Fernando Luiz Affonso Fonseca

Bisphosphonate therapy in patients under androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis

The objective of this study was to clarify the role of bisphosphonates in the treatment of osteoporosis in patients with prostate adenocarcinoma under androgen deprivation therapy (ADT). The Medline, EMBASE, Cancerlit and the American Society of Clinical Oncology abstract databases were searched for published randomized, placebo-controlled trials evaluating the usage of bisphosphonates in patients with prostate cancer (PC) under ADT. The outcomes assessed were fracture, osteoporosis, incidence of adverse events and changes in bone mineral density (BMD) during treatment. A total of 15 articles (2634 participants) were included in the meta-analysis. Treatment with bisphosphonates showed a substantial effect in preventing fractures (risk ratio (RR), 0.80; P=0.005) and osteoporosis (RR, 0.39; P <0.00001). Zoledronic acid showed the best number needed to treat (NTT), compared with placebo, in relation to fractures and osteoporosis (NNT=14.9 and NNT=2.68, respectively). The between-group difference (bisphosphonates vs placebo) in the lumbar spine and femoral neck BMD were 5.18±3.38% and 2.35±1.16%, respectively. This benefit of bone loss prevention could be reached without major side effects (cardiovascular or gastrointestinal events). Bisphosphonates are effective in preventing bone loss in patients with PC who are under ADT.

Her-2/neu expression in prostate adenocarcinoma: a systematic review and meta-analysis.

PURPOSE HER-2/neu has been linked to the clinical progression of hormone independent prostate cancer. We performed a meta-analysis to investigate the prognostic impact of HER-2/neu over expression in patients with prostate adenocarcinoma, and its correlation with other pathological and clinical variables. MATERIALS AND METHODS We searched the MEDLINE, Embase, CancerLit and ASCO abstract databases for published studies of HER-2/neu protein expression in primary prostate cancer tissue with a median followup of greater than 2 years and data on survival in patients with and without HER-2/neu over expression. We separately analyzed studies reporting HER-2/neu soluble receptor levels in patients with prostate cancer. RESULTS We included 38 articles with a total of 5,976 patients. The overall RR of death in those with HER-2/neu over expression in the primary tumor was 1.63 (95% CI 1.47-1.82, p <0.0001). In the presence of over expression the recurrence RR was 1.87 (95% CI 1.59-2.21, p <0.0001). High HER-2/neu extracellular domain levels also correlated with death (RR 2.01, 95% CI 1.21-3.35, p = 0.007) and recurrence (RR 1.74, 95% CI 1.41-2.15, p <0.0001). CONCLUSIONS There is a consistent association of HER-2/neu over expression and Gleason less than 7 with a higher RR of death and recurrence in patients with prostate cancer. Further clinical trials should test the hypothesis that HER-2/neu is a marker of a clinically worse outcome in patients with prostate cancer and a potential target for therapy.

AMH: An ovarian reserve biomarker in assisted reproduction☆

Ovarian reserve tests provide knowledge of a possible response to controlled ovarian hyperstimulation in patients undergoing assisted reproduction treatment, allowing management and alteration of treatment protocol with the appropriate dose of gonadotrophin. Several parameters have been used as predictors of ovarian response. The basal FSH serum level on the third day of the menstrual cycle seemed to be the best predictor, but with significant intraindividual variability from one cycle to another. Thus, the anti-Müllerian hormone (AMH) emerges as a new ovarian test marker. AMH is produced exclusively in the gonads, by the granulosa cells, and plays an important role in folliculogenesis, acting on the modulation of follicular recruitment in the granulosa cells in order to limit the number of recruited oocytes and to regulate the number of growing follicles and their selection for ovulation. It has been suggested that AMH is strongly associated with oocyte yield after ovarian stimulation and could therefore be capable of predicting the ovarian response and the quality of oocytes and embryos. In this review, we discuss the role of AMH in assisted reproduction outcomes.

Lipodystrophy, lipid profile changes, and low serum retinol and carotenoid levels in children and adolescents with acquired immunodeficiency syndrome

OBJECTIVE To assess serum retinol and levels of carotenoids in children and adolescents with acquired immunodeficiency syndrome (AIDS) and to correlate low serum retinol and carotenoid levels with the presence of lipodystrophy, lipid profile changes, lipid peroxidation, and insulin resistance. METHODS A cross-sectional, controlled observational study was carried out with 30 children and adolescents with AIDS (mean age 9.1 y) receiving antiretroviral therapy (median length of treatment 28.4 mo), including 30 uninfected healthy controls matched for age and gender. Clinical and laboratory assessments were performed to determine nutritional status, presence of lipodystrophy, serum concentrations of retinol, beta-carotene, lycopene, lipid profile (high-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triacylglycerols), lipid peroxidation (thiobarbituric acid-reactive substances), glycemia, and serum insulin (homeostasis model assessment for insulin resistance, cutoff point >3). Statistical analysis was done with chi-square test and Students t test. RESULTS Lipodystrophy was observed in 53.3% of patients with AIDS, and dyslipidemia was detected in 60% and 23% of subjects with human immunodeficiency virus and control subjects, respectively (P = 0.004). A higher prevalence of retinol deficiency (60% versus 26.7%, P = 0.009) and beta-carotene deficiency (23.3% versus 3.3%, P = 0.026) was found in the group with human immunodeficiency virus than in the control group. No correlation was found for low retinol and beta-carotene levels, changes in lipid and glucose metabolism, or lipodystrophy in children and adolescents with AIDS. CONCLUSION Despite the high frequency of dyslipidemia, lipodystrophy, and retinol and beta-carotene deficiencies, it was not possible to demonstrate a correlation of these findings with lipid peroxidation and insulin resistance. More studies are needed to investigate the causes of retinol and beta-carotene deficiencies in this population and the clinical consequences of these findings.

Systemic chemotherapy induces microsatellite instability in the peripheral blood mononuclear cells of breast cancer patients

IntroductionSystemic chemotherapy is an important part of treatment for breast cancer. We conducted the present study to evaluate whether systemic chemotherapy could produce microsatellite instability (MSI) in the peripheral blood mononuclear cell fraction of breast cancer patients.MethodsWe studied 119 sequential blood samples from 30 previously untreated breast cancer patients before, during and after chemotherapy. For comparison, we also evaluated 20 women who had no relevant medical history (control group).ResultsIn 27 out of 30 patients we observed MSI in at least one sample, and six patients had loss of heterozygosity. We found a significant correlation between the number of MSI events per sample and chemotherapy with alkylating agents (P < 0.0001). We also observed an inverse correlation between the percentage of cells positive for hMSH2 and the number of MSI events per sample (P = 0.00019) and use of alkylating agents (P = 0.019).ConclusionWe conclude that systemic chemotherapy may induce MSI and loss of heterozygosity in peripheral blood mononuclear cells from breast cancer patients receiving alkylating agents, possibly mediated by a chemotherapy-induced decrease in the expression of hMSH2. These effects may be related to the generation of secondary leukaemia in some patients, and may also intensify the genetic instability of tumours and increase resistance to treatment.

CK-19 Expression by RT-PCR in the Peripheral Blood of Breast Cancer Patients Correlates with Response to Chemotherapy

AbstractBackground. The recent introduction of sensitive RT-PCR-based techniques for the detection of epithelial antigen expression, such as CK-19, in the peripheral blood and bone marrow of breast cancer patients may provide an opportunity to evaluate tumor response at the molecular level, even in the absence of measurable disease while patients are still receiving chemotherapy. Methods. We studied serially collected blood samples of 53 patients with breast cancer before, during, and after adjuvant, neoadjuvant, and palliative chemotherapy to evaluate its effects on the expression of CK-19 measured by RT-PCR. Results. The percentage of CK-19 RT-PCR positivity decreased consistently from 43% (23/53) before chemotherapy to 14.3% (7/49), and to 18.9% (7/37) after 3 and 6 cycles, respectively (chi-square for linear trend=7.948; p=0.0048). Furthermore, there was a significant correlation between a negative CK-19 at three months and the response to chemotherapy (p=0.024). Conclusion. We conclude that RT-PCR negativity for CK-19 expression at 3 months after the beginning of chemotherapy correlates with tumor response and, as treatment progresses, there is a significant trend for the occurrence of more negative RT-PCR results. Further studies are needed to confirm if this technique can be useful to assess response to chemotherapy in patients without measurable disease and if negativation of CK-19 expression while on chemotherapy is of prognostic significance.

Individual and social vulnerabilities upon acquiring tuberculosis: a literature systematic review

Tuberculosis is a contagious infectious disease mainly caused by the bacteria Mycobacterium tuberculosis that still meets the priority criteria - high magnitude, transcendence and vulnerability - due to the threat it poses to public health. When taking into consideration the vulnerability conditions that favor the onset of the disease, this article aimed to investigate the implications originated from individual and social vulnerability conditions in which tuberculosis patients are inserted. Databases like MEDLINE, LILACS and SciELO were searched in Portuguese, Spanish and English using the descriptors tuberculosis and vulnerability, and 183 articles were found. After the selection criterion was applied, there were 22 publications left to be discussed. Some of the aspects that characterize the vulnerability to tuberculosis are: low-income and low-education families, age, poor living conditions, chemical dependency, pre-existing conditions/aggravations like diabetes mellitus and malnutrition, indigenous communities, variables related to health professionals, intense border crossings and migration, difficulty in accessing information and health services and lack of knowledge on tuberculosis. Much as such aspects are present and favor the onset of the disease, several reports show high incidence rates of tuberculosis in low vulnerability places, suggesting that some factors related to the disease are still unclear. In conclusion, health promotion is important in order to disfavor such conditions or factors of vulnerability to tuberculosis, making them a primary target in the public health planning process and disease control.Tuberculosis is a contagious infectious disease mainly caused by the bacteria Mycobacterium tuberculosis that still meets the priority criteria - high magnitude, transcendence and vulnerability - due to the threat it poses to public health. When taking into consideration the vulnerability conditions that favor the onset of the disease, this article aimed to investigate the implications originated from individual and social vulnerability conditions in which tuberculosis patients are inserted. Databases like MEDLINE, LILACS and SciELO were searched in Portuguese, Spanish and English using the descriptors tuberculosis and vulnerability, and 183 articles were found. After the selection criterion was applied, there were 22 publications left to be discussed. Some of the aspects that characterize the vulnerability to tuberculosis are: low-income and low-education families, age, poor living conditions, chemical dependency, pre-existing conditions/aggravations like diabetes mellitus and malnutrition, indigenous communities, variables related to health professionals, intense border crossings and migration, difficulty in accessing information and health services and lack of knowledge on tuberculosis. Much as such aspects are present and favor the onset of the disease, several reports show high incidence rates of tuberculosis in low vulnerability places, suggesting that some factors related to the disease are still unclear. In conclusion, health promotion is important in order to disfavor such conditions or factors of vulnerability to tuberculosis, making them a primary target in the public health planning process and disease control.

Homocysteine and cysteine levels in prepubertal children: Association with waist circumference and lipid profile

OBJECTIVE To evaluate homocysteine and total cysteine levels in prepubertal children and to determine the association between these levels and obesity, increased waist circumference, glucose levels, and lipid profile alterations. METHODS Using a cross-sectional study, 677 prepubertal students 6 to 11 y old were assessed. The weight, height, and waist circumference of the students were measured. Laboratory analyses included triacylglycerols, total cholesterol and its fractions, glucose, vitamin B12, folate, homocysteine, and cysteine. Chi-square tests and logistic regression (forward-stepwise) were used for statistical analysis; the significance level was set at 5%. RESULTS The median age of the students was 8.9 y (6.5-11.5), and the prevalences of overweight and obesity were 90 in 677 (13.3%) and 81 in 677 (12.0%), respectively. An increase in waist circumference was observed in 180 of 677 children (26.6%). Inadequate levels of low-density lipoprotein cholesterol, triacylglycerols, and high-density lipoprotein cholesterol were found in 95 (14.0%), 129 (19.1%), and 179 (26.4%) of the 677 students, respectively. The median homocysteine and total cysteine plasma levels were 5.6 μmol/L (0.1-11.7) and 365.7 μmol/L (191.5-589.2), respectively. A multivariate analysis showed that children with a waist circumference above the 90th percentile (7.3 μmol/L) were 2.4 times (95% confidence interval 1.4-4.0) more likely to have increased homocysteine levels and that children with increased waist circumferences and those with high low-density lipoprotein cholesterol levels were 2.7 (95% confidence interval 1.6-4.6) and 2.1 (95% confidence interval 1.1-4.0) times more likely, respectively, to have total cysteine levels above the 90th percentile (445.0 μmol/L). CONCLUSION The association of abdominal obesity in prepuberty with levels of homocysteine and cysteine found in this study of a prepubertal population could be an early and independent predictor of cardiovascular risk.

IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients.

Community-acquired pneumonia (CAP) is amongst the leading causes of death worldwide. As inflammatory markers, cytokines can predict outcomes, if interpreted together with clinical data and scoring systems such as CURB-65, CRB, and Acute Physiology and Chronic Health Evaluation II (APACHE II). The aim of this study was to determine the impact of inflammatory biomarkers on the early mortality of hospitalized CAP patients. Twenty-seven CAP patients needing hospitalization were enrolled for the study and samples of interleukin-1 (IL-1) and interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and homocystein were collected at the time of admission (day 1) as well as on the seventh day of the treatment. There was a significant reduction in the levels of IL-6 between the first and the second collections. Median IL-6 values decreased from 24 pg/mL (day 1) to 8 pg/mL (day 7) (P=0.016). The median levels of TNF-α were higher in patients: i) with acute kidney injury (AKI) (P=0.045), ii) requiring mechanical ventilation (P=0.040), iii) with short hospital stays (P=0.009), iv) admitted to the intensive care unit (ICU) (P=0.040), v) who died early (P=0.003), and vi) with worse CRB scores (P=0.013). In summary, IL-6 and TNF-α levels were associated with early mortality of CAP patients. Longer admission levels demonstrated greater likelihood of early death and overall mortality, necessity of mechanical ventilation, and AKI.

Mild Systemic Oxidative Stress in the Subclinical Stage of Alzheimer’s Disease

Alzheimers disease (AD) is a late-onset, progressive degenerative disorder that affects mainly the judgment, emotional stability, and memory domains. AD is the outcome of a complex interaction among several factors which are not fully understood yet; nevertheless, it is clear that oxidative stress and inflammatory pathways are among these factors. 65 elderly subjects (42 cognitively intact and 23 with probable Alzheimers disease) were selected for this study. We evaluated erythrocyte activities of superoxide dismutase, catalase, and glutathione peroxidase as well as plasma levels of total glutathione, α-tocopherol, β-carotene, lycopene, and coenzyme Q10. These antioxidant parameters were confronted with plasmatic levels of protein and lipid oxidation products. Additionally, we measured basal expression of monocyte HLA-DR and CD-11b, as well as monocyte production of cytokines IL1-α, IL-6, and TNF-α. AD patients presented lower plasmatic levels of α-tocopherol when compared to control ones and also higher basal monocyte HLA-DR expression associated with higher IL-1α production when stimulated by LPS. These findings support the inflammatory theory of AD and point out that this disease is associated with a higher basal activation of circulating monocytes that may be a result of α-tocopherol stock depletion.