Rosuvastatin and Cardiovascular Events in Patients Undergoing Hemodialysis

Background Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not been proved. Methods We conducted an international, multicenter, randomized, double-blind, prospective trial involving 2776 patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis. We randomly assigned patients to receive rosuvastatin, 10 mg daily, or placebo. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events. Results After 3 months, the mean reduction in low-density lipoprotein (LDL) cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline level of 100 mg per deciliter (2.6 mmol per liter). During a median follow-up period of 3.8 years, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point (9.2 and 9.5 events per 100 patient-years, respectively; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group, 0.96; 95% confidence interval [CI], 0.84 to 1.11; P = 0.59). Rosuvastatin had no effect on individual components of the primary end point. There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P = 0.51). Conclusions In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (ClinicalTrials.gov number, NCT00240331.)

Association of Changes in Bone Remodeling and Coronary Calcification in Hemodialysis Patients: A Prospective Study

Background: Vascular calcification is common and constitutes a prognostic marker of mortality in the hemodialysis population. Derangements of mineral metabolism may influence its development. The aim of this study is to prospectively evaluate the association between bone remodeling disorders and progression of coronary artery calcification (CAC) in hemodialysis patients. Study Design: Cohort study nested within a randomized controlled trial. Setting & Participants: 64 stable hemodialysis patients. Predictor: Bone-related laboratory parameters and bone histomorphometric characteristics at baseline and after 1 year of follow-up. Outcomes: Progression of CAC assessed by means of coronary multislice tomography at baseline and after 1 year of follow-up. Baseline calcification score of 30 Agatston units or greater was defined as calcification. Change in calcification score of 15% or greater was defined as progression. Results: Of 64 patients, 26 (40%) had CAC at baseline and 38 (60%) did not. Participants without CAC at baseline were younger (P < 0.001), mainly men (P = 0.03) and nonwhite (P = 0.003), and had lower serum osteoprotegerin levels (P = 0.003) and higher trabecular bone volume (P = 0.001). Age (P 0.003; beta coefficient = 1.107; 95% confidence interval [Cl], 1.036 to 1.183) and trabecular bone volume (P = 0.006; beta coefficient = 0.828; 95% Cl, 0.723 to 0.948) were predictors for CAC development. Of 38 participants who had calcification at baseline, 26 (68%) had CAC progression in 1 year. Progressors had lower bone-specific alkaline phosphatase (P = 0.03) and deoxypyridinoline levels (P = 0.02) on follow-up, and low turnover was mainly diagnosed at the 12-month bone biopsy (P = 0.04). Low-turnover bone status at the 12-month bone biopsy was the only independent predictor for CAC progression (P = 0.04; beta coefficient = 4.5; 95% Cl, 1.04 to 19.39). According to bone histological examination, nonprogressors with initially high turnover (n = 5) subsequently had decreased bone formation rate (P = 0.03), and those initially with low turnover (n = 7) subsequently had increased bone formation rate (P = 0.003) and osteoid volume (P = 0.001). Limitations: Relatively small population, absence of patients with severe hyperparathyroidism, short observational period. Conclusions: Lower trabecular bone volume was associated with CAC development, whereas improvement in bone turnover was associated with lower CAC progression in patients with high- and low-turnover bone disorders. Because CAC is implicated in cardiovascular mortality, bone derangements may constitute a modifiable mortality risk factor in hemodialysis patients.

Fibroblast Growth Factor 23 in Hemodialysis Patients: Effects of Phosphate Binder, Calcitriol and Calcium Concentration in the Dialysate

Background: Fibroblast growth factor 23 (FGF23) concentrations increase early in chronic kidney disease (CKD), and the influence of current CKD-mineral and bone disorder (MBD) therapies on serum FGF23 levels is still under investigation. Methods: In this post-hoc analysis of a randomized clinical trial, phosphate binders and calcitriol were washed out of 72 hemodialysis patients who were then submitted to bone biopsy, coronary tomography and biochemical measures, including FGF23. They were randomized to receive sevelamer or calcium acetate for 1 year and the prescription of calcitriol and the calcium concentration in the dialysate were adjusted according to serum calcium, phosphate and PTH and bone biopsy diagnosis. Results: At baseline, bone biopsy showed that 58.3% had low-turnover bone disease, whereas 38.9% had high-turnover bone disease, with no significant differences between them with regard to FGF23. Median baseline FGF23 serum levels were elevated and correlated positively with serum phosphate. After 1 year, serum FGF23 decreased significantly. Repeated measures ANOVA analysis showed that the use of a 3.5-mEq/l calcium concentration in the dialysate, as well as the administration of calcitriol and a calcium-based phosphate binder were associated with higher final serum FGF23 levels. Conclusions: Taken together, our results confirm that the current CKD-MBD therapies have an effect on serum levels of FGF23. Since FGF23 is emerging as a potential treatment target, our findings should be taken into account in the decision on how to manage CKD-MBD therapy. Copyright (C) 2010 S. Karger AG, Basel

Angioplasty and Stent Placement in Symptomatic Internal Carotid Occlusion

PURPOSE: To report a series of patients with symptomatic internal carotid artery (ICA) occlusion treated with angioplasty and stents. MATERIALS AND METHODS: From a consecutive series of 50 patients experiencing neurologic ischemic symptoms and shown by conventional ultrasonography (US) to have a total ICA occlusion, 16 patients (ages 45-79 years; mean, 63 y; 10 men) were selected between August 2006 to September 2008 to be treated with angioplasty based on discovery of an open ICA distal to the occlusion through contrast-enhanced echo Doppler imaging and/or multislice contrast computed tomography (CT). Angioplasty and stent placement were performed under cerebral protection. Follow-up duplex imaging was performed at 14 days and 3 months and every 6 months thereafter and CT follow-up was performed at 2-9 months; the mean follow-up period was 9.9 months. RESULTS: Lesion crossing and stent placement was successful in 13 of 16 patients. There were no deaths, conversions, cardiac complications, or major strokes. One patient had a transient mild hemiparesis in the upper limb, with total recovery in 3 months. At follow-up, all 13 patients with a good initial result remained with patent arterial lumens and resolution of neurologic ischemic symptoms. After 2-9 months, ICAs with a ""string sign"" had calibers close or equal to those of normal arteries. CONCLUSIONS: Angioplasty with stent placement is an effective treatment with a low morbidity rate for selected patients who continue to experience neurologic ischemic symptoms despite US findings of total occlusion of the ICA.

Menstrual and hormonal alterations in juvenile systemic lupus erythematosus

Menstrual cycles of 30 patients with juvenile systemic lupus erythematosus (JSLE) were compared with 30 age-matched controls. The mean age of patients with JSLE and controls was similar (17.4 +/- 3.2 vs 17.06 +/- 2.08 years, P = 0.66). The mean menarche age was higher in JSLE than controls (13.13 +/- 1.4 vs 11.56 +/- 1.5 years, P = 0.0008). On the contrary, the mean maternal menarche age was similar in both groups (P = 0.62). Menstrual abnormalities and longer length cycles were more frequently observed in JSLE than controls (63% vs 10%, P = 0.0001; 23% vs 0%, P = 0.0105, respectively). The median of follicle stimulating hormone was significantly higher in patients with JSLE compared with controls (4.6 vs 3.4 IU/L, P = 0.0207), and the median of progesterone was lower (32.5 vs 70 ng/mL, P = 0.0033). The median Of luteinizing hormone was lower in patients with JSLE with menstrual abnormalities versus normal cycles (2.9 vs 5.5 IU/L, P = 0.019) and both had a high percentage of decreased progesterone levels (63% vs 73%, P = 0.70). Our findings support the notion that menstrual disturbances are frequent and may be associated with pituitary dysfunction leading to a decreased progesterone production. We also reported that in spite of premature ovarian failure being a rare event in JSLE the follicular reserve seems to be low regardless of intravenous cyclophosphamide treatment. Lupus (2009) 18, 38-43.

The influence of lean mass in trabecular and cortical bone in juvenile onset systemic lupus erythematosus

The aim of this study was to evaluate risk factors for low bone mineral density (BMD) and vertebral fractures, in juvenile systemic lupus (JSLE). Thirty-one consecutive patients with JSLE were compared with 31 gender- and age-matched healthy controls. BNID and body composition from all participants were measured using dual-energy X-ray absorptiometry. Vertebral fractures were defined as a reduction of >= 20% of the vertebral height for all patients. Lumbar spine and total femur BMD was significantly decreased in patients compared with controls (P = 0.021 and P = 0.023, respectively). A high frequency of vertebral fractures (22.58%) was found in patients with JSLE. Analysis of body composition revealed lower lean mass (P = 0.033) and higher fat mass percentage (P = 0.003) in patients than in controls. Interestingly, multiple linear regression using BMD as a dependent variable showed a significant association with lean mass in lumbar spine (R(2) = 0.262; P = 0.004) and total femur (R(2) = 0.419, P = 0.0001), whereas no association was observed with menarche age, SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology, and glucocorticoid. This study indicates that low BMD and vertebral fractures are common in JSLE, and the former is associated with low lean mass, suggesting that muscle rehabilitation may be an additional target for bone therapeutic approach.

Outpatient treatment with intravenous antimicrobial therapy and oral levofloxacin in patients with febrile neutropenia and hematological malignancies

The purpose of this study was to evaluate outcomes such as success of the initial therapy, failure of outpatient treatment, and death in outpatient treatment during intravenous antimicrobial therapy in patients with febrile neutropenia (FN) and hematological malignancies. In addition, clinical and laboratory data and the Multinational Association for Supportive Care of Cancer index (MASCC) were compared with failure of outpatient treatment and death. In a retrospective study, we evaluated FN following chemotherapy events that were treated initially with cefepime, with or without teicoplanin and replaced by levofloxacin after 48 h of defervescence in patients with good general conditions and ANC > 500/mm(3). Of the 178 FN episodes occurred in 126 patients, we observed success of the initial therapy in 63.5% of the events, failure of outpatient treatment in 20.8%, and death in 6.2%. The success rate of oral levofloxacin after defervescence was 99% (95 out of 96). Using multivariate analysis, significant risks of failure of outpatient treatment were found to be smoking (odds ratio (OR) 3.14, confidence interval (CI) 1.14-8.66; p = 0.027) and serum creatinine levels > 1.2 mg/dL (OR 7.97, CI 2.19-28.95; p = 0.002). With regard to death, the risk found was oxygen saturation by pulse oximetry < 95% (OR 5.8, IC 1.50-22.56; p = 0.011). Using the MASCC index, 165 events were classified as low risk and 13 as high risk. Failure of outpatient treatment was reported in seven (53.8%) high-risk and 30 (18.2%) low-risk episodes (p = 0.006). In addition, death occurred in seven (4.2%) low-risk and four (30.8%) high-risk events (p = 0.004). Ours results show that MASCC index was able to identify patients with high risk. In addition, non-smoking, serum creatinine levels a parts per thousand currency sign1.2 mg/dL, and oxygen saturation by pulse oximetry a parts per thousand yen95% were protection factors.

Menstrual and hormonal alterations in juvenile dermatomyositis

Objective To evaluate age at menarche, menstrual cycles and hormone profile in juvenile dermatomyositis (JDM) patients and controls. Methods Twelve consecutive JDM patients were compared to 24 age-matched healthy subjects. Age at menarche and age of maternal menarche were recorded. Menstrual cycle was evaluated prospectively for 6 consecutive months and the mean cycle length and flow were calculated. The hormone profile was collected on the last menstrual cycle. Demographic data, clinical features, muscle enzymes, JDM scores and treatment were analysed. Results The median of current age of JDM patients and controls was similar (18 vs. 17 years, p=0.99). The median age at menarche of the JDM patients was higher than in the control group (13 vs. 11 years, p=0.02) whereas the median age of maternal menarche was alike in both groups (12 vs. 13 years, p=0.67). Menstrual disturbances were not observed, except for one patient who had longer length of menstrual cycle. The median of follicle stimulating hormone (FSH) was significantly higher in JDM patients compared to controls (4.5 vs. 3.0 IU/L, p=0.02) and none of them had premature ovarian failure (POF). The median of progesterone was significantly lower in JDM patients (0.3 vs. 0.7 ng/mL, p=0.01) with a higher frequency of decreased progesterone compared to controls (75% vs. 29%, p=0.01). Conclusions Our study identifies in JDM patients delayed menarche with normal cycles and low follicular reserve. The decreased progesterone levels may suggest an underlying subclinical corpus luteum dysfunction in this disease.

Causes of death and cardiovascular complications in adolescents and adults with congenitally malformed hearts: an autopsy study of 102 cases

Objectives: To identify the causes of death and main cardiovascular complications in adolescents and adults with congenitally malformed hearts. Design: Retrospective review of 102 necropsy reports from a tertiary centre obtained over a period of 19 years. Methods: The diagnosis, the operated or non-operated state of the main defect, the cause of death, and main complications were related to the age and gender. Other clinically relevant conditions, and identifiable sequels of previous diseases, were also noted. Results: The ages ranged from 15 to 69 years, with a mean of 31.1 and a median of 28 years, with no difference detected according to the gender. Of the patients, two-thirds had been submitted to at least one cardiac surgery. The mean age of death was significantly higher in non-operated patients (p = 0.003). The most prevalent cause of death in the whole group was related to recent surgery, found in one-third. From them, two-fifths corresponded to reoperations. Among the others, cardiac failure was the main terminal cause in another third, and the second cause was pulmonary thromboembolism in just over one-fifth, presenting a significant association with histopathological signs of pulmonary hypertension (p = 0.011). Infection was the cause of death in 7.8% of the patients, all previously operated. Acute infective endocarditis was present or was the indication for the recent surgery in one-tenth of the patients, this cohort having a mean age of 27.8 years. There was a statistically significant association between the occurrence of endocarditis and defects causing low pulmonary blood flow (p = 0.043). Conclusions: Data derived from necropsies of adults with congenital heart defects can help the multidisciplinary team refine both their diagnosis and treatment.

Accuracy of store-and-forward diagnosis in leproy

Telemedicine might increase the speed of diagnosis for leprosy and reduce the development of disabilities. We compared the accuracy of diagnosis made by telemedicine with that made by in-person examination. The cases were patients with suspected leprosy at eight public health clinics in outlying areas of the city of Sao Paulo. The case history and clinical examination data, and at least two clinical images for each patient, were stored in a web-based system developed for teledermatology. After the examination in the public clinic, patients then attended a teaching hospital for an in-person examination. The benchmark was the clinical examination of two dermatologists at the university hospital. From August 2005 to April 2006, 142 suspected cases of leprosy were forwarded to the website by the doctors at the clinics. Of these, 36 cases were excluded. There was overall agreement in the diagnosis of leprosy in 74% of the 106 remaining cases. The sensitivity was 78% and the specificity was 31%. Although the specificity was low, the study suggests that telemedicine may be a useful low-cost method for obtaining second opinions in programmes to control leprosy.

Peginterferon alfa-2b and Ribavirin: Effective in Patients With Hepatitis C Who Failed Interferon alfa/Ribavirin Therapy

Background & Aims: Treatment with peginterferon alfa and ribavirin produces a sustained virologic response (SVR) in approximately 60% of hepatitis C virus (HCV)-infected patients. Alternate options are needed for patients who relapse or do not respond to therapy. Methods: This prospective, international, multicenter, open-label study evaluated efficacy and safety of peginterferon alfa-2b (1.5 mu g/kg/wk) plus weight-based ribavirin (800-1400 mg/day) in 2333 chronic HCV-infected patients with significant fibrosis/cirrhosis whose previous interferon alfa/ribavirin therapy failed. Patients with undetectable HCV-RNA at treatment week (TW) 12 received 48 weeks of therapy; patients with detectable HCV-RNA at TW12 could enter maintenance studies at TW18; 188 patients with low/detectable HCV-RNA at TW12 continued therapy at the investigator`s request. Results: Overall, 22% of the patients attained SVR (56% with undetectable HCV-RNA and 12% with low/detectable HCV-RNA at TW12). SVR was better in relapsers (38%) than nonresponders (14%), regardless of previous treatment, and in patients previously treated with interferon-alfa/ribavirin (25%) than peginterferon alfa-ribavirin (17%). Predictors of response in patients with undetectable HCV-RNA at TW12 were genotype (2/3 vs 1, respectively; odds ratio [OR] 2.4; P < .0001), fibrosis score (F2 vs F4; OR, 2.2; F3 vs F4; OR, 1.7; P < .0001), and baseline viral load (<= 600,000 vs >600,000 IU/mL; OR, 1.4; P = .0223). These factors plus previous treatment and response were overall predictors of SVR. Safety was similar among fibrosis groups. Conclusions: Peginterferon alfa-2b plus weight-based ribavirin is effective and safe in patients who failed interferon alfa/ribavirin therapy. Genotype, baseline viral load, and fibrosis stage were predictors of response.

Gastric secretory and hormonal patterns in end-stage chagasic achalasia

P>Achalasia surgical treatment alters the esophagogastric junction anatomy (cardiomyotomy plus fundoplication or esophagectomy and gastric pull-up), thus favoring a certain degree of gastroesophageal reflux. Gastric secretory and hormonal functioning is not completely known in chagasic patients. The aim of this study was to evaluate the gastric secretory and hormonal response in patients with end-stage chagasic achalasia compared with normal subjects. Gastric secretion and hormonal response were assessed by estimation of gastric acid secretion (GAS) in basal condition and after pentagastrin stimulation, basal serum gastrin, and serum pepsinogen (SP) in basal condition and after betazole hydrochloride (Histalog (R); Eli Lilly and Company, Indianapolis, IN, USA) stimulation in 27 patients with chagasic achalasia. The results were then compared with those of 24 normal subjects. In the chagasic group, the mean basal and stimulated GAS were significantly lower than in the control group (basal: 1.277 vs. 3.13, P = 0.002; stimulated: 15.9 vs. 35.8, P = 0.0001). Chagasic patients` SG levels showed a significantly higher basal value than the control group (83.3 vs. 36.8, P = 0.0001). There was a significant increase of SP after stimulation compared with the basal levels in both chagasic and control groups. Although the chagasic patients` SP values were higher than the controls, this difference was not statistically significant, either in basal and stimulated conditions (basal: 122.0 vs. 108.9, stimulated 120 min: 177.1 vs. 158.9). In patients with chronic Chagas` disease (ChD), although autonomic denervation does not suppress the strength of the gastric mucosal cells` secretory response to stimulation, it reduces GAS (parietal cell) without, however, affecting SP production (chief cells). On the other hand, the gastrin-producing cells have continuously been stimulated by low GAS.

Polymorphisms of APOE and LRP genes in Brazilian individuals with Alzheimer disease

Alzheimer disease (AD) is the most frequent cause of dementia in Western countries. Putative genetic risk factors for AD are polymorphisms in the apolipoprotein E (APOE) gene and in the low-density lipoprotein receptor-related protein (LRP) gene. Our objective was to investigate the role of the APOE coding region polymorphisms epsilon 2, epsilon 3, and epsilon 4 and APOE promoter variants A/T at position -491 and G/T at -219, as well as LRP polymorphism C/T, as risk factors for AD in Brazilian individuals. One hundred and twenty patients with probable AD, along with 120 controls were analyzed. A significant difference between patients and controls for 64 alleles was observed: frequency of this allele in AD was 0.31, and 0.10 in controls. Individuals with 2 FA alleles had a higher risk for AD than subjects with only 1 such allele; presence of 1 epsilon 2 allele proved protective. The presence of the T allele of the -219 polymorphism was also associated with an increased risk of AD, but this polymorphism is in linkage disequilibrium with APOE F polymorphisms. No significant differences between patients and controls were observed for -491 APOE or LRP polymorphisms. In this Brazilian population, both the epsilon 4 allele and T -219 polymorphism were associated with an increased risk for AD.

Height and weight gains in a nutrition rehabilitation day-care service

Objective: To evaluate nutritional recovery patterns in 106 undernourished children assisted by the Center of Nutritional Recovery and Education (CREN, in Portuguese) between January 1995 and December 1999. Design: CREN assists undernourished children aged 0 to 72 months living in the southern regions of Sao Paulo, in an outpatient setting. Nutritional status was assessed by Z-scores of weight-for-age, height-for-age and weight-for-height. Nutritional recovery evaluation considered Z-score gains in weight-for-age and height-for-age, grouping into four categories (Z-score increment of 0.50 between groups). Children with birth weight less than 2500 g were classified as low birth weight (LBW), while those born at term and with LBW were classified as small for gestational age. Setting: CREN (Center of Nutritional Recovery and Education in Portuguese), Sao Paulo, Brazil. Subjects: One hundred and six children from CREN. Results: Among the 106 evaluated children, ninety-eight (92.5%)recovered their weight or height and seventy-two (67.9%) recovered both. Nearly half of studied children presented a nutritional recovery (increase in Z-score) of more than 0.50 in height-for-age (46.2%) and about 40% in weight-for-age (38.7%). Multivariate analysis showed that treatment duration and initial weight-for-age contributed to weight-for-age Z-score increment, explaining 25% of the variation; and treatment duration, initial height-for-age and weight-for-age Z-score increment contributed to height-for-age Z-score increment, explaining 62% of the variation. Conclusions: Our findings show that nutritional recovery among children who attended CREN was influenced primarily by the degree of nutritional deficit at admission. It has also been shown that biological variables are more important than socio-economic status in determining the rate of nutritional recovery.

Erectile Dysfunction and Correlated Factors in Brazilian Men Aged 18-40 years

Introduction. Few population-based studies in erectile dysfunction (ED) included subjects less than 40 years old and analyzed the several factors and consequences potentially associated with this condition. Aim. Evaluation of the prevalence of erectile dysfunction (ED) and associated factors in a sample of Brazilian men aged 18 to 40 years old. Methods. Cross-sectional study in which subjects were contacted in public places of 18 major Brazilian cities and interviewed using an anonymous questionnaire. Survey data were submitted to chi-squared, student`s t-test and logistic regression analyses. Main Outcome Measures. The data were collected by means of a self-administered questionnaire with 87 questions about sociodemographic variables, general health, habits and lifestyle-related factors, sexual behavior and sexual difficulties, including ED which was assessed by a single question. Results. Prevalence of ED in 1,947 men was 35.0% (73.7% mild, 26.3% moderate/complete). Greater frequency of ED was seen in subjects that never had information about sex, experienced difficulties in the beginning of sexual life and have never masturbated. ED was associated to lower level of education, but not to race, sexual orientation, employment or marital status. Also, no association was found between ED and smoking, alcoholism, obesity, sedentary life, diabetes, hypertension, cardiovascular disease, hyperlipidemia, depression or anxiety. ED caused negative impact in men`s self-esteem, interpersonal relationships, work and leisure activities, and in sexual life satisfaction. Less than 10% of men with ED had received medical treatment for this problem. Conclusions. Prevalence of ED in this young population was high, mostly of mild severity. Low education and psychosocial problems were associated to ED and, due probably to the sample subjects` young age, no association was found with organic problems. Measures in the fields of education and psychosocial difficulties prevention would have a positive impact in the control of erectile dysfunction in the young population. Martins FG, and Abdo CHN. Erectile dysfunction and correlated factors in Brazilian men aged 18-40 years. J Sex Med 2010;7:2166-2173.