Impact of urgent coronary artery bypass grafting on acute kidney injury : A matched cohort study.

OBJECTIVES: There is limited knowledge regarding the specific interrelationships between urgent coronary artery bypass graft (U-CABG) surgery and postoperative acute kidney injury (AKI). We aimed to (1) analyze the impact of urgent CABG (U-CABG) on the incidence and severity of postoperative AKI, (2) estimate the influence of AKI after U­CABG or elective CABG (E-CABG) on mortality and (3) identify risk factors for AKI depending on the urgency of operation. RESULTS: U­CABG patients showed a higher incidence of AKI (49.8% vs. E­CABG: 39.7%; p = 0.026), especially for higher AKI stages 2 + 3. In-hospital mortality was higher in U­CABG patients (12.6%) compared to E­CABG patients (2.3%; p < 0.001). The impact of AKI on mortality did not differ, but showed a strong coherency between higher AKI stages (2 + 3) and mortality (stage 1: OR 2.409, 95% CI 1.017-5.706; p = 0.046 vs. stage 2 + 3: OR 5.577; 95% CI 2.033-15.3; p = 0.001). Univariate logistic regression analysis revealed that preoperative renal impairment, peripheral vascular disease and transfusion of more than two red blood cell concentrates were predictors for postoperative AKI in both groups. CONCLUSIONS: U­CABG is a risk factor for postoperative AKI and even "mild" AKI leads to a significantly higher mortality. Hence, the prevention of modifiable risk factors might reduce the incidence of postoperative AKI and thus improve outcome.

Sociodemographic factors associated with COVID-19 in-hospital mortality in Brazil.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has highlighted inequalities in access to healthcare systems, increasing racial disparities and worsening health outcomes in these populations. This study analysed the association between sociodemographic characteristics and COVID-19 in-hospital mortality in Brazil. STUDY DESIGN: A retrospective analysis was conducted on quantitative reverse transcription polymerase chain reaction-confirmed hospitalised adult patients with COVID-19 with a defined outcome (i.e. hospital discharge or death) in Brazil. Data were retrieved from the national surveillance system database (SIVEP-Gripe) between February 16 and August 8, 2020. METHODS: Clinical characteristics, sociodemographic variables, use of hospital resources and outcomes of hospitalised adult patients with COVID-19, stratified by self-reported race, were investigated. The primary outcome was in-hospital mortality. The association between self-reported race and in-hospital mortality, after adjusting for clinical characteristics and comorbidities, was evaluated using a logistic regression model. RESULTS: During the study period, Brazil had 3,018,397 confirmed COVID-19 cases and 100,648 deaths. The study population included 228,196 COVID-19-positive adult in-hospital patients with a defined outcome; the median age was 61 years, 57% were men, 35% (79,914) self-reported as Black/Brown and 35.4% (80,853) self-reported as White. The total in-hospital mortality was 37% (85,171/228,196). Black/Brown patients showed higher in-hospital mortality than White patients (42% vs 37%, respectively), were admitted less frequently to the intensive care unit (ICU) (32% vs 36%, respectively) and used more invasive mechanical ventilation (21% vs 19%, respectively), especially outside the ICU (17% vs 11%, respectively). Black/Brown race was independently associated with high in-hospital mortality after adjusting for sex, age, level of education, region of residence and comorbidities (odds ratio = 1.15; 95% confidence interval = 1.09-1.22). CONCLUSIONS: Among hospitalised Brazilian adults with COVID-19, Black/Brown patients showed higher in-hospital mortality, less frequently used hospital resources and had potentially more severe conditions than White patients. Racial disparities in health outcomes and access to health care highlight the need to actively implement strategies to reduce inequities caused by the wider health determinants, ultimately leading to a sustainable change in the health system.

Predicting acquisition of carbapenem-resistant Gram-negative pathogens in intensive care units.

BACKGROUND: Infections by multidrug-resistant Gram-negative (MDRGN) bacteria are among the greatest contemporary health concerns, especially in intensive care units (ICUs), and may be associated with increased hospitalization time, morbidity, costs, and mortality. AIM: The study aimed to predict carbapenem-resistant MDRGN acquisition in ICUs, to determine its risk factors, and to assess the impact of this acquisition on mortality rate. METHODS: A matched case-control study was performed in patients admitted to the ICU at a large Brazilian hospital over a five-year period. Cases were defined as patients who acquired carbapenem-resistant MDRGN bacteria during hospitalization. Controls were defined as patients who had no detection of carbapenem-resistant MDRGN bacteria. Cases were matched to controls according to the admission period. Risk factors were identified by multiple logistic regression using a stepwise selection method. FINDINGS: In total, 343 cases and 1029 controls were analysed. The 30-day mortality rate for subjects with ICU-associated carbapenem-resistant MDRGN was 37.6%. Five variables were identified as statistically significant and more relevant for the acquisition of multidrug-resistant strains: increased Simplified Acute Physiology Score 3, patients with severe chronic obstructive pulmonary disease and exposure to haemodialysis catheter, central venous catheter, or mechanical ventilation. Models developed displayed good results with an accuracy of ∼90%. Patients who acquired MDRGN were 2.72 times more likely to die than non-MDRGN acquisition patients. CONCLUSION: Finding risk factors and developing predictive models may benefit patients through early detection and by controlling the spread of MDR. The presence of mechanical ventilation and central venous catheter were the main risk factors demonstrated, and their use requires special attention.

Enzyme autoinduction by mitotane supported by population pharmacokinetic modelling in a large cohort of adrenocortical carcinoma patients.

OBJECTIVE: Mitotane is used for the treatment of adrenocortical carcinoma. High oral daily doses of typically 1- 6 g are required to attain therapeutic concentrations. The drug has a narrow therapeutic index and patient management is difficult because of a high volume of distribution, very long elimination half-life, and drug interaction through induction of metabolizing enzymes. The present evaluation aimed at the development of a population pharmacokinetic model of mitotane to facilitate therapeutic drug monitoring. METHODS: Appropriate dosing information, plasma concentrations (1137 data points) and covariates were available from therapeutic drug monitoring (TDM) of 76 adrenocortical carcinoma patients treated with mitotane. Using nonlinear mixed effects modeling, a simple structural model was first developed, with subsequent introduction of metabolic autoinduction. Covariate data were analyzed to improve overall model predictability. Simulations were performed to assess the attainment of therapeutic concentrations with clinical dosing schedules. RESULTS: A one-compartment pharmacokinetic model with first order absorption was found suitable to describe the data, with an estimated central volume of distribution of 6086 L related to a high interindividual variability of 81.5%. Increase in clearance of mitotane during treatment could be modeled by a linear enzyme autoinduction process. Body mass index was found to have an influence upon disposition kinetics of mitotane. Model simulations favor a high dose regimen to rapidly attain therapeutic concentrations, with the first TDM suggested on day 16 of treatment to avoid systemic toxicity. CONCLUSION: The proposed model describes mitotane pharmacokinetics and can be used to facilitate therapy by predicting plasma concentrations.

Are there effects of age, gender, height, and body fat on the functional muscle-bone unit in children and adults?

The aim was to describe the effect of age, gender, height, different stages of human life, and body fat on the functional muscle-bone unit. All these factors had a significant effect on the functional muscle-bone unit and should be addressed when assessing functional muscle-bone unit in children and adults. INTRODUCTION: For the clinical evaluation of the functional muscle-bone unit, it was proposed to evaluate the adaptation of the bone to the acting forces. A frequently used parameter for this is the total body less head bone mineral content (TBLH-BMC) determined by dual-energy X-ray absorptiometry (DXA) in relation to the lean body mass (LBM by DXA). LBM correlates highly with muscle mass. Therefore, LBM is a surrogate parameter for the muscular forces acting in everyday life. The aim of the study was to describe the effect of age and gender on the TBLH-BMC for LBM and to evaluate the impact of other factors, such as height, different stages of human life, and of body fat. METHODS: As part of the National Health and Nutrition Examination Survey (NHANES) study, between the years 1999-2006 whole-body DXA scans on randomly selected Americans from 8 years of age were carried out. From all eligible DXA scans (1999-2004), three major US ethnic groups were evaluated (non-Hispanic Whites, non-Hispanic Blacks, and Mexican Americans) for further statistical analysis. RESULTS: For the statistical analysis, the DXA scans of 8190 non-Hispanic White children and adults (3903 female), of 4931 non-Hispanic Black children and adults (2250 female) and 5421 of Mexican-American children and adults (2424 female) were eligible. Age, gender, body height, and especially body fat had a significant effect on the functional muscle-bone unit. CONCLUSIONS: When assessing TBLH-BMC for LBM in children and adults, the effects of age, gender, body fat, and body height should be addressed. These effects were analyzed for the first time in such a large cohort.

The functional muscle-bone unit in children with cerebral palsy.

Our results suggest that the prevalence of bone health deficits in children with CP was overestimated, when using only age- and height-adjusted bone mineral content (BMC) and areal bone mineral density (aBMD). When applying the functional muscle-bone unit diagnostic algorithm (FMBU-A), the prevalence of positive results decreased significantly. We recommend applying the FMBU-A when assessing bone health in children with CP. INTRODUCTION: The prevalence of bone health deficits in children with cerebral palsy (CP) might be overestimated because age- and height-adjusted reference percentiles for bone mineral content (BMC) and areal bone mineral density (aBMD) assessed by dual-energy X-ray absorptiometry (DXA) do not consider reduced muscle activity. The aim of this study was to compare the prevalence of positive DXA-based indicators for bone health deficits in children with CP to the prevalence of positive findings after applying a functional muscle-bone unit diagnostic algorithm (FMBU-A) considering reduced muscle activity. METHODS: The present study was a monocentric retrospective analysis of 297 whole body DXA scans of children with CP. The prevalence of positive results of age- and height-adjusted BMC and aBMD defined as BMC and aBMD below the P3 percentile and of the FMBU-A was calculated. RESULTS: In children with CP, the prevalence of positive results of age-adjusted BMC were 33.3% and of aBMD 50.8%. Height-adjusted results for BMC and aBMD were positive in 16.8 and 36.0% of cases. The prevalence of positive results applying the FMBU-A regarding BMC and aBMD were significantly (p < 0.001) lower than using age- and height-adjusted BMC and aBMD (8.8 and 14.8%). CONCLUSIONS: Our results suggest that the prevalence of bone health deficits in children with CP was overestimated, when using age- and height-adjusted BMC and aBMD. When applying the FMBU-A, the prevalence decreased significantly. We recommend applying the FMBU-A when assessing bone health in children with CP.

[Extracellular matrix -- from basic research to clinical significance. An overview with special consideration of matrix metalloproteinases]. / Extrazelluläre Matrix -- von der Grundlagenforschung zur klinischen Bedeutung. Eine Ubersicht unter besonderer Berücksichtigung der Matrix Metalloproteinasen.

Matrix metalloproteinases (MMPs) hydrolyze most components of the extracellular matrix (ECM). These proteinases play a central role in many biological processes such as normal tissue remodeling, embryogenesis, wound healing and angiogenesis. Currently about 26 MMP genes have been identified, and most are multidomain zinc endopeptidases. Knowledge of their tertiary structure is crucial for the understanding of the functional properties of MMPs. In healthy tissue a strict regulation of MMPs is critical in order to maintain proper ECM homeostasis. Among other levels of regulation, MMPs are precisely regulated by their main endogenous protein inhibitors (TIMPs). Disruption of this balance results in serious diseases such as fibrosis, arthritis, and tumour growth. Several studies have documented the importance of MMP-mediated ECM destruction for tumour initiation, growth, migration, angiogenesis, invasion and metastasis. Certain MMPs such as gelatinases (MMP-2, MMP-9) have special mechanisms to localize at leading edges in tumour tissue. MMPs can no longer be thought of solely as ECM destructionists, but as part of an elegant communication system through which epithelial and tumor cells interact with the stroma.