Gabriel Cavada

A Randomized, Double-Blind, Placebo-Controlled Trial of Spironolactone on Carotid Intima-Media Thickness in Nondiabetic Hemodialysis Patients

BACKGROUND AND OBJECTIVES Hemodialysis patients (HD) display high rates of cardiac diseases and mortality. In chronic kidney disease, vascular injury leads to coronary artery disease, heart failure, and stroke. Carotid intima-media thickness (CIMT) measurements are currently widely used in randomized controlled trials (RCTs) to study the efficacy of interventions. An RCT was designed for the assessment of the safety and effectiveness of spironolactone to inhibit the progression of CIMT in HD patients as a primary outcome. Secondary outcomes included measurements of plasma potassium. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS HD patients were randomly assigned to receive 50 mg spironolactone or placebo thrice weekly after dialysis. In between dialysis sessions, plasma potassium concentrations were measured every month. Ultrasonographic measurements of CIMT were done at the beginning of the study and after 2 years. RESULTS Fifty-three age- and sex-adjusted patients (30 with drug and 23 with placebo) successfully completed the trial. There were no significant differences between the two groups in all profiles studied at baseline. Measurements of CIMT after 2 years showed a progression in the placebo group, whereas in the spironolactone group a significant decrease or even reversed CIMT was observed. Progression rates (mm/yr) were: common carotid, placebo: 0.06 +/- 0.07, spironolactone: 0.01 +/- 0.04; carotid bifurcation, placebo: 0.15 +/- 0.27, spironolactone: 0.0001 +/- 0.01; internal carotid, placebo: 0.10 +/- 0.12, spironolactone: -0.10 +/- 0.15. No episodes of hyperkalemia were observed, but a slight increase in plasma potassium was found in the spironolactone group. CONCLUSIONS Fifty milligrams of spironolactone thrice weekly significantly reduced the progression of CIMT in HD patients.

Early steroid withdrawal in pediatric renal transplant on newer immunosuppressive drugs.

Abstract:  Steroids have been a cornerstone in renal transplant immunosuppression. New immunosuppressive drugs have led to protocols using early steroid withdrawal or complete avoidance. A prospective protocol in 23 pediatric renal transplant (ages 2–14 yr) who received decreasing steroid doses stopping at day 7 post‐Tx, FK, and MMF were compared with a CsA, AZT, historically matched steroid‐based control group. Basiliximab was used in two doses. Anthropometric, biochemical variables, AR rates, and CMV infection were evaluated and compared using Student’s t‐test and regression analysis. A better growth pattern was seen in steroid withdrawal group. GFR rate and serum glucose were similar in both groups. Total serum cholesterol levels were significantly lower in steroid withdrawal group. The incidence of AR at 12 months was 4.3% in steroid withdrawal group vs. 8.6% in steroid‐based group (p = ns). No difference in CMV infection was observed. Hemoglobin levels were low during the first months in both groups; reached normal values after six months. SBP became higher at 12 months in steroid‐based group. Patient and graft survival was 98% in both groups at one‐yr post‐transplant. Early steroid withdrawal was efficacious, safe, and did not increase risk of rejection, preserving optimal growth, renal function, and reducing cardiovascular risk factors.

Leptin and IGF-I/II during the first weeks of life determine body composition at 2 years in infants born with very low birth weight.

Abstract Rapid early growth is associated with adverse metabolic outcome. The aim of this study was to determine whether there are differences in body composition (BC) between very-low-birth-weight preterm (VLBWPT) infants born appropriate for gestational age (AGA) and small for gestational age (SGA) and whether these differences relate to first-year growth. Twenty-six VLBWPT (15 AGA and 11 SGA). The BC was analyzed by dual X-ray absorptiometry at 2 years, and insulin-like growth factors (IGFs) I and II and leptin were administered weekly for 8 weeks and at 1, 3, 6, and 12 months. At 24 months, the VLBW SGA infants were lighter and had less peripheral fat and lean mass than VLBW AGA infants. In all patients, the percentage of fat mass correlated inversely with the change in weight [standard deviation scores (SDS)] from newborn to 2 and 4 weeks and the 1-month leptin and lean mass (SDS) correlated inversely with the change in weight (SDS) from newborn to 2, 4, and 8 weeks and with 4-week IGF-I and 8-week IGF-II. Lean mass (SDS) inversely correlated with 6-month IGF-I and directly correlated with 1-week and 3-month IGF-I in SGA VLBW infants only. A longer follow-up period will show whether additional differences will develop later.

La razón cintura estatura en escolares no varía con el género, la edad ni la maduración puberal

Background: Waist-to-height ratio (WHtR) is a cardiometabolic risk indicator in children. A value greater than or equal to 0.55 is an effective screening tool for identifying obese children with metabolic syndrome. However, it is unclear whether this cutoff can be applied equally to any age or gender. Aim: To analyze the variability of WHtR by age, gender and pubertal stage in elementary school children. Patients and methods: Cross-sectional study in 2,980 school children (6-14 years old, 51% male) of Santiago, Chile. We measured weight, height and waist circumference and calculated body mass index and WHtR. Pubertal stage was assessed and classified as peripubertal (Tanner I and II) and pubertal (Tanner III, IV and V). Results: The mean age was 9.9 ± 2.3 years, with no gender difference (p = 0.5). Eighty one percent of boys and 59.4 % of girls were peripubertal (p<0.001). The association between age- adjusted WHtR by gender and pubertal stage was not significant (p= 0.409). Therefore mean, standard deviation and percentiles of WHtR were calculated without sex and pubertal stage segmentations. Conclusions: Since WHtR does not vary with age, gender and pubertal status in elementary school children, it is possible to use a single cutoff value, previously defined in this population, to identify children with cardiometabolic risk.

Bariatric surgery decreases carotid intima-media thickness in obese subjects

BACKGROUND Obesity has long been associated with an increased risk of cardiovascular disease (CVD). The aim of this study was to evaluate the impact of substantial weight loss induced by bariatric surgery on carotid intima media thickness (C-IMT) (surrogate marker of early atherosclerosis) and classic factors of cardiovascular risk (CVRFs). METHODS thirty-one obesity patients were evaluated for bariatric surgery. Twenty-seven were undergone surgery, 14 Roux-en-Y gastric bypass surgery (GBS) and 13 sleeve gastrectomy. The four obese patients who did not undergo surgery, were performed the same evaluations. MEASUREMENTS Body weight, BMI, blood pressure, total cholesterol, TC levels, LDL-C, HDL-C, TG, fasting plasma glucose and insulin, HOMA IR, and US B-mode C-IMT was measured. RESULTS After 354 ± 92 days follow up, 27 patients that underwent bariatric surgery evidenced a mean body mass index decrease from 38 to 27 k/m² (p < 0.001), simultaneously was observed improvement in CVRFs, 10 years Framingham risk and a significant reduction of therapeutic requirements. C-IMT diminished from a mean of 0.58 ± 0.14 mm to 0.49 ± 0.09 mm (p = 0.0001). Four patients that did not undergo surgery increased C-IMT from 0.52 ± 0.12 to 0.58 ± 0.13 mm (p = 0.03) with no significant changes in CVRFs. CONCLUSION Weight loss, one year after bariatric surgery, GBS and sleeve gastrectomy, decreases C-IMT; improve CVRFs and 10 years Framingham risk.

Metabolic profile in women with polycystic ovary syndrome across adult life

OBJECTIVE To assess insulin sensitivity, insulin secretion and metabolic profile in women with polycystic ovary syndrome (PCOS) in different stages of reproductive life. MATERIALS AND METHODS In a cross-sectional study, 190 PCOS women (PCOSw) and 99 controls (Cw) aged between 18 and 55years were included. PCOSw and Cw were distributed into 3 stages of reproductive life: early reproductive age (18-34years old), late reproductive age (35-40years old) and perimenopausal period (41-55years old). Waist circumference (WC), body mass index (BMI) and blood pressure (BP) were recorded. An oral glucose tolerance test (OGTT) with measurement of glucose and insulin was performed. Sex steroids and lipid profile were also determined in the fasting sample. Insulin sensitivity was assessed by HOMA-IR and ISI composite, and insulin secretion by HOMA-β and insulinogenic index. Visceral adiposity index (VAI) and lipid accumulation product (LAP) were also calculated. Metabolic syndrome (MS) was assessed by the IDF and ATPIII criteria. RESULTS At early reproductive age, PCOSw showed higher BMI, WC, and VAI and a higher prevalence of MS compared to Cw (p<0.05). In addition, at late reproductive age PCOSw also showed elevated total cholesterol, triglycerides, insulin secretion, LAP and BP. At perimenopausal period, these parameters were not different between Cw and PCOSw. Within the PCOSw group, HOMA-β was lower at late reproductive and perimenopausal periods compared to the early reproductive age. Regarding control women, a deterioration of anthropometric and metabolic parameters was observed in perimenopausal women compared to early and late reproductive women. CONCLUSIONS Our results suggest that metabolic derangements associated with PCOS are more evident at the early and late reproductive ages. On the other hand, during perimenopause, there is no further deterioration of metabolic parameters. Nevertheless, a disruption in pancreatic β-cell function is evidenced at this stage.

Two Chronic Stress Models Based on Movement Restriction in Rats Respond Selectively to Antidepressant Drugs: Aldolase C As a Potential Biomarker

Background: Clinically depressed individuals respond to different types of antidepressants, suggesting that different neurobiological mechanisms may be responsible for their depression. However, animal models to characterize this are not yet available. Methods: We induced depressive-like behaviors in rats using 2 different chronic stress models: restraint in small cages or immobilization in adaptable plastic cones. Both models increased anxiety responses evaluated by novelty-suppressed feeding and the elevated plus-maze; increased learned helplessness evaluated by the tail suspension and forced swimming tests; and increased anhedonia evaluated by the sucrose preference test. Results: We assessed the ability of 2 different types of antidepressants to ameliorate depressive-like behaviors. We administered the serotonin reuptake inhibitor fluoxetine or the noradrenaline reuptake inhibitor reboxetine once daily for 28 days to rats that received either chronic restraint or immobilization stress, or no stress. Behavioral analysis revealed that fluoxetine ameliorated depressive-like behaviors when induced by chronic restraint stress, whereas reboxetine ameliorated these behaviors when induced by chronic immobilization stress. To further test biological differences between both models, we evaluated the levels of Aldolase C, an enzyme expressed by forebrain astrocytes that is regulated by antidepressant treatment, in the cerebrospinal fluid: chronic restraint stress, but not immobilization stress, increased the levels of Aldolase C. Moreover, the presence of astrocyte-derived Aldolase C-GFP in the cerebrospinal fluid indicates its central origin. Conclusions: Two stress paradigms induced depressive-like behaviors that were sensitive to different antidepressant treatments. Biomarkers such as Aldolase C could help determine optimal antidepressant treatments for clinically depressed patients.

Prevalence of meningococcal carriage in children and adolescents aged 10–19 years in Chile in 2013

In 2011, Chile experienced an increase in the number of cases of IMD caused by Neisseria meningitidis group W. This epidemiological scenario prompted authorities to implement prevention strategies. As part of these strategies, the Institute of Public Heath of Chile conducted a cross-sectional study to determine the prevalence of pharyngeal carriage of N. meningitidis in a representative sample of healthy children and adolescents aged 10-19 years. The identification of presumptive N. meningitidis strains was performed by testing carbohydrate utilization in the National Reference Laboratory at the ISP. Association of meningococcal carriage with risk factors was analyzed by calculating the Odds Ratio. Selected variables were included in a logistic model for risk analyses. The prevalence of carriage of N. meningitidis was 6.5% (CI: 5.7-7.3%). Older age (carriers: 14.2±0.29 vs. non-carriers: 13.8±0.08 years old; p=0.009), cohabitation with children (carriers: 0.9±0.13 vs. non-carriers: 0.7±0.03; p=0.028), number of smoking cohabitants (carriers: 0.55±0.13 vs. non-carriers: 0.44±0.03) and frequent attendance to crowded social venues (carriers: 49% vs. non-carriers: 37%; p=0.008) were determined to favor carriage. Statistical modeling showed that meningococcal carriage was associated with older age (OR: 1.077, p-value: 0.002) and cohabitation with children (OR: 1.182, p-value: 0.02).

Accelerated early pubertal progression, ovarian morphology, and ovarian function in prospectively followed low birth weight (LBW) girls

Abstract Aim: To compare pubertal development in age-matched healthy girls born with low birth weight (LBW) or appropriate birth weight for gestational age (AGA). Subjects and methods: Girls with breast in Tanner stage II and normal body mass index were followed for 3 years with a complete physical exam, bone age, pelvic ultrasound, and measurement of gonadal hormones using a leuprolide test. Results: Forty-one girls (AGA 25/LBW 16) were followed up for 3 years. By 3 years, they had similar bone age, adjusted height, and body composition. In LBW girls, breast Tanner stage advanced faster during the first 2 years of follow-up, which was associated with higher serum androgens. Hirsutism score, ovarian volume, and number of follicles between AGA and LBW were not different nor was age of menarche. By the third year, basal and poststimulated levels of gonadotropins and androgens anti-Müllerian hormone and inhibin B were similar in both groups and did not show differences related to birth weight or degree of catch-up growth. Conclusion: LBW recruits showed a slightly faster breast development but no differences in androgen excess signs, internal genitalia, and gonadal hormonal patterns.

Microstructural Brain and Multivoxel Spectroscopy in Very Low Birth Weight Infants Related to Insulin-Like Growth Factor Concentration and Early Growth

Background: Very low birth weight (VLBW) children have higher risk of neurologic disabilities and growth factors are essential for brain maturation. Aim: To assess whether there are differences in neurologic findings, psychometric parameters and microstructural brain morphology in 1-year-old VLBW infants versus term healthy controls and whether these differences are related to hormonal/growth changes. Methods: Prospective anthropometry, prefeed venous blood sample [insulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor-II (IGF-II), leptin, glucose], neurologic and imaging assessment, at age 1 year in 34 VLBW infants (12 SGA; 10 M) and 10 healthy term controls (5 M). Results: IGF-I concentrations at 1 month of corrected age were 20% lower in SGA versus appropriate for gestational age VLBW (p < 0.02). Gray and white matter volume and fractional anisotropy in 15/27 regions were decreased (p < 0.001). Abnormal spectroscopy was observed in 4 zones in VLBW versus term controls (p < 0.001). Some of these changes were associated with different periods of first-year growth and IGF-I/IGF-II, leptin and HOMA-IR. Conclusions: VLBW infants show differences in brain volumes and microstructural brain morphology as compared to term controls, changes related to circulating growth factor and anthropometry changes in the first year. This apparent reorganization of the developing brain offers a unique opportunity to investigate the relationship between changes in cortical anatomy, cognitive and social impairments and periods of early growth.