Methylene blue in sepsis and septic shock: a systematic review and meta-analysis.

Background: Methylene blue is an interesting approach in reducing fluid overload and vasoactive drug administration in vasodilatory shock. The inhibition of guanylate cyclase induced by methylene blue infusion reduces nitric oxide production and improves vasoconstriction. This systematic review and meta-analysis aimed to assess the effects of methylene blue administration compared to placebo on the hemodynamic status and clinical outcomes in patients with sepsis and septic shock. Methods: The authors specifically included randomized controlled trials that compared the use of methylene blue with placebo in adult patients with sepsis and septic shock. The outcomes were length of intensive care unit stay, hemodynamic parameters [vasopressor use], and days on mechanical ventilation. We also evaluated the abnormal levels of methemoglobinemia. This systematic review and meta-analysis were recorded in PROSPERO with the ID CRD42023423470. Results: During the initial search, a total of 1,014 records were identified, out of which 393 were duplicates. Fourteen citations were selected for detailed reading, and three were selected for inclusion. The studies enrolled 141 patients, with 70 of them in the methylene blue group and 71 of them in the control group. Methylene blue treatment was associated with a lower length of intensive care unit stay (MD -1.58; 95%CI -2.97, -0.20; I2 = 25%; p = 0.03), decreased days on mechanical ventilation (MD -0.72; 95%CI -1.26, -0.17; I2 = 0%; p = 0.010), and a shorter time to vasopressor discontinuation (MD -31.49; 95%CI -46.02, -16.96; I2 = 0%; p < 0.0001). No association was found with methemoglobinemia. Conclusion: Administering methylene blue to patients with sepsis and septic shock leads to reduced time to vasopressor discontinuation, length of intensive care unit stay, and days on mechanical ventilation. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023423470, CRD42023423470.

Body fat predicts urinary tract infection in kidney transplant recipients: a prospective cohort study.

BACKGROUND: The association between obesity and infectious diseases is increasingly reported in the literature. There are scarce studies on the association between obesity and urinary tract infection after kidney transplantation (KTx). These studies defined obesity based on body mass index, and their results were conflicting. The present study aimed to evaluate this association using bioelectrical impedance analysis for body composition evaluation, and obesity definition. METHODS: A single-center cohort study was conducted. Demographic, clinical, anthropometric, and laboratory data were collected at KTx admission, and bioelectrical impedance analysis was performed to measure the visceral fat area, waist circumference, and total fat mass. The occurrence of urinary tract infection (symptomatic bacteriuria and/or histological evidence of pyelonephritis) was evaluated within three months after KTx. RESULTS: Seventy-seven patients were included in the cohort, and 67 were included in the final analysis. Urinary tract infection was diagnosed in 23.9% of the transplanted patients. Waist circumference (HR: 1.053; 95% CI 1.005-1.104; p = 0.032), visceral fat area (HR: 1.015; 95% CI 1.003-1.027; p = 0.014), and total fat mass (HR: 1.075; 95% CI 1.008-1.146; p = 0.028) were associated with urinary tract infection occurrence after KTx, using Cox regression models. Patients with high waist circumference (above 102 cm for men and above 88 cm for women) had a 4.7 times higher risk of a urinary tract infection than those with normal waist circumference (HR: 4.726; 95% CI 1.267-17.630; p = 0.021). Kaplan-Meier curves showed that patients with high waist circumference, high visceral fat area, and high total fat mass had more urinary tract infections (Log-rank test p = 0.014, p = 0.020, and p = 0.018, respectively). Body mass index was not able to predict urinary tract infection in the study sample. CONCLUSIONS: Waist circumference, visceral fat area, and total fat mass, assessed by bioelectrical impedance analysis, were predictors of urinary tract infection risk within the first three months after KTx.

Serum urea increase during hospital stay is associated with worse outcomes after in-hospital cardiac arrest.

BACKGROUND: Evaluate the association between serum urea at admission and during hospital stay with return of spontaneous circulation (ROSC) and in-hospital mortality in patients with in-hospital cardiac arrest (IHCA). METHODS: This retrospective study included patients over 18 years with IHCA attended from May 2018 to December 2022. The exclusion criteria were the absence of exams to calculate delta urea and the express order of "do-not-resuscitate". Data were collected from the electronic medical records. Serum admission urea and urea 24 hours before IHCA were also collected and used to calculate delta urea. RESULTS: A total of 504 patients were evaluated; 125 patients were excluded due to the absence of variables to calculate delta urea and 5 due to "do-not-resuscitate" order. Thus, we included 374 patients in the analysis. The mean age was 65.0 ± 14.5 years, 48.9% were male, 45.5% had ROSC, and in-hospital mortality was 91.7%. In logistic regression models, ROSC was associated with lower urea levels 24 hours before IHCA (OR: 0.996; CI95%: 0.992-1.000; p: 0.032). In addition, increased levels of urea 24 hours before IHCA (OR: 1.020; CI95%: 1.008-1.033; p: 0.002) and of delta urea (OR: 1.001; CI95%: 1.001-1.019; p: 0.023) were associated with in-hospital mortality. ROC curve analysis showed that the area under the ROC curve for mortality prediction was higher for urea 24 hours before IHCA (Cutoff > 120.1 mg/dL) than for delta urea (Cutoff > 34.83 mg/dL). CONCLUSIONS: In conclusion, increased serum urea levels during hospital stay were associated with worse prognosis in IHCA.

FRAIL scale as a screening tool and a predictor of mortality in non-dialysis dependent patients.

BACKGROUND: This study aimed to compare the diagnostic yield of the FRAIL scale with respect to the physical frailty phenotype measure and their association with mortality in non-dialysis-dependent patients. METHODS: In this prospective cohort study, non-dialysis dependent patients with chronic kidney disease (CKD) stages 3b-5 seen in the nephrology outpatient clinics of two university hospitals were included. The presence of frailty was evaluated by physical frailty phenotype measure and the FRAIL scale. Patients were evaluated for six months, and mortality was recorded. The Kappa test was used to evaluate the diagnostic properties between the methods, and logistic regression to test the association between frailty and mortality. RESULTS: One hundred fifty-three patients were evaluated; average age was 65 (56-70) years, 50.9% were women, and the all-cause mortality rate was 2.6%. Forty-six patients were classified as living with frailty according to the physical frailty phenotype while 36 patients were rated frail by the FRAIL scale. In adults < 60 years of age, the FRAIL scale showed good accuracy (84.9%) and specificity (93.2%) but had low sensitivity (41.3%) and moderate agreement (Kappa = 0.41; p < 0.001) compared to the definition of the physical frailty phenotype. The adjusted logistic regression model showed that the patients with frailty assessed by the FRAIL scale had a greater chance of mortality than the non-frail patients (OR: 6.8; CI95%:1.477-31.513; p = 0.014). CONCLUSION: Physical frailty phenotype identifies more patients as having pre-frailty and frailty in non-dialysis dependent patients as compared to the FRAIL scale. However, the FRAIL scale is a simple bedside tool that can be useful for screening for frailty and whose results were associated with mortality.

Challenges in adapting a stroke unit in a middle-income country: warning about costs and underfunding to achieve the Brazilian Ministry of Health's benchmark.

Background: Since the implementation of the stroke care line in Brazil, the relationship (adequacy) of costs spent during hospitalization with the Brazilian Ministry of Health indicators for a stroke unit have not yet been analyzed. Aims: This study aimed to assess the adequacy of a comprehensive stroke center for key performance indicators and analyze the costs involved in hospitalization. We verified the association between stroke severity at admission and care costs during hospitalization. Methods: A retrospective medical chart review of 451 patients was performed using semiautomatic electronic data from a single comprehensive stroke center in Brazil between July 2018 and January 2020. Clinical and resource utilization data were collected, and the mean acute treatment cost per person was calculated. The Kruskal-Wallis test with Dunn's post-test was used to compare the total costs between stroke types and reperfusion therapies. A robust linear regression test was used to verify the association between stroke severity at hospital admission and the total hospitalization costs. Good adequacy rates were observed for several indicators. Results: Data from 451 patients were analyzed. The stroke unit had good adaptation to key performance indicators, but some critical points needed revision and improvement to adapt to the requirements of the Ministry of Health. The average total cost of the patient's stay was the USD 2,637.3, with the daily hospitalization, procedure, operating room, and materials/medication costs equating to USD 2,011.1, USD 220.7, USD 234.1, and USD 98.8, respectively. There was a positive association between the total cost and length of hospital stay (p < 0.001). Conclusion: The stroke unit complied with most of the main performance indicators proposed by the Brazilian Ministry of Health. Underfunding of the costs involved in the hospitalization of patients was verified, and high costs were associated with the length of stay, stroke severity, and mechanical thrombectomy.

Reduced mobility is associated with adverse outcomes after in-hospital cardiac arrest.

OBJECTIVE: In-hospital cardiac arrest is a critical medical emergency. Knowledge of prognostic factors could assist in cardiopulmonary resuscitation decision-making. Frailty and functional status are emerging risk factors and may play a role in prognostication. The objective was to evaluate the association between reduced mobility and in-hospital cardiac arrest outcomes. METHODS: This retrospective cohort study included patients over 18 years of age with in-hospital cardiac arrest in Botucatu, Brazil, from April 2018 to December 2021. Exclusion criteria were patients with a do-not-resuscitate order or patients with recurrent in-hospital cardiac arrest. Reduced mobility was defined as the need for a bed bath 48 h before in-hospital cardiac arrest. The outcomes of no return of spontaneous circulation and in-hospital mortality were evaluated. RESULTS: A total of 387 patients were included in the analysis. The mean age was 65.4±14.8 years; 53.7% were males and 75.4% had reduced mobility. Among the evaluated outcomes, the no return of spontaneous circulation rate was 57.1%, and in-hospital mortality was 94.3%. In multivariate analysis, reduced mobility was associated with no return of spontaneous circulation when adjusted by age, gender, initial shockable rhythm, duration of cardiopulmonary resuscitation, and epinephrine administration. However, in multiple logistic regression, there was no association between reduced mobility and in-hospital mortality. CONCLUSION: In patients with in-hospital cardiac arrest, reduced mobility is associated with no return of spontaneous circulation. However, there is no relation to in-hospital mortality.

Effect of a Physical Exercise Program on the Inflammatory Response, Cardiac Functions, Functional Capacity, and Quality of Life in Patients with Sickle Cell Disease.

INTRODUCTION: The beneficial effects of physical exercise on functional capacity and inflammatory response are well-known in cardiovascular diseases; however, studies on sickle cell disease (SCD) are limited. It was hypothesized that physical exercise may exert a favorable effect on the inflammatory response of SCD patients, contributing to an improved quality of life. This study aimed to evaluate the effect of a regular physical exercise program on the anti-inflammatory responses in SCD patients. METHODS: A non-randomized clinical trial was conducted in adult SCD patients. The patients were divided into two groups: 1-Exercise Group, which received a physical exercise program three times a week for 8 weeks, and; 2-Control Group, with routine physical activities. All patients underwent the following procedures initially and after eight weeks of protocol: clinical evaluation, physical evaluation, laboratory evaluation, quality of life evaluation, and echocardiographic evaluation. STATISTICAL ANALYSIS: Comparisons between groups were made using Student's t-test, Mann-Whitney test, chi-square test, or Fisher's exact test. Spearman's correlation coefficient was calculated. The significance level was set at p < 0.05. RESULTS: There was no significant difference in inflammatory response between the Control and Exercise Groups. The Exercise Group showed an improvement in peak VO2 values (p < 0.001), an increase in the distance walked (p < 0.001), an improvement in the limitation domain due to the physical aspects of the 36-Item Short Form Health Survey (SF-36) quality of life questionnaire (p = 0.022), and an increase in physical activity related to leisure (p < 0.001) and walking (p = 0.024) in the International Physical Activity Questionnaire (IPAQ). There was a negative correlation between IL-6 values and distance walked on the treadmill (correlation coefficient -0.444, p = 0.020) and the estimated peak VO2 values (correlation coefficient -0.480; p = 0.013) in SCD patients in both groups. CONCLUSIONS: The aerobic exercise program did not change the inflammatory response profile of SCD patients, nor did it show unfavorable effects on the parameters evaluated, and patients with lower functional capacity were those with the highest levels of IL-6.

Higher urea-to-albumin ratio is associated with mortality risk in critically ill COVID-19 patients.

BACKGROUND: This study aimed to evaluate the ability of the urea-to-albumin ratio (UAR) to predict mortality in critically ill coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study included adult patients admitted with COVID-19 at two intensive care units (ICUs) at the University Hospital. Serum urea and albumin concentrations at ICU admission were used to calculate the UAR. All patients were followed up during hospitalization, and the ICU mortality rate was recorded. RESULTS: Two hundred and eleven patients were evaluated. The mean age was 57.8 ± 15.5 years, and 54% were male. Approximately 84.4% of patients were considered to be at nutritional risk by the NRS 2002, and the median UAR was 18.3 (10.5-34.8). The length of stay in the ICU was 10 (6-16) days, 38.4% of the patients required dialysis, and 64.9% died. Age, male sex, need of hemodialysis, lactate level, and inflammatory parameters were associated with higher mortality. Patients non-survivors had a higher UAR (23.7 [13.6-41.8] vs. 10.9 [8.5-16.8]; p < 0.001). The cutoff point with the best performance of UAR in the ROC curve for predicting mortality was ≥12.17 (AUC: 0.7201; CI 95%: 0.656-0.784). Additionally, the risk of mortality was 2.00-fold in the group of patients with UAR ≥12.17 (HR: 2.00 CI: 1.274-3.149; p = 0.003) and remained significant after adjusted analyzes (models 1 and 2). CONCLUSION: Our data suggest that a UAR ≥12.17 increased the risk of mortality by 2.00-fold in critically ill COVID-19 patients.

Beans comsumption can contribute to the prevention of cardiovascular disease.

Cardiovascular diseases (CVD) are the major cause of global mortality, accounting for 31% of deaths worldwide. Healthy eating habits based on the consumption of bioactive molecules present in plant-based diets can contribute to the prevention of CVD. In this context, the consumption of common beans (Phaseolus vulgaris L.) is relevant. There are several species of beans, all of which provide proteins, carbohydrates, dietary fiber, vitamins, minerals, and phenolic compounds. More recently, the complexity of phytochemical components has expanded, including the role of antinutritional factors in nutrient bioavailability and immune responses. Experimental and clinical studies have shown that the consumption of beans results in less food consumption, control of body weight, and improvement of metabolic biochemical parameters. Thus, the consumption of beans is associated with a decrease in CVD risk factors. To date, there have been no interventional studies assessing CVD outcomes, such as hospitalization, infarction, and mortality, in the context of bean consumption. Furthermore, studies on the effect of bean consumption on metabolomics and intestinal microbiota are lacking. The purpose of this review is to explore the nutritional properties of beans and discuss the main effects of the consumption of beans on cardiovascular health. In conclusion, eating habits based on the consumption of bioactive molecules present in beans can contribute to the prevention of cardiovascular disease. Furthermore, there is a large gap in the literature regarding the consumption of beans associated with clinical outcomes, such as hospitalization and mortality.

Circulating miRNAs are associated with frailty and ST-elevation myocardial infarction pathways.

BACKGROUND: Frailty and ST-Elevation Myocardial Infarction (STEMI) share similar molecular pathways. Specific biomarkers, such as microRNAs (miRNAs), may provide insights into the molecular mechanisms that cause the relationship between frailty and STEMI. OBJECTIVE: Our aim was to identify and compare circulating miRNA levels between frail and non-frail older adults following STEMI and comprehend the regulatory miRNA-gene networks and pathways involved in this condition. METHODS: This exploratory study is a subanalysis of a larger observational study. In this study, we selected patients ≥ 65 years old, following STEMI, with pre-frail/frail (n=5) and non-frail (n=4) phenotype evaluated using the Clinical Frailty Scale and serum circulating miRNA levels were analyzed. RESULTS: Pre-frail/frail patients had greater serum levels of 53 miRNAs, compared with non-frail patients. Notably, miR-103a-3p, miR-598-3p, and miR-130a-3p were the top three significantly deregulated miRNAs predicted to modulate gene expression associated with aging. Additional computational analyses showed 7,420 predicted miRNA gene targets, which were regulated by at least two of the 53 identified miRNAs. Pathway enrichment analysis showed that axon guidance and MAPK signaling were among pathways regulated by miRNA target genes. CONCLUSIONS: These novel findings suggest a correlation between the identified miRNAs, target genes, and pathways in pre-frail and frail patients with myocardial infarction.

Comparison between FRAIL Scale and Clinical Frailty Scale in predicting hospitalization in hemodialysis patients.

BACKGROUND: To assess the prevalence of frailty by the Clinical Frailty Scale (CFS) and the 5-item FRAIL scale and their association with hospitalization in hemodialysis (HD) patients. METHODS: This was a prospective observational study. We included patients of both genders ≥ 18 years old in HD treatment for at least 3 months. Demographic, clinical, and routine laboratory data were retrieved from the medical charts. Two different frailty assessment tools were used, the CFS and the FRAIL scale. Participants were followed up for 9 months and hospitalizations for all causes were evaluated. A Venn diagram was constructed to show the overlap of possible frailty and pre-frailty. Cox regression was used to identify the association between frailty and hospitalization. The significance level was 5%. RESULTS: A total of 137 subjects were included in the analysis. The median age was 61 (52-67) years and 60% were male. The hospitalization rate and mortality in 9 months were 22.6% and 7.29%, respectively. Regarding frailty, the overall prevalence was 13.8% assessed by CFS and 36.5% according to the FRAIL scale. In the Cox regression, frailty by FRAIL scale was associated with a 2.8-fold increase in the risk of hospitalization (OR = 2.880; 95% CI = 1.361-6.096; p = 0.006), but frailty assessed by the CFS was not associated with the need for hospitalization. CONCLUSION: In HD patients, the FRAIL scale proved to be an easy-to-apply tool, identifying a high prevalence of frailty and being a predictor of hospital admission.

Serum myostatin levels are associated with physical function and hospitalization in peritoneal dialysis patients.

BACKGROUND: Myostatin functions as a negative regulator of skeletal muscle growth. The association of myostatin with muscle parameters in dialysis patients is inconsistent, and there are no studies associating myostatin with physical function and outcomes in peritoneal dialysis (PD) patients. Therefore, we assessed the association of serum myostatin with lean mass, physical function, and hospitalization in a prospective cohort of PD patients. METHODS: Lean mass, physical function, and serum myostatin were assessed at baseline. Patients were followed up for at least 24 months and hospitalization was recorded. RESULTS: Serum myostatin levels were positively correlated with handgrip strength and Appendicular Lean Mass Index among male patients. Binary logistic regression models were performed including myostatin levels and physical function parameters as independent variables. Serum myostatin, handgrip strength, gait speed, and Short Physical Performance Battery were associated with hospitalization. CONCLUSION: Lower serum myostatin and physical function were associated with hospitalization in PD patients.

Reduced mobility is associated with adverse outcomes after in-hospital cardiac arrest

SUMMARY OBJECTIVE: In-hospital cardiac arrest is a critical medical emergency. Knowledge of prognostic factors could assist in cardiopulmonary resuscitation decision-making. Frailty and functional status are emerging risk factors and may play a role in prognostication. The objective was to evaluate the association between reduced mobility and in-hospital cardiac arrest outcomes. METHODS: This retrospective cohort study included patients over 18 years of age with in-hospital cardiac arrest in Botucatu, Brazil, from April 2018 to December 2021. Exclusion criteria were patients with a do-not-resuscitate order or patients with recurrent in-hospital cardiac arrest. Reduced mobility was defined as the need for a bed bath 48 h before in-hospital cardiac arrest. The outcomes of no return of spontaneous circulation and in-hospital mortality were evaluated. RESULTS: A total of 387 patients were included in the analysis. The mean age was 65.4±14.8 years; 53.7% were males and 75.4% had reduced mobility. Among the evaluated outcomes, the no return of spontaneous circulation rate was 57.1%, and in-hospital mortality was 94.3%. In multivariate analysis, reduced mobility was associated with no return of spontaneous circulation when adjusted by age, gender, initial shockable rhythm, duration of cardiopulmonary resuscitation, and epinephrine administration. However, in multiple logistic regression, there was no association between reduced mobility and in-hospital mortality. CONCLUSION: In patients with in-hospital cardiac arrest, reduced mobility is associated with no return of spontaneous circulation. However, there is no relation to in-hospital mortality.

Oxidative Stress as a Therapeutic Target of Cardiac Remodeling.

Cardiac remodeling is defined as a group of molecular, cellular, and interstitial changes that clinically manifest as changes in the heart's size, mass, geometry, and function after different stimuli. It is important to emphasize that remodeling plays a pathophysiological role in the onset and progression of ventricular dysfunction and subsequent heart failure. Therefore, strategies to mitigate this process are critical. Different factors, including neurohormonal activation, can regulate the remodeling process and increase cell death, alterations in contractile and regulatory proteins, alterations in energy metabolism, changes in genomics, inflammation, changes in calcium transit, metalloproteases activation, fibrosis, alterations in matricellular proteins, and changes in left ventricular geometry, among other mechanisms. More recently, the role of reactive oxygen species and oxidative stress as modulators of remodeling has been gaining attention. Therefore, this review assesses the role of oxidative stress as a therapeutic target of cardiac remodeling.