Impaired Reverse Cholesterol Transport is Associated with Changes in Fatty Acid Profile in Children and Adolescents with Abdominal Obesity.

BACKGROUND: Abdominal obesity is an important cardiovascular disease risk factor. Plasma fatty acids display a complex network of both pro and antiatherogenic effects. High density lipoproteins (HDL) carry out the antiatherogenic pathway called reverse cholesterol transport (RCT), which involves cellular cholesterol efflux (CCE), and lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities. OBJECTIVES: Our aim was to characterize RCT and its relation to fatty acids present in plasma in pediatric abdominal obesity. METHODS: Seventeen children and adolescents with abdominal obesity and 17 healthy controls were studied. Anthropometric parameters were registered. Glucose, insulin, lipid levels, CCE employing THP-1 cells, LCAT and CETP activities, plus fatty acids in apo B-depleted plasma were measured. RESULTS: The obese group showed a more atherogenic lipid profile, plus lower CCE (Mean±Standard Deviation) (6 ± 2 vs. 7 ± 2%; P < 0.05) and LCAT activity (11 ± 3 vs. 15 ±5 umol/dL.h; P < 0.05). With respect to fatty acids, the obese group showed higher myristic (1.1 ± 0.3 vs. 0.7 ± 0.3; P < 0.01) and palmitic acids (21.5 ± 2.8 vs. 19.6 ± 1.9; P < 0.05) in addition to lower linoleic acid (26.4 ± 3.3 vs. 29.9 ± 2.6; P < 0.01). Arachidonic acid correlated with CCE (r = 0.37; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05), palmitioleic acid with CCE (r = -0.35; P < 0.05), linoleic acid with CCE (r = 0.37; P < 0.05), lauric acid with LCAT (r = 0.49; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05) ecoisatrienoic acid with CCE (r = 0.40; P < 0.05) and lignoseric acid with LCAT (r = -0.5; P < 0.01). CONCLUSIONS: Children and adolescents with abdominal obesity presented impaired RCT, which was associated with modifications in proinflammatory fatty acids, such as palmitoleic and myristic, thus contributing to increased cardiovascular disease risk.

Metabolic alterations, HFE gene mutations and atherogenic lipoprotein modifications in patients with primary iron overload.

Iron overload (IO) has been associated with glucose metabolism alterations and increased risk of cardiovascular disease (CVD). Primary IO is associated with mutations in the HFE gene. To which extent HFE gene mutations and metabolic alterations contribute to the presence of atherogenic lipoprotein modifications in primary IO remains undetermined. The present study aimed to assess small, dense low-density lipoprotein (LDL) levels, chemical composition of LDL and high-density lipoprotein (HDL) particles, and HDL functionality in IO patients. Eighteen male patients with primary IO and 16 sex- and age-matched controls were recruited. HFE mutations (C282Y, H63D and S65C), measures of insulin sensitivity and secretion (calculated from the oral glucose tolerance test), chemical composition and distribution profile of LDL and HDL subfractions (isolated by gradient density ultracentrifugation) and HDL functionality (as cholesterol efflux and antioxidative activity) were studied. IO patients compared with controls exhibited insulin resistance (HOMA-IR (homoeostasis model assessment-estimated insulin resistance): +93%, P< 0.001). Metabolic profiles differed across HFE genotypes. C282Y homozygotes (n=7) presented a reduced ß-cell function and insulin secretion compared with non-C282Y patients (n=11) (-58% and -73%, respectively, P< 0.05). In addition, C282Y homozygotes featured a predominance of large, buoyant LDL particles (C282Y: 43±5; non-C282Y: 25±8; controls: 32±7%; P< 0.001), whereas non-C282Y patients presented higher amounts of small, dense LDL (C282Y: 23±5; non-C282Y: 39±10; controls: 26±4%; P< 0.01). HDL particles were altered in C282Y homozygotes. However, HDL functionality was conserved. In conclusion, metabolic alterations and HFE gene mutations are involved in the presence of atherogenic lipoprotein modifications in primary IO. To what extent such alterations could account for an increase in CVD risk remains to be determined.

Treatment patterns and outcomes in light chain amyloidosis: An institutional registry of amyloidosis report in Argentina.

Light chain (AL) amyloidosis is a form of systemic amyloidosis, causing organ dysfunction, mainly affecting the heart and kidney. Patient-tailored and risk-adapted decision making is critical in AL amyloidosis management. There is limited real-world evidence data from Argentina and Latin America regarding the treatment approaches for AL amyloidosis. This retrospective cohort study aimed to describe the treatment patterns and outcomes in adult patients (>18 years) diagnosed with AL amyloidosis at the Hospital Italiano in Buenos Aires, Argentina, using a 10-yearfollow-up data (June 1, 2010 to May 31, 2019) from the institutional registry of amyloidosis (IRA). The study population had a mean age of 63 years and 54.4% weremale. Heart and kidney were the most frequently affected organs. Of the 90 eligible patients included in the study, 70underwent treatment. Bortezomib-based regimen was the preferred first-line treatment (75.7% patients). Overall,54.4% of the patients presented a deep response (complete or very good partial response). Median overall survival (OS) was 5years, the 1-year OS and progression free survival rates were 80% (95% confidence interval [CI]: 68-87) and 80% (95%CI 68-87)), respectively. This study provides vital real-world evidence for the long-term treatment patterns and survival in a large cohort of AL amyloidosis patients in Argentina.

Effect of Tocilizumab on LDL and HDL Characteristics in Patients with Rheumatoid Arthritis. An Observational Study.

BACKGROUND: In patients with rheumatoid arthritis (RA), qualitative alterations of low and high-density lipoproteins (LDL and HDL, respectively) might partially explain their increased cardiovascular risk. Tocilizumab has been associated with an increase in lipids, including triglyceride (TG) and cholesterol levels. The aim of this study is to evaluate the effect of tocilizumab on certain LDL and HDL characteristics (oxidized LDL levels, HDL-associated enzymes, chemical composition of both total HDL and HDL3c subpopulation, and their capacity to promote cellular cholesterol efflux) at baseline and 3 months after the start of treatment in patients with RA. METHODS: Twenty-eight RA patients (ACR/EULAR 2010 criteria) with indication of treatment with tocilizumab were included in the present study. Clinical assessment [Health assessment questionnaire (HAQ)], disease activity score 28 (DAS28), high-sensitivity C reactive protein (hsCRP) concentration, lipid profile, and lipoprotein (a) [Lp(a)] levels were evaluated in all patients at baseline and after 3 months of treatment with tocilizumab. Lipoprotein characteristics were evaluated through the levels of oxidized LDL (OxLDL), the activity of paraoxonase (PON) 1, the composition of total HDL and small, dense HDL3c subpopulation, and their ability to promote cellular cholesterol efflux. RESULTS: After 3 months of treatment with tocilizumab, HAQ (- 23%, p < 0.05), DAS28 (- 49%, p < 0.001), and hsCRP (- 94%, p < 0.01) levels decreased significantly. Total cholesterol (TC), LDL-C, non-HDL-C, and apo B levels showed a significant increase after treatment (TC: + 7.0%, p < 0.01; LDL-C: + 10%, p < 0.01; non-HDL-C: + 9.9%, p < 0.01; and apo B: + 9.6%, p < 0.05). Decreases in Lp(a) and OxLDL levels were also observed after treatment [Lp(a): - 50%, p < 0.01; and oxLDL: - 5.4%, p < 0.05]. The latter was in accordance with the increment detected in PON activity. No changes were observed in HDL capacity to promote cholesterol efflux (p > 0.05) in the whole group. CONCLUSIONS: Treatment with tocilizumab reduced hsCRP levels and displayed positive effects on certain lipoprotein-related parameters, such as a potent decrease inLp(a) and a reduction in OxLDL levels. Moreover, HDL capacity to promote cellular cholesterol efflux was maintained after 3 months of treatment.

Validation of CSF free light chain in diagnosis and prognosis of multiple sclerosis and clinically isolated syndrome: prospective cohort study in Buenos Aires.

BACKGROUND: The objective was to evaluate the precision of kappa and lambda free light chains (KFLC and LFLC) in CSF for the diagnosis of multiple sclerosis (MS) and prognosis of clinically isolated syndrome (CIS). METHODS: CSF and serum samples from CIS, MS and other neurological non-MS disease were collected between 2015 and 2017. FLC concentrations were measured using immunoassay Freelite™. Results were correlated with the patients' diagnoses and ROC curve analysis was used to determine accuracy. In CIS patients, analysis of FLC were compared in CIS converters vs. non-converter during follow-up. RESULTS: In the MS group (n = 41), the optimal cut-off for KFLC determined was 7 mg/L, with a diagnostic sensitivity and specificity of 95% and 97%, respectively. The optimal cut-off for LFLC was 0.7 mg/L, with a diagnostic sensitivity and specificity of 71% and 81%, respectively. 36 CIS patients were included; mean follow-up time was 28 ± 9 months, and 22 (61.1%) patients converted to MS. The median concentration of CSF K and LFLCs at CIS diagnosis was slightly higher in CIS-converters compared to non-converters, but this did not reach statistical significance (KFLC: median 7 ± 5.3 mg/L vs. 5 ± 2.3 mg/L, p = 0.11; LFLC 0.7 ± 0.33 mg/L vs. 0.5 ± 0.23 mg/L p = 0.16). A strong correlation was observed between the concentration of K and L FLCs at diagnosis and the change in PBVC during follow-up (r = 0.72 and r = 0.65, respectively). CONCLUSION: KFLCs have a high sensitivity and specificity for the diagnosis of MS. FLC concentrations at CIS diagnosis were not significantly higher in CIS-converters.

Oxidative stress, HDL functionality and effects of intravenous iron administration in women with iron deficiency anemia.

BACKGROUND AND AIMS: Iron deficiency anemia (IDA) affects around 20-30% of adults worldwide. An association between IDA and cardiovascular disease (CVD) has been reported. Oxidative stress, inflammation and low concentration of high-density lipoproteins (HDL) were implicated on endothelial dysfunction and CVD in IDA. We studied the effects of iron deficiency and of an intravenous iron administration on oxidative stress and HDL characteristics in IDA women. METHODS: Two studies in IDA women are presented: a case-control study, including 18 patients and 18 age-matched healthy women, and a follow-up study 72hr after the administration of intravenous iron (n = 16). Lipids, malondialdehyde, cholesteryl ester transfer protein (CETP), paraoxonase-1 (PON-1) and HDL chemical composition and functionality (cholesterol efflux and antioxidative activity) were measured. Cell cholesterol efflux from iron-deficient macrophages to a reference HDL was also evaluated. RESULTS: IDA patients showed higher triglycerides and CETP activity and lower HDL-C than controls (all p < 0.001). HDL particles from IDA patients showed higher triglyceride content (+30%,p < 0.05) and lower antioxidative capacity (-23%,p < 0.05). Although HDL-mediated cholesterol efflux was similar between the patients and controls, iron deficiency provoked a significant reduction in macrophage cholesterol efflux (-25%,p < 0.05). Arylesterase activity of PON-1 was significantly lower in IDA patients than controls (-16%,p < 0.05). The intravenous administration of iron was associated with a decrease in malondialdehyde levels and an increase in arylesterase activity of PON-1 (-22% and +18%, respectively, p < 0.05). CONCLUSION: IDA is associated with oxidative stress and functionally deficient HDL particles. It remains to be determined if such alterations suffice to impair endothelial function in IDA.

[Not Available]. / Insatisfacción corporal y conductas de control del peso en chicas adolescentes con sobrepeso: papel mediador de la ansiedad y la depresión.

Introducción: los problemas relacionados con el peso constituyen un problema importante de salud pública debido a su alta prevalencia y a las adversas consecuencias que tienen para la salud.Objetivo: el objetivo principal de este estudio fue analizar si la depresión y la ansiedad tienen un papel mediador en la relación entre la insatisfacción corporal y las conductas de control del peso en chicas adolescentes con sobrepeso.Material y métodos: en el estudio participaron 140 mujeres de 16 a 20 años con sobrepeso. Las participantes tuvieron que cumplimentar la escala de insatisfacción corporal del EDI-2, las escalas de ansiedad y depresión del GHQ-28 y una adaptación de las escalas del EAT survey para evaluar las conductas de control del peso. Para los análisis estadísticos se utilizaron métodos de diferencias de medias, correlaciones y de mediación secuencial.Resultados: las adolescentes con sobrepeso y alta insatisfacción corporal presentaban más sintomatología ansiosa y depresiva, así como mayor cantidad de conductas de control del peso. Los resultados del análisis de mediación secuencial evidencian que el efecto de la insatisfacción corporal en las conductas de control del peso está parcialmente mediado por las variables depresión y ansiedad. Mientras que la sintomatología ansiosa presenta efectos directos e indirectos sobre las conductas de control de peso, la sintomatología depresiva solamente presenta un efecto indirecto.Conclusiones:los resultados del estudio destacan el rol mediador de la sintomatología depresiva y, especialmente, de la ansiedad en el desarrollo de conductas no saludables de control del peso.

Alpha-1 Antitrypsin Deficiency in COPD Patients: A Cross-Sectional Study.

INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with early onset chronic obstructive pulmonary disease (COPD) and liver disease. It is also a highly under-diagnosed condition. As early diagnosis could prompt specific interventions such as smoking cessation, testing of family members, genetic counselling and use of replacement therapy, screening programs are needed to identify affected patients. OBJECTIVE: To estimate the prevalence of severe AATD in COPD patients by routine dried blood spot testing and subsequent genotyping in patients with alpha-1 antitrypsin (AAT) levels below an established threshold. MATERIALS AND METHODS: Cross-sectional study of adult COPD patients attending the Hospital Dr. Antonio Cetrángolo (Buenos Aires, Argentina) between 2009 and 2012. The study consisted of capillary blood collection via finger stick to determine AAT levels, clinical evaluation and lung function tests. Genotype was determined in AAT-deficient patients. RESULTS: A total of 1,002 patients were evaluated, of whom 785 (78.34%) had normal AAT levels, while low AAT levels were found in 217 (21.66%). Subsequent genotyping of the latter sub-group found: 15 (1.5%, 95% CI 0.75-2.25) patients with a genotype associated with severe AATD, of whom 12 were ZZ (1.2%, 95% CI 0.52-1.87) and 3 SZ (0.3%, 95% CI 0-0.64). The remaining 202 patients were classified as: 29 Z heterozygotes (2.89%, 95% CI 1.86-3.93), 25 S heterozygotes (2.5%, 95% CI 1.53-3.46) and 4 SS (0.4%, 95% CI 0.01-0.79). A definitive diagnosis could not be reached in 144 patients (14.37%, 95% CI 12.2-16.54). CONCLUSION: The strategy using an initial serum AAT level obtained by dried blood spot testing and subsequent genotyping was a satisfactory initial approach to a screening program for severe AAT, as a definitive diagnosis was achieved in 87% of patients. However, results were not obtained for logistical reasons in the remaining 13%. This major obstacle may be overcome by the use of dried blood spot phenotyping techniques. We believe this approach for detecting AATD in COPD patients, in compliance with national and international guidelines, is supported by our results.

Un caso de amiloidosis AL / A case report of AL amyloidosis

Antecedentes: la amiloidosis es una enfermedad sistémica que resulta del depósito de proteínas mal plegadas; en la amiloidosis de cadena ligera de la inmunoglobulina (AL), las fibrillas están compuestas de fragmentos de cadenas ligeras monoclonales. En la Argentina, la densidad de incidencia de amiloidosis AL es 4,54 cada millón de personas/año. Caso: paciente femenina de 71 años que consulta por dolor neural localizado en miembro superior izquierdo, asociado a edemas en ambos miembros inferiores y disnea de esfuerzo, pérdida de peso, constipación y macroglosia. Al examen físico presenta tensión arterial de 100/60 mm Hg; está afebril, saturando 98% de aire ambiente; peso de 46 kg y un índice de masa corporal de 18,9. Se constatan cadenas livianas libres Kappa: 5,8 mg/L, Lambda: 430 mg/L y con relación K/L: 0,13 mg/L y un ProBNP de 1686 pg/mL. La biopsia de grasa abdominal informó depósitos de amiloide, tinción de rojo Congo positivo. Resonancia magnética (RM) de corazón con contraste (gadolinio), compatible con amiloidosis cardíaca. La tomografía computarizada (TC) de tórax demostró un área de consolidación en lóbulo superior del pulmón derecho, rojo Congo positivo focal. Ante el diagnóstico de amiloidosis AL se realiza tratamiento con CYBORD. Se consolidó el tratamiento con un trasplante autólogo de médula ósea. Discusión: la afectación cardíaca es la principal causa de morbilidad y mortalidad dentro de la amiloidosis. (AU)

Background: amyloidosis is a systemic disease resulting from the deposition of misfolding proteins, in immunoglobulin light chain amyloidosis (AL) fibrils are composed of fragments of monoclonal light chains. In Argentina the incidence density of AL amyloidosis is 4.54 per million people year. Case: a 71-year-old female patient who consults for neural pain located in the left upper limb, associated with edemas in both lower limbs and exertional dyspnea, weight loss, constipation and macroglossia. On physical examination she had blood pressure of 100/60 mmHg, afebrile, saturating 98% of ambient air, weight of 46 kg and body mass index of 18.9. The peripheral blood laboratory has Kappa free light chains: 5.8 mg/L, Lambda: 430 mg/L with K L ratio: 0.13 mg/L and a ProBNP of 1686 pg/mL. Abdominal fat biopsy reports positive Congo red staining. Cardiac magnetic resonance with contrast (gadolinium) has been performed and result compatible with cardiac amyloidosis. Chest CT showed an area of consolidation in the upper lobe of the right lung; positive congo red. With the diagnosis of AL amyloidosis she was treated with CYBORD. Autologous stem cell transplantation was performed. Discussion: cardiac involvement is the main cause of morbidity and mortality by amyloidosis. (AU)

Imagen corporal y realización de dieta: diferencias entre adolescentes españolas y latinoamericanas / Body Image and Dieting: Differences between Spanish Adolescents and Latinamericans Adolescents

Se realizó un estudio comparativo para analizar las diferencias entre adolescentes españolas e inmigrantes latinoamericanas en diferentes componentes de la imagen corporal y conductas de control del peso que suponen un riesgo para el desarrollo de trastornos de la conducta alimentaria (TCA). Asimismo, se determinó cuáles variables tienen un mayor valor predictivo para la realización de dieta en las adolescentes. La muestra estaba compuesta por 403 mujeres de 13 a 17 años, 191 españolas y 212 inmigrantes latinoamericanas. Se recogieron variables sociodemográficas, imagen corporal (estado nutricional, autopercepción, insatisfacción y miedo a ganar peso), hábitos de alimentación y conductas de control del peso (dieta, vómitos autoinducidos y toma de laxantes). Los resultados mostraron que no había diferencias entre las adolescentes españolas y las latinoamericanas en el estado nutricional, en la forma de autopercepción, en sus expectativas de imagen, ni en el nivel de insatisfacción corporal. Sin embargo, había diferencias en la autopercepción del atractivo físico, en el miedo a ganar peso, en los hábitos de alimentación y en la realización de dieta. Un porcentaje significativamente mayor de adolescentes latinoamericanas se percibía atractiva, tenía más miedo a ganar peso, presentaba peores hábitos alimenticios y había realizado dieta.

A comparative study was done to analyze the differences between Spanish adolescent and Latin American immigrants at the same age in various components of body image and weight control behaviors related to development of eating disorders (ED). Likewise the study analysed what variables had a major predictive value of dieting among the adolescents. The sample group was formed by 403 females from 13 to 17 years old, 191 Spanish and 212 Latin American immigrants. Certain variables were collected such as socio-demographic, body image (nutritional state, self-perception, dissatisfaction and fear about gain weight), eating habits and weight control behaviors (diet, self-induce vomiting and taking laxatives). The results showed there were not differences between the Spanish and Latin American adolescent girls in the nutritional state, in how they perceived their body image, in their desired figure, nor in the level of body dissatisfaction. However, there were differences in their self-perception of physical attractiveness, in their fear of gaining weight, in their eating habits and dieting. A significant percentage of the Latin American adolescents perceived themselves as attractive, they were more fearful of gaining weight; they had worse eating habits and dieted more.