Combining familial hypercholesterolemia and statin genetic studies as a strategy for the implementation of pharmacogenomics. A multidisciplinary approach.

The diagnostic process of familial hypercholesterolemia frequently involves the use of genetic studies. Patients are treated with lipid-lowering drugs, frequently statins. Although pharmacogenomic clinical practice guidelines focusing on genotype-based statin prescription have been published, their use in routine clinical practice remains very modest.We have implemented a new NGS strategy that combines a panel of genes related to familial hypercholesterolemia with genomic regions related to the pharmacogenomics of lipid-lowering drugs described in clinical practice guidelines and in EMA and FDA drug labels. A multidisciplinary team of doctors, biologists, and pharmacists creates a clinical report that provides diagnostic and therapeutic findings using a knowledge management and clinical decision support system, as well as an algorithm for treatment selection.For 12 months, a total of 483 genetic diagnostic studies for familial hypercholesterolemia were carried out, of which 221 (45.8%) requested a complementary pharmacogenomic test. Of these 221 patients, 66.5% were carriers of actionable variants in any of the studied pharmacogenomic pathways: 46.6% of patients in one pathway, 19.0% in two pathways, and 0.9% in three pathways. 45.7% of patients could have a response to atorvastatin different from that of the reference population, 45.7% for simvastatin and lovastatin, 29.0% for fluvastatin, and 6.7% patients for pitavastatin.This implementation approach facilitates the incorporation of pharmacogenomic studies in clinical care practice, it does not add complexity nor additional steps to laboratory processes, and improves the pharmacotherapeutic process of patients.

[Osteoarticular pneumococcal infections observed in a tertiary hospital over a period of 11 years]. / Infección osteoarticular neumocócica en un hospital terciario durante un período de 11 años.

INTRODUCTION: Osteoarticular pneumococcal infection is an infrequent complication of pneumococcal bacteremia, due to the advances in antibiotic therapy and in the pattern of immunization. METHODS: A retrospective study was conducted on patients diagnosed with osteoarticular pneumococcal infection between January 2003 and December 2013 in the University Hospital Marqués de Valdecilla in Santander. RESULTS: Five out of 321 patients diagnosed with pneumococcal bacteremia had osteoarticular infection. All of them had at least one chronic underlying disease and had been immunized according to the standard vaccination schedule. Hip and vertebra were the most common joints involved. Outcome was favorable in all cases. CONCLUSIONS: The clinical findings of pneumococcal osteoarticular infection should be borne in mind. Its optimal prevention in high-risk patients should include the 13V conjugate vaccine.

Classification of Cucumber Leaves Based on Nitrogen Content Using the Hyperspectral Imaging Technique and Majority Voting.

Improper usage of nitrogen in cucumber cultivation causes nitrate accumulation in the fruit and results in food poisoning in humans; therefore, mandatory evaluation of food products becomes inevitable. Hyperspectral imaging has a very good ability to evaluate the quality of fruits and vegetables in a non-destructive manner. The goal of the present paper was to identify excess nitrogen in cucumber plants. To obtain a reliable result, the majority voting method was used, which takes into account the unanimity of five classifiers, namely, the hybrid artificial neural network-imperialism competitive algorithm (ANN-ICA), the hybrid artificial neural network-harmonic search (ANN-HS) algorithm, linear discrimination analysis (LDA), the radial basis function network (RBF), and the K-nearest-neighborhood (KNN). The wavelengths of 723, 781, and 901 nm were determined as optimal wavelengths using the hybrid artificial neural network-biogeography-based optimization (ANN-BBO) algorithm, and the performance of classifiers was investigated using the optimal spectrum. The results of a t-test showed that there was no significant difference in the precision of the algorithm when using the optimal wavelengths and wavelengths of the whole range. The correct classification rate of the classifiers ANN-ICA, ANN-HS, LDA, RBF, and KNN were 96.14%, 96.11%, 95.73%, 64.03%, and 95.24%, respectively. The correct classification rate of majority voting (MV) was 95.55% for test data in 200 iterations, which indicates the system was successful in distinguishing nitrogen-rich leaves from leaves with a standard content of nitrogen.

Lipid profile and serum folate, vitamin B12 and homocysteine levels in patients with retinal vein occlusion. / Perfil lipídico y concentraciones séricas de ácido fólico, vitamina B12 y homocisteína en pacientes con obstrucción venosa retiniana.

BACKGROUND: Retinal vein occlusion (RVO) is mainly related with vascular risk factors (VRF). OBJECTIVES: To analyze the lipid profile and serum folate, vitamin B12 and homocysteine levels, in patients with RVO and a population-based control group. PATIENTS AND METHODS: Case-control study. Patients with RVO were assessed during an 11-year period. RESULTS: We included 368 patients and 325 controls of similar age and sex. HDL cholesterol and folate levels were lower (52 [43-63] mg/dL vs. 55 [46-66]; p = 0.016 and 7 [5-10] ng/mL vs. 9 [7-13]; p < 0.0001, respectively) and non-HDL cholesterol and homocysteine levels higher (148.9 ± 37.3 mg/dL vs. 142.9 ± 34.5; p = 0.03 and 13.4 [11.2-18.2] µmol/L vs. 11.1 [9.0-14.4]; p < 0.001) in patients with RVO than controls. Although total cholesterol, LDL-C, and triglyceride levels were higher and serum vitamin B12 levels were lower in RVO patients, these differences did not reach statistical significance. CONCLUSIONS: RVO-patients have lower serum HDL-C and folate levels and higher non-HDL-C and serum homocysteine levels than population-based controls of similar age and sex. In patients with RVO, apart from the lipid profile, determination of serum homocysteine, folate and vitamin B12 levels might be useful, as well as the treatment of their alterations.

[Rendu-Osler disease with hepatic involvement: first transplant in Spain]. / Enfermedad de Rendu-Osler con afectación hepática: primer trasplante en España.

BACKGROUND AND OBJECTIVE: Rendu-Osler's disease (RO) is a rare systemic vascular disorder due to a fibrovascular dysplasia in the endothelium of vessels. Recurrent epistaxis is the main clinical manifestation, but arteriovenous malformations (AVMs) can involve many organs, including the liver. Hepatic involvement can develop refractory heart failure due to large shunts between the hepatic veins and the hepatic artery. Embolization and hepatic artery ligation have also demonstrated to reduce cardiac output in RO, but these therapeutic options have significant morbidity and complications such as necrosis or liver failure. CASE REPORT: We report the case of a 48 years old woman diagnosed in 1987 with RO and significant hepatic involvement, with multiple fistulas between veins and hepatic artery. In the following years she developed progressive heart failure that limited her quality of life. RESULTS: She was admitted on more times with heart failure and her dyspnea worsened progressively up to NYHA IV. At this time, an echocardiograph control showed an output cardiac about 10.6l/min. On December 2004, although the medical treatment, the worsening of the patient went on, so we finally decided to conduct a liver transplant that resolved the symptoms and the hyperdynamic circulation. Despite the fact that liver transplant has become without doubt into the best treatment for these patients in the last years. CONCLUSIONS: This is the first one done in Spain. There are different therapies available for these patients, but the indications for transplantation are greater each day, mainly due to the risks of the other options. Currently the stated guidelines are heart failure and portal hypertension refractory to medical treatment. So in these situations, liver transplantation should be proposed in the early stages of the disease and may be the only viable option.

A Computer Vision System Based on Majority-Voting Ensemble Neural Network for the Automatic Classification of Three Chickpea Varieties.

Since different varieties of crops have specific applications, it is therefore important to properly identify each cultivar, in order to avoid fake varieties being sold as genuine, i.e., fraud. Despite that properly trained human experts might accurately identify and classify crop varieties, computer vision systems are needed since conditions such as fatigue, reproducibility, and so on, can influence the expert's judgment and assessment. Chickpea (Cicer arietinum L.) is an important legume at the world-level and has several varieties. Three chickpea varieties with a rather similar visual appearance were studied here: Adel, Arman, and Azad chickpeas. The purpose of this paper is to present a computer vision system for the automatic classification of those chickpea varieties. First, segmentation was performed using an Hue Saturation Intensity (HSI) color space threshold. Next, color and textural (from the gray level co-occurrence matrix, GLCM) properties (features) were extracted from the chickpea sample images. Then, using the hybrid artificial neural network-cultural algorithm (ANN-CA), the sub-optimal combination of the five most effective properties (mean of the RGB color space components, mean of the HSI color space components, entropy of GLCM matrix at 90°, standard deviation of GLCM matrix at 0°, and mean third component in YCbCr color space) were selected as discriminant features. Finally, an ANN-PSO/ACO/HS majority voting (MV) ensemble methodology merging three different classifier outputs, namely the hybrid artificial neural network-particle swarm optimization (ANN-PSO), hybrid artificial neural network-ant colony optimization (ANN-ACO), and hybrid artificial neural network-harmonic search (ANN-HS), was used. Results showed that the ensemble ANN-PSO/ACO/HS-MV classifier approach reached an average classification accuracy of 99.10 ± 0.75% over the test set, after averaging 1000 random iterations.

Non-Destructive Prediction of Titratable Acidity and Taste Index Properties of Gala Apple Using Combination of Different Hybrids ANN and PLSR-Model Based Spectral Data.

Non-destructive estimation of the internal properties of fruits and vegetables is very important, because better management can be provided for subsequent operations. Researchers and scientists around the world are focusing on non-destructive methods because if they are developed and commercialized, there will be an impressive change in the food industry. In this regard, this paper aims to present a non-destructive method based on Vis-NIR spectral data. The different stages of the proposed algorithm are: (1) Collection of samples of Gala apples, (2) Spectral data extraction by spectroscopy, (3) Pre-processing of spectral data, (4) Measurement of chemical properties of titratable acidity (TA) and taste index, (5) Selection of key wavelengths using hybrid artificial neural network-firefly algorithm (ANN-FA), (6) Non-destructive estimation of the properties using two methods of hybrid ANN- Particle swarm optimization algorithm and partial least squares regression. For considering the reliability of methods for estimating the chemical properties, the prediction operation was executed in 300 iterations. The results represented that the mean and standard deviation of the correlation coefficient and the root mean square error of hybrid ANN-PSO and PLSR for TA were 0.9095 ± 0.0175, 0.0598 ± 0.0064, 0.834 ± 0.0313 and 0.0761 ± 0.0061 respectively. These values for taste index were 0.918 ± 0.02, 3.2 ± 0.39, 0.836 ± 0.033 and 4.09 ± 0.403, respectively. Therefore, it can be concluded that the hybrid ANN-PSO has a better performance for non-destructive prediction of the two mentioned chemical properties than the PLSR method. In general, the proposed method can predict the chemical properties of TA and taste index non-destructively, which is very useful for mechanized harvesting and management of post-harvest operation.

Non-Destructive Estimation of Total Chlorophyll Content of Apple Fruit Based on Color Feature, Spectral Data and the Most Effective Wavelengths Using Hybrid Artificial Neural Network-Imperialist Competitive Algorithm.

Non-destructive assessment of the physicochemical properties of food products, especially fruits, makes it possible to examine the internal quality without any damage. This is applicable at different stages of fruit growth, harvesting stage, and storage as well as at the market stage. In this regard, the present study aimed to estimate the total chlorophyll content using three types of data: color data, spectral data, and spectral data related to the most effective wavelengths. The most important steps of the proposed algorithms include extracting spectral and color data from each sample of Fuji cultivar apple, selecting the most effective wavelengths at the range of 660-720 nm using hybrid artificial neural network-particle swarm optimization (ANN-PSO), non-destructive assessment of the chemical property of total chlorophyll content based on color data, and spectral data using hybrid artificial neural network-Imperialist competitive algorithm (ANN-ICA). In order to assess the reliability of the hybrid ANN-ICA, 1000 iterations were performed after selecting the optimal structure of the artificial neural network. According to the results, in the best training mode and using spectral data and the most effective wavelength, total chlorophyll content was predicted with the R2 and RMSE of 0.991 and 0.0035, 0.997 and 0.001, 0.997 and 0.0006, respectively.

Weed Classification for Site-Specific Weed Management Using an Automated Stereo Computer-Vision Machine-Learning System in Rice Fields.

Site-specific weed management and selective application of herbicides as eco-friendly techniques are still challenging tasks to perform, especially for densely cultivated crops, such as rice. This study is aimed at developing a stereo vision system for distinguishing between rice plants and weeds and further discriminating two types of weeds in a rice field by using artificial neural networks (ANNs) and two metaheuristic algorithms. For this purpose, stereo videos were recorded across the rice field and different channels were extracted and decomposed into the constituent frames. Next, upon pre-processing and segmentation of the frames, green plants were extracted out of the background. For accurate discrimination of the rice and weeds, a total of 302 color, shape, and texture features were identified. Two metaheuristic algorithms, namely particle swarm optimization (PSO) and the bee algorithm (BA), were used to optimize the neural network for selecting the most effective features and classifying different types of weeds, respectively. Comparing the proposed classification method with the K-nearest neighbors (KNN) classifier, it was found that the proposed ANN-BA classifier reached accuracies of 88.74% and 87.96% for right and left channels, respectively, over the test set. Taking into account either the arithmetic or the geometric means as the basis, the accuracies were increased up to 92.02% and 90.7%, respectively, over the test set. On the other hand, the KNN suffered from more cases of misclassification, as compared to the proposed ANN-BA classifier, generating an overall accuracy of 76.62% and 85.59% for the classification of the right and left channel data, respectively, and 85.84% and 84.07% for the arithmetic and geometric mean values, respectively.

Interobserver agreement using Schlapbach graded scale for diffuse idiopathic skeletal hyperostosis (DISH): can we reduce the cut-off point of vertebral affection?

Resnick-Niwayama criteria for diagnosing DISH depict an advanced stage, and a new reduced cut-off point with three contiguous vertebrae affected (two bone bridges) has been proposed. The aim has been to know the interobserver agreement by using a graded scale of DISH in which grade II matches with the new proposed cut-off point and grade III matches with the first criterion of Resnick-Niwayama. Males ≥ 50 years and postmenopausal women included in a population-based prospective study (the Camargo Cohort) were analyzed. Sample size was obtained according to an expected kappa of 0.95 and an accuracy of ± 8%. Three physicians applied independently Schlapbach graded scale (ranged from grade 0, no ossification, to grade III, ≥ 3 consecutive bone bridges) on the lateral radiographs of thoracic and lumbar spine of participants. We calculated inter- and intra-observer agreement and correlation. One hundred and fifty eight radiographs (79 patients, 68 ± 9 years) were assessed. Kappa values (95% confidence interval) for grades 0, I, II, and III were 0.63 (0.50-0.77), 0.49 (0.37-0.62), 0.32 (0.17-0.47), and 0.69 (0.60-0.77), respectively. Weighted kappa for the three pairs of raters were 0.87 (0.82-0.93), 0.84 (0.77-0.91), and 0.81 (0.72-0.90). Grade III was the image that generated greater agreement, while a significant decrease was noted in grade II, the new proposed criterion. The simultaneous presence of an incomplete DISH and osteoarthritis, in a thoracic spinal segment with peculiar anatomical characteristics (reduced disk spaces, kyphotic curve), is thought to be a major cause of variability in the results.

Vascular cognitive impairment: prodromal stages of ischemic vascular dementia.

BACKGROUND/AIMS: To describe the natural history of the prodromal stages of ischemic vascular dementia (pVaD). METHODS: A sample of 314 inpatients with pVaD or a clini- cal diagnosis of vascular dementia (VaD; lacunar state, Binswanger's disease, pure cortical VaD, corticosubcortical and strategic infarctions) admitted to a teaching tertiary center during a 13-year period was assessed (retrospectively n = 88, prospectively n = 226). Prospective neuropsychological assessment consisted of Mini Mental State Examination, Revised Wechsler Adult Intelligence Scale, Exit-25, Trail Making tests, Blessed Dementia Scale and Camdex H, Global Depression Scale and Hamilton Depression Rating Scale tests. Univariate analysis and logistic regressions are displayed. RESULTS: An unrecognized pVaD was related with a clinical onset with cognitive impairment no dementia (CIND) versus symptomatic cerebrovascular events (p < 0.0001), and with being under therapy with anticoagulant or antiplatelet agents (p < 0.01). Age <85 years at diagnosis of VaD (p < 0.01) correlated with a delayed pVaD diagnosis. CIND onset was associated with a longer prodromal stage (p < 0.01), no clinical strokes during pVaD (p < 0.001), silent ischemia (p < 0.01) and Binswanger's disease (p < 0.01). CONCLUSIONS: Vascular cognitive impairment remains an underdiagnosed, yet treatable entity. A brief neuropsychological examination and informant interviews should become standard practice in elderly populations with vascular risk factors. Small-vessel disease is a prevalent condition with a distinct natural history.

[Metabolic syndrome: how about bone?]. / Síndrome metabólico, también del hueso?

In the last decades, the association between cardiovascular disease and osteoporosis has been a matter of an extensive clinical and basic investigation, and in fact, common pathogenic links have been recently proposed. The metabolic syndrome includes a series of cardiovascular risk factors that confer a high risk of morbimortality. On the other hand, osteoporosis and its more serious consequence, fracture, represent a true epidemic nowadays. The aim of the present article is to perform a brief update of the association between the individual components of the metabolic syndrome and bone metabolism, and to analyze the publications that have studied the same association, but considering the metabolic syndrome as a whole.

Relationship between diffuse idiopathic skeletal hyperostosis, abdominal aortic calcification and associated metabolic disorders: Data from the Camargo Cohort. / Relación entre hiperostosis esquelética idiopática difusa, calcificación de la aorta abdominal y las alteraciones metabólicas asociadas: datos de la Cohorte Camargo.

BACKGROUND AND OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) and abdominal aortic calcification (AAC) are related to an increased cardiovascular risk. The aim of this study was to analyse a possible relationship between both entities and also the association between metabolic disorders and DISH. PATIENTS AND METHOD: Analytic cross-sectional study in a population-based cohort. DISH (with Resnick-Niwayama criteria) and AAC (with AAC-24 scale) were assessed on plain x-ray images. Interaction terms between DISH and forty clinical covariates were also investigated, through correlation analysis and multivariate regression. RESULTS: Nine hundred eighty-seven males aged≥50 years, with a mean age=65,5±9 years, were evaluated. Prevalence rates of DISH and AAC were 21.6% and 58.7%, respectively. DISH+ subjects were older (68.1±9 vs. 63.8±9 years; P=.0001) and more likely to be affected by metabolic syndrome (MS) (55.6% vs. 36.6%; P=.0001). In DISH+ subjects, the AAC was 3.7±5 points, whereas in DISH- subjects it was 3.3±5 (P=.25). AAC was associated with an increased risk of prevalent DISH (unadjusted OR=1.4 [CI95%: 1.01-1.9]; P=.04), that disappeared when it was adjusted for age (adjusted OR=1.1 [CI95%: 0.8-1.5];P=.47]. No association was found between DISH and hypertension, diabetes or dyslipidaemia; however, age (OR=2.2 [CI95%: 1.6-3]; P=.0001), BMI (OR=1.5 [CI95%: 1.1-2]; P=.007), waist circumference (OR=1.5 [CI95%: 1.04-2,3]; P=.03) and MS (OR=1.7 [CI95%: 1.1-2.4]; P=.005) showed a significant relationship with DISH after adjusting for confounders. CONCLUSIONS: The study was not able to demonstrate a consistent association between DISH and AAC, proving only a weak and age-dependent relationship between them. DISH proved to be significantly associated with age, BMI, waist circumference and MS.

A Computer-Aided Detection System for Digital Chest Radiographs.

Computer-aided detection systems aim at the automatic detection of diseases using different medical imaging modalities. In this paper, a novel approach to detecting normality/pathology in digital chest radiographs is proposed. The problem tackled is complicated since it is not focused on particular diseases but anything that differs from what is considered as normality. First, the areas of interest of the chest are found using template matching on the images. Then, a texture descriptor called local binary patterns (LBP) is computed for those areas. After that, LBP histograms are applied in a classifier algorithm, which produces the final normality/pathology decision. Our experimental results show the feasibility of the proposal, with success rates above 87% in the best cases. Moreover, our technique is able to locate the possible areas of pathology in nonnormal radiographs. Strengths and limitations of the proposed approach are described in the Conclusions.

[Intravenous bisphosphonates]. / Bisfosfonatos intravenosos.

Bisphosphonates possess a fundamental role in the treatment of bone metabolic diseases. Yet their main limitations are poor oral absorption and gastrointestinal side effects, mainly esophageal irritation. Indeed, oral administration is unpleasant for many patients, and it is difficult in bed-confined subjects. Therefore, intravenous administration of these agents can be very useful in several clinical scenarios, especially to improve the compliance. Recently, it has been showed that intravenous bisphosphonates are very useful to control hypercalcemia of malignancy, and to prevent bone complications related to metastases. Their use has also been analyzed in the prevention of bone disease after organ transplantation. Thus, their application to control Paget's disease of bone is well-known, and probably they could have an important role as antiresorptive agents in postmenopausal and steroidal osteoporosis. We present here a state of the art of the use of intravenous bisphosphonates for the aforementioned disorders.

[Relationship between the plasmatic level of thyrotropin and cardiovascular disease (the Camargo Cohort)]. / Relación entre la concentración plasmática de tirotropina y enfermedad cardiovascular (Cohorte Camargo).

BACKGROUND AND OBJECTIVE: Age seems to modify the relationship between hypothyroidism and cardiovascular disease (CVD). Although hypothyroidism in very elderly subjects has been associated with longevity, subclinical hypothyroidism in people ≤ 65 years seems to be related with an increased cardiovascular risk (CVR). The aim of this study was to determine the explanatory power of plasmatic TSH (pTSH) for the CVD, in different strata determined by age (≤ 55, 56-74, ≥ 75 years), sex and CVR factors. PATIENTS AND METHODS: Six hundred and sixty-four men and women were differentiated into 18 strata and their explanatory models were developed using the multiple linear regression analysis. The dependent variable is the abdominal aortic calcification (AAC) according to the AAC-24 scale. The independent variables are: pTSH, age, smoking, BMI, SBP, DBP, fasting glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol and C-reactive protein. RESULTS: Age is the main explanatory factor of AAC. The highest explanatory value of the ß-standardized coefficient of the pTSH is observed in males ≤ 55 years (ß=0.235, P=.043) and in females ≥ 75 years (ß=0.405, P=.042). With increasing age, the prediction power improves in women and decreases in men. In men ≥ 75 years there is a negative correlation between pTSH and AAC (rho-Spearman=-0.213, P=.049). CONCLUSIONS: A positive association is observed between pTSH and CVD in males ≤ 55 years and in women ≥ 75 years. The combination of multiple regression and the stratified analysis shows the complex influence of age in the relation between both variables.