Acute kidney injury in septic patients admitted to emergency clinical room: risk factors and outcome

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sepsis and AKI in clinical emergency room patients: the role of urinary NGAL

Few studies have investigated the predictive properties of urinary (u) NGAL as an AKI marker in septic population. This study evaluated the efficacy of uNGAL as predictor of AKI and death in septic patients admitted to the clinical emergency room (ER). We prospectively studied patients with sepsis admitted to the ER. Urine was analyzed for NGAL within the first 24 hours after admission (classified as NGAL1), between 24 and 48 h (NGAL2), and at moment of AKI diagnosis (NGAL3). Among 168 septic patients admitted to ER, 72% developed AKI. The uNGAL and its relationship with creatinine (Cr) were high in septic patients but statistically higher in those with sepsis and AKI. The uNGAL1 and uNGAL2, as well as uNGAL1/uCr1 and uNGAL2/uCr2, were good predictors for AKI (AUC-ROC 0.73, 0.70, 0.77, and 0.84, resp.). The uNGAL1 and uNGAL1/uCr1 were poor predictors for death (AUC-ROC 0.66 and 0.68, resp.), whereas uNGAL2 and uNGAL2/uCr2 were better predictors (AUC-ROC 0.70 and 0.81, resp.). The uNGAL is highly sensitive but nonspecific predictor of AKI and death in septic patients admitted into ER.

Do bagaço da pintura às pictocartografias

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Comparative analysis of the replication of bovine herpesvirus 1 (BHV1) and BHV5 in bovine derived-neuron-like cells

Members of the subfamily Alphaherpesvirinae use the epithelium of the upper respiratory and/or genital tract as preferential sites for primary replication. However, bovine herpesvirus 5 (BoHV5) is neurotropic and neuroinvasive and responsible for meningoencephalitis in cattle and in animal models. A related virus, BoHV1 has also been occasionally implicated in natural cases of neurological infection and disease in cattle. The aim of the present study was to assess the in vitro effects of BoHV1 and BoHV5 replication in neuron-like cells. Overall, cytopathic effects, consisting of floating rounded cells, giant cells and monolayer lysis, induced by both viruses at 48 h postinfection (p.i.) resulted in a loss of cell viability and high virus titres (r = 0.978). The BoHV1 Cooper strain produced the lowest titres in neuron-like cells, although viral DNA was detected in infected cells during all experiments. Virus replication in infected cells was demonstrated by immunocytochemistry, flow cytometry and qPCR assays. BoHV antigens were better visualized at 48 h p.i. and flow cytometry analysis showed that SV56/90 and Los Angeles antigens were present at higher levels. In spite of the fact that BoHV titres dropped at 48 h p.i, viral DNA remained detectable until 120 h p.i. Sensitive TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) and annexin V assays were used to identify apoptosis. BoHV5 induced death in approximately 50 % of cells within 24 h p.i., similar to what has been observed for BoHV1 Los Angeles. Infection with the BoHV1 Cooper strain resulted in 26.37 % of cells being in the early stages of apoptosis; 63.69 % of infected cells were considered viable. Modulation of mitochondrial function, as measured by mitochondrial membrane depolarization, was synchronous with the virus replication cycle, cell viability and virus titres at 48 h p.i. Our results indicate that apoptosis plays an important role in preventing neuronal death and provides a bovine-derived in vitro system to study herpesvirus-neuron interactions.

In Vitro Safety Evaluation of Caffeic Acid

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Occluded Tunneled Venous Catheter in Hemodialysis Patients: Risk Factors and Efficacy of Alteplase

Thrombosis of tunneled central venous catheters (CVC) in hemodialysis (HD) patients is common and it can lead to the elimination of vascular sites. This study aimed to evaluate the incidence of thrombotic obstruction of tunneled CVC in HD patients and the efficacy of occlusion treatment with alteplase use, and identify factors associated with thrombotic occlusion. It was a prospective cohort study performed in two centers which evaluated the diagnosis and treatment of thrombotic occlusion of CVC in HD patients for 24 consecutive months. The catheter occlusion was defined as the difficulty infusing or withdrawing fluid from their paths. Alteplase dose was infused to fill the lumen of the occluded catheter and remained for 50 min. As there was no obstruction of the catheter, the procedure was repeated. Three hundred and thirty-nine CVC in 247 patients were evaluated and followed, totalling 67 244 CVC-days. One hundred fifty-seven patients had only one CVC, 88 patients had two CVC during the study, and two patients had three CVC. The median age was 58 (47–66) years, patients were predominantly men (54%), with diabetic nephropathy as the main cause of chronic kidney disease (44%), the internal jugular vein as the main site of implantation (82%), and duration of dialysis before CVC implantation of 119 (41.5 to 585.5) days. Eight hundred and fifteen occlusion episodes were diagnosed (12 episodes/1000 CVC-days), with primary success with alteplase in 596 episodes (77%) and secondary in 81 cases (10%). In 99 episodes (13%), success was not achieved after the second dose of alteplase. Two hundred and thirty CVC were removed during the study and the removal causes were arteriovenous fistula use in 88 patients (38.3%), infectious and mechanical complications in 89 (38.7%) and 21 (9.1%), respectively, and others (transplantation, transfer, or death) in 32 patients (13.9%). Adverse effects were also not observed. In the multivariate analysis, we identified the greatest number of days with CVC (OR = 1.02, CI = 1.01–1.04, P = 0.004), the presence of diabetes (OR = 1.560, CI = 1.351–1.894, P = 0.015), and exit site infection (ESI) (OR = 1.567 CI = 1347–1926, P = 0.023) as factors associated with obstruction. Thrombotic occlusion showed frequent mechanical complication in CVC of HD patients. We observed 12 episodes of obstruction per 1000 CVC-days, with a high success rate after alteplase use (87%). In the multivariate analysis, the time with CVC, the presence of diabetes, and ESI were identified as variables associated with thrombotic obstruction.

Modeling spatial distribution of cancer incidence in Cordoba, Argentina

Background: Cancer is the second leading cause of death in Argentina, and there is little knowledge about its incidence. The first study based on population-based cancer registry described spatial incidence and indicated that there existed at least county-level aggregation. The aim of the present work is to model the incidence patterns for the most incidence cancer in Córdoba Province, Argentina, using information from the Córdoba Cancer Registry by performing multilevel mixed model approach to deal with dependence and unobserved heterogeneity coming from the geo-reference cancer occurrence. Methods: Standardized incidence rates (world standard population) (SIR) by sex based on 5-year age groups were calculated for 109 districts nested on 26 counties for the most incidence cancers in Cordoba using 2004 database. A Poisson twolevel random effect model representing unobserved heterogeneity between first level-districts and second level-counties was fitted to assess the spatial distribution of the overall and site specific cancer incidence rates. Results: SIR cancer at Córdoba province shown an average of 263.53±138.34 and 200.45±98.30 for men and women, respectively. Considering the ratio site specific mean SIR to the total mean, breast cancer ratio was 0.25±0.19, prostate cancer ratio was 0.12±0.10 and lower values for lung and colon cancer for both sexes. The Poisson two-level random intercepts model fitted for SIR data distributed with overdispersion shown significant hierarchical structure for the cancer incidence distribution. Conclusions: a strong spatial-nested effect for the cancer incidence in Córdoba was observed and will help to begin the study of the factors associated with it.

FGFR4 Profile as a Prognostic Marker in Squamous Cell Carcinoma of the Mouth and Oropharynx

Background: Fibroblast growth factor receptor 4 (FGFR4) is a member of a receptor tyrosine kinase family of enzymes involved in cell cycle control and proliferation. A common single nucleotide polymorphism (SNP) Gly388Arg variant has been associated with increased tumor cell motility and progression of breast cancer, head and neck cancer and soft tissue sarcomas. The present study evaluated the prognostic significance of FGFR4 in oral and oropharynx carcinomas, finding an association of FGFR4 expression and Gly388Arg genotype with tumor onset and prognosis. Patients and Methods: DNA from peripheral blood of 122 patients with oral and oropharyngeal squamous cell carcinomas was used to determine FGFR4 genotype by PCR-RFLP. Protein expression was assessed by immunohistochemistry (IHC) on paraffin-embedded tissue microarrays. Results: Presence of allele Arg388 was associated with lymphatic embolization and with disease related premature death. In addition, FGFR4 low expression was related with lymph node positivity and premature relapse of disease, as well as disease related death. Conclusion: Our results propose FGFR4 profile, measured by the Gly388Arg genotype and expression, as a novel marker of prognosis in squamous cell carcinoma of the mouth and oropharynx.

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

One of the greatest challenges in urological oncology is renal cell carcinoma (RCC), which is the third leading cause of death in genitourinary cancers. RCCs are highly vascularized and respond positively to antiangiogenic therapy. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the potential of ES-based antiangiogenic therapy to activate tumor-associated endothelial cells in metastatic RCC (mRCC). Balb/c-bearing Renca cells were treated with NIH/3T3-LendSN or, as a control, with NIH/3T3-LXSN cells. The T-cell subsets and lymphocyte populations of tumors, mediastinal lymph nodes and the spleen were assessed by flow cytometry. The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was assessed by real-time PCR, flow cytometry and immunohistochemistry analysis. ES gene therapy led to an increase in the percentage of infiltrating CD4-interferon (IFN)-gamma cells (P<0.05), CD8-IFN-gamma cells (P<0.01) and CD49b-tumor necrosis factor-alpha cells (P<0.01). In addition, ES therapy caused an increase at the mRNA level of ICAM-1 (1.4-fold; P<0.01) and VCAM-1 (1.5-fold) (control vs treated group; P<0.001). Through flow cytometry, we found a significant increase in the CD34/ICAM-1 cells (8.1-fold; P<0.001) and CD34/VCAM-1 cells (1.6-fold; P<0.05). ES gene therapy induced a significant increase in both T CD4 and CD8 cells in the lymph nodes and the spleen, suggesting that ES therapy may facilitate cell survival or clonal expansion. CD49b cells were also present in increased quantities in all of these organs. In this study, we demonstrate an antitumor inflammatory effect of ES in an mRCC model, and this effect is mediated by an increase in ICAM-1 and VCAM-1 expression in tumor-associated endothelial cells.

HOPE IN HIV-POSITIVE WOMEN

The objective of this study was to assess the hope in the lives of HIV-positive women, using the Herth Hope Scale (HHS). Participants were 111 HIV-positive women who attended a referral outpatient clinic in Fortaleza-CE. From January to May 2009, interviews were held to collect biopsychosocial variables, and the HHS was applied. Data were analyzed using SPSS-8.0 and revealed an average hope index of 34.86, indicating that these women have little hope in life in view of their diagnosis of HIV. The scale item with the highest score was faith. This probably derives from the fact that Aids is incurable, transmissible and generates negative stigma, in addition to its relation with the idea of imminent death. In conclusion, measuring hope among HIV patients through the use of an instrument permits intervention assessment and planning, promoting assistance and motivation to live better and maintain a hopeful attitude.

Proteasome inhibition and ROS generation by 4-nerolidylcatechol induces melanoma cell death

Induction of apoptotic cell death in response to chemotherapy and other external stimuli has proved extremely difficult in melanoma, leading to tumor progression, metastasis formation and resistance to therapy. A promising approach for cancer chemotherapy is the inhibition of proteasomal activity, as the half-life of the majority of cellular proteins is under proteasomal control and inhibitors have been shown to induce cell death programs in a wide variety of tumor cell types. 4-Nerolidylcatechol (4-NC) is a potent antioxidant whose cytotoxic potential has already been demonstrated in melanoma tumor cell lines. Furthermore, 4-NC was able to induce the accumulation of ubiquitinated proteins, including classic targets of this process such as Mcl-1. As shown for other proteasomal inhibitors in melanoma, the cytotoxic action of 4-NC is time-dependent upon the pro-apoptotic protein Noxa, which is able to bind and neutralize Mcl-1. We demonstrate the role of 4-NC as a potent inducer of ROS and p53. The use of an artificial skin model containing melanoma also provided evidence that 4-NC prevented melanoma proliferation in a 3D model that more closely resembles normal human skin.

Hypotheses, rationale, design, and methods for prognostic evaluation of cardiac biomarker elevation after percutaneous and surgical revascularization in the absence of manifest myocardial infarction. A comparative analysis of biomarkers and cardiac magnetic resonance. The MASS-V Trial

Background: Although the release of cardiac biomarkers after percutaneous (PCI) or surgical revascularization (CABG) is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR) consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis. Methods/Design: The study will include 150 patients with multivessel coronary artery disease (CAD) with left ventricle ejection fraction (LVEF) and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB); 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR. Discussion: The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice, the inappropriate use of these necrosis markers has led to misdiagnosis and therefore wrong treatment. The appearance of a more sensitive tool such as CMR provides an unprecedented diagnostic accuracy of myocardial damage when correlated with necrosis enzyme markers. We aim to correlate laboratory data with imaging, thereby establishing more refined data on the presence or absence of irreversible myocardial injury after the procedure, either percutaneous or surgical, and this, with or without the use of cardiopulmonary bypass.

Long-Term Prospective Study of the Influence of Estrone Levels on Events in Postmenopausal Women with or at High Risk for Coronary Artery Disease

Background. The link between endogenous estrogen, coronary artery disease (CAD), and death in postmenopausal women is uncertain. We analyzed the association between death and blood levels of estrone in postmenopausal women with known coronary artery disease (CAD) or with a high-risk factor score for CAD. Methods. 251 postmenopausal women age 50-90 years not on estrogen therapy. Fasting blood for estrone and heart disease risk factors were collected at baseline. Women were grouped according to their estrone levels (<15 and >= 15 pg/mL). Fatal events were recorded after 5.8 perpendicular to 1.4 years of followup. Results. The Kaplan-Meier survival curve showed a significant trend (P = 0.039) of greater all-cause mortality in women with low estrone levels (< 15 pg/mL). Cox multivariate regression analysis model adjusted for body mass index, diabetes, dyslipidemia, family history, and estrone showed estrone (OR = 0.45; P = 0.038) as the only independent variable for all-cause mortality. Multivariate regression model adjusted for age, body mass index, hypertension, diabetes, dyslipidemia, family history, and estrone showed that only age (OR = 1.06; P = 0.017) was an independent predictor of all-cause mortality. Conclusions. Postmenopausal women with known CAD or with a high-risk factor score for CAD and low estrone levels (< 15 pg/mL) had increased all-cause mortality.

Nursing diagnoses in trauma victims with fatal outcomes in the emergency scenario

The objective of this study was to identify and analyze the nursing diagnoses that constitute risk factors for death in trauma victims in the first 6 hours post-event. This is a cross-sectional, descriptive and exploratory study using quantitative analysis. A total of 406 patients were evaluated over six months of data collection in a tertiary hospital in the municipality of Sao Paulo, according to an instrument created for this purpose. Of the total, 44 (10.7%) suffered death. Multivariate analysis indicated the nursing diagnoses ineffective respiratory pattern, impaired spontaneous ventilation, risk of bleeding and risk of ineffective gastrointestinal tissue perfusion as risk factors for death and ineffective airway clearance, impaired comfort, and acute pain as protective factors, data that can direct health teams for different interventionist actions faced with the complexity of the trauma.

SMALL INTERFERING RNA TARGETING FOCAL ADHESION KINASE PREVENTS CARDIAC DYSFUNCTION IN ENDOTOXEMIA

Sepsis and septic shock are associated with cardiac depression. Cardiovascular instability is a major cause of death in patients with sepsis. Focal adhesion kinase (FAK) is a potential mediator of cardiomyocyte responses to oxidative and mechanical stress. Myocardial collagen deposition can affect cardiac compliance and contractility. The aim of the present study was to determine whether the silencing of FAK is protective against endotoxemia-induced alterations of cardiac structure and function. In male Wistar rats, endotoxemia was induced by intraperitoneal injection of lipopolysaccharide (10 mg/kg). Cardiac morphometry and function were studied in vivo by left ventricular catheterization and histology. Intravenous injection of small interfering RNA targeting FAK was used to silence myocardial expression of the kinase. The hearts of lipopolysaccharide-injected rats showed collagen deposition, increased matrix metalloproteinase 2 activity, and myocyte hypertrophy, as well as reduced 24-h +dP/dt and -dP/dt, together with hypotension, increased left ventricular end-diastolic pressure, and elevated levels of FAK (phosphorylated and unphosphorylated). Focal adhesion kinase silencing reduced the expression and activation of the kinase in cardiac tissue, as well as protecting against the increased collagen deposition, greater matrix metalloproteinase 2 activity, and reduced cardiac contractility that occur during endotoxemia. In conclusion, FAK is activated in endotoxemia, playing a role in cardiac remodeling and in the impairment of cardiac function. This kinase represents a potential therapeutic target for the protection of cardiac function in patients with sepsis.