Arthroscopic Matrix-Assisted Autologous Chondrocyte Transplantation Versus Microfracture: A 6-Year Follow-up of a Prospective Randomized Trial.

BACKGROUND: Few randomized controlled trials with a midterm follow-up have compared matrix-assisted autologous chondrocyte transplantation (MACT) with microfracture (MFx) for knee cartilage lesions. PURPOSE: To compare the structural, clinical, and safety outcomes at midterm follow-up of MACT versus MFx for treating symptomatic knee cartilage lesions. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 48 patients aged between 18 and 50 years, with 1- to 4-cm2 International Cartilage Repair Society (ICRS) grade III to IV knee chondral lesions, were randomized in a 1:1 ratio to the MACT and MFx treatment groups. A sequential prospective evaluation was performed using magnetic resonance imaging (MRI) T2 mapping, the MOCART (magnetic resonance observation of cartilage repair tissue) score, second-look arthroscopic surgery, patient-reported outcome measures, the responder rate (based on achieving the minimal clinically important difference for the Knee injury and Osteoarthritis Outcome Score [KOOS] pain and KOOS Sport/Recreation), adverse events, and treatment failure (defined as a reoperation because of symptoms caused by the primary defect and the detachment or absence of >50% of the repaired tissue during revision surgery). RESULTS: Overall, 35 patients (18 MACT and 17 MFx) with a mean chondral lesion size of 1.8 ± 0.8 cm2 (range, 1-4 cm2) were followed up to a mean of 6 years postoperatively (range, 4-9 years). MACT demonstrated significantly better structural outcomes than MFx at 1 to 6 years postoperatively. At final follow-up, the MRI T2 mapping values of the repaired tissue were 37.7 ± 8.5 ms for MACT versus 46.4 ± 8.5 ms for MFx (P = .003), while the MOCART scores were 59.4 ± 17.3 and 42.4 ± 16.3, respectively (P = .006). More than 50% defect filling was seen in 95% of patients at 2 years and 82% at 6 years in the MACT group and in 67% at 2 years and 53% at 6 years in the MFx group. The second-look ICRS scores at 1 year were 10.7 ± 1.3 for MACT and 9.0 ± 1.8 for MFx (P = .001). Both groups showed significant clinical improvements at 6 years postoperatively compared with their preoperative status. Significant differences favoring the MACT group were observed at 2 years on the KOOS Activities of Daily Living (P = .043), at 4 years on all KOOS subscales (except Symptoms; P < .05) and the Tegner scale (P = .008), and at 6 years on the Tegner scale (P = .010). The responder rates at 6 years were 53% and 77% for MFx and MACT, respectively. There were no reported treatment failures after MACT; the failure rate was 8.3% in the MFx group. Neither group had serious adverse events related to treatment. CONCLUSION: Patients who underwent MACT had better structural outcomes than those who underwent MFx at 1 to 6 years postoperatively. Both groups of patients showed significant clinical improvements at final follow-up compared with their preoperative status. MACT showed superiority at 4 years for the majority of the KOOS subscales and for the Tegner scale at 4 to 6 years. The MACT group also had a higher responder rate and lower failure rate at final follow-up. REGISTRATION: NCT01947374 (ClinicalTrials.gov identifier).

First Clinical Application of Polyurethane Meniscal Scaffolds with Mesenchymal Stem Cells and Assessment of Cartilage Quality with T2 Mapping at 12 Months.

BACKGROUND: Complex meniscal lesions often require meniscectomy with favorable results in the short term but a high risk of early osteoarthritis subsequently. Partial meniscectomy treated with meniscal substitutes may delay articular cartilage degeneration. PURPOSE: To evaluate the status of articular cartilage by T2 mapping after meniscal substitution with polyurethane scaffolds enriched with mesenchymal stem cells (MSC) and comparison with acellular scaffolds at 12 months. METHODS: Seventeen patients (18-50 years) with past meniscectomies were enrolled in 2 groups: (1) acellular polyurethane scaffold (APS) or (2) polyurethane scaffold enriched with MSC (MPS). Patients in the MPS group received filgrastim to stimulate MSC production, and CD90+ cells were obtained and cultured in the polyurethane scaffold. The scaffolds were implanted arthroscopically into partial meniscus defects. Concomitant injuries (articular cartilage lesions or cartilage lesions) were treated during the same procedure. Changes in the quality of articular cartilage were evaluated with T2 mapping in femur and tibia at 12 months. RESULTS: In tibial T2 mapping, values for the MPS group increased slightly at 9 months but returned to initial values at 12 months (P > 0.05). In the APS group, a clear decrease from 3 months to 12 months was observed (P > 0.05). This difference tended to be significantly lower in the APS group compared with the MPS group at the final time point (P = 0.18). In the femur, a slight increase in the MPS group (47.8 ± 3.4) compared with the APS group (45.3 ± 4.9) was observed (P > 0.05). CONCLUSION: Meniscal substitution with polyurethane scaffold maintains normal T2 mapping values in adjacent cartilage at 12 months. The addition of MSC did not show any advantage in the protection of articular cartilage over acellular scaffolds (P > 0.05).

Arthroscopic Matrix-Encapsulated Autologous Chondrocyte Implantation: A Pilot Multicenter Investigation in Latin America.

Objective. To evaluate minimum biosecurity parameters (MBP) for arthroscopic matrix-encapsulated autologous chondrocyte implantation (AMECI) based on patients' clinical outcomes, magnetic resonance imaging (MRI) T2-mapping, Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and International Cartilage Repair Society (ICRS) second-look arthroscopic evaluation, laying the basis for a future multicenter study. Design. Pilot clinical study. We analyzed the logistics to perform AMECI to treat focal chondral lesions in different hospitals following strict biosecurity parameters related to tissue and construct transportation, chondrocyte isolation, and cell expansion. Patient progress was analyzed with patient-reported outcome measures, MRI T2-mapping, MOCART, and ICRS arthroscopic second-look evaluation. Results. Thirty-five lesions in 30 patients treated in 7 different hospitals were evaluated. Cell viability before implantation was >90%. Cell viability in construct remnants was 87% ± 11% at 24 hours, 75% ± 17.1% at 48 hours, and 60% ± 8% at 72 hours after implantation. Mean final follow-up was 37 months (12-72 months). Patients showed statistically significant improvement in all clinical scores and MOCART evaluations. MRI T2-mapping evaluation showed significant decrease in relaxation time from 61.2 ± 14.3 to 42.9 ± 7.2 ms (P < 0.05). Arthroscopic second-look evaluation showed grade II "near normal" tissue in 83% of patients. Two treatment failures were documented. Conclusions. It was feasible to perform AMECI in 7 different institutions in a large metropolitan area following our biosecurity measures without any implant-related complication. Treated patients showed improvement in clinical, MRI T2-mapping, and MOCART scores, as well as a low failure rate and a favorable ICRS arthroscopic evaluation at a mid-term follow-up. Level of Evidence. 2b.

Radiographic displacement of acute acromioclavicular joint dislocations fixed with AC TightRope.

BACKGROUND: The arthroscopic approach to acromioclavicular (AC) dislocation with methods such as AC TightRope fixation has reported radiographic failure rates between 18% and 50% with functional results graded as good or excellent. Our objective was to review the outcomes after arthroscopic fixation for acute AC joint dislocation using the TightRope device. METHODS: We reviewed the records of 52 patients, with a mean age of 31 years, who underwent arthroscopic fixation with the TightRope device for acute AC joint dislocation. Outcomes were evaluated using the Constant and University of California, Los Angeles scores. The coracoclavicular (CC) distance before and after surgery was compared by radiography. RESULTS: The mean follow-up period was 36.7 months (range, 6-65 months). Postoperatively, the mean Constant score was 97.13 and the mean University of California, Los Angeles score was 33.2. The CC distance was maintained in 73% of the patients, whereas partial loss of reduction occurred in 19.2% and failure of reduction occurred in 7.7%. CONCLUSION: Arthroscopic fixation using the TightRope device for acute AC joint dislocation achieves satisfactory clinical outcomes. However, CC reconstruction appears to result in subluxation in cases with AC dislocation for a period of more than 10 days.

Document of recommendations of the SEA 2018. Lifestyle in cardiovascular prevention. / Documento de recomendaciones de la SEA 2018. El estilo de vida en la prevención cardiovascular.

Lifestyle is a complex concept that includes aspects external to ourselves that can modulate and influence our health. The knowledge of the relationship between lifestyle and cardiovascular risk does not attain the level of evidence achieved with clinical trials with drugs, because clinical studies are scarce and mainly of observational nature, albeit based on large cohorts. Nutritional epidemiology has the added difficulty of being based mostly on subjective dietary recall methods to ascertain nutrient and food intake over time, with the additional problems of incomplete data collection, variable measurements of adherence due to seasonal and geographical differences in food composition, and the changing eating behavior that human beings have over time. The purpose of this document is to carry out an updated and hierarchical review of the relationship between lifestyle and cardiovascular disease based on current evidence, paying attention to three aspects that are of great pathogenic importance and are directly modifiable: physical activity, tobacco consumption, and diet. With this, we intend to update the knowledge on this relationship, construct evidence-based recommendations, and provide a simple tool for clinical practice especially directed to health professionals involved in the care of people at cardiovascular risk, defining simple and easy strategies for individuals who receive advice for the primary and secondary prevention of cardiovascular diseases.

Influence of gender and menopausal status on gut microbiota.

OBJECTIVES: We explore the differences in the gut microbiota associated with gender and hormonal status. STUDY DESIGN: We included 76 individuals in this study: 17 pre-menopausal women, 19 men matched by age, as a control group for the pre-menopausal women, 20 post-menopausal women and 20 men matched by age as a control group for the post-menopausal women; all 4 groups were also matched by body mass index (BMI) and nutritional background. MAIN MEASUREMENTS: We analyzed the differences in the gut microbiota, endotoxemia, intestinal incretins, pro-inflammatory cytokines, and plasma levels of energy homeostasis regulatory hormones between pre- and post-menopausal women and compared them with their respective male control groups. RESULTS: We found a higher Firmicutes/Bacteroidetes ratio, a higher relative abundance of Lachnospira and Roseburia, and higher GLP-1 plasma levels in pre-menopausal women than in post-menopausal women, who had similar levels to men. In contrast, we observed a lower relative abundance of the Prevotella, Parabacteroides and Bilophila genera, and IL-6 and MCP-1 plasma levels in pre-menopausal women than in post-menopausal women, who had similar levels to the men. We also found higher GiP and leptin plasma levels in women than in men, irrespective of the menopausal status of the women. In addition, adiponectin levels were higher in pre-menopausal women than in their corresponding age-matched male control group. CONCLUSIONS: Our results suggest that the differences in the composition of gut microbiota between genders and between women of different hormonal status may be related to the sexual dimorphism observed in the incidence of metabolic diseases and their co-morbidities.

Mediterranean Diet Supplemented With Coenzyme Q10 Modulates the Postprandial Metabolism of Advanced Glycation End Products in Elderly Men and Women.

Advanced glycation end products (AGEs) and oxidative stress are elevated with aging and dysmetabolic conditions. Because a Mediterranean (Med) diet reduces oxidative stress, serum AGEs levels, and gene expression related to AGEs metabolism in healthy elderly people, we studied whether supplementation with coenzyme Q10 (CoQ) was of further benefit. Twenty participants aged ≥ 65 (10 men and 10 women) were randomly assigned to each of three isocaloric diets for successive periods of 4 weeks in a crossover design: Med diet, Med + CoQ, and a Western high-saturated-fat diet (SFA diet). After a 12-hour fast, volunteers consumed a breakfast with a fat composition similar to the previous diet period. Analyses included dietary AGEs consumed, serum AGEs and AGE receptor-1 (AGER1), receptor for AGEs (RAGE), glyoxalase I (GloxI), and estrogen receptor α (ERα) mRNA levels. Med diet modulated redox-state parameters, reducing AGEs levels and increasing AGER1 and GloxI mRNA levels compared with the SFA diet. This benefit was accentuated by adding CoQ, in particular, in the postprandial state. Because elevated oxidative stress/inflammation and AGEs are associated with clinical disease in aging, the enhanced protection of a Med diet supplemented with CoQ should be assessed in a larger clinical trial in which clinical conditions in aging are measured.

Lifestyle recommendations for the prevention and management of metabolic syndrome: an international panel recommendation.

The importance of metabolic syndrome (MetS) lies in its associated risk of cardiovascular disease and type 2 diabetes, as well as other harmful conditions such as nonalcoholic fatty liver disease. In this report, the available scientific evidence on the associations between lifestyle changes and MetS and its components is reviewed to derive recommendations for MetS prevention and management. Weight loss through an energy-restricted diet together with increased energy expenditure through physical activity contribute to the prevention and treatment of MetS. A Mediterranean-type diet, with or without energy restriction, is an effective treatment component. This dietary pattern should be built upon an increased intake of unsaturated fat, primarily from olive oil, and emphasize the consumption of legumes, cereals (whole grains), fruits, vegetables, nuts, fish, and low-fat dairy products, as well as moderate consumption of alcohol. Other dietary patterns (Dietary Approaches to Stop Hypertension, new Nordic, and vegetarian diets) have also been proposed as alternatives for preventing MetS. Quitting smoking and reducing intake of sugar-sweetened beverages and meat and meat products are mandatory. Nevertheless, there are inconsistencies and gaps in the evidence, and additional research is needed to define the most appropriate therapies for MetS. In conclusion, a healthy lifestyle is critical to prevent or delay the onset of MetS in susceptible individuals and to prevent cardiovascular disease and type 2 diabetes in those with existing MetS. The recommendations provided in this article should help patients and clinicians understand and implement the most effective approaches for lifestyle change to prevent MetS and improve cardiometabolic health.

La resistina se asocia con la proteína C reactiva y marcadores de riesgo cardiovascular en niños obesos / Resistin is associated with C reactive protein and cardiovascular risk markers in obese children / A resistina associa-se à proteína C reativa e aos marcadores de risco cardiovascular em crianças obesas

El objetivo del trabajo fue evaluar los niveles de resistina sérica y su asociación con la proteína C reactiva (PCR-hs), óxido nítrico (NO) y lípidos plasmáticos (LP) en sujetos de edad pediátrica. Participaron 366 niños y adolescentes (10-16 años), agrupados en eutróficos (n=162) y obesos (n=204). Se les estudió peso, talla, circunferencia de la cintura, resistina sérica, glucosa e insulina basal, LP, NO, PCR-hs, malondialdehído y tensión arterial. Se calculó el IMC, el índice cintura-talla (IC/T) y el HOMA-IR. Se utilizaron las pruebas t de Student, ANOVA, U de Mann y Whitney o Kruskal- Wallis para comparar entre grupos y la correlación de Spearman para determinar asociación entre variables. Los obesos masculinos presentaron niveles superiores de resistina (p<0,05). El género femenino presentó valores más altos de resistina en eutróficos (p=0,012) y con IC/T normal (p=0,011). A mayor concentración de resistina los eutróficos presentaron niveles más altos de triacilglicéridos, pero los obesos mostraron niveles más bajos de triacilglicéridos, HDLc y NO, más altos de PCR-hs y mayor IMC. Los resultados sugieren que la resistina podría ser un factor de riesgo para la enfermedad cardiovascular por su asociación positiva con la PCR-hs e inversa con el NO y la HDLc, parámetros involucrados en la inflamación y la disfunción endotelial.

The aim of this study was to evaluate seric levels of resitin and their association with high-sensitivity C Reactive Protein (hs-CRP), nitric oxide (NO) and plasmatic lipids (PL) in a pediatric age population. A total of 366 children and adolescents (between 10-16 years old) participated, and were grouped into eutrophic (n=162) and obese (n=204). Weight, height, waist circumference, resistin, fasting blood glucose and insulin levels, PL, hs-CRP, NO, malondialdehyde and blood pressure were measured. BMI, waist to height ratio (W/HR) and HOMA-IR were calculated. T-student, ANOVA, Mann-Whitney U-value or Kruskal-Wallis were used to compare between groups and Spearman correlation was used to determine association among variables. Male obese subjects showed higher resistin levels (p<0.05). Female subjects showed higher resistin values in the eutrophic group (p=0.012) and in the normal W/HR (p=0.011). At higher levels of resistin, the eutrophic group showed higher levels of triacylglycerides, but the obese group showed lower triacylglycerides, HDLc and NO levels and higher hs-CRP levels and BMI. These results suggest that resistin could be a risk factor for cardiovascular disease because of its positive association with hs-CRP and inverse association with NO and HDLc, parameters involved in inflammation and endothelial dysfunction.

O objetivo da pesquisa foi avaliar os níveis séricos de resistina sérica e sua associação com a proteína C-reativa (PCR-hs), óxido nítrico (NO) e lipídios plasmáticos (LP) em crianças e adolescentes. O estudo envolveu 366 crianças e adolescentes (10-16 anos), agrupados em eutróficos (n=162) e obesos (n=204). Os sujeitos foram estudados em relação ao peso, altura, circunferência da cintura, resistina sérica, glicose e insulina basal, LP, NO, PCR-hs, malondialdeído e pressão arterial. Os IMC, índice cintura-altura (IC/A) e HOMA-IR foram calculados. Foram utilizados os Testes t de Student, ANOVA, U de Mann e Whitney ou Kruskal-Wallis para comparar entre os grupos e a correlação de Spearman para verificar a associação entre variáveis. Os obesos masculinos mostraram níveis mais elevados de resistina (p<0,05). O sexo feminino apresentou valores mais altos de resistina em eutróficos (p=0,012) e com IC/T normal (p=0,011). À maior concentração de resistina, os eutróficos apresentaram maiores níveis de triacilglicerídeos, mas os obesos apresentaram níveis mais baixos de triacilglicerídeos, HDLc e NO, mais altos de PCR-hs e maior IMC. Os resultados sugerem que a resistina poderia ser um fator de risco para a doença cardiovascular devido à sua associação positiva com a PCR-hs e inversa com o NO e a HDLc, parâmetros envolvidos na inflamação e disfunção endotelial.

Frying oils with high natural or added antioxidants content, which protect against postprandial oxidative stress, also protect against DNA oxidation damage.

PURPOSE: Using sunflower oil as frying oil increases postprandial oxidative stress, which is considered the main endogenous source of DNA oxidative damage. We aimed to test whether the protective effect of virgin olive oil and oil models with added antioxidants against postprandial oxidative stress may also protect against DNA oxidative damage. METHODS: Twenty obese people received four breakfasts following a randomized crossover design consisting of different oils [virgin olive oil (VOO), sunflower oil (SFO), and a mixed seed oil (SFO/canola oil) with added dimethylpolysiloxane (SOX) or natural antioxidants from olives (SOP)], which were subjected to 20 heating cycles. RESULTS: We observed the postprandial increase in the mRNA levels of p53, OGG1, POLB, and GADD45b after the intake of the breakfast prepared with SFO and SOX, and an increase in the expression of MDM2, APEX1, and XPC after the intake of the breakfast prepared with SFO, whereas no significant changes at the postprandial state were observed after the intake of the other breakfasts (all p values <0.05). We observed lower 8-OHdG postprandial levels after the intake of the breakfast prepared with VOO and SOP than after the intake of the breakfast prepared with SFO and SOX (all p values <0.05). CONCLUSIONS: Our results support the beneficial effect on DNA oxidation damage of virgin olive oil and the oil models with added antioxidants, as compared to the detrimental use of sunflower oil, which induces p53-dependent DNA repair pathway activation.

[Association between resistin serum levels and dimension and body composition variables in children and adolescents]. / Asociación de la resistina con variables de dimensión y composición corporal en eutróficos y obesos.

BACKGROUND: Resistin is an adipokine secreted in adipose tissue that may be associated with the metabolic and endocrine disorders of obesity. AIM: To assess the association between serum resistin levels and body composition variables, in children and adolescents. MATERIAL AND METHODS: Cross-sectional assessment of 302 subjects, aged 10-16 years. According to body mass index, 124 were classified as eutrophic and 178 as obese. A clinical examination and pubertal assessment were performed. Body weight, height, waist and arm circumferences were measured. Serum resistin levels were measured using an immunoenzymatic assay. RESULTS: Male obese children had significantly higher resistin levels than their eutrophic counterparts. Eutrophic women had higher levels than eutrophic males. No significant association between resistin and pubertal status was observed. In the whole sample and among obese subjects, resistin levels correlated with body mass index, tricipital skinfold, arm circumference, arm fat area and fat mass. CONCLUSIONS: There is a significant association between resistin levels and body composition variables, particularly with indicators of fat accretion.

CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (the CORDIOPREV study): Rationale, methods, and baseline characteristics: A clinical trial comparing the efficacy of a Mediterranean diet rich in olive oil versus a low-fat diet on cardiovascular disease in coronary patients.

Coronary heart disease (CHD) represents a major global health burden. However, despite the well-known influence that dietary habits exert over the progression of this disease, there are no well-established and scientifically sound dietary approaches to prevent the onset of clinical outcomes in secondary prevention. The objective of the CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study, clinical trials number NCT00924937) is to compare the ability of a Mediterranean diet rich in virgin olive oil versus a low-fat diet to influence the composite incidence of cardiovascular events after 7 years in subjects with documented CHD at baseline. For this purpose, we enrolled 1,002 coronary patients from Spain. Baseline assessment (2009-2012) included detailed interviews and measurements to assess dietary, social, and biological variables. Results of baseline characteristics: The CORDIOPREV study in Spain describes a population with a high body mass index (37.2% overweight and 56.3% obesity) and with a median of low-density lipoprotein cholesterol of 88.5 mg/dL (70.6% of the patients having <100 mg/dL and 20.3% patients <70 mg/dL). A total of 9.6% of the participants were active smokers, and 64.4% were former smokers. Metabolic syndrome was present in 58% of this population. To sum up, we describe here the rationale, methods, and baseline characteristics of the CORDIOPREV study, which will test for the first time the efficacy of a Mediterranean diet rich in extra virgin olive oil as compared with a low-fat diet on the incidence of CHD recurrence in a long-term follow-up study.

Asociación de la resistina con variables de dimensión y composición corporal en eutróficos y obesos / Association between resistin serum levels and dimension and body composition variables in children and adolescents

Background: Resistin is an adipokine secreted in adipose tissue that may be associated with the metabolic and endocrine disorders of obesity. Aim: To assess the association between serum resistin levels and body composition variables, in children and adolescents. Material and Methods: Cross-sectional assessment of 302 subjects, aged 10-16 years. According to body mass index, 124 were classified as eutrophic and 178 as obese. A clinical examination and pubertal assessment were performed. Body weight, height, waist and arm circumferences were measured. Serum resistin levels were measured using an immunoenzymatic assay. Results: Male obese children had significantly higher resistin levels than their eutrophic counterparts. Eutrophic women had higher levels than eutrophic males. No significant association between resistin and pubertal status was observed. In the whole sample and among obese subjects, resistin levels correlated with body mass index, tricipital skinfold, arm circumference, arm fat area and fat mass. Conclusions: There is a significant association between resistin levels and body composition variables, particularly with indicators of fat accretion.

Virgin olive oil rich in phenolic compounds modulates the expression of atherosclerosis-related genes in vascular endothelium.

PURPOSE: Previous studies have shown the anti-inflammatory and antioxidant properties of phenolic compounds of virgin olive oil (VOO). However, the effect of bioavailable phenolic compounds on the vascular endothelium is unknown. We aimed to evaluate the effect of the consumption of virgin olive oil rich in phenolic compounds on the vascular endothelium. METHODS: We treated HUVEC with human serum obtained in fasting state and after the intake of a breakfast prepared with VOO with a high or low content of phenolic compounds. RESULTS: Treatment of HUVEC with serum obtained 2 h after the intake of the high-phenol VOO-based breakfast decreased p65 and MCP-1 gene expression (p < 0.001 and p = 0.002, respectively) and increased MT-CYB, SDHA and SOD1 gene expression (p = 0.004, p = 0.012 and p = 0.001, respectively), as compared with the treatment of HUVEC with the serum obtained 2 h after the intake of the low-phenol VOO-based breakfast. The treatment with serum obtained 4 h after the intake of the high-phenol VOO-based breakfast decreased MCP-1 and CAT gene expression (p < 0.001 and p = 0.003, respectively) and increased MT-CYB gene expression (p < 0.001), as compared to the treatment with serum obtained 4 h after the intake of the low-phenol VOO-based breakfast. CONCLUSION: Our results suggest that the consumption of virgin olive oil rich in phenolic compounds may reduce the risk of atherosclerosis development by decreasing inflammation and improving the antioxidant profile in the vascular endothelium.

[Diagnosis and treatment of familial hypercholesterolemia in Spain: consensus document]. / Diagnóstico y tratamiento de la hipercolesterolemia familiar en España: documento de consenso.

Familial hypercholesterolemia (FH) is a common genetic disorder, clinically manifested since birth, and associated with very high levels of plasma LDL-cholesterol (LDL-c), xanthomas, and premature coronary heart disease. Its early detection and treatment reduces coronary morbidity and mortality. Despite effective treatment being available, FH is under-diagnosed and under-treated. Identification of index cases and cascade screening using LDL-c levels and genetic testing are the most cost-effective strategies for detecting new cases and starting early treatment. Long-term treatment with statins has decreased the vascular risk to the levels of the general population. LDL-c targets are < 130 mg/dL for children and young adults, <100mg/dL for adults, and < 70 mg/dL for adults with known coronary heart disease or diabetes. Most patients do not to reach these goals, and combined treatments with ezetimibe or other drugs may be necessary. When the goals are not achieved with the maximum tolerated drug treatment, a reduction ≥ 50% in LDL-c levels can be acceptable. Lipoprotein apheresis can be useful in homozygous, and in treatment-resistant severe heterozygous, cases. This Consensus Paper gives recommendations on the diagnosis, screening, and treatment of FH in children and adults, and specific advice to specialists and general practitioners with the objective of improving the clinical management of these patients, in order to reduce the high burden of coronary heart disease.

[Diagnosis and treatment of familial hypercholesterolemia in Spain: Consensus document]. / Diagnóstico y tratamiento de la hipercolesterolemia familiar en España: documento de consenso.

Familial hypercholesterolemia (FH) is a common genetic disorder, clinically manifested since birth, and associated with very high levels of plasma LDL-cholesterol (LDL-c), xanthomas, and premature coronary heart disease. Its early detection and treatment reduces coronary morbidity and mortality. Despite effective treatment being available, FH is under-diagnosed and under-treated. Identification of index cases and cascade screening using LDL-c levels and genetic testing are the most cost-effective strategies for detecting new cases and starting early treatment. Long-term treatment with statins has decreased the vascular risk to the levels of the general population. LDL-c targets are <130mg/dL for children and young adults, <100mg/dL for adults, and <70mg/dL for adults with known coronary heart disease or diabetes. Most patients do not to reach these goals, and combined treatments with ezetimibe or other drugs may be necessary. When the goals are not achieved with the maximum tolerated drug treatment, a reduction ≥50% in LDL-c levels can be acceptable. Lipoprotein apheresis can be useful in homozygous, and in treatment-resistant severe heterozygous, cases. This Consensus Paper gives recommendations on the diagnosis, screening, and treatment of FH in children and adults, and specific advice to specialists and general practitioners with the objective of improving the clinical management of these patients, in order to reduce the high burden of coronary heart disease.

Elevated GH/IGF-I promotes mammary tumors in high-fat, but not low-fat, fed mice.

Growth hormone (GH) and/or insulin-like growth factor I (IGF-I) are thought to promote breast cancer based on reports showing circulating IGF-I levels correlate, in epidemiological studies, with breast cancer risk. Also, mouse models with developmental GH/IGF-I deficiency/resistance are less susceptible to genetic- or chemical-induced mammary tumorigenesis. However, given the metabolic properties of GH, medical strategies have been considered to raise GH to improve body composition and metabolic function in elderly and obese patients. Since hyperlipidemia, inflammation, insulin resistance and obesity increase breast cancer risk, elevating GH may serve to exacerbate cancer progression. To better understand the role GH/IGF-I plays in tumor formation, this study used unique mouse models to determine if reducing GH/IGF-I in adults protects against 7,12-dimethylbenz[α]anthracene (DMBA)-induced mammary tumor development, and if moderate elevations in endogenous GH/IGF-I alter DMBA-induced tumorigenesis in mice fed a standard-chow diet or in mice with altered metabolic function due to high-fat feeding. We observed that adult-onset isolated GH-deficient mice, which also have reduced IGF-I levels, were less susceptible to DMBA-treatment. Specifically, fewer adult-onset isolated GH-deficient mice developed mammary tumors compared with GH-replete controls. In contrast, chow-fed mice with elevated endogenous GH/IGF-I (HiGH mice) were not more susceptible to DMBA-treatment. However, high-fat-fed, HiGH mice showed reduced tumor latency and increased tumor incidence compared with diet-matched controls. These results further support a role of GH/IGF-I in regulating mammary tumorigenesis but suggest the ultimate consequences of GH/IGF-I on breast tumor development are dependent on the diet and/or metabolic status.

Olive oil phenolic compounds decrease the postprandial inflammatory response by reducing postprandial plasma lipopolysaccharide levels.

We investigated the molecular mechanisms by which phenolic compounds (phenols) in virgin olive oil reduce the postprandial inflammatory response with the aim of identifying the transcription factor involved and the downstream effects. Olive oil-based breakfasts prepared with virgin olive oil (VOO) with high (398 ppm), intermediate (149 ppm) and low (70 ppm) phenol content were administered to 49 metabolic syndrome patients following a randomized crossover design. The consumption of a high-phenol VOO-based breakfast limited the increase of lipopolysaccharide plasma levels, TLR4, and SOCS3 proteins (p<0.001, p=0.041 and p=0.008, respectively), the activation of NF-κB (p=0.016) and the IL6 (p=0.007 and p=0.048, low and intermediate oil, respectively), IL1B (p=0.002, intermediate oil), and CXCL1 (p=0.001) postprandial gene expression, in peripheral blood mononuclear cells, as compared with the consumption of a breakfast prepared with the same oil but with low or intermediate phenol content. Virgin olive oil phenolic compounds reduce the postprandial inflammatory response in association with postprandial plasma lipopolysaccharide levels.