Frailty identification and management among Brazilian healthcare professionals: a survey.

BACKGROUND: National and international guidelines on frailty assessment and management recommend frailty screening in older people. This study aimed to determine how Brazilian healthcare professionals (HCPs) identify and manage frailty in practice. METHODS: An anonymous online survey on the assessment and management of frailty was circulated virtually through HCPs across Brazil. RESULTS: Most of the respondants used non-specific criteria such as gait speed (45%), handgrip strength (37.6%), and comprehensive geriatric assessment (33.2%). The use of frailty-specific criteria was lower than 50%. The most frequently used criteria were the Frailty Index (19.1%), Frailty Phenotype (13.2%), and FRAIL (12.5%). Only 43.5% felt confident, and 40% had a plan to manage frailty. In the multivariate-adjusted models, training was the most crucial factor associated with assessing frailty, confidence, and having a management plan (p < 0.001 for all). Those with fewer years of experience were more likely to evaluate frailty (p = 0.009). Being a doctor increased the chance of using a specific tool; the opposite was true for dietitians (p = 0.03). Those who assisted more older people had a higher likelihood of having a plan (p = 0.011). CONCLUSION: Frailty assessment was heterogeneous among healthcare professions groups, predominantly using non-specific criteria. Training contributed to frailty assessment, use of specific criteria, confidence, and having a management plan. This data informs the need for standardized screening criteria and management plans for frailty, in association with increasing training at the national level for all the HCPs who assist older people.

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.

Association between pre-operative complications, comorbidities, and in-hospital mortality in a hip fracture cohort: a register study in a tertiary hospital in Brazil.

PURPOSE: The incidence of hip fractures is increasing exponentially due to an aging Brazilian population. Older people had significant comorbidities which increases the risk of post-operative mortality. Our purpose was to examine the association between pre-operative infections and comorbidities on the risk of post-operative in-hospital mortality after proximal femur fracture surgery's, beyond that, to evaluate the association between comorbidities and time to surgery. METHODS: This is a population-based cohort retrospective study, using medical records of all six year consecutive surgical procedures for correction of hip fracture in a tertiary teaching Hospital in Brazil. The exclusion criteria aimed to exclusively allocate patients who had their first hip fracture secondary to low-energy trauma. Multivariate logistical regression was performed and receiver operating characteristic (ROC) curve with area under curve (AUC) to evaluate the sensitivity and specificity of the model. p-value < 0.05 was considered significant. RESULTS: Final sample was composed by 856 consecutive patients with 81 years of median and 164 patients were excluded. The median length of hospital say was five days with - l mortality at 3.6%. Significant variables for increased mortality included the presence of pre-operative infection (odds ratio (OR): 3.9(1.12-8.54), chronic obstructive pulmonary disease (COPD) (OR: 3.83(1.36-10.82)), and systemic arterial hypertension (SAH) (OR: 4.1(1.18-14.25)). Development of pre-operative infection was associated with a delay to surgery (OR: 1.1 (1.08-1.13)). CONCLUSIONS: In older people with proximal femur fracture, the presence of pre-operative infection, COPD and SAH were the strongest risk factor for post-operative in-hospital mortality. Pre-operative infection was associated with statistically significant delay to surgery.

Evaluating the performance of the PRISMA-7 frailty criteria for predicting disability and death after acute ischemic stroke.

OBJECTIVES: We aimed to evaluate the predictive performance of the PRISMA-7 frailty criteria regarding the composite outcome of disability or death in patients with an acute ischemic stroke, and to compare it with the Frailty Index and the National Institutes of Health Stroke Scale (NIHSS). MATERIALS AND METHODS: This prospective cohort study involved all patients aged ≥ 40 years admitted with an acute ischemic stroke between March 2019 and January 2020. We performed survival analyses, calculated risk ratios, sensitivity, specificity, and predictive values for the combined outcome of disability or death according to the presence of frailty as determined by the PRISMA-7 and the Frailty Index, and stroke severity based on the NIHSS. RESULTS: In 174 patients with acute ischemic stroke, being frail in the week before the stroke according to the PRISMA-7 was associated with a Risk Ratio of 4·50 (95%CI 1·77-11·43, P <0·001) and a Positive Predictive Value of 89% (95%CI 77-99%) for being disabled or dead 90 days after the stroke, and a Hazard Ratio of 3·33 (95%CI 1·48-7·51, P = 0·004) for the survival outcome. The predictive performance of the PRISMA-7 was not significantly different from the Frailty Index or the NIHSS. CONCLUSIONS: We provide evidence that the PRISMA-7 frailty criteria may be a useful prognostication tool in acute ischemic stroke.

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.

Safety of the effective radiation dose received during stroke hospitalization.

BACKGROUND: Neuroimaging is widely used for diagnosis and treatment of stroke. However, little is known about whether the radiation doses received by patients comply with international safety guidelines. OBJECTIVES: The aim of this study was to evaluate the effective radiation dose received while in hospital for stroke and analyze its safety according to current guidelines. METHODS: This cross-sectional study included 109 patients who were hospitalized and diagnosed with ischemic stroke. The National Institutes of Health Stroke Scale was used to evaluate stroke severity, the Bamford clinical classification was used for topography, and the TOAST classification was used for etiology. The computed tomography dose index and size-specific dose estimates were used to calculate the effective radiation dose (ERD) received while in hospital. A Mann-Whitney test was used to compare the ERD received by thrombolysed and non-thrombolysed patients. Non-parametric statistics were used to analyze the data with a 95% confidence interval. RESULTS: During the study period, the median ERD received was 10.9 mSv. Length of stay was not associated with radiation exposure. No differences were demonstrated in ERD according to stroke etiology or Bamford clinical classification. Patients who had CT perfusion (only or in addition to CT or angiotomography) received the highest ERD (46.5 mSv) and the difference compared to those who did not (10.8 mSv) was statistically significant (p<0.001). No differences were found in the ERD between thrombolysed and non-thrombolysed patients. There was no correlation between ERD while in hospital and stroke severity. CONCLUSIONS: According to the current national guidelines, the protocol for examining images at our stroke unit is safe in terms of the ERD received by the patient while in hospital. There was no difference in the ERD received by patients stratified by thrombolytic treatment or stroke severity.

CONTEXTO: A neuroimagem é amplamente utilizada para o diagnóstico e tratamento do acidente vascular cerebral (AVC). No entanto, pouco se sabe se a dose de radiação recebida nesses exames está de acordo com as diretrizes internacionais de segurança. OBJETIVOS: O objetivo deste estudo foi avaliar a dose de radiação efetiva (DRE) durante a hospitalização por AVC. MÉTODOS: Trata-se de estudo transversal com 109 pacientes hospitalizados com diagnóstico de AVC isquêmico. A gravidade do AVC foi avaliada pela National Institutes of Health Stroke Scale, a topografia pela classificação clínica de Bamford e a etiologia pelo Trial of ORG 10172 in Acute Stroke Treatment (TOAST). O índice de dose recebida no exame de tomografia computadorizada (TC) e as estimativas de dose específicas foram usados ​​para calcular a DRE recebida durante a hospitalização. O teste de Mann-Whitney foi utilizado para comparar a DRE recebida por pacientes trombolisados ​​e não trombolisados. Estatísticas não paramétricas foram utilizadas para analisar os dados. RESULTADOS: Durante o período do estudo, a DRE foi de 10,9 mSv. O tempo de internação não foi associado à exposição à radiação. Nenhuma diferença foi demonstrada na DRE de acordo com a etiologia e classificação clínica de Bamford. Os pacientes que fizeram perfusão (isolada, associada à TC ou angiotomografia) receberam a maior DRE (46,5 mSv) em comparação aos que não fizeram (10,8 mSv), sendo estatisticamente significativo (p <0,001). Não foram encontradas diferenças na DRE entre pacientes trombolisados e não trombolisados. Não houve correlação entre a DRE durante a hospitalização com a gravidade do AVC. CONCLUSÕES: De acordo com as atuais diretrizes nacionais, o protocolo de exame de imagens na unidade de AVC é seguro em relação à DRE recebido pelo paciente durante a internação. Não houve diferença na DRE dos pacientes de acordo com o tratamento trombolítico e a gravidade do AVC.

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.

Comparison of morphometry and ventricular function of healthy and smoking young people.

BACKGROUND: Tobacco smoke is one of the most significant risk factors for cardiovascular diseases and damages in the myocardial tissue directly. Cardiac magnetic resonance (CMR) has been used and is a promising tool to evaluate morphometry and cardiac function in humans. The objective of this study was to evaluate associations of smoking with morphometry and cardiac function by CMR technique in young adult smokers. METHODS: Altogether, 49 volunteers (22 smokers and 27 non-smokers) were included in the study. The comparisons between groups were performed by multiple linear regression adjusting for body mass index and gender. RESULTS: In the morphometric and functional evaluation of the left ventricle, we observed statistical significant lower values of end-diastolic volume (EDV) (p = 0.02), ejection volume (EV) (p = 0.001) and indexed ejection volume (IEV) (p = 0.007) in smokers when compared to no-smoker group. Right ventricle showed statistical significant lower values of EDV (p = < 0.001), end-systolic volume (p = 0.01), EV (p = < 0.001), IEV (p = 0.001), indexed end-diastolic volume (p = 0.001) and major axis (p = 0.01) in smokers when compared to non-smokers group. CONCLUSIONS: There is a strongly association of smoking in young adult and cardiac function decline, even adjusted by cofounders, which compromises the proper functioning of the heart. Evidence confirms that smoking can directly influence the cardiac function, even without atherosclerosis or other chronic comorbidities, associated with increased risk of cardiovascular diseases.

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.

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.

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.

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.