[Real-life efficacy and safety of PCSK9 inhibitors treatment: Experience in three hospitals in Asturias]. / Efectividad y seguridad del tratamiento con iPCSK9 en vida real: experiencia de tres hospitales asturianos.

BACKGROUND: Inhibitors of proprotein convertase subtilisin/kexin type9 (PCSK9 inhibitors) are a treatment option for those patients with familial hypercholesterolemia or in secondary prevention who do not reach the LDL-C target with other therapeutic measures. The aim of this study is to assess the effectiveness and safety of these drugs. METHODS: Retrospective, multicentric, descriptive study. We collected data from all patients that have started PCSK9 inhibitors treatment in three hospitals in Asturias since the beginning of its use in 2016. We analysed changes in lipid profile with PCSK9 inhibitors and its side effects. RESULTS: We registered 98 patients, 75 of them affected by familial hypercholesterolemia (FH) and 23 unaffected. Two months after the beginning of PCSK9 inhibitors treatment, a 61% reduction rate in LDL-C in patients with FH and 52% in those without this condition was observed. This statistically significant reduction remained stable during follow-up. A significant decrease in total cholesterol was observed, without significant changes in HDL-C and triglycerides. 96% of patients had no complications. CONCLUSIONS: PCSK9 inhibitors are safe drugs that rapidly achieve significant reductions in LDL-C after the beginning of treatment, which are maintained over time. Hence, the use of PCSK9 inhibitors is an alternative for the control of LDL-C in those patients in which the LDL-C target is not reached with other therapeutic measures.

Comparative study of 18F-FDG PET/CT and CT angiography in detection of large vessel vasculitis. / Estudio comparativo de la PET/TC con 18F-FDG y la angiografía por TC en la detección de la vasculitis de grandes vasos.

OBJECTIVE: Compare 18F-FDG PET/CT and CTangio in the diagnosis of extracraneal large vessel involvement in patients with suspicion of large vessel vasculitis (LVV). MATERIAL AND METHODS: A retrospective database reviewed 59 patients with clinical suspicion of LVV undergoing 18F-FDG PET/CT and CTangio. In 55 patients PET/TC and CTangio were done simultaneously in the same machine and in 4 patients with a scan interval of<1 month. PET/CT analyses included qualitatively and quantitative analysis (ratio SUVmax 18F-FDG vessel/SUVmax liver). CTangio was assessed for concentric mural thickening, contrast wall enhancement and structural vascular changes as potential complications of vasculitis. RESULTS: 18F-FDG PET/CT and CTangio show high specificity (97.2%) for LVV diagnosis, with an excellent sensitivity for 18F-FDG PET/CT (95.6%) and lower for CTangio (60.9%), which leads to a high negative predictive value for 18F-FDG PET/CT (97.2%) and a high false negative rate for CTangio (39.1%). A 70% concordance between 18F-FDG PET/CT and CTangio was obtained (Kappa index 0.70± 0.095 (P<.001). CONCLUSION: The results show the greater potential of 18F-FDG PET/CT for the detection and extension of LVV. Therefore, 18F-FDG PET/CT should be exploited to the maximum and consider as the first line imaging technique in the extracranial diagnosis of LVV and its possible association with polymyalgia rheumatica. The addition of CTangio could be more indicated in patients with Takayasu arteritis and in long-standing and/or severe vasculitis since it increases the accuracy in the detection of possible vascular complications.

Preoperative localization of an insulinoma: selective arterial calcium stimulation test performance.

PURPOSE: Preoperative localization of an insulinoma is recommended to improve the cure rate, but non-invasive procedures can fail to detect the tumour. The objective of the study was to assess the performance of a selective arterial calcium stimulation test in the preoperative localization of insulinomas that were not detected by conventional imaging procedures. METHODS: We conducted a monocenter retrospective case review of 13 patients who had endogenous hyperinsulinism and were treated between 1994 and 2013. Patients were selected on the basis of negative or doubtful non-invasive preoperative imaging. A selective arterial calcium stimulation test was performed by pancreatic and hepatic arteriography with selective intra-arterial calcium stimulation and hepatic venous sampling in order to obtain the plasma insulin measurement. We evaluated the efficacy of the test by comparing the results with an endoscopic ultrasound. RESULTS: Twelve of the 13 patients underwent surgery, and the presence of an insulinoma was proven in 11 patients by pathological analysis of the tumour. An endoscopic ultrasound was consistent with surgery in 71.4 % of cases, while selective arterial calcium stimulation was consistent with surgery in 90.9 % and allowed detection of an insulinoma in two additional patients with a negative endoscopic ultrasound. One false-negative and one false-positive arterial calcium test were observed. No adverse events were recorded except transient skin flush following calcium injection in one patient. CONCLUSION: The selective arterial calcium stimulation test is a sensitive diagnostic procedure for localizing insulinomas and may be considered when non-invasive radiological imaging does not allow the detection of an occult insulinoma.

Management and outcomes in chronic thromboembolic pulmonary hypertension: From expert centers to a nationwide perspective.

BACKGROUND: The Spanish "Registry of Pulmonary Arterial Hypertension" (REHAP), started in 2007, includes chronic thromboembolic hypertension (CTEPH) patients. Based on data provided by this registry and retrospective data from patients diagnosed during 2006 (≤ 12 months since the registry was created), clinical management and long-term outcomes of CTEPH patients are analyzed nationwide for the first time in a scenario of a decentralized organization model of CTEPH management. METHODS AND RESULTS: A total of 391 patients (median [Q1:Q3] age 63.7 [48.0;73.3] years, 58% females) with CTEPH included during the period January 1, 2006-December 31, 2013 in the REHAP registry were analyzed. Rate of pulmonary endarterectomy (PEA) was 31.2%, and highly asymmetric among centers: rate was 47.9% at two centers designated as CTEPH expert centers, while it was 4.6% in other centers. Among patients not undergoing PEA, 82% were treated with therapies licensed for pulmonary arterial hypertension (PAH). Five-year survival rate was 86.3% for PEA patients, and 64.9% for non-PEA patients. Among non-PEA patients, presenting proximal lesions (42% of non-referred patients) was associated with a 3-fold increase in mortality. PEA patients achieved significantly better hemodynamic and clinical outcomes at one-year follow-up compared to non-PEA patients. Patients not being referred for PEA assessment were older and had a worse functional capacity. Older age was the most deterrent factor for non-operability. CONCLUSION: Despite the increase in diagnosis and expertise in PEA-specialized centers, an important percentage of patients do not benefit of PEA in a decentralized organization model of CTEPH management.

[Evaluation of diabetic retinopathy screening using non-mydriatic fundus camera performed by physicians' assistants in the endocrinology service]. / Évaluation du dépistage de la rétinopathie diabétique par rétinographe non mydriatique effectué par des aides-soignant(e)s d'un service d'endocrinologie.

INTRODUCTION: Since 2010, the High Authority for health (HAS) recommends the use of non-mydriatic fundus camera for diabetic retinopathy screening. The purpose of this study is to evaluate the results of screening for diabetic retinopathy using the non-mydriatic retinal camera by a physician's assistant in the endocrinology service. MATERIALS AND METHODS: This is a retrospective study of all diabetic patients hospitalized in the endocrinology department between May 2013 and November 2013. For each endocrinology patient requiring screening, a previously trained physician's assistant performed fundus photos. The ophthalmologist then provided a written interpretation of the photos on a consultant's sheet. RESULTS: Of the 120 patients screened, 40 (33.3%) patients had uninterpretable photos. Among the 80 interpretable photos, 64 (53.4%) patients had no diabetic retinopathy, and 16 (13.3%) had diabetic retinopathy. No patient had diabetic maculopathy. DISCUSSION: Specific quality criteria were established by the HAS for screening for diabetic retinopathy using the non-mydriatic retinal camera in order to ensure sufficient sensitivity and specificity. In our study, the two quality criteria were not achieved: the rates of uninterpretable photos and the total number of photos analyzed in a given period. CONCLUSION: In our center, we discontinued this method of diabetic retinopathy screening due to the high rate of uninterpretable photos. Due to the logistic impossibility of the ophthalmologists taking all the fundus photos, we proposed that the ophthalmic nurses take the photos. They are better trained in the use of the equipment, and can confer directly with an ophthalmologist in questionable cases and to obtain pupil dilation as necessary.

All night analysis of time interval between snores in subjects with sleep apnea hypopnea syndrome.

Sleep apnea-hypopnea syndrome (SAHS) is a serious sleep disorder, and snoring is one of its earliest and most consistent symptoms. We propose a new methodology for identifying two distinct types of snores: the so-called non-regular and regular snores. Respiratory sound signals from 34 subjects with different ranges of Apnea-Hypopnea Index (AHI = 3.7-109.9 h(-1)) were acquired. A total number of 74,439 snores were examined. The time interval between regular snores in short segments of the all night recordings was analyzed. Severe SAHS subjects show a shorter time interval between regular snores (p = 0.0036, AHI cp: 30 h(-1)) and less dispersion on the time interval features during all sleep. Conversely, lower intra-segment variability (p = 0.006, AHI cp: 30 h(-1)) is seen for less severe SAHS subjects. Features derived from the analysis of time interval between regular snores achieved classification accuracies of 88.2 % (with 90 % sensitivity, 75 % specificity) and 94.1 % (with 94.4 % sensitivity, 93.8 % specificity) for AHI cut-points of severity of 5 and 30 h(-1), respectively. The features proved to be reliable predictors of the subjects' SAHS severity. Our proposed method, the analysis of time interval between snores, provides promising results and puts forward a valuable aid for the early screening of subjects suspected of having SAHS.

[Aneurysmal subarachnoid hemorrhage: group of study of cerebrovascular pathology of the Spanish society of neurosurgery management guideline]. / Hemorragia subaracnoidea aneurismática: guía de tratamiento del grupo de patología vascular de la sociedad Española de neurocirugía.

An actualized revision of the most important aspects of aneurismal subarachnoid hemorrhage is presented from the guidelines previously published by the group of study of cerebrovascular pathology of the Spanish Society of Neurosurgery. The proposed recommendations should be considered as a general guide for the management of this pathological condition. However, they can be modified, even in a significant manner according to the circumstances relating each clinical case and the variations in the therapeutic and diagnostic procedures available in the center attending each patient.

[Does decompressive craniectomy improve other parameters besides ICP? Effects of the decompressive craniectomy on tissular pressure?]. / ¿Mejora la craniectomía descompresiva otros parámetros además de la PIC? Efectos de la craniectomía descompresiva en la presión tisular.

Second level therapeutic maneuvres for controlling intracranial hypertension (ICH) proposed by the European Brain Injury Consortium and the American Association of Neurological Surgeons include barbiturates, moderate hypothermia and more recently the decompressive craniectomy (DC).In most patients, ICP can be maintained below 25 mmHg after a DC. However, the exact effect of DC on brain oxygenation (PtiO2) still unclear. From our point of view the ptIo2 monitoring with the probe located in the healthy area of the most severely damaged cerebral hemisphere is not only a important tool for timing craniectomy in the future but also for evaluating the therapeutic effectivity of DC.

Normal non-regular snores as a tool for screening SAHS severity.

Snoring is one of the earliest and most consistent sign of upper airway obstruction leading to Sleep Apnea-Hypopnea Syndrome (SAHS). Several studies on post-apneic snores, snores that are emitted immediately after an apnea, have already proven that this type of snoring is most distinct from that of normal snoring. However, post-apneic snores are more unlikely and sometimes even inexistent in simple snorers and mild SAHS subjects. In this work we address that issue by proposing the study of normal non-regular snores. They correspond to successive snores that are separated by normal breathing cycles. The results obtained establish the feasibility of acoustic parameters of normal non-regular snores as a promising tool for a prompt screening of SAHS severity.

Regular and non regular snore features as markers of SAHS.

Sleep Apnea-Hypopnea Syndrome (SAHS) diagnosis is still done with an overnight multi-channel polysomnography. Several efforts are being made to study profoundly the snore mechanism and discover how it can provide an opportunity to diagnose the disease. This work introduces the concept of regular snores, defined as the ones produced in consecutive respiratory cycles, since they are produced in a regular way, without interruptions. We applied 2 thresholds (TH(adaptive) and TH(median)) to the time interval between successive snores of 34 subjects in order to select regular snores from the whole all-night snore sequence. Afterwards, we studied the effectiveness that parameters, such as time interval between successive snores and the mean intensity of snores, have on distinguishing between different levels of SAHS severity (AHI (Apnea-Hypopnea Index) < 5h(-1), AHI <10 h(-1), AHI < 15 h(-1), AHI < 30 h(-1)). Results showed that TH(adaptive) outperformed TH(median) on selecting regular snores. Moreover, the outcome achieved with non-regular snores intensity features suggests that these carry key information on SAHS severity.

Noninvasive measurement of inspiratory muscle performance by means of diaphragm muscle mechanomyographic signals in COPD patients during an incremental load respiratory test.

The study of mechanomyographic (MMG) signals of respiratory muscles is a promising noninvasive technique in order to evaluate the respiratory muscular effort and efficiency. In this work, the MMG signal of the diaphragm muscle it is evaluated in order to assess the respiratory muscular function in Chronic Obstructive Pulmonary Disease (COPD) patients. The MMG signals from left and right hemidiaphragm were acquired using two capacitive accelerometers placed on both left and right sides of the costal wall surface. The MMG signals and the inspiratory pressure signal were acquired while the COPD patients carried out an inspiratory load respiratory test. The population of study is composed of a group of 6 patients with severe COPD (FEV1>50% ref and DLCO < 50% ref). We have found high positive correlation coefficients between the maximum inspiratory pressure (IPmax) developed in a respiratory cycle and different amplitude parameters of both left and right MMG signals (RMS, left: 0.68 ± 0.11 - right: 0.69 ± 0.12; Rényi entropy, left: 0.73 ± 0.10 - right: 0.77 ± 0.08; Multistate Lempel-Ziv, left: 0.73 ± 0.17 - right: 0.74 ± 0.08), and negative correlation between the Pmax and the maximum frequency of the MMG signal spectrum (left: -0.39 ± 0.19 - right: -0.65 ± 0.09). Furthermore, we found that the slope of the evolution of the MMG amplitude parameters, as the load increases during the respiratory test, has positive correlation with the %FEV1/FVC pulmonary function test parameter of the six COPD patients analyzed (RMS, left: 0.38 - right: 0.41; Rényi entropy, left: 0.45 - right: 0.63; Multistate Lempel-Ziv, left: 0.39 - right: 0.64). These results suggest that the information provided by MMG signals could be used in order to evaluate the respiratory effort and the muscular efficiency in COPD patients.

The possible role of epigenetics in gestational diabetes: cause, consequence, or both.

Gestational diabetes mellitus (GDM) is defined as the glucose intolerance that is not present or recognized prior to pregnancy. Several risk factors of GDM depend on environmental factors that are thought to regulate the genome through epigenetic mechanisms. Thus, epigenetic regulation could be involved in the development of GDM. In addition, the adverse intrauterine environment in patients with GDM could also have a negative impact on the establishment of the epigenomes of the offspring.

Epigenetic regulation of the immune system in health and disease.

Epigenetics comprises various mechanisms that mold chromatin structures and regulate gene expression with stability, thus defining cell identity and function and adapting cells to environmental changes. Alteration of these mechanisms contributes to the inception of various pathological conditions. Given the complexity of the immune system, one would predict that a higher-order, supragenetic regulation is indispensable for generation of its constituents and control of its functions. Here, we summarize various aspects of immune system physiology and pathology in which epigenetic pathways have been implicated. Increasing knowledge in this field, together with the development of specific tools with which to manipulate epigenetic pathways, might form a basis for new strategies of immune function modulation, both to optimize immune therapies for infections or cancer and to control immune alterations in aging or autoimmunity.

Interpretation of the approximate entropy using fixed tolerance values as a measure of amplitude variations in biomedical signals.

A new method for the quantification of amplitude variations in biomedical signals through moving approximate entropy is presented. Unlike the usual method to calculate the approximate entropy (ApEn), in which the tolerance value (r) varies based on the standard deviation of each moving window, in this work ApEn has been computed using a fixed value of r. We called this method, moving approximate entropy with fixed tolerance values: ApEn(f). The obtained results indicate that ApEn(f) allows determining amplitude variations in biomedical data series. These amplitude variations are better determined when intermediate values of tolerance are used. The study performed in diaphragmatic mechanomyographic signals shows that the ApEn(f) curve is more correlated with the respiratory effort than the standard RMS amplitude parameter. Furthermore, it has been observed that the ApEn(f) parameter is less affected by the existence of impulsive, sinusoidal, constant and Gaussian noises in comparison with the RMS amplitude parameter.

Variability and effects of bronchial colonisation in patients with moderate COPD.

Sputum and lung function were periodically assessed in stable moderate chronic obstructive pulmonary disease (COPD) outpatients to determine relationships between bronchial colonisation and inflammation. Relationships between potentially pathogenic microorganism (PPM) typology, bronchial inflammation (neutrophilia, tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10 and IL-12) and post-bronchodilator decline in forced expiratory volume in 1 s (FEV(1)) were analysed. PPMs periodically showing the same molecular profile using pulse field gel electrophoresis were considered long-term persistent. Bronchial colonisation was observed in 56 out of 79 follow-up examinations (70.9%) and was mainly due to Haemophilus influenzae, Pseudomonas aeruginosa and enterobacteria (n = 47). These PPMs were all related to sputum neutrophilia (p< or =0.05, Chi-squared test), and H. influenzae was related to higher levels of IL-1beta (p = 0.005) and IL-12 (p = 0.01), with a dose-response relationship (Spearman's correlation coefficient of 0.38 for IL-1beta (p = 0.001), and of 0.32 for IL-12 (p = 0.006)). Haemophilus parainfluenzae was not associated with an identifiable inflammatory response. Long-term persistence of the same strain was observed in 12 examinations (21.4%), mainly due to P. aeruginosa or enterobacteria. A neutrophilic bronchial inflammatory response was associated with a statistically significant decline in FEV(1) during follow-up (OR 2.67, 95% CI 1.07-6.62). A load-related relationship to bronchial inflammation in moderate COPD was observed for colonisation by H. influenzae, but not for colonisation by H. parainfluenzae.

Efficacy of moxifloxacin in the treatment of bronchial colonisation in COPD.

This study was designed to investigate the efficacy of moxifloxacin for the eradication of bacterial colonisation of the airways in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Out of 119 stable patients with COPD screened, 40 (mean age 69 yrs, mean forced expiratory volume in 1 s 50% predicted) were colonised with potentially pathogenic microorganisms (PPMs) and were included in a randomised, double-blind, placebo-controlled trial with moxifloxacin 400 mg daily for 5 days. Eradication rates were 75% with moxifloxacin and 30% with placebo at 2 weeks (p = 0.01). Bacterial persistence at 8 weeks was still higher (not significantly) in the placebo arm (five (25%) out of 20 versus one (5%) out of 20; p = 0.18). The frequencies of acquisition of a new PPM were high and similar in both treatment groups; consequently, the prevalence of colonisation at 8 weeks was also similar between treatment arms. No difference was found in the number of patients with exacerbations during the 5-month follow-up. Only the acquisition of a new PPM during follow-up showed a statistically significant relationship with occurrence of an exacerbation. Moxifloxacin was effective in eradicating PPMs in patients with positive sputum cultures. However, most patients were recolonised after 8 weeks of follow-up. Acquisition of a new strain of bacteria was associated with an increased risk of developing an exacerbation.