Iron overload, an immunosuppression marker in HIV-infected patients.

Purpose: Iron overload (IO) has been associated with increased cardiovascular risk (CVR) and metabolic syndrome (MS) in the general population; both elevated CVR and MS are frequent in HIV- patients. Our aim was to analyze the prevalence of IO in a cohort of asymptomatic patients with HIV infection, and related factors. Methods: Cross-sectional study of a cohort of HIV outpatients in regular follow-up. Demographic, epidemiological, clinical, analytical and therapeutic data were collected. Patients completed a questionnaire about CVR factors and 10-year CV disease risk estimation (Framingham score), underwent a physical exam, and a fasting blood analysis. IO was defined as a plasma ferritin level higher than 200 m/L in women and 300 m/L in men. Results: 571 patients (446 men, 125 women), with a mean age of 43.2 years, sexual transmission of HIV in 68.5%, median CD4 count 474 cell/μL (IQR: 308-666), and 36.3% Aids cases 86.2% were on antiretroviral therapy (ART), and 74.8% of them had undetectable HIV viral load 14.6% met MS criteria, and mean CVR at 10 years was 6.67%. IO was detected in 11% of cases. Patients with IO were more immunosuppressed (CD4 count 369 vs 483/μL, p<0.0001), presented a higher prevalence of detectable HIV viral load (17.6% vs 8.9%; p<0.005), and of Aids cases (14.9% vs 8.7%; p<0.023), and lower plasma levels of cholesterol, HDLc and LDLc (154 vs 183, 34 vs 43, 93 vs 110 mg/dL, respectively; p<0.0001. In the multivariate analysis, the only related factor was CD4 count <350 cell/μL (OR 2.86, 95% CI 1.6-4.9; p<0.0001). IO was not associated with CVR nor with MS. Conclusions: IO is not uncommon in HIV patients, and it is only related with immunosuppression defined as CD4 count <350 cell/ mL, and in contrast to general population, it is not related with increased CVR nor with MS.

Nevirapine vs efavirenz in virologically supressed patients: Differences in lipoprotein subclasses and inflammatory biomarkers.

Background: The interaction between lipid disturbances and inflammatory markers is not well known in patients on antiretroviral therapy (ART). As nevirapine (NVP) is associated with a better lipid profile than efavirenz (EFV), we investigated the relationships between lipid profiles, lipoprotein subclasses and inflammatory biomarkers in patients with prolonged viral suppression with either NVP or EFV and no obvious clinical inflammation. Methods: 122 clinically stable HIV-infected patients with HIV-1 RNA <20 copies longer than 6 months on NNRTI therapy were studied. 72 (59%) were on EFV and 50 (41%) on NVP. Any potentially inflammatory co-morbid diseases (concurrent viral hepatitis, diabetes, hypertension, chronic liver or renal diseases), or statin treatment, were exclusion criteria. Inflammatory biomarkers included hsCRP, LpPLA2, sCD40L, IL-6, IL-8, t-PA, MCP-1, p-selectin and VCAM-1. Lipoprotein subclass measures (VLDL, LDL, IDL and HDL particle number and size) were obtained by the use of proton nuclear magnetic resonance spectroscopy. Results: 82% were male; median age 45 years. Median CD4 count 550/μL (IQR 324). Median time since HIV diagnosis 96 months (IQR 102) and accumulated time on ART 50 months (IQR 101). Patients on NVP had higher time since HIV diagnosis (126.9 [66.7] vs 91.3 [6.6] months, p=0.008) a prolonged time on ART (89.6 [54.6] vs 62.3 [52.2] months, p=0.01) and were older (47.7 vs 40.7 years, p=0.001) than those on EFV. NVP-treated patients presented increased HDL-c (55.8 [16] vs 48.8 [10.7] mg/dL, p=0.007) and apoA1 levels (153.4 [31.9] vs 141.5 [20.5] mg/dL, p=0.02), and reduced apoB/apoA1 ratio (0.68 [0.1] vs 0.61 [0.1], p=0.003) than EFV-treated patients. No differences in inflammatory markers or lipoprotein subclasses were found between NVP and EFV. In patients with extreme lipid values (less favorable: 75th percentiles of LDL, small/dense LDLp and small HDLp, or more favorable: HDL p75 and apoB/apoA1 ratio p25), no consistent differences in inflammatory biomarkers were found. Conclusions: Patients with prolonged viral suppression on NVP present significantly higher HDL and apoA1 levels and reduced apoB/apoA1 ratios than those on EFV, but no differences were found in lipoprotein particles nor inflammatory biomarkers. Relationships between lipid parameters and inflammatory biomarkers in NNRTItreated patients are complex and do not show a linear relationship in this study.

Referrals of cancer versus non-cancer patients to a palliative care consult team: do they differ?

This retrospective study compared 100 consecutive non-cancer (NC) patients referred to a palliative care consult team (PCT) in a Swiss university hospital to 506 cancer (C) patients referred during the same period. The frequencies of reported symptoms were similar in both groups. The main reasons for referral in the NC group were symptom control, global evaluation, and assistance with discharge. Requests for symptom control predominated in the C group. Prior to the first visit, 50% of NC patients were on opioids, compared to 58% of C patients. After the first visit, the proportion of NC patients on opioids increased to 64% and the proportion of C patients to 73%. The median daily oral morphine equivalent dose for NC patients taking opioids prior to the first PCT visit was higher than that for C patients (60 mg versus 45 mg). At the time of death or discharge, the percentage of NC patients on opioids was 64%, while that of C patients was 76%. Moreover, NC patients were on significantly lower median doses of opioids than C patients (31 mg versus 60 mg). Over half the NC patients died during hospitalization, as compared to 33% of C patients. Only 6% of NC patients were discharged to palliative care units, as compared to 22% of C patients.

El proyecto EMECAS: protocolo del estudio multicéntrico en España de los efectos a corto plazo de la contaminación atmosférica sobre la salud.

The EMECAM Project demonstrated the short-term effect of air pollution on the death rate in 14 cities in Spain throughout the 1990-1995 period. The Spanish Multicentre Study on Health Effects of Air Pollution (EMECAS) is broadening these objectives by incorporating more recent data, information on hospital disease admissions and totaling 16 Spanish cities. This is an ecological time series study in which the response variables are the daily deaths and the emergency hospitalizations due to circulatory system diseases and respiratory diseases among the residents in each city. Pollutants analyses: suspended particles, SO2, NO2, CO and O3. Control variables: meteorological, calendar, seasonality and influenza trend and incidence. Statistical analysis: estimate of the association in each city by means of the construction of generalized additive Poisson regression models and metanalysis for obtaining combined estimators. The EMECAS Project began with the creation of three working groups (Exposure, Epidemiology and Analysis Methodology) which defined the protocol. The average levels of pollutants were below those established under the current regulations for sulfur dioxide, carbon monoxide and ozone. The NO2 and PM10 values were around those established under the regulations (40 mg/m3). This is the first study of the relationship between air pollution and disease rate among one group of Spanish cities. The pollution levels studied are moderate for some pollutants, although for others, especially NO2 and particles, these levels could entail a problem with regard to complying with the regulations in force.

Selection of Reference Genes for Quantitative Real Time PCR (qPCR) Assays in Tissue from Human Ascending Aorta.

Dilatation of the ascending aorta (AAD) is a prevalent aortopathy that occurs frequently associated with bicuspid aortic valve (BAV), the most common human congenital cardiac malformation. The molecular mechanisms leading to AAD associated with BAV are still poorly understood. The search for differentially expressed genes in diseased tissue by quantitative real-time PCR (qPCR) is an invaluable tool to fill this gap. However, studies dedicated to identify reference genes necessary for normalization of mRNA expression in aortic tissue are scarce. In this report, we evaluate the qPCR expression of six candidate reference genes in tissue from the ascending aorta of 52 patients with a variety of clinical and demographic characteristics, normal and dilated aortas, and different morphologies of the aortic valve (normal aorta and normal valve n = 30; dilated aorta and normal valve n = 10; normal aorta and BAV n = 4; dilated aorta and BAV n = 8). The expression stability of the candidate reference genes was determined with three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable genes for the three algorithms employed were CDKN1β, POLR2A and CASC3, independently of the structure of the aorta and the valve morphology. In conclusion, we propose the use of these three genes as reference genes for mRNA expression analysis in human ascending aorta. However, we suggest searching for specific reference genes when conducting qPCR experiments with new cohort of samples.

Transient global amnesia associated with an acute infarction at the cingulate gyrus.

Background. Transient global amnesia (TGA) is a syndrome of sudden, unexplained isolated short-term memory loss. In the majority of TGA cases, no causes can be identified and neuroimaging, CSF studies and EEG are usually normal. We present a patient with TGA associated with a small acute infarct at the cingulate gyrus. Case Report. The patient, a 62 year-old man, developed two episodes of TGA. He had hypertension and hypercholesterolemia. He was found to have an acute ischemic stroke of small size (15 mm of maximal diameter) at the right cerebral cingulate gyrus diagnosed on brain magnetic resonance imaging. No lesions involving other limbic system structures such as thalamus, fornix, corpus callosum, or hippocampal structures were seen. The remainder of the examination was normal. Conclusion. Unilateral ischemic lesions of limbic system structures may result in TGA. We must bear in mind that TGA can be an associated clinical disorder of cingulate gyrus infarct.

Resuscitated sudden cardiac death caused by left main coronary artery compression by an aneurysm of the sinus of Valsalva.

A 49-year-old woman, without known cardiovascular risk factors. Hoarseness of voice caused by a paralysis of left vocal cord. She was admitted to hospital because of acute coronary syndrome, associated to resuscitated cardiac arrest (asystolia documented) without later neurology sequels. Physical examination was anodyne. Echocardiographic study demonstrated a compatible image with a large left sinus of Valsalva aneurysm (SVA) (Panel A) and mild aortic regurgitation. Cardiac catheterization confirmed the presence of left SVA (Panel B) that produced extrinsic compression of the left main coronary artery (Panels C and D). Repair surgery was made by means of closing the aneurysmal orifice with a patch of dacron. Intra-operatory echocardiographic control study found severe aortic regurgitation, so valvular replacement with 19 mm mechanical prosthesis and extension of the valve annulus with patch of dacron was performed, associated with bypass with safena vein graft to left coronary artery. SVA is a very infrequent cardiac anomaly, generally with silent clinical course until it ruptures. Myocardial ischaemia caused by coronary artery compression is unusual. We described the case of a patient diagnosed of left SVA, whose initial clinical manifestation was the appearance of resuscitated sudden cardiac death in the context of an acute coronary syndrome.

Preinfarction angina prior to first myocardial infarction does not influence long-term prognosis: a retrospective study with subgroup analysis in elderly and diabetic patients.

BACKGROUND AND HYPOTHESIS Although prodromal angina occurring shortly before an acute myocardial infarction (MI) has protective effects against in-hospital complications, this effect has not been well documented after initial hospitalization, especially in older or diabetic patients. We examined whether angina 1 week before a first MI provides protection in these patients. METHODS A total of 290 consecutive patients, 143 elderly (>64 years of age) and 147 adults (<65 years of age), 68 of whom were diabetic (23.4%) and 222 nondiabetic (76.6%), were examined to assess the effect of preceding angina on long-term prognosis (56 months) after initial hospitalization for a first MI. RESULTS No significant differences were found in long-term complications after initial hospitalization in these adult and elderly patients according to whether or not they had prodromal angina (44.4% with angina vs 45.4% without in adults; 45.5% vs 58% in elderly, P < 0.2). Nor were differences found according to their diabetic status (61.5% with angina vs 72.7% without in diabetics; 37.3% vs 38.3% in nondiabetics; P = 0.4). CONCLUSION The occurrence of angina 1 week before a first MI does not confer long-term protection against cardiovascular complications after initial hospitalization in adult or elderly patients, whether or not they have diabetes.

Popliteal pseudoaneurysm after unicompartmental knee replacement: a case report.

Popliteal pseudoaneurysm is a rare but important complication of knee arthroplasties. To our knowledge, this complication has not been reported previously in the literature after unicompartmental knee arthroplasty. Apart from intraoperatively caused arterial injuries, obese patients and other previous cardiovascular diseases may be potential factors of risks for pseudoaneurysm in knee surgeries. As it is an uncommon complication and it has inconspicuous symptoms, both diagnosis and treatment can be delayed. This means that a high level of suspicion is necessary to prevent serious complications derived from pseudoaneurysms. LEVEL OF EVIDENCE Level IV.

Guía de práctica clínica para la prevención y cuidados de las úlceras arteriales

Publicaciones complementarias: Folleto: Guía de prevención y cuidado de las úlceras arteriales para personas cuidadoras. Folleto desplegable: Guía rápida de consulta para la prevención y cuidados de las úlceras arteriales.

Influencia de un programa de actividad física en niños y adolescentes obesos con apnea del sueño; protocolo de estudio.

Recent studies show an alarming increase in the rate of overweight / obesity among the infant - juvenile population. Obesity in childhood is associated with a significant number of complications, such as sleep apnea syndrome, insulin resistance and type 2 diabetes, hypertension, cardiovascular disease and some cancers. It is estimated that the prevalence of sleep apnea in children is 2-3% in the general population, while in obese adolescents, varies between 13% and 66%, according to various studies. It is associated with impairment of neurocognitive function, behavior, cardiovascular system, metabolic disorders and growth. Sleep apnea is a serious public health problem that increases when children and adolescents are overweight or obese. We hypothesize that aerobic endurance exercise can be an effective treatment for obesity and apnea at the same time. The aim of this study was to determine the influence of physical activity in children and adolescents with overweight / obesity in sleep apnea. An observational, descriptive, prospective, longitudinal study will be carried out in children with sleep apnea and obesity. The universe will be made up of 60 children and adolescents aged between 10 and 18 years, attending the endocrinology service for suffering of obesity in the Hospital Clinico San Cecilio of Granada during the period September 2012-September 2013. The smple will consist of children and adolescents that meet these characteristics and to hom their arents/tutors have authorized through the informed consent. Sleep apnea in children wil be measured by polysomnography and sleep quality questionnaire. There will also be a nutritional assessment by a food frequency questionnaire and an anthropometric assessment. Among the expected results are the lower overweight and obesity in children through the physical activity program. To reduce apnea and to improve sleep quality

Unanswered clinical questions in the management of cardiometabolic risk in the elderly: a statement of the Spanish society of internal medicine.

BACKGROUND Despite the progressive increase in life expectancy and the relationship between aging with multi-morbidities and the increased use of healthcare resources, current clinical practice guidelines (CPG) on cardiometabolic risk cannot be adequately applied to elderly subjects with multiple chronic conditions. Its management frequently becomes complicated by both, an excessive use of medications that may lead to overtreatment, drug interactions and increased toxicity, and errors in dosage and non-compliance. Concerned by this gap, the Spanish Society of Internal Medicine created a group of independent experts on cardiometabolic risk who discussed what they considered to be unanswered questions in the management of elderly patients. DISCUSSION Current guidelines do not specifically address the problem of elderly with multiple chronic conditions. For this reason, the combined use of the limited available evidence, clinical experience and common sense, could all help us to address this unmet need. In very old people, life expectancy and functionality are the most important factors for guiding potential treatments. Their higher propensity to develop serious adverse events and their shorter lifespan could prevent them from obtaining the potential benefits of the interventions administered. SUMMARY In this document, experts on cardiometabolic risk factors have established a number of consensual recommendations that have taken into account international guidelines and clinical experience, and have also considered the more effective use of healthcare resources. This document is intended to provide general recommendations for clinicians and to promote the effective use of procedures and medications.

The systemic administration of oleoylethanolamide exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism.

Oleoylethanolamide (OEA) is an agonist of the peroxisome proliferator-activated receptor α (PPARα) and has been described to exhibit neuroprotective properties when administered locally in animal models of several neurological disorder models, including stroke and Parkinson's disease. However, there is little information regarding the effectiveness of systemic administration of OEA on Parkinson's disease. In the present study, OEA-mediated neuroprotection has been tested on in vivo and in vitro models of 6-hydroxydopamine (6-OH-DA)-induced degeneration. The in vivo model was based on the intrastriatal infusion of the neurotoxin 6-OH-DA, which generates Parkinsonian symptoms. Rats were treated 2 h before and after the 6-OH-DA treatment with systemic OEA (0.5, 1, and 5 mg/kg). The Parkinsonian symptoms were evaluated at 1 and 4 wk after the development of lesions. The functional status of the nigrostriatal system was studied through tyrosine-hydroxylase (TH) and hemeoxygenase-1 (HO-1, oxidation marker) immunostaining as well as by monitoring the synaptophysin content. In vitro cell cultures were also treated with OEA and 6-OH-DA. As expected, our results revealed 6-OH-DA induced neurotoxicity and behavioural deficits; however, these alterations were less severe in the animals treated with the highest dose of OEA (5 mg/kg). 6-OH-DA administration significantly reduced the striatal TH-immunoreactivity (ir) density, synaptophysin expression, and the number of nigral TH-ir neurons. Moreover, 6-OH-DA enhanced striatal HO-1 content, which was blocked by OEA (5 mg/kg). In vitro, 0.5 and 1 μM of OEA exerted significant neuroprotection on cultured nigral neurons. These effects were abolished after blocking PPARα with the selective antagonist GW6471. In conclusion, systemic OEA protects the nigrostriatal circuit from 6-OH-DA-induced neurotoxicity through a PPARα-dependent mechanism.

Prospective registry of symptomatic severe aortic stenosis in octogenarians: a need for intervention.

OBJECTIVE To study the factors associated with choice of therapy and prognosis in octogenarians with severe symptomatic aortic stenosis (AS). STUDY DESIGN Prospective, observational, multicenter registry. Centralized follow-up included survival status and, if possible, mode of death and Katz index. SETTING Transnational registry in Spain. SUBJECTS We included 928 patients aged ≥80 years with severe symptomatic AS. INTERVENTIONS Aortic-valve replacement (AVR), transcatheter aortic-valve implantation (TAVI) or conservative therapy. MAIN OUTCOME MEASURES All-cause death. RESULTS Mean age was 84.2 ± 3.5 years, and only 49.0% were independent (Katz index A). The most frequent planned management was conservative therapy in 423 (46%) patients, followed by TAVI in 261 (28%) and AVR in 244 (26%). The main reason against recommending AVR in 684 patients was high surgical risk [322 (47.1%)], other medical motives [193 (28.2%)], patient refusal [134 (19.6%)] and family refusal in the case of incompetent patients [35 (5.1%)]. The mean time from treatment decision to AVR was 4.8 ± 4.6 months and to TAVI 2.1 ± 3.2 months, P < 0.001. During follow-up (11.2-38.9 months), 357 patients (38.5%) died. Survival rates at 6, 12, 18 and 24 months were 81.8%, 72.6%, 64.1% and 57.3%, respectively. Planned intervention, adjusted for multiple propensity score, was associated with lower mortality when compared with planned conservative treatment: TAVI Hazard ratio (HR) 0.68 (95% confidence interval [CI] 0.49-0.93; P = 0.016) and AVR HR 0.56 (95% CI 0.39-0.8; P = 0.002). CONCLUSION Octogenarians with symptomatic severe AS are frequently managed conservatively. Planned conservative management is associated with a poor prognosis.