The influence of menopausal status on bone turnover and disease control in breast cancer patients with metastatic bone disease treated with chemotherapy plus zoledronic acid : an exploratory retrospective cohort study

RESUMO: Introdução: Uma meta-análise recente demonstrou que uso adjuvante de ácido zoledrónico (AZ) em mulheres pós-menopáusicas com cancro da mama precoce (CM) conduz a redução do risco de morte por CM em 17%. Investigámos o efeito do estado hormonal (pré [PrM] vs pós-menopausa tardia [PoM]) na remodelação óssea e controlo de doença em mulheres com CM e metástases ósseas (MO) tratadas com AZ e quimioterapia (QT). Métodos: Neste estudo de coorte retrospetivo, colhemos variáveis clinico-patológicas e quantificámos o telopéptido N-terminal (NTX) urinário e marcadores tumorais (MT) séricos em mulheres com CM e MO tratadas com QT e AZ. As doentes foram divididas em PrM (<45 anos) e PoM (>60 anos). Endpoints do estudo: variação do NTX, CA15.3 e CEA nos meses 3, 6 e 9, tempo até falência de QT de primeira-linha e sobrevivência. Quando apropriado foram usados os testes de Wilcoxon rank-sum, modelo de efeitos lineares mistos, teste log-rank e modelo de Cox. Resultados: Quarenta doentes foram elegíveis para análise (8 PrM e 32 PoM). Depois da introdução de AZ e QT, os níveis de NTX e MT caíram no coorte global. O perfil de resposta não diferiu entre grupos no mês 3 ou em tempos posteriores (valor-p para interação tempo-estado hormonal no mês 3=0.957). Ademais, o perfil de resposta dos MT também não diferiu entre grupos. O tempo mediano até falência de primeira-linha de QT em PrM e PoM foi de 15.2 e 17.4 meses, respetivamente. Não foi identificada diferença significativa entre grupos, quer em análise univariada quer após controlo para envolvimento visceral (p=0.399 e 0.469, respetivamente). Igualmente, não houve diferenças em termos de sobrevivência. Conclusões: Neste coorte, não foram identificadas diferenças no controlo de NTX ou MT em função do estado menopausico. Igualmente, não foi identificada diferença no tempo até falência de primeira-linha de CT ou sobrevivência.----------- ABSTRACT: Background: A recent meta-analysis showed that the adjuvant use of zoledronic acid (ZA) in postmenopausal women with early breast cancer (BC) leads to a reduction in the risk of breast cancer death by 17%. We investigated the effect of the hormonal status (pre [PrM] vs late post menopause [PoM]) on bone turnover and disease control among women with BC and boné metastases (BM) treated with ZA and chemotherapy (CT). Methods: In this retrospective cohort study, we collected clinicopathologic variables, urinary Nterminal telopeptide (NTX) and serum tumor marker levels from women with BC and BM treated with CT and ZA. Patients were divided in PrM (<45 years) and PoM (>60 years). Study endpoints were NTX, CA15.3 and CEA variation at 3, 6 and 9 months, and time to first-line CT failure and survival. We performed multilevel mixed-effects linear regression models to assess the variation of repeated measures and cox regression models for time to event outcomes. Results: Forty patients were eligible for analysis (8 PrM and 32 PoM). After introduction of ZA and CT, NTX and tumor markers declined in the overall cohort. Response profile was similar between menopausal groups at month 3 and at later time points (p-value for time-hormonal status interaction at month 3=0.957). Furthermore, tumor markers response profile was also equal between groups. Median time to first-line CT failure in PrM and PoM women was 15.2 and 17.4 months, respectively. No significant difference between groups was found, either using a univariate analysis or after controlling for visceral disease involvement (p=0.399 and 0.469, respectively). Likewise, no differences in survival were found. Conclusions: In this cohort, no differences were found in terms of NTX or tumor markers control according to menopausal status. Similarly, no difference in time to first-line CT failure or survival was found.

Clinical and hepatic evaluation in adult dengue patients: a prospective two-month cohort study

INTRODUCTION: To analyze the liver dysfunction and evolution of signs and symptoms in adult dengue patients during a two-month follow-up period. METHODS: A prospective cohort study was conducted in Campos dos Goytacazes, Rio de Janeiro, Brazil, from January to July, 2008. The evolution of laboratory and clinical manifestations of 90 adult dengue patients was evaluated in five scheduled visits within a two-month follow-up period. Twenty controls were enrolled for the analysis of liver function. Patients with hepatitis B, hepatitis C, those known to be human immunodeficiency virus (HIV) seropositive and pregnant women were excluded from the study. RESULTS: At the end of the second month following diagnosis, we observed that symptoms persisted in 33.3% (30/90) of dengue patients. We also observed that, 57.7% (15/26) of the symptoms persisted at the end of the second month. The most persistent symptoms were arthralgia, fatigue, weakness, adynamia, anorexia, taste alteration, and hair loss. Prior dengue virus (DENV) infection did not predispose patients to a longer duration of symptoms. Among hepatic functions, transaminases had the most remarkable elevation and in some cases remained elevated up to the second month after the disease onset. Alanine aminotransferase (ALT) levels overcame aspartate aminotransferase (AST) during the convalescent period. Male patients were more severely affected than females. CONCLUSIONS: Dengue fever may present a wide number of symptoms and elevated liver transaminases at the end of the second month.

Acute kidney injury in a tropical country: a cohort study of 253 patients in an infectious diseases intensive care unit

Introduction: Acute kidney injury (AKI) is a frequent and potentially fatal complication in infectious diseases. The aim of this study was to investigate the clinical aspects of AKI associated with infectious diseases and the factors associated with mortality. Methods: This retrospective study was conducted in patients with AKI who were admitted to the intensive care unit (ICU) of a tertiary infectious diseases hospital from January 2003 to January 2012. The major underlying diseases and clinical and laboratory findings were evaluated. Results: A total of 253 cases were included. The mean age was 46±16 years, and 72% of the patients were male. The main diseases were human immunodeficiency virus (HIV) infection, HIV/acquired immunodeficiency syndrome (AIDS) (30%), tuberculosis (12%), leptospirosis (11%) and dengue (4%). Dialysis was performed in 70 cases (27.6%). The patients were classified as risk (4.4%), injury (63.6%) or failure (32%). The time between AKI diagnosis and dialysis was 3.6±4.7 days. Oliguria was observed in 112 cases (45.7%). The Acute Physiology and Chronic Health Evaluation (APACHE) II scores were higher in patients with HIV/AIDS (57±20, p-value=0.01) and dengue (68±11, p-value=0.01). Death occurred in 159 cases (62.8%). Mortality was higher in patients with HIV/AIDS (76.6%, p-value=0.02). A multivariate analysis identified the following independent risk factors for death: oliguria, metabolic acidosis, sepsis, hypovolemia, the need for vasoactive drugs, the need for mechanical ventilation and the APACHE II score. Conclusions: AKI is a common complication in infectious diseases, with high mortality. Mortality was higher in patients with HIV/AIDS, most likely due to the severity of immunosuppression and opportunistic diseases.

Vitamin A, vitamin E, iron and zinc status in a cohort of HIV-infected mothers and their uninfected infants

Introduction We hypothesized that nutritional deficiency would be common in a cohort of postpartum, human immunodeficiency virus (HIV)-infected women and their infants. Methods Weight and height, as well as blood concentrations of retinol, α-tocopherol, ferritin, hemoglobin, and zinc, were measured in mothers after delivery and in their infants at birth and at 6-12 weeks and six months of age. Retinol and α-tocopherol levels were quantified by high performance liquid chromatography, and zinc levels were measured by atomic absorption spectrophotometry. The maternal body mass index during pregnancy was adjusted for gestational age (adjBMI). Results Among the 97 women 19.6% were underweight. Laboratory abnormalities were most frequently observed for the hemoglobin (46.4%), zinc (41.1%), retinol (12.5%) and ferritin (6.5%) levels. Five percent of the women had mean corpuscular hemoglobin concentrations < 31g/dL. The most common deficiency in the infants was α-tocopherol (81%) at birth; however, only 18.5% of infants had deficient levels at six months of age. Large percentages of infants had zinc (36.8%) and retinol (29.5%) deficiencies at birth; however, these percentages decreased to 17.5% and 18.5%, respectively, by six months of age. No associations between infant micronutrient deficiencies and either the maternal adjBMI category or maternal micronutrient deficiencies were found. Conclusions Micronutrient deficiencies were common in HIV-infected women and their infants. Micronutrient deficiencies were less prevalent in the infants at six months of age. Neither underweight women nor their infants at birth were at increased risk for micronutrient deficiencies.

Hormone replacement therapy and the risk of breast cancer: assessment of therapy acceptance in a cohort of previously treated breast cancer patients

INTRODUCTION: In the postmenopausal period, an average of 25% of women will present symptomatic ovarian failure requiring hormonal replacement therapy. Estrogen can relieve vasomotor symptoms. Hormonal replacement therapy is generally not recommended for breast cancer patients due to the potential risk of tumor recurrence. To answer the questions about the safety of hormonal replacement therapy in this subgroup of women, it is necessary to establish the acceptance of treatment. METHODS: Between September 1998 and February 2001, a cohort of 216 breast cancer patients were asked to complete a questionnaire. All patients had completed their treatment and were informed about survival rates after breast cancer and hormonal replacement therapy. RESULTS: Among the 216 patients, 134 (62%) would refuse hormonal replacement therapy. A hundred patients were afraid of relapse (74.6%). Adjuvant tamoxifen therapy was the only statistically significant variable (70.3% versus 29.7% p=0.003). Understanding clinical stage (p= 0.045) and type of medical assistance (private versus public , p=0.033) also seemed to influence the decision. Early stage disease (p= 0.22), type of surgical procedure (radical versus conservative, p=0.67), adjuvant chemotherapy (p=0.082) or marital status (p=0.98 ) were not statistically significant in decision making. Several patients submitted to adjuvant chemotherapy (41.6%) would accept hormonal replacement therapy under medical supervision, as did most of advanced clinical stage patients (58.3%; p=0.022). CONCLUSION: There is a high level of rejection for hormonal replacement therapy among breast cancer patients when current data on tumor cure rates, and potential risks of estrogen use is available. Adverse effects of tamoxifen in the adjuvant setting may be the reason for refusal of hormonal replacement therapy .

Light responsive multilayer surfaces with controlled spatial extinction capability

Multilayer systems obtained using the Layer-by-Layer (LbL) technology have been proposed for a variety of biomedical applications in tissue engineering and regenerative medicine. LbL assembly is a simple and highly versatile method to modify surfaces and fabricate robust and highly-ordered nanostructured coatings over almost any type of substrates and with a wide range of substances. The incorporation of polyoxometalate (POM) inorganic salts as constituents of the layers presents a possibility of promoting light-stimuli responses in LbL substrates. We propose the design of a biocompatible photo-responsive multilayer system based on a Preyssler-type POM ([NaP5W30O110]14â ) and a natural origin polymer, chitosan, using the LbL methodology. The photo-reduction properties of the POM allow the spatially controlled disruption of the assembled layers due to the weakening of the electrostatic interactions between the layers. This system has found applicability in detaching devices, such as the cell sheet technology, which may solve the drawbacks actually found in other cell treatment proposals.

An epidemiological study determining blood pressure in a Portuguese cohort: the Guimaraes/Vizela study

Surveying the evolution of blood pressure (BP) levels and hypertension (HTN) prevalence is important. A stringent strategy was utilized in a population cohort study. The BP was measured at two visits at least 3 months apart, and the results were analyzed using the following two methods: the Surveillance method (three BP measurements were performed in one visit, and the results were compared with those published previously for the identical method) and the Clinical method (three measurements per visit for two visits, and the concordant results in both visits were used to determine the BP classification). A total of 2542 subjects completed the evaluation. Using the Clinical method, an average systolic/diastolic BP value of 129.8/76.8?mm?Hg was obtained, and the prevalence of HTN was 31.6%. Of the hypertensive patients, 74.3% were aware of his/her condition; 69.1% were treated and 40.8% of those treated had adequate BP control. A total of 24.7% of subjects changed his/her BP classification between visits, and 13.7% misreported HTN. Using the Surveillance method, we determined that the average global SBP has been maintained, with HTN prevalence increasing in this region, drifting from reported trends nationally and worldwide. There has been improvement in the proportion of treated and controlled subjects; however, the Surveillance method overestimated the HTN prevalence and underestimated the proportion of treated and controlled subjects. The BP levels were higher than observed worldwide in high-cardiovascular (CV) risk countries as well as higher than the minimum risk exposure level for developing CV disease.

Pulse wave velocity distribution in a cohort study: from arterial stiffness to early vascular aging

BACKGROUND: By contrast with other southern European people, north Portuguese population registers an especially high prevalence of hypertension and stroke incidence. We designed a cohort study to identify individuals presenting accelerated and premature arterial aging in the Portuguese population. METHOD: Pulse wave velocity (PWV) was measured in randomly sampled population dwellers aged 18-96 years from northern Portugal, and used as a marker of early vascular aging (EVA). Of the 3038 individuals enrolled, 2542 completed the evaluation. RESULTS: Mean PWV value for the entire population was 8.4?m/s (men: 8.6?m/s; women: 8.2?m/s; P??10?m/s). Logistic regression models indicated gender differences concerning the risk of developing large artery damage, with women having the same odds of PWV above 10?m/s 10 years later than men. CONCLUSION: The population PWV values were higher than expected in a low cardiovascular risk area (Portugal). High prevalence rates of EVA and noteworthy large artery damage in young ages were found.

Blow-up and finite time extinction for p(x, t)-curl systems arising in electromagnetism

"Available online 22 March 2016"

Intrauterine ductus arteriosus constriction: analysis of a historic cohort of 20 cases

OBJECTIVE: To describe the relative incidence, presentation, and evolvement of fetuses with early ductus constriction. METHODS: Twenty fetal echocardiograms indicating ductus constriction were reviewed in a population of 7000 pregnants. RESULTS: The cases were divided into group A (related to maternal use of cyclooxygenase inhibitors [n=7] and group B (idiopathics [n=13]). Mean gestational age was 32.5±3.1 (27-38) weeks and maternal age was 28.2±8.5 (17-42) years. Mean systolic velocity in the ductus was 2.22±0.34 (1.66-2.81) m/s, diastolic velocity 0.79±0.28 (0.45-1.5) m/s, and pulsatility index 1.33±0.36 (0.52-1.83). Two cases of ductal occlusion were noted. In 65% of the cases, an increase occurred in the right cavities; in 90% of the cases, tricuspid or pulmonary regurgitation, or both, occurred, with functional pulmonary atresia in 1 case. Diastolic velocity was greater in group A (1.13±0.33) than in group B (0.68±0.15) (P=0.008). The other data were similar in the 2 groups. The evolvement was not favorable in 4 patients from group B, including 1 death and 2 cases of persistent pulmonary hypertension. CONCLUSION: The high incidence of idiopathic constriction of the ductus arteriosus suggests that its diagnosis is underestimated and that many cases of persistence of fetal circulation in newborns may be related to constriction of the ductus arteriosus not diagnosed during intrauterine life. Group B had a lower severity but a risk of an unfavorable evolvement, suggesting a distinct alteration.

role of the anterior cingulate cortex in extinction learning of avoidance behavior and in the retrieval of its extinction memory

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2012

Evaluation of Sexual Dimorphism in the Efficacy and Safety of Simvastatin/Atorvastatin Therapy in a Southern Brazilian Cohort

Background: Dyslipidemia is the primary risk factor for cardiovascular disease, and statins have been effective in controlling lipid levels. Sex differences in the pharmacokinetics and pharmacodynamics of statins contribute to interindividual variations in drug efficacy and toxicity. Objective: To evaluate the presence of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin treatment. Methods: Lipid levels of 495 patients (331 women and 164 men) were measured at baseline and after 6 ± 3 months of simvastatin/atorvastatin treatment to assess the efficacy and safety profiles of both drugs. Results: Women had higher baseline levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared with men (p < 0.0001). After treatment, women exhibited a greater decrease in plasma TC and LDL-C levels compared with men. After adjustment for covariates, baseline levels of TC and LDL-C influenced more than 30% of the efficacy of lipid-lowering therapy (p < 0.001), regardless of sex. Myalgia [with or without changes in creatine phosphokinase (CPK) levels] occurred more frequently in women (25.9%; p = 0.002), whereas an increase in CPK and/or abnormal liver function was more frequent in in men (17.9%; p = 0.017). Conclusions: Our results show that baseline TC and LDL-C levels are the main predictors of simvastatin/atorvastatin therapy efficacy, regardless of sex. In addition, they suggest the presence of sexual dimorphism in the safety of simvastatin/atorvastatin. The effect of sex differences on receptors, transporter proteins, and gene expression pathways needs to be better evaluated and characterized to confirm these observations.

Blood Pressure Variation Throughout Pregnancy According to Early Gestational BMI: A Brazilian Cohort

Background: The maternal cardiovascular system undergoes progressive adaptations throughout pregnancy, causing blood pressure fluctuations. However, no consensus has been established on its normal variation in uncomplicated pregnancies. Objective: To describe the variation in systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels during pregnancy according to early pregnancy body mass index (BMI). Methods: SBP and DBP were measured during the first, second and third trimesters and at 30-45 days postpartum in a prospective cohort of 189 women aged 20-40 years. BMI (kg/m2) was measured up to the 13th gestational week and classified as normal-weight (<25.0) or excessive weight (≥25.0). Longitudinal linear mixed-effects models were used for statistical analysis. Results: A decrease in SBP and DBP was observed from the first to the second trimester (βSBP=-0.394; 95%CI: -0.600- -0.188 and βDBP=-0.617; 95%CI: -0.780- -0.454), as was an increase in SBP and DBP up to 30-45 postpartum days (βSBP=0.010; 95%CI: 0.006-0.014 and βDBP=0.015; 95%CI: 0.012-0.018). Women with excessive weight at early pregnancy showed higher mean SBP in all gestational trimesters, and higher mean DBP in the first and third trimesters. Excessive early pregnancy BMI was positively associated with prospective changes in SBP (βSBP=7.055; 95%CI: 4.499-9.610) and in DBP (βDBP=3.201; 95%CI: 1.136-5.266). Conclusion: SBP and DBP decreased from the first to the second trimester and then increased up to the postpartum period. Women with excessive early pregnancy BMI had higher SBP and DBP than their normal-weight counterparts throughout pregnancy, but not in the postpartum period.

Effect on renal function of tenofovir co-administered with either efavirenz or boosted lopinavir or boosted atazanavir: the Swiss HIV Cohort Study

Reduced re'nal function has been reported with tenofovir disoproxil fumarate (TDF). It is not clear whether TDF co-administered with a boosted protease inhibitor (PI) leads to a greater decline in renal function than TDF co-administered with a non-nucleoside reverse transcriptase inhibitor (NNRTI).Methods: We selected ail antiretroviral therapy-naive patients in the Swiss HIV Cohort Study (SHCS) with calibrated or corrected serum creatinine measurements starting antiretroviral therapy with TDF and either efavirenz (EFV) or the ritonavir-boosted PIs, lopinavir (LPV/r) or atazanavir (ATV/r). As a measure of renal function, we used the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate the glomerular filtration rate (eGFR). We calculated the difference in eGFR over time between two therapies using a marginal model for repeated measures. In weighted analyses, observations were weighted by the product of their point of treatment and censoring weights to adjust for differences both in the sort of patients starting each therapy and in the sort of patients remaining on each therapy over time.Results: By March 2011, 940 patients with at least one creatinine measurement on a first therapy with either TDF and EFV (n=484), TDF and LPVlr (n=269) or TDF and ATV/r (n=187) had been followed for a median of 1. 7, 1.2 and 1.3 years, respectively. Table 1 shows the difference in average estimated GFR (eGFR) over time since starting cART for two marginal models. The first model was not adjusted for potential confounders; the second mode! used weights to adjust for confounders. The results suggest a greater decline in renal function during the first 6 months if TDF is used with a PI rather than with an NNRTI, but no further difference between these therapies after the first 6 months. TDF and ATV/r may lead to a greater decline in the first 6 months than TDF and LPVlr.Conclusions: TDF co-administered with a boosted PI leads to a greater de cline in renal function over the first 6 months of therapy than TDF co-administered with an NNRTI; this decline may be worse with ATV/r than with LPV/r.