Protective Effects of Omega-3 Supplementation against Doxorubicin-Induced Deleterious Effects on the Liver and Kidneys of Rats.

Anthracycline doxorubicin (DOX) is still widely used as a chemotherapeutic drug for some solid tumors. Although DOX is highly effective, its side effects are limiting factors, such as cardio, nephro and hepatotoxicity. As such, approaches used to mitigate these adverse effects are highly encouraged. Omega 3 (ω-3), which is a class of long-chain polyunsaturated fatty acids, has been shown to have anti-inflammatory and antioxidant effects in preclinical bioassays. Thus, we evaluated the protective effects of ω-3 supplementation on hepatotoxicity and nephrotoxicity induced by multiple DOX administrations in rodents. Male Wistar rats (10 rats/group) were treated daily with ω-3 (400 mg/kg/day) by gavage for six weeks. Two weeks after the first ω-3 administration, the rats received DOX (3.5 mg/kg, intraperitoneal, 1×/week) for four weeks. DOX treatment reduced body weight gain increased systemic genotoxicity and caused liver-related (increase in serum ALT levels, thickness of the Glisson's capsule, compensatory proliferation and p65 levels) and kidney-related (increase in serum urea and creatinine levels, and incidence of tubular dilatation) deleterious outcomes. In contrast, ω-3 supplementation was safe and abrogated the DOX-related enhancement of systemic genotoxicity, serum urea and creatinine levels. Furthermore, ω-3 intervention reduced by 50% the incidence of kidney histological lesions while reducing by 40-50% the p65 protein level, and the proliferative response in the liver induced by DOX. Our findings indicate that ω-3 intervention attenuated the DOX-induced deleterious effects in the liver and kidney. Therefore, our findings may inspire future mechanistical investigations and clinical interventions with ω-3 on the reported outcomes.

A Review of Current Clinical Concepts in the Pathophysiology, Etiology, Diagnosis, and Management of Hypercalcemia.

Calcium is the most abundant extracellular cation in the body, and it is responsible for structural and enzymatic functions. Calcium homeostasis is regulated by 3 factors: calcitonin, vitamin D, and parathyroid hormone (PTH). Hypercalcemia is defined by a serum calcium concentration >10.5 mg/dL, and it is classified into mild, moderate, and severe, depending on calcium values. Most cases are caused by primary hyperparathyroidism and malignancies. Various mechanisms are involved in the pathophysiology of hypercalcemia, such as excessive PTH production, production of parathyroid hormone-related protein (PTHrp), bone metastasis, extrarenal activation of vitamin D, and ectopic PTH secretion. The initial approach is similar in most cases, but a definitive treatment depends on etiology, that is why etiological investigation is mandatory in all cases. The majority of patients are asymptomatic and diagnosed during routine exams; only a small percentage of patients present with severe manifestations which can affect neurological, muscular, gastrointestinal, renal, and cardiovascular systems. Clinical manifestations are related to calcium levels, with higher values leading to more pronounced symptoms. Critically ill patients should receive treatment as soon as diagnosis is made. Initial treatment involves vigorous intravenous hydration and drugs to reduce bone resorption such as bisphosphonates and, more recently, denosumab, in refractory cases; also, corticosteroids and calcitonin can be used in specific cases. This review aims to provide a clinical update on current concepts of the pathophysiology of calcium homeostasis, epidemiology, screening, clinical presentation, diagnosis, and management of hypercalcemia.

Clinical trials in cardiac xenotransplantation: Are we ready to overcome barriers?

Heart allotransplantation has become one of the methods of choice in the treatment of severe heart failure. In the face of its difficulties, such as the unmet balance between organ supply and demand, the use of xenotransplantation (XTx) might be an attractive option shortly, even more with the ongoing progress achieved regarding the avoidance of hyperacute rejection and primary organ disfunction, maintenance of xenograft function and control of xenograft growth. To make possible this translational challenge, some points must be taken into account indeed, and they are the equipoise of human benefit and animal suffering, the risk of unknown infections, a well prepared informed consent, ethical and religious beliefs, and the role of cardiac XTx in a ventricular assistance device era.

Spondias mombin L. attenuates ventricular remodelling after myocardial infarction associated with oxidative stress and inflammatory modulation.

The objective of this study was to evaluate Spondias mombin L. (SM) pulp and its influence on cardiac remodelling after myocardial infarction (MI). Male Wistar rats were assigned to four groups: a sham group (animals underwent simulated surgery) that received standard chow (S; n = 20), an infarcted group that received standard chow (MI; n = 24), an infarcted group supplemented with 100 mg of SM/kg bodyweight/d, (MIS100; n = 23) and an infarcted group supplemented with 250 mg of SM/kg bodyweight/d (MIS250; n = 22). After 3 months of treatment, morphological, functional and biochemical analyses were performed. MI induced structural and functional changes in the left ventricle with worsening systolic and diastolic function, and SM supplementation at different doses did not influence these variables as analysed by echocardiography and an isolated heart study (P > .05). However, SM supplementation attenuated cardiac remodelling after MI, reducing fibrosis (P = .047) and hypertrophy (P = .006). Biomarkers of oxidative stress, inflammatory processes and energy metabolism were further investigated in the myocardial tissue. SM supplementation improved the efficiency of energy metabolism and decreased lipid hydroperoxide in the myocardium [group S (n = 8): 267.26 ± 20.7; group MI (n = 8): 330.14 ± 47.3; group MIS100 (n = 8): 313.8 ± 46.2; group MIS250: 294.3 ± 38.0 nmol/mg tissue; P = .032], as well as decreased the activation of the inflammatory pathway after MI. In conclusion, SM supplementation attenuated cardiac remodelling processes after MI. We also found that energy metabolism, oxidative stress and inflammation are associated with this effect. In addition, SM supplementation at the highest dose is more effective.

Euterpe oleracea Mart. (Açai) Supplementation Attenuates Acute Doxorubicin-Induced Cardiotoxicity in Rats.

BACKGROUND/AIMS: Doxorubicin, a chemotherapy drug used successfully for years, could induce cardiotoxicity. Euterpe oleracea Mart. (açai) is a fruit high in antioxidant properties. The aim of this study was to evaluate doxorubicin-induced cardiotoxicity prevention after açai administration. METHODS: A total of 64 male Wistar rats were allocated into 4 groups: control (C), açai (A), doxorubicin (D) and açai-doxorubicin (DA). Rats received regular chow (C and D groups) or chow supplemented with açai 5% (A and DA groups) for 4 weeks. Subsequently, rats received doxorubicin 20 mg/kg (D and DA groups) or saline (C and A groups). Euthanasia was performed 48 hours after doxorubicin injection. Left ventricular function was evaluated by echocardiography in vivo and by isolated heart study ex vivo. Oxidative stress, myocardial metabolism and nitric oxide metabolite were evaluated by spectrophotometry, MMP-2 activity by zymography and caspase-3 and Bcl-2 protein expression by Western blot. RESULTS: Doxorubicin induced decreases in body weight, food and water ingestion. We observed decreases in left ventricular fractional shortening in rats treated with doxorubicin. Additionally, the same rats showed lower +dP/dt and -dP/dt during isolated heart study than those who did not receive doxorubicin. Doxorubicin injection increased caspase-3 protein expression, myocardium lipid hydroperoxide concentration, MMP-2 activity, phosphofructokinase and lactate dehydrogenase activity, and decreased ß-hydroxyacyl-CoA dehydrogenase, pyruvate dehydrogenase, citrate synthase, complex I, complex II and ATP synthase activity in myocardium. Açai supplementation improved left ventricular fractional shortening, decreased myocardium lipid hydroperoxide concentration, MMP-2 activity, and improved ß-hydroxyacyl-CoA dehydrogenase, phosphofructokinase, citrate synthase, complex II and ATP synthase enzymatic activities. We did not observe differences in nitric oxide metabolite concentrations between groups. CONCLUSION: Doxorubicin induced left ventricular dysfunction, increases in oxidative stress, changes in myocardium metabolism and MMP-2 activation. Açai supplementation was able to prevent these alterations.

Protein Carbonyl, But Not Malondialdehyde, Is Associated With ICU Mortality in Patients With Septic Shock.

BACKGROUND: The objective of our study was to evaluate the association of serum malondialdehyde (MDA) and protein carbonyl concentration with intensive care unit (ICU) mortality in patients with septic shock. METHODS: We prospectively evaluated 175 patients aged over 18 years with septic shock upon ICU admission. However, 16 patients were excluded. Thus, 159 patients were enrolled in the study. In addition, we evaluated 16 control patients. At the time of the patients' enrollment, demographic information was recorded. Blood samples were taken within the first 24 hours of the patient's admission to determine serum MDA and protein carbonyl concentrations. RESULTS: The mean age was 67.3 ± 15.9 years, 44% were males, and the ICU mortality rate was 67.9%. Median MDA concentration was 1.53 (0.83-2.22) µmol/L, and median protein carbonyl concentration was 24.0 (12.7-32.8) nmol/mL. Patients who died during ICU stay had higher protein carbonyl concentration. However, there was no difference in MDA levels between these patients. Receiver operating characteristic curve analysis showed that higher levels of protein carbonyl were associated with ICU mortality (area under the curve: 0.955; 95% confidence interval [CI]: 0.918-0.992; P < .001) at the cutoff of >22.83 nmol/mL (sensibility: 80.4% and specificity: 98.1%). In the logistic regression models, protein carbonyl concentrations (odds ratio [OR]: 1.424; 95% CI: 1.268-1.600; P < .001), but not MDA concentrations (OR: 1.087; 95% CI: 0.805-1.467; P = .59), were associated with ICU mortality when adjusted for age, gender, and Acute Physiology and Chronic Health Evaluation (APACHE) II score; and when adjusted by APACHE II score, lactate, and urea; protein carbonyl concentrations (OR: 1.394; 95% CI: 1.242-1.564; P < .001); and MDA (OR: 1.054; 95% CI: 0.776-1.432; P = .73). CONCLUSION: In conclusion, protein carbonyl, but not MDA, concentration is associated with ICU mortality in patients with septic shock.

Peptidylarginine deiminase 4 concentration, but not PADI4 polymorphisms, is associated with ICU mortality in septic shock patients.

The objective of our study was to evaluate the association between peptidylarginine deiminase 4 (PAD4) concentration and its polymorphisms with mortality in patients with septic shock. We prospectively evaluated 175 patients aged over 18 years with septic shock upon intensive care unit (ICU) admission. However, 48 patients were excluded. Thus, 127 patients were enrolled in the study. At the time of the patients' enrollment, demographic information was recorded. Blood samples were taken within the first 24 hours of the patient's admission to determine serum PAD4 concentrations and its polymorphism PADI4_89 [rs11203366], PADI4_94 [rs2240340] and PADI4_104 [rs1748033]. The mean age was 63.3 ± 15.2 years, 56.7% were male, PAD4 concentration was 4.62 (2.48-6.20) ng/mL and the ICU mortality rate was 67.7%. The patients who died in the ICU had higher APACHE II and Sequential Organ Failure Assessment (SOFA) scores. In addition, PAD4 concentration was higher in patients who died during ICU stay. However, there were no differences regarding PADI4 polymorphisms and ICU mortality. In the logistic regression models, PAD4 concentrations were associated with ICU mortality when adjusted for APACHE II score and lactate (OR: 1.477; CI 95%: 1.186-1.839; P < .001), and when adjusted for age, gender and APACHE II score (OR: 1.392; CI 95%: 1.145-1.692; P < .001). In conclusion, PAD4 concentration, but not PADI4_89, PADI4_94 and PADI4_104 polymorphisms, is associated with ICU mortality in septic shock patients.

Spondias mombin supplementation attenuated cardiac remodelling process induced by tobacco smoke.

The objective of this study was to investigate the influence of Spondias mombin (SM) supplementation on the cardiac remodelling process induced by exposure to tobacco smoke (ETS) in rats. Male Wistar rats were divided into 4 groups: group C (control, n = 20) comprised animals not exposed to cigarette smoke and received standard chow; group ETS (n = 20) comprised animals exposed to cigarette smoke and received standard chow; group ETS100 (n = 20) received standard chow supplemented with 100 mg/kg body weight/d of SM; and group ETS250 (n = 20) received standard chow supplemented with 250 mg/kg body weight/d of SM. The observation period was 2 months. The ETS animals had higher values of left cardiac chamber diameters and of left ventricular mass index. SM supplementation attenuated these changes. In addition, the myocyte cross-sectional area (CSA) was lower in group C compared with the ETS groups; however, the ETS250 group had lower values of CSA compared with the ETS group. The ETS group also showed higher cardiac levels of lipid hydroperoxide (LH) compared with group C; and, groups ETS100 and ETS250 had lower concentrations of LH compared with the ETS group. Regarding energy metabolism, SM supplementation decreased glycolysis and increased the ß-oxidation and the oxidative phosphorylation. There were no differences in the expression of Nrf-2, SIRT-1, NF-κB, interferon-gamma and interleukin 10. In conclusion, our results suggest that ETS induced the cardiac remodelling process. In addition, SM supplementation attenuated this process, along with oxidative stress reduction and energy metabolism modulation.

Adductor Pollicis Muscle Thickness and Obesity Are Associated with Poor Outcome after Stroke: A Cohort Study.

BACKGROUND: Nutritional status may influence outcome after stroke. It is possible that some obese individuals present reduced fat-free mass. AIMS: We aimed to determine if bedside evaluation of body composition by the body mass index (BMI), adductor pollicis muscle thickness (APMT) and arm muscle area (AMA), and the combination of low APMT or AMA with obesity are associated with disability 90 days after stroke. METHODS: A cohort study evaluating 120 patients hospitalized at the Stroke Unit was carried out. Data were expressed as average ± standard deviation or median and percentiles. Obesity was evaluated by BMI and fat-free mass by the APMT and AMA. Receiver operating characteristic (ROC) curves and multivariate logistic regression analysis were used to measure whether APMT and obesity were associated with modified Rankin Scale (mRS) ≥3 (disability) within 90 days of stroke. The data were adjusted for National Institutes of Health Stroke Scale (NIHSS), sex, age, type of stroke, and thrombolysis. The significance level was 5%. RESULTS: Of 120 patients, we came up with the following demographics: men: 66 (55.0%); mean age: 66.6 ± 13.2 years; ischemic stroke: 109 (90.8%); mean NIHSS: 4 (2-10); thrombolysis: 18 (16.5%). Considering mRS ≥3, ROC curve analysis showed that the value of the cutoff for APMT was <12.5 mm. In multivariate analysis adjusted for the above factors, each 1 mm of increase in APTM reduced the chance of disability by 31%. The intersection of obesity with APMT <12.5 mm increased by 37-fold the risk of disability. AMA was not associated with mRS ≥3. CONCLUSION: Lower APMT alone or in combination with obesity was associated with poor functional status.

Goldman score, but not Detsky or Lee indices, predicts mortality 6 months after hip fracture.

BACKGROUND: Over the past years, several cardiac risk indices were evaluated and modified, including Goldman, Detsky, and Lee scores. The predictive capacity of these scores in hip fracture patients is lacking. Thus, our objective was to compare the Goldman, Detsky, and Lee scores as predictors of mortality in 6 months after hip fracture. METHODS: We prospectively evaluated 80 consecutive patients with hip fractures, over the age of 65 admitted to an orthopedic ward at Botucatu Medical School. Patient demographic information, Goldman, Detsky and Lee scores were recorded. All patients were followed for 6 months after hip fracture, and mortality was recorded. Multiple logistic regression analyses were performed for mortality prediction. RESULTS: The mortality rate was 23% after a 6-month follow-up period. Patients who died had advanced age and the majority of them were male. They also had lower values of handgrip strength, and higher values of creatinine and urea. In the multiple logistic regression models when adjusted by age, gender, handgrip strength and creatinine, Goldman's score (OR:3.025; 95%CI:1.022-8.953; p:0.046), but not Detsky (OR:2.328; 95%CI:0.422-12.835; p:0.332) and Lee (OR:1.262; 95%CI:0.649-2.454; p:0.494), was associated with mortality 6 months after hip fracture. Each 1 category increase in Goldman score increased the mortality to more than 3-fold. CONCLUSIONS: In conclusion, our data suggest that Goldman score, but not Detsky or Lee indices, predicts mortality associated with hip fracture at up to 6 months post-injury.

Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats.

BACKGROUND: Cardiotoxicity is the major side effect of doxorubicin. As mechanisms that are involved in cardiotoxicity are ambiguous, new methods for attenuating cardiotoxicity are needed. Recent studies have shown that bisphosphonates can decrease oxidative stress. Therefore, the objective of this study was to evaluate the effect of pamidronate on preventing acute doxorubicin-induced cardiotoxicity. METHODS: Sixty-four male Wistar rats were allocated into four groups: the control group (C), the pamidronate group (P), the doxorubicin group (D) and the doxorubicin/pamidronate group (DP). The rats in the P and DP groups received pamidronate injections (3 mg/kg, IP). After 24 hours, the rats in the D and DP groups received doxorubicin injections (20 mg/kg, IP). Forty-eight hours after doxorubicin injection, the rats were killed. Echocardiography, isolated heart study and biochemical analysis were performed. RESULTS: Doxorubicin-induced acute cardiotoxicity showed increased matrix metalloproteinases (MMP)-2 activation, oxidative damage and induced alterations in myocardial energetic metabolism. Pamidronate did not inhibit MMP-2 activation but attenuated oxidative stress and improved myocardial energetic metabolism. Regarding cardiac function, the DP group exhibited a decrease in the left ventricular ejection fraction in the echocardiography and a decrease in +dP/dt in the isolated heart study compared with other groups. The same DP group presented serum hypocalcaemia. CONCLUSIONS: Despite its ability to reduce oxidative stress and improve energy metabolism in the heart, pamidronate worsened systolic function in rats treated with doxorubicin, and therefore we cannot recommend its use in conjunction with anthracycline chemotherapy.

Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats.

BACKGROUND: Doxorubicin can cause cardiotoxicity. Matrix metalloproteinases (MMP) are responsible for degrading extracellular matrix components which play a role in ventricular dilation. Increased MMP activity occurs after chronic doxorubicin treatment. In this study we evaluated in vivo and in vitro cardiac function in rats with acute doxorubicin treatment, and examined myocardial MMP and inflammatory activation, and gene expression of proteins involved in myocyte calcium transients. METHODS: Wistar rats were injected with doxorubicin (Doxo, 20 mg/kg) or saline (Control). Echocardiogram was performed 48 h after treatment. Myocardial function was assessed in vitro in Langendorff preparation. RESULTS: In left ventricle, doxorubicin impaired fractional shortening (Control 0.59 ± 0.07; Doxo 0.51 ± 0.05; p < 0.001), and increased isovolumetric relaxation time (Control 20.3 ± 4.3; Doxo 24.7 ± 4.2 ms; p = 0.007) and myocardial passive stiffness. MMP-2 activity, evaluated by zymography, was increased in Doxo (Control 141338 ± 8924; Doxo 188874 ± 7652 arbitrary units; p < 0.001). There were no changes in TNF-α, INF-γ, IL-10, and ICAM-1 myocardial levels. Expression of phospholamban, Serca-2a, and ryanodine receptor did not differ between groups. CONCLUSION: Acute doxorubicin administration induces in vivo left ventricular dysfunction and in vitro increased myocardial passive stiffness in rats. Cardiac dysfunction is related to myocardial MMP-2 activation. Increased inflammatory stimulation or changed expression of the proteins involved in intracellular calcium transients is not involved in acute cardiac dysfunction.

Erythrocyte selenium concentration predicts intensive care unit and hospital mortality in patients with septic shock: a prospective observational study.

INTRODUCTION: Selenoenzymes can modulate the extent of oxidative stress, which is recognized as a key feature of septic shock. The pathophysiologic role of erythrocyte selenium concentration in patients with septic shock remains unknown. Therefore, the objective of this study was to evaluate the association of erythrocyte selenium concentration with glutathione peroxidase (GPx1) activity, GPx1 polymorphisms and with ICU and hospital mortality in septic shock patients. METHODS: This prospective study included all patients older than 18 years with septic shock on admission or during their ICU stay, admitted to one of the three ICUs of our institution, from January to August 2012. At the time of the patients' enrollment, demographic information was recorded. Blood samples were taken within the first 72 hours of the patients' admission or within 72 hours of the septic shock diagnosis for determination of selenium status, protein carbonyl concentration, GPx1 activity and GPx1 Pro198Leu polymorphism (rs 1050450) genotyping. RESULTS: A total of 110 consecutive patients were evaluated. The mean age was 57.6 ± 15.9 years, 63.6% were male. Regarding selenium status, only erythrocyte selenium concentration was lower in patients who died in the ICU. The frequencies for GPx1 Pro198Leu polymorphism were 55%, 38% and 7% for Pro/Pro, Pro/Leu and Leu/Leu, respectively. In the logistic regression models, erythrocyte selenium concentration was associated with ICU and hospital mortality in patients with septic shock even after adjustment for protein carbonyl concentration and acute physiology and chronic health evaluation II score (APACHE II) or sequential organ failure assessment (SOFA). CONCLUSIONS: Erythrocyte selenium concentration was a predictor of ICU and hospital mortality in patients with septic shock. However, this effect was not due to GPx1 activity or Pro198Leu polymorphism.

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.

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.

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.

Organizing pneumonia and COVID-19.

Organizing pneumonia (OP) is an interstitial lung disease, and can be cryptogenic, if no cause is identified, or secondary to several conditions. COVID-19-induced persistent inflammation can be associated with interstitial lung disease. We present a review of literature of OP and COVID-19-induced OP with an illustrative case. A 38-year-old man was admitted with COVID-19 that required mechanical ventilation for 56 days. Initial chest computed tomography (CT) revealed diffuse bilateral ground-glass opacities in the lungs with consolidation areas involving 75 % of the parenchyma. After weaning from MV, the patient still required oxygen supplementation. A new chest CT scan also showed extensive diffuse areas of consolidation and ground-glass opacity. OP was hypothesized and 40 mg/day prednisone initiated and continued for six months with resolution of lung functional and image abnormalities. Organizing pneumonia should be included in the differential diagnosis of COVID-19 patients with respiratory symptoms after partial pulmonary recovery.

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.

Jaboticaba (Myrciaria jaboticaba) Attenuates Ventricular Remodeling after Myocardial Infarction in Rats.

The cardiac remodeling after myocardial infarction is characterized by inflammation and oxidative stress. Thus, this study aimed to test the hypothesis that jaboticaba, due to its anti-inflammatory and antioxidants properties, attenuates cardiac remodeling after myocardial infarction. Wistar rats were submitted to myocardial infarction due to coronary artery occlusion, and divided into four experimental groups: C, sham control animals; I, animals submitted to myocardial infarction, received a standard diet; IJ2, animals submitted to myocardial infarction, received a standard diet plus 2% jaboticaba; and IJ4, animals submitted to myocardial infarction, received a standard diet plus 4% jaboticaba. After a three-month follow-up, echocardiography, histology, oxidative stress, and cardiac energy metabolism were analyzed. There was no difference in infarct size or mortality among the infarcted groups. The IJ4 group displayed improved diastolic function, as assessed by isovolumetric relaxation time normalized to the heart rate. As expected, the percentage of collagen was higher in all infarcted groups than in the C group. However, the IJ2 group had less collagen than groups I and IJ4. The IJ4 group presented lower PFK activity than I and IJ2, and lower pyruvate dehydrogenase activity than controls, whereas the IJ2 group showed no differences compared to the control group in both LDH and ATP synthase activity. The 2% and 4% doses attenuated lipid peroxidation and increased the activity of glutathione peroxidase compared with the I group. In conclusion, jaboticaba attenuated the remodeling process after myocardial infarction, which was associated with decreased oxidative stress and improved energy metabolism.