

Resumo Introdução: A investigação de microRNAs (miRNAs) circulantes e da resposta inflamatória associada aos diferentes estágios da DRC pode revelar biomarcadores da patogênese da doença. Nosso objetivo foi identificar diferenças na expressão de miRNAs circulantes entre pacientes em diálise peritoneal (DP) e não dialíticos (ND), determinando redes regulatórias da interação miRNA-gene-alvo e vias potencialmente envolvidas na patogênese da doença. Métodos: Estudo transversal exploratório incluindo pacientes ND e em DP com DRC estágio 5 e idade superior a 18 anos. Avaliaram-se biomarcadores inflamatórios e perfis de expressão de miRNA circulantes. Resultados: Foram incluídos 20 pacientes (57,2 ± 11,8 anos). Níveis de proteína C-reativa de alta sensibilidade [0,37 (0,07–1,40) vs. 3,90 (2,50–5,79); p = 0,038] e interleucina-6 [3,35 ± 3,08 vs. 6,82 ± 4,08; p = 0,046] foram significativamente menores no grupo ND comparados ao grupo DP, respectivamente. Nove miRNAs apresentaram desregulação significativa (fold change (FC) ≥ 2 e p ≤ 0,05) no grupo DP comparado ao grupo ND. Análises computacionais revelaram grande número de genes-alvo comumente regulados por pelo menos dois dos miRNAs identificados. A análise de enriquecimento de vias demonstrou que sinalização por receptor acoplado à proteína G (GPCR), secreção/resistência à insulina e metabolismo energético estiveram entre as vias significativas reguladas pelos genes-alvo do miRNA. Conclusões: Pacientes em tratamento com DP apresentaram níveis circulantes desregulados dos 9 miRNAs identificados e biomarcadores inflamatórios séricos mais elevados, comparados aos pacientes ND. Genes regulados pelos miRNAs associam-se principalmente à sinalização por GPCR, resistência à insulina e metabolismo energético, desempenhando papéis na fibrose e funções associadas à inflamação.

Introduction: The investigation of circulating microRNAs (miRNAs) and inflammatory response associated with the different stages of chronic kidney disease (CKD) may reveal biomarkers of disease pathogenesis. Our goal was to identifying differences in the circulating miRNAs expression between peritoneal dialysis (PD) and non-dialytic (ND) patients and determine the regulatory miRNA-target gene networks and pathways potentially involved in disease pathogenesis. Methods: This was an exploratory cross-sectional study that included ND and PD patients with CKD stage 5 over 18 years of age. Inflammatory biomarkers and circulating miRNA expression profiles were evaluated. Results: The study included 20 patients (57.2 ± 11.8 years). Levels of high-sensitivity C-reactive protein [0.37 (0.07–1.40) vs. 3.90 (2.50–5.79), p = 0.038] and interleukin-6 [3.35 ± 3.08 vs. 6.82 ± 4.08, p = 0.046] were significantly lower in the ND group in comparison to the PD group, respectively. Nine miRNAs were significantly deregulated (fold change (FC) ≥ 2 and p ≤ 0.05) in the PD compared to the ND group. Computational analyses showed a large number of target genes commonly regulated by at least two of the identified miRNAs. Pathway enrichment analysis showed that G protein-coupled receptor (GPCR) signaling, insulin secretion/resistance, and energy metabolism were among significant pathways regulated by miRNA target genes. Conclusions: Patients on PD treatment showed deregulated circulating levels of the 9 identified miRNAs and higher serum inflammatory biomarkers, compared to ND patients. Genes regulated by miRNAs are mainly associated with GPCR signaling, insulin resistance, and energy metabolism, playing roles in fibrosis and inflammatory-associated functions.

Background: Obesity-associated inflammation arises from adipose dysfunction and intestinal disturbances, including altered microbiota and short-chain fatty acid (SCFA) metabolism. Beans (Phaseolus vulgaris) are rich in non-digestible carbohydrates and polyphenols, but whether kidney bean varieties differing in seed coat colour exert distinct effects on inflammation in obesity remains unclear. Objective: To determine whether supplementation of an obesogenic high-fat (HF) diet with white or dark red kidney beans modulates gut microbiota, SCFAs, and intestinal, systemic, and neuroinflammatory outcomes. Methods: Male C57Bl/6N mice (n = 12/group) were fed a basal diet (BD; modified AIN-93G), an HF diet (60% kcal from fat), or an HF diet supplemented with 15% cooked white (HF + WK) or dark red kidney beans (HF + DK) for nine weeks. Outcomes included cecal microbiota composition, predicted KEGG pathways with taxon contributors mapped with BURRITO (a tool for linking predicted microbial functions to contributing taxa), and SCFA-related pathways; cecal and fecal SCFA concentrations; colon histomorphometry and expression of gut barrier junction and inflammatory genes; serum cytokines and adipose hormones; and hippocampal inflammatory and barrier genes. Results: Mice consuming bean-supplemented HF diets had higher microbial diversity, enrichment of SCFA-producing taxa (Prevotella, Lactobacillus, Muribaculaceae), and lower obesity-associated genera versus HF alone (Mucispirillum, rc4-4). Bean diets elevated cecal acetate and butyrate concentrations, which aligned with increases in predicted acetate kinase in both bean groups versus HF and BD, and butyrate kinase in HF + DK versus BD. Bean supplementation attenuated HF-induced reduction of goblet cells and systemic interleukin (IL)-10. The HF + DK group had lower colonic tumour necrosis factor (TNF)-α and partially attenuated hippocampal IL-6. SCFAs were inversely associated with systemic and neuroinflammatory markers in HF + DK mice. Conclusions: Kidney bean supplementation mitigated HF diet-induced intestinal, systemic, and neuroinflammatory disturbances in male mice, with microbiota and SCFA modulation. Further, dark red beans exerted stronger anti-inflammatory effects, highlighting the role of seed coat colour in bean-mediated obesity outcomes.

SUMMARY OBJECTIVE: The aim of this study was to compare the return of spontaneous circulation and survival to discharge of patients who experienced in-hospital cardiac arrest assisted by a rapid response team during the day versus night and weekdays versus weekends. METHODS: This retrospective observational study was conducted at a tertiary teaching hospital. Patients aged 18 years or older who experienced a cardiac arrest in the wards between March 2018 and December 2021 were included. Patients with an express order of “natural death permission” were excluded. Data regarding the period of in-hospital cardiac arrest occurrence, return of spontaneous circulation, and survival to discharge were collected from medical records. In addition, data related to nursing staff leave were collected. RESULTS: A total of 387 patients were included in the analysis. The mean age was 65.4±14.8 years, and 53.7% were men. In the multivariate logistic regression, in-hospital cardiac arrest during the day versus night was not associated with return of spontaneous circulation. However, in-hospital cardiac arrest during weekdays versus weekends showed a significant association with return of spontaneous circulation (odds ratio=2.073; 95%CI 1.206–3.564; p=0.008). No differences were found in survival to discharge between daytime versus nighttime or weekdays versus weekends. CONCLUSION: There is no difference in return of spontaneous circulation rates between in-hospital cardiac arrest events occurring during the day versus night. However, a significant difference in return of spontaneous circulation rates was observed between weekdays and weekends, although this difference did not extend to in-hospital survival rates.

Introduction: Hip fracture is an important cause of hospitalization, with high morbidity and mortality. Evidence suggests that vegetarians and vegans have lower bone mineral density, and plant-based diets are gaining popularity. However, the impact of these diets on the occurrence of hip fracture risk remains unclear. Objective: This systematic review aimed to assess the impact of vegetarian and vegan diets on the risk of hip fracture in adults. Methods: We conducted a systematic review of studies comparing vegetarians and vegans with meat-eaters. We searched Medline, EMBASE, LILACS, CINAHL, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL). Two reviewers independently and in duplicate performed study selection, risk-of-bias assessment, and data extraction. Hazard ratios (HRs) with 95% CIs were calculated as an estimate of the effect of vegetarian and vegan diets. The quality of evidence was determined according to the Grading of Recommendations Assessment, Development, and Evaluation. Results: Four cohort studies with 529 672 participants were included. Both vegetarian and vegan diets were associated with a higher risk of hip fracture after adjusting for confounders. Vegetarians had a 25% higher risk than meat-eaters (HR, 1.25; 95% CI, 1.11–1.39; 38 433 vegetarians; I2 = 0%; low certainty of evidence). Vegans had a 75% higher risk (HR, 1.75; 95% CI, 1.17–2.63; 5344 vegans; I2 =64%; very low certainty of evidence). Conclusion: These findings emphasize the importance of incorporating dietary patterns into strategies for promoting bone health, especially among individuals following plant-based diets. Healthcare providers should offer guidance to individuals adopting vegetarian or vegan diets to ensure adequate nutrient intake and support bone health. Systematic Review Registration: PROSPERO no. CRD 42024592448.

Background: Pain detection and management in older people with impaired cognition is an unmet need, leading to healthcare inequalities. This study aimed to enhance pain detection by translating and culturally adapting the PAIC-15 questionnaire into Brazilian Portuguese, establishing its content validity and comparing findings with a similar Dutch study. Methods: Following the same international standards used in the English-to-Dutch validation, we translated and culturally adapted PAIC-15 for Brazil. Content validity was assessed using two questions: (A) whether the item indicated pain and (B) whether it was specific to pain. An online form was distributed to ‘target users’ (nurses and geriatricians in LTCFs or other settings) and other healthcare professionals (HCPs) experienced in pain assessment in people with cognitive decline. Results were compared with the English-to-Dutch validation. Results: A total of 103 HCPs responded (mean age 45.2 ± 11.4 years)—76 (74%) were female and 54 (52%) had previously used pain assessment tools. Among the 63 target users, 13 items (87%) were validated as indicative and/or specific to pain. Comparing Brazilian and Dutch users, 10 items (67%) showed agreement on pain specificity. Conclusions: The Brazilian Portuguese PAIC-15 is now available, showing acceptable content validity. Linguistic challenges highlight the need for training and further validation in larger samples.

Background: Patients with acute heart failure exhibit high rates of early rehospitalization accompanied by significant mortality. Therefore, identifying high-risk patients who are prone to disease exacerbation may enable early therapeutic interventions for improved disease management. Methods: This single-center, prospective observational study was conducted at a Brazilian hospital. Adult patients hospitalized for acute heart failure were enrolled. On the day of hospital discharge, NT-pro-BNP and body weight data were collected, and bedside lung and inferior vena cava ultrasound examinations were performed. The patients were followed up for up to 30 days after discharge. The primary outcome was rehospitalization for acute heart failure. Results: A total of 100 patients were included in the final analysis, of whom 10% were readmitted within 30 days owing to acute heart failure. The number of patients with total B-line scores >3 in the readmitted and non-readmitted groups was 6 and 19, respectively (60% and 21%, respectively; absolute risk difference: 39%; p = 0.014). The mean inferior vena cava collapsibility index was significantly lower in readmitted compared to that in non-readmitted patients (25.5% vs. 39.8%, standard deviation: 15.4% and 18.4%, respectively; p = 0.020). However, mean body weight and mean NT-pro-BNP levels at discharge did not differ between the groups. In a multivariate logistic regression model adjusted for sex, age, discharge body weight, and left ventricular ejection fraction, a total B-lines score >3 had an odds ratio of 4.72 (95% confidence interval (CI): 1.01–22.13; p = 0.049), while the inferior vena cava collapsibility index had an odds ratio of 0.96 (95% CI: 0.91–1.01; p = 0.091). Conclusions: A total B-line score >3 at discharge in patients hospitalized for acute heart failure was associated with 30-day rehospitalization. In contrast, inferior vena cava ultrasound, discharge body weight, and NT-pro-BNP at discharge were not significant predictors of rehospitalization.